REDUCED INFARCT SIZE IN THE RABBIT HEART IN-VIVO BY ETHYLISOPROPYL-AMILORIDE - A ROLE FOR NA+ H+ EXCHANGE/

Inhibition of Na+H+ exchange with amiloride analogues has been shown t o offer functional protection during ischemia and reperfusion and redu ce infarct size in isolated rat hearts and intact pigs. The aim of the present study was to examine if pre- or postischemic treatment with e thylisopropylamiloride (EIPA), a selective Na+/H+ exchange inhibitor, could reduce infarct size in an in situ rabbit model of regional ische mia and reperfusion. Anesthetized, open-chest rabbits were subjected t o 30 min of regional ischemia and 180 min of reperfusion. The risk zon e was determined by fluorescent particles, and infarct size was determ ined by TTC staining. Preischemic treatment with EIPA (0.65 mg/kg) sig nificantly reduced infarct size from 45.8 +/- 3.5% of the risk zone in the control group to 10.6 +/- 3.1% (p < 0.01). EIPA-treatment during the first part of the reperfusion period did not reduce infarct size c ompared to controls (41.9 +/- 3.5%). We conclude that EIPA, when admin istered prior to ischemia, reduces infarct size in the rabbit heart in situ, a protection most likely due to inhibition of Na+/H+ exchange.