EFFECTS OF DIMETHYL PROPRANOLOL (UM-272-SC-27761) ON MYOCARDIAL ISCHEMIC-INJURY IN CANINE HEART AFTER TEMPORARY CORONARY-ARTERY OCCLUSION

Myocardial ischemic injury after temporary occlusion of the left anterior descending coronary artery (LAD) for 90 min followed by reperfusion was estimated from the epicardial ST-segment elevation 15 min after occlusion (ST(15m)), changes in QRS complex, myocardial creatine kinase (CPK) activity and nitro-blue-tetrazolium (NBT) staining at 24 hours. At all sites exhibiting ST(15m) greater than 2 mV, there was a small development of epicardial Q waves after 90 min of occlusion (Σ ΔQ = 0.74 ± 0.11 mV) which was enhanced during reperfusion, reaching a maximum at 60 min (Σ ΔQ = 6.94 ± 0.52 mV) and was maintained for 24 hours. Good correlations were obtained between CPK activity at 24 hours and the development of Q waves at 24 hours as well as at 60 min after reperfusion (r = 0.49; N = 56). Pretreatment with UM-272 significantly reduced the development of Q-waves (Σ ΔQ(1hr) = 2.23 ± 0.75 mV) which was correlated with less CPK depletion and smaller infarct size as determined on the basis of NBT staining for myocardial tissue dehydrogenases at 24 hours. It appears, therefore, that the assessment of pathologic Q wave development provides an accurate and early estimate of the extent of the ultimate cardiac damage due to ischemia and that pretreatment with UM-272 exerts a protective effect on the ischemic myocardium.