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.     

The significance of multidose cardioplegia and hypothermia in myocardial preservation during ischemic arrest

A standard experimental protocol was developed to explore the optimal technique for myocardial preservation during 120 minutes of ischemic arrest followed by 30 minutes of reperfusion. Eight different experimental groups were evaluated with the use of an in vivo pig heart preparation. The parameters measured included myocardial contractility and compliance, myocardial blood flow, and endocardial/epicardial blood flow ratio. Myocardial preservation was inadequate after hypothermic arrest alone, cardioplegic arrest alone (at normothermia), and single-dose cardioplegia plus hypothermia. Adequate myocardial preservation was found only after hypothermia and multidose cardioplegia with either potassium (35 mEq. per liter) or magnesium-procaine solutions. Continuous cardioplegia and hypothermia, while providing a moderate degree of myocardial preservation, was not as satisfactory as multidose cardioplegia and hypothermia. No difference in myocardial preservation was apparent when potassium-induced cardioplegia was compared with magnesium-procaine-induced cardioplegia.     

Experimental evaluation of secondary blood cardioplegia

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.     

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.     

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.     

Rapid cooling contracture of the myocardium. The adverse effect of prearrest cardiac hypothermia

Hypothermic total circulatory arrest for repair of congenital heart lesions in neonates requires a period of rapid core cooling on cardiopulmonary bypass during which the myocardium is also exposed to hypothermic perfusion. Myocardial hypothermia in the nonarrested state results in an increase in contractility due to elevation of intracellular calcium levels. This study was designed to test the hypothesis that rapid myocardial cooling before cardioplegic ischemic arrest results in damage, with impaired recovery during reperfusion. Two groups of 10 rabbit hearts were perfused on an isolated Langendorff apparatus. Group N (normothermia) was perfused at 37 degrees C before 2 hours of cardioplegic ischemic arrest at 10 degrees C. Group C (cooling) was perfused at 15 degrees C in the unarrested state for 20 minutes before the same cardioplegic arrest conditions as group N. Left ventricular isovolumic pressure measurements, biochemical measurements from right ventricular biopsy specimens, and ventricular necrosis as defined by tetrazolium staining were used to compare the groups at 30 and 60 minutes of normothermic reperfusion. Developed pressure at a constant volume was preserved in group N at 90.7 +/- 4.5 mm Hg versus 76.9 +/- 6.3 in group C after reperfusion (p less than 0.05). Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure during reperfusion (group N = 6.8 +/- 2.5 mm Hg versus group C = 38.9 +/- 6.1 after reperfusion; p less than 0.001). Adenosine triphosphate levels were significantly higher in group N both at end-ischemia and after reperfusion versus group C (group N = 17.0 +/- 1.1 nmol/mg protein versus group C = 7.7 +/- 1.0 after reperfusion; p less than 0.001). Group N had 0.4% +/- 0.4% necrosis of ventricular mass versus 19.3% +/- 2.2% with prearrest cooling in group C (p less than 0.0001). These results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage. The mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioplegic arrest. Although hypothermia is an essential component to ischemic preservation, rapid cooling contracture can adversely influence cardioplegic myocardial protection.     

Cellular and molecular therapeutic targets for treatment of contractile dysfunction after cardioplegic arrest

