Volume Number
121 3, Part
Late streptokinase
1
U, Wegscheider K. Impact of late coronary artery reperfusion on left ventricular function one month after acute mvocardial infarction. Am J Cardiol 1989;64:878-84. 16. Silberherg J, Haichin R, Stewart S, Lisbona R, Sniderman A. Long-term stepwise sustained improvement in left ventricular eiection fraction after mvocardial infarction. AM HEART J iy89;117:532-7. 17. Force I. Kemner A. Leavitt M. Parisi AF. Acute reduction in functional infarct expansion with late coronary reperfusion:
in AMI
assessment with quantitative two-dimensional echocardioprauhv. J Am Co11 Cardiol 1988:11:192-200. 18. be -Wbod MT, Spores J, Notski R, et al. Prevalence of total coronary occlusion during the early hours of myocardial infarction. N Engl J Med 1980;303:897-902. 19. De Wood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction. N Engl J Med 1986:315:417-23.
Impedance measurement of absolute blood flow using an angioplasty catheter: A validation study An angioplasty catheter was developed to allow measurement of absolute coronary blood flow during interventional procedures. This method uses electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator-dilution principles. The indicator is injected through a port located just proximal to the dilating balloon and the resulting changes in blood impedance are measured by electrodes at the catheter tip. Excellent linear correlations were found between known flow in 2 to 4 mm to diameter plastic tubes and catheter measurements (I = 0.99) and between timed collection canine femoral artery flow and catheter measurements (r = 0.97). Final validation was performed in canine coronary arteries using electromagnetic flowmeter data as the standard (r = 0.94). Thus accurate clinical determination of absolute coronary blood flow can be accomplished using this relatively inexpensive and simple catheter technique. (AM HEART J 1991;121:745.)
Lisa W. Martin, MD, Rodney A. Johnson, MD, Helen Scott, Shawn Robinson, MD, Glenn Beauman, Mark Englehardt, MD, and Robert A. Vogel, MD. Baltimore, Md.
Despite the increasing use of coronary angioplasty for the management of acute and long-standing coronary disease, the indications for and the results of this important intervention are largely determined by means of anatomic criteria. These criteria may not adequately assess the significance of a coronary stenosis. Estimates of percent stenosis have been found to have marked interobserver and intraobserver variabilitylm3 and correlate poorly with findings at autopsy. 4, 5 Assessment of the severity of a stenosis is From
filiate Received
Reprint Iiniversity 21201. 411126528
of Cardiology, Department of Medicine, University School of Medicine. in part by the University of Maryland, and by the Maryland
the Division
Maryland Supported
of the American
Heart
for publication
requests:
Robert
of Maryland
Association,
Inc.
Dec. 26, 1989;
accepted
A. Vogel, MD, Hospital
Aug.
Division
, 22 South
Greene
of
Af-
16, 1990.
METHODS
of Cardiology/N3W77, St., Baltimore.
particularly difficult during angioplasty. Importantly, percent stenosis, as utilized clinically, correlates poorly with the functional significance of coronary stenoses.6 Direct measurements of blood flow may more accurately define the hemodynamic effects of stenoses. This report describes a new angioplasty catheter system for measuring absolute blood flow in the catheterization laboratory, which is compatible with standard angioplasty techniques. It utilizes electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and the indicator-dilution principle. The purpose of this investigation was to study the operating characteristics of the catheter, and to validate its ability to measure blood flow.
MD
Catheter design. The catheter system (USC1 Division of C.R. Bard, Inc., Billerica, Mass.) differed from a standard angioplasty catheter only by the addition of a third lumen 745
746
Martin
et al.
. . . . . . . . . . . . . . . . . . . .
Fig. dard third mal and tip.
1. Diagram of the catheter. The catheter is a stanangioplasty catheter, modified by the addition of a lumen terminating in a side port located just proxito the dilating balloon for flow indicator injection, with two pairs of electrodes located at the catheter
terminating in a side port located just proximal to the dilating balloon, through which the flow indicator bolus was injected, and by the presence of two pairs of electrodes located on the catheter tip. The microelectrodes were approximately 0.1 by 1.0 mm in size and were located 4 cm distal to the infusion port. The electrode pairs were separated by 2 mm. Insulated continuations of the electrode wires traversed the length of the catheter, allowing connection to the external electrical circuit and permitting impedance measurement (Fig. 1). Reference solution. A 5r;, aqueous dextrose solution (D5W) was used as the flow indicator. The dextrose solution is hyposmolar with respect to blood, and increases impedance proportional to the concentration of D5W. One half milliliter D5W, injected as a bolus from the sideport over 3 to 5 seconds, produced a measurable first-pass impedance curve. Flow measurements. Impedance was measured across the catheter electrodes using a constant 10 PA current produced by a sine-wave generator at a frequency of 50 kHz. Cardiac stimulation or other biologic effects of this current were not seen. Impedance was measured by the electrical potential (voltage) generated across the two sets of electrodes. The gap potential was amplified, rectified, and filtered to produce a direct current output. The output was continuously recorded at a paper speed of 5 mm/set on a multichannel recorder (Model 3800, Gould Inc., Cleveland, Ohio). The recorded voltage was calibrated to ohms by comparison with known resistances. Flow was calculated by the Stewart-Hamilton principle as the volume of indicator injected (0.5 ml), multiplied by the “sensitivity constant” (KS), divided by the area under the impedance-time curve. The area under the transit curve was measured by planimetry. KS, the factor converting impedance to indicator concentration, was determined experimentally. in vitro validation. The linearity of the impedance response? reference bolus mixing, and accuracy of flow measurements were first studied in phantom arteries. The linearity of impedance response to increasing concentrations of D5W was evaluated by placing the distal segment of the catheter in solutions of 0.45 % saline diluted with increasing concentrations of D5W (to 30% D5W by volume). Impedance was compared with D5W concentration by linear regression analysis. The slope of the relationship of impedance to D5W concentration was recorded as KS. KS was also determined in plastic tubes of 2,3, and 4 mm internal diameter. The impedance response to concentration of
American
March 1991 Heart Journal
