THE EFFECT OF PROPIONYL L-CARNITINE ON SKELETAL-MUSCLE METABOLISM IN RENAL-FAILURE

The effect of propionyl L-carnitine on skeletal muscle metabolism in c hronic renal failure. Carnitine deficiency, resulting in defective oxi dative ATP synthesis, has been implicated in the myopathy of chronic r enal failure. Using P-31 magnetic resonance spectroscopy we examined c alf muscle metabolism in 10 dialysed patients before and after 8 weeks of propionyl L-carnitine (PLC) 2 g p.o. daily. Resting phosphocreatin e/ATP (4.41 +/- 0.20 [SEM]) decreased to normal control levels on PLC (3.98 +/- 0.14; controls 4.00 +/- 0.06). In contrast, there was no eff ect of PLC on aerobic and anaerobic metabolism of muscle during or fol lowing 2-10 min exercise. The maximal calculated oxidative capacity (Q (max)) remained below normal (28 +/- 3 mM/min before and 24 +/- 3 mM/m in after PLC; controls 49 +/- 3 mM/min). Q(max) correlated positively with hemoglobin concentration ([Hb]) after PLC (p < 0.03). Oxidative c apacity assessed by phosphocreatine recovery T significantly improved with PLC administration (0.93 +/- 0.1 to 0.74 +/- 0.08 min) in those p atients (n = 6) with [Hb] > 10 g/dl. [Hb] was rate limiting to oxidati ve metabolism in recovery from exercise but only following treatment w ith PLC. Patients. with anemia or those subjects who use relatively mo re non-oxidatively synthesized ATP during exercise, do not respond to PLC. Oxidative metabolism did not normalize on PLC suggesting that ane mia and carnitine deficiency are not the only causes of mitochondrial dysfunction in renal failure.