Evaluation of Skeletal Muscle Metabolic Responses Following Exercise Training in Patients with Intermittent Claudication

Abstract

Objective: Factors responsible for the exercise intolerance occurring in patients with peripheral arterial occlusive disease (PAOD) manifesting intermittent claudication (IC) and contributing to the observed improvements in walking capacity after exercise training have not been elucidated. The authors characterized the resting and exercise responses of high-energy phosphate species in affected calf skeletal muscle as detected by phosphorus (P)-31 magnetic resonance spectroscopy (MRS) to determine whether metabolic derangements were present in patients with mild to moderate PAOD and IC and whether these abnormalities could be altered by training. Subjects: Thirteen patients evaluated for IC with resting ankle-brachial indices (ABIs) < 0.9 and positive exercise testing were enrolled in a supervised 10-week walking exercise program (IC training). Separate control groups were composed of (1) patients with PAOD and IC (IC control, n = 4) and (2) healthy, age-matched individuals (n = 4) without PAOD or IC who did not undergo exercise training. Outcome Measures: Resting ABIs and constant-load treadmill testing were performed prior to and following exercise training. ABIs, ankle pressure drop, and calf muscle bioenergetic response (P-31 MRS) of the most symptomatic limb were measured during inmagnet, lowand high-intensity calf exercise done before and after training. Results: Compared with healthy controls, patients with PAOD and IC before training had lower resting ABIs (0.66 ±0.11), larger ankle pressure drops (35 ±15%), shorter symptom-free walking distances during treadmill testing and significantly slower phosphocreatine recovery (Pcr t½) during in-magnet low-intensity (61 ±46 v. 36 ±40 sec, p=0.05) and high (119 ±93 v. 31 ±10 sec, p=0.003) exercise but had otherwise similar bioenergetic responses. Despite improved symptom-free walking distance (1,080 ±316 v. 498 ±367 ft, p < 0.001), patients with PAOD and IC exhibited no changes in resting ABI, ankle pressure drop or high-energy phosphate responses after training. Furthermore, no significant correlation was found between high-energy phosphate species and limb hemodynamics. Conclusions: The relatively subtle abnormalities in high-energy phosphate muscle metabolism present in patients with PAOD and IC may only partially account for their marked exercise intolerance and do not appear to contribute to the observed improvement in walking capacity after supervised training.