D5W was then tested in blood warmed to 37’ C, with a range of hematocrit from Ofi (plasma) to 55”, . The values obtained for KS were then compared with hematocrit using linear regression analysis. The linearity of impedance response to increasing volumes of D5W boluses was tested in vitro in 3 mm diameter plastic tubes. A solution of 0.45% saline (impedance similar to blood) was power injected through the tube (Medrad Inc., Pittsburgh, Pa.) at a constant rate of 30 ml/min to simulate blood flow. Boluses of 0.1 to 1.0 ml D5W were injected through the catheter’s side port located proximal to the balloon. The areas under the transit curve were compared with volume of indicator injected, using linear regression analysis. The adequacy of mixing was tested in plastic tubes by comparing calculated flow with known flow, varying injection time over a wide range. A solution of O-45“, saline was injected through a 3 mm diameter plastic tube over a wide range of flow (10 to 300 ml/min). Boluses of 0.5 ml D5W were given at rates varying from 3 to 16 seconds. Flow was calculated as above. Comparison of known flow with catheter-measured flow was performed in 2,3, and 4 mm diameter plastic tubes. As previously, 0.45’;. saline injected at 10 to 300 ml/min was utilized to simulate coronary blood flow. One half milliliter D5W was injected as a reference bolus over 3 to 5 seconds. Calculated and known flow were compared by linear regression analysis. Femoral artery validation. Flow measurements were validated in 3 to 4 mm diameter canine femoral arteries using timed collection data as the standard. Four mongrel dogs underwent general anesthesia with pentobarbital sodium (35 mg/kg) and were ventilated with a Harvard respirator (Harvard Apparatus Inc., Millis, Mass.) (guiding principles of the American Physiological Society were followed). A femoral artery was isolated and cannulated for collection of blood flow. The carotid artery was cannulated to allow catheter introduction. Heparin (3000 units) was given, and the catheter was advanced to the femoral artery under fluoroscopic guidance. An electromagnetic flow probe was positioned around the artery to document steady-state flow. The catheter injection lumen was flushed with D5W prior to flow measurements. Boluses of 0.1 to 1.0 ml of D5W were injected, and the areas under the transit curves were compared with the amount injected by linear regression analysis. Flow was altered by adjusting the screw occluder on the distal femoral cannula. Simultaneous timed collections and catheter flow measurements were made at each level of flow. At the end of the experiment, KS was determined in situ by measuring impedance during retrograde injection of canine blood diluted with varying concentrations of D5W. Subsequent values of KS were normalized to correct for vessel diameter, hematocrit, and individual catheter electrical properties. Normalization was achieved by multiplying KS initially obtained experimentally by the ratio of baseline impedances obtained in subsequent experiments to the initial baseline impedance. Calculated flow values were compared with timed collections by linear regression analysis.
Volume Number
121 3, Part
Catheter
1
11501 0.000
0.020
0.040
0.060
CONCENTRATION Fig. 2. Relationship between D5W concentration sensitivity constant of the system (KS).
350
0.080
300
i
E
250
g E! E? 4
200 11
of absolute blood flow
747
0.100
OF D5W
and impedance.
The slope of this relationship
A
z-5
measurement
A A 0 0
A
~300 = 120 - 30 = 10
is the
ml/min ml/min ml/min ml/min
A
150--
A
AA A
100 0
2
0a
50
0
0
l mDO. . QOO 0 0 0, 5
TIM: &C)
0
4
15
INJECTION Fig.
3. Dependence
of calculated
Coronary artery validation. Seven mongrel dogs were anesthetized with pentobarbital sodium (35 mg/kg), intubated, and ventilated with a Harvard respirator with room air. A left thoracotomy was performed and the heart was suspended in a pericardial cradle. The proximal left anterior descending artery (two dogs) or circumflex artery (five dogs) was dissected free from surrounding tissue and an appropriately sized electromagnetic flow probe (Carolina Medical Electronics, Inc., King, N.C.) and snare were placed around the vessel. Small side branches were ligated if required. The right carotid artery was cannulated, a sheath was inserted, and heparin was given. A multipurpose guiding catheter was inserted in the carotid artery sheath and was appropriately positioned at the ostium of the left main coronary artery under fluoroscopic guidance. The angioplasty catheter was then advanced to the appro-
flow on injection
time.
priate coronary artery, with the injection port of the catheter located adjacent to the electromagnetic flow probe. Flow probes were frequently rezeroed, and phasic arterial tracings and reactive hyperemia were noted to ensure proper flow probe fit. Flow was varied using a snare to reduce flow, and by the administration of papaverine and/or epinephrine to increase flow. Electromagnetic and catheter flow measurements were made at each flow state and were compared by linear regression analysis. RESULTS In vitro studies.
An example of the relationship between D5W concentration and impedance is shown in Fig. 2 for data obtained in a 3 mm tube. The impedance response to D5W concentration was found to be
748
Martin
et al.
American
March 1991 Heart Journal
400 A
350 :
L
300
.E.
2501
cf
150+
E = 2
lOOi
.-L
o = 4mm
tube
l = 3mm A= 2mm
tube tube
./ 0
,I -/,i ,
N
50
/
--
/
0
50
= 26
r = 0.99
100 ACTUAL
4. Comparison
G
Y = 1.09x-3.53
0
Fig.
_,
0
of catheter-calculated
linear. The slope of this relationship is the sensitivity constant (KS). Linear relationships were found between hematocrit (Hct) and KS (KS = 4.3 X Hct + 475.4; r = 0.72, n = 13) and between hematocrit and baseline impedance (Impedance = 9.2 x Hct + 567.7; r = 0.92, n = 13). Baseline impedance was also linearly related to KS (r = 0.835). This relationship served as the basis for normalizing KS to baseline impedance. As is necessary for use of the indicator-dilution principle, alinear relationship was found between the volume of indicator injected in plastic tubes and the area under the first-pass curve (n = 10, r = 0.995). Varying injection times from 3 to 6 seconds had no influence on curve area and resulted in accurate flow determinations, suggesting complete mixing. Prolonged injection times of more than 10 seconds caused flow to be slightly overestimated, suggesting incomplete mixing (Fig. 3). Fig. 4 depicts calculated flow in 2,3, and 4 mm diameter tubes over a range from 10 to 300 ml/min. An excellent correlation (y = 1.09X - 3.53; r = 0.99, n = 26) was found, with a slope near unity. Femoral artery studies. As in the in vitro studies, a linear relationship was found between the volume of indicator injected in canine femoral arteries and the area under the first-pass curve (area = 1228 X volume injected + 9.27; r = 0.997, n = 7). Fig. 5 depicts calculated flow versus timed collection data in canine femoral arteries. The flow range was varied from 6 to 240 ml/min. A good correlation between the catheter method and the timed collection standard was found, with accurate prediction of flow (y = 1.10X + 9.31; r = 0.97, n = 45).
200
150 FLOW
i-+----i 250
300
350
(ml/min>
and actual 0.45”,, saline flow in plastic tubes.
