JOURNAL OF APPLIED PHYSIOLOGY Vol. 4, No. 3, September 1976. Printed
Myocardial
in U.S.A.
interaction
between
the ventricles
WILLIAM P. SANTAMORE, PETER R. LYNCH, GEORGE MEIER, JAMES HECKMAN, AND ALFRED A. BOVE Departments of Medicine and Physiology, Temple University Health Sciences Philadelphia, Pennsylvania 19140
SANTAMORE, WILLIAM P., PETER R. LYNCH, GEORGE MEIER, JAMES HECKMAN, AND ALFRED A. BOVE. Myocardial interaction between the ventricles. J. Appl. Physiol. 41(3): 362368. 1976. -The myocardial interaction between the ventricles was studied using isolated, flow-perfused, paced rabbit hearts beating isovolumically. In general, increasing left ventricular (LV) volume increased right ventricular (RV) diastolic and developed pressures. In particular, with a peak RV volume (RVV), increasing LV volume (LVV) from zero to twothirds of its peak volume increase RV diastolic pressure by 1.7 mmHg (N = 10, P < 0.001) and RV developed pressure by 1.5 mmHg (N = 10, P < 0.001). For the LV, small RVV caused LV diastolic and developed pressure to increase, while large RVV increased LV diastolic pressure but decreased LV developed pressure. With a LVV held at two-third of peak volume, increasing RVV from zero to its peak volume caused LV diastolic pressure to increase by 2.5 mmHg (N = 10, P < 0.001) and LV developed pressure to decrease by 2.0 mmHg ( N = 10, P < 0.001). Th e position of the interventricular septum correlated with LV diastolic pressure and RV diastolic and developed pressure changes (P < 0.01). The results demonstrate that the diastolic and developed pressure-volume relationships of either ventricle can be acutely altered by varying the volume of the other ventricle. diastolic pressure-volume relationship, volume relationship, rabbits
developed
Center,
isolated rabbit heart preparation was employed. By use of a pulsatile pump (Harvard Apparatus blood pump, model 1405), the perfusate was pumped from a reservoir through a bubble trap and a glass filter to an aortic cannula for perfusion of the coronary circulation. The emuent was collected in a glass funnel and returned to a temperature-controlled reservoir (29OC). All interconnections in the perfusion system were made with glass tubing (ID = 3.4 mm, OD = 5 mm) or Tygon tubing (ID = 3/~sin., OD = 5/16 in > The perfusate was equilibrated with a gaseous mixture of 95% 0, and 5% CO*, and consisted of a Krebs-Henseleit solution modified to contain 2.5 mm Ca2+, insulin (1 U/l), and EDTA (ethylenediaminetetraacetic acid; 50 pg/l) (15, 21). Left ventricular, right ventricular, and perfusion pressures were measured by Statham arterial pressure transducers (P23db). The heart was paced by means of a Grass stimulator (Grass Instruments stimulator, model SDS), while the pressures and the stimulator pulse were recorded on a multichannel recorder (Electronics for Medicine, model DR7). Rubber balloons that were inserted into the ventricles were made by attaching either the ends of finger cots or surgical gloves to polyethylene 160 tubing. The deflated volume of the left ventricular balloon was 0.4 ml, as measured by water displacement, while the deflated volume of the right ventricular balloon was 0.6 ml. The balloons did not develop significant pressure over the range of volumes encountered in the experiments and were of sufficient size to fill the ventricular cavities when expanded as determined by cineradiogrpahic observations. Initial experimental procedure. All the experiments began with the following procedure: rabbits weighing between 2.8 and 4.6 kg were anesthetized with pentobarbital sodium (40 mg/kg) and a thoracotomy was performed through a median sternotomy. The heart was quickly removed and attached to the support apparatus. Once the heart was attached, the tricuspid valve was cut and the His bundle was ligated to prevent atrioventricular conduction. A balloon was inserted into the right ventricle via the right atrium, and the catheter end of the balloon was passed through the pulmonary artery. Expulsion of the balloon was prevented by means of a half-moon-shaped, Teflon button sutured into the right atrioventricular orifice. Through both atrioventricular orifices, small catheters were placed into the ventricles to remove any perfusate that seeped into the ventricles. A balloon was inserted into the left ventricle through the slit in the left auricle. The balloon
pressure-
BECAUSE OF THE CLOSE ANATOMIC association between the ventricles of the heart (16, 17, 20), the volume of one ventricle might be expected to effect the performance of the other ventricle. Indeed, Taylor et al. (22) and Laks et al. (10) in postmortem hearts observed acute changes in ventricular distensibility caused by changing the volume of the opposite ventricle. Right ventricular volume overload has been shown not only to alter left ventricular diastolic pressure (1) but also to effect left ventricular performance (9, 12) and shape (1, 19). In an isolated heart preparation in which the ventricles ejected and filled independently, Elzinga and colleagues (5) found th at w h en the atria1 filling pressure is increased on one side, the output from the opposite side of the heart decreases. The purpose of this study was to examine the alterations in the ventricular pressurevolume relationships and ventricle configuration caused by varying the volume of the opposite ventricle. METHODS
Experimental setup. To eliminate neural, humoral, pericardial, and pulmonary circulatory influences, an 362
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MYOCARDIAL
INTERACTION
BETWEEN
THE
363
VENTRICLES
was secured by tying a suture around both the left auricle and the connecting tubing of the left ventricular balloon. An electrode (an alligator clip with each side electrically isolated from the other) was attached to the His bundle and the heart was paced by means of a Grass stimulator. Pressure-volume experiments. In 10 experiments, the effects of varying right ventricular volume on left ventricular pressure-volume characteristics were analyzed by the following procedure: after preparing the heart as described above and ascertaining that the preparation was stable, the left ventricular volume (the volume of the left ventricular balloon) was established at 0.4 ml, while the right ventricular volume (volume of the right ventricular balloon) was set at 0.0 ml. After 1 min of equilibration, the left ventricular pressure was recorded at both a low sensitivity for systolic pressures and a high sensitivity for diastolic pressure. Then the right ventricular volume was increased in three steps. Each increment in right ventricular volume corresponded to one-third of the peak right ventricular volume. (The peak right ventricular volume was the right ventricular volume that generated maximal right ventricular isovolumic developed presure.) At each increment in right ventricular volume, left ventricular pressure was recorded. The fluid was then removed from