MYOCARDIAL BIOENERGETIC ABNORMALITIES IN A CANINE MODEL OF LEFT-VENTRICULAR DYSFUNCTION

Objectives. The purpose of this study was to assess high energy phosph ate compound metabolism in remodeled left ventricular myocardium. Back ground. The development of heart failure several years after myocardia l infarction is often unexplained. Certain abnormalities of remodeled myocardium suggest that structural changes occurring in viable myocard ium after discrete myocardial damage may contribute to the later appea rance of heart failure, Whether these abnormalities alter metabolism i n the surviving muscle and thereby possibly contribute to ventricular dysfunction is unknown. Methods. High energy phosphate compound metabo lism was assessed using spatially localized phosphorus-31 nuclear magn etic resonance spectroscopy. Eleven dogs with documented left ventricu lar 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 radi oactive microspheres. Results. The creatine phosphate/adenosine tripho sphate (CP/ATP) ratio was significantly reduced in the left ventricula r 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 signi ficant coronary hyperemia in both groups but was less marked in dogs w ith left ventricular dysfunction. The improvement in myocardial perfus ion was accompanied by a significant increase in the subendocardial CP /ATP ratio (from 1.71 +/- 0.07 to 1.99 +/- 0.08, p = 0.01) in dogs wit h left ventricular dysfunction. Conclusions. An abnormal transmural di stribution of high energy phosphate compounds is evident in remodeled myocardium. This abnormality may be related in part to mismatch of oxy gen delivery and demand.