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Title: Sildenafil improves skeletal muscle oxygenation during exercise in men with intermittent claudication
Authors: Roseguini, Bruno T. [UNIFESP]
Hirai, Daniel M. [UNIFESP]
Alencar, Maria C. [UNIFESP]
Ramos, Roberta P. [UNIFESP]
Silva, Bruno M. [UNIFESP]
Wolosker, Nelson
Neder, J. Alberto [UNIFESP]
Nery, Luiz E. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Queens Univ
Kingston Gen Hosp
Keywords: intermittent claudication
blood flow
Issue Date: 15-Aug-2014
Publisher: Amer Physiological Soc
Citation: American Journal of Physiology-regulatory Integrative and Comparative Physiology. Bethesda: Amer Physiological Soc, v. 307, n. 4, p. R396-R404, 2014.
Abstract: Endothelial dysfunction caused by defective nitric oxide (NO) signaling plays a pivotal role in the pathogenesis of intermittent claudication (IC). in the present study, we evaluated the acute effects of sildenafil, a phosphodiesterase type 5 inhibitor that acts by prolonging NO-mediated cGMP signaling in vascular smooth muscle, on blood pressure (BP), skeletal muscle oxygenation, and walking tolerance in patients with IC. A randomized, double-blind, crossover study was conducted in which 12 men with stable IC received two consecutive doses of 50 mg of sildenafil or matching placebo and underwent a symptom-limited exercise test on the treadmill. Changes in gastrocnemius deoxy-hemoglobin by near-infrared spectroscopy estimated peripheral muscle O-2 delivery-to-utilization matching. Systolic BP was significantly lower during the sildenafil trial relative to placebo during supine rest (similar to 15 mmHg), submaximal exercise (similar to 14 mmHg), and throughout recovery (similar to 18 mmHg) (P < 0.05). Diastolic BP was also lower after sildenafil during upright rest (similar to 6 mmHg) and during recovery from exercise (similar to 7 mmHg) (P < 0.05). Gastrocnemius deoxygenation was consistently reduced during submaximal exercise (similar to 41%) and at peak exercise (similar to 34%) following sildenafil compared with placebo (P < 0.05). However, pain-free walking time (placebo: 335 +/- 42 s vs. sildenafil: 294 +/- 35 s) and maximal walking time (placebo: 701 +/- 58 s vs. sildenafil: 716 +/- 62 s) did not differ between trials. Acute administration of sildenafil lowers BP and improves skeletal muscle oxygenation during exercise but does not enhance walking tolerance in patients with IC. Whether the beneficial effects of sildenafil on muscle oxygenation can be sustained over time and translated into positive clinical outcomes deserve further consideration in this patient population.
ISSN: 0363-6119
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