Objectives. The purpose of this study was to assess high energy phosphate compound metabolism in remodeled left ventricular myocardium. Background. The development of heart failure several years after myocardial infarction is often unexplained. Certain abnormalities of remodeled myocardium suggest that structural changes occurring in viable myocardium after discrete myocardial damage may contribute to the later appearance of heart failure. Whether these abnormalities alter metabolism in the surviving muscle and thereby possibly contribute to ventricular dysfunction is unknown. Methods. High energy phosphate compound metabolism was assessed using spatially localized phosphorus-31 nuclear magnetic resonance spectroscopy. Eleven dogs with documented left ventricular dysfunction, resulting from infarction produced by transmyocardial direct current shock, were compared with eight normal dogs. Analyses were performed at baseline and during coronary hyperperfusion induced by intravenous adenosine. Myocardial blood flow was measured with radioactive microspheres. Results. The creatine phosphate/adenosine triphosphate (CP ATP) ratio was significantly reduced in the left ventricular dysfunction group in both the subepicardium ([mean ± SE] 1.94 ± 0.08 vs. 2.32 ± 0.13, p = 0.019) and the subendocardium (1.71 ± 0.07 vs. 2.05 ± 0.07, p = 0.004). Intravenous adenosine produced significant coronary hyperemia in both groups but was less marked in dogs with left ventricular dysfunction. The improvement in myocardial perfusion was accompanied by a significant increase in the subendocardial CP ATP ratio (from 1.71 ± 0.07 to 1.92 ± 0.08, p = 0.01) in dogs with left ventricular dysfunction. Conclusions. An abnormal transmural distribution of high energy phosphate compounds is evident in remodeled myocardium. This abnormality may be related in part to mismatch of oxygen delivery and demand.
Bibliographical noteFunding Information:
Twenty-five percent of patients surviving myocardial infarc-don develop congestive heart failure within 5 years (1) . Progressive left ventricular dysfunction in such patients can be due to further infarction or to continuing ischemia as a result of epieWial coronary artery disease. Alternatively, altered loading conditions, secondary to factors such as mitral regurgitation or systemic hypertension, may further imp* ventricular function and result in heart failure. How- ever, in some cases there is no obvious reason for the delayed development of heart failure after an apparently uncomplicated myocardial infarction . It is possible that From the Cardiovascular Division, Department of Medicine and Department of Biochemistry and Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, Minnesota. This study was supported by ft*t Grant POIHL32427 from the National Heart, Lung, and Institute, National Institutes of Health, Bethesda, Maryland and by U.S . Public Health Service Grants HL33600, HL32470 and HL50470 . It was presented in abstract form at the 64th Annual Scientific Sessions of the America Heart Association, Anaheim, California, November 1991 . Manuscript received June 7, 1993 ; revised manuscript received October 18, 1993, accepted October 26, 1993 . Addrassforg=Ljgmd=: Dr. Kenneth M. McDonald, Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Box 508 UMHC, 420 Delaware Street SE, Minneapolis, Minnesota 55455 .