Circulation, Vol 89, 1624-1631, Copyright © 1994 by American Heart Association
JR Stratton, GJ Kemp, RC Daly, M Yacoub and B Rajagopalan
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 [Pi]) 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 (Vmax) was determined. Analysis was by ANOVA.
There were no differences between groups in pH or PCr/(PCr + Pi) 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 + Pi) ratio (0.58 +/- 0.11
versus 0.76 +/- 0.08, P < .05), a reduced PCr resynthesis rate (13 +/- 6
versus 22 +/- 9 mmol/L per minute, P < .05), and a lower calculated Vmax
(26 +/- 14 versus 53 +/- 26 mmol/L per minute, P < .05). In the group
studied early after transplantation, all the changes noted in the
pretransplant group persisted and were if anything somewhat worse. In the
group studied late after transplantation, there was a significant
improvement in the PCr resynthesis rate compared with the early-
posttransplant group (27 +/- 6 late versus 15 +/- 6 mmol/L per minute
early, P < .05) and statistically nonsignificant trends toward
improvements in submaximal exercise pH (6.86 +/- 0.24 late versus 6.72 +/-
0.24 early) and submaximal PCr/(PCr + Pi) ratio (0.56 +/- 0.14 late versus
0.44 +/- 0.15 early) and Vmax (45 +/- 21 late versus 33 +/- 15 mmol/L per
minute early). However, compared with normal subjects, exercise duration
and submaximal PCr/(PCr + Pi) 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.
ARTICLES
Effects of cardiac transplantation on bioenergetic abnormalities of skeletal muscle in congestive heart failure
Department of Medicine, Seattle VA Medical Center, WA 98108.
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