Effects of Local Cardiac Hypothermia on the Magnitude and Distribution of Coronary Blood Flow and on Myocardial Function and Metabolism Lawrence H. Cohn, M.D., Yasuyuki Fujiwara, M.D., Edward Kirk, Ph.D., and John J. Collins, Jr., M.D. ABSTRACT Changes in hemodynamics, metabolism, and the distribution and magnitude of coronary blood flow were evaluated in 10 dog hearts before and after 60 minutes of cardiac anoxia with the myocardium protected by local cardiac hypothermia. The data indicate that following myocardial protection with this technique, hemodynamic performance is not impaired very greatly and there is a noticeable reactive hyperemia, particularly to the subendocardial layers of the myocardium.
I
n 1959 Shumway and associates [ 161 demonstrated experimentally that local cardiac hypothermia produced by a circulating cold saline bath affords satisfactory protection to the myocardium during periods of cardiac anoxia. Although many cardiac surgery units [7, 14, 15, 171 are using local cardiac hypothermia for myocardial protection during operations on the aortic root or when flaccidity of the heart facilitates the operative procedure, relatively little is known of the physiological adjustments following its use. This study was undertaken to evaluate myocardial function, changes in coronary blood flow and metabolism, and distribution of coronary blood flow in the dog heart following hypothermia for local cardiac protection of the anoxic ventricle.
Methods Ten mongrel dogs weighing between 15 and 25 kg were the experimental subjects. After pentobarbital anesthesia (2 mg per kilogram of body weight) was given, a median sternotomy was made and catheterization of the femoral artery and vein for measurement of systemic arterial pressure From the Departments of Surgery and Medicine, Harvard Medical School, and the Division of Thoracic and Cardiac Surgery, Peter Bent Brigham Hospital, Boston, Mass. Supported in part by grants from the Massachusetts Heart Association and the Hartford Foundation. We wish to thank Anna Mae Fosberg, Susan Tracey, Stuart Solomon, and Joel Davis for their technical assistance. Accepted for publication July 10, 1974. Address reprint requests to Dr. Cohn, Division of Thoracic and Cardiac Surgery, Peter Bent Brigham Hospital, 721 Huntington Ave., Boston, Mass. 02115.
10
THE ANNALS OF THORACIC SURGERY
Eflecls of Local Cardiac Hypothermia
and central venous pressure was carried out. A catheter connected to a Statham pressure transducer was introduced into the apex of the left ventricle to record left ventricular pressure on high and low gain. A coronary sinus catheter was placed for coronary lactate, potassium, and blood gas determinations. An Instrumentation Laboratories glass electrode especially designed for sensing surface pH measured the right ventricular myocardial surface pH; readings were recorded on a Dow Corning research electrometer. A large-bore catheter connected to a gravity collection device in the heartlung machine was placed in the right atrium for collection of coronary sinus blood flow. When caval flow was returned directly to the pump, thus excluding systemic venous blood from the right atrium, this catheter collected coronary sinus flow. Coronary sinus flow was measured for a period of 1 minute three times successively and averaged at each intervention. Intramyocardial temperature was measured by a thermistor, the sensitive tip of which was inserted midway between the epicardium and endocardium of the left ventricular free wall and connected to a Yellow Springs temperature gauge. Cardiac output was calculated by the thermodilution method using a Swan-Ganz catheter placed in the main pulmonary artery; measurements were made in triplicate. Correlations (25 to loyo) with electromagnetic flowmeter and indocyanine green techniques have been reported [l]. Control measurements of heart rate, systemic arterial blood pressure, left ventricular pressure, left ventricular end-diastolic pressure, cardiac output, arterial and coronary sinus pH, Poz, and Pco2 were determined, as were the arterial and coronary sinus values of p,otassium and lactate. Cardiopulmonary bypass was then instituted by inserting venous cannulas into the right internal jugular vein and right femoral vein and an arterial perfusion cannula in the right femoral artery. During cardiopulmonary bypass the blood temperature was maintained at 35"C, and the hematocrit averaged 37y0 at flow rates of approximately 1.5 liters per minute. After institution of cardiopulmonary bypass the heart was electrically fibrillated, blood flow in the cavae was excluded from the right atrium, and measurements were made of the coronary sinus blood gas tensions, lactate and potassium, and coronary venous flow. T h e aorta was then cross-clamped for 60 minutes, during which time the heart was protected by local cardiac hypothermia (as illustrated in the Figure appearing in A n n T h o r u c Surg 17:137, 1974). T h e heart was positioned so that the left ventricle was the most dependent cardiac structure and was bathed in a continuous bath of iced Ringer's lactate solution. T h e left ventricle was decompressed during cardiopulmonary bypass using a sump catheter inserted through the apex. Five minutes and 30 minutes after removal of the aortic clamp, coronary blood flow, Poz, PCOB,potassium, and lactate were measured from the coronary sinus catheter. T h e heart was then defibrillated, the animal taken
VOL.19, NO.
