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The effectiveness of topical cardiac hypothermia
The effectiveness of topical cardiac hypothermia The effectiveness of cooling the subendocardial myocardium by five different methods was evaluated in a group of 100 patients. The most effective and consistent method to cool the heart was by total body hypothermia with the heat exchanger in the cardiopulmonary bypass system. Myocardial temperature became equal to vena caval blood temperature after only a one minute lag. The least effective methods of myocardial cooling were those in which a bath of chilled fluid enveloped the outside surface of the heart, with and without aortic cross-clamping. The drop in ventricular septal temperature was so small that topical hypothermia, by itself, may be worthless. Two methods in which chilled fluid was perfused through the coronary system produced a significant lowering of myocardial temperature. One of these methods employs coronary perfusion with a cold cardioplegic solution in addition to total body hypothermia. It is our current choice for myocardial protection during cross-clamping of the ascending aorta.
Quentin R. Stiles, M.D., Richard K. Hughes, M.D., and George G. Lindesmith, M.D., Los Angeles, Calif.
V_y wing to the small size of the coronary vessels and the demanding technical requirements of coronary artery bypass surgery, optimal conditions are sought for the performance of this operation. Ischemic arrest usually is used to produce the required quiet operative field. The safety of ischemic arrest is time limited, since the aortic cross-clamp time and interruption of coronary flow required to perform multiple vein-tocoronary artery anastomoses will, in some cases, result in the very ischemic damage to the heart that the operation is designed to prevent. Therefore, means have been sought to protect the myocardium from ischemic damage during aortic cross-clamping. The most common method of maintaining myocardial integrity during prolonged aortic cross-clamping has been to employ hypothermia. Metabolic demands of the heart are progressively lowered and the myocardium is increasingly protected against prolonged ischemia with each increment the myocardial temperature is lowered.1' 2 From the Department of Surgery, Hospital of the Good Samaritan, Los Angeles, Calif. This study was partially funded by the Heart and Lung Surgery Foundation, Los Angeles, Calif. Read at the Second Annual Meeting of The Samson Thoracic Surgical Society, Banff, Alberta, Canada, June 1-4, 1976. Address for reprints: Quentin R. Stiles, M.D., 1136 W. Sixth Street, Los Angeles, Calif. 90017.
176
The purpose of this report is to evaluate the effectiveness of several of the methods used to reduce myocardial temperatures. It is the deeper, subendocardial layers of the myocardium that are most at risk and most commonly damaged as a result of prolonged ischemic arrest.3 Therefore, we have studied the subendocardial temperatures in the ventricular septum. Materials and methods One hundred patients undergoing coronary artery bypass grafting were studied. In all, total body hypothermia was obtained by cooling the blood via the heat exchanger incorporated in the disposable oxygenator. Cooling was continued until the temperature of the venous return blood reached 27° C. The temperature of the left ventricular septum, 1 cm. below the epicardial surface, was measured numerous times in each patient. The probe was inserted into the septum to the left of the left anterior descending coronary artery about midway between the diagonal branch and the apex of the heart. The temperature sensing device used was a Yellow Springs thermistor probe.* This is a 20 gauge needle probe which contains a semi-conductor at its tip, in which a change in tempera-
Yellow Springs Instrument Co., Yellow Springs, Ohio (Catalogue Number 513).
Volume 73 Number 2 February, 1977
Topical cardiac hypothermia
17 7
Fig. 1. Composite drawing demonstrating the various features discussed. A, Aortic cannula which returns cold blood from the heat exchanger in the oxygenator system. B, Aortic cross-clamp which occludes the ascending aorta above the coronary arteries and also the main pulmonary artery. C, Infusion cannula for instilling chilled cardioplegic solution into the aortic root. D, Venous return cannula where measurements are made of the venous blood temperature. E, Left ventricular vent which enters the left atrium through a pulmonary vein and passes into the left ventricle through the mitral valve. Chilled fluid was instilled into the left ventricle in Group 3 patients. F, Thermistor probe used to measure the ventricular septal temperature 1 cm. below the epicardial surface.
