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Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep
J
THoRAc CARDfOVASC SURG
1988;95:511-5
Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep Implications after the Fontan operation The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial. left atrial. and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevationof coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg ± 1 to levels of 19 mm Hg ± 1 and 34 mm Hg ± 1, no significant changes were observed in right atrial. left atrial. or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/ epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe.
Kent E. Ward, MD, David J. Fisher, MD, and Lloyd Michael, PhD, Houston. Texas
~ntricular
dysfunction, both at rest and with exercise, has been observed in patients who have undergone the Fontan or modified Fontan procedure.!' This dysfunction has been attributed to a combination of longstanding preoperative myocardial disease, chronic hypoxemia, elevated pulmonary vascular resistance, and absence of a pulmonary ventricle. The nature of this abnormality of cardiac function, however, has not been fully elucidated. Hemodynamic changes that occur after the Fontan operation include moderate to marked elevation of right atrial pressure. Mean pressures as high as 30 mm Hg have been observed both in the early postoperative period at rest and late postoperatively during exercise
From the Department of Pediatrics and Medicine, Baylor College of Medicine, Houston, Texas. Received for publication Feb. 9, 1987.
testing.t' Markedly high right atrial pressures early postoperatively have been associated with increased morbidity and mortality in some studies.l' Unless coronary sinus drainage is altered during the procedure, coronary sinus pressure will increase proportionately with increases in right atrial pressure. Limited studies in the animal model have shown that increases in coronary sinus pressure by intermittent occlusion of the coronary sinus decrease coronary blood flow. 6.7 We have speculated that elevated coronary sinus pressures postoperatively in the patient undergoing the Fontan procedure may adversely affect coronary hemodynamics and thus may contribute to the myocardial dysfunction that has been observed. This possibility was evaluated through a study of the effects of isolated elevation of coronary sinus pressure on myocardial blood flow and ventricular contractile function in the mature sheep.
Accepted for publication April 2, 1987.
Methods
Address for reprints: Kent E. Ward, MD, Oklahoma Children's Memorial Hospital, P.O. Box 26307, Oklahoma City, OK 73126.
Materials. Seven adult ewes were anesthetized with intravenous sodium pentobarbital (10 to 20 mg/kg) and intubated and the lungs mechanically ventilated. Additional intravenous 'i 11
The Journal of Thoracic and Cardiovascular Surgery
5 I 2 Ward, Fisher, Michael
LV Pressure
']JVV1
LV dP/dl
~m
II
>000
I
PacIng
W"es
;" Left Atrial Catheter
Coronary SInus Catheter
\ . . . : Balloon Catheter
Hemiazygos Vetn
Fig. 1. Experimental preparation. Ao, Aorta. RA, Right atrium. RV, Right ventricle. PA, Pulmonary artery. LA, Left atrium. LV, Left ventricle.
Table I Control
CSI
Pressures (mean, mm Hg) Coronary sinus 2±1 19 ± Right atrial I ± 0.1 2± 4±1 4.5 ± Left atrial 88 ± Aortic 90 ± 5 888 ± 117 963 ± LV dP/dt (mm Hg/sec)
I" 0.4 0.7 4 128
CSll
34 I 5 90 892
± ± ± ± ±
I" 0.3 0.7 6 101
Legend: Values are expressed as mean ± standard error. LV. Left ventricular.
CSt, Moderate elevation of coronary sinus pressures. CSII. Marked elevation of coronary sinus pressures.
•p < 0.05 versus control.