Transient left ventricular (LV) dysfunction can occur after hypothermic hyperkalemic cardioplegic arrest. This laboratory has developed an isolated LV myocyte system of simulated cardioplegic arrest and rewarming in order to examine cellular and molecular events that may contribute to the LV dysfunction after cardioplegic arrest. Contractile function was examined using high-speed video microscopy after reperfusion and rewarming. After cardioplegic arrest and reperfusion, indices of myocyte contractility were reduced by over 40% from normothermic control values. The capacity of the myocyte to respond to an inotropic stimulus was examined through beta-adrenergic receptor stimulation with isoproterenol. After cardioplegic arrest, the contractile response to isoproterenol was reduced by over 50% from normothermic values. The next series of studies focused upon preventing these changes in myocyte contractile processes after cardioplegic arrest. First, the cardioplegic solutions were augmented with adenosine or an ATP-sensitive potassium channel opener, aprikalim. Both adenosine and aprikalim augmentation significantly improved myocyte function compared with cardioplegia alone values. A potential intracellular mechanism for the protective effects of either adenosine or the ATP-sensitive potassium channel is the activation of protein kinase C (PKC). A brief period of PKC activation before cardioplegic arrest provided protective effects on myocyte contractility with subsequent reperfusion and rewarming. In another set of studies, the potential protective effects of the active form of thyroid hormone (T3) were examined. In myocytes pretreated with T3, myocyte contractile function and beta-adrenergic responsiveness were significantly improved after hypothermic cardioplegic arrest and rewarming. Thus, endogenous means of providing improved myocardial protection during prolonged cardioplegic arrest can be achieved through a brief period of PKC activation or pretreatment with T3. Future studies, which more carefully deduce the basis for these pretreatment effects, will likely yield novel methods by which to protect myocyte contractile processes during cardioplegic arrest.     

The effect of temperature and hematocrit level of oxygenated cardioplegic solutions on myocardial preservation

The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia.     

Anoxic hypothermic cardioplegia compared to intermittent anoxic fibrillatory cardiac arrest. Clinical and metabolic experience with 1080 patients.

Appropriately applied, hypothermic cardioplegia allows an excellent surgical setting that can significantly reduce the myocardial ischemic injury resulting from anoxia. One thousand eighty adult and pediatric patients underwent a variety of corrective cardial surgical procedures utilizing cold potassium cardioplegic solution injected into the coronary arteries via the aortic root. Myocardial septal temperature was maintained at 18--20 degrees during arrested time. This group of patients was compared to a group of 220 patients that underwent intermittent normothermic ischemic arrest to perform cardiac surgical procedures. Significant reduction in morbidity, mortality, perioperative myocardial infarction was noted in favor of the cardioplegic group. Metabolic coronary sinus blood analysis in the group undergoing surgery with cardioplegia revealed favorable changes in myocardial lactate and oxygen extraction.     

Paradoxical effects of cardiac arrest by multidose potassium cardioplegia on myocardial lysosome integrity and phospholipid content

Multidose potassium cardioplegia is known to result in greater preservation of myocardial ATP content and better recovery of function as compared to cardiac arrest induced by aortic clamping. The present study was undertaken to assess the effects of this procedure on biochemical markers of tissue damage. Rat hearts undergoing either multidose cardioplegia or ischemic cardiac arrest were maintained at 18 degrees C for 1 or 2 hr and processed without reperfusion. Control hearts were processed at time zero. The activity of two lysosomal enzymes (beta-glucuronidase and acid phosphatase), as well as membrane phospholipid content, was measured in cardiac homogenates. One hour of arrest by either technique did not induce significant changes in these parameters. Two hours of arrest affected lysosomal integrity, as indicated by release of lysosomal enzymes into the cytosol. Soluble acid phosphatase activity averaged 44.7 +/- 1.3 mU/mg of protein in the hearts processed after 2 hr of cardioplegic arrest, and was significantly higher than that of control hearts (12.3 +/- 3.8 mU/mg of protein; P less than 0.01) and that of hearts subjected to 2 hr of ischemic arrest (29.2 +/- 4.5 mU/mg of protein; P less than 0.01 vs cardioplegic arrest; P less than 0.01 vs controls). Phospholipid content in hearts subjected to 2 hr of cardioplegic arrest was lower than in controls (0.49 +/- 0.06 micrograms Pi/mg of protein vs 0.76 +/- 0.03 micrograms Pi/mg of protein; P less than 0.01). In conclusion, 2 hr of hypothermic cardiac arrest was associated with biochemical indices of tissue damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary blood flow and myocardial metabolism during reperfusion after hypothermic cardioplegia in the dog

