EFFECTS OF CARDIAC TRANSPLANTATION ON BIOENERGETIC ABNORMALITIES OF SKELETAL-MUSCLE IN CONGESTIVE-HEART-FAILURE

Background Patients with advanced heart failure have bioenergetic abno rmalities of skeletal muscle metabolism during exercise. Using P-31 ma gnetic 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=1 0), subjects <6 months (mean, 4 months) after transplant (n=9), and su bjects >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 f unctional class, or symptom duration among the three patient groups. M etabolic responses were monitored in the dominant arm during increment al weight pull exercise and 10 minutes of recovery by P-31 magnetic re sonance spectroscopy, with measurement of pH and the phosphocreatine ( PCr)/(PCr+inorganic phosphate P-i) ratio, an index of PCr concentrat ion. In addition, based on recovery data, the rate of PCr resynthesis was calculated as a measure of oxidative metabolism that is independen t of work level, recruitment, or muscle mass, and the effective maxima l 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 pretrans plant group had a decreased exercise duration (11.31+/-2.5 versus 15.0 +/-1.3 minutes, P=.02), a lower submaximal exercise PCr/(PCr+P-i) rati o (0.58+/-0.11 versus 0.76+/-0.08, P<.05), a reduced PCr resynthesis r ate (13+/-6 versus 22+/-9 mmol/L per minute, P<.05), and a lower calcu lated V-max (26+/-14 versus 53+/-26 mmol/L per-minute, P<.05), In the group studied early after transplantation, all the changes noted in th e pretransplant group persisted and were if anything somewhat worse. I n the group studied late after transplantation, there was a significan t improvement in the PCr resynthesis rate compared with the early-post transplant group (27+/-6 late versus 15+/-6 mmol/L per minute early, P <.05) and statistically nonsignificant trends toward improvements in s ubmaximal exercise pH (6.86+/-0.24 late versus 6.72+/-0.24 early) and submaximal PCr/(PCr+P-i) ratio (0.56+/-0.14 late versus 0.44+/-0.15 ea rly) and V-max (45+/-21 late versus 33+/-15 mmol/L per minute early). However, compared with normal subjects, exercise duration and submaxim al PCr/(PCr+P-i) were still reduced in the late-posttransplant group. Conclusions Despite successful heart transplantation, skeletal muscle abnormalities of advanced heart failure persist for indefinite periods , although partial improvement occurred at late times. The persistent abnormalities may contribute to the reduced exercise capacity that is present in most patients after transplantation.