SODIUM-HYDROGEN EXCHANGE INHIBITORS IMPROVE POSTISCHEMIC RECOVERY OF FUNCTION IN THE PERFUSED RABBIT HEART

Objective: The aim was to examine the effects of the Na+/H+ exchange i nhibitors amiloride and methylisobutyl amiloride (MIA) in buffer perfu sed rabbit hearts subjected to one hour of normothermic ischaemia (37 degrees C) followed by reperfusion. Methods: Experiments were carried out in five groups of Langendorff perfused rabbit hearts: (1) control, (2) amiloride, and (3) MIA (agents in both the preischaemic and reper fusion perfusate), (4) amiloride-R and (5) MIA-R (agents added at repe rfusion only). Functional evaluation included serial measurement of re sting tension, force, rates of ventricular force development and relax ation, and coronary perfusion pressure, Samples of coronary effluent w ere obtained for creatine kinase assay and hearts were freeze clamped for metabolite assays. Results: Reperfusion resulted in a marked incre ase in resting tension in group (1) which was statistically significan t compared to groups (2) and (3). Groups (2) and (3) also showed signi ficantly improved recovery of ventricular force. rate of force develop ment, and rate of ventricular relaxation. Addition of either agent onl y during reperfusion failed to produce a significant beneficial effect . There were no significant differences among the groups with respect to postreperfusion creatine kinase release or end reperfusion metaboli te levels. Conclusion: This study shows for the first time that both o f the Na+H+ exchange inhibitors amiloride and MIA produce improved rec overy of ventricular function in rabbit hearts subjected to ischaemia and reperfusion, although the beneficial effect was not obtained with drug administration at the time of reperfusion only.