Coronary artery studies. Examples of first-pass impedance-time curves obtained after a bolus administration of 0.5 ml D5W are shown in Fig. 6 for three different flow levels in two dogs. (The impedance curves are offset and magnified). These demonstrate maximal and minimal observed cardiac cyclical variation. Corresponding electromagnetic flow recordings are also shown. The electromagnetic flow recordings show little perturbation of intrinsic flow by the D5W injection. No significant changes in blood pressure or cardiac rhythm were noted during D5W administration. At increasing flow rates, the area under the curve diminishes, as expected from the indicatordilution principle. The calculated flows were found to be reproducible. Comparison of repeated measurements at the same flow rate demonstrated a close correlation (y = 11.9 + 0.82X; r = 0.91, n = 8). The correlation between flow obtained from catheter measurements and electromagnetic flow probe readings for each dog was calculated, and ranged from 0.90 to 0.99 (mean 0.94 +_ 0.013 SE). Fig. 7 demonstrates catheter versus electromagnetic flow for all seven subjects, over a range from 3 to 300 ml/min. An excellent correlation between these two techniques was found (y = 0.85X + 11.4; r = 0.94, n = 82). DISCUSSION Previous flow
methods. Coronary sinus flow has been measured using thermodilution catheters to determine global coronary flowa However, regional blood flow measurements are necessary in the setting of segmental coronary artery disease. Great cardiac vein flow has been measured by this technique to assess left anterior descending flow selectively. How-
Volume
121
Number
3.
Part
Catheter
1
measurement
absolute blood poul
of
749
250
100
N = 45 Y = 1.10x+9.31
50 0
c=
0
50
100
150
200
TIMED COLLECTION FLOW Fig.
Comparison
5.
of catheter-calculated
and timed
collection
0.97
250
300
(ml/min)
blood flow data in canine femoral
arte-
ries.
CORONARY BLOOD 150 FLOW (ml/min)
IMPEDANCE (400 ohms full scale)
TIME (1
second
=
1
major
division)
6. Examples of first-pass impedance-time curves for three different flow levels obtained in two caFig. nine coronary studies. These examples demonstrate maximal and minimal observed cardiac cyclical variation. Corresponding mean electromagnetic flow recordings are shown above.
ever, consistent placement of the catheter in the great cardiac vein may be difficult to obtain, and blood flow cannot be measured. to other territories Recent developments in digital radiographic para-
sessment of absolute coronary blood flow has been reported in relatively straight, non-bifurcating vessels.12 Recently,13 radiographic assessment of coro-
metric
principles. This approach requires absence of patient motion and digital radiographic equipment. Indicator dilution principle. Indicator dilution methods, first studied by Stewart in 1897,14 have been employed for the measurement of absolute blood flow.14, l5 The indicator can be injected either at a constant rate (e.g., coronary sinus thermodilution catheter) or as a bolus from a proximal location (e.g., cardiac output thermodilution catheter). The indicator concentration downstream is diluted proportionally to blood flow, which is the basis for measur-
flow imaginga, g and in Doppler
technology10
have permitted
the assessment
catheter of coro-
nary flow ratios such as coronary flow reserve. Factors other than the severity of coronary stenoses may, however, affect flow reserve.ll Especially in the comthis relative paplex setting of acute angioplasty, rameter can give false estimates of the significance of individual coronary lesions and the efficacy of dilatations. This problem may in part be due to the variability in baseline coronary flow, which constitutes the denominator in this parameter. Radiographic as-
nary flow has been described
using
indicatordilution
750
Martin
et al.
T
300
c
250
E Fi
200
d
150
E t
100
.-
N
- 82
F
Y -
8
r = 0.94
50 0
0
50
100
150
200
ELECTROMAGNETIC Fig. 7. Comparison of catheter-calculated nine coronary arteries.
300
350
FLOW (ml/min)
and electromagnetic
ing absolute flow. Flow is calculated by the equation: Flow = (Volume of indicator x Ks)/(Area under first-pass curve), where KS is the transformation of detector units to absolute indicator concentration units. Flow, as derived in this equation, is determined at the point of indicator injection. Sampling can be performed at any point in the vascular tree after adequate mixing has occurred. Impedance changes occurring after an injection of an indicator have been utilized to measure cardiac output. This technique was first used by Stewart,14, l5 who employed hypertonic saline asthe indicator. The concentration of saline in blood samples withdrawn from the sampling site was determined by matching the conductivity (inverse of impedance) of the sample with that of blood to which a known amount of saline had been added. White16 utilized the bolus indicator technique to measure cardiac output, employing hypodermic needle electrodes inserted directly into an artery. The intraarterial impedance was recorded continuously as the bolus of saline passed the electrodes, generating an impedance-time curve. More recently, coronary sinus flow has been measured by impedance techniques.17 This technology has not previously been applied to the measurement of blood flow in coronary arteries, as an appropriate detector system has not been available. Requirements for a method to assesscoronary arterial blood flow include the use of a nontoxic indicator that does not alter flow itself, and a detector system that can be placed on a small diameter flexible catheter to allow subselective positioning in a coronary artery. Advantages of the current method. Catheter mea-
250
0.85w+11.4
flowmeter
blood flow data obtained
in ca-
surement of absolute coronary blood flow has not previously been accomplished. This inexpensive method provides rapid determination of blood flow without radiographic image processing. The dextrose solution indicator is readily available and meets the requirements for application of indicator dilution theory in that it mixes easily with blood and produces a linear impedance indicator signal. There is no alteration in intrinsic flow, as demonstrated by the electromagnetic flow tracings. There is no evidence that vasodilation or hemolysis occurs as a result of injection of this small volume of dextrose solution. Extravascular loss of indicator during the first-pass transit is minimal. Repeated measurements can be performed without concern for toxicity. Recirculation is not evident in the impedance-time curves. Mixing of the indicator and intrinsic blood flow appears to be adequate, resulting in impedance-time curves that accurately predict flow independent of injection rate. (According to indicator dilution principles, the rate of injection and the shape of the transit curve should not influence flow calculations). Laminar flow in straight plastic tubes represents a worst case for mixing. Tortuosity of the artery, branching, and stenoses would tend to increase turbulence and thus improve mixing. The administration of the indicator through a pinhole side port, which causes spraying of the solution, may also play an important role in providing adequate mixing over the 3 cm separation from port to electrodes.18 Other factors taken into consideration in the design of the catheter are important for impedance measurements. Close electrode spacing (2 mm) allows sensing of local indicator concentration within a
Volume
121
Number
3, Part
Catheter
1
short range. Parallel conduction by surrounding structures beyond 3 mm has been found to have minimal effect (little difference between impedance in 3 and 4 mm tubes and arteries). Additionally, it has been shown in canine femoral arteries that the addition of a 0.45 % saline bath (simulating parallel conductance) changes baseline impedance minimally.18 The relationship between calculated and known flow appears to be linear over a wide range, allowing measurements of reactive hypermia. Cannulation of the coronary sinus or great cardiac vein, needed for thermodilution methods, is not necessary. Assessment of coronary flow by this technique should not lengthen the procedure significantly, as the dilation catheter can be employed directly. Finally, this method measures absolute Aow and is therefore not subject to the variance in baseline flow, as are flow reserve measurements. Potential limitations. It is necessary that flow remain constant for approximately 5 seconds during application of this technique, and phasic flow cannot be obtained. Total coronary flow, without transmural segmentation, is obtained. However, this method is not subject to the limitations encountered in measuring perfusion by the Kety-Schmidt washout method in circumstances of high flow or regional or transmural inhomogeneous distribution.‘g Arterial branching may affect flow measurement accuracy. Using the indicator dilution principle, flow is measured at the site of indicator injection and concentration may be measured at any location downstream. Care must be taken to ensure that the indicator is not injected directly into a branch artery before mixing occurs. Loss of indicator into a side branch would cause underestimation of indicator concentration and overestimation of coronary blood flow. With catheter placement at a wide variety of distances from side branches and a wide variety of mixing distances during our coronary artery validation studies, this did not appear to be a problem. The chance that the indicator is lost in a side branch before mixing is small. The indicator dilution principle requires linearity of indicator concentration detection. Some degree of nonlinear impedance response occurs at concentrations of D5W above approximately 20 % . This would have a significant effect only at very low flow rates. A four-electrode system, with application of the current between the outer two electrodes and measurement of the potential difference between the inner two electrodes, has a theoretical advantage over the two-electrode system utilized.20 However, a fourelectrode system would be very difficult to place on a catheter small enough to be utilized clinically.
