Enhancement of salvage of reperfused myocardium by early beta-adrenergic blockade (timolol).
Although reperfusion of severely ischemic myocardium with thrombolytic agents or surgery has shown reduction in infarct size, the time after coronary occlusion during which reperfusion can salvage ischemic myocardium is limited. To determine whether beta-adrenergic blockade could enhance the salvage of ischemic myocardium by reperfusion, the left anterior descending coronary artery was occluded in 18 anesthetized dogs. An in vivo area at risk was determined by injecting technetium-99m-labeled albumin microspheres into the left atrium 5 minutes after occlusion and carrying out radioautography to define the poorly perfused tissue. Fifteen minutes after coronary occlusion, the dogs were randomized either to a control (saline-treated) group (n = 8) or to a timolol-treated group (n = 10). Timolol was administered until a decrease of 20% in heart rate or blood pressure occurred (mean total dose = 0.85 +/- 0.22 mg/kg +/- standard error of the mean). Coronary occlusion was maintained for 3 hours and was followed by 3 hours of reperfusion in both groups. At the end of 6 hours, infarct size was defined by triphenyltetrazolium chloride staining and masses of infarct and risk were calculated. Percent left ventricular mass at risk was similar for both groups (control = 20.9 +/- 2.4%, timolol-treated = 23.7 +/- 2.1%, p = not significant). Mass of necrosis/mass at risk was significantly smaller in the timolol-treated reperfusion group (27.3 +/- 2.7%) versus saline reperfusion alone (46.5 +/- 5.6%) (p less than 0.005). Thus, beta-adrenergic blockade administered early after coronary occlusion results in substantial enhancement of the salvage achieved by reperfusion alone.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004452:Echocardiography / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy; D009206:Myocardium / Q000473:pathology*; D013318:Stroke Volume / Q000187:drug effects; D013999:Timolol / Q000627:therapeutic use*
D013999:Timolol