Significant left ventricular contribution to right ventricular systolic function RALPH 3. DAMIANO, JR., PAUL LA FOLLETTE, JR., JAMES L. COX, JAMES E. LOWE, AND WILLIAM P. SANTAMORE Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710; Department of Computer and Information Sciences, Temple University, Philadelphia; and Philadelphia Heart Institute, Presbyterian Medical Center, Philadelphia, Pennsylvania 19104
DAMIANO, RALPH J., JAMES E. LOWE,
L. Cox,
JR., PAUL LA FOLLETTE, AND
WILLIAM
P.
JR., JAMES
SANTAMORE.
Sig-
nificant left ventricular contribution to right ventricular systolic function. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): HM4-
H1524, 1991.-To examine the importance of systolic ventricular interdependenceon right ventricular function, we used a unique electrically isolated right ventricular free wall preparation. Double-peakedwaveforms for right ventricular pressure and pulmonary arterial blood flow occurred over a wide range of pacing intervals between the left and right ventricles. One component of the waveforms could be directly related to right ventricular free wall contraction, whereasthe other component was directly related to left ventricular and septal contraction. For left ventricular pressure, the left ventricular component was significantly larger than the right ventricular free wall component (92.7 t 3.2 vs. 7.3 & 3.2% peak-to-peak value, P < 0.01). For right ventricular pressure,the left ventricular and septal component wassignificantly greater than the right ventricular component (63.5 t 10.9 vs. 36.5 t 10.9%peak-to-peak value, P < 0.05). Similarly, for pulmonary arterial blood flow, the left ventricular component was significantly greater than the right ventricular component. When right ventricular free wall pacing stopped in diastole, 68 t 4% of right ventricular systolic pressureand 80 t 4% of pulmonary flow were obtained in the subsequentbeat. The results of this study indicate that left ventricular contraction is very important for right ventricular developedpressureand volume outflow. ventricular interdependence;cardiac mechanics;left ventricle; right ventricle FUNCTION of the right ventricle has been questioned since Starr and co-workers (29) demonstrated that severe damage to the right ventricular free wall does little to impair right ventricular pressure development. Extending this work, Kagan (13) in acute experiments on dogs destroyed most of the free wall of the right ventricle by cauterization. This destruction of the free wall had little effect on arterial and peripheral venous pressure. Donald and Essex (7) injected vinyl acetate into the right coronary arteries of dogs, thereby destroying -80% of the right ventricular free wall. This massive damage of the free wall caused no observable decrease in the ability to exercise; indeed, all the dogs showed an increase in the degree of work with training. Bakos (1) postulated that right ventricular function was maintained by the assistance of the left ventricle,
THE INDEPENDENT
H1514
whereas others postulated that the surviving fibers in the right ventricular free wall were sufficient to maintain right ventricular function. Consistent with the concept of left ventricular assistance to right ventricular contraction, Oboler and colleagues (21) observed experimentally that the derivative of right ventricular pressure was broad or double peaked, with one peak occurring coincidentally with the peak in the first time derivative of the left ventricular pressure (dP/dt ). Variations in electrical stimulation caused by bundle branch blocks further separated the right ventricular peaks, with one peak always coinciding with left ventricular peak dP/dt. In a complementary clinical study, Feneley and colleagues (10) demonstrated that in patients with conduction abnormality, one right ventricular peak always corresponded to the peak or maximum rate of left ventricular developed pressure. While the above studies suggest an important contribution of left ventricular contraction to right ventricular systolic function, they have significant shortcomings. Studies on right ventricular free wall damage are subject to multiple interpretations. Incomplete right ventricular free wall damage may have occurred and could imply that the right ventricular function was maintained by the surviving right ventricular fibers. Additionally, right ventricular function was poorly quantitated. More recent studies have demonstrated significant right ventricular dysfunction after right ventricular injury (11, 12). In their studies, Oboler et al. (21) and Feneley et al. (10) could observe only limited time variations in right and left ventricular pacing. More importantly, these studies provided no insight into the magnitude of this possible left ventricular assistance. To quantify this dependency of right ventricular function on the left ventricle, we utilized an electrically isolated right ventricular free wall preparation (3-5). This preparation allowed for wide controlled variations in the timing interval between right ventricular and left ventricular contractions. Utilizing this preparation, we observed very apparent double-peaked waveforms for both right ventricular pressure and right ventricular volume outflow. Numerical analysis indicated that right ventricular pressure and volume outflow waveforms were due to two components. One component could be directly related to right ventricular free wall contraction, whereas the other component was directly attributable to left and
0363-6135/91 $1.50 Copyright 0 1991 the American Physiological Society
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RIGHT
VENTRICULAR
DEPENDENCY
septal ventricular contraction. Furthermore, the analysis indicated that the left ventricular component was significantly greater than the right ventricular component for the right ventricular pressure and volume outflow. METHODS
Six adult mongrel dogs weighing from 25 to 35 kg were anesthetized with intravenous pentobarbital sodium (30 mg/kg) and were then maintained on a continuous intravenous infusion of 2 mg/min throughout each experiment. A median sternotomy was performed, and the heart was suspended in a pericardial cradle. Lead II of the peripheral electrocardiogram was monitored continuously. Multiple bipolar epicardial pacing and sensing electrodes were sutured to the right atrium, right ventricle, and left ventricle (Fig. 1). Right ventricular bipolar epicardial pacing electrodes were placed over the trabecular zone of the right ventricle, adjacent to the septum, and approximately midway between the pulmonary valve and the ventricular apex. This electrode placement was chosen to mimic as closely as possible the site of earliest epicardial activation of the normal right ventricle (31). The right ventricular bipolar recording electrodes were placed near the atrioventricular groove approximately midway between the pulmonary valve and the apex. The left ventricular bipolar electrodes were placed at the left ventricular apex. The sinoatrial node was identified and excised in all animals so that each animal could be paced during the study at a uniform heart rate of 150 beats/ min. Stimulus strength was twice the diastolic threshold, and pulse duration was 2.0 ms. All electrograms were filtered with Hewlett-Packard high-gain bioelectric amplifiers with a high-pass frequency of 0.5 Hz and a lowpass frequency of 1 kHz. Right and left ventricular pressures were monitored
\
TEMPERATURE
J
AORTIC PRESSURE
L
‘/
\’
FIG. 1. Schematic diagram of experimental protocol. RA, right atrial; RV, right ventricular; LV, left ventricular; PA, pulmonary arterial. Bipolar epicardial pacing and sensing electrodes-were sutured to right atrium, right ventricle, and left ventricle. RV and LV pressures were monitored with micromanometer-tipped transducers. Pulmonary blood flow was monitored with electromagnetic flow probe.
ON
LEFT
VENTRICLE
H1515
with high-fidelity Millar micromanometer-tipped pressure transducers. Right atria1 and central aortic pressures were monitored with fluid-filled catheters and Statham P23l D pressure transducers. An electromagnetic flow probe was placed around the main pulmonary artery, and flow was displayed on a Howell HMSlOOO blood flow meter (Howell Instruments, Camarilla, CA). Regional pulse transit piezoelectric crystals (1.5 mm OD, Vernitron no. l-l015-5A, Bedford, OH) were implanted in the subendocardium of the right ventricular and left ventricular free wall. The right ventricular pair was aligned loto 15-mm apart parallel to the atrioventricular groove and midway between the pulmonary valve and the ventricular apex. The left ventricular pair was aligned in the minor axis circumference midway between the base and apex. The piezoelectric transducer connectors were attached directly to a sonomicrometer constructed in our laboratory. The sonomicrometer had a sampling rate of 1,000 Hz with a frequency response of O-50 Hz. Minimal resolution was 0.08 mm, and maximal electronic drift was 0.05 mm/h. All physiological signals were recorded continuously and displayed on an 8-channel oscilloscope. Blood temperature was measured by a thermistor in the inferior vena cava. The femoral artery was cannulated for arterial perfusion, and the vena cavae were cannulated individually for venous return to the cardiopulmonary bypass unit. The azygous vein was ligated. Serum potassium and arterial blood gases were determined at regular intervals during each study. During all periods of data acquisition, systemic temperature was maintained at 37”C, and serum potassium levels were kept between 3.5 and 4.5 meq/l. All animals were then subjected to right atria1 bipolar epicardial pacing. The right atria1 to left ventricular conduction time was calculated in each animal during right atria1 pacing. Regional systolic function and unstressed myocardial segment length (L,) were then assessed by recording data continuously during volume loading and rapid vena cava occlusion. Heparin was administered (100 U/kg), and the animals were placed on cardiopulmonary bypass. Asanguinous priming solution and pediatric Shiley model lOOA bubble oxygenators were used. The animals were perfused at flow rates of 2.0-2.5 lmin-’ *mm*, adjusted to maintain mean aortic perfusion pressure at 70-100 mmHg. A full-thickness right ventriculotomy was made adjacent and parallel to the ventricular septum, extending from the anterior pulmonary valve annulus, around the apex of the heart, and back to the posterior tricuspid valve annulus (Fig. 2). A separate incision was then made from the posterior aspect of the pulmonary valve annulus, across the supracrystal ventricular septum, and down to the anterior tricuspid valve annulus. To complete the isolation and ablate all remaining interventricular fibers, cryolesions were placed at each end of both incisions with a g-mm diameter cryoprobe cooled to -60°C with internally expanding nitrous oxide. Each ventriculotomy was then closed with a continuous 4-O nonabsorbable suture. The animals were allowed to recover for 30 min. The animals were then weaned from cardiopulmonary bvpass and allowed to stabilize hemodynamically. All
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H1516
RIGHT
FIG. 2. was made was made muscle in tached to
VENTRICULAR
DEPENDENCY
Surgical technique for RV isolation. Right ventriculotomy adjacent and parallel to ventricular septum. Separate incision across supracrystal ventricular septum. Anterior papillary canine right ventricle (unlike that in human heart) is atseptum rather than to RV free wall.
