Myocardial Protection from Permanent Injury during Aortic Cross-Clamping: Effectiveness of Pharmacological Cardiac Arrest Combined with Topical Cardiac Hypothermia

In two groups of animals (6 and 9 dogs), the aorta was cross-clamped 60 and 90 minutes, respectively, during hypothermic cardiopulmonary bypass. Immediately after cross-clamping, pharmacological cardiac arrest was induced by injecting 100 ml of a cold cardioplegic solution into the aortic root. Topical cardiac hypothermia was added. In hearts undergoing 90 minutes of ischemia, a repeat injection of the cardioplegic solution was done at 45 minutes. In 14 dogs (control group), only topical cardiac hypothermia was instituted for myocardial protection during 60 minutes of ischemia. Seven weeks after operation the surviving animals (6 in each group) were killed.Study of myocardial performance failed to demonstrate significant differences among the groups. Microscopic examination of transmural samples taken from anatomically defined sides of both ventricles, disclosed isolated, punctuate subendocardial scars in only 2 hearts of the control group. All the hearts having 90 minutes of pharmacological cardiac arrest and topical cardiac hypothermia exhibited diffuse fibrosis replacing 10 to 20% of the left ventricular myocardium. Extent and incidence of fibrosis were significantly higher in these hearts in comparison to those of the other groups.We conclude that pharmacological cardiac arrest plus topical cardiac hypothermia makes a safe and efficient method of myocardial protection during aortic cross-clamping only if the ischemic interval is limited to 60 minutes. It cannot prevent permanent myocardial injury if the ischemic arrest is extended to 90 minutes.     

Functional and metabolic effects of nicardipine on ischemic rat hearts with multidose potassium cardioplegia

This study was undertaken to assess the effect of a calcium antagonist, nicardipine (N), added in a cardioplegic solution on the ischemic myocardium. Isolated rat hearts were perfused with oxygenated Krebs Ringer Bicarbonate (KRB) solution by Langendorff's perfusion method and were subjected to 2 hours of ischemic arrest at 30 degrees C with multidose cardioplegia (every 30 min, for 5 min) and a subsequent 60 min of reperfusion. HR, LVP, coronary flow and oxygen tension of coronary effluent were monitored. Oxygen saturation of intracellular myoglobin and redox state of mitochondrial cytochrome aa3 in the myocardial cell were continuously measured throughout studies by a spectrophotometer. Oxygenated crystalloid cardioplegic solution (KRB) containing 25 mM of potassium was used. 40 rats were divided into 4 groups (10 rats each) according to the concentration of N (none, 0.5, 1 and 2 mg/L) in fully oxygenated potassium cardioplegic solution (PO2: 601 +/- 31 mmHg). The percent recovery of pressure-rate product after reperfusion was compared in each group and the optimal concentration of N was found to be 1 mg per liter of cardioplegic solution. No significant difference was found between Group Ia (N = 0 mg/L) and Group Ib (N = 1 mg/L) in metabolic or hemodynamic recovery after reperfusion. In other experiments, 40 rats in Group IIa (N = 0 mg/L, n = 20) and Group IIb (N = 1 mg/L, n = 20) received 10 ml of poorly oxygenated cardioplegic solution (PO2: 215 +/- 10 mmHg) on each reinfusion followed by a 25 min interval of ischemic arrest. The index of oxygen utilization, MVO2/pressure-rate product after reperfusion was significantly lower in Group IIb than in Group IIa (p less than 0.05). The results show that the addition of N (1 mg/L) to the cardioplegic solution preserved a more aerobic state (higher intracellular oxygen level) in the myocardium by further suppressing myocardial oxygen demand during the ischemic period which resulted in better myocardial protection. Therefore, it is concluded that the addition of N to the cardioplegic solution enhances myocardial preservation during myocardial ischemia.     