I , JANUARY,
1975
11
COHN E T AL.
off cardiopulmonary bypass, and hemodynamic measurements repeated 30 minutes after the animal’s condition had stabilized off cardiopulmonary bypass. T h e distribution of coronary blood flow was determined with radioactive labeled microspheres in 6 animals. Microspheres* 15 p in diameter labeled with cesium 141 and strontium 85 were used. Steps taken to prevent settling or aggregation of the microspheres prior to use included: (1) addition of a drop of Tween 80 to each shipment of microspheres; (2) suspension of the microspheres in a glucose solution with a specific gravity of 1.3, the same as the microspheres; and (3) ultrasonification of the solution immediately prior to infusion. Within 5 minutes after discontinuance of aortic cross-clamping, 141Cs-tagged microspheres (300,000 microspheres representing 1 to 7 pCi in 3 ml) were injected into the return line from the bypass pump. At this point the heart was not ejecting blood, so mixing of the microspheres with coronary blood flow occurred along the entire length of the aorta. Thirty minutes later, when the heart was pumping normally after defibrillation, a similar injection of S5Sr microspheres was made into the left atrium. Subsequently, the heart was removed and sectioned into two fullthickness samples from the left ventricular wall, a full-thickness sample from the interventricular septum, and a sample from the right ventricular wall. T h e left ventricle and septum samples were divided into endocardia1 and epicardial halves. T h e seven samples, each weighing 4 to 8 gm, were placed in tubes and the radioactivity determined with a gamma well counter utilizing a dual channel pulse-height analyzer.? Pulses corresponding to energies around 750 kev (strontium) and 141 kev (cesium) were counted. Cesium contributed negligible counting to the strontium channel, but strontium was counted in the cesium channel at a rate one-sixth that in the higher energy channel. T h e data corrected for background and strontium crossover were expressed as counts per minute per milligram for each isotope. T h e endocardial/epicardial ratio of radioactivity represents the ratio of absolute blood flow at the time the microspheres were injected.
Results All animals survived the period of aortic cross-clamping and cardiac anoxia during which the myocardium was protected by local cardiac hypothermia on cardiopulmonary bypass. T h e results of the hemodynamic studies are summarized in Table 1. There was no statistically significant difference in any of these measurements before and after bypass. Table 2 shows the mean and range of coronary sinus blood lactate, potassium, Po,, and Pcoz before, immediately after, and 30 minutes after cardiac anoxia and local cardiac hypothermia. Immediately after restoration of coronary blood flow there was a decrease in the coronary sinus potassium, *3M Co., St. Paul, Minn. +Nuclear-Chicago Co., Chicago, Ill.
12
THE ANNALS OF THORACIC SURGERY
Eflects of Local Cardiac Hypothermia TABLE 1. HEMODYNAMIC DATA BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Measurement
Range
Before LCH MAP (mm Hg) Heart rate (beats/min) LVEDP (mm Hg) Cardiac output (L/min) After LCH (and cardiopulmonary bypass) .MAP (mm Hg) Heart rate (beats/min) LVEDP (mm Hg) Cardiac output (L/min)
Mean
75-105 150-200 4-9 1.25-2.74
100 170 6 2.1
60- 100 90-240 5-1 1 1.2-2.8
85 190
7
2.05
MAP = mean arterial pressure: LVEDP = left ventricular end-diastolic pressure.