ture produces a change in electrical resistance. The measurement of this resistance gives a direct reading of the temperature at the thermistor position. In addition to total body hypothermia to 27° C. for all patients, the heart was locally cooled by one of four methods: 1. Topical cooling was achieved by bathing the entire external surface of the heart with 2 to 3 L. of 10° C. isotonic solution for 3 minutes. The heart was kept completely immersed and the fluid continuously poured into the pericardial space and aspirated into the wall suction during this 3 minute period. This theoretically would cool the blood in the epicardial coronary vessels and thence cool the entire thickness of the myocardium. 2. Topical cardiac cooling for 3 minutes was per-
formed by the same pericardial bath but, in addition, the ascending aorta was cross-clamped. This should cool the heart with the maximum effect on the outside surface, and cessation of coronary flow would eliminate the heat exchanging effect of the coronary circulation. 3. The heart was cooled topically, simultaneously, both externally by the same pericardial bath and internally by instillation of 250 ml. of 10° C. solution into the left ventricle via the left ventricular vent. The fluid was injected under pressure with a bulb syringe. The aorta was clamped above the coronary ostia during this instillation. In addition to the topical effect, by this method the coronary arteries perfused this chilled solution through the myocardium. 4. The heart was cooled by infusing 250 ml. of 10°
1 7 8 Stiles, Hughes, Lindesmith
C. cardioplegic fluid under pressure into the aortic root and coronary bed after aortic cross-clamping. Septal temperatures were measured before the local cooling procedures in each case and at the end of the 3 minute bath for Groups 1 and 2, and after the injection of chilled solution in Groups 3 and 4. The cooling period for these latter two groups was usually 2 minutes (Fig. 1). Results Venous return blood of all patients was lowered to a temperature of 27° C. by means of the heat exchanger in the oxygenator. The temperature of the ventricular septum was found to become equal to the temperature of the venous return blood quickly, with a lag of only about one minute. Group 1. In the 23 patients in this group, the heart was bathed externally with 10° C. fluid for 3 minutes with the aorta undamped. The average temperature was lowered to 26.3° C , a fall of 0.7° C. (range -2.8° to +1.5° C , standard deviation 1.23). Group 2. In the 23 patients in this group, the heart was bathed externally with 10° C. fluid for 3 minutes with the aorta clamped. The average temperature was lowered to 26.3° C , a fall of 0.7° C. (range -3.4° to + 1.5° C , standard deviation 1.19). Group 3. The 32 patients in this group had an external bath and internal topical cooling by instillation of 250 ml. of 10° C. fluid into the left ventricle via the vent. The average temperature was lowered to 21° C , a fall of 6.0° C. (range -9.0° to -1.2° C , standard deviation 1.68). Group 4. The 22 patients in this group had internal cooling by infusion of 250 ml. of 10° C. cardioplegic solution into the aortic root. The average temperature was lowered to 20.7° C , a fall of 6.3° C. (range -10.0° to -4.3° C , standard deviation 1.99). Discussion We found the most effective and reliable method of cooling the heart is total body hypothermia via the heat exchanger in the cardiopulmonary bypass perfusion system. The temperatures of the ventricular septal and vena caval blood are nearly identical. This study demonstrates that, when further local cooling of the heart is attempted, a very commonly employed practice of bathing the external surface of the heart in a chilled solution for 3 minutes with the aorta either clamped or undamped above the coronary arteries has very little effect in lowering the temperature of the deeper layers of the heart. This method may give the surgeon a false sense of security. A paradoxical effect was noted upon
The Journal of Thoracic and Cardiovascular Surgery
