Equal reduction in infarct size by ethylisopropyl-amiloride pretreatment and ischemic preconditioning in the in situ rabbit heart

Abstract

Inhibition of Na+/H+ exchange with amiloride analogues has been shown to provide functional protection during ischemia and reperfusion and to reduce infarct size in isolated rat hearts. In rat hearts, treatment with ethylisopropyl-amiloride (EIPA, a selective Na+/H- exchange inhibitor) was additive to the protection afforded by ischemic preconditioning. In addition, such compounds have been demonstrated to reduce infarct size in in situ rabbit hearts. The aim of the present study was to determine to what extent preischemic treatment with EIPA could reduce infarct size in an in situ rabbit model of regional ischemia and reperfusion. We also wished to determine if this effect was additive to the 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 particles and infarct size was determined by TTC staining. Four groups were investigated: control, ischemic preconditioned (IP) (5 min of ischemia followed by 10 min reperfusion), EIPA (0.65 mg/kg iv given preischemically) and EIPA + IP. The main results expressed as percent infarction 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. control), 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 administered prior to ischemia, caused a reduction in infarct size in the in situ rabbit heart which was similar to that seen with ischemic preconditioning, however, the effect was not additive to ischemic preconditioning.