pentobarbital was given throughout the study, as needed, for sedation (62 ± 12 rng/kg total dose, mean ± standard error). The internal jugular vein and carotid artery were isolated in the neck and ligated distally. A fluid-filled catheter was placed in the right atrium via the jugular vein and a 5F transducertipped catheter (PC 350, Millar Instruments, Inc., Houston, Texas) was placed in the carotid artery and passed retrograde to the left ventricle to measure the first derivative of pressure (dP /dt), By means of a left thoracotomy, a catheter was placed in the ascending aorta via the internal mammary artery, The heart was suspended in a pericardial cradle. A catheter was placed directly in the left atrium through the appendage and secured with a purse-string suture. The hemiazygos vein (Fig, 1), which in sheep regularly empties directly into the distal coronary sinus, was exposed and ligated distally to exclude thoracic wall drainage. Studies have shown that under these conditions coronary sinus effluent represents only coronary flow draining the majority of the left ventricular myocardium." A 5F balloon atrioseptostomy catheter (American Edwards Laboratories, Santa Ana, Calif.) was advanced from this vein to the proximal coronary sinus near its entry into
the right atrium. This position was confirmed by palpation of the inflated balloon posteriorly at the crux of the heart. A separate fluid-filled catheter was placed in the distal coronary sinus for pressure monitoring (Fig. I). Variable inflation of the balloon with a saline solution led to stable and reproducible elevation of coronary sinus pressure without total occlusion. Total coronary sinus occlusion could be distinguished from partial occlusion because total occlusion produces equalization of coronary sinus and left ventricular systolic pressures." Pacing wires were sewn to the left atrium and attached to a pulse generator (model SD9 single-channel stimulator, Grass Instrument Company, Quincy, Mass.). Fluid-filled catheters were connected to pressure transducers (Statham P23Db, Oxnard, Calif.) that were zeroed at midatriallevel. Heart rate; phasic and mean pressures from the right and left atria, left ventricle, and aorta; and left ventricular dP/dt were monitored continuously with a physiologic recorder (model 2800, Gould Inc., Cleveland, Ohio). Radioactive microspheres 15 J.!m in diameter (niobium [95Nb], strontium [85Sr], tin ['llSn], scandium [46S C], and cobalt [571Co]) were used to measure regional left ventricular blood flow by the reference sample technique. to Counts per sample were measured with a well-type gamma counter with a curve stripping algorithm (LKB Instruments Inc., Gaithersburg, Md.). All animals were handled according to the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by National Institutes of Health (No. 80-23, revised 1978). Protocol. In all animals, the heart rate was held constant at 100 beats/min by atrial pacing. Arterial blood gases were monitored and ventilator adjustments were made as needed to maintain partial pressure of oxygen between 80 and 150 torr, partial pressure of carbon dioxide between 35 and 45 torr, and arterial pH between 7.35 and 7.50. Measured variables included right atrial, left atrial, coronary sinus, and aortic pressures and left ventricular dP /dt.
Volume 95 Number 3 March 1988
Coronary sinus pressure after Fontan operation
J
.2
5 13
240
... - 200 '0.=
8~ 160
mE
<08'120
'E~
"';;,. 80
-gl:lE
40
Ul
CSI
C
.2
OJ
a:
CSII
Q.
• p<005vsConlrol
•
2.0
1.2
~
0.8
.fj
0.4
'0
CSIl
i ±SEM
2.4
~ 1.6
u: ._
CSI
C
C
CSI
CSlI
Fig. 2. Endocardial and epicardial blood flow (top) and endocardial-epicardial blood flow ratio (bottom) during elevation of coronary sinus pressure. Values are expressed as mean ± standard error. C. Control. CSI, Moderate elevation of coronary sinus pressures. CSIl, Marked elevation of coronary sinus pressures. *P < 0.05 versus control. Measurements were taken at control and at moderate (15 to 20 mm Hg, CSI) and marked (30 to 35 mm Hg, CSII) elevations of coronary sinus mean pressures after an 8 to lO-minute stabilization period. After pressure measurements were taken, a microsphere injection was performed. After completion of the study, the animals were killed with intravenous hypertonic potassium chloride, and the hearts were removed. Two sections of mid-left ventricular free wall were divided into an inner, a middle, and an outer third, weighed, and later submitted for isotope counting. An average of two samples from the same area was used in calculation of blood flow. Values were expressed in milliliters per 100 gm of tissue per minute. Data analysis consisted of analysis of variance with randomized block to control variability between animals. Values are reported as mean ± standard error. A probability value less than 0.05 was regarded as significant.