data were recorded with the pericardium open. After this operation, the left ventricle and right ventricular free wall were electrically isolated and could be paced independently. This was accomplished without altering normal right atria1 to left ventricular conduction through the intact atrioventricular node (4-6). Regional systolic function and L, were reexamined utilizing volume loading and vena cava occlusions. The hemodynamic effects of varying the right atria1 and right ventricular pacing interval were examined. The interval between right atria1 and right ventricular pacing was increased from 0 to 300 ms in 20-ms increments. With a O-s delay, the right ventricular free wall contracted simultaneously with the atria and more than 100 ms before the left ventricle, which was activated through normal atrioventricular nodal conduction. With a delay of 300 ms, the right ventricular free wall was contracting more than 100 ms after the left ventricle. At each increment in pacing, all hemodynamic data were recorded. Sufficient time was allowed between each pacing interval to obtain hemodynamic stability. After this experimental protocol was completed, right ventricular pacing was ceased, and all hemodynamic data were recorded. After each experiment, the right atria1 waveform was carefully examined to ensure that tricuspid valve function was unaffected by the operative procedure. The animals were then killed with an overdose of pentobarbital sodium, and the hearts were examined. DATA
ANALYSIS
Regional function. Physiological data were filtered with a SO-Hz low-pass analog filter, recorded on analog tape,
ON LEFT
VENTRICLE
and digitized with a sampling rate of 200 Hz by an ADAC A/D converter. Data were stored on magnetic tape, and analyses were performed on a DEC PDP 11/23 microprocessor using interactive programs developed in our laboratory. The dP/dt was determined using a &point polyorthogonal transformation of the digital left ventricular waveform. The cardiac cycle was defined using dP/dt. Diastole was defined as beginning at the first zero crossing of dP/ dt after peak negative dP/dt and ending 40 ms before peak positive dP/dt. Beginning ejection was placed 20 ms after peak positive dP/dt, and end ejection was set 40 ms before peak negative dP/dt. Ejection shortening was calculated as the change in myocardial segment length over the ejection period. The L, was determined from vena caval occlusion data as the length at a left ventricular pressure of 0 mmHg. L, was defined at beginning diastole where dP/dt was zero. Right ventricular stroke volume was defined as the area under the pulmonary flow trace. An index of stroke work was determined as follows: (right ventricular peak systolic pressure - right ventricular mean diastolic pressure) X stroke volume x 0.0136. A one-way analysis of variance was used to compare repeated measurements over time. Variability in L, was expressed as the variance not attributable to variance between dogs or between times. Linear regressions were compared by the method of Snedecor and Cochran (28). Numerical analysis. To examine systolic ventricular interdependence, we hypothesized that the measured right ventricular pressure and volume outflow were the sum of two components, a contribution from the right ventricle and a contribution from the left ventricle. The actual data consisted of measured left and right ventricular pressures and pulmonary blood flow generated by pacing the ventricles at the same rate but with a series of different delays between the stimulation of the left and right ventricles. These delays were of the form Od, 2d, 3d. . .Nd, where d equaled 20 ms. This gave us two families of measured pressure functions: the pressure measured in the left ventricle when the interventricular delay was kd [m&t)] and the pressure measured in the right ventricle when the interventricular delay was kd [mHk(t)]. These pressure measurements were assumed to be sampled values of periodic functions with the period inversely related to the heart rate. Again, we hypothesized that the measured pressure in the right ventricle was the sum of two components: a contribution from the right ventricle [r(t)] and a contribution from the left ventricle [l(t)], plus errors in the measurements [edt)]. Thus by our hypothesis mrlk(t)
= l(t) + r(t - kd) - ek(t)
(1)
or, equivalently ek(t) = l(t) + r(t - kd) - mak(t)
To estimate these hypothesized left and right components, we first took the Fourier transform of Eq. 1, yielding Ek(u) = L(w) + e-lUkdR(w) - MR~(w)
(2)
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RIGHT
VKNTRICULAR
We solved for R and L to minimize over all the pacing delays
DEPENDENCY
the error function
kio sm EkbYQW = kio lm Straightforward to this problem that minimized
[L(o) + emiwkdR(w) - M,tk(~)2d~]
application of the calculus of variations indicated that the estimates for R and L this expression were given by
(N + l)R(w) + L(w) i
emwM -
$ M~k(u)
k=il
k=O
(3)
N
R(o)
g erwkd+ (IV + l)L(o)
= C Mm(o)e
k=O
rwkd
k=O
From the strip chart record, the actual physiological data were traced on a digitizer tablet (True Grid, Houston Instruments), digitized at 200 samples/s (or 75 samples/ heartbeat), and stored in an Apple II+ microcomputer (Apple Computer, Cupertino, CA). The data files were A
CONTROL
ON
LEFT
H1517
VENTRICLE
transferred to an IBM computer for the remainder of the data analysis. To facilitate the calculation of the discrete Fourier transform, these sampled data were interpolated to provide 64 evenly spaced samples per period. Two periods worth of these interpolated data were created for each of 16 different interventricular pacing delays (0, 20. . .300 ms). The equations (3) were then applied to calculate the left and right components of the measured right ventricular pressure. Analogous equations were used to find the left and right components of the left ventricular pressure (which we expected to consist primarily of a left component) and the left and right components of the right ventricular volume outflow. r(t) and l(t) were calculated and then recombined to determine how well the functions represented the original data. For each delay kd, we calculated C,,(t) = l(t) + r(t - kd) + ek. These recalculated waveforms were then plotted along with the original measured points so that we could determine how well the calculated data fit the original measurements. In each experiment, for left ventricular pressure, right ventricular pressure, and pulmonary arterial blood flow, the peakto-peak values for the right and left ventricular compo160ms
180ms
18 RV SEGMENTAL WALL MOTION (mm) 9 100 RV PRESSURE CmmHg) 0 18 LV SEGMENTAL WALL MOTION (mm)
9
200 LV PRESSURE (mmlig) 0 178 PA FLOW (cc/set)
I3 PRE ----POST
//
/
i FIG. 3. A: typical segmental shortening in RV free wall. b/t: control data; right: data after RV free wall isolation and 160- and 180.ms delay between RA and RV pacing. B: plots for 6 experiments of regional RV wall shortening vs. end-diastolic Length. Two curves are presented: pre- and post-RV free wall isolation. Slope of segment shortening vs. end-diastolic length (EDL) was unaltered by RV isolation. However, unstressed myocardial segment length was shlfted to right. SW, stroke work.
SW=-6977t496EDt
jSW=-9378t6llEDL
04
I , , I3 END-DIASTOLIC ,
II
,
~
,
15
,
, I9
LENGT;:MMI
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HE18
RIGHT
VENTRICULAR
DEPENDENCY
nents and the root mean square value for the right and left ventricular components were calculated. RESULTS
Right ventricular isolation was successfully performed in every animal. There were no detrimental effects of the procedure on pulmonary or tricuspid valve function as documented by careful examination of right atrial, right ventricular, and pulmonary arterial pressure waveforms. After the procedure, the isolated right ventricular free wall, when not paced, was either electrically silent or exhibited a slow idioventricular rhythm between 10 and 20 beats/min. The right atrial-to-left ventricular conduction interval was 121 t 5 ms preoperatively and 123 t 7 ms postoperatively (P = NS). Figure 3A shows a typical right ventricular segmental wall motion curve. In Fig. 3A, the control data are shown before surgery at left while data are shown after right ventricular free wall isolation at right. Note for this typical example the similarity in the segmental wall motion curves. The end-diastolic lengths and segmental shortening were almost identical between control and after right ventricular free wall isolation. For the group data, analysis of right ventricular regional systolic function was performed by analyzing the relationship between end-diastolic length and stroke work. The linear regression analysis of all six experiments before and after right ventricular free wall isolation revealed that the slope of this relationship was not changed by this procedure (Fig. 3B). L, was shifted in these animals from 11.9 t 0.1 to 13.3 t 0.1 (P C 0.03). This change in L,, however, resulted in no significant change in the slope of the linear regression (P > 0.05). An analysis of left ventricular regional myocardial function revealed no significant change in either L, or in the slope of the relationship between stroke work and end-diastolic length. The left ventricular pressure, right ventricular pressure, and pulmonary blood flow from one experiment are shown in Fig. 4. The interval between right atria1 and right ventricular pacing was increased in 2O-ms increments from 0 to 300 ms. The data at 60, 120, 180, and 240 ms are presented in Fig. 4. When the right ventricular RA-RV 60 MSEC
RA-RV 120 MSEC
ON
LEFT
VENTRICLE
free wall contracts before the left ventricle (60 ms), right ventricular pressure and pulmonary blood flow show double-peaked waveforms. This double peak disappears when the right and left ventricles contract synchronously at 120 ms. Because the right ventricular free wall contracts later than the left ventricle (as the pacing delay is increased beyond 120 ms), the right ventricular pressure waveform and pulmonary blood flow waveform again develop double peaks with one peak occurring later. Figures 5 and 6 show the data analysis for Fig. 4. The ventricular pressures and pulmonary blood flow waveforms were digitized at each pacing interval. Then after we assumed that each waveform was composed of a right ventricular free wall component and a left ventricular free wall plus septal component, the computer calculated these components to minimize the error function. Figure 5A presents the left and right components of left ventricular pressure. As anticipated, most of the left ventricular pressure, especially during systole, can be attributed to the left ventricular free wall septal component, the left ventricular contraction. The right ventricular free wall component, right ventricular contraction, had only a minimal contribution to left ventricular systolic pressure. Figure 5B presents the left and right components for right ventricular pressure. As indicated in Fig. 5B, the left ventricular free wall septal component (left ventricular contraction) is larger than the right ventricular free wall component. Thus, for this experiment, most of the right ventricular systolic pressure could be attributed to left ventricular contraction. Figure 5C presents the left and right components of right ventricular volume outflow. Similar to right ventricular pressure, most of right ventricular volume outflow can be directly attributed to left ventricular free wall septal contraction. In Fig. 6, the left and right components were used to reconstruct the ventricular pressure waveforms and right ventricular volume outflow at 60, 120, 180, and 240 ms. The reconstructed waveforms were very similar to the actual data with high correlation coefficients. For the six experiments, Table 1 presents the statistical analysis for the left and right components for the ventricular pressures and right ventricular outflow. For RA-RV 180 MSEC
RA-RV 240 MSEC
RV
FIG. 4. Local electrograms, LV 240-ms delays between RA and waveforms with 1 peak occurring are again double peaked but with
pressure, RV pressure, and RV volume outflow are presented at 60-, 120-, MO-, and RV pacing. At 60-ms delay, RV pressure and volume outflow are double-peaked before LV pressure. At 240-ms delay, RV pressure and volume outflow waveforms 1 peak occurring after LV development.
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RIGHT
VENTRICULAR
DEPENDENCY
ON
LEFT
B
A CASE LEFT 125mm
Hg
S216 CCNlPWENT
OF
LEFT
PRESSURE 1Smm
-
Hg
HE519
VENTRICLE CASE LEFT
916 COllPONENT
(Y
RIGHT
PRESSURE
-
O-
RIGHT 75mm
Hg
COWONENT
OF
LEFT
RIGHT
PRESSURE
,
15mm
1
Hg
COWONENT
OF
RIGHT
PRESURE
-
OI
CRSE LEFT
400
S216 COWWENT
OF
ms
PuCHOtMY
t
I
COCPWNT
I
OF
PlMOMRY
400 ms
ms
I
FLOU
FIG.