several occasions when ventricular fibrillation occurred as the cold solution was poured over the heart. In 7 patients the septal temperatures actually rose from 0.2° to 1.5° C , presumably because of the heat generated by the ventricular fibrillation. The most effective method for local cooling of the deeper myocardial layers was perfusion of the coronary system with a chilled solution. Septal temperatures of 20° C. usually can be obtained by this method. Instilling solution via the left ventricular vent or into the aortic root with a small plastic cannula were equally effective in lowering the temperature of the septum. Our current method for obtaining myocardial protection during prolonged aortic cross-clamping is as follows: In addition to using total body hypothermia to 25° to 27° C , we try to obtain rapid metabolic arrest of the heart by infusion of a chilled cardioplegic solution into the aortic root immediately after aortic cross-clamping. The solution used is 1 L. of Normosol-R, pH 7.4,* to which several substances are added. First, 20 mEq. potassium chloride is added to provide cardiac arrest. Next, 1 Gm. of procaine hydrochloride is added to supplement the cardioplegic effect of potassium chloride and produce rapid pharmacologic cardiac arrest with a lower concentration of extracellular potassium. Then, 30 ml. of 50 per cent dextrose solution is added to raise the osmolarity of the solution to about 400 mOsm. per liter. Use of the concentrated dextrose exerts a hyperosmolar effect and may prevent myocardial edema. It also adds glucose to the glycogen stores of the cardiac cell and may prolong the ability of the myocardium to metabolize anaerobically during the period of aortic cross-clamping. Twenty units of insulin is added to enhance this latter capability. Finally, 25 mEq. of sodium bicarbonate is added to raise the pH of the solution to about 7.8. Sodium bicarbonate may prolong the ability of the heart to metabolize anaerobically by buffering hydrogen ions. It is the increased concentration of the hydrogen ion that limits anaerobic metabolism. The use of these drugs is well based upon animal experimentation, but the concentration of each and the actual benefits of some, such as the glucose and insulin, may be somewhat controversial.4' 5 ' 6 The solution is chilled to 10° C. At the moment the aorta and main pulmonary artery are cross-clamped, the solution is infused under pressure into the aortic root through a 16 gauge plastic cannula. The infusion is continued until cardiac arrest occurs, which is in only a few seconds, and after about 250 ml. of the chilled cardioplegic solution has been given. The left ventricu* Abbott Laboratories, North Chicago, III.
Volume 73 Number 2 February, 1977
lar vent is clamped during this infusion to prevent the solution from refluxing through the aortic valve and being aspirated by the vent into the cardiopulmonary bypass system before passing through the myocardium. Once cardiac arrest has occurred, pressure is released from the infusion, which is then continued by a slow drip until the coronary anastomoses are completed. The total amount of fluid administered via the aortic root is usually about 400 ml. in the adult patient. All coronary artery anastomoses are completed during a single period of aortic cross-clamping. With proper planning and the ideal operative conditions produced by this type of cardioplegia, it rarely is necessary to maintain this ischemic period more than 60 minutes, even when five or six coronary anastomoses are constructed. Rewarming is commenced slowly as the last anastomosis is started. With the aorta cross-clamped and an insulating laparotomy pad soaked in cold solution packed underneath, the temperature of the heart will lag considerably as the body is rewarmed. During the performance of the aortic anastomoses, care should be taken that the partially occluding clamp to the aorta does not obstruct the natural coronary ostia. In this way there is ample time for cardiac recovery. The heart usually recovers quickly, although often the first rhythm established is atrioventricular dissociation. This almost always reverts to a conducted pattern in a matter of minutes, and we have not had to resort to a pacemaker beyond the operative phase. So far as we can evaluate clinically, no myocardial damage occurs when this method is used during a 60 to 70 minute interval of ischemia. The method is equally applicable to the very severely damaged as well as the normally performing left ventricle. We express our gratitude to Gerald D. Buckberg, M.D., for his cooperative and very valuable contributions to this study. REFERENCES 1 Griepp, R. B., Stinson, E. B., and Shumway, N. E.: Profound Local Hypothermia for Myocardial Protection During Open-Heart Surgery, J. THORAC. CARDIOVASC. SURG.
66: 731, 1973. 2 Buckberg, G. D.: Personal communication. 3 Buckberg, G. D., Olinger, G. N., Mulder, D. G., and Maloney, J. V., Jr.: Depressed Postoperative Cardiac
Topical cardiac hypothermia
17 9
5 Weissler, A. M., Altschuld, R. A., Gibb, L. E., Pollack, M. E., and Kruger, F. A.: Effect of Insulin on the Performance and Metabolism of the Anoxic Isolated Perfused Rat Heart, Circ. Res. 32: 108, 1973. 6 Rovetto, M. J., Whitmer, J. T., and Neely, J. R.: Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts, Circ. Res. 32: 699, 1973. Discussion DR. BENSON B. ROE San Francisco, Calif.