Effects of varied cardioplegic perfusion pressure on myocardial preservation with critical coronary stenosis

Inadequate delivery of cardioplegic solution distal to coronary artery stenosis may result in increased injury during ischemic arrest. This study was performed to determine the effects of cardioplegic perfusion pressure on cardioplegia delivery and myocardial preservation in hearts with critical coronary artery stenosis. Twenty dogs underwent 90 minutes of cold potassium cardioplegic arrest with partial occlusion of the circumflex coronary artery. Group 1 received cardioplegia at 50 mm Hg pressure, Group 2 at 90 mm Hg pressure, and Group 3 at 130 mm Hg pressure. It was found that cooling rates were 5.4 degrees, 9.1 degrees, and 18.2 degrees C per minute in the nonischemic area (p = 0.004) and 2.0 degrees, 4.5 degrees, and 7.9 degrees C in the ischemic area (p = 0.008) in Groups 1, 2, and 3, respectively. Total of cardioplegic solution flows were 86, 188, and 262 ml per minute per 100 gm in Groups 1, 2, and 3, respectively (p = 0.001). However, flow did not differ significantly between groups in the ischemic area. Rate of rise of left ventricular (LV) pressure decreased significantly in Groups 1 and 2 but not in Group 3 (p = 0.002). Other measured variables did not differ significantly between groups, although LV function curves showed less deterioration in the high-pressure groups. It is concluded that higher cardioplegic perfusion pressure resulted in more rapid cooling in normal and ischemic areas and slightly better preservation of ventricular function as measured by some indexes. However, preservation was generally good for each of the pressures for up to 90 minutes of ischemia when the septum was consistently cooled to 10 degrees C.     

Effects of reperfusion after acute coronary occlusion on the beating, working heart compared to the arrested heart treated locally and globally with cardioplegia

To determine whether acutely ischemic myocardium could be more effectively salvaged by reperfusion on cardiopulmonary bypass (CPB) in the cardioplegia-treated heart than with reperfusion in the beating, working heart, 52 greyhound dogs underwent 3 hours of left anterior descending (LAD) occlusion and were randomly assigned to one of four groups. In Group I (19 dogs) the LAD occlusion was released at 3 hours and reperfusion continued in the beating, working heart for an additional 3 hours. Group II (six dogs), Group III (14 dogs), and Group IV (13 dogs) were placed on CPB and underwent 45 minutes of hypothermic ischemic arrest protected by aortic root potassium cardioplegia. In Group II, only aortic root potassium cardioplegia was given; in Group III, the ischemic area was perfused with potassium cardioplegic solution via a graft from the internal mammary artery (IMA) to the LAD. In Group IV, blood cardioplegic solution via the IMA-LAD graft was used. After the cross-clamp and local occlusion were removed, CPB was discontinued after an additional 45 minutes and reperfusion was continued off CPB for an additional 1 1/2 hours (total 6 hours). The ischemic area at risk was determined by injecting monastryl blue dye via the left atrium while the LAD was briefly reoccluded. After the animal had been sacrificed and the left ventricle had been sectioned, the area of myocardial necrosis was determined by nonstaining with triphenyltetrazolium chloride (TTC). For each group, the ratios of area of necrosis/area at risk (AN/AR) were calculated and postreperfusion arrhythmias were documented. Postreperfusion arrhythmias were noted in 11 of 12 animals in the beating, working heart group and only two of 24 in the combined CPB groups. The mean AN/AR was 66% +/- 2% in the beating, working heart (Group I), 59% +/- 6% after infusion of potassium cardioplegic solution into the aortic root (Group II), 57% +/- 6% with blood cardioplegia (Group IV), and 38% +/- 6.5% after global and local application of the potassium cardioplegic solution into the ischemic area (Group III). This study suggests that the reperfused ischemic myocardium will sustain less necrosis and less postreperfusion arrhythmias when the heart is protected by global and local cold potassium cardioplegia on CPB.     

The time course of myocardial high-energy phosphate degradation during potassium cardioplegic arrest