measurement
of absolute blood flow
751
The results obtained with the two-electrode system appear to be sufficiently accurate for clinical practice. As the sensitivity constant (KS) was found to vary proportionally to baseline impedance, normalization of KS was employed. This appproach tends to correct for alteration for Hct, temperature, vessel diameter, and electrode characteristics. Although only an estimate, this value appears to be adequate for clinical application. Normalization of Ks in humans would be done in a similar fashion. Minor drift in baseline impedance was occasionally observed, possibly due to catheter movement within the arterial lumen. Changes in saline content, Hct, temperature, and distending blood pressure may occur during the extensive procedure in the animal laboratory. These factors may alter baseline impedance. The baseline normalization used to obtain KS is only an estimate. This estimate provided the appropriate calculation for flow in femoral arteries with timed collection as the standard, as the slope of the regression line between timed collections and calculated flow was close to unity. (For flow in coronary arteries, the slope of the regression line is less than unity, possibly due in part to problems inherent in the use of electromagnetic flow probes.) Finally, the catheter itself is large enough to interfere with hyperemic flow in smaller coronary arteries or when it is placed across a stenosis. In clinical practice, the catheter would have to be positioned proximal to a stenosis. To eliminate this problem, we are currently investigating a similar approach using an electrode angioplasty guide wire.21 Despite these limitations, this method for measuring absolute coronary blood flow appears to be relatively simple, safe, inexpensive, and accurate over a wide range of flow. We thank USC1 Division of C. R. Bard, Inc., Billerica, supplying the catheters used in this study.
Mass.,
for
REFERENCES
1. Cameron P, Swaye P, Ryan T, Maynard C, Bourassa M, Kennedy J, Gosselin A, Kemp H, Faxon D, Wexler L, Davis K. Reproducibility of coronary arteriographic reading in the coronary artery surgery study (CA%). Cathet Cardiovasc Diagn 1982;8:565-75. 2. Zir LM, Miller SW, Dinsmore RE, Gilbert JP, Hawthorne JW. Interobserver variability in coronary arteriography. Circulation 1976;53:627-32. 3. Detre KM, Wright E, Murphy ML, Takaro T. Observer agreement in evaluating coronary angiograms. Circulation 1975;52:979-86. 4. Arnett E, Isner J, Redwood D, Kent K, Baker W, Ackerstein H, Roberts W. Coronary artery narrowing in coronary heart disease: comparison of cineangiographic and necropsy findings. Ann Intern Med 1979;91:350-6. 5. Grondin C, Dydra I, Pasternac A, Campeau L, Bourassa M,
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Lesperance J. Discrepancies between cineangiographic and postmortem findings in patients with coronary artery disease and recent myocardial infarction. Circulation 1974;49:703-8. 6. White CW, Wright CB, Doty DB, Hiratzka LF, Eastham CL, Harrison DG, Marcus ML. Does visual interpretation of the coronary arteriogram predict the physiologic importance of a coronary stenosis? N Engl J Med 1984;310:819-24. I. Ganz WW, Tamura K, Marcus HS, Donoso R, Yoshida S, Swan HJC. Measurement of coronary sinus blood flow by continuous thermodilution in man. Circulation 1976;44:18195. 8. Vogel RA, LeFree M, Bates E, O’Neill W, Foster R, Kirlin P, Smith D, Pitt B. Application of digital techniques to selective coronary arteriography: use of myocardial contrast appearance time to measure coronary flow reserve. AM HEART J 1984:107:X3-64. 9. Hodgson JM, LeGrand V, Bates ER, Mancini GBJ, Aueron FM. O’Neill WW. Simon SB. Beauman GJ. LeFree MT. Vogel RA. Validation in dogs of a rapid digital angiographic technique to measure relative coronary blood flow during routine cardiac catheterization. Am J Cardiol 1985;55:188-93. 10. Wilson RF, Laughlin DE, Ackell PH, Chilian WM, Holida MD, Hartley CJ, Armstrong ML, Marcus ML, White CW. Transluminal, subselective measurement of coronary artery blood flow velocity and vasodilator reserve in man. Circulation 1985;72:82-92. 11. Vogel RA. The radiographic assessment of coronary blood flow parameters. Circulation 1985;72:460-5. 12. Spiller P, Schmiel FK, Politz B, Block M, Fermor U, Hackbarth W, Jehle J, Korfer R, Pannek H. Measurement of sys-
American
13.
14. 15. 16. 17.
18.
19.
20.
21.