elevation of coronary sinus lactate, and significant increases in Po2 and PCOZ; these changes had returned toward control values by the next set of measurements taken 30 minutes later. Myocardial surface pH (MpH) and left ventricular intramyocardial temperature (Tm) values are summarized in Table 3. MpH fell to a mean of 6.5 (range 6.2 to 7.1) from a control mean of 7.9 (range 7.6 to 8.2). After the period of anoxia, MpH returned to control values (mean 7.85, range 7.8 to 8.0). T h e T m fell to a mean of 152°C (range 14.0 to 16.5"C) during the period of maximum local hypothermia. T h e magnitude of coronary blood flow before and after local cardiac hypothermia (LCH) is shown in the Figure. Control coronary blood flow measured by coronary venous flow during ventricular fibrillation ranged from 120 to 250 ml with a mean of 157 ml per minute+ 36 (SD). Immediately following release of the aortic cross-clamp there was significant coronary hyperemia with a flow of 336 ml per minute k 132; this persisted for approximately 20 minutes and decreased toward control values by 30 minutes (165 ml per minute 2 44). Table 4 shows the distribution of coronary flow determined by injection TABLE 2. CORONARY SINUS BLOOD FLOW MEASUREMENTS BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Measurement
Before LCH
Lactate (moles/L)
1.14-3.15 2.20
Potassium (mEq/L)
2.3-3.8
Po2 (mm Hg)
15-40
26
PCO, (mm Hg)
22-43
%
5 Minutes after LCH
30 Minutes
7.03 (P < 0.001) 1.4-2.5 2.0 (P < 0.01)
1.5-2.8 2.53
6.2-7.7
3.2
46-104
60
( p < 0.001) 27-64 44
(P < 0.01)
VOL.
19, NO.
1, JANUARY,
after LCH
-
2.4-3.4 17-41
2.8 2s
22-40 2 8
1975
13
COHN E T AL. TABLE 3. MYOCARDIAL p H AND TEMPERATURE BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Before LCH Myocardial surface PH Intramyocardial temperature ("C)
7.6-8.2 34-38
7.9
36
During LCH 6.2-7.1 6.5 14-16.5
15.2
After LCH 7.8-8.0
32-36
7.9 34
of radioactive microspheres following protection of the left ventricle by local hypothermia for 60 minutes. The results indicate that during the period following LCH and aortic cross-clamping there was increased coronary blood flow, due predominantly to increased perfusion of the endomyocardium. At 30 minutes after removal of the aortic cross-clamp the subendomyocardial hyperemia appeared to have abated.
C o m men t Several experimental studies have suggested the feasibility of local cardiac hypothermia combined with anoxic arrest for extended protection of the nonperfused heart. Fuhrman, Fuhrman, and Field [lo] showed that the metabolic rate of isolated slices of rat heart was reduced 90% by lowering the temperature from 37" to 10°C. Gott and co-workers [12] demonstrated that the metabolic rate of the arrested heart under normothermia was only 8% of the rate of the working, beating heart. Shumway, Lower, and Stofer [16] reported that dogs can survive if their hearts are protected by a circulating bath of cold saline despite interruption of the coronary circulation, and Enright and co-workers [9] have demonstrated that left ventricular function is preserved if systemic hypothermia is used to protect the myocardium during cardiac anoxia. Finally, Angel1 and associates [Z] have shown that the interval of anoxia compatible with viability of an isolated heart is an inverse linear function of the temperature of the heart. Coronary blood flow before and after local cardiac hypothermia (LCH). (Vertical lines represent standard deviation.)
0
t
Before LCH
I4
5
10
After LCH
30 rnin
THE ANNALS OF THORACIC SURGERY
Eflects of Local Cardiac Hypothermia TABLE 4. DISTRIBUTION OF CORONARY BLOOD FLOW IN G DOCS MEASURED BY RADIOACTIVE MICROSPHERES" AFTER LOCAL CARDIAC HYPOTHERMIA
Left Ventricular Base-Wall Endocardium/ Epicardium 5 rnin 30 min 1.42 1.25 1.28 1.21 1.22 1.51
0.86 0.97 0.81 0.65 0.88 0.87
Left Ventricular Base-Apex Endocardium/ Epicardium 5 min 30 rnin 1.37 1.46 1.30 1.14 1.10 2.16
Septum (LV/RV) 5 min 30 rnin
0.98 0.67 0.77 0.81 0.86 1.01
1.55 1.15 1.41 1.28 1.17 0.74
RV/ LV (5 min)
0.99 0.85 1.17 1.31 1.oo 0.94
0.24 0.64 0.85 0.77 1.06 0.82
*Five-minute injection with cesium 141; SO-minute injection with strontium 85. LV = left ventricle; RV =right ventricle.