Results Coronary sinus mean pressure was increased from a control value of 2 mm Hg ± 1 to levels of 19 mm Hg ± 1 at CSI and 34 mm Hg ± 1 at CSII (Table I). There were no significant changes observed in right atrial, left atrial, or aortic mean pressures or left ventricular dP /dt, Endocardial blood flow averaged 115 ± 40 mI/lOO gm of tissue per minute (range 42 to 197) during the control period, 160 ± 42 mI/lOO gm of tissue per minute (range 118 to 246) at CSI, and 142 ± 38 mI/lOO gm of tissue per minute (range 130 to 176) at CSII. These changes were not significant. Epicardial blood flow was similarly unchanged (Fig. 2).
When endocardial/epicardial flow ratios were compared, a significant increase was noted at CSI (1.62 ± 0.2) as compared with control values (1.34 ± 0.3; p < 0.05). This was not observed at CSII. Discussion The determinants of the pressure gradient for coronary perfusion have been extensively studied and recently reviewed by Feigl." The downstream pressure for coronary perfusion during diastole is affected by intraventricular (cavity) pressure, intramyocardial (tissue) pressure, or coronary sinus pressure, whichever is greatest. Because left atrial pressure remained constant under the present experimental conditions, left ventricular cavity pressure and probably tissue pressure were likely unaffected. Under conditions of a constant heart rate and general anesthesia, changes in coronary sinus pressure should have been the only factor responsible for any observed changes in coronary blood flow in our model. Both Gregg and Dewald" and Jacobs and associates? observed decreases in total coronary blood flow during intermittent complete coronary sinus occlusion in the canine model. Bellamy and co-workers? were the first to demonstrate that graded total occlusions of the coronary sinus in the dog produced graded changes in the diastolic coronary artery pressure-flow relationship. They showed that, during artificially prolonged diastole, the pressure at which flow ceased was predictably increased with
The Journal of
5 I 4 Ward, Fisher, Michael
stepwise increases in coronary sinus pressure from 5 to 38 mm Hg. They speculated that increases in coronary sinus pressure caused an increase in intramyocardial tissue pressure, which became the effective back pressure opposing arterial flow.' Unlike the aforementioned studies, our study did not demonstrate a decrease in myocardial blood flow with increases in coronary venous pressure. The previously cited studies, however, differed from ours in two aspects. First, we used graded subtotal occlusions rather than complete occlusions to elevate coronary sinus pressure in an effort to more closely simulate the hemodynamics observed postoperatively in the patient who has undergone the Fontan procedure. Second, we did not use adenosine-induced maximal coronary vasodilation. Under these conditions, an alteration in myocardial perfusion may become apparent during elevation of coronary venous pressure,' especially during interventions that increase myocardial oxygen demand (rapid pacing, inotropic stimulation). Although maximal coronary vasodilation may occur clinically during extreme prolonged exercise, it does not occur under normal circumstances and thus was not used in our protocol. Ilbawi and associates" recently reported a decrease in coronary blood flow and depressed ventricular function during stepwise elevation of coronary sinus pressure in open chest dogs. It is possible that variations in coronary venous anatomy and the extent of thebesian vein development could account for the different responses observed in dogs and sheep. Thus an extensive thebesian system in the sheep could preserve coronary blood flow and ventricular function despite marked elevation of coronary sinus pressure. Such a system is thought to exist in man" and accounts for the correlation of coronary sinus occlusion pressure and left ventricular end-diastolic pressure. There was no evidence of selective subendocardial ischemia in our animals. However, the endocardial/ epicardial flow ratio did reveal a significant increase at moderate elevation of coronary sinus pressure. This observation, in the absence of changes in the upstream pressure for coronary perfusion (mean aortic pressure), suggests selective vasodilation of subendocardial vessels. Subendocardial muscle is affected first during periods of metabolic stress," and this localized increase in blood flow may signal an early response to increased metabolic demand. Jacobs and colleagues? demonstrated a marked reactive hyperemia after release of intermittent total coronary sinus occlusion but observed no signs of ischemic myocardial dysfunction during occlusion. They speculated that factors other than ischemia are responsible for this reactive vasodilation. It is possible that