March 1991 Heart Journal
tolic and diastolic flow rates in the coronary artery system by x-ray densitometry. Circulation 1983;68:337-47. Gurley JC, Nissen SE, Haynie D, Elion JZ, Booth D, DeMaria A. A new method for measurement of absolute arterial blood flow bv dieital anaioarauhv [Abstract]. Circulation 1989; 8Ofsuppl II;II-413.- - ” Stewart GN. Researches on the circulation time and on the influences which affect it. J Physiol 1897;22:158-83. Stewart GN. The output of the heart in dogs. Am J Physiol 1921;57:27-50. White HL. Measurement of cardiac-output by a continuously recording conductivity method. Am J Physiol1947;151:45-57. Tommasini G, Tamagni F, Poluzzi C, Oddone A, Orlandi M, Cornalba C, Malusardi R. Coronary sinus hemodynamics in transient iscbemia. IEEE Comput Cardiol 1985;511-4. Martin LW, Zawodny R, Vogel RA. Impedance measurement of absolute arterial diameter using a standard angioplasty catheter [Abstract]. J Am Co11 Cardiol 1988;11:130A. Klocke F, Koberstein R, Pittman D, Bunnell I, Greene D. Rosing D. Effects of heterogeneous myocardial perfusion on coronary venous Hs desaturation curves and calculations of coronary flow. J Clin Invest 1968;47:2711-24. Vorhees WD, Bourland JD, Lamp ML, Mullikin JC, Geddes LA. Validation of the saline-dilution method for measuring cardiac output by simultaneous measurement with a perivascular electromagnetic flow probe. Med Instrum 1985;10:34-7. Martin LW. Scott H. Enelehardt M, Beauman G, Johnson RA, Vogel RA. kbsolute’blogd flow measurement using an angioplasty guidewire [Abstract]. Circulation 1989;8O(suppl II):II-
357.
121 3, Part
Late streptokinase
1
U, Wegscheider K. Impact of late coronary artery reperfusion on left ventricular function one month after acute mvocardial infarction. Am J Cardiol 1989;64:878-84. 16. Silberherg J, Haichin R, Stewart S, Lisbona R, Sniderman A. Long-term stepwise sustained improvement in left ventricular eiection fraction after mvocardial infarction. AM HEART J iy89;117:532-7. 17. Force I. Kemner A. Leavitt M. Parisi AF. Acute reduction in functional infarct expansion with late coronary reperfusion:
in AMI
assessment with quantitative two-dimensional echocardioprauhv. J Am Co11 Cardiol 1988:11:192-200. 18. be -Wbod MT, Spores J, Notski R, et al. Prevalence of total coronary occlusion during the early hours of myocardial infarction. N Engl J Med 1980;303:897-902. 19. De Wood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction. N Engl J Med 1986:315:417-23.
Impedance measurement of absolute blood flow using an angioplasty catheter: A validation study An angioplasty catheter was developed to allow measurement of absolute coronary blood flow during interventional procedures. This method uses electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator-dilution principles. The indicator is injected through a port located just proximal to the dilating balloon and the resulting changes in blood impedance are measured by electrodes at the catheter tip. Excellent linear correlations were found between known flow in 2 to 4 mm to diameter plastic tubes and catheter measurements (I = 0.99) and between timed collection canine femoral artery flow and catheter measurements (r = 0.97). Final validation was performed in canine coronary arteries using electromagnetic flowmeter data as the standard (r = 0.94). Thus accurate clinical determination of absolute coronary blood flow can be accomplished using this relatively inexpensive and simple catheter technique. (AM HEART J 1991;121:745.)
Lisa W. Martin, MD, Rodney A. Johnson, MD, Helen Scott, Shawn Robinson, MD, Glenn Beauman, Mark Englehardt, MD, and Robert A. Vogel, MD. Baltimore, Md.
Despite the increasing use of coronary angioplasty for the management of acute and long-standing coronary disease, the indications for and the results of this important intervention are largely determined by means of anatomic criteria. These criteria may not adequately assess the significance of a coronary stenosis. Estimates of percent stenosis have been found to have marked interobserver and intraobserver variabilitylm3 and correlate poorly with findings at autopsy. 4, 5 Assessment of the severity of a stenosis is From
filiate Received
Reprint Iiniversity 21201. 411126528
of Cardiology, Department of Medicine, University School of Medicine. in part by the University of Maryland, and by the Maryland
the Division
Maryland Supported
of the American
Heart
for publication
requests:
Robert
of Maryland
Association,
Inc.
Dec. 26, 1989;
accepted
A. Vogel, MD, Hospital
Aug.
Division
, 22 South
Greene
of
Af-
16, 1990.
METHODS
of Cardiology/N3W77, St., Baltimore.
particularly difficult during angioplasty. Importantly, percent stenosis, as utilized clinically, correlates poorly with the functional significance of coronary stenoses.6 Direct measurements of blood flow may more accurately define the hemodynamic effects of stenoses. This report describes a new angioplasty catheter system for measuring absolute blood flow in the catheterization laboratory, which is compatible with standard angioplasty techniques. It utilizes electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and the indicator-dilution principle. The purpose of this investigation was to study the operating characteristics of the catheter, and to validate its ability to measure blood flow.
MD
Catheter design. The catheter system (USC1 Division of C.R. Bard, Inc., Billerica, Mass.) differed from a standard angioplasty catheter only by the addition of a third lumen 745
746
Martin
et al.
. . . . . . . . . . . . . . . . . . . .
Fig. dard third mal and tip.