RIGHT
400
analysis, and right apparent, nent. B outflow, left and
FLOU
5. Computer analysis pressure and volume components. A: left vast majority of LV and C: left and right respectively. Both RV right components.
of data in Fig. 3. With the use of numerical outflow waveforms were separated into left and right components for LV pressure. As is pressure can be associated with left compocomponents for RV pressure and volume pressure and volume outflow have significant
I
left ventricular pressure, the vast majority (92.7 t 3.2% peak-to-peak value, 95.2 t 1.8% root mean square value) of the waveform can be explained solely by left ventricular contraction. The right ventricular pressure waveform was dependent on both left and right ventricular contraction. However, the left ventricular free wall septal component of right ventricular pressure was significantly
greater than the right ventricular free wall component of right ventricular pressure (63.5 t 10.9 vs. 36.5 t 10.9% peak-to-peak value; 65.2 t 10.4 vs. 34.8 t 10.4% root mean square value). Similarly, right ventricular volume outflow was a function of both a left and a right component. Again, the left ventricular free wall septal component was significantly greater than the right ventricular
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H1520
RIGHT
VENTRICULAR
DEPENDENCY
ON
LEFT
VENTRICLE
J
1
400 ms
Cofrelatnn
= 0 9991
6
50
Correlation
= 0.9931
Delay = .060
1
Correlation
50
= 0.9941
400 ms Correlation
50
= 0.9994
Delay = .1&l
Correlation
50
= 0.9929
Delay = .240
1
0 1 FIG. 6. Left and right components of LV and RV contraction were employed to reconstruct ventricular pressure waveforms and RV volume outflow at pacing delays of 60, 120, 180, and 240 ms. A: LV pressure; B: RV pressure; C: RV volume outflow. Circles, measured pressures; solid line, reconstructed pressures. Reconstructed pressures are very similar to measured pressure waveforms and RV volume outflow with high correlation coefficients.
free wall component (67.5 t 9.0 vs. 32.5 t 9.0% peak-topeak value; 68.3 t 8.9 vs. 31.8% root mean square value). In Table 1, all the sampled data are used to calculate the left and right components of pressure and flow. These left and right components were then tested on the same data set. To be sure this did not bias results, we used one
set of data to calculate the left and right component and tested the accuracy on another set of data. Table 2 summarizes the results. For the six studies, we used the data sampled at 0-, 40-, 80-. . .240-, and 280-ms delay between right atria1 and right ventricular pacing to determine the left and right ventricular components of left
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RIGHT
VENTRICULAR
I
ON LEFT
VENTRICLE
H1521
Correlation
= 0.9880
Delay = .120
Correlation
= 0.9867
Deiay = .240
1
400 ms
100.
DEPENDENCY
Cormlat ion = 0.9786
.f.. /I Delay = .1&l
FIG. 6. Continued.
TABLE 1. Comparison of L V and R V components for ventricular pressures and RV volume outflow
TABLE
2. Test of accuracy analysis Left
Parameter
Left Ventricular Pressure
Right Ventricular Pressure
Right Ventricular Volume-Outflow
Peak-to-peak value of 8.46k3.98 21.80t8.28 44.89k16.17 RV component Peak-to-peak value of 106.96&14.34* 37.80t9.12* 90.88t23.06* LV component RV component 7.35t3.22 36.49t 10.90 32.54t9.04 represents % LV component 92.65&3.22* 63.51&10.90* 67.46&9.04* represents % RMS value of RV 2.1 lt0.65 6.94k2.70 13.58k4.79 component RMS value of LV 42.82t5.70* 12.83&2.64* 28.82*7.83* component RV component 4.79k1.83 34.82t10.37 31.76t8.92 represents % LV component 95.22t1.83* 65.18k10.37' 68.25k8.92' represents % All data values are means * SD. LV, left ventricular; RV, right ventricular; RMS, root mean square. * P < 0.05, LV component significantly greater than RV component.
ventricular pressure and right ventricular pressure. We then tested the accuracy of these left and right ventricular components on the data obtained at ZO-, 60-, lOO. .300-ms delay. The correlation coefficients and absolute percent error between the measured and predicted ventricular pressures are presented. In each subset, these left and right ventricular components were tested on all the data (total), on the data sampled at 0, 40. . 280 ms (trained), and on the data sampled at 20, 60. . .300 ms (test). Table 2 shows no statistically significant differ-
Ventricular
Correlation coefficient
Pressure Absolute percent error
Right
Ventricular
Correlation coefficient
Pressure Absolute percent error
Total 0.992*0.013 3.35k2.65 0.929t0.059 3.60k1.71 Trained 0.992kO.013 3.OOk2.91 0.932t0.064 3.70t1.92 Test 0.991t0.013 3.58k2.56 0.925t0.060 3.52& 1.54 All data are means * SD. Total, all sampled time intervals; trained, data sampled at 0, 40 . . . 280 ms and used to calculate left and right component of pressure; test, data sampled at 20, 60 . . . 300 ms.
ences between the subsets. The analysis was as accurate when applied and tested on the same data (i.e., data sampled at 0,40. . .280 ms) as when tested on a different set of data (i.e., data sampled at 20, 60. . .300 ms). In four experiments, right atrial-to-right ventricular pacing interval was set to the measured control values (between 120 and MO ms). Left ventricular pressure, right ventricular pressure, and pulmonary blood flow were then recorded continuously while right ventricular free wall pacing was halted in diastole. The measurements of localized electrical activity and regional wall motion verified a cessation of right ventricular free wall electrical activity and active wall shortening on the subsequent contraction. Because preload or contractility was not altered, any developed right ventricular pressure or outflow demonstrates left ventricular assistance. The typical results are shown in Fig. 7. The first beat after the cessation of pacing showed a significant reduction in right ventricular developed pressure and volume outflow. For the four experiments, on the first beat after cessation of pacing, right ventricular neak svstolic nressure and
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H1522
RIGHT
VENTRICULAR
DEPENDENCY
volume outflow averaged 68 t 4 and 80 t 4%, respectively, of the values recorded on the preceding beat. Because the right ventricular free wall did not contract, observed right ventricular pressure development or outflow demonstrates a direct left ventricular free wall septal assistance to right ventricular systolic contraction. DISCUSSION
Because of ventricular interdependence, right ventricular systolic function should be very dependent on the left ventricle. In the present study, the contributions of left ventricular contraction to right ventricular developed pressure and volume outflow were examined with an electrically isolated right ventricular free wall preparation. This preparation enabled the right ventricular free wall and left ventricle to be independently paced. Accordingly, the timing interval between right and left ventricular contraction could be varied over a wide range. With the use of this preparation, both the right ventricular pressure and volume outflow waveforms were observed to have double peaks. Numerical analysis indicated that these pressures and volume waveforms were due to two components. One component could be directly related to right ventricular free wall contraction, whereas the latter component was directly attributable to left ventricular contraction. Furthermore, the numerical analysis indicated that left ventricular contraction was more important than the right ventricular free wall contraction for right ventricular pressure development and volume outflow. The influence of left ventricular conRA ELECTROGRAM
LV ELECTROGRAM
RV ELECTROGRAM
LV PRESSURE (mmHg)
'O" o
RV
PA FLOW (cc /set I
180
I
0 FIG. 7. Local electrograms, LV pressure, RV pressure, and pulmonary blood flow were recorded while RV pacing was discontinued. First beat after cessation of pacing shows considerable RV pressure development and volume outflow, without RV free wall contraction.