the right ventricle and left ventricular pressure was again recorded. Left ventricular volume was then incremented in steps of 0.2 ml until a value of left ventricular volume close to the peak of the pressure-volume curve was obtained. At each increment, left ventricular pressure was recorded with the right ventricular volume set at 0.0 ml, one-third the peak right ventricular volume, two-third the peak right ventricular volume, the peak right ventricular volume, and 0.0 ml, as outlined above. The advantage of this procedure was that the influence of right ventricular volume on left ventricular isovolumic pressure could be accurately determined. In any isolated heart preparation, ventricular function changes with time. In the method outlined above, the effects of right ventricular volume on left ventricular pressure for each left ventricular volume were measured within five minutes. Thus, the alterations in left ventricular pressure that occur with time were minimized. To analyze the effects of varying left ventricular volume on right ventricular pressure-volume characteristics, an analogous procedure to the one outlined above was used. Cineradiography experiment. After the initial experimental procedures, the left ventricular balloon was filled with a radiopaque solution (1 M NaI) to a volume two-thirds the peak left ventricula r volume. To obtain a base to apex view, the X-ray unit, a C-mount (C-mount with Sin. Philips image tubing and GE tube llGF3), was moved to a v,ertical position. Thus, the X rays passed from their source through the apex and then base of the heart to the image intensifier. The measured resolution for this X-ray unit with the rabbit heart thus positioned was 0.025 cm. A cinecamera recorded the Xray image from the image intensifier. LeR ventricular pressure was recorded on the cinefilm (plus X reversal Kodak) by means of an oscilloscope (6). With the left
ventricular pressure parameter on the film and the heart properly positioned, four to six heart cycles were recorded on cinefilm at a rate of 24 frames/s. The Cmount was then turned to the horizontal position and cineangiograms were again taken. Next, the right ventricle was filled to its peak volume with a NaI solution. Horizontal and vertical angiograms were taken with both ventricular balloons containing NaI. The NaI solution was removed from the left ventricular balloon, and the vertical and horizontal angiograms were again recorded. Data analysis. Data analysis was performed on a LINC/8 computer system (11). For the cineradiographic experiments, ventricular silhouettes were projected onto a Thompson (Digitizer) table (d-mat, Ltd., Glascow), converted to spatial coordinates and stored on digital magnetic tape. The distances from the left side of the silhouette to the right side of the ventricular silhouette were determined (18). For each outline, 19 distances were calculated, each distance being equally spaced and perpendicular to a predefined axis (Figs. 5,6). Using the stored numerical data obtained from the tine images, calculation of the ventricular configurational changes for each experimental condition was possible. In particular, changes in ventricular dimensions, septal radii of curvature and septal displacement were studied. The septal radii of curvature (R) were calculated by (1 + y’2)2/:~ R = Y”
where Y = axz+bx+c dY
y’ = z
=2ax+b
dZy y” =z=
2a
The equation for y was derived from a second-order least-squares fit of the spatial coordinates describing the ventricular outline (2) . RESULTS
Pressure-volume experiments. Figure 1 shows a typical left ventricular pressure-volume relationship that was obtained from 1 of the 10 experiments. As can be seen from Fig. 1, varying right ventricular volume changes both left ventricular diastolic and developed pressures. The results of the 10 pressure-volume experiments are combined in Fig. 2. Figure 2A is a plot of normalized left ventricular volume versus the changes in left ventricular diastolic pressure. If increasing right ventricular volume had no effect on left ventricu-. lar diastolic pressure, all the data points would lie along the zero change line (RVV = 0.0 ml). Figure 2A indicates that an increase in right ventricular volume increased left ventricular diastolic pressure. The greater the increase in right ventricular volume, the greater the resulting increase in left ventricular diastolic pressure. Furthermore, this increase in left ventricular diastolic pressure (in mmHg) was greater for
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364
SANTAMORE VENTRICULAR
A
ET
AL.
PRESSURE
DIASTOLIC (uVV=O.Oml)
X -6.3
-2.4
-3.6
-.4
.l
1.9
4.6
A
z) 0
4
X
: X 0
z X 0
0 0 X
0
II
10
20
III
:RVV=~Xml
I
30
LEff
0
RVV=%Xml
40
I
50
VENTRICULAR
I
60
I
70
I
80
NORMALIZED
I
90
100x
VOLUME
b MEAN
LEFT
VENTRICULAR
B
LEFT
VENTRICULRR
VOLUME
0 O
0
Q
X
II
0
0 0 X a
I LEFT
I
4
I
.6
I
.8
VENTRICULRR
I
1.0
I
1.2
VOLUME
I
1.4
I
1.6
I
1.8
(ML)
1. Results from one experiment showing effects of right ventricular volume of 1eR ventricular diastolic pressure (A) and left ventricular developed pressure (B). Developed pressure = systolic pressure minus diastolic pressure. 0 Represents values of left ventricular pressures recorded with no fluid in the right ventricular balloon; #, 0, X represent values of 1eR ventricular pressures reFIG.
LEFT
VENTRICULAR
103
110
117
119
122
125
126
0
0 0
.2
90
RESSUREkmHg)
= O.Oml)
WlMHCl
ii 0 51
85
l
DEVELOPED (RVV
NORMALIZED
VOLUME
2. Effects of altering right ventricular volume (RVV) on left ventricular diastolic and developed pressures in 10 experiments. l/3 X ml indicates one-third of the peak RVV; 2/3 X ml indicates two-. third of the peak RVV; X ml represents the peak RVV. (l/3 X ml, 2/3 X ml, and X ml correspond to RVV of 0.5, 1.0, and 1.5 ml in Fig. 1.) Data values at top are average left ventricular diastolic and developed pressures recorded with RVV = 0.0 ml. Bars represent the standard error of the mean about the data points. For visual clarity, only every third standard error of the mean is shown. For each experiment, left ventricular volume was normalized by giving the peak left ventricular volume (volume at the peak of pressure-volume curve) a value of 100%. All other volumes in the experiment were expressed as a percent of the peak left ventricular volume. For example, in Fig. 1 the left ventricular volume 1.8 ml received a value of lOO%, while the volume 1.2 ml received a value of 67%. Since all the volumes did not occur in regular increments, plotted points represent a range in volume of 10%. FIG.
larger left ventricular volumes. Figure 23 is a plot of normalized left ventricular volumes versus the changes in left ventricular developed pressure. Figure ZB shows that small right ventricular volumes (RVV = l/3 X ml) were associated with increased left ventricular developed pressure, while large right ventricular volumes (RVV = X ml) were associated with reduced corded when the right 1.5 ml accordingly.