1. Diagram of the catheter. The catheter is a stanangioplasty catheter, modified by the addition of a lumen terminating in a side port located just proxito the dilating balloon for flow indicator injection, with two pairs of electrodes located at the catheter
terminating in a side port located just proximal to the dilating balloon, through which the flow indicator bolus was injected, and by the presence of two pairs of electrodes located on the catheter tip. The microelectrodes were approximately 0.1 by 1.0 mm in size and were located 4 cm distal to the infusion port. The electrode pairs were separated by 2 mm. Insulated continuations of the electrode wires traversed the length of the catheter, allowing connection to the external electrical circuit and permitting impedance measurement (Fig. 1). Reference solution. A 5r;, aqueous dextrose solution (D5W) was used as the flow indicator. The dextrose solution is hyposmolar with respect to blood, and increases impedance proportional to the concentration of D5W. One half milliliter D5W, injected as a bolus from the sideport over 3 to 5 seconds, produced a measurable first-pass impedance curve. Flow measurements. Impedance was measured across the catheter electrodes using a constant 10 PA current produced by a sine-wave generator at a frequency of 50 kHz. Cardiac stimulation or other biologic effects of this current were not seen. Impedance was measured by the electrical potential (voltage) generated across the two sets of electrodes. The gap potential was amplified, rectified, and filtered to produce a direct current output. The output was continuously recorded at a paper speed of 5 mm/set on a multichannel recorder (Model 3800, Gould Inc., Cleveland, Ohio). The recorded voltage was calibrated to ohms by comparison with known resistances. Flow was calculated by the Stewart-Hamilton principle as the volume of indicator injected (0.5 ml), multiplied by the “sensitivity constant” (KS), divided by the area under the impedance-time curve. The area under the transit curve was measured by planimetry. KS, the factor converting impedance to indicator concentration, was determined experimentally. in vitro validation. The linearity of the impedance response? reference bolus mixing, and accuracy of flow measurements were first studied in phantom arteries. The linearity of impedance response to increasing concentrations of D5W was evaluated by placing the distal segment of the catheter in solutions of 0.45 % saline diluted with increasing concentrations of D5W (to 30% D5W by volume). Impedance was compared with D5W concentration by linear regression analysis. The slope of the relationship of impedance to D5W concentration was recorded as KS. KS was also determined in plastic tubes of 2,3, and 4 mm internal diameter. The impedance response to concentration of
American
March 1991 Heart Journal
D5W was then tested in blood warmed to 37’ C, with a range of hematocrit from Ofi (plasma) to 55”, . The values obtained for KS were then compared with hematocrit using linear regression analysis. The linearity of impedance response to increasing volumes of D5W boluses was tested in vitro in 3 mm diameter plastic tubes. A solution of 0.45% saline (impedance similar to blood) was power injected through the tube (Medrad Inc., Pittsburgh, Pa.) at a constant rate of 30 ml/min to simulate blood flow. Boluses of 0.1 to 1.0 ml D5W were injected through the catheter’s side port located proximal to the balloon. The areas under the transit curve were compared with volume of indicator injected, using linear regression analysis. The adequacy of mixing was tested in plastic tubes by comparing calculated flow with known flow, varying injection time over a wide range. A solution of O-45“, saline was injected through a 3 mm diameter plastic tube over a wide range of flow (10 to 300 ml/min). Boluses of 0.5 ml D5W were given at rates varying from 3 to 16 seconds. Flow was calculated as above. Comparison of known flow with catheter-measured flow was performed in 2,3, and 4 mm diameter plastic tubes. As previously, 0.45’;. saline injected at 10 to 300 ml/min was utilized to simulate coronary blood flow. One half milliliter D5W was injected as a reference bolus over 3 to 5 seconds. Calculated and known flow were compared by linear regression analysis. Femoral artery validation. Flow measurements were validated in 3 to 4 mm diameter canine femoral arteries using timed collection data as the standard. Four mongrel dogs underwent general anesthesia with pentobarbital sodium (35 mg/kg) and were ventilated with a Harvard respirator (Harvard Apparatus Inc., Millis, Mass.) (guiding principles of the American Physiological Society were followed). A femoral artery was isolated and cannulated for collection of blood flow. The carotid artery was cannulated to allow catheter introduction. Heparin (3000 units) was given, and the catheter was advanced to the femoral artery under fluoroscopic guidance. An electromagnetic flow probe was positioned around the artery to document steady-state flow. The catheter injection lumen was flushed with D5W prior to flow measurements. Boluses of 0.1 to 1.0 ml of D5W were injected, and the areas under the transit curves were compared with the amount injected by linear regression analysis. Flow was altered by adjusting the screw occluder on the distal femoral cannula. Simultaneous timed collections and catheter flow measurements were made at each level of flow. At the end of the experiment, KS was determined in situ by measuring impedance during retrograde injection of canine blood diluted with varying concentrations of D5W. Subsequent values of KS were normalized to correct for vessel diameter, hematocrit, and individual catheter electrical properties. Normalization was achieved by multiplying KS initially obtained experimentally by the ratio of baseline impedances obtained in subsequent experiments to the initial baseline impedance. Calculated flow values were compared with timed collections by linear regression analysis.
Volume Number
121 3, Part
Catheter
1
11501 0.000
0.020
0.040
0.060
CONCENTRATION Fig. 2. Relationship between D5W concentration sensitivity constant of the system (KS).
350
0.080
300
i
E
250
g E! E? 4
200 11
of absolute blood flow
747
0.100
OF D5W
and impedance.
The slope of this relationship
A
z-5
measurement
A A 0 0
A
~300 = 120 - 30 = 10
is the
ml/min ml/min ml/min ml/min
A
150--
A
AA A
100 0
2
0a
50
0
0
l mDO. . QOO 0 0 0, 5
TIM: &C)
0
4
15
INJECTION Fig.
3. Dependence
of calculated
Coronary artery validation. Seven mongrel dogs were anesthetized with pentobarbital sodium (35 mg/kg), intubated, and ventilated with a Harvard respirator with room air. A left thoracotomy was performed and the heart was suspended in a pericardial cradle. The proximal left anterior descending artery (two dogs) or circumflex artery (five dogs) was dissected free from surrounding tissue and an appropriately sized electromagnetic flow probe (Carolina Medical Electronics, Inc., King, N.C.) and snare were placed around the vessel. Small side branches were ligated if required. The right carotid artery was cannulated, a sheath was inserted, and heparin was given. A multipurpose guiding catheter was inserted in the carotid artery sheath and was appropriately positioned at the ostium of the left main coronary artery under fluoroscopic guidance. The angioplasty catheter was then advanced to the appro-
flow on injection
time.
priate coronary artery, with the injection port of the catheter located adjacent to the electromagnetic flow probe. Flow probes were frequently rezeroed, and phasic arterial tracings and reactive hyperemia were noted to ensure proper flow probe fit. Flow was varied using a snare to reduce flow, and by the administration of papaverine and/or epinephrine to increase flow. Electromagnetic and catheter flow measurements were made at each flow state and were compared by linear regression analysis. RESULTS In vitro studies.
An example of the relationship between D5W concentration and impedance is shown in Fig. 2 for data obtained in a 3 mm tube. The impedance response to D5W concentration was found to be
748
Martin
et al.
American
March 1991 Heart Journal
400 A
350 :
L
300
.E.
2501
cf
150+
E = 2
lOOi
.-L
o = 4mm
tube
l = 3mm A= 2mm
tube tube
./ 0
,I -/,i ,
N
50
/
--
/
0
50
= 26
r = 0.99
100 ACTUAL
4. Comparison
G
Y = 1.09x-3.53
0
Fig.
