INHIBITION OF SODIUM-HYDROGEN EXCHANGE REDUCES INFARCT SIZE IN THE ISOLATED RAT-HEART - A PROTECTIVE ADDITIVE TO ISCHEMIC PRECONDITIONING

Objectives: Inhibition of Na+/H+ exchange with amiloride analogues has been shown to protect the ischaemic and reperfused heart. The aim of this study was to examine if preischaemic or postischaemic treatment w ith the selective Na+/H+ exchange inhibitor ethyl-isopropyl amiloride (EIPA, 1 mu M) influenced infarct size in an isolated rat heart model of regional ischaemia and reperfusion, and if any such protection was additive to the protection afforded by ischaemic preconditioning. Meth ods: Langendorff perfused rat hearts were subjected to 30 or 45 min of regional ischaemia and 120 min of reperfusion. The risk zone was dete rmined by fluorescent particles and infarct size was determined by sta ining with triphenyltetrazolium chloride. Results: Treatment with EIPA for 20 min before 30 min regional ischaemia significantly reduced inf arct size (in % of the risk zone) compared to untreated controls [3.1( SEM 1.0)% v 38.1(5.8)%, P < 0.001], a protection similar to that affor ded by ischaemic preconditioning [6.1(2.5)%]. Combination of preischae mic EIPA treatment and ischaemic preconditioning also reduced infarct size [5.2(2.0)%, P < 0.01 v control group]. When EIPA was added to the buffer only during the first 30 min of reperfusion, no protection was observed [infarct size = 37.8(5.8)%, NS v control group]. In order to clarify if the protection observed with EIPA treatment was additive t o protection by ischaemic preconditioning, another set of experiments was performed. In these experiments regional ischaemia was extended to 45 min. Preischaemic EIPA treatment reduced infarct size also in this model compared to controls [15.3(2.9)% v 64.3(2.9)%, P < 0.001] , as did ischaemic preconditioning [23.5(4.2)%, P < 0.001 v controls, NS v EIPA treated hearts]. Combination of ischaemic preconditioning and pre ischaemic EIPA treatment further reduced infarct size significantly [3 .9(0.6)%, P < 0.05 v all other groups with 45 min regional ischaemia]. Conclusions: Inhibition of Na+/H+ exchange reduces infarct size in th e isolated rat heart infarct model if the exchanger is inhibited durin g the ischaemic period, and this protection is additive to the protect ion afforded by ischaemic preconditioning.