Skeletal muscle carnitine metabolism in patients with unilateral peripheral arterial disease.
Patients with peripheral arterial disease (PAD) have abnormalities of carnitine metabolism that may contribute to their functional impairment. To test the hypothesis that muscle acylcarnitine generation (intermediates in oxidative metabolism) in patients with PAD provides a marker of the muscle dysfunction, 10 patients with unilateral PAD and 6 age-matched control subjects were studied at rest, and the patients were studied during exercise. At rest, biopsies of the gastrocnemius muscle in the patients' nonsymptomatic leg revealed a normal carnitine pool and lactate content compared with control subjects. In contrast, the patients' diseased leg had higher contents of lactate and long-chain acylcarnitines than controls. The muscle short-chain acylcarnitine content in the patients' diseased leg at rest was inversely correlated with peak exercise performance (r = -0.75, P less than 0.05). With graded treadmill exercise, only patients who exceeded their individual lactate threshold had an increase in muscle short-chain acylcarnitine content in the nonsymptomatic leg, which was identical to the muscle carnitine response in normal subjects. In the patients' diseased leg, muscle short-chain acylcarnitine content increased with exercise from 440 +/- 130 to 900 +/- 200 (SE) nmol/g (P less than 0.05). In contrast to the nonsymptomatic leg, there was no increase in muscle lactate content in the diseased leg with exercise, and the change in muscle carnitine metabolism was correlated with exercise duration (r = 0.82, P less than 0.01) and not with the lactate threshold. We conclude that energy metabolism in ischemic muscle of patients with PAD is characterized by the accumulation of acylcarnitines.(ABSTRACT TRUNCATED AT 250 WORDS)
Hiatt
W R
WR
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Wolfel
E E
EE
Regensteiner
J G
JG
Brass
E P
EP
D000368:Aged; D001157:Arterial Occlusive Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002331:Carnitine / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D006801:Humans; D007773:Lactates / Q000378:metabolism; D007866:Leg / Q000098:blood supply; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012039:Regional Blood Flow / Q000502:physiology; D016138:Walking
D007773:Lactates; D002331:Carnitine