_,
0
of catheter-calculated
linear. The slope of this relationship is the sensitivity constant (KS). Linear relationships were found between hematocrit (Hct) and KS (KS = 4.3 X Hct + 475.4; r = 0.72, n = 13) and between hematocrit and baseline impedance (Impedance = 9.2 x Hct + 567.7; r = 0.92, n = 13). Baseline impedance was also linearly related to KS (r = 0.835). This relationship served as the basis for normalizing KS to baseline impedance. As is necessary for use of the indicator-dilution principle, alinear relationship was found between the volume of indicator injected in plastic tubes and the area under the first-pass curve (n = 10, r = 0.995). Varying injection times from 3 to 6 seconds had no influence on curve area and resulted in accurate flow determinations, suggesting complete mixing. Prolonged injection times of more than 10 seconds caused flow to be slightly overestimated, suggesting incomplete mixing (Fig. 3). Fig. 4 depicts calculated flow in 2,3, and 4 mm diameter tubes over a range from 10 to 300 ml/min. An excellent correlation (y = 1.09X - 3.53; r = 0.99, n = 26) was found, with a slope near unity. Femoral artery studies. As in the in vitro studies, a linear relationship was found between the volume of indicator injected in canine femoral arteries and the area under the first-pass curve (area = 1228 X volume injected + 9.27; r = 0.997, n = 7). Fig. 5 depicts calculated flow versus timed collection data in canine femoral arteries. The flow range was varied from 6 to 240 ml/min. A good correlation between the catheter method and the timed collection standard was found, with accurate prediction of flow (y = 1.10X + 9.31; r = 0.97, n = 45).
200
150 FLOW
i-+----i 250
300
350
(ml/min>
and actual 0.45”,, saline flow in plastic tubes.
Coronary artery studies. Examples of first-pass impedance-time curves obtained after a bolus administration of 0.5 ml D5W are shown in Fig. 6 for three different flow levels in two dogs. (The impedance curves are offset and magnified). These demonstrate maximal and minimal observed cardiac cyclical variation. Corresponding electromagnetic flow recordings are also shown. The electromagnetic flow recordings show little perturbation of intrinsic flow by the D5W injection. No significant changes in blood pressure or cardiac rhythm were noted during D5W administration. At increasing flow rates, the area under the curve diminishes, as expected from the indicatordilution principle. The calculated flows were found to be reproducible. Comparison of repeated measurements at the same flow rate demonstrated a close correlation (y = 11.9 + 0.82X; r = 0.91, n = 8). The correlation between flow obtained from catheter measurements and electromagnetic flow probe readings for each dog was calculated, and ranged from 0.90 to 0.99 (mean 0.94 +_ 0.013 SE). Fig. 7 demonstrates catheter versus electromagnetic flow for all seven subjects, over a range from 3 to 300 ml/min. An excellent correlation between these two techniques was found (y = 0.85X + 11.4; r = 0.94, n = 82). DISCUSSION Previous flow
methods. Coronary sinus flow has been measured using thermodilution catheters to determine global coronary flowa However, regional blood flow measurements are necessary in the setting of segmental coronary artery disease. Great cardiac vein flow has been measured by this technique to assess left anterior descending flow selectively. How-
Volume
121
Number
3.
Part
Catheter
1
measurement
absolute blood poul
of
749
250
100
N = 45 Y = 1.10x+9.31
50 0
c=
0
50
100
150
200
TIMED COLLECTION FLOW Fig.
Comparison
5.
of catheter-calculated
and timed
collection
0.97
250
300
(ml/min)
blood flow data in canine femoral
arte-
ries.
CORONARY BLOOD 150 FLOW (ml/min)
IMPEDANCE (400 ohms full scale)
TIME (1
second
=
1
major
division)
6. Examples of first-pass impedance-time curves for three different flow levels obtained in two caFig. nine coronary studies. These examples demonstrate maximal and minimal observed cardiac cyclical variation. Corresponding mean electromagnetic flow recordings are shown above.
ever, consistent placement of the catheter in the great cardiac vein may be difficult to obtain, and blood flow cannot be measured. to other territories Recent developments in digital radiographic para-
sessment of absolute coronary blood flow has been reported in relatively straight, non-bifurcating vessels.12 Recently,13 radiographic assessment of coro-
metric
principles. This approach requires absence of patient motion and digital radiographic equipment. Indicator dilution principle. Indicator dilution methods, first studied by Stewart in 1897,14 have been employed for the measurement of absolute blood flow.14, l5 The indicator can be injected either at a constant rate (e.g., coronary sinus thermodilution catheter) or as a bolus from a proximal location (e.g., cardiac output thermodilution catheter). The indicator concentration downstream is diluted proportionally to blood flow, which is the basis for measur-
flow imaginga, g and in Doppler
technology10
have permitted
the assessment
catheter of coro-
nary flow ratios such as coronary flow reserve. Factors other than the severity of coronary stenoses may, however, affect flow reserve.ll Especially in the comthis relative paplex setting of acute angioplasty, rameter can give false estimates of the significance of individual coronary lesions and the efficacy of dilatations. This problem may in part be due to the variability in baseline coronary flow, which constitutes the denominator in this parameter. Radiographic as-
nary flow has been described
using
indicatordilution
750
Martin
et al.
T
300
c
250
E Fi
200
d
150
E t
100
.-
N
- 82
F
Y -
8
r = 0.94
50 0
0
50
100
150
200
ELECTROMAGNETIC Fig. 7. Comparison of catheter-calculated nine coronary arteries.
