Metabolic myopathy as a cause of the exercise limitation in lung transplant recipients

Background: Cardiopulmonary exercise (CPEx) studies of lung transplant (LTx ) recipients have found low maximum oxygen consumptions because of an as ye t unexplained mechanism. Although it is likely that a significant problem r esides within the mitochondria, this study determines whether a defect in o xygen uptake or utilization is present. Methods: Six LTx recipients and six age- and sex-matched, healthy control s ubjects were studied to assess the possibility of a mitochondrial myopathy in LTx recipients. We used standard CPEx testing in conjunction with near-i nfrared spectroscopy (NIRS), a noninvasive optical technique to assess peri pheral oxygen uptake in exercising muscle. NIRS analyzes the absorption spe ctra of hemoglobin and myoglobin at 760 and 850 nm to determine the relativ e oxygen saturation of these compounds during exercise with respect to base line values. Relative changes in oxygen saturation ate determined from the application of Beers law to changes in absorbance to compute changes in opt ical density (Delta OD). The LTx recipients and control subjects performed maximal noninvasive CPEx studies with NIRS analysis of the vastus lateralis muscle. Results: All subjects had a circulatory limitation to exercise. The LTx gro up had a significantly lower percent predicted maximum oxygen consumption t han the control group (45.3% +/- 14% vs 100.8% +/- 15.6%, [mean +/- SD] P < .001) and earlier onset of the anaerobic threshold (30.3% +/- 7.6% vs 60.3% +/- 8.0% of predicted VO(2)max, P <.0001) The LTx recipients demonstrated a significantly smaller Delta OD at maximum exercise as determined by NIRS analysis (0.024 +/- 0.005 Delta OD vs 0.054 +/- 0.03 Delta OD, P <.05). Conclusions: LTx recipients have an impaired maximal exercise capacity beca use of a disorder of peripheral oxygen utilization. This may be caused by a cyclosporine-induced mitochondrial myopathy.