ON
LEFT
VENTRICLE
traction was further demonstrated when right ventricular free wall pacing was halted in diastole. More than 65% of the pressure development and volume outflow OCcurred on the first beat after the cessation of pacing. These data clearly indicate a normally present significant left ventricular assistance to right ventricular contraction. Mechanism and comparison to literature. Recently, several studies have examined potential mechanisms for this left ventricular assistance. Little and colleagues (17) considered the ventricle to be divided into two compartments. One compartment, composed of the intraventricular septum, has as its external pressure the contralateral ventricular pressure. The other compartment, composed of the left ventricular free wall, has as its external pressure the pericardial pressure. Using another approach, Sunagawa and colleagues (19, 30) proposed that the properties of one ventricle were partially a function of the properties of the contralateral ventricle. We analyzed ventricular interdependence based on the balance of forces across the septum (23, 24). Interestingly, all three studies showed that the transfer of pressure from the left to the right ventricle could be expressed as the relative ratios of the septal, left ventricular free wall, and right ventricular free wall elastances. Thus, at least on a theoretical basis, left ventricular systolic pressure can affect right ventricular systolic pressure. This effect will depend on the relative wall characteristics and the contraction of both the interventricular septum and left ventricular free wall. Several studies (8, 14, 18, 27) have measured the systolic gain or cross talk between the ventricles. In general, these studies have measured the changes in systolic pressure caused by abrupt changes in afterload of the opposite ventricle. The studies show that the rightto-left ventricular gain is larger than the left-to-right ventricular gain. Right-to-left ventricular systolic gains ranged from 13.6 to 34.5%, whereas left-to-right ventricular systolic gains ranged from 8.6 to 14% (8, 14, 18, 27). On a philosophical point, systolic gains do not directly indicate the relative importance of interdependence. For example, if the left-to-right gain was 10% and the rightto-left gain was 30%, one might assume that systolic ventricular interdependence is more important for left ventricular systolic function. However, if one examines the absolute magnitude of this cross talk, the conclusions are totally different. This is because left ventricular systolic pressure is much greater than right ventricular systolic pressure. If we assume that all the left ventricular systolic pressure (120 mmHg, for example) is transmitted (10%) to the right ventricle, then 12 mmHg (or -50%) of the total measured right ventricular pressure was generated by the left ventricle. Thus the studies that measured systolic gains imply a large (50%) left ventricular contribution to right ventricular systolic pressure, similar to the results of the present study. Finally, this study implies that this left ventricular assist is from the entire left ventricle (left ventricular free wall plus septum). Comparison to our previous studies shows that ventricular interdependence involves the whole ventricle. In diastolic ventricular interdependence
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RIGHT
VENTRICULAR
DEPENDENCY
studies, changing left ventricular volume or pressure alters right ventricular filling characteristics (2). Furthermore, changing left ventricular free wall compliance also altered right ventricular filling characteristics (26). In whole animal studies, rapid abrupt changes in left ventricular systolic pressure caused immediate changes in right ventricular systolic pressure (32). In isolated heart preparations, right ventricular developed pressure was dependent on left ventricular free wall function. Ischemia, restricted solely to the left ventricular free wall, decreased right ventricular developed pressure (25). Cutting the left ventricular free wall from the base to apex decreased right ventricular developed pressure by >60%. Interestingly, resuturing the left ventricular free wall reestablished right ventricular developed pressure (16). Stiffening the left ventricular free wall or interventricular septum with glutaraldehyde injection depressed right ventricular developed pressure (16). Thus the results of this study and previous studies show that the left component of right ventricular pressure and volume outflow is composed of both left ventricular free wall and septal contractions. This ventricular interdependence is probably due to stresses in the muscle fibers influencing both the right and left ventricles. The myocardial stress would influence the pressure development and volume outflow as measured in the present study. Implications. The analysis or assessment of right ventricular function has been difficult and problematic. The complex shape of the right ventricle has made detailed volume determinations difficult. The results of the present study suggest that even with accurate volume measurements the assessment of right ventricular function will be complicated by the status of the left ventricle. If a significant portion of the measured right ventricular pressure and volume outflow is actually generated by the left ventricle, then any change in left ventricular volume or functional status will alter the assessment of right ventricular function. Critique of methods. The potential technical limitations of this study need to be kept in mind. The effects of right ventricular free wall isolation procedure have been examined in several previous studies (3-6, 31). Myocardial blood flow to the right ventricular free wall has been shown in this laboratory to be well preserved (5). The electrophysiological properties of the right ventricular free wall, including pacing threshold, refractory period, and conduction velocity, also remain unchanged (4). The procedure does not affect normal atrioventricular conduction. In this study regional myocardial function was examined utilizing piezoelectric crystals. Systolic function was assessed by evaluating the relationship between enddiastolic length and stroke work. The systolic properties of the left and right ventricles, as assessed by this index, were unchanged after right ventricular isolation. However, our use of a global parameter, left ventricular dP/ dt, to establish the timing of regional shortening might have influenced our analysis of regional wall motion. Also, the unstressed diastolic myocardial segment length changed probably due to geometrical rearrangements. The isolated right ventricular free wall, despite a preservation of most rheologic. electrophvsioloeical. and
ON
LEFT
H1523
VENTRICLE
functional properties, represents a preparation that is markedly different from the intact heart and may have biased our results. Subtle right ventricular dysfunction in this model may have led to an underestimation of the contribution of the right ventricular free wall to overall right ventricular pressure development and volume outflow. However, even if this study did underestimate the relative contribution of the right ventricular free wall, this would not detract from the principal finding of this study that right ventricular systolic function is significantly dependent on the left ventricle. For example, assuming that we overestimated by 50% the left ventricular contribution, this would still mean that 30-35% of the measured right ventricular pressure and volume outflow were generated by the left ventricle. A final limitation of this model is that it does not truly isolate the entire right ventricle but simply the right ventricular free wall from the remainder of the heart. Thus these findings examine the interdependent contribution of the right ventricular free wall versus the left ventricle and septum rather than the right versus the left ventricle. Even when this shortcoming is considered, these data clearly demonstrate the importance of left ventricular and septal contraction to right ventricular performance. The authors thank Joye Zafuto and April L. Jackson for careful preparation of this manuscript. This study was supported in part by National Heart, Lung, and Blood Institute Grant HL-36051. Address for reprints requests: R. J. Damiano, Jr., Dept. of Cardiothoracic Surgery, Medical College of Virginia, PO Box 68, Richmond, VA 23298. Received
10 December
1990; accepted
in final
form
12 June
1991.
REFERENCES 1. BAKOS, A. C. P. The question of the function of the right ventricular myocardium: an experimental study. Circulation 1: 724-732, 1950. 2. BOVE, A. A., AND W. P. SANTAMORE. Ventricular interdependence. Prog. Cardiovasc. Dis. 23: 365-388, 1981. 3. Cox, J. L., G. H. BARDY, R. J. DAMIANO, JR., L. D. GERMAN, J. M. FEDOR, J. A. KISSLO, L. PACKER, AND J. J. GALLAGHER. Right ventricular isolation procedures for nonischemic ventricular tachycardia. J. Thorac. Cardiovasc. Surg. 90: 212-224, 1985. 4. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., AND J. L. COX. Right ventricular free wall isolation: effects on regional myocardial blood flow. Ann. Thorac. Surg. 46: 391-395, 1988. 5. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., AND J. L. COX. The functional consequences of right ventricular isolation. J. Thorac. Cardiovasc. Surg. 100: 569-579, 1990. 6. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., J. M. DOUGLAS, JR., AND J. L. Cox. Electrophysiologic effects of surgical isolation of the right ventricle. Ann. Thorac. Surg. 42: 65-72, 1986. 7. DONALD, D. E., AND H. E. ESSEX. Pressure studies after inactivation of the major portion of the canine right ventricle. An. J. Physiol. 176: 155-161, 1954. 8. ELIZINGA, G., R. VAN GRONDELLE, N. WESTERHOF, AND G. C. VAN DEN BOS. Ventricular interference. Am. J. Physiol. 226: 941947,1974. 9. ERHARDT, L. F. Right ventricular involvement in acute myocardial infarction. Eur. J. Cardiol. 4: 411-418, 1976. 10. FENELEY, M. P., T. P. GAVAGHAN, D. W. BARON, J. A. BRANSON, P. R. ROY, AND J. J. MORGAN. Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart. Circulation 71: 473-481,1985.
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11. GOLDSTEIN, J. A., G. J. VLAHAKES, E. D. VERRIER, N. B. SCHILLER, J. V. TYBERG, T. A. PORTS, W. W. PARMLEY, AND K. K. CHATTERJEE. The role of right ventricular systolic dysfunction and elevated interpericardial pressure in the genesis of low output in experimental right ventricular infarction. Circulation 65: 513521,1982. 12. GUIHA, N. H., C. J. LIMAS, AND N. J. COHN. Predominant right ventricular dysfunction after right ventricular destruction in the dog. Am. J. Cardiol. 33: 254-258, 1974. 13. KAGAN, A. Dynamic responses of the right ventricle following extensive damage by cauterization. Circulation 5: 816-823, 1952. 14. LANGILLE, B. L., AND D. R. JONES. Mechanical interaction between the ventricles during systole. Can. J. Physiol. Pharmacol. 55: 373-382,1977. 15. LEGRAND, V., P. RIGO, J. P. SMEETS, J. C. DEMOULIN, P. COLLIGNON, AND H. E. KULBERTUS. Right ventricular myocardial infarction diagnosed by 99 m technetium pyrophosphate scintigraphy: clinical course and follow-up. Eur. Heart J. 4: 9-19, 1983. 16. LI, K. S., W. E. JOHNSTON, AND W. P. SANTAMORE. Contribution of each wall to right ventricular function (Abstract). FASEB J. 4: A821,1990. 17. LITTLE, W. C., F. R. BADKE, AND R. A. O’ROURKE. Effect of right ventricular pressure on the end-diastolic left ventricular pressurevolume relationship before and after chronic right ventricular pressure overload in dogs without pericardia. Circ. Res. 54: 719730,1984. 18. MAUGHAN, W. L., A. A. SHOUKAS, K. SAGAWA, AND M. L. WEISFELDT. Instantaneous pressure-volume relationship of the canine right ventricle. Circ. Res. 44: 309-315, 1979. 19. MAUGHAN, W. L., K. SUNAGAWA, M. KRONENBERG, M. L. WEISFELDT, AND K. SAGAWA. Ventricular systolic interdependence: volume elastance model in isolated canine hearts. Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H1381-H1390, 1987. 20. MIDDELHOF, C. J., W. BUTHKEN, AND A. E. BECKER. Pure right ventricular infarction. Eur. Heart. J. 1: 369-374, 1980. 21. OBOLER, A. A., J. F. KEEFE, W. H. GAASCH, 3. S. BANAS, JR., AND H. J. LEVINE. Influence of left ventricular isovolumic pressure upon right ventricular pressure transients. Cardiology 58: 32-44, 1973.
ON
LEFT
VENTRICLE
22. RIGO, P., M. MURRAY, D. R. TAYLOR, M. L. WEISFELDT, D. T. KELLY, H. W. STRAUSS, AND B. PITT. Right ventricular dysfunction detected by gated scintophotography in patients with acute inferior myocardial infarction. Circulation 52: 268-274, 1976. 23. SANTAMORE, W. P., P. R. LYNCH, J. L. HECKMAN, A. A. BOVE, AND G. D. MEIER. Left ventricular effects on right ventricular developed pressure. J. Appl. Physiol. 41: 925-930, 1976. 24. SANTAMORE, W. P., AND L. PAPA. Alterations in diastolic ventricular interdependence due to myocardial infarction. Cardiouasc. Res. 22: 726-731,1988. 25. SANTAMORE, W. P., AND T. SHAFFER. Ventricular interdependence: theoretical and experimental model results. Proc. Cardiovast. System Dyn. Sot. 6: 33-36, 1984. 26. SANTAMORE, W. P., T. SHAFFER, AND D. HUGHES. A theoretical and experimental model of ventricular interdependence. Basic Res. Cardiol. 81: 529-537, 1986. 27. SLINKER, B. K., A. C. P. CHAGAS, AND S. A. GLANTZ. Chronic pressure overload hypertrophy decreases direct ventricular interaction. Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H347-H357, 1987. 28. SNEDECOR, G. W., AND W. G. COCHRAN. Statistical Methods. Ames: Iowa State Univ., 1967, p. 186. 29. STARR, I., W. A. JEFFERS, AND R. H. MEADE. The absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am. Heart J. 26: 291-301, 1943. 30. SUNAGAWA, K., W. L. MAUGHAN, M. L. WEISFELDT, AND K. SAGAWA. Effect of systolic transseptal pressure on septal elastance and ventricular cross talk (Abstract). Circulation 64, Suppl. IV: 180,198l. 31. WALLACE, A. G., M. S. SPACH, E. M. ESTES, AND J. P. BOINEAR. Activation of the normal and hypertrophied human right ventricle.
Am. Heart J. 75: 728-735,1968. 32. YAMAGUCHI, S., AND W. P. SANTAMORE. in systolic ventricular interdependence A1026, 1990.
