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

Objective: To examine the effects of pretreatment with hemin, an inducer of the potential antioxidative enzyme heme-oxygenase 1 (HO-1) or heat-shock p rotein 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 he modynamics and myocardial wall thickening fraction (WTF). Experiments with 12 dogs were performed on separate days in a crossover fashion: (1) 10 minu tes of left anterior descending (LAD) coronary artery occlusion after appli cation of hemin (9 mg/kg/d) for 1 week and (2) 10 minutes of LAD coronary a rtery occlusion without hemin pretreatment. In control experiments (n = 32) , the reversible induction of HO-1, using gel electrophoresis and Western b lotting, was determined. Measurements and Main Results: WTF was measured as a baseline value before hemin administration and at predetermined time poi nts until complete recovery from stunning. LAD artery occlusion caused a si gnificant reduction in the WTF in the LAD-perfused area with and without he min, without significant hemodynamic changes. At all time points, after 1 m inute of reperfusion, the WTF as percentage of baseline values was signific antly 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 (C) 2001 by WB. Saunders Company.