CHANGES IN VENTRICULAR REPOLARIZATION DURING ACIDOSIS AND LOW-FLOW ISCHEMIA

Myocardial ischemia, primarily a metabolic insult, is also defined by altered cardiac mechanical and electrical activity. We have investigat ed the metabolic contributions to the electrophysiological changes dur ing low-flow ischemia (7.5% of the control flow) using P-31 NMR spectr oscopy to monitor metabolic parameters, suction electrodes to study ep icardial monophasic action potentials, and Rb-86 as a tracer for K(+-) equivalent efflux during low-flow ischemia in the Langendorff-perfused ferret heart. Shortening of the action potential duration at 90% repo larization (APD(90)) was most marked between 1 and 5 min after inducti on of ischemia, at which time it shortened from 261 +/- 4 to 213 +/- 8 ms. The period of marked APD(90) shortening was accompanied by a five fold increase in the rate of 86Rb efflux, both of which were inhibited by the ATP-sensitive K+ (K-ATP)-channel blockers glibenclamide and 5- hydroxydecanoate (5-HD), as well as by a significant fall in intracell ular pH (pH(i)) from 7.14 +/- 0.02 to 6.83 +/- 0.03 but no change in i ntracellular ATP concentration ([ATP](i)). We therefore investigated w hether a fall in pHi could be the metabolic change responsible for mod ulating cardiac KATP channel activity in the intact heart during ische mia. Both metabolic (30 mM lactate added to extracellular solution) an d respiratory (Pco(2) increased to 15%) acidosis caused an initial len gthening of APD(90) to 112 +/- 1.5 and 113 +/- 0.9%, respectively, fol lowed by shortening during continued acidosis to 106 +/- 1.2 and 106 /- 1.4%, respectively. The shortening of APD(90) during continued acid osis was inhibited by glibenclamide, consistent with acidosis causing activation of KATP channels at normal [ATP]i. The similar responses to metabolic (induced by adding either l- or d-lactate) and respiratory acidosis suggest that lactate has no independent metabolic effect on a ction potential repolarization.