Data from our study indicate that after 60 minutes' interruption of the coronary circulation and myocardial protection with local hypothermia in the dog, no significant alteration in hemodynamic function occurred. There was an early release of anaerobic metabolites in the coronary circulation, a marked increase in coronary sinus oxygen content consistent with reperfusion, and significant reactive hyperemia lasting about 20 minutes. There also appeared to be a selective increase in the perfusion of the myocardium. These findings are consistent with the fact that reactive hyperemia occurs following a period of circulatory cessation to any arterial bed or organ [13]. T h e noteworthy findings are the magnitude, duration, and distribution of the coronary hyperemia. T h e increased coronary blood flow, particularly to the subendocardial myocardium following anoxic cardiac arrest with .protection by local hypothermia, is similar to the findings of Brantigan and associates [2] following anoxic cardiac arrest in dogs with nonhypertrophied ventricles. Recent work using radioactive microspheres has suggested that major alterations may occur in the distribution of coronary blood flow during and after various forms of ventricular protection in the fibrillating heart supported by coronary perfusion [4] or after isoproterenol infusions [5]. These studies have suggested that the left ventricular endomyocardium is the area most vulnerable to ischemia even if the heart is not hypertrophied; left ventricular dysfunction after open-heart operations may result from subendocardial ischemia [6, 171. T h e so-called stone heart (subendomyocardia1 ischemia) described by Wukasch and associates [17] has been very rare following local cardiac hypothermia [7, 141 for operations in human beings.
References 1. Anderson, W., Collins, J. J., Jr., Fahl, J., and Morgan, A. Methods €or thermodilution and cardiac output measurements in intensive care using a flow-directed catheter. Bull Znt Chir SOC (In press.) VOL.
19,
NO. 1, JANUARY,
1975
15
COHN E T AL. 2. Angell, W. W., Rikkers, L., Dong, E., Jr., and Shumway, N. E. Organ viability with hypothermia. J Thorac Cardiovasc Surg 58:619, 1969. 3. Brantigan, J. W., Perna, A. M., Gardner, T. J., and Gott, V. L. Intramyocardial gas tensions in the canine heart during anoxic cardiac atrest. Surg Gynecol Obstet 134:67, 1972. 4. Buckberg, G. D., Fixler, D. E., Archie, J. P., and Hoffman, J. I. E. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 30:67, 1972. 5. Buckberg, G. D., and Ross, G. Effects of isoprenoline on coronary blood now. Cardiovasc Res 7:429, 1973. Subendocardial 6. Chu-Jeng, C., Mersereau, W. A., and Scott, H. J. hemorrhagic necrosis: T h e role of direct mechanical trauma on the endocardium. J Thoroc Cardiovasc Surg 64:66, 1972. 7. Colin, L. H., and Collins, J . J., Jr. Local cardiac hypothermia for myocardial protection. Ann Thorac Surg 17: 135, 1974. 8. Domenech, R. J., Hoffman, J. I. E., Noble, M. I. M., Saunders, K. B., Henson, J. R., and Subijanto, S. Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs. Circ Res 25:581, 1969. 9. Enright, L. P., Staroscik, R. N., and Reis, R. I. Left ventricular function after occlusion of the ascending aorta: Assessments of various methods for myocardial protection. J Thorac Cardiovasc Surg 60:737, 1970. 10. Fuhrman, G. J., Fuhrman, F. A., and Field, J. Metabolism of rat heart slices with special reference to effects of temperature and anoxia. A m Physiol 163:642, 1950. 11. GanL, W., and Swan, H. 1. C. Measurement of blood flow by thermodilution. A m J Cardiol29:241, 1972. 12. Gott, V. L., Bartlett, M., Long, D. M., Lillehei, C. W., and Johnson, J . A. Myocardial energy substances in the dog heart during potassium and hypotliermic arrest. .I A p p l Physiol 17:815, 1962. 13. Gregg, D. E., and Fisher, L. C. Blood Supply to the Heart. I n W. F. Hamilton (Ed), Handbook of Physiology. Section 2: Circulation. Washington, D.C.: American Physiological Society, 1963. Vol 11, p 1517. 14. Griepp, R. B., Stinson, E. B., and Shumway, N. E. Profound local hypothermia for myocardial protection during open-heart surgery. J Thorac Cardtovasc Surg 66:731, 1973. 15. Sanger, P. W., Robicsek, F., Daugherty, H. K., Gallucci, V., and Lesage, M. A. Topical cardiac hypothermia in lieu of coronary perfusion. J Thorac Cardiovasc Surg 52:533, 1966. 16. Shumway, N. E., Lower, R. E., and Stofer, R. C. Selective hypothermia of the heart in anoxic cardiac arrest. Surg Gynecol Obstet 109:750, 1959. 17. Wukasch, D. C., Reul, G. J., Milam, 1. D., Hallman, G. L., and Cooley, D. A. T h e stone heart syndrome. Siirgery 72: 1071, 1972.