Myocardial high-energy phosphate and glucose-6-phosphate levels were determined in the in vivo pig heart model during ischemic arrest and reperfusion to determine the effectiveness of potassium cardioplegia in myocardial protection. Thirty-five pigs were divided into six experimental groups consisting of 2-hour normothermic arrest, 2-hour hypothemic arrest, 2-hour normothermic cardioplegic arrest, and 1-, 2-, and 3-hour hypothermic cardioplegic arrest. Myocardial biopsies from the left ventricle were obtained prior to arrest, every 30 minutes during the arrest interval, and at 30 and 60 minutes of reperfusion. The measurement of adenosine triphosphate and creatine phosphate showed that (1) cardioplegic arrest requires hypothermia to preserve high-energy phosphate levels in myocardial tissue; (2) hypothermia, while not completely protective alone, is more effective than potassium cardioplegia alone in providing myocardial preservation during 2-hour ischemic arrest; (3) the combination of potassium cardioplegia and hypothermia is additive in providing an effective means of maintaining myocardial high-energy phosphate stores during 1, 2, and 3 hours of ischemic arrest; (4) myocardial reperfusion does not allow a return to preischemic adenosine triphosphate (ATP) levels after 2 hours of arrest, except following hypothermic cardioplegia; and (5) extension of the duration of ischemic arrest to 3 hours using hypothermic cardioplegia prevents recovery of high-energy phosphate stores to preischemic levels during reperfusion. Optimal preservation can be achieved during 2 hours of ischemic arrest by using hypothermic potassium cardioplegia. The effects of myocardial reperfusion, however, prevent full ATP and creatine phosphate (CP) recovery following 3 hours of arrest. No other technique studied was as effective in providing myocardial preservation.     

Effect of increasing volume of cardioplegic solution on postischemic myocardial recovery

Multidose cardioplegia has been reported to be superior to single-dose cardioplegia in protecting the heart during ischemia. However, large volumes of cardioplegic solution may be detrimental because of washout of adenine nucleotide degradation products that accumulate during ischemia, which limits recovery of adenosine triphosphate. We designed an experiment to test the effects of increasing the volume of cardioplegic solution on postischemic myocardial recovery. Four groups were studied: Group 1, initial 2 minute single dose of cardioplegic solution; Group 2, infusion of cardioplegic solution every 30 minutes for 1 minute; Group 3, infusion of cardioplegic solution every 20 minutes for 1 minute; and Group 4, infusion of cardioplegic solution every 20 minutes for 2 minutes. All groups were ischemic for 2 hours at 20 degrees C. Although washout of nucleotide degradation products during the ischemic interval increased with higher volumes of cardioplegic infusion, the total washout (infusion plus initial 5 minutes of reperfusion) was not different among all groups. The multidose groups recovered function better and had significantly higher levels of total tissue purines after 30 minutes of reperfusion. There was no difference in adenosine triphosphate levels among all groups after reperfusion. We conclude that increasing the volume of cardioplegic solution, within a clinically relevant range is not associated with increasing loss of adenine nucleotides from the cell or with impaired functional recovery of the heart.     

The Optimal Potassium Concentration in Cardioplegic Solutions

High-energy phosphates provide a sensitive index of myocardial preservation. This experiment was designed to use this index in order to assess the efficacy of various potassium concentrations in a crystalloid cardioplegic solution in protecting the myocardium during hypothermic ischemic arrest. The in vivo ischemic pig-heart model was used, measuring left ventricular levels of adenosine triphosphate (ATP) before, during, and after a two-hour arrest period and after 30 minutes of reperfusion. Thirty-eight animals were divided into seven groups of 5 to 6 animals each. Each group received a different potassium concentration in the cardioplegic solution, namely 5, 10, 15, 20, 25, 30, and 35 mEq/L. The results were as follows: the ATP moiety was best preserved during ischemia and reperfusion in the 15 mEq/L group, while it remained significantly lower in the 5 mEq/L group. The 10, 20, 25, 30, and 35 mEq/L groups showed an intermediate range of ATP preservation. We conclude from these results that cardioplegic solutions containing 5 mEq/L of potassium seem to be inadequate for myocardial preservation during ischemic arrest; that solutions with 15 mEq/L of potassium may offer the best myocardial protection of all concentrations tested; and that solutions with potassium concentrations of 15 to 35 mEq/L are significantly better than normokalemic (5 mEq/L) cardioplegic solutions.     

Effect of an oxygen-enriched solution and multiple dosing of antegrade crystalloid cardioplegic solution on myocardial metabolism during coronary artery bypass graft operations.

