Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P-MRS.

Abstract

Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after lung transplantation, peak VO2 was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in VO2max after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity.

Limiting Factors of Exercise Performance 1 Year After Lung Transplantation

“…For example, systemic steroids, frequently prescribed pre-and post-LTx, may induce atrophy and myopathy in all peripheral muscles. 7 Our data also show a significant, but weak correlation between time on the waiting list and muscle force of the quadriceps 1 year after transplantation. This correlation suggests that lung transplant recipients with a long waiting period have less muscle force 1 year after transplantation.…”

“…6 Reduced oxygen utilization by the vastus lateralis muscle was demonstrated after LTx by 31-phosphorus ( 31 P)-magnetic resonance spectroscopy and by optical near-infrared spectroscopy. 7,8 Skeletal muscle biopsies from the quadriceps exhibited lower activity of the oxidative enzymes, lower proportion of type 1 (fatigue-resistant) fibers, higher lactate concentration, low intramyocyte pH, and reduced adenosine triphosphate (ATP) content. 9 Together, these studies support the hypothesis that the limited exercise capacity found after LTx may be due, at least in part, to limited muscle strength and limited endurance capacity of the lower limbs.…”

Exercise training in COPD patients: the basic questions

“…Another observation that points to the significance of muscle weakness in limiting exercise capacity is that, in spite of significant differences in lung function measurements, no significant differences were seen in post-transplant exercise capacity between single or double lung transplantation [44]. This may partly be explained by the fact that peripheral muscle weakness or dysfunction plays an important role in exercise limitation in these patients [45]. Finally, MALTAIS et al [25] observed significant reductions in oxidative capacity of the peripheral muscles in COPD patients.…”

Haemodynamic response to dynamic exercise after heart-lung transplantation

“…Factors responsible for this muscle dysfunction may include pretransplant deconditioning, chronic steroid intake, cyclosporin-induced mitochondrial myopathy, and muscle wasting, in particular in patients with cystic fibrosis [2, 19,26,27]. Peripheral muscle dysfunction may also account for the early anaerobiosis and the associated hyperventilation which were observed in the current patients.…”