The prolonged myocardial dysfunction observed after reversible ischemia (stunned myocardium) has been postulated to result from an inability of the myocytes to replenish ATP stores. Accordingly, one would expect inotropic stimulation to result in minimal increase in contractile function, or possibly even further deterioration. To test this hypothesis, studies were performed in open-chest dogs undergoing a 15-minute occlusion of the left anterior descending coronary artery (LAD) followed by 4 hours of reperfusion. Systolic wall thickening, an index of regional myocardial function, was measured in the LAD-dependent territory with ultrasonic crystals. Thickening fraction was 20.8 ± 3.0% (mean ± standard error of the mean) under baseline conditions, decreased to -18.6 ± 1.6% during LAD occlusion, and was still severely depressed after 3 hours of reperfusion (2.6 ± 3.4%). Thickening fraction remained stable between 3 and 4 hours of reperfusion in 5 untreated control dogs. In 9 treated dogs, isoproterenol (0.1 μg/kg/min intravenously for 30 minutes starting 3 hours after reperfusion) increased thickening fraction to values (24.8 ± 4.5%) that were similar to those at baseline. Thirty minutes after discontinuation of isoproterenol administration, thickening fraction had returned to pre-isoproterenol levels. Thus, reperfused, severely depressed myocardium responds dramatically to β-adrenergic stimulation without subsequent adverse effects on function in the short-term. These findings imply that the stunned myocardium can generate ATP, and therefore do not support the view that an inability to replenish ATP stores is the cause of postischemic dysfunction. More important, this study suggests that postischemic dysfunction in humans may be effectively reversed with inotropic therapy without short-term deleterious sequelae.
Bibliographical noteFunding Information:
From the Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030. This study was supported in part by Grant 85G-225 from the American Heart Association, Texas Affiliate, Austin, Texas, and by Grant HL-22512 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. This paper was presented in part at the National Meeting of the AAP/ASCl/AFCR in Washington, D.C., May, 1985. Manuscript received March 25, 1985; revised manuscript received May 15, 1985, accepted May 17, 1985. Address for reprints: Roberto Bolli, MD, Director, Experimental Animal Laboratory, Baylor College of Medicine, 6535 Fannin/MS F-905, Houston, Texas 77030.