The Effects of Heptanol on Electrical Coupling during Ischemia in the Perfused Isolated Rat Heart

The aims of the present study were to examine the effect of heptanol on electrical coupling during ischemia, and to assess whether changes in electrical coupling by heptanol is associated with its cardiac protection. Perfused isolated rat hearts were subjected to a 24 min infusion of heptanol (0.05, 0.1, 0.5 or 1.0 mmol/L) followed by 70 min of global no-flow ischemia or by 20 min of regional ischemia and 60 min of reperfusion. Heptanol markedly decreased arrhythmia scores during ischemia and reperfusion as well as reduced infarct size to a degree similar to that induced by ischemic preconditioning. In the prolonged ischemia model, heptanol delayed the onset of uncoupling, increased time to plateau, and decreased the maximal rate of uncoupling during ischemia. Ischemic preconditioning had similar effects on these parameters. These results demonstrate that treatment with the gap junction uncoupler heptanol confers cardioprotection against ischemia, and this effect is related to delayed electrical uncoupling during prolonged ischemia.