ROLE OF SODIUM CALCIUM EXCHANGE IN THE MECHANISM OF MYOCARDIAL STUNNING - PROTECTIVE EFFECT OF REPERFUSION WITH HIGH SODIUM SOLUTION

Objectives. This study was conducted to elucidate the role of sodium/calcium (Na+/Ca2+) exchange in the mechanism of myocardial stunning. Background. Cellular Ca2+ overload mediated by Na+/Ca2+ exchange during reperfusion has been proposed as a mechanism for myocardial stunning. Because no specific pharmacologic inhibitors of the exchanger are available, we increased extracellular sodium concentration ([Na]o) during the early phase of reperfusion to decrease the driving force for Ca2+ influx through the pathway. Methods. Isovolumetric left ventricular pressure and phosphorus-31 nuclear magnetic resonance spectra were measured in isolated perfused ferret hearts. Hearts were reperfused with different solutions after 15 min of total global ischemia at 37-degrees-C. Results. Hearts reperfused with standard solution ([Na]o = 140 mmol/liter; the stunned hearts. n = 8) showed only 69 +/- 3% (mean +/- SEM) recovery of developed pressure relative to preischemic control developed pressure. In contrast, hearts reperfused with a high [Na]o) solution ([Na]o = 268 mmol/liter) during the initial 5 min, followed by a gradual decrease of [Na]o to the standard level over 25 min (the high [Na]o group, n = 8) showed significantly better recovery of developed pressure (85 +/- 2%, p < 0.05 vs. the stunned hearts). In contrast, reperfusion with solutions in which the additional Na was substituted either by 256 mmol/liter sucrose or 128 mmol/liter choline chloride did not improve functional recovery, indicating that the beneficial effects of high [Na]o reperfusion are not due to either high ionic strength or high osmolarity. Phosphorus-31 nuclear magnetic resonance spectra showed no correlation between functional recovery and intramyocardial contents of phosphorus compounds or pH. Conclusions. High [Na]o reperfusion protects against stunning, supporting the concept that Na+/Ca2+ exchange plays an important role in the mechanism of stunned myocardium.