ventricular
balloon
was filled
with
0.5,l.O
and
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MYOCARDIAL
INTERACTION
BETWEEN
THE
365
VENTRICLES
left ventricular developed pressure. However, the magnitudes of these changes in left ventricular developed pressure were small. Figure 3 is a typical right ventricular pressure-volume relationship showing the effects of varying left ventricular volume on right ventricular diastolic and developed pressures. Figure 4A is a plot of normalized right ventricular volume versus the changes in right ventricular diastolic pressure. Left ventricular volume changes produce significant alterations in right ventricular diastolic pressure. Increasing left ventricular volume increased right ventricular diastolic pressure, while decreasing left ventricular volume decreased right ventricular diastolic pressure. Figure 4B is a plot of normalized right ventricular volume versus the changes in right ventricular developed pressure. The salient feature of Fig. 4B is the consistency of the increase in right ventricular developed pressure caused by increasing left ventricular volume. Except for the combination of peak right and left ventricular volumes, small, moderate and large left ventricular’ volumes were associated with similar effects on right ventricular isovolumic developed pressure. Cineradiographic experiments. Increasing right ventricular volume from 0.0 ml to its peak volume caused left ventricular diastolic septal-to-free wall distances, as measured in the horizontal view, to decrease by 4.8% (N = 5, P < 0.001) from 1.09 t 0.03 to 1.03 t .03 cm. Figure 5 is a typical diastolic left ventricular,horizontal outline before and after increasing right ventricular volume. (Because of the small size of the rabbit hearts, the magnitude of the dimensions are accordingly small.) The vertical view showed a flattening of the septum (an increase in the septal radii of curvature) caused by increasing right ventricular volume from 0.0 ml to its peak volume. Septal radii of curvature increased by 49.9% (N = 5, P < 0.002) from 1.66 to 2.49 cm. Both the decrease in the septal-to-free wall distance and the increase in the septal radii of curvature are indicative of a shift of the septum toward the left ventricle as a result of the increase in right ventricular volume. In a reciprocal manner, an increase in left ventricular volume was observed to shift the septum toward the right ventricular cavity. The vertical tine view showed that increasing left ventricular volume from 0.0 ml to two-thirds to peak volume caused the septal radii of curvature to decrease by 72.8% (N = 5, P < 0.001) from 29.2 t 12.8 to 8.1 t 2.1 cm, and septal displacement to increase by 15.1% (N = 5, P < 0.001) from 0.59 t 0.02 to 0.68 t 0.03 cm. Figure 6 is a diastolic right ventricular vertical outline before and after increasing left ventricular volume. Thus, changes in ventricular diastolic volume can alter the position and shape of the septum. In addition, these changes in septal shape are not restricted to individual areas of the septum, but appear to effect the entire septum. Note in Figs. 5 and 6 the uniformity of septal shape with changes in ventricular volume. Because of the small, biphasic response of the left ventricular isavolumic developed pressure to increasing right ventricular volume (Fig. 2B), left ventricular
e
A
14-
0 * 0
t-4 CY b-
-
P + 6 c( a
0
X 0 0 X a l
o-
0 0
l u
0
c!
-2-
I
l2
RIGHT 4a
I
.4
I
l6
I
me
VENTRICULfW
I
I
1lo
VOLUME
1.2
I
1.4
[ML)
6
0
0
X
0
0 X 0 0 X 0
0 0 X 0
0 X
a 10
I
.2
RIGHT
I
.4
I
.6
VENTRICULW
I
98
I
1 .o
VOLUME
I
1.2
I
1.4
(ML1
3. Results from one experiment showing effects of left ventricular volume on right ventricular diastolic pressure (A) and right ventricular developed pressure (B). 0 Represents values of right ventricular pressures recorded with no fluid in the left ventricular balloon; #, 0, X represent values of right ventricular pressure recorded when the left ventricular balloon was filled with 0.6, 1.2, and 1.8 ml accordingly. Note data in Figs. 1 and 3 come from the same experiment. FIG.
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366
SANTAMORE MEAN
RIGHT
VENTRICULAR
A
( Vl V= -4.0
-3.1
DIASTOLIC 0.0
ml
-1.2
-22
FRESSUREimnr)
-.I
.a
2J
3.9
Loft
Atrium
Axis
0’04--
\\
I
I RIGHT
11
4.0
a
3.5
VINTRICULAR
B
MEAN
NORMALIZED
RIGHT
Loft Ventricular
VOLUME
VENTRICULAR
DEVELOPED
3.o
zz
1.0
)3 *ia
Wll a.6
9.7
:f 5 Y ;r2 H Y ca XI 8 ;;a p'
fro.
?RESSlJRE
(LVV= o.oml)
';^p
316
s
2.5
I I I I I I I \ \
--k Left
\\ ‘\
Ventricular
: U
Soptum
\
Diastolic
I I I I I I
&the
\
2.0
I I I I I
1.5
Y UN soy
AL.
pressures, caused by varying the contralateral ventricular volume, represent changes in ventricular function that are transmitted from one ventricle to the other through the myocardium. The basis for this myocardial interaction lies in the close anatomical association between the ventricles of the heart (16, 17, 20). In addition to the intraventricular septum, common muscle bundles encircle both ventricles. Hence, the degree of contrac-
I -.2
ET
0.5
! 0.0
I
vv=o ml - .I
I
-7
L 0
II 10
I 20 RIGHT
30 VENTRICULAR
II 40
I SO
60 NORMALlZtD
I
I
70
80
II 90
100%
VOLUME
FIG. 4. Effects of altering left ventricular volume (LVV) on right ventricular diastolic and developed pressures in 10 experiments. ‘13 X, *I3 X, and X indicate fraction of leak LVV(X) (corresponding to 0.6, 1.2, and 1.8 ml in Fig. 3). Data values at top are average right ventricular diastolic and developed pressures recorded with LVV = 0.0 ml. For each experiment, right ventricular volume was normalized by giving the peak right ventricular volume a value of 100%. All the other volumes in the experiment were expressed as a percent of For example, in Fig. 3 the right peak right ventricular volume. ventricular volume 1.4 ml received a value of 10096, while the volume 1.0 ml received a value of 71%.
--
Right
Ventricular
Volume
-
Right
Ventricular
Volume=
= Ooml 23
ml
5. Typical horizontal 1eR ventricular diastolic increasing right before (- - -) and after (-)
FIG.
tained volume.
Right
developed pressure changes resulting from right ventricular volume alterations were not investigated in the cineangiographic experiments. On the tine images, the septum was readily observed to bulge into the right ventricular cavity during systole. Increasing left ventricular volume from 0.0 ml to two-thirds its peak volume caused the septum to bulge further into the right ventricular cavity as measured by a 24.8% (N = 5, P < 0.1) decreased in the septal radii of curvature from 6.0 t 1.6 cmto 4.4 +- 0 .8 cm and by a 4.3% (N = 5, P < 0.01) increase in the septal displacement from 0.68 t 0.03 to 0.71 t 0.03 cm.
Diastolic
Ventricular
Free
Out
Wall
line
I
2.00cm DISCUSSION
In this study, an isolated heart preparation was used because it removes all neural, humoral, pericardial, and pulmonary circulatory influence upon the heart. Thus the only way one ventricle could effect the other ventricle was through the myocardium. Therefore, the observed changes in ventricular diastolic and developed
outline obventricular
Displacement -FIG.
tained ume.