The metabolic effect of excessive oxygenation and frequency of administration of antegrade crystalloid cardioplegic solution was assessed in 33 patients undergoing routine coronary artery bypass graft operations. Four patient groups were designed in which the initial aortic root injection was 1000 ml and then 100 ml administered through the vein grafts after completion of each distal anastomosis. The groups were divided as follows: group 1, single dose, normally oxygenated cardioplegic solution infused via the aortic root; group 2, single dose, high oxygen content cardioplegic solution infused via the aortic root; group 3, normally oxygenated cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes; group 4, high oxygen content cardioplegic solution with additional 250 ml doses via the aortic root every 20 minutes. In all groups myocardial mean septal temperature showed an immediate fall to approximately 11 degrees C with the initial aortic root doses and then a gradual rewarming to approximately 20 degrees C during the crossclamp period (mean 58.6 minutes). Metabolic parameters measured or calculated from the coronary sinus effluent were myocardial oxygen extraction, lactate production, base deficit, inorganic phosphate, glucose, potassium, creatine kinase (total and myocardial band fraction), and catecholamine production. There was no statistically significant difference in any of these determinations between each patient group. Furthermore, myocardial recovery, myocardial performance, and postoperative recovery characteristics were not different. We conclude that single or multidose aortic root crystalloid cardioplegic solution (either oxygen enriched or normally oxygenated) is equally effective in routine coronary artery bypass graft operations when septal temperatures are maintained between 15 degrees and 21 degrees C for a total arrest time of 60 minutes or less. In this study, increasing the volume cardioplegic solution given in multiple doses appeared to offer no significant metabolic or functional advantage in patients without complications who had satisfactory left ventricular function.     

Experimental myocardial preservation study of adding perfluorochemicals (FC43) in lidocaine cardioplegia.

OBJECTIVE: Lidocaine exhibits a cardioplegic action via acute inhibition of sodium influx into the myocardial cells. In terms of the cardiac function and calcium dynamics in the myocardial cells, we investigated the myocardial protective effect of addition of FC43 of Perfluorochemicals, which has an excellent oxygen transport function to meet the myocardial oxygen demand, on lidocaine-induced cardioplegia. METHODS: Isolated rat hearts were perfused with Langendorff mode and were divided to three experimental groups. During of preservation, these hearts were perfused continuously with the next three solution, potassium chloride was added to Krebs-Henseleit bicarbonate buffer to make potassium concentration of 20 mM in the first group (Group A), 2 mM lidocaine was added to Krebs-Henseleit bicarbonate buffer in the second group (Group B), and 2 mM lidocaine and 20% FC43 were added to Krebs-Henseleit bicarbonate buffer in the third group (Group C). After 60 minutes of continuous perfusion, the cardiac function and the intracellular calcium concentration in Groups A and B during cardioplegia were measured. Furthermore, after 360 minutes of continuous coronary perfusion, the cardiac function were measured in Group B and Group C. RESULTS AND CONCLUSIONS: Lidocaine cardioplegia showed a good recovery of cardiac function, because lidocaine induced prompt cardiac arrest by blocking sodium influx and inhibited the intracellular calcium overload by the following inhibition of sodium-calcium channels. Moreover, our results suggested that combining Perfluorochemicals with lidocaine produced a more effective myocardial-preservation that meets the myocardial oxygen demand during long-term cardiac arrest.     

Myocardial protection by intermittent perfusion with cardioplegic solution versus intermittent coronary perfusion with cold blood

The myocardial protection provided by cardioplegic solution using buffered, isosmotic potassium (30 mEq. per liter) was compared with intermittent cold coronary perfusion for 2 hours of aortic cross-clamping in dogs. The cardioplegic solution (Group CS) or cold blood (Group CB) was infused every 15 minutes through a cooling coil to reduce the perfusate temperature to 5 degrees C. Myocardial function after 30 minutes of reperfusion and rewarming was reduced in Group CB with a significant reduction in peak systolic pressure at a left ventricular (LV) balloon volume of 20 ml. and a significant reduction of dp/dt. In contrast, in Group CS, LV function was unchanged from the base-line period. LV compliance also was significantly reduced in Group CB while being unchanged in Group CS. Myocardial extravascular water content, obtained by dessication, was significantly higher in Group CB than in Group CS, which may explain the reduction in compliance. Electron microscopy showed normal ultrastructure in Group CS but extracellular edema in Group CB. Total coronary blood flow showed a sustained increase during reperfusion in both groups. Oxygen consumption rose with rewarming to base-line levels in both groups, whereas lactate and pyruvate consumption was reduced in both groups, particularly Group CB. Cardioplegic solution thus appears to be superior to the intermittent perfusion of cold blood for myocardial protection. The addition of potassium arrest, by markedly reducing myocardial metabolism, improves the protection afforded by cold blood perfusion alone.     

