Regional energy metabolism of failing hearts following myocardial infarction

Abstract

To elucidate the relationship between functional alterations and disturbances in myocardial energy metabolism of rats with heart failure following coronary artery ligation, the left coronary artery of the rat was ligated and the time course of changes in cardiac function and myocardial energy state of the animal were examined for 12 weeks after the ligation. Coronary artery ligation resulted in approximately 40% infarction of the left ventricle, an increase in the right ventricular weight, a decrease in left ventricular developed pressure, an increase in left ventricular end-diastolic pressure throughout the experiment, suggesting the development of cardiac failure after the operation. Cardiac output and stroke volume indices were not altered during the first 4 weeks, but were significantly decreased on the 8th and 12th weeks, suggesting that cardiac function had further aggravated by 8 weeks after the operation. Myocardial energy profiles of the scar tissue, the remaining left ventricle and interseptum, and the right ventricle were determined. Tissue ATP (27.54 +/- 0.82 to 26.38 +/- 1.58 mumol/g dry tissue; n = 8-10) and creatine phosphate (26.73 +/- 1.63 to 24.38 +/- 1.83 mumol/g dry tissue; n = 8-10) of the remaining viable left ventricle were lower than control (33.17 +/- 0.73 and 40.04 +/- 1.07 mumol/g dry tissue; n = 8) throughout the experiment. A marked decrease in tissue ATP and CP was seen in the scar tissue throughout the experiment. Increases in tissue lactate of the remaining left ventricle and the right ventricle were detected from 1 to 2 weeks after the operation, but returned to the control levels thereafter. Mitochondrial oxygen consumption rates of isolated myocardial bundles from the 8th and 12th weeks (21.03 +/- 2.22 and 17.79 +/- 3.24 ng oxygen/min/mg dry tissue; n = 8) were lower than control (33.15 +/- 1.95 ng oxygen/min/mg dry tissue; n = 5), and those of the interseptum (23.71 +/- 1.33 ng oxygen/min/mg dry tissue; n = 8) and the right ventricle (22.44 +/- 2.73 ng oxygen/min/mg dry tissue; n = 8) on the 12th week after the operation were lower than control (33.58 +/- 2.80 and 34.83 +/- 2.64 ng oxygen/min/mg dry tissue; n = 5). The results provide evidence for a decline in myocardial energy store and energy producing ability associated with the development of cardiac failure.