left
Ventricular
Volume=O.O
ml
Left
Ventricular
Volume+2
ml
6. Typical vertical right before (- - -) and aRer (->
ventricular increasing
diastolic outline left ventricular
obvol-
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MYOCARDIAL
INTERACTION
BETWEEN
THE
VENTRICLES
tion or distension of one ventricle effects the other ventricle via the myocardium. The results of these experiments demonstrate that varying left ventricular volume in the beating heart can acutely change the right ventricular diastolic pressurevolume relationship. Increasing left ventricular volume caused an increase in right ventricular diastolic pressure, while decreasing left ventricular volume caused a decrease in right ventricular diastolic pressure. The results also demonstrate acute changes in left ventricular diastolic pressure-volume relationship caused by varying right ventricular volume. In particular, increasing right ventricular volume caused an increase in left ventricular diastolic pressure, while decreasing right ventricular volume caused a decrease in left ventricular diastolic pressure. Prior to these experiments, similar acute alterations in the diastolic pressure-volume characteristics of the ventricles had been shown in the postmortem state (9, 10, 22) and had been implied to occur in vivo (1 5) The intraventricular septum is an important element in the relationship between right and left ventricular diastolic pressure-v01 ume characteristic. As observed in the cineradiographic experiments, increasing left ventricular volume shifts the septum toward the right ventricular cavity, thereby increasing right ventricular diastolic pressure. In a reciprocal manner, increasing right ventricular volume causes the septum to shift toward the left ventricle, thereby increasing left ventricular diastolic pressure. This leftward displacement of the septum with increasing right ventricular volume has also been reported bY Be&s et al. (1) and Stool et al. (19). The changes in ventricular diastolic pressure-volume characteristics may be important in the development of systemic venous congestion following acute myocardial infarction in man (22) and in the normal cardiovascular response to changes in posture and respiration. In an acute myocardial infarction with elevated left ventricular end-diastolic pressure, the right ventricle has to pump against an increased pulmonary arterial pressure. In addition, left ventricular distension can change the right ventricular diastolic pressure-volume relationship (Fig. 4A). The combination of these two effects can lead to abnormally high right ventricular filling pressure and systemic venous congestion. Changes in posture evoke a wide range of cardiovascular responses which act to maintain an adequate cardiac output. Hoffman et al. (8) observed in dogs tilted from supine to erect position an immediate fall in right ventricular stroke volume. However, left ventricular stroke volume remained constant for another l-3 beats. After the initial rapid fall, the stroke volume of each ventricle decline gradually to reach an equilibrium at a new low level which occurs about 6 beats earlier on the right than on the left. Hoffman and co-workers attribute this delayed onset and slower time course of responses of the left ventricle to the pulmonary blood reservoir. From the results of this study, an alternative or additional mechanism can be postulated. When changing from a recumbent to a standing position, right ven .tricu lar volume decreases d ue to reduced venous return . This 9
l
367 decrease in right ventricular volume will change the left ventricular diastolic pressure-volume characteristics (Fig. 2A), in eff ect making it easier to fill the 1eR ventricle. Thus, despite the decrease in right ventricular stroke volume and pulmonary arterial pressure, left ventricular filling and stroke volume would initially be maintained. In effect, this change in left ventricular diastolic pressure-volume characteristics would help to buffer the sudden decrease in right ventricular output. During inspiration, right ventricular end-diastolic volume and stroke volume increase, while left ventricular stroke volume remains constant or decreases. If inspiration is deep, left ventricular stroke volume always falls (8). It is generally believed that the decrease in left ventricular stroke volume is due to a decrease in left ventricular filling pressure (3, 14). (Left ventricular filling pressure is equal to the mean pulmonary capillary pressure minus left ventricular diastolic pressure.) The pericardium was initially believed to be responsible for the decrease in left ventricular filling pressure because of competition by the two ventricles for fixed intrapericardial volume (4). Guntheroth et al. (7) in a study of dogs demonstrated that this theory was not correct. The results presented in this study can be used to explain the observed decrease in left ventricular stroke volume during inspiration. With inspiration right ventricular volume increases. This increase in right ventricular volume causes a change in the left ventricular diastolic pressure-volume characteristics (Fig. 2A), making it harder to fill the left ventricle. Thus, without a change in left ventricular filling pressure, left ventricular diastolic volume would be decreased. By the Starling mechanism, this decrease in left ventricular diastolic volume would result in the observed decrease in left ventricular stroke volume. From the active pressure-volume experiments, the influence of right ventricular volume on left ventricular isovolumic developed pressure was shown to be biphasic. Small right ventricular volumes augmented left ventricular isovolumic developed pressure, while large right ventricular volumes reduced left ventricular isovolumic developed pressure. The crossover point was on the upper portion of the ascending limb of the right ventricular pressure-volume curve. However, right ventricular volume effects on left ventricular developed pressure are small and probably insignificant under normal physiological conditions. For the right ventricle, the left-ventricular volume effects on right ventricular developed pressure were more consistent and of a larger magnitude. Except for the combination of largest left and right ventricul ar volume, increasing left ventricular volume resulted in an increase-in right ventricular developed pressure. Thus, in the normal physiological range, left ventricular volume augments right ventricular pressure development. Other studies (13) also noted a strong influence of the left ventricle on right ventricular developed pressure. Oboler et al. (13) observed that the first derivative of right ventricular pressure is double peaked with one peak corresponding in time to the maximum derivative of left ventricular pressure. He speculated that the right ventricle is normally assisted in its pumping action by the left ventricle. The results
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368 obtained in this study support Oboler’s observations. In addition, left ventricular ischemia and structural damage have also been demonstrated in this laboratory to effect right ventricular developed pressure, independent of neural, humoral, pericardial, and pulmonary circulatory influences.
SANTAMORE
ET
AL.
The authors thank Drs. B. Rusy and R. Tallarida for their advice and assistance and Ms. Barbara McDonald and Dorothy Kallio for their help in the preparation of the manuscript. Address of G. Meier: Dept. of Biomedical Engineering and Science, Drexel University, Philadelphia, Pa. Received
for publication
24 December
1975.
REFERENCES 1. BEMIS, C. E., J. R. SERUR, D. BORKENHAGEN, E. H. SONNENBLICK, AND C. W. URSCHEL. Influences of right ventricular filling pressure on left ventricular pressure and dimensions. CircuZation Res. 34: 498404, 1974. 2. BOVE, A. A. Radiographic evaluation of dynamic geometry of the left ventricle. J. Appl. PhysioZ. 31: 227-234, 1971. 3. COLERIDGE, J. C. G., AND R. J. LINDEN. The variations with respiration in effective right and left atria1 pressure in the dog. J. Physiol., London 145: 482-493, 1959. 4. DORNHORST, A. C., P. HOWARD, AND G. L. LEATHART. Respiratory variations in blood pressure. CircuZation 6: 533, 1952. 5. ELZINGA, G., R. VAN GRONDELLE, N. WESTERHOF, AND G. C. VAN DEN Bos. Ventricular interference. Am. J. PhysioZ. 226: 941-947, 1974. 6. GIMENEZ, J. L., A. A. BOVE, AND A. BLACKSTONE. Superimposed front lens oscillography in cinefluorography. RadioLogy 85: 352355, 1965. 7. GUNTHEROTH, W. G., B. C. MORGAN, AND G. L. MULLINS. Effects of respiration on venous return and stroke volume in cardiac tamponade. Mechanism of pulsus paradoxus. CircuZation Res. 20: 381-390, 1967. 8. HOFFMAN, J. I. E., A. Guz, A. A. CHARLIER, AND D. E. L. WILCKEN. Stroke volume in conscious dogs; effect of respiration, posture, and vascular occlusion. J. AppZ. Physiol. 20: 865, 1965. 9. KELLY, D. T., H. M. SPOTNITZ, G. D. BEISSER, J. E. PIERCE, AND S. E. EPSTEIN. Effects of chronic right ventricular volume and pressure loading on left ventricular performance. CircuZutjon 44: 403, 1971. 10. LAKS, M. M., D. GARNER, AND H. J. C. SWAN. Volumes and compliances measured simultaneously in the right and left ventricles of the dog. CircuZation Res. 20: 565-569, 1967. 11. LYNCH, P. R., AND G. H. STEWART. High-speed cineradiography. A technique for obtaining physiologic data. In: CardiouascuZar Imaging and Image Processing. Society of Photo-Optical Instrumentation Engineers. 1975, p. 97-102. 12. MOULOPOULOS, S. D., A. SARCAS, S. STAMATELOPOULOS, AND E.
