Role of Intravenous β-Blockers in the Treatment of ST-Elevation Myocardial Infarction

Abstract

But Mouse, thou are not alone, In proving foresight may be in vain: The best laid schemes of mice and men, Often go awry, And leave us nought but grief and pain, For promised joy! — —Robert Burns, “To a Mouse” (1785) Reimer et al1 have been widely acclaimed for helping to usher in the reperfusion era in the treatment of ST-elevation myocardial infarction (STEMI). Using a dog model of proximal circumflex artery ligation for different periods of time, they demonstrated that a “wave of cell death” develops first in subendocardial myocardium and progressively spreads to midepicardial and subepicardial myocardium over hours. Transmural infarct size was 38% after 40 minutes, 57% after 3 hours, 71% after 6 hours, and 85% after 24 hours of ischemic injury. The presence of a subepicardial zone of ischemic but viable myocardium that might be salvaged by early reperfusion established the anatomic justification for fibrinolytic therapy and primary percutaneous coronary intervention to modify infarct size in patients with STEMI. Article p 2909 Interestingly, the article that immediately followed the Reimer et al article in the November 1977 issue of Circulation was by the same group and was entitled “Infarct Size Reduction by Propranolol Before and After Coronary Ligation in Dogs.”2 Using the same animal model, they randomized dogs to intravenous propranolol before coronary occlusion, intravenous propranolol 3 hours after coronary occlusion, or saline infusion and euthanized the dogs at 24 hours without restoring reperfusion. Pretreatment with propranolol decreased transmural infarct size from 85% to 52%, whereas delayed treatment was about half as effective, decreasing infarct size to 71%. Whether other pharmacological or mechanical interventions added to reperfusion therapy can further reduce myocardial infarct size has been a major area of preclinical and clinical investigation for 3 decades.3 There have been dozens of …