Thoracic and Cardiovascular Surgery
prolonged subtotal coronary sinus occlusion with moderate elevation of coronary sinus pressure provoked a similar response that selectively dilated the subendocardium and, in the absence of changes in transmural perfusion, resulted in an increased endocardial/epicardial flow ratio. The clinical implications of this experimental work need consideration. Incorporation of the coronary sinus into the low-pressure left atrium has been recommended by some investigators both to avoid the conduction tissue in cases of univentricular heart? and to discourage coronary venous hypertension and "cardiac edema" formation. 13. 16 Although the former concern is well founded, the latter has been, until recently, only theoretical. Our data suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal heart. However, we speculate that the coronary reserve in patients undergoing the Fontan operation may be impaired because of long-standing cardiac dilatation, hypertrophy, endocardial fibrosis, or a combination of these conditions. It would seem likely that under these circumstances increases in myocardial oxygen demand, in the face of moderate to marked increases in coronary outflow pressure, may lead to regional perfusion abnormalities potentially deleterious to cardiac performance. Further studies to characterize the coronary microcirculation preoperatively and postoperatively in the patient undergoing the Fontan procedure are needed to answer this question. We would like to thank Susan Chisholm for the excellent secretarial assistance in the preparation of this manuscript. We would also like to thank Arthur Nunnery, MD, for his assistance in the statistical analysis of the data. REFERENCES 1. Sanders SP, Wright GB, Keane JF, Norwood WI,
Casteneda AR. Clinical and hemodynamic results of the Fontan operation for tricuspid atresia. Am J Cardiol 1982;49: 1733-40.
2. Laks H, Milliken JC, PerloffJK, et al. Experience with the Fontan procedure. J THoRAc CARDJOV ASC SURG 1984;88:939-51. 3. Del Torso S, Kelly MJ, Kalff V, Venables AW. Radio-
nuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle. Am J Cardiol 1985; 55:1127-32.
4. Shachar GB, Fuhrman BP, Wang Y, Lucas RV Jr, Lock JE. Rest and exercise hemodynamics after the Fontan procedure. Circulation 1982;65: I043-8. 5. Williams DB, Kiernan PO, Schaff HV, Marsh HM, Danielson GK. The hemodynamic response to dopamine
Volume 95 Number 3
March 1988
6.
7.
8.
9.
10.
and nitroprusside following right atrium-pulmonary artery bypass (Fontan procedure) Ann Thorac Surg 1982; 34:51-7. Scharf SM, Bromberger-Barnea B, Permutt S. Distribution of coronary venous flow. J Appl Physiol 1971;30:65761. Bellamy RF, Lowensohn HS, Ehrlich W, Baer RW. Effect of coronary sinus occlusion on coronary pressureflow relations. Am J Physiol 1980;239:H57-64. Downing SE, Lee JC, Taylor JF, et al. Influence of norepinephrine and digitalis on myocardial oxygen consumption in the newborn lamb. Circ Res 1973;32:471-6. Jacobs AK, Faxon DP, Coats WD, et al. Coronary sinus occlusion pressure, hemodynamic correlates. Clin Res 1983;31:194A. Heymann MA, Payne BD, Hoffman JI, et al. Blood flow measurements with radionuclide labeled particles. Prog Cardiovasc Dis 1977;20:55-60.
Coronary sinus pressure after Fontan operation
5I5
11. Feigl EO. Coronary physiology. Physiol Rev 1983;63:1205. 12. Gregg DE, Dewald D. Immediate effects of coronary sinus ligation on dynamics of coronary circulation. Proc Soc Exp Bioi Med 1938;39:202-4. 13. Ilbawi MN, Idriss FS, Muster AJ, et al. Effects of elevated coronary sinus pressure on left ventricular function after the Fontan operation. J THoRAc CARDIOVASC SURG 1986;92:231-7. 14. Faxon DP, Jacobs AK, Kellett MA, McSweeney SW, Coats WD, Ryan TJ. Coronary sinus occlusion pressure and its relation to intracardiac pressure. Am J Cardiol 1985;56:457-60. 15. Hoffman JIE. Determinants and prediction of transmural myocardial perfusion. Circulation 1978;58:381-90. 16. Doty DB, Marvin WJJR, Lauer RM. Modified Fontan procedure. J THORAC CARDIOVASC SURG 1981;81:470-5.