Dr. Stiles has provided valuable data to document explicitly the thesis which led to our own similar technique for myocardial preservation. It stands to reason that topical cooling would be inefficient and extremely variable in a container such as the pericardium which lacks the physical characteristics of a proper circulating water bath. In addition, conduction through muscle is slow and central myocardial cooling in the hypertrophied heart is delayed for significant periods. On the basis of our extensive experience, I would encourage even greater confidence in this technique for prolonged ischemia in complex intracardiac procedures. DR. GORDON N. O L I N G E R Los Angeles, Calif.
The principles of myocardial protection which Dr. Stiles has outlined to us have been well substantiated in our laboratory and in those of others. In addition to so-called membrane stabilization with either steroids or procaine hydrochloride or both, and the alteration of physical and biochemical milieu during aortic occlusion, alteration of the coronary perfusate terminating arrest to ameliorate reperfusion injury is being investigated. Purely ischemic arrest is a technique necessary for certain aspects of cardiac surgery. I would stress, however, that the safest and most efficacious combination of techniques to protect against ischemic injury in patients remains to be established, and we anticipate soon the initiation of controlled clinical trials with hemodynamic observations to evaluate pharmacologically modified arrest as opposed to our currently well-established and successful methods of myocardial management. Regarding specifically the hypothermic aspects of your study, Dr. Stiles, have you followed the time course of intramyocardial temperature during the duration of ischemic arrest? Also, I would like to know how fast the central cardiac temperature approaches the ambient temperature of the environment, that is, 27° C.
Performance, J. THORAC. CARDIOVASC. SURG. 70: 974,
1975. 4 Hearse, D. J., Stewart, D. A., and Braimbridge, M. V.: Cellular Protection During Myocardial Ischemia: The Development and Characterization of a Procedure for the Induction of Reversible Ischemic Arrest, Circulation 54: 193, 1976.
DR. E D W A R D A. S M E L O F F Sacramento, Calif.
I would like to reinforce much of what Quentin Stiles has said. We have felt that the arrested heart rather than the fibrillating heart would be better from the standpoint of myocardial preservation.
180
Stiles, Hughes,
Lindesmith
In the past 4 years we have done research in the experimental laboratory with 0.2 per cent lidocaine solution as a cardioplegic drug, comparing it with fibrillatory arrest and hypothermic anoxic arrest. We used the Vmax as a point of comparison, and we were surprised to see that there appeared to be an ionotropic effect with the use of lidocaine. Although unable to totally explain this effect, we feel that it may be related to the preservation of the sarcolemmal membrane and the high-energy phosphates and perhaps to calcium stores in the myocardium. Clinically, our technique has been to perfuse the aortic route with 0.2 per cent lidocaine in Normosol, pH 7.4, at 4° C. to the point of cardiac arrest. This usually requires the injection of 100 to 125 c.c. of the solution and takes approximately 30 seconds. We are in the process of evaluating these patients in a triple blind study. One of my partners, Dr. George Miller, has been using Dr. Roe's technique, and my other two partners, Dr. Paul Kelly and Dr. Forrest Junod, have been using fibrillatory arrest with external cold. We are evaluating the CPK, MB, and SGOT studies as well as the electrocardiogram and clinical status of these patients. These data are in the process of being prepared for computer analysis. All I would like to say at this point is that lidocaine has not been deleterious. It produces cardiac arrest rapidly and, upon release of the aortic cross-clamp, sinus rhythm returns in approximately 30 seconds. I feel that this method of cardioplegia deserves further study, and we shall continue to evaluate it.
The Journal of Thoracic and Cardiovascular Surgery
D R . S T I L E S (Closing) I would like to thank the discussers for their kind remarks. In answer to Gordon Olinger, we monitored the temperature during the course of the procedure, after the local cooling event. The myocardial temperature will rise slowly to equal the vena caval blood temperature, 27° C , with a lag period of about 10 to 15 minutes. This period can be extended by placing a laparotomy pad soaked in the cold solution underneath the heart to insulate it from the lung behind it. It is interesting that the heart is not the same temperature all over and I believe—although I cannot prove it from our data—that the temperature depends upon the coronary flow. On some occasions in which the left anterior descending coronary artery has been 100 per cent occluded, the temperature has not fallen in the anterior septum as much as was expected, compared to the other patients. At times, I have pushed the needle probe into the septum posteriorly and found as much as an 8° difference in the myocardial temperature. Currently, we are using this cardioplegic solution to arrest the heart but then continue dripping the solution after the heart arrests. Usually about 200 c.c. is necessary for the heart to arrest, but we continue using this cold solution as an aortic root infusion for the duration of the aortic cross-clamping, using as much as 500 ml. This will keep the heart cool during the entire ischemic period.