16
THE ANNA1.S OF THORACIC SURGERY
I
n 1959 Shumway and associates [ 161 demonstrated experimentally that local cardiac hypothermia produced by a circulating cold saline bath affords satisfactory protection to the myocardium during periods of cardiac anoxia. Although many cardiac surgery units [7, 14, 15, 171 are using local cardiac hypothermia for myocardial protection during operations on the aortic root or when flaccidity of the heart facilitates the operative procedure, relatively little is known of the physiological adjustments following its use. This study was undertaken to evaluate myocardial function, changes in coronary blood flow and metabolism, and distribution of coronary blood flow in the dog heart following hypothermia for local cardiac protection of the anoxic ventricle.
Methods Ten mongrel dogs weighing between 15 and 25 kg were the experimental subjects. After pentobarbital anesthesia (2 mg per kilogram of body weight) was given, a median sternotomy was made and catheterization of the femoral artery and vein for measurement of systemic arterial pressure From the Departments of Surgery and Medicine, Harvard Medical School, and the Division of Thoracic and Cardiac Surgery, Peter Bent Brigham Hospital, Boston, Mass. Supported in part by grants from the Massachusetts Heart Association and the Hartford Foundation. We wish to thank Anna Mae Fosberg, Susan Tracey, Stuart Solomon, and Joel Davis for their technical assistance. Accepted for publication July 10, 1974. Address reprint requests to Dr. Cohn, Division of Thoracic and Cardiac Surgery, Peter Bent Brigham Hospital, 721 Huntington Ave., Boston, Mass. 02115.
10
THE ANNALS OF THORACIC SURGERY
Eflecls of Local Cardiac Hypothermia
and central venous pressure was carried out. A catheter connected to a Statham pressure transducer was introduced into the apex of the left ventricle to record left ventricular pressure on high and low gain. A coronary sinus catheter was placed for coronary lactate, potassium, and blood gas determinations. An Instrumentation Laboratories glass electrode especially designed for sensing surface pH measured the right ventricular myocardial surface pH; readings were recorded on a Dow Corning research electrometer. A large-bore catheter connected to a gravity collection device in the heartlung machine was placed in the right atrium for collection of coronary sinus blood flow. When caval flow was returned directly to the pump, thus excluding systemic venous blood from the right atrium, this catheter collected coronary sinus flow. Coronary sinus flow was measured for a period of 1 minute three times successively and averaged at each intervention. Intramyocardial temperature was measured by a thermistor, the sensitive tip of which was inserted midway between the epicardium and endocardium of the left ventricular free wall and connected to a Yellow Springs temperature gauge. Cardiac output was calculated by the thermodilution method using a Swan-Ganz catheter placed in the main pulmonary artery; measurements were made in triplicate. Correlations (25 to loyo) with electromagnetic flowmeter and indocyanine green techniques have been reported [l]. Control measurements of heart rate, systemic arterial blood pressure, left ventricular pressure, left ventricular end-diastolic pressure, cardiac output, arterial and coronary sinus pH, Poz, and Pco2 were determined, as were the arterial and coronary sinus values of p,otassium and lactate. Cardiopulmonary bypass was then instituted by inserting venous cannulas into the right internal jugular vein and right femoral vein and an arterial perfusion cannula in the right femoral artery. During cardiopulmonary bypass the blood temperature was maintained at 35"C, and the hematocrit averaged 37y0 at flow rates of approximately 1.5 liters per minute. After institution of cardiopulmonary bypass the heart was electrically fibrillated, blood flow in the cavae was excluded from the right atrium, and measurements were made of the coronary sinus blood gas tensions, lactate and potassium, and coronary venous flow. T h e aorta was then cross-clamped for 60 minutes, during which time the heart was protected by local cardiac hypothermia (as illustrated in the Figure appearing in A n n T h o r u c Surg 17:137, 1974). T h e heart was positioned so that the left ventricle was the most dependent cardiac structure and was bathed in a continuous bath of iced Ringer's lactate solution. T h e left ventricle was decompressed during cardiopulmonary bypass using a sump catheter inserted through the apex. Five minutes and 30 minutes after removal of the aortic clamp, coronary blood flow, Poz, PCOB,potassium, and lactate were measured from the coronary sinus catheter. T h e heart was then defibrillated, the animal taken
VOL.19, NO.
