Preserved response of mitochondrial function to short-term endurance training in skeletal muscle of heart transplant recipients.
OBJECTIVE
We sought to determine whether intrinsic mitochondrial function and regulation were altered in heart transplant recipients (HTRs) and to investigate the response of mitochondrial function to six-week endurance training in these patients.


BACKGROUND
Despite the normalization of central oxygen transport during exercise, HTRs are still characterized by limited exercise capacity, which is thought to result from skeletal muscle metabolic abnormalities.


METHODS
Twenty HTRS agreed to have vastus lateralis biopsies and exercise testing: before and after training for 12 of them and before and after the same control period for eight subjects unwilling to train. Mitochondrial respiration was evaluated on saponin-permeabilized muscle fibers in the absence or presence (maximum respiration rate [V(max)]) of saturating adenosine diphosphate.


RESULTS
Mitochondrial function was preserved at the level of sedentary subjects in untrained HTRs, although they showed 28 +/- 5% functional aerobic impairment (FAI). After training, V(max), citrate synthase, cytochrome c oxidase, and mitochondrial creatine kinase (CK) activities were significantly increased by 48%, 40%, 67%, and 53%, respectively (p < 0.05), whereas FAI decreased to 12 +/- 5% (p < 0.01). The control of mitochondrial respiration by creatine and mitochondrial CK was also improved (p < 0.01), suggesting that phosphocreatine synthesis and transfer by the mitochondrial CK become coupled to oxidative phosphorylation, as shown in trained, healthy subjects.


CONCLUSIONS
In HTRs, the mitochondrial properties of skeletal muscle were preserved and responded well to training, reaching values of physically active, healthy subjects. This suggests that, in HTRs, immunosuppressive drugs do not alter the intrinsic muscle oxidative capacities and that the patients' physical handicap results from nonmitochondrial mechanisms.
Zoll
Joffrey
J
Service de Physiologie Clinique et des Explorations Fonctionnelles, Département de Physiologie, Faculté de Médecine, 11 rue Humann, 67000 Strasbourg, France. Zolljoffrey@yahoo.com
N'Guessan
Benoit
B
Ribera
Florence
F
Lampert
Eliane
E
Fortin
Dominique
D
Veksler
Vladimir
V
Bigard
Xavier
X
Geny
Bernard
B
Lonsdorfer
Jean
J
Ventura-Clapier
Renée
R
Mettauer
Bertrand
B
D019069:Cell Respiration / Q000502:physiology; D003402:Creatine Kinase / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D010085:Oxidative Phosphorylation; D010807:Physical Endurance / Q000502:physiology*
D003402:Creatine Kinase