Ischemia/Reperfusion Injury and Ion Channel Blockade

Abstract

To examine the effects of ion channel blockade on ischemia/ reperfusion injury, ion channel blockers were tested in isolated rat hearts subjected to 30-min global ischemia and 60-min reperfusion. Treatment with ion channel blockers was carried out for the last 3 min of preischemia. Sodium channel blockers quinidine (10–30 μM) and lidocaine (30–100 μM) enhanced the postischemic recovery of left-ventricular developed pressure (LVDP) and suppressed the release of creatine kinase (CK) in a concentration-dependent manner. Potassium channel blockers tetraethylammonium (3–100 μM) and sematilide (1–30 μM) neither improved the postischemic recovery of LVDP nor suppressed the release of CK. A calcium channel blocker, diltiazem (0.1– 3 μM), enhanced the postischemic recovery of LVDP and suppressed the release of CK, while nicardipine (0.1–1 μM) did not elicit appreciable improvement. Reperfusion-induced increase in myocardial Na and Ca contents and decrease in myocardial K and Mg contents were related to the reduction in LVDP at the end of reperfusion. Content of myocardial Na and K, but not of Ca and Mg, was altered in ischemia, and the suppression of this sodium accumulation by the sodium channel blockers and diltiazem was related to the enhancement of postischemic recovery of LVDP. The sodium channel blockers and diltiazem, but not the potassium-channel blockers and nicardipine, attenuated the ionic disturbances in ischemia as well as in reperfusion concentration-dependently. The results suggest that sodium channel blockade attenuates myocardial sodium overload in the ischemic heart, which may lead to better recovery of the postischemic contractile function.