Quentin R. Stiles, M.D., Richard K. Hughes, M.D., and George G. Lindesmith, M.D., Los Angeles, Calif.
V_y wing to the small size of the coronary vessels and the demanding technical requirements of coronary artery bypass surgery, optimal conditions are sought for the performance of this operation. Ischemic arrest usually is used to produce the required quiet operative field. The safety of ischemic arrest is time limited, since the aortic cross-clamp time and interruption of coronary flow required to perform multiple vein-tocoronary artery anastomoses will, in some cases, result in the very ischemic damage to the heart that the operation is designed to prevent. Therefore, means have been sought to protect the myocardium from ischemic damage during aortic cross-clamping. The most common method of maintaining myocardial integrity during prolonged aortic cross-clamping has been to employ hypothermia. Metabolic demands of the heart are progressively lowered and the myocardium is increasingly protected against prolonged ischemia with each increment the myocardial temperature is lowered.1' 2 From the Department of Surgery, Hospital of the Good Samaritan, Los Angeles, Calif. This study was partially funded by the Heart and Lung Surgery Foundation, Los Angeles, Calif. Read at the Second Annual Meeting of The Samson Thoracic Surgical Society, Banff, Alberta, Canada, June 1-4, 1976. Address for reprints: Quentin R. Stiles, M.D., 1136 W. Sixth Street, Los Angeles, Calif. 90017.
176
The purpose of this report is to evaluate the effectiveness of several of the methods used to reduce myocardial temperatures. It is the deeper, subendocardial layers of the myocardium that are most at risk and most commonly damaged as a result of prolonged ischemic arrest.3 Therefore, we have studied the subendocardial temperatures in the ventricular septum. Materials and methods One hundred patients undergoing coronary artery bypass grafting were studied. In all, total body hypothermia was obtained by cooling the blood via the heat exchanger incorporated in the disposable oxygenator. Cooling was continued until the temperature of the venous return blood reached 27° C. The temperature of the left ventricular septum, 1 cm. below the epicardial surface, was measured numerous times in each patient. The probe was inserted into the septum to the left of the left anterior descending coronary artery about midway between the diagonal branch and the apex of the heart. The temperature sensing device used was a Yellow Springs thermistor probe.* This is a 20 gauge needle probe which contains a semi-conductor at its tip, in which a change in tempera-
Yellow Springs Instrument Co., Yellow Springs, Ohio (Catalogue Number 513).
Volume 73 Number 2 February, 1977
Topical cardiac hypothermia
17 7
Fig. 1. Composite drawing demonstrating the various features discussed. A, Aortic cannula which returns cold blood from the heat exchanger in the oxygenator system. B, Aortic cross-clamp which occludes the ascending aorta above the coronary arteries and also the main pulmonary artery. C, Infusion cannula for instilling chilled cardioplegic solution into the aortic root. D, Venous return cannula where measurements are made of the venous blood temperature. E, Left ventricular vent which enters the left atrium through a pulmonary vein and passes into the left ventricle through the mitral valve. Chilled fluid was instilled into the left ventricle in Group 3 patients. F, Thermistor probe used to measure the ventricular septal temperature 1 cm. below the epicardial surface.
