Skeletal muscle oxidative capacity, fiber type, and metabolites after lungtransplantation

Lung transplant (LTx) recipients have a low peak work rate, peak oxygen con sumption ((V) over dot o(2)peak), and early lactate threshold on incrementa l exercise. We hypothesized that LTx recipients have reduced oxidative func tion and altered fiber type proportion in peripheral skeletal muscle. Seven stable LTx recipients and seven age- and sex-matched control subjects were studied. Incremental exercise testing with arterialized venous sampling an d a resting quadriceps femoris punch muscle biopsy were performed. Muscle s pecimens were analyzed for fiber type proportion, metabolites, oxidative an d glycolytic enzyme activities, and mitochondrial ATP production rate (MAPR ) using standard techniques. The results showed that mean (V) over dot o(2) peak in LTx recipients was 52% of control subjects. Compared with the contr ol subjects, LTx skeletal muscle exhibited: (1) a lower MAPR; (2) lower act ivity of the mitochondrial enzymes glutamate dehydrogenase (CDH), citrate s ynthase (CS), 2-oxogluterate dehydrogenase (OGDH), and 3-hydroxyacyl-CoA-de hydrogenase (HAD). There was no difference in the activities of anaerobic e nzymes, except for higher phosphofructokinase activity; (3) a lower proport ion of type I fibers; (4) a higher lactate and inosine monophosphate (IMP) content and a lower ATP content at rest indicating a high reliance on anaer obic metabolism. The reduced type I fiber proportion and severely reduced m itochondrial oxidative capacity may play an important role in exercise limi tation after LTx.