title: Reducing myocardial injury by minimizing imbalance between oxygen supply and demand.
abstract: The purpose of this study was to determine whether hemodynamic and pharmacologic factors can influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion each increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure with methoxamine reduced the occlusion-induced S-T segment elevation, and lowering of the mean arterial pressure by hemorrhage had the opposite effect. In 19 additional experiments, propranolol, isoproterenol, and alterations in arterial pressure produced similar alterations in S-T segment elevation when these interventions were applied as long as 3 hr after ligation. Myocardial creatine phosphokinase (CPK) activity determined 24 hr after coronary artery ligation correlated well with S-T segment elevation at the same sites recorded 15 min after ligation. Moreover, isoproterenol increased and propranolol decreased the area of depression of myocardial CPK activity. We conclude that the hemodynamic status and neurohumoral background at the time of coronary occlusion and for at least 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis.
authors.affiliation: Harvard Medical School, and Brigham and Women's Hospital, Boston, MA, USA. ebraunwald@partners.org
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000776:Anesthesiology / Q000266:history*; D000818:Animals; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use; D003327:Coronary Disease / Q000473:pathology / Q000517:prevention & control; D004285:Dogs; D006331:Heart Diseases / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use; D049673:History, 20th Century; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000473:pathology; D009204:Myocardial Revascularization / Q000266:history; D009336:Necrosis; D010100:Oxygen / Q000008:administration & dosage*; D011758:Pyrroles / Q000627:therapeutic use
chemical_list: D002317:Cardiovascular Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D010100:Oxygen