ture produces a change in electrical resistance. The measurement of this resistance gives a direct reading of the temperature at the thermistor position. In addition to total body hypothermia to 27° C. for all patients, the heart was locally cooled by one of four methods: 1. Topical cooling was achieved by bathing the entire external surface of the heart with 2 to 3 L. of 10° C. isotonic solution for 3 minutes. The heart was kept completely immersed and the fluid continuously poured into the pericardial space and aspirated into the wall suction during this 3 minute period. This theoretically would cool the blood in the epicardial coronary vessels and thence cool the entire thickness of the myocardium. 2. Topical cardiac cooling for 3 minutes was per-
formed by the same pericardial bath but, in addition, the ascending aorta was cross-clamped. This should cool the heart with the maximum effect on the outside surface, and cessation of coronary flow would eliminate the heat exchanging effect of the coronary circulation. 3. The heart was cooled topically, simultaneously, both externally by the same pericardial bath and internally by instillation of 250 ml. of 10° C. solution into the left ventricle via the left ventricular vent. The fluid was injected under pressure with a bulb syringe. The aorta was clamped above the coronary ostia during this instillation. In addition to the topical effect, by this method the coronary arteries perfused this chilled solution through the myocardium. 4. The heart was cooled by infusing 250 ml. of 10°
1 7 8 Stiles, Hughes, Lindesmith
C. cardioplegic fluid under pressure into the aortic root and coronary bed after aortic cross-clamping. Septal temperatures were measured before the local cooling procedures in each case and at the end of the 3 minute bath for Groups 1 and 2, and after the injection of chilled solution in Groups 3 and 4. The cooling period for these latter two groups was usually 2 minutes (Fig. 1). Results Venous return blood of all patients was lowered to a temperature of 27° C. by means of the heat exchanger in the oxygenator. The temperature of the ventricular septum was found to become equal to the temperature of the venous return blood quickly, with a lag of only about one minute. Group 1. In the 23 patients in this group, the heart was bathed externally with 10° C. fluid for 3 minutes with the aorta undamped. The average temperature was lowered to 26.3° C , a fall of 0.7° C. (range -2.8° to +1.5° C , standard deviation 1.23). Group 2. In the 23 patients in this group, the heart was bathed externally with 10° C. fluid for 3 minutes with the aorta clamped. The average temperature was lowered to 26.3° C , a fall of 0.7° C. (range -3.4° to + 1.5° C , standard deviation 1.19). Group 3. The 32 patients in this group had an external bath and internal topical cooling by instillation of 250 ml. of 10° C. fluid into the left ventricle via the vent. The average temperature was lowered to 21° C , a fall of 6.0° C. (range -9.0° to -1.2° C , standard deviation 1.68). Group 4. The 22 patients in this group had internal cooling by infusion of 250 ml. of 10° C. cardioplegic solution into the aortic root. The average temperature was lowered to 20.7° C , a fall of 6.3° C. (range -10.0° to -4.3° C , standard deviation 1.99). Discussion We found the most effective and reliable method of cooling the heart is total body hypothermia via the heat exchanger in the cardiopulmonary bypass perfusion system. The temperatures of the ventricular septal and vena caval blood are nearly identical. This study demonstrates that, when further local cooling of the heart is attempted, a very commonly employed practice of bathing the external surface of the heart in a chilled solution for 3 minutes with the aorta either clamped or undamped above the coronary arteries has very little effect in lowering the temperature of the deeper layers of the heart. This method may give the surgeon a false sense of security. A paradoxical effect was noted upon
The Journal of Thoracic and Cardiovascular Surgery
several occasions when ventricular fibrillation occurred as the cold solution was poured over the heart. In 7 patients the septal temperatures actually rose from 0.2° to 1.5° C , presumably because of the heat generated by the ventricular fibrillation. The most effective method for local cooling of the deeper myocardial layers was perfusion of the coronary system with a chilled solution. Septal temperatures of 20° C. usually can be obtained by this method. Instilling solution via the left ventricular vent or into the aortic root with a small plastic cannula were equally effective in lowering the temperature of the septum. Our current method for obtaining myocardial protection during prolonged aortic cross-clamping is as follows: In addition to using total body hypothermia to 25° to 27° C , we try to obtain rapid metabolic arrest of the heart by infusion of a chilled cardioplegic solution into the aortic root immediately after aortic cross-clamping. The solution used is 1 L. of Normosol-R, pH 7.4,* to which several substances are added. First, 20 mEq. potassium chloride is added to provide cardiac arrest. Next, 1 Gm. of procaine hydrochloride is added to supplement the cardioplegic effect of potassium chloride and produce rapid pharmacologic cardiac arrest with a lower concentration of extracellular potassium. Then, 30 ml. of 50 per cent dextrose solution is added to raise the osmolarity of the solution to about 400 mOsm. per liter. Use of the concentrated dextrose exerts a hyperosmolar effect and may prevent myocardial edema. It also adds glucose to the glycogen stores of the cardiac cell and may prolong the ability of the myocardium to metabolize anaerobically during the period of aortic cross-clamping. Twenty units of insulin is added to enhance this latter capability. Finally, 25 mEq. of sodium bicarbonate is added to raise the pH of the solution to about 7.8. Sodium bicarbonate may prolong the ability of the heart to metabolize anaerobically by buffering hydrogen ions. It is the increased concentration of the hydrogen ion that limits anaerobic metabolism. The use of these drugs is well based upon animal experimentation, but the concentration of each and the actual benefits of some, such as the glucose and insulin, may be somewhat controversial.4' 5 ' 6 The solution is chilled to 10° C. At the moment the aorta and main pulmonary artery are cross-clamped, the solution is infused under pressure into the aortic root through a 16 gauge plastic cannula. The infusion is continued until cardiac arrest occurs, which is in only a few seconds, and after about 250 ml. of the chilled cardioplegic solution has been given. The left ventricu* Abbott Laboratories, North Chicago, III.