13.
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21.
22.
AREALIS. Left ventricular performance during bypass or distension of the right ventricle. CircuZution Res. 17: 484-491, 1965. OBOLER, A. A., J. F. KEEFE, W. H. GAASCH, J. S. BANAS, JR., AND H. J. LEVINE. Influences of left ventricular isovolumic pressure upon right ventricular pressure transidents. CardioZogy 58: 32-44, 1973. OPDYKE, D. F., AND G. A. BRECHER. Effect of normal and abnormal changes of intrathoracic pressure in effective right and left atria1 pressures. Am. J. Physiol. 160: 556-566, 1950. OPIE, L. H. Metabolism of the heart in health and disease. Am. Heart J. 76: 685-698, 1968. ROBB, J. S., AND R. C. ROBB. The normal heart. Anatomy and physiology of the structural units. Am. Heart J. 23: 455-467, 1942. RUSHMER, R. F., D. K. CRYSTAL, AND C. WAGNER. The functional anatomy of ventricular contraction. CircuZation Res. 1: 162-170, 1953. SANTAMORE, W. P., F. N. DIMEO, AND P. R. LYNCH. A comparative study of various single plane cineangiographic methods to measure left ventricular volume. IEEE Trans. Biomed. Eng. BME20: 417-421, 1973. STOOL, E. W., C. B. MULLINS,%. J. LESHIN, AND J. H. MITCHELL. Dimensional changes of the left ventricle during acute pulmonary arterial hypertension in dogs. Am. J. CardioZ. 33: 868-875, 1974. STREETER, D. D., JR., AND D. L. BASSETT. An engineering analysis of myocardial fiber orientation in pigs left ventricle in systole. Anat. Record 155: 503-511, 1966. SURAWICZ, B., E. LEPESCHKIN, H. C. HERRLICH, AND B. F. HOFFMAN. Effect of potassium and calcium deficiency on the monophasic action potential, electrocardiogram and contractility of isolated rabbit hearts. Am. J. Physiol. 196: 1302-1307, 1959. TAYLOR, R. R., J. W. COVELL, E. H. SONNENBLICK, AND J. Ross, JR. Dependence of ventricular distensibility on filling of the opposite ventricle. Am. J. PhysioZ. 213: 711-718, 1967.
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Myocardial
in U.S.A.
interaction
between
the ventricles
WILLIAM P. SANTAMORE, PETER R. LYNCH, GEORGE MEIER, JAMES HECKMAN, AND ALFRED A. BOVE Departments of Medicine and Physiology, Temple University Health Sciences Philadelphia, Pennsylvania 19140
SANTAMORE, WILLIAM P., PETER R. LYNCH, GEORGE MEIER, JAMES HECKMAN, AND ALFRED A. BOVE. Myocardial interaction between the ventricles. J. Appl. Physiol. 41(3): 362368. 1976. -The myocardial interaction between the ventricles was studied using isolated, flow-perfused, paced rabbit hearts beating isovolumically. In general, increasing left ventricular (LV) volume increased right ventricular (RV) diastolic and developed pressures. In particular, with a peak RV volume (RVV), increasing LV volume (LVV) from zero to twothirds of its peak volume increase RV diastolic pressure by 1.7 mmHg (N = 10, P < 0.001) and RV developed pressure by 1.5 mmHg (N = 10, P < 0.001). For the LV, small RVV caused LV diastolic and developed pressure to increase, while large RVV increased LV diastolic pressure but decreased LV developed pressure. With a LVV held at two-third of peak volume, increasing RVV from zero to its peak volume caused LV diastolic pressure to increase by 2.5 mmHg (N = 10, P < 0.001) and LV developed pressure to decrease by 2.0 mmHg ( N = 10, P < 0.001). Th e position of the interventricular septum correlated with LV diastolic pressure and RV diastolic and developed pressure changes (P < 0.01). The results demonstrate that the diastolic and developed pressure-volume relationships of either ventricle can be acutely altered by varying the volume of the other ventricle. diastolic pressure-volume relationship, volume relationship, rabbits
developed
Center,
isolated rabbit heart preparation was employed. By use of a pulsatile pump (Harvard Apparatus blood pump, model 1405), the perfusate was pumped from a reservoir through a bubble trap and a glass filter to an aortic cannula for perfusion of the coronary circulation. The emuent was collected in a glass funnel and returned to a temperature-controlled reservoir (29OC). All interconnections in the perfusion system were made with glass tubing (ID = 3.4 mm, OD = 5 mm) or Tygon tubing (ID = 3/~sin., OD = 5/16 in > The perfusate was equilibrated with a gaseous mixture of 95% 0, and 5% CO*, and consisted of a Krebs-Henseleit solution modified to contain 2.5 mm Ca2+, insulin (1 U/l), and EDTA (ethylenediaminetetraacetic acid; 50 pg/l) (15, 21). Left ventricular, right ventricular, and perfusion pressures were measured by Statham arterial pressure transducers (P23db). The heart was paced by means of a Grass stimulator (Grass Instruments stimulator, model SDS), while the pressures and the stimulator pulse were recorded on a multichannel recorder (Electronics for Medicine, model DR7). Rubber balloons that were inserted into the ventricles were made by attaching either the ends of finger cots or surgical gloves to polyethylene 160 tubing. The deflated volume of the left ventricular balloon was 0.4 ml, as measured by water displacement, while the deflated volume of the right ventricular balloon was 0.6 ml. The balloons did not develop significant pressure over the range of volumes encountered in the experiments and were of sufficient size to fill the ventricular cavities when expanded as determined by cineradiogrpahic observations. Initial experimental procedure. All the experiments began with the following procedure: rabbits weighing between 2.8 and 4.6 kg were anesthetized with pentobarbital sodium (40 mg/kg) and a thoracotomy was performed through a median sternotomy. The heart was quickly removed and attached to the support apparatus. Once the heart was attached, the tricuspid valve was cut and the His bundle was ligated to prevent atrioventricular conduction. A balloon was inserted into the right ventricle via the right atrium, and the catheter end of the balloon was passed through the pulmonary artery. Expulsion of the balloon was prevented by means of a half-moon-shaped, Teflon button sutured into the right atrioventricular orifice. Through both atrioventricular orifices, small catheters were placed into the ventricles to remove any perfusate that seeped into the ventricles. A balloon was inserted into the left ventricle through the slit in the left auricle. The balloon
pressure-
BECAUSE OF THE CLOSE ANATOMIC association between the ventricles of the heart (16, 17, 20), the volume of one ventricle might be expected to effect the performance of the other ventricle. Indeed, Taylor et al. (22) and Laks et al. (10) in postmortem hearts observed acute changes in ventricular distensibility caused by changing the volume of the opposite ventricle. Right ventricular volume overload has been shown not only to alter left ventricular diastolic pressure (1) but also to effect left ventricular performance (9, 12) and shape (1, 19). In an isolated heart preparation in which the ventricles ejected and filled independently, Elzinga and colleagues (5) found th at w h en the atria1 filling pressure is increased on one side, the output from the opposite side of the heart decreases. The purpose of this study was to examine the alterations in the ventricular pressurevolume relationships and ventricle configuration caused by varying the volume of the opposite ventricle. METHODS