There have been many studies of reperfusion injury after normothermic ischemia. However, there have been few clinically relevant studies on the nature and time course of recovery of the myocardium during reperfusion after hypothermic cardioplegia. We studied reperfusion in the isolated dog heart supported by another dog. After 2 h of cardioplegic arrest at 20 degrees C, 11 normal hearts were reperfused for 30 min at optimal coronary pressures (60-100 mm Hg mean). The following events occurred: rapid rewarming, a transient hyperemia followed by a rapid return of both coronary blood flow and myocardial oxygen consumption to normal, washout of lactate, recovery of contractility and a slight decline in ATP. Most of these events occurred during the first 15 min of reperfusion. We concluded that, in normal hearts which are well protected during hypothermic cardioplegia, reperfusion at optimal coronary pressure results in recovery of the myocardium within 15 min, with the exception of recovery of ATP levels.     

Advantages of potassium cardioplegia and perfusion hypothermia in left ventricular hypertrophy.

An attempt was made to determine the effect of hypothermic potassium cardioplegia (35 mEq of potassium chloride) on the hypertrophic ventricle. Puppies with induced left ventricular hypertrophy were divided into four groups and studied after one hour on global ischemia. Myocardial adenosine triphosphate (ATP) was best preserved in the hypothermically perfused groups and correlated well with measurements of coronary sinus creatine phosphokinase (CPK). In Groups 1 and 2 (anoxic arrest at 37 degrees C and KC1 perfusion at 37 degrees C), CPK at 30 minutes of reperfusion was 1,031 and 198 IU, respectively, compared to 35 IU in Group 3 (KC1 perfusion at 4 degrees C) and 44 IU in Group 4 (Ringer's lactate at 4 degrees C). Myocardial injury was milder in Groups 3 and 4 regardless of whether potassium chloride was added. It is apparent that hypothermic perfusion of a hypertrophic ventricle was the major factor in myocardial preservation, as determined by myocardial ATP and coronary sinus CPK.     

Myocardial respiration and edema following hypothermic cardioplegia and anoxic arrest.

The effects of 1 and 2 hours of hypothermic anoxic arrest and cardioplegia induced by Mg-lidocaine, K-Mg, or K on left ventricular mitochondrial respiratory function, blood flow, and edema were studied in 41 mongrel dogs. Mitochondrial respiration was assessed by the indices of oxidative phosphorylation. Myocardial temperature recorded in ventricular septum was kept at 20 degrees C during ischemic arrest and 10 minutes of reperfusion. Cardioplegic solutions did not influence noncoronary blood flow during cross-clamping of the aorta. Mitochondrial respiratory function remained at control levels after 1 hour of ischemia induced by hypothermic anoxic arrest or by Mg-lidocaine or K-Mg hypothermic cardioplegia. Mitochondrial state 3 respiration after 2 hours of anoxic arrest was significantly higher in Mg-lidocaine cardioplegia than in anoxic arrest (p less than 0.05), but myocardial edema was equivalent in both groups. Mg in the cardioplegic solution suppressed mitochondrial nonphosphorylating oxygen consumption. These data suggest that mitochondrial function after 1 hour of ischemic arrest at 20 degrees C and 10 minutes of reperfusion is not significantly depressed, but at 2 hours of ischemic arrest, mitochondrial respiration is significantly impaired. However, hypothermic Mg-lidocaine cardioplegia appears to be more effective in sustaining myocardial respiration than does simple hypothermic anoxic arrest when the anoxic period is extended to 2 hours.     