I , JANUARY,
1975
11
COHN E T AL.
off cardiopulmonary bypass, and hemodynamic measurements repeated 30 minutes after the animal’s condition had stabilized off cardiopulmonary bypass. T h e distribution of coronary blood flow was determined with radioactive labeled microspheres in 6 animals. Microspheres* 15 p in diameter labeled with cesium 141 and strontium 85 were used. Steps taken to prevent settling or aggregation of the microspheres prior to use included: (1) addition of a drop of Tween 80 to each shipment of microspheres; (2) suspension of the microspheres in a glucose solution with a specific gravity of 1.3, the same as the microspheres; and (3) ultrasonification of the solution immediately prior to infusion. Within 5 minutes after discontinuance of aortic cross-clamping, 141Cs-tagged microspheres (300,000 microspheres representing 1 to 7 pCi in 3 ml) were injected into the return line from the bypass pump. At this point the heart was not ejecting blood, so mixing of the microspheres with coronary blood flow occurred along the entire length of the aorta. Thirty minutes later, when the heart was pumping normally after defibrillation, a similar injection of S5Sr microspheres was made into the left atrium. Subsequently, the heart was removed and sectioned into two fullthickness samples from the left ventricular wall, a full-thickness sample from the interventricular septum, and a sample from the right ventricular wall. T h e left ventricle and septum samples were divided into endocardia1 and epicardial halves. T h e seven samples, each weighing 4 to 8 gm, were placed in tubes and the radioactivity determined with a gamma well counter utilizing a dual channel pulse-height analyzer.? Pulses corresponding to energies around 750 kev (strontium) and 141 kev (cesium) were counted. Cesium contributed negligible counting to the strontium channel, but strontium was counted in the cesium channel at a rate one-sixth that in the higher energy channel. T h e data corrected for background and strontium crossover were expressed as counts per minute per milligram for each isotope. T h e endocardial/epicardial ratio of radioactivity represents the ratio of absolute blood flow at the time the microspheres were injected.
Results All animals survived the period of aortic cross-clamping and cardiac anoxia during which the myocardium was protected by local cardiac hypothermia on cardiopulmonary bypass. T h e results of the hemodynamic studies are summarized in Table 1. There was no statistically significant difference in any of these measurements before and after bypass. Table 2 shows the mean and range of coronary sinus blood lactate, potassium, Po,, and Pcoz before, immediately after, and 30 minutes after cardiac anoxia and local cardiac hypothermia. Immediately after restoration of coronary blood flow there was a decrease in the coronary sinus potassium, *3M Co., St. Paul, Minn. +Nuclear-Chicago Co., Chicago, Ill.
12
THE ANNALS OF THORACIC SURGERY
Eflects of Local Cardiac Hypothermia TABLE 1. HEMODYNAMIC DATA BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Measurement
Range
Before LCH MAP (mm Hg) Heart rate (beats/min) LVEDP (mm Hg) Cardiac output (L/min) After LCH (and cardiopulmonary bypass) .MAP (mm Hg) Heart rate (beats/min) LVEDP (mm Hg) Cardiac output (L/min)
Mean
75-105 150-200 4-9 1.25-2.74
100 170 6 2.1
60- 100 90-240 5-1 1 1.2-2.8
85 190
7
2.05
MAP = mean arterial pressure: LVEDP = left ventricular end-diastolic pressure.
elevation of coronary sinus lactate, and significant increases in Po2 and PCOZ; these changes had returned toward control values by the next set of measurements taken 30 minutes later. Myocardial surface pH (MpH) and left ventricular intramyocardial temperature (Tm) values are summarized in Table 3. MpH fell to a mean of 6.5 (range 6.2 to 7.1) from a control mean of 7.9 (range 7.6 to 8.2). After the period of anoxia, MpH returned to control values (mean 7.85, range 7.8 to 8.0). T h e T m fell to a mean of 152°C (range 14.0 to 16.5"C) during the period of maximum local hypothermia. T h e magnitude of coronary blood flow before and after local cardiac hypothermia (LCH) is shown in the Figure. Control coronary blood flow measured by coronary venous flow during ventricular fibrillation ranged from 120 to 250 ml with a mean of 157 ml per minute+ 36 (SD). Immediately following release of the aortic cross-clamp there was significant coronary hyperemia with a flow of 336 ml per minute k 132; this persisted for approximately 20 minutes and decreased toward control values by 30 minutes (165 ml per minute 2 44). Table 4 shows the distribution of coronary flow determined by injection TABLE 2. CORONARY SINUS BLOOD FLOW MEASUREMENTS BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Measurement
Before LCH
Lactate (moles/L)
1.14-3.15 2.20
Potassium (mEq/L)
2.3-3.8
Po2 (mm Hg)
15-40
26
PCO, (mm Hg)
22-43
%
5 Minutes after LCH
30 Minutes
7.03 (P < 0.001) 1.4-2.5 2.0 (P < 0.01)
1.5-2.8 2.53
6.2-7.7
3.2
46-104
60
( p < 0.001) 27-64 44
(P < 0.01)
VOL.