Experimental setup. To eliminate neural, humoral, pericardial, and pulmonary circulatory influences, an 362
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MYOCARDIAL
INTERACTION
BETWEEN
THE
363
VENTRICLES
was secured by tying a suture around both the left auricle and the connecting tubing of the left ventricular balloon. An electrode (an alligator clip with each side electrically isolated from the other) was attached to the His bundle and the heart was paced by means of a Grass stimulator. Pressure-volume experiments. In 10 experiments, the effects of varying right ventricular volume on left ventricular pressure-volume characteristics were analyzed by the following procedure: after preparing the heart as described above and ascertaining that the preparation was stable, the left ventricular volume (the volume of the left ventricular balloon) was established at 0.4 ml, while the right ventricular volume (volume of the right ventricular balloon) was set at 0.0 ml. After 1 min of equilibration, the left ventricular pressure was recorded at both a low sensitivity for systolic pressures and a high sensitivity for diastolic pressure. Then the right ventricular volume was increased in three steps. Each increment in right ventricular volume corresponded to one-third of the peak right ventricular volume. (The peak right ventricular volume was the right ventricular volume that generated maximal right ventricular isovolumic developed presure.) At each increment in right ventricular volume, left ventricular pressure was recorded. The fluid was then removed from the right ventricle and left ventricular pressure was again recorded. Left ventricular volume was then incremented in steps of 0.2 ml until a value of left ventricular volume close to the peak of the pressure-volume curve was obtained. At each increment, left ventricular pressure was recorded with the right ventricular volume set at 0.0 ml, one-third the peak right ventricular volume, two-third the peak right ventricular volume, the peak right ventricular volume, and 0.0 ml, as outlined above. The advantage of this procedure was that the influence of right ventricular volume on left ventricular isovolumic pressure could be accurately determined. In any isolated heart preparation, ventricular function changes with time. In the method outlined above, the effects of right ventricular volume on left ventricular pressure for each left ventricular volume were measured within five minutes. Thus, the alterations in left ventricular pressure that occur with time were minimized. To analyze the effects of varying left ventricular volume on right ventricular pressure-volume characteristics, an analogous procedure to the one outlined above was used. Cineradiography experiment. After the initial experimental procedures, the left ventricular balloon was filled with a radiopaque solution (1 M NaI) to a volume two-thirds the peak left ventricula r volume. To obtain a base to apex view, the X-ray unit, a C-mount (C-mount with Sin. Philips image tubing and GE tube llGF3), was moved to a v,ertical position. Thus, the X rays passed from their source through the apex and then base of the heart to the image intensifier. The measured resolution for this X-ray unit with the rabbit heart thus positioned was 0.025 cm. A cinecamera recorded the Xray image from the image intensifier. LeR ventricular pressure was recorded on the cinefilm (plus X reversal Kodak) by means of an oscilloscope (6). With the left
ventricular pressure parameter on the film and the heart properly positioned, four to six heart cycles were recorded on cinefilm at a rate of 24 frames/s. The Cmount was then turned to the horizontal position and cineangiograms were again taken. Next, the right ventricle was filled to its peak volume with a NaI solution. Horizontal and vertical angiograms were taken with both ventricular balloons containing NaI. The NaI solution was removed from the left ventricular balloon, and the vertical and horizontal angiograms were again recorded. Data analysis. Data analysis was performed on a LINC/8 computer system (11). For the cineradiographic experiments, ventricular silhouettes were projected onto a Thompson (Digitizer) table (d-mat, Ltd., Glascow), converted to spatial coordinates and stored on digital magnetic tape. The distances from the left side of the silhouette to the right side of the ventricular silhouette were determined (18). For each outline, 19 distances were calculated, each distance being equally spaced and perpendicular to a predefined axis (Figs. 5,6). Using the stored numerical data obtained from the tine images, calculation of the ventricular configurational changes for each experimental condition was possible. In particular, changes in ventricular dimensions, septal radii of curvature and septal displacement were studied. The septal radii of curvature (R) were calculated by (1 + y’2)2/:~ R = Y”
where Y = axz+bx+c dY
y’ = z
=2ax+b
dZy y” =z=
2a
The equation for y was derived from a second-order least-squares fit of the spatial coordinates describing the ventricular outline (2) . RESULTS
Pressure-volume experiments. Figure 1 shows a typical left ventricular pressure-volume relationship that was obtained from 1 of the 10 experiments. As can be seen from Fig. 1, varying right ventricular volume changes both left ventricular diastolic and developed pressures. The results of the 10 pressure-volume experiments are combined in Fig. 2. Figure 2A is a plot of normalized left ventricular volume versus the changes in left ventricular diastolic pressure. If increasing right ventricular volume had no effect on left ventricu-. lar diastolic pressure, all the data points would lie along the zero change line (RVV = 0.0 ml). Figure 2A indicates that an increase in right ventricular volume increased left ventricular diastolic pressure. The greater the increase in right ventricular volume, the greater the resulting increase in left ventricular diastolic pressure. Furthermore, this increase in left ventricular diastolic pressure (in mmHg) was greater for
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364
SANTAMORE VENTRICULAR
A
ET
AL.
PRESSURE
DIASTOLIC (uVV=O.Oml)
X -6.3
-2.4
-3.6
-.4
.l
1.9
4.6
A
z) 0
4
X
: X 0
z X 0
0 0 X
0
II
10
20
III
:RVV=~Xml
I
30
LEff
0
RVV=%Xml
40
I
50
VENTRICULAR
I
60
I
70
I
80
NORMALIZED
I
90
100x
VOLUME
b MEAN
LEFT
VENTRICULAR
B
LEFT
VENTRICULRR
VOLUME
0 O
0
Q
X
II
0
0 0 X a
I LEFT
I
4
I
.6
I
.8
VENTRICULRR
I
1.0
I
1.2
VOLUME
I
1.4
I
1.6
I
1.8
(ML)
1. Results from one experiment showing effects of right ventricular volume of 1eR ventricular diastolic pressure (A) and left ventricular developed pressure (B). Developed pressure = systolic pressure minus diastolic pressure. 0 Represents values of left ventricular pressures recorded with no fluid in the right ventricular balloon; #, 0, X represent values of 1eR ventricular pressures reFIG.
