Therapy and Prevention Peripheral Arterial Disease

A double-blind, cross-over study was designed to evaluate the effects of L-carnitine in patients with peripheral vascular disease. After drug washout, 20 patients were randomly assigned to receive placebo or L-carnitine (2 g bid, orally) for a period of 3 weeks and were then crossed over to the other treatment for an additional 3 weeks. The effect on walking distance at the end of each treatment period was measured by treadmill test. Absolute walking distance rose from 174 + 63 m with placebo to 306 122 m (p < .01) with carnitine. Biopsy of the ischemic muscle, carried out before and after 15 days of L-carnitine administration in four additional patients, showed that treatment significantly increased total carnitine levels. An additional goal of this study was to ascertain the elfects of L-carnitine on the metabolic changes induced by exercise in the affected limb. In six patients under control conditions, arterial and popliteal venous lactate and pyruvate concentrations were determined at rest, when the maximal walking distance was reached, and 5 min after the walking test. Twenty-four hours later, L-carnitine was administered intravenously (3 g as a bolus followed by an infusion of 2 mg/kg/min for 30 min) and metabolic assessments were repeated. Five minutes after the walking test, popliteal venous lactate concentration increased by 107 + 16% before treatment and by only 54 + 32% (p < .01) after carnitine. Furthermore, carnitine induced a more rapid recovery to the resting value of the lactate/pyruvate ratio. These data suggest that carnitine improves pyruvate utilization and oxidative phosphorylation efficiency in the skeletal muscle of the ischemic leg. L-Carnitine, administered intravenously to 18 patients at the same dosage as above, did not modify blood flow or the ankle/arm systolic blood pressure ratio. In an additional eight patients, this intravenous dose produced an increase in walking distance similar to that observed with oral treatment. In conclusion, this study demonstrates that L-carnitine, although not affecting the general or regional hemodynamics, improves the walking capacity of patients with intermittent claudication, probably through a metabolic mechanism. Circulation 77, No. 4, 767-773, 1988. THE MOST IMPORTANT problem in the treatment of obstructive vascular disease is to make the energy supply adequate to the metabolic demand in the hypoxic area. In peripheral vascular disease, this goal is sought only by interventions aimed at increasing blood flow to the ischemic muscle. Many reports on ischemic heart-disease, however, suggest that a metabolic agent such as carnitine (3-hydroxy-4N-trimethylaminobutyrate) may protect the ischemic myocardium' and improve the stress tolerance of the heart2-4 by increasFrom the Departments of Medicine, Cardiology and Surgery, Second Medical School, University of Naples, Naples; and the Institute of Biological Chemistry and the Neurological Clinic, University of Padua, Padua, Italy. Address for correspondence: Gregorio Brevetti, M.D., Via G. Jannelli n. 45/A, 80131 Napoli, Italia. Received Dec. 9, 1985; revision accepted Dec. 17, 1987. Vol. 77, No. 4, April 1988 ing the availability of substrates required for energy production. A decrease in myocardial free L-carnitine content has been observed in experimental animals as a result of acute5' 6 and chronic7 myocardial ischemia. Similarly, a decrease in free carnitine concentration has been demonstrated in the skeletal muscle during exercise.8 Therefore, we designed this study to evaluate whether L-carnitine may enhance the walking ability of patients with intermittent claudication by interfering with the metabolic events taking place in the ischemic skeletal muscle. Patients and methods A total of 56 patients referred to our outpatient clinic for intermittent claudication were enrolled in the study. They gave 767 by gest on July 5, 2017 http://ciajournals.org/ D ow nladed from