Volume 73 Number 2 February, 1977
lar vent is clamped during this infusion to prevent the solution from refluxing through the aortic valve and being aspirated by the vent into the cardiopulmonary bypass system before passing through the myocardium. Once cardiac arrest has occurred, pressure is released from the infusion, which is then continued by a slow drip until the coronary anastomoses are completed. The total amount of fluid administered via the aortic root is usually about 400 ml. in the adult patient. All coronary artery anastomoses are completed during a single period of aortic cross-clamping. With proper planning and the ideal operative conditions produced by this type of cardioplegia, it rarely is necessary to maintain this ischemic period more than 60 minutes, even when five or six coronary anastomoses are constructed. Rewarming is commenced slowly as the last anastomosis is started. With the aorta cross-clamped and an insulating laparotomy pad soaked in cold solution packed underneath, the temperature of the heart will lag considerably as the body is rewarmed. During the performance of the aortic anastomoses, care should be taken that the partially occluding clamp to the aorta does not obstruct the natural coronary ostia. In this way there is ample time for cardiac recovery. The heart usually recovers quickly, although often the first rhythm established is atrioventricular dissociation. This almost always reverts to a conducted pattern in a matter of minutes, and we have not had to resort to a pacemaker beyond the operative phase. So far as we can evaluate clinically, no myocardial damage occurs when this method is used during a 60 to 70 minute interval of ischemia. The method is equally applicable to the very severely damaged as well as the normally performing left ventricle. We express our gratitude to Gerald D. Buckberg, M.D., for his cooperative and very valuable contributions to this study. REFERENCES 1 Griepp, R. B., Stinson, E. B., and Shumway, N. E.: Profound Local Hypothermia for Myocardial Protection During Open-Heart Surgery, J. THORAC. CARDIOVASC. SURG.
66: 731, 1973. 2 Buckberg, G. D.: Personal communication. 3 Buckberg, G. D., Olinger, G. N., Mulder, D. G., and Maloney, J. V., Jr.: Depressed Postoperative Cardiac
Topical cardiac hypothermia
17 9
5 Weissler, A. M., Altschuld, R. A., Gibb, L. E., Pollack, M. E., and Kruger, F. A.: Effect of Insulin on the Performance and Metabolism of the Anoxic Isolated Perfused Rat Heart, Circ. Res. 32: 108, 1973. 6 Rovetto, M. J., Whitmer, J. T., and Neely, J. R.: Comparison of the Effects of Anoxia and Whole Heart Ischemia on Carbohydrate Utilization in Isolated Working Rat Hearts, Circ. Res. 32: 699, 1973. Discussion DR. BENSON B. ROE San Francisco, Calif.
Dr. Stiles has provided valuable data to document explicitly the thesis which led to our own similar technique for myocardial preservation. It stands to reason that topical cooling would be inefficient and extremely variable in a container such as the pericardium which lacks the physical characteristics of a proper circulating water bath. In addition, conduction through muscle is slow and central myocardial cooling in the hypertrophied heart is delayed for significant periods. On the basis of our extensive experience, I would encourage even greater confidence in this technique for prolonged ischemia in complex intracardiac procedures. DR. GORDON N. O L I N G E R Los Angeles, Calif.