Comparison of the protective properties of four clinical crystalloid cardioplegic solutions in the rat heart

Although few surgeons dispute the benefits of high-potassium crystalloid cardioplegia, objective comparison of the efficacy of various formulations is difficult in clinical practice. We compared four commonly used cardioplegic solutions in the isolated rat heart (N = 6 for each solution) subjected to 180 minutes of hypothermic (20 degrees C) ischemic arrest with multidose cardioplegia (3 minutes every half-hour). The clinical solutions studied were St. Thomas' Hospital solution, Tyers' solution, lactated Ringer's solution with added potassium, and a balanced saline solution with glucose and potassium. Postischemic recovery of function was expressed as a percentage of preischemic control values. Release of creatine kinase during reperfusion was measured as an additional index of protection. St. Thomas' Hospital solution provided almost complete recovery of all indexes of cardiac function following ischemia including 88.1 +/- 1.6% recovery of aortic flow, compared with poor recovery for the Tyers', lactated Ringer's, and balanced saline solutions (20.6 +/- 6.5%, 12.5 +/- 6.4%, and 9.6 +/- 4.2%, respectively) (p less than 0.001). Spontaneous defibrillation was rapid (less than 1 minute) and complete (100%) in all hearts in the St. Thomas' Hospital solution group, but much less satisfactory with the other formulations. Finally, St. Thomas' Hospital solution had a low postischemic level of creatine kinase leakage, contrasting with significantly higher enzyme release in the other solutions tested (p less than 0.001). Although differences in composition are subtle, all potassium crystalloid cardioplegic solutions are not alike in the myocardial protection they provide. Comparative studies under controlled conditions are important to define which formulation is superior for clinical application.     

The effect of amino acids on the ischemic heart. Improvement of oxygenated crystalloid cardioplegic solution by an enriched branched chain amino acid formulation

This study was designed to test the effect of glucose and a formulation enriched with branched chain amino acids as additives to oxygenated crystalloid cardioplegic solution in the ischemic heart. Energy-depleted isolated working rat hearts were subjected to 68 minutes of normothermic global ischemia during which oxygenated cardioplegic solution was used to protect them. The hearts were then reperfused in the nonworking mode for 10 minutes and for a further 30 minutes in the working mode. The hearts were randomly divided into three groups, in which various oxygenated cardioplegic solutions were perfused. Group 1 (control) was subjected to modified St. Thomas' Hospital cardioplegic solution and groups 2 and 3 to the same solution with the addition of glucose (11.1 mmol/L) and glucose (11.1 mmol/L) and branched chain amino acids, respectively. Recovery of aortic flow, coronary flow, cardiac output, aortic pressure, adenosine triphosphate, creatine phosphate, and oxygen consumption was significantly better in group 2 than in group 1. In addition, recovery of aortic flow, coronary flow, cardiac output, aortic pressure, stroke volume, minute work, adenosine triphosphate, and creatine phosphate was found to be significantly enhanced in group 3. Release of adenine catabolites and lactic dehydrogenase from these hearts during postischemic reperfusion was significantly decreased. Thus, during global ischemia in the energy-depleted heart, the presence of glucose and branched chain amino acids in oxygenated crystalloid cardioplegic solution enhanced myocardial protection.     