Enhanced myocardial preservation by nicotinic acid, an antilipolytic compound. Improved cardiac performance after hypothermic cardioplegic arrest

The effect of nicotinic acid, an antilipolytic drug, on myocardial preservation was studied on the basis of cardiac performance after 2 hours of cardioplegic arrest. Isolated in situ pig hearts were subjected to 120 minutes of hypothermic potassium (35 mEq) crystalloid cardioplegic arrest followed by 60 minutes of reperfusion. The experimental group received nicotinic acid 0.08 mmol/L 15 minutes before cardioplegic arrest, whereas the control group received 15 minutes of unmodified perfusion. There was a marked decline in myocardial creatine phosphate levels during cardioplegic arrest in both groups that returned to the baseline level during reperfusion without a significant intergroup difference, and adenosine triphosphate levels remained stable throughout the experiment in both groups. Myocardial oxygen consumption during reperfusion was significantly higher in hearts treated with nicotinic acid, which was consistent with a significantly greater cardiac contractile force as evaluated by isovolumetric left ventricular pressure measurements. There appeared to be less cardiac membrane damage as measured by creatine kinase release during reperfusion, which was significantly inhibited by treatment with nicotinic acid. The present study supports the conclusion that nicotinic acid improves cardiac performance after hypothermic cardioplegic arrest.     

Evaluation of myocardial preservation using 31P NMR

The purpose of this study was (1) to monitor myocardial high-energy phosphate content and recovery of left ventricular (LV) contractile function following normothermic graded cardiac ischemia and single-dose hypothermic potassium cardioplegia, and (2) to assess the temporal limits of LV functional recovery during single-dose cardioplegia maintained at 17 degrees C. Rabbit hearts (30) were perfused, equipped with an LV balloon, paced at 240 beats/min, and placed in a nuclear magnetic resonance (NMR) magnet. Hearts underwent either graded, global normothermic ischemia or potassium cardioplegia arrest maintained at 17 degrees C for 1 hr. Myocardial high-energy phosphate level, LV contractility, and temperature were monitored continuously. Phosphocreatine (PCr) fell to 10 +/- 2, 2 +/- 1, and 0% of control and ATP to 70 +/- 3, 19 +/- 7, and 0% of control at 10, 40, and 60 min of 37 degrees C ischemia. After 1 hr of reperfusion, regression analysis of final developed pressure (DP) on end ischemic ATP (EIATP) content revealed: DP = 1.02 EIATP + 18 (r = 0.95). Following single-dose cardioplegia, maintained at 17 degrees C, PCr fell to 16 +/- 3% of control at 60 min while ATP fell only to 92 +/- 5% control. With reperfusion, recovery of DP was 100%. It was concluded that (1) PCr serves as an energy buffer for ATP, (2) EIATP predicts recovery of LV function, (3) single-dose cardioplegia maintained at 17 degrees C provides complete myocardial preservation for up to 60 min.     

Continuous versus intermittent cardioplegia in the presence of a coronary occlusion

Coronary artery occlusions can alter the distribution of cardioplegia and result in ischemic damage. This study was undertaken to determine whether continuous antegrade cardioplegia delivery would result in colder temperatures and provide better washout of acid metabolites than is possible with intermittent antegrade cardioplegia when coronary occlusions are present. Twenty pigs were placed on cardiopulmonary bypass and underwent 2 hours of ischemic arrest with occlusion of the middle left anterior descending coronary artery followed by 1 hour of reperfusion without occlusion of that artery. Ten pigs received intermittent (every 20 minutes) antegrade potassium crystalloid cardioplegia (4 degrees C), and 10 others had the same solution given continuously (30 mL/min). Cardioplegia distribution was assessed by continuous monitoring of myocardial pH (Khuri pH probe) and temperature in the region beyond the occlusion of the left anterior descending coronary artery. Both cardioplegic techniques resulted in tissue acidosis (continuous group, 6.69 +/- 0.08, versus intermittent group, 6.73 +/- 0.07; not significant). Average temperature in the left anterior descending coronary artery during arrest was also similar in both groups (continuous group, 18.3 degrees +/- 0.5 degrees C, versus intermittent group, 18.2 degrees +/- 0.5 degrees C). Because of these metabolic changes, both cardioplegic techniques resulted in abnormal wall motion in the anteroseptal region using two-dimensional echocardiography, but the scores were not significantly different (continuous group, 1.5 +/- 0.3, versus intermittent group, 1.6 +/- 0.4; 4 = normal to 0 = dyskinesia).(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.     