The principles of myocardial protection which Dr. Stiles has outlined to us have been well substantiated in our laboratory and in those of others. In addition to so-called membrane stabilization with either steroids or procaine hydrochloride or both, and the alteration of physical and biochemical milieu during aortic occlusion, alteration of the coronary perfusate terminating arrest to ameliorate reperfusion injury is being investigated. Purely ischemic arrest is a technique necessary for certain aspects of cardiac surgery. I would stress, however, that the safest and most efficacious combination of techniques to protect against ischemic injury in patients remains to be established, and we anticipate soon the initiation of controlled clinical trials with hemodynamic observations to evaluate pharmacologically modified arrest as opposed to our currently well-established and successful methods of myocardial management. Regarding specifically the hypothermic aspects of your study, Dr. Stiles, have you followed the time course of intramyocardial temperature during the duration of ischemic arrest? Also, I would like to know how fast the central cardiac temperature approaches the ambient temperature of the environment, that is, 27° C.
Performance, J. THORAC. CARDIOVASC. SURG. 70: 974,
1975. 4 Hearse, D. J., Stewart, D. A., and Braimbridge, M. V.: Cellular Protection During Myocardial Ischemia: The Development and Characterization of a Procedure for the Induction of Reversible Ischemic Arrest, Circulation 54: 193, 1976.
DR. E D W A R D A. S M E L O F F Sacramento, Calif.
I would like to reinforce much of what Quentin Stiles has said. We have felt that the arrested heart rather than the fibrillating heart would be better from the standpoint of myocardial preservation.
180
Stiles, Hughes,
Lindesmith
In the past 4 years we have done research in the experimental laboratory with 0.2 per cent lidocaine solution as a cardioplegic drug, comparing it with fibrillatory arrest and hypothermic anoxic arrest. We used the Vmax as a point of comparison, and we were surprised to see that there appeared to be an ionotropic effect with the use of lidocaine. Although unable to totally explain this effect, we feel that it may be related to the preservation of the sarcolemmal membrane and the high-energy phosphates and perhaps to calcium stores in the myocardium. Clinically, our technique has been to perfuse the aortic route with 0.2 per cent lidocaine in Normosol, pH 7.4, at 4° C. to the point of cardiac arrest. This usually requires the injection of 100 to 125 c.c. of the solution and takes approximately 30 seconds. We are in the process of evaluating these patients in a triple blind study. One of my partners, Dr. George Miller, has been using Dr. Roe's technique, and my other two partners, Dr. Paul Kelly and Dr. Forrest Junod, have been using fibrillatory arrest with external cold. We are evaluating the CPK, MB, and SGOT studies as well as the electrocardiogram and clinical status of these patients. These data are in the process of being prepared for computer analysis. All I would like to say at this point is that lidocaine has not been deleterious. It produces cardiac arrest rapidly and, upon release of the aortic cross-clamp, sinus rhythm returns in approximately 30 seconds. I feel that this method of cardioplegia deserves further study, and we shall continue to evaluate it.
The Journal of Thoracic and Cardiovascular Surgery
D R . S T I L E S (Closing) I would like to thank the discussers for their kind remarks. In answer to Gordon Olinger, we monitored the temperature during the course of the procedure, after the local cooling event. The myocardial temperature will rise slowly to equal the vena caval blood temperature, 27° C , with a lag period of about 10 to 15 minutes. This period can be extended by placing a laparotomy pad soaked in the cold solution underneath the heart to insulate it from the lung behind it. It is interesting that the heart is not the same temperature all over and I believe—although I cannot prove it from our data—that the temperature depends upon the coronary flow. On some occasions in which the left anterior descending coronary artery has been 100 per cent occluded, the temperature has not fallen in the anterior septum as much as was expected, compared to the other patients. At times, I have pushed the needle probe into the septum posteriorly and found as much as an 8° difference in the myocardial temperature. Currently, we are using this cardioplegic solution to arrest the heart but then continue dripping the solution after the heart arrests. Usually about 200 c.c. is necessary for the heart to arrest, but we continue using this cold solution as an aortic root infusion for the duration of the aortic cross-clamping, using as much as 500 ml. This will keep the heart cool during the entire ischemic period.