EQUAL REDUCTION IN INFARCT SIZE BY ETHYLISOPROPYL-AMILORIDE PRETREATMENT AND ISCHEMIC PRECONDITIONING IN THE IN-SITU RABBIT HEART

Inhibition of Na+/H+ exchange with amiloride analogues has been shown to provide functional protection during ischemia and reperfusion and t o reduce infarct size in isolated rat hearts. In rat hearts, treatment with ethylisopropyl-amiloride (EIPA, a selective Na+/H+ exchange inhi bitor) was additive to the protection afforded by ischemic preconditio ning. In addition, such compounds have been demonstrated to reduce inf arct size in an situ rabbit hearts. The aim of the present study was t o determine to what extent preischemic treatment with EIPA could reduc e infarct size in an in sill rabbit model of regional ischemia and rep erfusion. We also wished to determine if this effect was additive to t he infarct reducing effect of ischemic preconditioning. Anaesthetized, open chest rabbits, were subjected to 45 min of regional ischemia and 150 min of reperfusion. The risk zone was determined by fluorescent p articles and infarct size was determined by TTC staining. Four groups were investigated: control, ischemic preconditioned (IP) (5 min of isc hemia followed by 10 min reperfusion), EIPA (0.65 mg/kg iv given preis chemically) and EIPA + IP. The main results expressed as percent infar ction of the risk zone + S.E.M. for the different groups were: control 59.2 +/- 3.3% (n = 6), IP 16.3 +/- 2.1% (n = 6) (p < 0.001 vs. contro l), EIPA 16.9 +/- 4.1% (n = 5) (p < 0.001 vs. control), EIPA + IP 22.5 +/- 9.5% (n = 6) (p < 0.001 vs. control). In conclusion: EIPA, when a dministered prior to ischemia, caused a reduction in infarct size in t he in situ rabbit heart which was similar to that seen with ischemic p reconditioning, however, the effect was not additive to ischemic preco nditioning.