19, NO.
1, JANUARY,
after LCH
-
2.4-3.4 17-41
2.8 2s
22-40 2 8
1975
13
COHN E T AL. TABLE 3. MYOCARDIAL p H AND TEMPERATURE BEFORE AND AFTER LOCAL CARDIAC HYPOTHERMIA (LCH)
Before LCH Myocardial surface PH Intramyocardial temperature ("C)
7.6-8.2 34-38
7.9
36
During LCH 6.2-7.1 6.5 14-16.5
15.2
After LCH 7.8-8.0
32-36
7.9 34
of radioactive microspheres following protection of the left ventricle by local hypothermia for 60 minutes. The results indicate that during the period following LCH and aortic cross-clamping there was increased coronary blood flow, due predominantly to increased perfusion of the endomyocardium. At 30 minutes after removal of the aortic cross-clamp the subendomyocardial hyperemia appeared to have abated.
C o m men t Several experimental studies have suggested the feasibility of local cardiac hypothermia combined with anoxic arrest for extended protection of the nonperfused heart. Fuhrman, Fuhrman, and Field [lo] showed that the metabolic rate of isolated slices of rat heart was reduced 90% by lowering the temperature from 37" to 10°C. Gott and co-workers [12] demonstrated that the metabolic rate of the arrested heart under normothermia was only 8% of the rate of the working, beating heart. Shumway, Lower, and Stofer [16] reported that dogs can survive if their hearts are protected by a circulating bath of cold saline despite interruption of the coronary circulation, and Enright and co-workers [9] have demonstrated that left ventricular function is preserved if systemic hypothermia is used to protect the myocardium during cardiac anoxia. Finally, Angel1 and associates [Z] have shown that the interval of anoxia compatible with viability of an isolated heart is an inverse linear function of the temperature of the heart. Coronary blood flow before and after local cardiac hypothermia (LCH). (Vertical lines represent standard deviation.)
0
t
Before LCH
I4
5
10
After LCH
30 rnin
THE ANNALS OF THORACIC SURGERY
Eflects of Local Cardiac Hypothermia TABLE 4. DISTRIBUTION OF CORONARY BLOOD FLOW IN G DOCS MEASURED BY RADIOACTIVE MICROSPHERES" AFTER LOCAL CARDIAC HYPOTHERMIA
Left Ventricular Base-Wall Endocardium/ Epicardium 5 rnin 30 min 1.42 1.25 1.28 1.21 1.22 1.51
0.86 0.97 0.81 0.65 0.88 0.87
Left Ventricular Base-Apex Endocardium/ Epicardium 5 min 30 rnin 1.37 1.46 1.30 1.14 1.10 2.16
Septum (LV/RV) 5 min 30 rnin
0.98 0.67 0.77 0.81 0.86 1.01
1.55 1.15 1.41 1.28 1.17 0.74
RV/ LV (5 min)
0.99 0.85 1.17 1.31 1.oo 0.94
0.24 0.64 0.85 0.77 1.06 0.82
*Five-minute injection with cesium 141; SO-minute injection with strontium 85. LV = left ventricle; RV =right ventricle.