Comparative (Abstract).
significance
FASEB J. 4:
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DAMIANO, RALPH J., JAMES E. LOWE,
L. Cox,
JR., PAUL LA FOLLETTE, AND
WILLIAM
P.
JR., JAMES
SANTAMORE.
Sig-
nificant left ventricular contribution to right ventricular systolic function. Am. J. Physiol. 261 (Heart Circ. Physiol. 30): HM4-
H1524, 1991.-To examine the importance of systolic ventricular interdependenceon right ventricular function, we used a unique electrically isolated right ventricular free wall preparation. Double-peakedwaveforms for right ventricular pressure and pulmonary arterial blood flow occurred over a wide range of pacing intervals between the left and right ventricles. One component of the waveforms could be directly related to right ventricular free wall contraction, whereasthe other component was directly related to left ventricular and septal contraction. For left ventricular pressure, the left ventricular component was significantly larger than the right ventricular free wall component (92.7 t 3.2 vs. 7.3 & 3.2% peak-to-peak value, P < 0.01). For right ventricular pressure,the left ventricular and septal component wassignificantly greater than the right ventricular component (63.5 t 10.9 vs. 36.5 t 10.9%peak-to-peak value, P < 0.05). Similarly, for pulmonary arterial blood flow, the left ventricular component was significantly greater than the right ventricular component. When right ventricular free wall pacing stopped in diastole, 68 t 4% of right ventricular systolic pressureand 80 t 4% of pulmonary flow were obtained in the subsequentbeat. The results of this study indicate that left ventricular contraction is very important for right ventricular developedpressureand volume outflow. ventricular interdependence;cardiac mechanics;left ventricle; right ventricle FUNCTION of the right ventricle has been questioned since Starr and co-workers (29) demonstrated that severe damage to the right ventricular free wall does little to impair right ventricular pressure development. Extending this work, Kagan (13) in acute experiments on dogs destroyed most of the free wall of the right ventricle by cauterization. This destruction of the free wall had little effect on arterial and peripheral venous pressure. Donald and Essex (7) injected vinyl acetate into the right coronary arteries of dogs, thereby destroying -80% of the right ventricular free wall. This massive damage of the free wall caused no observable decrease in the ability to exercise; indeed, all the dogs showed an increase in the degree of work with training. Bakos (1) postulated that right ventricular function was maintained by the assistance of the left ventricle,
THE INDEPENDENT
H1514
whereas others postulated that the surviving fibers in the right ventricular free wall were sufficient to maintain right ventricular function. Consistent with the concept of left ventricular assistance to right ventricular contraction, Oboler and colleagues (21) observed experimentally that the derivative of right ventricular pressure was broad or double peaked, with one peak occurring coincidentally with the peak in the first time derivative of the left ventricular pressure (dP/dt ). Variations in electrical stimulation caused by bundle branch blocks further separated the right ventricular peaks, with one peak always coinciding with left ventricular peak dP/dt. In a complementary clinical study, Feneley and colleagues (10) demonstrated that in patients with conduction abnormality, one right ventricular peak always corresponded to the peak or maximum rate of left ventricular developed pressure. While the above studies suggest an important contribution of left ventricular contraction to right ventricular systolic function, they have significant shortcomings. Studies on right ventricular free wall damage are subject to multiple interpretations. Incomplete right ventricular free wall damage may have occurred and could imply that the right ventricular function was maintained by the surviving right ventricular fibers. Additionally, right ventricular function was poorly quantitated. More recent studies have demonstrated significant right ventricular dysfunction after right ventricular injury (11, 12). In their studies, Oboler et al. (21) and Feneley et al. (10) could observe only limited time variations in right and left ventricular pacing. More importantly, these studies provided no insight into the magnitude of this possible left ventricular assistance. To quantify this dependency of right ventricular function on the left ventricle, we utilized an electrically isolated right ventricular free wall preparation (3-5). This preparation allowed for wide controlled variations in the timing interval between right ventricular and left ventricular contractions. Utilizing this preparation, we observed very apparent double-peaked waveforms for both right ventricular pressure and right ventricular volume outflow. Numerical analysis indicated that right ventricular pressure and volume outflow waveforms were due to two components. One component could be directly related to right ventricular free wall contraction, whereas the other component was directly attributable to left and
0363-6135/91 $1.50 Copyright 0 1991 the American Physiological Society
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RIGHT
VENTRICULAR
DEPENDENCY
septal ventricular contraction. Furthermore, the analysis indicated that the left ventricular component was significantly greater than the right ventricular component for the right ventricular pressure and volume outflow. METHODS
Six adult mongrel dogs weighing from 25 to 35 kg were anesthetized with intravenous pentobarbital sodium (30 mg/kg) and were then maintained on a continuous intravenous infusion of 2 mg/min throughout each experiment. A median sternotomy was performed, and the heart was suspended in a pericardial cradle. Lead II of the peripheral electrocardiogram was monitored continuously. Multiple bipolar epicardial pacing and sensing electrodes were sutured to the right atrium, right ventricle, and left ventricle (Fig. 1). Right ventricular bipolar epicardial pacing electrodes were placed over the trabecular zone of the right ventricle, adjacent to the septum, and approximately midway between the pulmonary valve and the ventricular apex. This electrode placement was chosen to mimic as closely as possible the site of earliest epicardial activation of the normal right ventricle (31). The right ventricular bipolar recording electrodes were placed near the atrioventricular groove approximately midway between the pulmonary valve and the apex. The left ventricular bipolar electrodes were placed at the left ventricular apex. The sinoatrial node was identified and excised in all animals so that each animal could be paced during the study at a uniform heart rate of 150 beats/ min. Stimulus strength was twice the diastolic threshold, and pulse duration was 2.0 ms. All electrograms were filtered with Hewlett-Packard high-gain bioelectric amplifiers with a high-pass frequency of 0.5 Hz and a lowpass frequency of 1 kHz. Right and left ventricular pressures were monitored
\
TEMPERATURE
J
AORTIC PRESSURE
L
‘/
\’
FIG. 1. Schematic diagram of experimental protocol. RA, right atrial; RV, right ventricular; LV, left ventricular; PA, pulmonary arterial. Bipolar epicardial pacing and sensing electrodes-were sutured to right atrium, right ventricle, and left ventricle. RV and LV pressures were monitored with micromanometer-tipped transducers. Pulmonary blood flow was monitored with electromagnetic flow probe.
ON
LEFT
VENTRICLE
H1515
with high-fidelity Millar micromanometer-tipped pressure transducers. Right atria1 and central aortic pressures were monitored with fluid-filled catheters and Statham P23l D pressure transducers. An electromagnetic flow probe was placed around the main pulmonary artery, and flow was displayed on a Howell HMSlOOO blood flow meter (Howell Instruments, Camarilla, CA). Regional pulse transit piezoelectric crystals (1.5 mm OD, Vernitron no. l-l015-5A, Bedford, OH) were implanted in the subendocardium of the right ventricular and left ventricular free wall. The right ventricular pair was aligned loto 15-mm apart parallel to the atrioventricular groove and midway between the pulmonary valve and the ventricular apex. The left ventricular pair was aligned in the minor axis circumference midway between the base and apex. The piezoelectric transducer connectors were attached directly to a sonomicrometer constructed in our laboratory. The sonomicrometer had a sampling rate of 1,000 Hz with a frequency response of O-50 Hz. Minimal resolution was 0.08 mm, and maximal electronic drift was 0.05 mm/h. All physiological signals were recorded continuously and displayed on an 8-channel oscilloscope. Blood temperature was measured by a thermistor in the inferior vena cava. The femoral artery was cannulated for arterial perfusion, and the vena cavae were cannulated individually for venous return to the cardiopulmonary bypass unit. The azygous vein was ligated. Serum potassium and arterial blood gases were determined at regular intervals during each study. During all periods of data acquisition, systemic temperature was maintained at 37”C, and serum potassium levels were kept between 3.5 and 4.5 meq/l. All animals were then subjected to right atria1 bipolar epicardial pacing. The right atria1 to left ventricular conduction time was calculated in each animal during right atria1 pacing. Regional systolic function and unstressed myocardial segment length (L,) were then assessed by recording data continuously during volume loading and rapid vena cava occlusion. Heparin was administered (100 U/kg), and the animals were placed on cardiopulmonary bypass. Asanguinous priming solution and pediatric Shiley model lOOA bubble oxygenators were used. The animals were perfused at flow rates of 2.0-2.5 lmin-’ *mm*, adjusted to maintain mean aortic perfusion pressure at 70-100 mmHg. A full-thickness right ventriculotomy was made adjacent and parallel to the ventricular septum, extending from the anterior pulmonary valve annulus, around the apex of the heart, and back to the posterior tricuspid valve annulus (Fig. 2). A separate incision was then made from the posterior aspect of the pulmonary valve annulus, across the supracrystal ventricular septum, and down to the anterior tricuspid valve annulus. To complete the isolation and ablate all remaining interventricular fibers, cryolesions were placed at each end of both incisions with a g-mm diameter cryoprobe cooled to -60°C with internally expanding nitrous oxide. Each ventriculotomy was then closed with a continuous 4-O nonabsorbable suture. The animals were allowed to recover for 30 min. The animals were then weaned from cardiopulmonary bvpass and allowed to stabilize hemodynamically. All
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H1516
RIGHT
FIG. 2. was made was made muscle in tached to
VENTRICULAR
DEPENDENCY
Surgical technique for RV isolation. Right ventriculotomy adjacent and parallel to ventricular septum. Separate incision across supracrystal ventricular septum. Anterior papillary canine right ventricle (unlike that in human heart) is atseptum rather than to RV free wall.
