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 investigated the metabolic contributions to the electrophysiological changes during low-flow ischemia (7.5% of the control flow) using³¹P NMR spectroscopy to monitor metabolic parameters, suction electrodes to study epicardial monophasic action potentials, and ⁸⁶Rb 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% repolarization (APD₉₀) was most marked between 1 and 5 min after induction of ischemia, at which time it shortened from 261 ± 4 to 213 ± 8 ms. The period of marked APD₉₀ shortening was accompanied by a fivefold increase in the rate of⁸⁶Rb 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 intracellular pH (pH_i) from 7.14 ± 0.02 to 6.83 ± 0.03 but no change in intracellular ATP concentration ([ATP]_i). We therefore investigated whether a fall in pH_i could be the metabolic change responsible for modulating cardiac K_ATP channel activity in the intact heart during ischemia. Both metabolic (30 mM lactate added to extracellular solution) and respiratory ($P{\text{CO}}_2$ increased to 15%) acidosis caused an initial lengthening of APD₉₀ to 112 ± 1.5 and 113 ± 0.9%, respectively, followed by shortening during continued acidosis to 106 ± 1.2 and 106 ± 1.4%, respectively. The shortening of APD₉₀ during continued acidosis was inhibited by glibenclamide, consistent with acidosis causing activation of K_ATP channels at normal [ATP]_i. The similar responses to metabolic (induced by adding eitherl- ord-lactate) and respiratory acidosis suggest that lactate has no independent metabolic effect on action potential repolarization.