Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure

Abstract

Background: Patients with advanced heart failure have bioenergetic abnormalities of skeletal muscle metabolism during exercise. Using 31P magnetic resonance spectroscopy, we sought to determine whether skeletal metabolic responses to exercise are normalized by orthotopic cardiac transplantation. Methods and Results: Four groups were studied: healthy normal volunteers (n=9), subjects awaiting heart transplantation (n=10), subjects <6 months (mean, 4 months) after transplant (n=9), and subjects >6 months (mean, 15 months) after transplant (n=8). None of the posttransplant patients had biopsy evidence of rejection at the time of study. There were no significant differences in age, preoperative functional class, or symptom duration among the three patient groups. Metabolic responses were monitored in the dominant arm during incremental weight pull exercise and 10 minutes of recovery by 31P magnetic resonance spectroscopy, with measurement of pH and the phosphocreatine (PCr)/(PCr + inorganic phosphate [P(i)]) ratio, an index of PCr concentration. In addition, based on recovery data, the rate of PCr resynthesis was calculated as a measure of oxidative metabolism that is independent of work level, recruitment, or muscle mass, and the effective maximal rate of mitochondrial ATP synthesis (V(max)) was determined. Analysis was by ANOVA. There were no differences between groups in pH or PCr/(PCr+P(i)) at rest. Compared with the normal control group, the pretransplant group had a decreased exercise duration (11.3±2.5 versus 15.0±1.3 minutes, P=.02), a lower submaximal exercise PCr/(PCr+P(i)) ratio (0.58±0.11 versus 0.76±0.08, P