Bound volumes available to subscribers Bound volumes of THE JOURNAL OFTHORACIC AND CARDIOVASCULAR SURGERY are available to subscribers (only) for the 1988 issues from the Publisher, at a cost of $51.00 ($68.00 international) for Vol. 95 (January-June) and Vol. 96 (July-December). Shipping charges are included. Each bound volume contains a subject and author index and all advertising is removed. Copies are shipped within 60 days after publication of the last issue of the volume. The binding is durable buckram with the JOURNAL name, volume number, and year stamped in gold on the spine. Payment must accompany all orders. Contact The C. V. Mosby Company, Circulation Department, 11830 Westline Industrial Drive, St. Louis. Missouri 63146, USA; phone (800) 325-4177, ext. 351. Subscriptions must be in force to qualify. Bound volumes are not available in place of a regular JOURNAL subscription.
THoRAc CARDfOVASC SURG
1988;95:511-5
Elevated coronary sinus pressure does not alter myocardial blood flow or left ventricular contractile function in mature sheep Implications after the Fontan operation The hypothesis that elevation of coronary sinus pressure affects coronary blood flow and ventricular function was tested in this study of seven adult ewes placed under pentobarbital anesthesia. Coronary sinus pressure was elevated by partial balloon occlusion. Right atrial. left atrial. and aortic mean pressures and rate of rise of left ventricular pressure were measured. Coronary blood flow was determined with radioactive microspheres. Studies were performed at control and at moderate (15 to 20 mm Hg) and marked (30 to 35 mm Hg) elevationof coronary sinus mean pressures. Despite increase of coronary sinus pressure from a control value of 2 mm Hg ± 1 to levels of 19 mm Hg ± 1 and 34 mm Hg ± 1, no significant changes were observed in right atrial. left atrial. or aortic mean pressure or rate of rise of left ventricular pressure. Both endocardial and epicardial blood flows were unaffected. The endocardial/ epicardial flow ratio at moderate coronary sinus pressure elevation was significantly increased, which suggested local subendocardial vasodilation in the absence of changes in transmural perfusion. The findings suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal ewe.
Kent E. Ward, MD, David J. Fisher, MD, and Lloyd Michael, PhD, Houston. Texas
~ntricular
dysfunction, both at rest and with exercise, has been observed in patients who have undergone the Fontan or modified Fontan procedure.!' This dysfunction has been attributed to a combination of longstanding preoperative myocardial disease, chronic hypoxemia, elevated pulmonary vascular resistance, and absence of a pulmonary ventricle. The nature of this abnormality of cardiac function, however, has not been fully elucidated. Hemodynamic changes that occur after the Fontan operation include moderate to marked elevation of right atrial pressure. Mean pressures as high as 30 mm Hg have been observed both in the early postoperative period at rest and late postoperatively during exercise
From the Department of Pediatrics and Medicine, Baylor College of Medicine, Houston, Texas. Received for publication Feb. 9, 1987.
testing.t' Markedly high right atrial pressures early postoperatively have been associated with increased morbidity and mortality in some studies.l' Unless coronary sinus drainage is altered during the procedure, coronary sinus pressure will increase proportionately with increases in right atrial pressure. Limited studies in the animal model have shown that increases in coronary sinus pressure by intermittent occlusion of the coronary sinus decrease coronary blood flow. 6.7 We have speculated that elevated coronary sinus pressures postoperatively in the patient undergoing the Fontan procedure may adversely affect coronary hemodynamics and thus may contribute to the myocardial dysfunction that has been observed. This possibility was evaluated through a study of the effects of isolated elevation of coronary sinus pressure on myocardial blood flow and ventricular contractile function in the mature sheep.
Accepted for publication April 2, 1987.
Methods
Address for reprints: Kent E. Ward, MD, Oklahoma Children's Memorial Hospital, P.O. Box 26307, Oklahoma City, OK 73126.
