title: Local beta-adrenergic blockade does not reduce infarct size after coronary occlusion and reperfusion: a study of coronary venous retroinfusion of metoprolol.
abstract: Previous studies have demonstrated pronounced ischemic zone myocardial concentrations of metoprolol following coronary venous retroinfusion in pigs with coronary artery ligation. The effect of coronary venous retroinfusion of metroprolol on myocardial infarct size was studied in 16 pentobarbital-anesthetized open-chest pigs undergoing 60-minute occlusion of the left anterior descending coronary artery followed by 3 hours of reperfusion. Pigs in the experimental group (n = 8) were given 0.4 mg/kg (1.0 mg/ml) of metroprolol via the anterior interventricular vein over a period of 5 minutes, beginning immediately after coronary occlusion followed by 0.2 mg/kg/hr intravenously. Control pigs (n = 8) received the same volume of saline as the treated group. The risk area and the necrotic area were assessed by monastral blue dye and triphenyl tetrazolium chloride staining, respectively. Metoprolol did not influence hemodynamics. Plasma concentrations of metoprolol were within therapeutic levels. The administration of the beta-blocker resulted in a trend toward reduced norepinephrine concentrations, both in the aorta and coronary vein after coronary occlusion, but it did not prevent norepinephrine overflow following reperfusion. Infarct size expressed as a percentage of the risk area was 77 +/- 11% in the control group and 75 +/- 12% (mean +/- SD; NS) in the treated group. Thus, metoprolol retroinfusion did not reduce infarct size and did not prevent catecholamine overflow after reperfusion. It is concluded that the beneficial effects of metroprolol in acute infarction are probably unrelated to local beta-adrenergic blockade, at least in the pig, an animal with a paucity of coronary collateral blood flow.
authors.affiliation: Department of Medicine, Cedars-Sinai Medical Center, University of California, Los Angeles.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Tadokoro
authors.forename: L
authors.initials: L
authors.lastname: Rydén
authors.forename: P O
authors.initials: PO
authors.lastname: Sjöquist
authors.forename: R V
authors.initials: RV
authors.lastname: Haendchen
authors.forename: E
authors.initials: E
authors.lastname: Corday
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000627:therapeutic use; D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008790:Metoprolol / Q000097:blood / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000097:blood / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000097:blood / Q000188:drug therapy; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D009638:Norepinephrine / Q000097:blood; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol; D009638:Norepinephrine