Effect of Myocardial Protection by a new Na+/H+ Exchanger Inhibitor, HOE642 : A Study with Cross-flow Langendorff Circulation Model using Isolated Rat Hearts

【OBJECTIVE】 Na+/H+ exchanger （NHE） on myocardial cell membrane plays an important role in the ionic changes observed during myocardial ischemia and reperfusion. HOE642 is a new NHE inhibitor which has been reported its cardioprotective activity. In this study, we investigated the cardioprotective effect of HOE642 with cross-flow Langendorff circulation model using isolated rat hearts. 【MATERIALS and METHODS】 Isolated rat hearts were perfused with whole blood using crossflow Langendorff circuit for 20 minutes and were induced to cardioplegic arrest with St Thomas solution （STS） （C group）, STS plus HOE642 0.03 mg/kg （H1 group）, and STS plus HOE642 0.3 mg/kg （H2 group）. Immediately after 30 minutes ischemia at 37℃, the hearts were reperfused again. Left ventricle （LV） performances and Troponin-T （Tn-T） in coronary venous blood were measured at pre-ischemic stage, 30 and 60 minutes after the reperfusion. Then, the hearts were divided into two pieces, and frozen in liquid Nitrogen for further measurements of myocardial highenergy phosphates and the other was evaluated as water content. 【RESULTS】 H2 group indicated significant superior preservation as compared with control group in respect to better recovery of LV performances at 60 min （%LVP10; C=46.9% vs H2=71.2% （p<0.02）, %dp/dt10; C=47.8% vs H2=75.9% （p<0.02））, smaller level of Tn-T （C=104.9±19.8 （mean±SE） ng/ml vs H1=61.9±7.6 （p<0.03）, vs H2=51.3±4.9 （p<0.007））, better preservation of myocardial high-energy phosphates of ATP at 60 min （C=0.57±0.14 vs H1=1.21±0.08 （p<0.006）, vs H2=1.40±0.19 （p<0.001））, and lower water content in myocardial tissue （C=3.82±0.09 ml/g dryweight vs H1=3.48±0.05 （p<0.001）, vs H2=3.39±0.04 （p