Materials. Seven adult ewes were anesthetized with intravenous sodium pentobarbital (10 to 20 mg/kg) and intubated and the lungs mechanically ventilated. Additional intravenous 'i 11
The Journal of Thoracic and Cardiovascular Surgery
5 I 2 Ward, Fisher, Michael
LV Pressure
']JVV1
LV dP/dl
~m
II
>000
I
PacIng
W"es
;" Left Atrial Catheter
Coronary SInus Catheter
\ . . . : Balloon Catheter
Hemiazygos Vetn
Fig. 1. Experimental preparation. Ao, Aorta. RA, Right atrium. RV, Right ventricle. PA, Pulmonary artery. LA, Left atrium. LV, Left ventricle.
Table I Control
CSI
Pressures (mean, mm Hg) Coronary sinus 2±1 19 ± Right atrial I ± 0.1 2± 4±1 4.5 ± Left atrial 88 ± Aortic 90 ± 5 888 ± 117 963 ± LV dP/dt (mm Hg/sec)
I" 0.4 0.7 4 128
CSll
34 I 5 90 892
± ± ± ± ±
I" 0.3 0.7 6 101
Legend: Values are expressed as mean ± standard error. LV. Left ventricular.
CSt, Moderate elevation of coronary sinus pressures. CSII. Marked elevation of coronary sinus pressures.
•p < 0.05 versus control.
pentobarbital was given throughout the study, as needed, for sedation (62 ± 12 rng/kg total dose, mean ± standard error). The internal jugular vein and carotid artery were isolated in the neck and ligated distally. A fluid-filled catheter was placed in the right atrium via the jugular vein and a 5F transducertipped catheter (PC 350, Millar Instruments, Inc., Houston, Texas) was placed in the carotid artery and passed retrograde to the left ventricle to measure the first derivative of pressure (dP /dt), By means of a left thoracotomy, a catheter was placed in the ascending aorta via the internal mammary artery, The heart was suspended in a pericardial cradle. A catheter was placed directly in the left atrium through the appendage and secured with a purse-string suture. The hemiazygos vein (Fig, 1), which in sheep regularly empties directly into the distal coronary sinus, was exposed and ligated distally to exclude thoracic wall drainage. Studies have shown that under these conditions coronary sinus effluent represents only coronary flow draining the majority of the left ventricular myocardium." A 5F balloon atrioseptostomy catheter (American Edwards Laboratories, Santa Ana, Calif.) was advanced from this vein to the proximal coronary sinus near its entry into
the right atrium. This position was confirmed by palpation of the inflated balloon posteriorly at the crux of the heart. A separate fluid-filled catheter was placed in the distal coronary sinus for pressure monitoring (Fig. I). Variable inflation of the balloon with a saline solution led to stable and reproducible elevation of coronary sinus pressure without total occlusion. Total coronary sinus occlusion could be distinguished from partial occlusion because total occlusion produces equalization of coronary sinus and left ventricular systolic pressures." Pacing wires were sewn to the left atrium and attached to a pulse generator (model SD9 single-channel stimulator, Grass Instrument Company, Quincy, Mass.). Fluid-filled catheters were connected to pressure transducers (Statham P23Db, Oxnard, Calif.) that were zeroed at midatriallevel. Heart rate; phasic and mean pressures from the right and left atria, left ventricle, and aorta; and left ventricular dP/dt were monitored continuously with a physiologic recorder (model 2800, Gould Inc., Cleveland, Ohio). Radioactive microspheres 15 J.!m in diameter (niobium [95Nb], strontium [85Sr], tin ['llSn], scandium [46S C], and cobalt [571Co]) were used to measure regional left ventricular blood flow by the reference sample technique. to Counts per sample were measured with a well-type gamma counter with a curve stripping algorithm (LKB Instruments Inc., Gaithersburg, Md.). All animals were handled according to the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by National Institutes of Health (No. 80-23, revised 1978). Protocol. In all animals, the heart rate was held constant at 100 beats/min by atrial pacing. Arterial blood gases were monitored and ventilator adjustments were made as needed to maintain partial pressure of oxygen between 80 and 150 torr, partial pressure of carbon dioxide between 35 and 45 torr, and arterial pH between 7.35 and 7.50. Measured variables included right atrial, left atrial, coronary sinus, and aortic pressures and left ventricular dP /dt.