LEFT
VENTRICULAR
103
110
117
119
122
125
126
0
0 0
.2
90
RESSUREkmHg)
= O.Oml)
WlMHCl
ii 0 51
85
l
DEVELOPED (RVV
NORMALIZED
VOLUME
2. Effects of altering right ventricular volume (RVV) on left ventricular diastolic and developed pressures in 10 experiments. l/3 X ml indicates one-third of the peak RVV; 2/3 X ml indicates two-. third of the peak RVV; X ml represents the peak RVV. (l/3 X ml, 2/3 X ml, and X ml correspond to RVV of 0.5, 1.0, and 1.5 ml in Fig. 1.) Data values at top are average left ventricular diastolic and developed pressures recorded with RVV = 0.0 ml. Bars represent the standard error of the mean about the data points. For visual clarity, only every third standard error of the mean is shown. For each experiment, left ventricular volume was normalized by giving the peak left ventricular volume (volume at the peak of pressure-volume curve) a value of 100%. All other volumes in the experiment were expressed as a percent of the peak left ventricular volume. For example, in Fig. 1 the left ventricular volume 1.8 ml received a value of lOO%, while the volume 1.2 ml received a value of 67%. Since all the volumes did not occur in regular increments, plotted points represent a range in volume of 10%. FIG.
larger left ventricular volumes. Figure 23 is a plot of normalized left ventricular volumes versus the changes in left ventricular developed pressure. Figure ZB shows that small right ventricular volumes (RVV = l/3 X ml) were associated with increased left ventricular developed pressure, while large right ventricular volumes (RVV = X ml) were associated with reduced corded when the right 1.5 ml accordingly.
ventricular
balloon
was filled
with
0.5,l.O
and
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MYOCARDIAL
INTERACTION
BETWEEN
THE
365
VENTRICLES
left ventricular developed pressure. However, the magnitudes of these changes in left ventricular developed pressure were small. Figure 3 is a typical right ventricular pressure-volume relationship showing the effects of varying left ventricular volume on right ventricular diastolic and developed pressures. Figure 4A is a plot of normalized right ventricular volume versus the changes in right ventricular diastolic pressure. Left ventricular volume changes produce significant alterations in right ventricular diastolic pressure. Increasing left ventricular volume increased right ventricular diastolic pressure, while decreasing left ventricular volume decreased right ventricular diastolic pressure. Figure 4B is a plot of normalized right ventricular volume versus the changes in right ventricular developed pressure. The salient feature of Fig. 4B is the consistency of the increase in right ventricular developed pressure caused by increasing left ventricular volume. Except for the combination of peak right and left ventricular volumes, small, moderate and large left ventricular’ volumes were associated with similar effects on right ventricular isovolumic developed pressure. Cineradiographic experiments. Increasing right ventricular volume from 0.0 ml to its peak volume caused left ventricular diastolic septal-to-free wall distances, as measured in the horizontal view, to decrease by 4.8% (N = 5, P < 0.001) from 1.09 t 0.03 to 1.03 t .03 cm. Figure 5 is a typical diastolic left ventricular,horizontal outline before and after increasing right ventricular volume. (Because of the small size of the rabbit hearts, the magnitude of the dimensions are accordingly small.) The vertical view showed a flattening of the septum (an increase in the septal radii of curvature) caused by increasing right ventricular volume from 0.0 ml to its peak volume. Septal radii of curvature increased by 49.9% (N = 5, P < 0.002) from 1.66 to 2.49 cm. Both the decrease in the septal-to-free wall distance and the increase in the septal radii of curvature are indicative of a shift of the septum toward the left ventricle as a result of the increase in right ventricular volume. In a reciprocal manner, an increase in left ventricular volume was observed to shift the septum toward the right ventricular cavity. The vertical tine view showed that increasing left ventricular volume from 0.0 ml to two-thirds to peak volume caused the septal radii of curvature to decrease by 72.8% (N = 5, P < 0.001) from 29.2 t 12.8 to 8.1 t 2.1 cm, and septal displacement to increase by 15.1% (N = 5, P < 0.001) from 0.59 t 0.02 to 0.68 t 0.03 cm. Figure 6 is a diastolic right ventricular vertical outline before and after increasing left ventricular volume. Thus, changes in ventricular diastolic volume can alter the position and shape of the septum. In addition, these changes in septal shape are not restricted to individual areas of the septum, but appear to effect the entire septum. Note in Figs. 5 and 6 the uniformity of septal shape with changes in ventricular volume. Because of the small, biphasic response of the left ventricular isavolumic developed pressure to increasing right ventricular volume (Fig. 2B), left ventricular
e
A
14-
0 * 0
t-4 CY b-
-
P + 6 c( a
0
X 0 0 X a l
o-
0 0
l u
0
c!
-2-
I
l2
RIGHT 4a
I
.4
I
l6
I
me
VENTRICULfW
I
I
1lo
VOLUME
1.2
I
1.4
[ML)
6
0
0
X
0
0 X 0 0 X 0
0 0 X 0
0 X
a 10
I
.2
RIGHT
I
.4
I
.6
VENTRICULW
I
98
I
1 .o
VOLUME
I
1.2
I
1.4
(ML1
3. Results from one experiment showing effects of left ventricular volume on right ventricular diastolic pressure (A) and right ventricular developed pressure (B). 0 Represents values of right ventricular pressures recorded with no fluid in the left ventricular balloon; #, 0, X represent values of right ventricular pressure recorded when the left ventricular balloon was filled with 0.6, 1.2, and 1.8 ml accordingly. Note data in Figs. 1 and 3 come from the same experiment. FIG.
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366
SANTAMORE MEAN
RIGHT
VENTRICULAR
A
( Vl V= -4.0
-3.1
DIASTOLIC 0.0
ml
-1.2
-22
FRESSUREimnr)
-.I
.a
2J
3.9
Loft
Atrium
Axis
0’04--
\\
I
I RIGHT
11
4.0
a
3.5
VINTRICULAR
B
MEAN
NORMALIZED
RIGHT
Loft Ventricular
VOLUME
VENTRICULAR
DEVELOPED
3.o
zz
1.0
)3 *ia
Wll a.6
9.7
:f 5 Y ;r2 H Y ca XI 8 ;;a p'
fro.
?RESSlJRE
(LVV= o.oml)
';^p
316
s
2.5
I I I I I I I \ \
--k Left
\\ ‘\
Ventricular
: U
Soptum
\
Diastolic
I I I I I I
&the
\
2.0
I I I I I
1.5
Y UN soy
AL.
pressures, caused by varying the contralateral ventricular volume, represent changes in ventricular function that are transmitted from one ventricle to the other through the myocardium. The basis for this myocardial interaction lies in the close anatomical association between the ventricles of the heart (16, 17, 20). In addition to the intraventricular septum, common muscle bundles encircle both ventricles. Hence, the degree of contrac-
I -.2
ET
0.5
! 0.0
I
vv=o ml - .I
I
-7
L 0
II 10
I 20 RIGHT
30 VENTRICULAR
II 40
I SO
60 NORMALlZtD
I
I
70
80
II 90
100%
VOLUME
FIG. 4. Effects of altering left ventricular volume (LVV) on right ventricular diastolic and developed pressures in 10 experiments. ‘13 X, *I3 X, and X indicate fraction of leak LVV(X) (corresponding to 0.6, 1.2, and 1.8 ml in Fig. 3). Data values at top are average right ventricular diastolic and developed pressures recorded with LVV = 0.0 ml. For each experiment, right ventricular volume was normalized by giving the peak right ventricular volume a value of 100%. All the other volumes in the experiment were expressed as a percent of For example, in Fig. 3 the right peak right ventricular volume. ventricular volume 1.4 ml received a value of 10096, while the volume 1.0 ml received a value of 71%.
--
Right
Ventricular
Volume
-
Right
Ventricular
Volume=
= Ooml 23
ml
5. Typical horizontal 1eR ventricular diastolic increasing right before (- - -) and after (-)
FIG.
tained volume.
