SUMMARY Hypothermic potassium cardioplegia is now commonly used to protect the myocardium during surgically induced ischemia. Because the potassium-related membrane depolarization has been shown to increase calcium influx, we undertook this study to define the effects of varying the calcium content in hyperkalemic perfusates and the effects of using magnesium instead of or in addition to potassium as the arresting agent on the ability of hearts to recover normal function after ischemic arrest. We subjected isolated perfused working rat hearts to 60 minutes of cardioplegic arrest followed by 30 minutes of reperfusion, and measured high-energy phosphate levels every 2'/2 minutes by phosphorus-31 nudear magnetic resonance spectroscopy. These data were correlated with postischemic recovery of function. Our results show that potassium cardioplegia may be harmful when the calcium concentration is greater than 1 mM. The kalemic injury is significantly reduced when the calcium content is lowered to 0.25 mM and the greatest extent of preservation is provided by a calcium-poor perfusate (0.25 mM) containing 13 mM magnesium. The beneficial effects of magnesium are not enhanced by subsequent addition of potassium. Close correlations were found between all observed metabolic changes during arrest and the degree of recovery of contractile performance after reperfusion. We conclude that the ability of the myocardium to maintain or resynthesize high-energy phosphate after cardioplegic arrest may be an important determinant of postischemic mechanical performance. These results show that phosphorus-31 nuclear magnetic resonance spectroscopy is a valuable method for evaluating interventions to reduce the severity of ischemic damage.PRESERVATION of the myocardium during surgically induced ischemic arrest is commonly achieved through a combination of hypothermia and administration of cardioplegic solutions. The requirement for immediate arrest has been emphasized.' Studies have documented that significant utilization of high-energy phosphates occurs during the brief period of electromechanical activity between the onset of ischemia and onset of asystole.2 The most widely used cardioplegic agent is potassium chloride. Although at the concentrations generally used (30 mM), authentic contracture is unlikely to occur,3 hyperkalemically mediated calcium entry into the cell could result in increased myocardial wall tension and, consequently, increased ATP breakdown during asystole. We undertook the present study to assess the effects of calcium in hyperkalemic perfusates and the effects of magnesium and potassium, alone and in combination, on high-energy phosphate metabolism during hypothermic cardioplegic arrest.Generally, such a problem requires extensive analysis of freeze-clamped myocardial tissue, from which metabolites are extracted for analysis. This is a destructive and tedious process that offers ample oppor- tunity for the introduction of artifacts. Phosphorus-3 1 nuclear magnetic resonance (P-3 1 NMR) spectroscopy has been used...
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