Volume 95 Number 3 March 1988
Coronary sinus pressure after Fontan operation
J
.2
5 13
240
... - 200 '0.=
8~ 160
mE
<08'120
'E~
"';;,. 80
-gl:lE
40
Ul
CSI
C
.2
OJ
a:
CSII
Q.
• p<005vsConlrol
•
2.0
1.2
~
0.8
.fj
0.4
'0
CSIl
i ±SEM
2.4
~ 1.6
u: ._
CSI
C
C
CSI
CSlI
Fig. 2. Endocardial and epicardial blood flow (top) and endocardial-epicardial blood flow ratio (bottom) during elevation of coronary sinus pressure. Values are expressed as mean ± standard error. C. Control. CSI, Moderate elevation of coronary sinus pressures. CSIl, Marked elevation of coronary sinus pressures. *P < 0.05 versus control. Measurements were taken at control and at moderate (15 to 20 mm Hg, CSI) and marked (30 to 35 mm Hg, CSII) elevations of coronary sinus mean pressures after an 8 to lO-minute stabilization period. After pressure measurements were taken, a microsphere injection was performed. After completion of the study, the animals were killed with intravenous hypertonic potassium chloride, and the hearts were removed. Two sections of mid-left ventricular free wall were divided into an inner, a middle, and an outer third, weighed, and later submitted for isotope counting. An average of two samples from the same area was used in calculation of blood flow. Values were expressed in milliliters per 100 gm of tissue per minute. Data analysis consisted of analysis of variance with randomized block to control variability between animals. Values are reported as mean ± standard error. A probability value less than 0.05 was regarded as significant.
Results Coronary sinus mean pressure was increased from a control value of 2 mm Hg ± 1 to levels of 19 mm Hg ± 1 at CSI and 34 mm Hg ± 1 at CSII (Table I). There were no significant changes observed in right atrial, left atrial, or aortic mean pressures or left ventricular dP /dt, Endocardial blood flow averaged 115 ± 40 mI/lOO gm of tissue per minute (range 42 to 197) during the control period, 160 ± 42 mI/lOO gm of tissue per minute (range 118 to 246) at CSI, and 142 ± 38 mI/lOO gm of tissue per minute (range 130 to 176) at CSII. These changes were not significant. Epicardial blood flow was similarly unchanged (Fig. 2).
When endocardial/epicardial flow ratios were compared, a significant increase was noted at CSI (1.62 ± 0.2) as compared with control values (1.34 ± 0.3; p < 0.05). This was not observed at CSII. Discussion The determinants of the pressure gradient for coronary perfusion have been extensively studied and recently reviewed by Feigl." The downstream pressure for coronary perfusion during diastole is affected by intraventricular (cavity) pressure, intramyocardial (tissue) pressure, or coronary sinus pressure, whichever is greatest. Because left atrial pressure remained constant under the present experimental conditions, left ventricular cavity pressure and probably tissue pressure were likely unaffected. Under conditions of a constant heart rate and general anesthesia, changes in coronary sinus pressure should have been the only factor responsible for any observed changes in coronary blood flow in our model. Both Gregg and Dewald" and Jacobs and associates? observed decreases in total coronary blood flow during intermittent complete coronary sinus occlusion in the canine model. Bellamy and co-workers? were the first to demonstrate that graded total occlusions of the coronary sinus in the dog produced graded changes in the diastolic coronary artery pressure-flow relationship. They showed that, during artificially prolonged diastole, the pressure at which flow ceased was predictably increased with
The Journal of
5 I 4 Ward, Fisher, Michael
stepwise increases in coronary sinus pressure from 5 to 38 mm Hg. They speculated that increases in coronary sinus pressure caused an increase in intramyocardial tissue pressure, which became the effective back pressure opposing arterial flow.' Unlike the aforementioned studies, our study did not demonstrate a decrease in myocardial blood flow with increases in coronary venous pressure. The previously cited studies, however, differed from ours in two aspects. First, we used graded subtotal occlusions rather than complete occlusions to elevate coronary sinus pressure in an effort to more closely simulate the hemodynamics observed postoperatively in the patient who has undergone the Fontan procedure. Second, we did not use adenosine-induced maximal coronary vasodilation. Under these conditions, an alteration in myocardial perfusion may become apparent during elevation of coronary venous pressure,' especially