NMR spectroscopy studies of severe hypokalemia in isolated rat hearts.

Abstract

Effects of acute tissue potassium depletion on cellular energy metabolism are poorly understood. To examine this issue, we performed the following studies in an isovolumic isolated perfused heart preparation. Perfusion of isolated hearts with media lacking potassium (K = 0 mmol/l) for 30 min resulted in ventricular fibrillation, rapid decreases in creatine phosphate (PCr) and ATP, and increases in Pi. During reinstitution of normal perfusate potassium, hearts did not resume normal contractions, and no increases in tissue ATP were observed. However, some normalization of PCr and Pi were noted during reinstitution of normal perfusate. Perfusion with media containing K = 2 mmol/l caused significant but less dramatic decreases in tissue ATP concentrations than perfusion with media containing K = 0 mmol/l. Reduction of perfusate calcium from 1.2 (normal) to 0.6 mmol/l in media containing K = 0 mmol/l attenuated the fall in ATP seen with media containing K = 0 mmol/l. Conversely, increasing perfusate calcium to 2.4 mmol/l in media containing K = 2 mmol/l markedly worsened the fall in tissue ATP seen in media containing K = 2 mmol/l. In this subgroup (K = 2 mmol/l, Ca = 2.4 mmol/l), ventricular fibrillation developed approximately one-half of the time. However, no differences in the rate of ATP fall were observed between those hearts that fibrillated and those that did not. During perfusion with media containing K = 0 mmol/l, nuclear magnetic resonance (NMR)-visible tissue potassium concentrations fell rapidly and dramatically. Significant but less severe reductions in NMR-visible potassium were seen during perfusion with media containing K = 2 mmol/l. With K = 2 mmol/l perfusate, the rate of cellular potassium loss was influenced by perfusate calcium concentration. When cardiac mitochondria were examined after perfusion with media containing K = 0 mmol/l, evidence for calcium loading as well as respiratory dysfunction was noted. These data indicate that reductions in perfusate potassium caused dramatic reductions in tissue ATP and NMR-visible potassium concentrations. The abnormal energy metabolism that results from acute cellular potassium depletion appears to be due, at least in part, to impaired energy production by cardiac mitochondria that become calcium loaded.