Drug Development Research zyx 8:417-424 (1986) An Efficient Method to Evaluate Protective Drugs Against Regional Ischemia of the Heart Godelieve Vandeplassche, zyxwv Luc Wouters, Carlo Hermans, Raymond Xhonneux, Marcel Borgers, and Willem Flameng zyx Department of Life Sciences, Janssen Pharmaceutica Research Laboratories (G. zyxwvut V., L. W , C. H., R.X., M. B.), Beerse, and Department of Cardiovascular Surgery (W. E), University of Leuven, Belgium ABSTRACT Vandeplassche, G., L. Wouters, C. Hermans, R. Xhonneux, M. Borgers, and W. Flameng: zyxwvuts An efficient method to evaluate protective drugs against regional ischemia of the heart. Drug Dev. Res. 8:417-424, 1986. The variables related to infarct size were examined in order to develop an efficient procedure for the assessment of cardioprotective action in the dog. In the open chest model the left anterior descending coronary artery was ligated for 90 or 240 min. Regional myocardial blood flow was measured by tracer microspheres and infarct size was studied using triphenyltetrazoliumchloride. Infarct size was measured in relation to perfusion area, collateral flow, and rate pressure product. Using perfusion area as an independent vari- able, only 61% of the variance in infarct size could be explained. Including collateral flow also, this percentage increased to 80. Using perfusion area and collateral flow, infarct size could be predicted accurately. The usefulness of this procedure is demonstrated by data obtained with test compound R 51 430. Key words: infarct size reduction, coronary occlusion, collateral flow INTRODUCTION zyxwvuts The existing experimental procedures (in dogs) for evaluating drugs that limit infarct sue are not very efficient, reproducible, and economical. Because of the great variability in infarct sue after coronary artery occlusion, a large number of animals is required in these Received final version March 3, 1986; accepted March 3, 1986. Address reprint requests to G. Vandeplassche, Lab. of Cell Biology, Dept. of Life Sciences, Janssen Pharmaceutica, Turnhoutseweg 30, B-2340 Beerse, Belgium. zyxwv 0 1986 Alan R. Liss, Inc.