INTERMITTENT PERFUSION OF ISCHEMIC MYOCARDIUM - POSSIBLE MECHANISMS OF PROTECTIVE EFFECTS ON MECHANICAL FUNCTION IN ISOLATED RAT-HEART

Intermittent restoration of coronary flow during ischemia reduced myocardial damage and improved recovery of function. The mechanisms of the protective effects of intermittent perfusion were investigated in isolated rat hearts. Ventricular function was assessed as the product of developed pressure (left ventricular systolic pressure minus end-diastolic pressure) and heart rate. Recovery of function was calculated by division of the product at the end of reperfusion by that before ischemia. After 40 minutes of sustained global ischemia, intracellular Na+ (Na(i)) increased from 11 to 74 μmol/g dry wt. During 30 minutes of reperfusion, these hearts took up a large amount of 45Ca2+ (10 μmol/g dry wt), recovered only 24% of preischemic function, and had an increased left ventricular end-diastolic pressure (48 mm Hg). When the 40-minute period of ischemia was interrupted at 10-minute intervals by intermittent perfusion (three periods of 3 minutes) with either oxygenated or hypoxemic buffer. Na(i) increased to only 12 or 17 μmol/g dry wt, and reperfusion resulted in much lower 45Ca2+ uptake (0.5 and 0.5 μmol/g dry wt, respectively). Recovery of function was 100% of the preischemic value. When hypoxemic buffer without glucose was used for intermittent perfusion, Na(i) increased to 50 μmol/g dry wt, ATP was depleted, and reperfusion resulted in reduced recovery of function (76%) and moderately increased 45Ca2+ uptake (2.1 μmol/g dry wt). The role of Na+-K+ pump activity in maintaining low Na(i) was assessed by removing K+ from oxygenated or hypoxemic buffers used during intermittent perfusion. Under these conditions, Na(i) rose to 64 or 102 μmol/g dry wt, 45Ca2+ uptake increased to 4.4 or 9.4 μmol/g dry wt, and recovery of function was poor. There was a highly significant correlation between Na(i) during ischemia and reperfusion Ca2+ overload (r = 0.87) or impaired recovery of function (r = 0.96). These results indicate that prevention of an increase in Na(i) by maintenance of Na+-K+ pump activity is associated with a reduction of Ca2+ overload through Na+/Ca2+ exchange.