Beneficial Effects of Quinidine on Post-ischemic Contractile Failure of Isolated Rat Hearts

Abstract

The present study was undertaken to determine whether quinidine may improve ischemia/reperfusion-induced functional and metabolic injury of isolated rat hearts. Thirty-five-min ischemia and the subsequent 60-min reperfusion resulted in no post-ischemic force generation, an increase in left ventricular end-diastolic pressure (about 1500%) and a sustained rise in perfusion pressure (136 ± 15% of initial). This was associated with an increase in the release of creatine kinase and ATP metabolites from the reperfused heart, a decrease in tissue high-energy phosphates, changes in tissue sodium, calcium, potassium and magnesium contents, and a reduction in the triphenyltetrazolium chloride (TTC)-stained area, an indicator of infarction. Hearts were treated with 3-100 μM quinidine 3 min before ischemia. Quinidine at concentrations of 10 μM or greater resulted in post-ischemic contractile recovery in a concentration-dependent manner (61 ± 8 to 95 ± 8% of initial). Ischemia/reperfusion-induced metabolic and histologic alterations were also suppressed by treatment with quinidine in a concentration-dependent manner. The results suggest that quinidine has a cardioprotective effect in ischemic/reperfused hearts. Because transmembrane fluxes of ions, substrates, and enzymes were suppressed by treatment with quinidine, protection of cardiac cell membrane function and/or integrity against ischemia/reperfusion-induced ionic imbalance, presumably sodium imbalance, across the sarcolemma is a possible mechanism by which quinidine may act. Slightly higher levels of ATP were detected in the treated hearts at 10 and 15 min, but not at 35 min of ischemia. Such preservation of high-energy phosphates might also be beneficial for protecting myocardial cells against ischemic damage.