data were recorded with the pericardium open. After this operation, the left ventricle and right ventricular free wall were electrically isolated and could be paced independently. This was accomplished without altering normal right atria1 to left ventricular conduction through the intact atrioventricular node (4-6). Regional systolic function and L, were reexamined utilizing volume loading and vena cava occlusions. The hemodynamic effects of varying the right atria1 and right ventricular pacing interval were examined. The interval between right atria1 and right ventricular pacing was increased from 0 to 300 ms in 20-ms increments. With a O-s delay, the right ventricular free wall contracted simultaneously with the atria and more than 100 ms before the left ventricle, which was activated through normal atrioventricular nodal conduction. With a delay of 300 ms, the right ventricular free wall was contracting more than 100 ms after the left ventricle. At each increment in pacing, all hemodynamic data were recorded. Sufficient time was allowed between each pacing interval to obtain hemodynamic stability. After this experimental protocol was completed, right ventricular pacing was ceased, and all hemodynamic data were recorded. After each experiment, the right atria1 waveform was carefully examined to ensure that tricuspid valve function was unaffected by the operative procedure. The animals were then killed with an overdose of pentobarbital sodium, and the hearts were examined. DATA
ANALYSIS
Regional function. Physiological data were filtered with a SO-Hz low-pass analog filter, recorded on analog tape,
ON LEFT
VENTRICLE
and digitized with a sampling rate of 200 Hz by an ADAC A/D converter. Data were stored on magnetic tape, and analyses were performed on a DEC PDP 11/23 microprocessor using interactive programs developed in our laboratory. The dP/dt was determined using a &point polyorthogonal transformation of the digital left ventricular waveform. The cardiac cycle was defined using dP/dt. Diastole was defined as beginning at the first zero crossing of dP/ dt after peak negative dP/dt and ending 40 ms before peak positive dP/dt. Beginning ejection was placed 20 ms after peak positive dP/dt, and end ejection was set 40 ms before peak negative dP/dt. Ejection shortening was calculated as the change in myocardial segment length over the ejection period. The L, was determined from vena caval occlusion data as the length at a left ventricular pressure of 0 mmHg. L, was defined at beginning diastole where dP/dt was zero. Right ventricular stroke volume was defined as the area under the pulmonary flow trace. An index of stroke work was determined as follows: (right ventricular peak systolic pressure - right ventricular mean diastolic pressure) X stroke volume x 0.0136. A one-way analysis of variance was used to compare repeated measurements over time. Variability in L, was expressed as the variance not attributable to variance between dogs or between times. Linear regressions were compared by the method of Snedecor and Cochran (28). Numerical analysis. To examine systolic ventricular interdependence, we hypothesized that the measured right ventricular pressure and volume outflow were the sum of two components, a contribution from the right ventricle and a contribution from the left ventricle. The actual data consisted of measured left and right ventricular pressures and pulmonary blood flow generated by pacing the ventricles at the same rate but with a series of different delays between the stimulation of the left and right ventricles. These delays were of the form Od, 2d, 3d. . .Nd, where d equaled 20 ms. This gave us two families of measured pressure functions: the pressure measured in the left ventricle when the interventricular delay was kd [m&t)] and the pressure measured in the right ventricle when the interventricular delay was kd [mHk(t)]. These pressure measurements were assumed to be sampled values of periodic functions with the period inversely related to the heart rate. Again, we hypothesized that the measured pressure in the right ventricle was the sum of two components: a contribution from the right ventricle [r(t)] and a contribution from the left ventricle [l(t)], plus errors in the measurements [edt)]. Thus by our hypothesis mrlk(t)
= l(t) + r(t - kd) - ek(t)
(1)
or, equivalently ek(t) = l(t) + r(t - kd) - mak(t)
To estimate these hypothesized left and right components, we first took the Fourier transform of Eq. 1, yielding Ek(u) = L(w) + e-lUkdR(w) - MR~(w)
(2)
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RIGHT
VKNTRICULAR
We solved for R and L to minimize over all the pacing delays
DEPENDENCY
the error function
kio sm EkbYQW = kio lm Straightforward to this problem that minimized
[L(o) + emiwkdR(w) - M,tk(~)2d~]
application of the calculus of variations indicated that the estimates for R and L this expression were given by
(N + l)R(w) + L(w) i
emwM -
$ M~k(u)
k=il
k=O
(3)
N
R(o)
g erwkd+ (IV + l)L(o)
= C Mm(o)e
k=O
rwkd
k=O
From the strip chart record, the actual physiological data were traced on a digitizer tablet (True Grid, Houston Instruments), digitized at 200 samples/s (or 75 samples/ heartbeat), and stored in an Apple II+ microcomputer (Apple Computer, Cupertino, CA). The data files were A
CONTROL
ON
LEFT
H1517
VENTRICLE
transferred to an IBM computer for the remainder of the data analysis. To facilitate the calculation of the discrete Fourier transform, these sampled data were interpolated to provide 64 evenly spaced samples per period. Two periods worth of these interpolated data were created for each of 16 different interventricular pacing delays (0, 20. . .300 ms). The equations (3) were then applied to calculate the left and right components of the measured right ventricular pressure. Analogous equations were used to find the left and right components of the left ventricular pressure (which we expected to consist primarily of a left component) and the left and right components of the right ventricular volume outflow. r(t) and l(t) were calculated and then recombined to determine how well the functions represented the original data. For each delay kd, we calculated C,,(t) = l(t) + r(t - kd) + ek. These recalculated waveforms were then plotted along with the original measured points so that we could determine how well the calculated data fit the original measurements. In each experiment, for left ventricular pressure, right ventricular pressure, and pulmonary arterial blood flow, the peakto-peak values for the right and left ventricular compo160ms
180ms
18 RV SEGMENTAL WALL MOTION (mm) 9 100 RV PRESSURE CmmHg) 0 18 LV SEGMENTAL WALL MOTION (mm)
9
200 LV PRESSURE (mmlig) 0 178 PA FLOW (cc/set)
I3 PRE ----POST
//
/
i FIG. 3. A: typical segmental shortening in RV free wall. b/t: control data; right: data after RV free wall isolation and 160- and 180.ms delay between RA and RV pacing. B: plots for 6 experiments of regional RV wall shortening vs. end-diastolic Length. Two curves are presented: pre- and post-RV free wall isolation. Slope of segment shortening vs. end-diastolic length (EDL) was unaltered by RV isolation. However, unstressed myocardial segment length was shlfted to right. SW, stroke work.
SW=-6977t496EDt
jSW=-9378t6llEDL
04
I , , I3 END-DIASTOLIC ,
II
,
~
,
15
,
, I9
LENGT;:MMI
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HE18
RIGHT
VENTRICULAR
DEPENDENCY
nents and the root mean square value for the right and left ventricular components were calculated. RESULTS
Right ventricular isolation was successfully performed in every animal. There were no detrimental effects of the procedure on pulmonary or tricuspid valve function as documented by careful examination of right atrial, right ventricular, and pulmonary arterial pressure waveforms. After the procedure, the isolated right ventricular free wall, when not paced, was either electrically silent or exhibited a slow idioventricular rhythm between 10 and 20 beats/min. The right atrial-to-left ventricular conduction interval was 121 t 5 ms preoperatively and 123 t 7 ms postoperatively (P = NS). Figure 3A shows a typical right ventricular segmental wall motion curve. In Fig. 3A, the control data are shown before surgery at left while data are shown after right ventricular free wall isolation at right. Note for this typical example the similarity in the segmental wall motion curves. The end-diastolic lengths and segmental shortening were almost identical between control and after right ventricular free wall isolation. For the group data, analysis of right ventricular regional systolic function was performed by analyzing the relationship between end-diastolic length and stroke work. The linear regression analysis of all six experiments before and after right ventricular free wall isolation revealed that the slope of this relationship was not changed by this procedure (Fig. 3B). L, was shifted in these animals from 11.9 t 0.1 to 13.3 t 0.1 (P C 0.03). This change in L,, however, resulted in no significant change in the slope of the linear regression (P > 0.05). An analysis of left ventricular regional myocardial function revealed no significant change in either L, or in the slope of the relationship between stroke work and end-diastolic length. The left ventricular pressure, right ventricular pressure, and pulmonary blood flow from one experiment are shown in Fig. 4. The interval between right atria1 and right ventricular pacing was increased in 2O-ms increments from 0 to 300 ms. The data at 60, 120, 180, and 240 ms are presented in Fig. 4. When the right ventricular RA-RV 60 MSEC
RA-RV 120 MSEC
ON
LEFT
VENTRICLE
free wall contracts before the left ventricle (60 ms), right ventricular pressure and pulmonary blood flow show double-peaked waveforms. This double peak disappears when the right and left ventricles contract synchronously at 120 ms. Because the right ventricular free wall contracts later than the left ventricle (as the pacing delay is increased beyond 120 ms), the right ventricular pressure waveform and pulmonary blood flow waveform again develop double peaks with one peak occurring later. Figures 5 and 6 show the data analysis for Fig. 4. The ventricular pressures and pulmonary blood flow waveforms were digitized at each pacing interval. Then after we assumed that each waveform was composed of a right ventricular free wall component and a left ventricular free wall plus septal component, the computer calculated these components to minimize the error function. Figure 5A presents the left and right components of left ventricular pressure. As anticipated, most of the left ventricular pressure, especially during systole, can be attributed to the left ventricular free wall septal component, the left ventricular contraction. The right ventricular free wall component, right ventricular contraction, had only a minimal contribution to left ventricular systolic pressure. Figure 5B presents the left and right components for right ventricular pressure. As indicated in Fig. 5B, the left ventricular free wall septal component (left ventricular contraction) is larger than the right ventricular free wall component. Thus, for this experiment, most of the right ventricular systolic pressure could be attributed to left ventricular contraction. Figure 5C presents the left and right components of right ventricular volume outflow. Similar to right ventricular pressure, most of right ventricular volume outflow can be directly attributed to left ventricular free wall septal contraction. In Fig. 6, the left and right components were used to reconstruct the ventricular pressure waveforms and right ventricular volume outflow at 60, 120, 180, and 240 ms. The reconstructed waveforms were very similar to the actual data with high correlation coefficients. For the six experiments, Table 1 presents the statistical analysis for the left and right components for the ventricular pressures and right ventricular outflow. For RA-RV 180 MSEC
RA-RV 240 MSEC
RV
FIG. 4. Local electrograms, LV 240-ms delays between RA and waveforms with 1 peak occurring are again double peaked but with
pressure, RV pressure, and RV volume outflow are presented at 60-, 120-, MO-, and RV pacing. At 60-ms delay, RV pressure and volume outflow are double-peaked before LV pressure. At 240-ms delay, RV pressure and volume outflow waveforms 1 peak occurring after LV development.
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RIGHT
VENTRICULAR
DEPENDENCY
ON
LEFT
B
A CASE LEFT 125mm
Hg
S216 CCNlPWENT
OF
LEFT
PRESSURE 1Smm
-
Hg
HE519
VENTRICLE CASE LEFT
916 COllPONENT
(Y
RIGHT
PRESSURE
-
O-
RIGHT 75mm
Hg
COWONENT
OF
LEFT
RIGHT
PRESSURE
,
15mm
1
Hg
COWONENT
OF
RIGHT
PRESURE
-
OI
CRSE LEFT
400
S216 COWWENT
OF
ms
PuCHOtMY
t
I
COCPWNT
I
OF
PlMOMRY
400 ms
ms
I
FLOU
FIG.