Ultrastructural integrity of human ventricular myocardium following cardioplegic arrest.

The appearance of the ventricular myocardium in 6 patients electing coronary bypass operation was evaluated by electron microscope before and after aortic cross-clamping. Bypassing protocol included the induction of hypothermic cardioplegia by intermittent aortic root perfusion, with potassium chloride added to cold blood serving as the cardioplegic agent. Cross-clamp intervals ranged from 66 to 125 minutes. Ultrastructural alterations following bypass manipulations, and distinct from those observed before cross-clamping, were limited to the presence of extensive myocardiocytic pooling of glycogen. Scrutiny of the intramyocardial capillary bed following perfusion with the cardioplegic solution revealed no abnormalities attributable to, or intensified by, the bypass maneuver. These findings indicate that hypothermic potassium cardioplegia, as specified, is not injurious to human myocardial ultrastructure.     

Myocardial preservation 1987: what is the state of the art?

The principles of myocardial preservation by hypothermic cardioplegia are: to induce cardiac arrest rapidly, to minimize energy requirements and prevent ischaemic damage during arrest, and to avoid reperfusion injury after arrest. These principles are put into practice by infusing an effective cold cardioplegic solution at the beginning of ischaemia and then every 20-30 min throughout ischaemia. Myocardial temperature should be maintained below 15 degrees C in all areas of the myocardium by topical cooling, efficient venous drainage and cardiac venting. The use of an oxygenated blood-based cardioplegic solution produces a modest improvement in myocardial recovery compared with a non-oxygenated crystalloid solution. During coronary reperfusion after arrest, ventricular distension should be avoided and coronary pressure should be sufficiently high to perfuse all areas of the myocardium, especially in patients with coronary stenoses. Developing areas in myocardial preservation include metabolic supplementation of the myocardium, the use of free radical scavengers, the prevention of atrial arrythmias and the use of coronary sinus cardioplegia. The increasing numbers of high risk patients presenting for surgery should stimulate the surgeon to adhere closely to the basic principles of myocardial preservation and to apply existing cardioplegic techniques meticulously. It should also challenge the investigator to increase basic understanding and improve methodology in this important area of cardiac surgery.     

Safety of prolonged aortic clamping with blood cardioplegia. I. Glutamate enrichment in normal hearts

This study compares the protection provided by prolonged (4 hours) aortic clamping with glutamate-enriched potassium blood cardioplegia (n = 8) to (1) prolonged (4 hours) aortic clamping with multidose potassium blood cardioplegia without glutamate (n = 4), (2) 4 hours of continuous perfusion of the beating empty heart (n = 7), and (3) 15 minutes of normothermic ischemia (n = 10). According to measurements of myocardial oxygen uptake, left ventricular compliance, left ventricular contractility, and stroke work performance, no statistical difference could be detected between those hearts receiving blood cardioplegia either with or without glutamate enrichment. In both of these groups, myocardial protection was excellent, as demonstrated by the following: postischemic myocardial oxygen uptake 43% (p less than 0.05) above control, 95% +/- 6% recovery of the left ventricular compliance, a 97% +/- 5% return of the left ventricular contractility, and a 91% +/- 6% recovery of stroke work index. Contrary to the excellent recovery of those hearts receiving blood cardioplegic protection, those hearts undergoing 4 hours of continuous perfusion showed a 45% +/- 16% (p less than 0.05) loss of left ventricular compliance and a 72% +/- 8% (p less than 0.05) recovery of stroke work index; those hearts experiencing 15 minutes of normothermic ischemia showed a 74% +/- 6% (p less than 0.05) return of left ventricular compliance, a 30% +/- 5% (p less than 0.05) decrease in contractility, and a 56% +/- 5% (p less than 0.05) recovery of postischemic left ventricular stroke work.