Abstract 198: Oxidative Stress Mediates the Augmented Muscle Mechanoreflex in Peripheral Arterial Disease Patients
Background Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in peripheral arterial disease (PAD) patients. However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants.
Methods Three physiological studies were conducted in PAD patients and controls. In Protocol 1, subjects underwent four minutes of low-intensity (0.5-2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, PAD patients received high dose ascorbic acid intravenously prior to exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was the change in mean arterial pressure (ΔMAP) during the first 20 seconds of exercise (i.e. when mechanoreceptors within skeletal muscle activate the sympathetic nervous system).
Results Compared to controls, PAD patients had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg of the most affected leg (11±2 vs. 2±1 mmHg) as well as the least affected leg (7±1 vs. 1±1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% (i.e. 6 mmHg) in the presence of ascorbic acid. Electrically evoked exercise also elicited larger hemodynamic changes in the PAD patients compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle-brachial index, indicating that patients with more severe resting limb ischemia had a larger BP response to exercise.
Conclusions The BP response to low intensity exercise was enhanced in PAD. Chronic limb ischemia may sensitize muscle afferents and potentiate the autonomic response to muscle contraction in a dose-dependent manner.
- © 2012 by American Heart Association, Inc.