RIGHT
400
analysis, and right apparent, nent. B outflow, left and
FLOU
5. Computer analysis pressure and volume components. A: left vast majority of LV and C: left and right respectively. Both RV right components.
of data in Fig. 3. With the use of numerical outflow waveforms were separated into left and right components for LV pressure. As is pressure can be associated with left compocomponents for RV pressure and volume pressure and volume outflow have significant
I
left ventricular pressure, the vast majority (92.7 t 3.2% peak-to-peak value, 95.2 t 1.8% root mean square value) of the waveform can be explained solely by left ventricular contraction. The right ventricular pressure waveform was dependent on both left and right ventricular contraction. However, the left ventricular free wall septal component of right ventricular pressure was significantly
greater than the right ventricular free wall component of right ventricular pressure (63.5 t 10.9 vs. 36.5 t 10.9% peak-to-peak value; 65.2 t 10.4 vs. 34.8 t 10.4% root mean square value). Similarly, right ventricular volume outflow was a function of both a left and a right component. Again, the left ventricular free wall septal component was significantly greater than the right ventricular
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H1520
RIGHT
VENTRICULAR
DEPENDENCY
ON
LEFT
VENTRICLE
J
1
400 ms
Cofrelatnn
= 0 9991
6
50
Correlation
= 0.9931
Delay = .060
1
Correlation
50
= 0.9941
400 ms Correlation
50
= 0.9994
Delay = .1&l
Correlation
50
= 0.9929
Delay = .240
1
0 1 FIG. 6. Left and right components of LV and RV contraction were employed to reconstruct ventricular pressure waveforms and RV volume outflow at pacing delays of 60, 120, 180, and 240 ms. A: LV pressure; B: RV pressure; C: RV volume outflow. Circles, measured pressures; solid line, reconstructed pressures. Reconstructed pressures are very similar to measured pressure waveforms and RV volume outflow with high correlation coefficients.
free wall component (67.5 t 9.0 vs. 32.5 t 9.0% peak-topeak value; 68.3 t 8.9 vs. 31.8% root mean square value). In Table 1, all the sampled data are used to calculate the left and right components of pressure and flow. These left and right components were then tested on the same data set. To be sure this did not bias results, we used one
set of data to calculate the left and right component and tested the accuracy on another set of data. Table 2 summarizes the results. For the six studies, we used the data sampled at 0-, 40-, 80-. . .240-, and 280-ms delay between right atria1 and right ventricular pacing to determine the left and right ventricular components of left
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RIGHT
VENTRICULAR
I
ON LEFT
VENTRICLE
H1521
Correlation
= 0.9880
Delay = .120
Correlation
= 0.9867
Deiay = .240
1
400 ms
100.
DEPENDENCY
Cormlat ion = 0.9786
.f.. /I Delay = .1&l
FIG. 6. Continued.
TABLE 1. Comparison of L V and R V components for ventricular pressures and RV volume outflow
TABLE
2. Test of accuracy analysis Left
Parameter
Left Ventricular Pressure
Right Ventricular Pressure
Right Ventricular Volume-Outflow
Peak-to-peak value of 8.46k3.98 21.80t8.28 44.89k16.17 RV component Peak-to-peak value of 106.96&14.34* 37.80t9.12* 90.88t23.06* LV component RV component 7.35t3.22 36.49t 10.90 32.54t9.04 represents % LV component 92.65&3.22* 63.51&10.90* 67.46&9.04* represents % RMS value of RV 2.1 lt0.65 6.94k2.70 13.58k4.79 component RMS value of LV 42.82t5.70* 12.83&2.64* 28.82*7.83* component RV component 4.79k1.83 34.82t10.37 31.76t8.92 represents % LV component 95.22t1.83* 65.18k10.37' 68.25k8.92' represents % All data values are means * SD. LV, left ventricular; RV, right ventricular; RMS, root mean square. * P < 0.05, LV component significantly greater than RV component.
ventricular pressure and right ventricular pressure. We then tested the accuracy of these left and right ventricular components on the data obtained at ZO-, 60-, lOO. .300-ms delay. The correlation coefficients and absolute percent error between the measured and predicted ventricular pressures are presented. In each subset, these left and right ventricular components were tested on all the data (total), on the data sampled at 0, 40. . 280 ms (trained), and on the data sampled at 20, 60. . .300 ms (test). Table 2 shows no statistically significant differ-
Ventricular
Correlation coefficient
Pressure Absolute percent error
Right
Ventricular
Correlation coefficient
Pressure Absolute percent error
Total 0.992*0.013 3.35k2.65 0.929t0.059 3.60k1.71 Trained 0.992kO.013 3.OOk2.91 0.932t0.064 3.70t1.92 Test 0.991t0.013 3.58k2.56 0.925t0.060 3.52& 1.54 All data are means * SD. Total, all sampled time intervals; trained, data sampled at 0, 40 . . . 280 ms and used to calculate left and right component of pressure; test, data sampled at 20, 60 . . . 300 ms.
ences between the subsets. The analysis was as accurate when applied and tested on the same data (i.e., data sampled at 0,40. . .280 ms) as when tested on a different set of data (i.e., data sampled at 20, 60. . .300 ms). In four experiments, right atrial-to-right ventricular pacing interval was set to the measured control values (between 120 and MO ms). Left ventricular pressure, right ventricular pressure, and pulmonary blood flow were then recorded continuously while right ventricular free wall pacing was halted in diastole. The measurements of localized electrical activity and regional wall motion verified a cessation of right ventricular free wall electrical activity and active wall shortening on the subsequent contraction. Because preload or contractility was not altered, any developed right ventricular pressure or outflow demonstrates left ventricular assistance. The typical results are shown in Fig. 7. The first beat after the cessation of pacing showed a significant reduction in right ventricular developed pressure and volume outflow. For the four experiments, on the first beat after cessation of pacing, right ventricular neak svstolic nressure and
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H1522
RIGHT
VENTRICULAR
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volume outflow averaged 68 t 4 and 80 t 4%, respectively, of the values recorded on the preceding beat. Because the right ventricular free wall did not contract, observed right ventricular pressure development or outflow demonstrates a direct left ventricular free wall septal assistance to right ventricular systolic contraction. DISCUSSION
Because of ventricular interdependence, right ventricular systolic function should be very dependent on the left ventricle. In the present study, the contributions of left ventricular contraction to right ventricular developed pressure and volume outflow were examined with an electrically isolated right ventricular free wall preparation. This preparation enabled the right ventricular free wall and left ventricle to be independently paced. Accordingly, the timing interval between right and left ventricular contraction could be varied over a wide range. With the use of this preparation, both the right ventricular pressure and volume outflow waveforms were observed to have double peaks. Numerical analysis indicated that these pressures and volume waveforms were due to two components. One component could be directly related to right ventricular free wall contraction, whereas the latter component was directly attributable to left ventricular contraction. Furthermore, the numerical analysis indicated that left ventricular contraction was more important than the right ventricular free wall contraction for right ventricular pressure development and volume outflow. The influence of left ventricular conRA ELECTROGRAM
LV ELECTROGRAM
RV ELECTROGRAM
LV PRESSURE (mmHg)
'O" o
RV
PA FLOW (cc /set I
180
I
0 FIG. 7. Local electrograms, LV pressure, RV pressure, and pulmonary blood flow were recorded while RV pacing was discontinued. First beat after cessation of pacing shows considerable RV pressure development and volume outflow, without RV free wall contraction.