Preliminary evaluation of cocarboxylase on myocardial protection of the rat heart

The presence of cocarboxylase (CC) is essential for the oxidation of pyruvate to acetylcoenzyme A (acetyl-CoA) and its subsequent degradation by means of the Krebs cycle. We compared the effects of various concentrations of CC in a cardioplegic solution on the survival and hemodynamic and metabolic recovery of 23 isolated, working rat hearts subjected to 60 minutes of hypothermic (23 degrees C) ischemic arrest. Group 1 (N = 6) consisted of hearts infused with the basic cardioplegic solution (Tyers' solution with glucose), to which no CC was added. In group 2 (N = 6) CC was added at 0.1 ml/L to the cardioplegic solution. In group 3 (N = 5) CC was added at 1 ml/L, and in group 4 (N = 6) CC was added at 10 ml/L. The cardioplegic infusions were performed at a pressure of 40 mm Hg for 2 minutes just before arrest; 30 minutes later they were performed again for 1 minute. Only two hearts (33.3%) recovered in group 1 whereas five recovered in group 2, five (100%) in group 3, and five (83.3%) in group 4. The recovery of hemodynamic performance as a percentage of preischemic control values showed marked improvement in the CC groups, especially group 3, when compared with group 1. The metabolic variables in the CC groups were also markedly improved, with significantly (p less than .05) decreased levels of tissue lactate and increased levels of creatine phosphate compared with those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of three cardioplegic solutions during hypothermic ischemic arrest in neonatal blood-perfused rabbit hearts

Inadequate myocardial preservation continues to be an important cause of postoperative morbidity and mortality after pediatric cardiac operations. To investigate methods of improving preservation in neonatal myocardium, we compared three cardioplegic solutions with topical hypothermia during 120 minutes of ischemic arrest in isolated, blood-perfused, neonatal rabbit hearts. Topical hypothermia (15 degrees C) without cardioplegia resulted in 71% +/- 5% recovery of preischemic contractile function. A high potassium (30 mEq/L) cardioplegic solution resulted in a 76% +/- 6% recovery of function, not significantly different from that obtained with hypothermia alone. In contrast, the St. Thomas' Hospital and H?pital Lariboisiere cardioplegic solutions resulted in recoveries of 89% +/- 6% and 88% +/- 7%, respectively, both of which were significantly greater (p less than 0.001) than recoveries obtained with the high potassium solution or hypothermia alone. Thus the cardioplegic solutions used at St. Thomas' Hospital and H?pital Lariboisiere provided excellent protection during 2 hours of hypothermic ischemic arrest in neonatal rabbit hearts and resulted in functional recovery superior to that achieved with hypothermia alone or with the high potassium cardioplegic solution.     

Cold storage of the rat heart for transplantation. Two types of solution required for optimal preservation

Two solutions, our cardioplegic solution and Collins' solution, were tested with regard to preservation of the heart under deep hypothermia before transplantation. The setup used was the isolated perfused working rat heart model and 4 hours of preservation at 0 degree C. The following three groups were prepared: Group 1: the heart was arrested with the cardioplegic solution (potassium: 20 mmol/L, sodium: 87 mmol/L) and then flushed with and stored in Collins' solution (potassium: 117 mmol/L, sodium: 10 mmol/L); Group 2: the heart was arrested with and stored in Collins' solution; and Group 3: the heart was arrested with and stored in the cardioplegic solution. The recovery of cardiac function was more satisfactory in Group 1 than in Groups 2 and 3. The increase in lactate was greater, and adenosine triphosphate and total adenine nucleotide were more depleted during storage in Group 2 than in Groups 1 and 3. In Group 3 myocardial sodium accumulation and potassium depletion during storage were greater than in Groups 1 and 2, and myocardial sodium and calcium overload after reperfusion were greater than in Group 1. Myocardial calcium overload after reperfusion in Group 2 was also greater than that in Group 1. These findings plus coronary vascular resistance analysis revealed that Collins' solution damages the heart during arrest procedures and that the cardioplegic solution is less effective for storage of the arrested heart under deep hypothermia. Therefore the heart should be first arrested with the cardioplegic solution and then flushed with and kept in Collins' solution for simple cold storage.     

