PREVENTION OF ISCHEMIC RIGOR CONTRACTURE DURING CORONARY-OCCLUSION BYINHIBITION OF NA-H+ EXCHANGE()

Objective: To determine the effect of Na+-H+ exchange blockade on isch emic rigor contracture and reperfusion-induced hypercontracture. Metho ds: Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic m icrocrystals was used to detect ischemic rigor (reduction in passive s egment length change) and hypercontracture (reduction in end-diastolic length). Results: Pretreatment with the new, highly selective Naf-Hf exchange inhibitor HOE642 before occlusion reduced ischemic rigor (P < 0.05), attenuated segment shrinkage (P < 0.05) during subsequent repe rfusion, dramatically reduced infarct size (P < 0.0001) and attenuated arrhythmias (P < 0.01). Inhibition of Na+-H+ exchange only during rep erfusion by means of direct intracoronary infusion of HOE642 into the area at risk prevented reperfusion arrhythmias but had no effect on fi nal infarct size, while treatment with intravenous HOE642 immediately before reperfusion had no detectable effects. Conclusion: These result s indicate that inhibition of Na+-H+ exchange during ischemia is neces sary to limit myocardial necrosis secondary to transient coronary occl usion, and that this action could be mediated by a protective effect a gainst ischemic contracture. Inhibition of Na+-H+ exchange only during reperfusion has a partial and transient beneficial effect, but only w hen the inhibitor reaches the area at risk before reflow. (C) 1997 Els evier Science B.V.