ON
LEFT
VENTRICLE
traction was further demonstrated when right ventricular free wall pacing was halted in diastole. More than 65% of the pressure development and volume outflow OCcurred on the first beat after the cessation of pacing. These data clearly indicate a normally present significant left ventricular assistance to right ventricular contraction. Mechanism and comparison to literature. Recently, several studies have examined potential mechanisms for this left ventricular assistance. Little and colleagues (17) considered the ventricle to be divided into two compartments. One compartment, composed of the intraventricular septum, has as its external pressure the contralateral ventricular pressure. The other compartment, composed of the left ventricular free wall, has as its external pressure the pericardial pressure. Using another approach, Sunagawa and colleagues (19, 30) proposed that the properties of one ventricle were partially a function of the properties of the contralateral ventricle. We analyzed ventricular interdependence based on the balance of forces across the septum (23, 24). Interestingly, all three studies showed that the transfer of pressure from the left to the right ventricle could be expressed as the relative ratios of the septal, left ventricular free wall, and right ventricular free wall elastances. Thus, at least on a theoretical basis, left ventricular systolic pressure can affect right ventricular systolic pressure. This effect will depend on the relative wall characteristics and the contraction of both the interventricular septum and left ventricular free wall. Several studies (8, 14, 18, 27) have measured the systolic gain or cross talk between the ventricles. In general, these studies have measured the changes in systolic pressure caused by abrupt changes in afterload of the opposite ventricle. The studies show that the rightto-left ventricular gain is larger than the left-to-right ventricular gain. Right-to-left ventricular systolic gains ranged from 13.6 to 34.5%, whereas left-to-right ventricular systolic gains ranged from 8.6 to 14% (8, 14, 18, 27). On a philosophical point, systolic gains do not directly indicate the relative importance of interdependence. For example, if the left-to-right gain was 10% and the rightto-left gain was 30%, one might assume that systolic ventricular interdependence is more important for left ventricular systolic function. However, if one examines the absolute magnitude of this cross talk, the conclusions are totally different. This is because left ventricular systolic pressure is much greater than right ventricular systolic pressure. If we assume that all the left ventricular systolic pressure (120 mmHg, for example) is transmitted (10%) to the right ventricle, then 12 mmHg (or -50%) of the total measured right ventricular pressure was generated by the left ventricle. Thus the studies that measured systolic gains imply a large (50%) left ventricular contribution to right ventricular systolic pressure, similar to the results of the present study. Finally, this study implies that this left ventricular assist is from the entire left ventricle (left ventricular free wall plus septum). Comparison to our previous studies shows that ventricular interdependence involves the whole ventricle. In diastolic ventricular interdependence
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RIGHT
VENTRICULAR
DEPENDENCY
studies, changing left ventricular volume or pressure alters right ventricular filling characteristics (2). Furthermore, changing left ventricular free wall compliance also altered right ventricular filling characteristics (26). In whole animal studies, rapid abrupt changes in left ventricular systolic pressure caused immediate changes in right ventricular systolic pressure (32). In isolated heart preparations, right ventricular developed pressure was dependent on left ventricular free wall function. Ischemia, restricted solely to the left ventricular free wall, decreased right ventricular developed pressure (25). Cutting the left ventricular free wall from the base to apex decreased right ventricular developed pressure by >60%. Interestingly, resuturing the left ventricular free wall reestablished right ventricular developed pressure (16). Stiffening the left ventricular free wall or interventricular septum with glutaraldehyde injection depressed right ventricular developed pressure (16). Thus the results of this study and previous studies show that the left component of right ventricular pressure and volume outflow is composed of both left ventricular free wall and septal contractions. This ventricular interdependence is probably due to stresses in the muscle fibers influencing both the right and left ventricles. The myocardial stress would influence the pressure development and volume outflow as measured in the present study. Implications. The analysis or assessment of right ventricular function has been difficult and problematic. The complex shape of the right ventricle has made detailed volume determinations difficult. The results of the present study suggest that even with accurate volume measurements the assessment of right ventricular function will be complicated by the status of the left ventricle. If a significant portion of the measured right ventricular pressure and volume outflow is actually generated by the left ventricle, then any change in left ventricular volume or functional status will alter the assessment of right ventricular function. Critique of methods. The potential technical limitations of this study need to be kept in mind. The effects of right ventricular free wall isolation procedure have been examined in several previous studies (3-6, 31). Myocardial blood flow to the right ventricular free wall has been shown in this laboratory to be well preserved (5). The electrophysiological properties of the right ventricular free wall, including pacing threshold, refractory period, and conduction velocity, also remain unchanged (4). The procedure does not affect normal atrioventricular conduction. In this study regional myocardial function was examined utilizing piezoelectric crystals. Systolic function was assessed by evaluating the relationship between enddiastolic length and stroke work. The systolic properties of the left and right ventricles, as assessed by this index, were unchanged after right ventricular isolation. However, our use of a global parameter, left ventricular dP/ dt, to establish the timing of regional shortening might have influenced our analysis of regional wall motion. Also, the unstressed diastolic myocardial segment length changed probably due to geometrical rearrangements. The isolated right ventricular free wall, despite a preservation of most rheologic. electrophvsioloeical. and
ON
LEFT
H1523
VENTRICLE
functional properties, represents a preparation that is markedly different from the intact heart and may have biased our results. Subtle right ventricular dysfunction in this model may have led to an underestimation of the contribution of the right ventricular free wall to overall right ventricular pressure development and volume outflow. However, even if this study did underestimate the relative contribution of the right ventricular free wall, this would not detract from the principal finding of this study that right ventricular systolic function is significantly dependent on the left ventricle. For example, assuming that we overestimated by 50% the left ventricular contribution, this would still mean that 30-35% of the measured right ventricular pressure and volume outflow were generated by the left ventricle. A final limitation of this model is that it does not truly isolate the entire right ventricle but simply the right ventricular free wall from the remainder of the heart. Thus these findings examine the interdependent contribution of the right ventricular free wall versus the left ventricle and septum rather than the right versus the left ventricle. Even when this shortcoming is considered, these data clearly demonstrate the importance of left ventricular and septal contraction to right ventricular performance. The authors thank Joye Zafuto and April L. Jackson for careful preparation of this manuscript. This study was supported in part by National Heart, Lung, and Blood Institute Grant HL-36051. Address for reprints requests: R. J. Damiano, Jr., Dept. of Cardiothoracic Surgery, Medical College of Virginia, PO Box 68, Richmond, VA 23298. Received
10 December
1990; accepted
in final
form
12 June
1991.
REFERENCES 1. BAKOS, A. C. P. The question of the function of the right ventricular myocardium: an experimental study. Circulation 1: 724-732, 1950. 2. BOVE, A. A., AND W. P. SANTAMORE. Ventricular interdependence. Prog. Cardiovasc. Dis. 23: 365-388, 1981. 3. Cox, J. L., G. H. BARDY, R. J. DAMIANO, JR., L. D. GERMAN, J. M. FEDOR, J. A. KISSLO, L. PACKER, AND J. J. GALLAGHER. Right ventricular isolation procedures for nonischemic ventricular tachycardia. J. Thorac. Cardiovasc. Surg. 90: 212-224, 1985. 4. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., AND J. L. COX. Right ventricular free wall isolation: effects on regional myocardial blood flow. Ann. Thorac. Surg. 46: 391-395, 1988. 5. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., AND J. L. COX. The functional consequences of right ventricular isolation. J. Thorac. Cardiovasc. Surg. 100: 569-579, 1990. 6. DAMIANO, R. J., JR., T. ASANO, P. K. SMITH, T. B. FERGUSON, JR., J. M. DOUGLAS, JR., AND J. L. Cox. Electrophysiologic effects of surgical isolation of the right ventricle. Ann. Thorac. Surg. 42: 65-72, 1986. 7. DONALD, D. E., AND H. E. ESSEX. Pressure studies after inactivation of the major portion of the canine right ventricle. An. J. Physiol. 176: 155-161, 1954. 8. ELIZINGA, G., R. VAN GRONDELLE, N. WESTERHOF, AND G. C. VAN DEN BOS. Ventricular interference. Am. J. Physiol. 226: 941947,1974. 9. ERHARDT, L. F. Right ventricular involvement in acute myocardial infarction. Eur. J. Cardiol. 4: 411-418, 1976. 10. FENELEY, M. P., T. P. GAVAGHAN, D. W. BARON, J. A. BRANSON, P. R. ROY, AND J. J. MORGAN. Contribution of left ventricular contraction to the generation of right ventricular systolic pressure in the human heart. Circulation 71: 473-481,1985.
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H1524
RIGHT
VENTRICULAR
DEPENDENCY
11. GOLDSTEIN, J. A., G. J. VLAHAKES, E. D. VERRIER, N. B. SCHILLER, J. V. TYBERG, T. A. PORTS, W. W. PARMLEY, AND K. K. CHATTERJEE. The role of right ventricular systolic dysfunction and elevated interpericardial pressure in the genesis of low output in experimental right ventricular infarction. Circulation 65: 513521,1982. 12. GUIHA, N. H., C. J. LIMAS, AND N. J. COHN. Predominant right ventricular dysfunction after right ventricular destruction in the dog. Am. J. Cardiol. 33: 254-258, 1974. 13. KAGAN, A. Dynamic responses of the right ventricle following extensive damage by cauterization. Circulation 5: 816-823, 1952. 14. LANGILLE, B. L., AND D. R. JONES. Mechanical interaction between the ventricles during systole. Can. J. Physiol. Pharmacol. 55: 373-382,1977. 15. LEGRAND, V., P. RIGO, J. P. SMEETS, J. C. DEMOULIN, P. COLLIGNON, AND H. E. KULBERTUS. Right ventricular myocardial infarction diagnosed by 99 m technetium pyrophosphate scintigraphy: clinical course and follow-up. Eur. Heart J. 4: 9-19, 1983. 16. LI, K. S., W. E. JOHNSTON, AND W. P. SANTAMORE. Contribution of each wall to right ventricular function (Abstract). FASEB J. 4: A821,1990. 17. LITTLE, W. C., F. R. BADKE, AND R. A. O’ROURKE. Effect of right ventricular pressure on the end-diastolic left ventricular pressurevolume relationship before and after chronic right ventricular pressure overload in dogs without pericardia. Circ. Res. 54: 719730,1984. 18. MAUGHAN, W. L., A. A. SHOUKAS, K. SAGAWA, AND M. L. WEISFELDT. Instantaneous pressure-volume relationship of the canine right ventricle. Circ. Res. 44: 309-315, 1979. 19. MAUGHAN, W. L., K. SUNAGAWA, M. KRONENBERG, M. L. WEISFELDT, AND K. SAGAWA. Ventricular systolic interdependence: volume elastance model in isolated canine hearts. Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H1381-H1390, 1987. 20. MIDDELHOF, C. J., W. BUTHKEN, AND A. E. BECKER. Pure right ventricular infarction. Eur. Heart. J. 1: 369-374, 1980. 21. OBOLER, A. A., J. F. KEEFE, W. H. GAASCH, 3. S. BANAS, JR., AND H. J. LEVINE. Influence of left ventricular isovolumic pressure upon right ventricular pressure transients. Cardiology 58: 32-44, 1973.
ON
LEFT
VENTRICLE
22. RIGO, P., M. MURRAY, D. R. TAYLOR, M. L. WEISFELDT, D. T. KELLY, H. W. STRAUSS, AND B. PITT. Right ventricular dysfunction detected by gated scintophotography in patients with acute inferior myocardial infarction. Circulation 52: 268-274, 1976. 23. SANTAMORE, W. P., P. R. LYNCH, J. L. HECKMAN, A. A. BOVE, AND G. D. MEIER. Left ventricular effects on right ventricular developed pressure. J. Appl. Physiol. 41: 925-930, 1976. 24. SANTAMORE, W. P., AND L. PAPA. Alterations in diastolic ventricular interdependence due to myocardial infarction. Cardiouasc. Res. 22: 726-731,1988. 25. SANTAMORE, W. P., AND T. SHAFFER. Ventricular interdependence: theoretical and experimental model results. Proc. Cardiovast. System Dyn. Sot. 6: 33-36, 1984. 26. SANTAMORE, W. P., T. SHAFFER, AND D. HUGHES. A theoretical and experimental model of ventricular interdependence. Basic Res. Cardiol. 81: 529-537, 1986. 27. SLINKER, B. K., A. C. P. CHAGAS, AND S. A. GLANTZ. Chronic pressure overload hypertrophy decreases direct ventricular interaction. Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H347-H357, 1987. 28. SNEDECOR, G. W., AND W. G. COCHRAN. Statistical Methods. Ames: Iowa State Univ., 1967, p. 186. 29. STARR, I., W. A. JEFFERS, AND R. H. MEADE. The absence of conspicuous increments of venous pressure after severe damage to the right ventricle of the dog, with a discussion of the relation between clinical congestive failure and heart disease. Am. Heart J. 26: 291-301, 1943. 30. SUNAGAWA, K., W. L. MAUGHAN, M. L. WEISFELDT, AND K. SAGAWA. Effect of systolic transseptal pressure on septal elastance and ventricular cross talk (Abstract). Circulation 64, Suppl. IV: 180,198l. 31. WALLACE, A. G., M. S. SPACH, E. M. ESTES, AND J. P. BOINEAR. Activation of the normal and hypertrophied human right ventricle.
Am. Heart J. 75: 728-735,1968. 32. YAMAGUCHI, S., AND W. P. SANTAMORE. in systolic ventricular interdependence A1026, 1990.
Comparative (Abstract).
significance
FASEB J. 4:
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