Effect of experimental cardioplegia methods on normal and hypertrophied rat hearts

The purpose of this study was to evaluate whether the addition of verapamil hydrochloride to oxygenated glucose-rich cardioplegic solution would improve myocardial preservation. The Langendorff preparation of the isolated rat heart was used. Groups of normal (WKY) and hypertrophied (SHR) hearts were treated by five different cardioplegic methods and subjected to 90 or 30 minutes of ischemia at 28 degrees to 29 degrees C and reperfusion at 37 degrees C. The following cardioplegic solutions were used: Group A, cold (16 degrees C) Krebs-Henseleit (KH) glucose free only; Group B, KH with KCL (30 mEq/L) (16 degrees C); Group C, same as B with verapamil (10 microM); Group D, perfusion with oxygenated KH solution containing KCL (30 mEq/L) for 15 minutes prior to ischemia; and Group E, same as D with verapamil (10 microM). Recovery of contraction amplitude, ischemic contracture, coronary perfusate volume, the amount of creatine kinase in the coronary perfusate, heart rate, time of revival, O2 consumption, and ischemic contracture were measured. After 30 minutes of ischemia, we did not find any significant difference among the combinations tested with respect to contraction amplitude recovery. The hearts recovered fully. After 90 minutes of ischemia, we found that the best-protected groups in the normal hearts were Groups D and E. In the hypertrophied hearts, the addition of verapamil to the enhancement solution was harmful. The use of enhancement solution without verapamil prior to ischemia provided the best myocardial protection in the hypertrophied hearts.     

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.     

Cold cardioplegia versus hypothermia for myocardial protection. Randomized clinical study.

Seventeen of 34 consecutive patients undergoing coronary artery bypass grafting were randomly assigned to one of two methods of myocardial preservation. With the cold cardioplegic method (Group A), a 4 degrees C. asanguineous solution with 30 mEq. of potassium per liter was infused into the aortic root for about 2 minutes immediately after aortic cross-clamping and again after about 45 minutes or when myocardial temperature rose above 19 degrees C. External cardiac cooling was provided by constant infusion of 4 degrees C. Ringer's solution into the pericardium. Seventeen patients were assigned to simple cardiac cooling by hypothermic systemic perfusion before aortic cross-clamping plus external cardiac cooling (Group B). Electromechanical activity ceased within 1 to 2 minutes in Group A but continued throughout the ischemic period in 14 patients in Group B. Myocardial temperature (mean for all observations) during aortic cross-clamping was 17.2 +/- 0.44 degrees C. In Group A and 24.0 +/- 0.70 degrees C. in Group B. Operating conditions were better in Group A. Card-ac function early postoperatively was good in both groups clinically and according to measurements, but only in the cold cardioplegic group (A) was cardiac index not adversely affected by longer cross-clamp time. Myocardial necrosis occurred in both groups but was probably less in the cold cardioplegic group. Thirteen patients (76 percent) in Group A had no electrocardiographic evidence of myocardial injury, compared with eight (47 percent) in Group B (p = 0.08). Eleven (65 percent of Group A had no or short-lived appearance of ceatine phosphokinase isoenzyme (CK-MB), compared with six (35 percent) of Group B (p = 0.08). Time-related CK-MB and SGOT mean levels were consistently lower in Group A.     

1，6—二磷酸果糖和巯甲丙脯酸对心脏术后心肌缺血—再灌注损伤的保护

目的：探讨1，6－二磷酸果糖（FDP）和巯甲丙腈酸（CAP）增强心脏停搏液对缺血心肌保护的临床效果，方法：将60例患者随机分成三组，I组：作为对照组，应用我院体外循环下心肌保护方法，即首剂应用冷钾晶体心脏停搏液，从第二剂量开始改用15度稀释氧合血灌注，Ⅱ组：在冷钾晶体心脏停搏液中加入FDP（5mmol/L)；Ⅲ组：在冷钾晶体心脏停搏液中加FDP（5mmol/L)和CAP（12．5mg/L)。观察血浆丙二醛（MDA），肌酸磷酸激酶同工酶（CPK－MB），血栓素B2（TXB2），6－酮－前列腺素F1（6－酮－PGF1a)及电子显微镜检查结果：结果：与I组比较，Ⅱ组和Ⅲ组MDA，CPK－MB明显降低，且Ⅲ组较好地维持了TXB2和6－酮－PGF1a二者的比例平衡，Ⅱ组和Ⅲ组对线粒体也有较好地保护及提高毛细血管通畅率的作用。结论：FDP和CAP能明显增加心脏停搏液对缺血心肌保护的效果。