Data from our study indicate that after 60 minutes' interruption of the coronary circulation and myocardial protection with local hypothermia in the dog, no significant alteration in hemodynamic function occurred. There was an early release of anaerobic metabolites in the coronary circulation, a marked increase in coronary sinus oxygen content consistent with reperfusion, and significant reactive hyperemia lasting about 20 minutes. There also appeared to be a selective increase in the perfusion of the myocardium. These findings are consistent with the fact that reactive hyperemia occurs following a period of circulatory cessation to any arterial bed or organ [13]. T h e noteworthy findings are the magnitude, duration, and distribution of the coronary hyperemia. T h e increased coronary blood flow, particularly to the subendocardial myocardium following anoxic cardiac arrest with .protection by local hypothermia, is similar to the findings of Brantigan and associates [2] following anoxic cardiac arrest in dogs with nonhypertrophied ventricles. Recent work using radioactive microspheres has suggested that major alterations may occur in the distribution of coronary blood flow during and after various forms of ventricular protection in the fibrillating heart supported by coronary perfusion [4] or after isoproterenol infusions [5]. These studies have suggested that the left ventricular endomyocardium is the area most vulnerable to ischemia even if the heart is not hypertrophied; left ventricular dysfunction after open-heart operations may result from subendocardial ischemia [6, 171. T h e so-called stone heart (subendomyocardia1 ischemia) described by Wukasch and associates [17] has been very rare following local cardiac hypothermia [7, 141 for operations in human beings.
References 1. Anderson, W., Collins, J. J., Jr., Fahl, J., and Morgan, A. Methods €or thermodilution and cardiac output measurements in intensive care using a flow-directed catheter. Bull Znt Chir SOC (In press.) VOL.
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COHN E T AL. 2. Angell, W. W., Rikkers, L., Dong, E., Jr., and Shumway, N. E. Organ viability with hypothermia. J Thorac Cardiovasc Surg 58:619, 1969. 3. Brantigan, J. W., Perna, A. M., Gardner, T. J., and Gott, V. L. Intramyocardial gas tensions in the canine heart during anoxic cardiac atrest. Surg Gynecol Obstet 134:67, 1972. 4. Buckberg, G. D., Fixler, D. E., Archie, J. P., and Hoffman, J. I. E. Experimental subendocardial ischemia in dogs with normal coronary arteries. Circ Res 30:67, 1972. 5. Buckberg, G. D., and Ross, G. Effects of isoprenoline on coronary blood now. Cardiovasc Res 7:429, 1973. Subendocardial 6. Chu-Jeng, C., Mersereau, W. A., and Scott, H. J. hemorrhagic necrosis: T h e role of direct mechanical trauma on the endocardium. J Thoroc Cardiovasc Surg 64:66, 1972. 7. Colin, L. H., and Collins, J . J., Jr. Local cardiac hypothermia for myocardial protection. Ann Thorac Surg 17: 135, 1974. 8. Domenech, R. J., Hoffman, J. I. E., Noble, M. I. M., Saunders, K. B., Henson, J. R., and Subijanto, S. Total and regional coronary blood flow measured by radioactive microspheres in conscious and anesthetized dogs. Circ Res 25:581, 1969. 9. Enright, L. P., Staroscik, R. N., and Reis, R. I. Left ventricular function after occlusion of the ascending aorta: Assessments of various methods for myocardial protection. J Thorac Cardiovasc Surg 60:737, 1970. 10. Fuhrman, G. J., Fuhrman, F. A., and Field, J. Metabolism of rat heart slices with special reference to effects of temperature and anoxia. A m Physiol 163:642, 1950. 11. GanL, W., and Swan, H. 1. C. Measurement of blood flow by thermodilution. A m J Cardiol29:241, 1972. 12. Gott, V. L., Bartlett, M., Long, D. M., Lillehei, C. W., and Johnson, J . A. Myocardial energy substances in the dog heart during potassium and hypotliermic arrest. .I A p p l Physiol 17:815, 1962. 13. Gregg, D. E., and Fisher, L. C. Blood Supply to the Heart. I n W. F. Hamilton (Ed), Handbook of Physiology. Section 2: Circulation. Washington, D.C.: American Physiological Society, 1963. Vol 11, p 1517. 14. Griepp, R. B., Stinson, E. B., and Shumway, N. E. Profound local hypothermia for myocardial protection during open-heart surgery. J Thorac Cardtovasc Surg 66:731, 1973. 15. Sanger, P. W., Robicsek, F., Daugherty, H. K., Gallucci, V., and Lesage, M. A. Topical cardiac hypothermia in lieu of coronary perfusion. J Thorac Cardiovasc Surg 52:533, 1966. 16. Shumway, N. E., Lower, R. E., and Stofer, R. C. Selective hypothermia of the heart in anoxic cardiac arrest. Surg Gynecol Obstet 109:750, 1959. 17. Wukasch, D. C., Reul, G. J., Milam, 1. D., Hallman, G. L., and Cooley, D. A. T h e stone heart syndrome. Siirgery 72: 1071, 1972.
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THE ANNA1.S OF THORACIC SURGERY