during interventions that increase myocardial oxygen demand (rapid pacing, inotropic stimulation). Although maximal coronary vasodilation may occur clinically during extreme prolonged exercise, it does not occur under normal circumstances and thus was not used in our protocol. Ilbawi and associates" recently reported a decrease in coronary blood flow and depressed ventricular function during stepwise elevation of coronary sinus pressure in open chest dogs. It is possible that variations in coronary venous anatomy and the extent of thebesian vein development could account for the different responses observed in dogs and sheep. Thus an extensive thebesian system in the sheep could preserve coronary blood flow and ventricular function despite marked elevation of coronary sinus pressure. Such a system is thought to exist in man" and accounts for the correlation of coronary sinus occlusion pressure and left ventricular end-diastolic pressure. There was no evidence of selective subendocardial ischemia in our animals. However, the endocardial/ epicardial flow ratio did reveal a significant increase at moderate elevation of coronary sinus pressure. This observation, in the absence of changes in the upstream pressure for coronary perfusion (mean aortic pressure), suggests selective vasodilation of subendocardial vessels. Subendocardial muscle is affected first during periods of metabolic stress," and this localized increase in blood flow may signal an early response to increased metabolic demand. Jacobs and colleagues? demonstrated a marked reactive hyperemia after release of intermittent total coronary sinus occlusion but observed no signs of ischemic myocardial dysfunction during occlusion. They speculated that factors other than ischemia are responsible for this reactive vasodilation. It is possible that
Thoracic and Cardiovascular Surgery
prolonged subtotal coronary sinus occlusion with moderate elevation of coronary sinus pressure provoked a similar response that selectively dilated the subendocardium and, in the absence of changes in transmural perfusion, resulted in an increased endocardial/epicardial flow ratio. The clinical implications of this experimental work need consideration. Incorporation of the coronary sinus into the low-pressure left atrium has been recommended by some investigators both to avoid the conduction tissue in cases of univentricular heart? and to discourage coronary venous hypertension and "cardiac edema" formation. 13. 16 Although the former concern is well founded, the latter has been, until recently, only theoretical. Our data suggest that isolated increase in coronary sinus pressure is not a major determinant of myocardial blood flow or ventricular performance in the normal heart. However, we speculate that the coronary reserve in patients undergoing the Fontan operation may be impaired because of long-standing cardiac dilatation, hypertrophy, endocardial fibrosis, or a combination of these conditions. It would seem likely that under these circumstances increases in myocardial oxygen demand, in the face of moderate to marked increases in coronary outflow pressure, may lead to regional perfusion abnormalities potentially deleterious to cardiac performance. Further studies to characterize the coronary microcirculation preoperatively and postoperatively in the patient undergoing the Fontan procedure are needed to answer this question. We would like to thank Susan Chisholm for the excellent secretarial assistance in the preparation of this manuscript. We would also like to thank Arthur Nunnery, MD, for his assistance in the statistical analysis of the data. REFERENCES 1. Sanders SP, Wright GB, Keane JF, Norwood WI,
Casteneda AR. Clinical and hemodynamic results of the Fontan operation for tricuspid atresia. Am J Cardiol 1982;49: 1733-40.
2. Laks H, Milliken JC, PerloffJK, et al. Experience with the Fontan procedure. J THoRAc CARDJOV ASC SURG 1984;88:939-51. 3. Del Torso S, Kelly MJ, Kalff V, Venables AW. Radio-
nuclide assessment of ventricular contraction at rest and during exercise following the Fontan procedure for either tricuspid atresia or single ventricle. Am J Cardiol 1985; 55:1127-32.
4. Shachar GB, Fuhrman BP, Wang Y, Lucas RV Jr, Lock JE. Rest and exercise hemodynamics after the Fontan procedure. Circulation 1982;65: I043-8. 5. Williams DB, Kiernan PO, Schaff HV, Marsh HM, Danielson GK. The hemodynamic response to dopamine
Volume 95 Number 3
March 1988
6.
7.
8.
9.
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