Beneficial actions of N-dimethyl propranolol on myocardial oxygen balance and transmural perfusion gradients distal to a severe coronary artery stenosis in the canine heart.
The purpose of the present study was to compare the effects of N-dimethyl propranolol (DMP), the quaternary derivative of propranolol, and propranolol on the transmural distribution (endo/epi) of coronary blood flow in normal and ischemic regions of the myocardium. The distribution of blood flow between subendocardium and subepicardium of a nonischemic region and one distal to a severe left circumflex coronary artery stenosis was determined by use of tracer microspheres (15 microgram) in intact dog hearts. DMP (1,5 and 10 mg/kg I.V.) produced a small dose-related increase in endo/epi of the nonischemic region (1.15 +/- 0.04--1.24 +/- 0.05), whereas a larger increase was observed in the ischemic region (0.61 +/- 0.08--1.09 +/- 0.10). DMP also produced a significant increase in ischemic subendocardial blood flow (0.59 +/- 0.12--0.76 +/- 0.11 ml/min/g). Similarly, propranolol (0.5 and 1.0 mg/kg I.V.) produced a small increase in endo/epi of the nonischemic region (1.18 +/- 0.08--1.30 +/- 0.07) and a larger increase in the ischemic region (0.72 +/- 0.17--1.18 +/- 0.09). However, propranolol did not increase ischemic subendocardial blood flow. It is concluded that DMP may be an alternative to propranolol in certain types of acute myocardial ischemia when beta-adrenergic blockade is undesirable.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D008863:Microspheres; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011433:Propranolol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D011433:Propranolol