300
350
FLOW (ml/min)
and electromagnetic
ing absolute flow. Flow is calculated by the equation: Flow = (Volume of indicator x Ks)/(Area under first-pass curve), where KS is the transformation of detector units to absolute indicator concentration units. Flow, as derived in this equation, is determined at the point of indicator injection. Sampling can be performed at any point in the vascular tree after adequate mixing has occurred. Impedance changes occurring after an injection of an indicator have been utilized to measure cardiac output. This technique was first used by Stewart,14, l5 who employed hypertonic saline asthe indicator. The concentration of saline in blood samples withdrawn from the sampling site was determined by matching the conductivity (inverse of impedance) of the sample with that of blood to which a known amount of saline had been added. White16 utilized the bolus indicator technique to measure cardiac output, employing hypodermic needle electrodes inserted directly into an artery. The intraarterial impedance was recorded continuously as the bolus of saline passed the electrodes, generating an impedance-time curve. More recently, coronary sinus flow has been measured by impedance techniques.17 This technology has not previously been applied to the measurement of blood flow in coronary arteries, as an appropriate detector system has not been available. Requirements for a method to assesscoronary arterial blood flow include the use of a nontoxic indicator that does not alter flow itself, and a detector system that can be placed on a small diameter flexible catheter to allow subselective positioning in a coronary artery. Advantages of the current method. Catheter mea-
250
0.85w+11.4
flowmeter
blood flow data obtained
in ca-
surement of absolute coronary blood flow has not previously been accomplished. This inexpensive method provides rapid determination of blood flow without radiographic image processing. The dextrose solution indicator is readily available and meets the requirements for application of indicator dilution theory in that it mixes easily with blood and produces a linear impedance indicator signal. There is no alteration in intrinsic flow, as demonstrated by the electromagnetic flow tracings. There is no evidence that vasodilation or hemolysis occurs as a result of injection of this small volume of dextrose solution. Extravascular loss of indicator during the first-pass transit is minimal. Repeated measurements can be performed without concern for toxicity. Recirculation is not evident in the impedance-time curves. Mixing of the indicator and intrinsic blood flow appears to be adequate, resulting in impedance-time curves that accurately predict flow independent of injection rate. (According to indicator dilution principles, the rate of injection and the shape of the transit curve should not influence flow calculations). Laminar flow in straight plastic tubes represents a worst case for mixing. Tortuosity of the artery, branching, and stenoses would tend to increase turbulence and thus improve mixing. The administration of the indicator through a pinhole side port, which causes spraying of the solution, may also play an important role in providing adequate mixing over the 3 cm separation from port to electrodes.18 Other factors taken into consideration in the design of the catheter are important for impedance measurements. Close electrode spacing (2 mm) allows sensing of local indicator concentration within a
Volume
121
Number
3, Part
Catheter
1
short range. Parallel conduction by surrounding structures beyond 3 mm has been found to have minimal effect (little difference between impedance in 3 and 4 mm tubes and arteries). Additionally, it has been shown in canine femoral arteries that the addition of a 0.45 % saline bath (simulating parallel conductance) changes baseline impedance minimally.18 The relationship between calculated and known flow appears to be linear over a wide range, allowing measurements of reactive hypermia. Cannulation of the coronary sinus or great cardiac vein, needed for thermodilution methods, is not necessary. Assessment of coronary flow by this technique should not lengthen the procedure significantly, as the dilation catheter can be employed directly. Finally, this method measures absolute Aow and is therefore not subject to the variance in baseline flow, as are flow reserve measurements. Potential limitations. It is necessary that flow remain constant for approximately 5 seconds during application of this technique, and phasic flow cannot be obtained. Total coronary flow, without transmural segmentation, is obtained. However, this method is not subject to the limitations encountered in measuring perfusion by the Kety-Schmidt washout method in circumstances of high flow or regional or transmural inhomogeneous distribution.‘g Arterial branching may affect flow measurement accuracy. Using the indicator dilution principle, flow is measured at the site of indicator injection and concentration may be measured at any location downstream. Care must be taken to ensure that the indicator is not injected directly into a branch artery before mixing occurs. Loss of indicator into a side branch would cause underestimation of indicator concentration and overestimation of coronary blood flow. With catheter placement at a wide variety of distances from side branches and a wide variety of mixing distances during our coronary artery validation studies, this did not appear to be a problem. The chance that the indicator is lost in a side branch before mixing is small. The indicator dilution principle requires linearity of indicator concentration detection. Some degree of nonlinear impedance response occurs at concentrations of D5W above approximately 20 % . This would have a significant effect only at very low flow rates. A four-electrode system, with application of the current between the outer two electrodes and measurement of the potential difference between the inner two electrodes, has a theoretical advantage over the two-electrode system utilized.20 However, a fourelectrode system would be very difficult to place on a catheter small enough to be utilized clinically.
measurement
of absolute blood flow
751
The results obtained with the two-electrode system appear to be sufficiently accurate for clinical practice. As the sensitivity constant (KS) was found to vary proportionally to baseline impedance, normalization of KS was employed. This appproach tends to correct for alteration for Hct, temperature, vessel diameter, and electrode characteristics. Although only an estimate, this value appears to be adequate for clinical application. Normalization of Ks in humans would be done in a similar fashion. Minor drift in baseline impedance was occasionally observed, possibly due to catheter movement within the arterial lumen. Changes in saline content, Hct, temperature, and distending blood pressure may occur during the extensive procedure in the animal laboratory. These factors may alter baseline impedance. The baseline normalization used to obtain KS is only an estimate. This estimate provided the appropriate calculation for flow in femoral arteries with timed collection as the standard, as the slope of the regression line between timed collections and calculated flow was close to unity. (For flow in coronary arteries, the slope of the regression line is less than unity, possibly due in part to problems inherent in the use of electromagnetic flow probes.) Finally, the catheter itself is large enough to interfere with hyperemic flow in smaller coronary arteries or when it is placed across a stenosis. In clinical practice, the catheter would have to be positioned proximal to a stenosis. To eliminate this problem, we are currently investigating a similar approach using an electrode angioplasty guide wire.21 Despite these limitations, this method for measuring absolute coronary blood flow appears to be relatively simple, safe, inexpensive, and accurate over a wide range of flow. We thank USC1 Division of C. R. Bard, Inc., Billerica, supplying the catheters used in this study.
Mass.,
for
REFERENCES
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tolic and diastolic flow rates in the coronary artery system by x-ray densitometry. Circulation 1983;68:337-47. Gurley JC, Nissen SE, Haynie D, Elion JZ, Booth D, DeMaria A. A new method for measurement of absolute arterial blood flow bv dieital anaioarauhv [Abstract]. Circulation 1989; 8Ofsuppl II;II-413.- - ” Stewart GN. Researches on the circulation time and on the influences which affect it. J Physiol 1897;22:158-83. Stewart GN. The output of the heart in dogs. Am J Physiol 1921;57:27-50. White HL. Measurement of cardiac-output by a continuously recording conductivity method. Am J Physiol1947;151:45-57. Tommasini G, Tamagni F, Poluzzi C, Oddone A, Orlandi M, Cornalba C, Malusardi R. Coronary sinus hemodynamics in transient iscbemia. IEEE Comput Cardiol 1985;511-4. Martin LW, Zawodny R, Vogel RA. Impedance measurement of absolute arterial diameter using a standard angioplasty catheter [Abstract]. J Am Co11 Cardiol 1988;11:130A. Klocke F, Koberstein R, Pittman D, Bunnell I, Greene D. Rosing D. Effects of heterogeneous myocardial perfusion on coronary venous Hs desaturation curves and calculations of coronary flow. J Clin Invest 1968;47:2711-24. Vorhees WD, Bourland JD, Lamp ML, Mullikin JC, Geddes LA. Validation of the saline-dilution method for measuring cardiac output by simultaneous measurement with a perivascular electromagnetic flow probe. Med Instrum 1985;10:34-7. Martin LW. Scott H. Enelehardt M, Beauman G, Johnson RA, Vogel RA. kbsolute’blogd flow measurement using an angioplasty guidewire [Abstract]. Circulation 1989;8O(suppl II):II-
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