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Ultrastructural evidence of increased tolerance of hibernating myocardium to cardioplegic ischemia-reperfusion injury

José Milei, MD, PhD^*, César G. Fraga, PhD, Daniel R. Grana, VMD^*, Ricardo Ferreira, MD and Giuseppe Ambrosio, MD, PhD, FACC^,*

^* Instituto de Investigaciones Cardiológicas (ININCA), Department of Medicine, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina
Department of Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina
Hospital Militar Central, Cirugía Cardiovascular, Buenos Aires, Argentina
Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy

Manuscript received December 29, 2003; revised manuscript received January 25, 2004, accepted January 28, 2004.

^* Reprint requests and correspondence: Dr. Giuseppe Ambrosio, Cardiology, Ospedale Silvestrini, S. Andrea delle Fratte, 06156 Perugia, Italy.
giuseppe.ambrosio{at}ospedale.perugia.it

Presented, in part, at the 2003 Scientific Sessions of the American Heart Association, Orlando, Florida, November 9 to 12, 2003.

OBJECTIVES: The goal of this study was to investigate the effects of ischemia-reperfusion on myocardial ultrastructure in patients with and without hibernating myocardium.

BACKGROUND: It is generally accepted that chronically dysfunctional, hibernating myocardium may remain nonetheless viable for a long time. It has been postulated that hibernating myocytes may survive, despite being subtended by a severe coronary artery stenosis, as they might be less susceptible to ischemic insults. However, whether hibernating myocardium is indeed more resistant to ischemia has never been investigated.

METHODS: Myocardial biopsies were taken before cardiac arrest and after reperfusion from the anterior wall of the left ventricle in patients undergoing coronary artery bypass surgery, divided according to presence (n = 7) or absence (n = 7) of hibernating myocardium. Ultrastructural changes were studied by electron microscopy. Because ischemia-reperfusion injury is related to oxidative stress, we also evaluated coronary sinus concentration of the antioxidants alpha-tocopherol, beta-carotene, and ubiquinol, and of lipid peroxidation products pre-ischemia and after reperfusion.

RESULTS: Both groups were similar with respect to length of ischemia and changes in the various indexes of oxidative stress. In normally contracting myocardium, ischemia/reperfusion induced moderate overall ultrastructural changes, and marked alterations at the mitochondrial level. In contrast, post-reperfusion biopsies of hibernating myocardium displayed only minor overall ultrastructural changes, and scored significantly better on mitochondrial damage.

CONCLUSIONS: Despite similar severity of ischemia/reperfusion, hibernating myocardium showed significantly less ultrastructural evidence of cell injury compared with normally contracting myocardium. These data indicate that human hibernating myocardium is intrinsically more resistant to ischemia/reperfusion injury.

Abbreviations and Acronyms   ANOVA = analysis of variance   ECG = electrocardiogram   LAD = left anterior descending   LV = left ventricle/ventricular   TBARS = thiobarbituric acid-reactive substances

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