Right
developed pressure changes resulting from right ventricular volume alterations were not investigated in the cineangiographic experiments. On the tine images, the septum was readily observed to bulge into the right ventricular cavity during systole. Increasing left ventricular volume from 0.0 ml to two-thirds its peak volume caused the septum to bulge further into the right ventricular cavity as measured by a 24.8% (N = 5, P < 0.1) decreased in the septal radii of curvature from 6.0 t 1.6 cmto 4.4 +- 0 .8 cm and by a 4.3% (N = 5, P < 0.01) increase in the septal displacement from 0.68 t 0.03 to 0.71 t 0.03 cm.
Diastolic
Ventricular
Free
Out
Wall
line
I
2.00cm DISCUSSION
In this study, an isolated heart preparation was used because it removes all neural, humoral, pericardial, and pulmonary circulatory influence upon the heart. Thus the only way one ventricle could effect the other ventricle was through the myocardium. Therefore, the observed changes in ventricular diastolic and developed
outline obventricular
Displacement -FIG.
tained ume.
left
Ventricular
Volume=O.O
ml
Left
Ventricular
Volume+2
ml
6. Typical vertical right before (- - -) and aRer (->
ventricular increasing
diastolic outline left ventricular
obvol-
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MYOCARDIAL
INTERACTION
BETWEEN
THE
VENTRICLES
tion or distension of one ventricle effects the other ventricle via the myocardium. The results of these experiments demonstrate that varying left ventricular volume in the beating heart can acutely change the right ventricular diastolic pressurevolume relationship. Increasing left ventricular volume caused an increase in right ventricular diastolic pressure, while decreasing left ventricular volume caused a decrease in right ventricular diastolic pressure. The results also demonstrate acute changes in left ventricular diastolic pressure-volume relationship caused by varying right ventricular volume. In particular, increasing right ventricular volume caused an increase in left ventricular diastolic pressure, while decreasing right ventricular volume caused a decrease in left ventricular diastolic pressure. Prior to these experiments, similar acute alterations in the diastolic pressure-volume characteristics of the ventricles had been shown in the postmortem state (9, 10, 22) and had been implied to occur in vivo (1 5) The intraventricular septum is an important element in the relationship between right and left ventricular diastolic pressure-v01 ume characteristic. As observed in the cineradiographic experiments, increasing left ventricular volume shifts the septum toward the right ventricular cavity, thereby increasing right ventricular diastolic pressure. In a reciprocal manner, increasing right ventricular volume causes the septum to shift toward the left ventricle, thereby increasing left ventricular diastolic pressure. This leftward displacement of the septum with increasing right ventricular volume has also been reported bY Be&s et al. (1) and Stool et al. (19). The changes in ventricular diastolic pressure-volume characteristics may be important in the development of systemic venous congestion following acute myocardial infarction in man (22) and in the normal cardiovascular response to changes in posture and respiration. In an acute myocardial infarction with elevated left ventricular end-diastolic pressure, the right ventricle has to pump against an increased pulmonary arterial pressure. In addition, left ventricular distension can change the right ventricular diastolic pressure-volume relationship (Fig. 4A). The combination of these two effects can lead to abnormally high right ventricular filling pressure and systemic venous congestion. Changes in posture evoke a wide range of cardiovascular responses which act to maintain an adequate cardiac output. Hoffman et al. (8) observed in dogs tilted from supine to erect position an immediate fall in right ventricular stroke volume. However, left ventricular stroke volume remained constant for another l-3 beats. After the initial rapid fall, the stroke volume of each ventricle decline gradually to reach an equilibrium at a new low level which occurs about 6 beats earlier on the right than on the left. Hoffman and co-workers attribute this delayed onset and slower time course of responses of the left ventricle to the pulmonary blood reservoir. From the results of this study, an alternative or additional mechanism can be postulated. When changing from a recumbent to a standing position, right ven .tricu lar volume decreases d ue to reduced venous return . This 9
l
367 decrease in right ventricular volume will change the left ventricular diastolic pressure-volume characteristics (Fig. 2A), in eff ect making it easier to fill the 1eR ventricle. Thus, despite the decrease in right ventricular stroke volume and pulmonary arterial pressure, left ventricular filling and stroke volume would initially be maintained. In effect, this change in left ventricular diastolic pressure-volume characteristics would help to buffer the sudden decrease in right ventricular output. During inspiration, right ventricular end-diastolic volume and stroke volume increase, while left ventricular stroke volume remains constant or decreases. If inspiration is deep, left ventricular stroke volume always falls (8). It is generally believed that the decrease in left ventricular stroke volume is due to a decrease in left ventricular filling pressure (3, 14). (Left ventricular filling pressure is equal to the mean pulmonary capillary pressure minus left ventricular diastolic pressure.) The pericardium was initially believed to be responsible for the decrease in left ventricular filling pressure because of competition by the two ventricles for fixed intrapericardial volume (4). Guntheroth et al. (7) in a study of dogs demonstrated that this theory was not correct. The results presented in this study can be used to explain the observed decrease in left ventricular stroke volume during inspiration. With inspiration right ventricular volume increases. This increase in right ventricular volume causes a change in the left ventricular diastolic pressure-volume characteristics (Fig. 2A), making it harder to fill the left ventricle. Thus, without a change in left ventricular filling pressure, left ventricular diastolic volume would be decreased. By the Starling mechanism, this decrease in left ventricular diastolic volume would result in the observed decrease in left ventricular stroke volume. From the active pressure-volume experiments, the influence of right ventricular volume on left ventricular isovolumic developed pressure was shown to be biphasic. Small right ventricular volumes augmented left ventricular isovolumic developed pressure, while large right ventricular volumes reduced left ventricular isovolumic developed pressure. The crossover point was on the upper portion of the ascending limb of the right ventricular pressure-volume curve. However, right ventricular volume effects on left ventricular developed pressure are small and probably insignificant under normal physiological conditions. For the right ventricle, the left-ventricular volume effects on right ventricular developed pressure were more consistent and of a larger magnitude. Except for the combination of largest left and right ventricul ar volume, increasing left ventricular volume resulted in an increase-in right ventricular developed pressure. Thus, in the normal physiological range, left ventricular volume augments right ventricular pressure development. Other studies (13) also noted a strong influence of the left ventricle on right ventricular developed pressure. Oboler et al. (13) observed that the first derivative of right ventricular pressure is double peaked with one peak corresponding in time to the maximum derivative of left ventricular pressure. He speculated that the right ventricle is normally assisted in its pumping action by the left ventricle. The results
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368 obtained in this study support Oboler’s observations. In addition, left ventricular ischemia and structural damage have also been demonstrated in this laboratory to effect right ventricular developed pressure, independent of neural, humoral, pericardial, and pulmonary circulatory influences.
SANTAMORE
ET
AL.
The authors thank Drs. B. Rusy and R. Tallarida for their advice and assistance and Ms. Barbara McDonald and Dorothy Kallio for their help in the preparation of the manuscript. Address of G. Meier: Dept. of Biomedical Engineering and Science, Drexel University, Philadelphia, Pa. Received
for publication
24 December
1975.
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