Hemin, inducer of heme-oxygenase 1, improves functional recovery from myocardial stunning in conscious dogs

Abstract

Objective: To examine the effects of pretreatment with hemin, an inducer of the potential antioxidative enzyme heme-oxygenase 1 (HO-1) or heat-shock protein 32, on myocardial stunning. Design: Randomized animal study. Setting: Animal laboratory of a university hospital. Participants: Chronically instrumented mongrel dogs (n = 44). Interventions: Dogs underwent chronic instrumentation for measurement of hemodynamics and myocardial wall thickening fraction (WTF). Experiments with 12 dogs were performed on separate days in a crossover fashion: (1) 10 minutes of left anterior descending (LAD) coronary artery occlusion after application of hemin (9 mg/kg/d) for 1 week and (2) 10 minutes of LAD coronary artery occlusion without hemin pretreatment. In control experiments (n = 32), the reversible induction of HO-1, using gel electrophoresis and Western blotting, was determined. Measurements and Main Results: WTF was measured as a baseline value before hemin administration and at predetermined time points until complete recovery from stunning. LAD artery occlusion caused a significant reduction in the WTF in the LAD-perfused area with and without hemin, without significant hemodynamic changes. At all time points, after 1 minute of reperfusion, the WTF as percentage of baseline values was significantly higher after hemin pretreatment (p < 0.05). Baseline WTF values were reached after 24 hours with and after >48 hours without hemin pretreatment (p < 0.05). Conclusion: Hemin pretreatment attenuates myocardial stunning in conscious dogs. Copyright © 2001 by W.B. Saunders Company