sildenafil-citrate and Intermittent-Claudication

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 O2 delivery-to-utilization matching. Systolic BP was significantly lower during the sildenafil trial relative to placebo during supine rest (∼15 mmHg), submaximal exercise (∼14 mmHg), and throughout recovery (∼18 mmHg) (P < 0.05). Diastolic BP was also lower after sildenafil during upright rest (∼6 mmHg) and during recovery from exercise (∼7 mmHg) (P < 0.05). Gastrocnemius deoxygenation was consistently reduced during submaximal exercise (∼41%) and at peak exercise (∼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.

Topics: Aged; Biomarkers; Blood Pressure; Brazil; Cross-Over Studies; Double-Blind Method; Exercise Test; Exercise Tolerance; Hemoglobins; Humans; Intermittent Claudication; Lower Extremity; Male; Middle Aged; Muscle, Skeletal; Oxygen; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Recovery of Function; Sildenafil Citrate; Spectroscopy, Near-Infrared; Sulfones; Time Factors; Treatment Outcome; Vasodilator Agents; Walking

Sildenafil, a phosphodiesterase-5-inhibitor (PDE5i), could represent a new treatment in addition to the medical treatment and advice to walk in peripheral arterial disease (PAD).. We report a case of a 62-year-old heavy smoker man who developed a buttock claudication and a severe walking limitation following an aorto-bi-femoral bypass in 1992. Since 2003, each year, he has been referred for investigation of bilateral buttock claudication on treadmill using transcutaneous oxygen pressure (tcpO2) measurement during exercise to argue for the vascular origin of the walking impairment. He had a severe bilateral buttock ischemia and the maximum walking distance (MWD) he reached was 258 m in 2011 despite the medical optimal treatment and walking rehabilitation. Ethical approval is not necessary for this case report according to the French legislation and written consent to publication was obtained from the patient.. Sildenafil, 100 mg/d, was introduced in February 2015 and the MWD increased to 310 m only after 2 h after the first oral intake, then to 713 m after 3 weeks, and finally to 1313 m in January 2017.. Recently, the patient is treated with Sildenafil 100 mg/d. He has no more pain during walking and his quality of life has improved.. Sildenafil, a PDE5i, may represent a new therapeutic option in addition to the conventional optimal medical therapy in patients with arterial claudication. tcpO2 measurement during exercise is a promising technique for the diagnosis and monitoring of patients with PAD. A crossover, double-blind, prospective randomized monocenter study (ARTERIOFIL-NCT02832570) and a double-blind prospective randomized multicenter study (VALSTAR-NCT02930811) are ongoing to confirm our original observation.

Topics: Buttocks; Exercise Therapy; Humans; Intermittent Claudication; Male; Middle Aged; Pain; Peripheral Arterial Disease; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Smoking; Vascular Grafting; Walking

A 57-year-old man presented with symptoms of intermittent claudication and was diagnosed with peripheral arterial disease. He was advised to stop smoking and start a walking programme. He had a background history of hypercholesterolaemia and erectile dysfunction, for which he was taking simvastatin and phosphodiesterase type-5 inhibitor sildenafil, respectively. After starting his exercise programme, he noted that his walking distance was more than doubled on the mornings after taking sildenafil, and he has been using sildenafil primarily for shopping trips since that time. Although this single-patient self-experiment has the potential for placebo confounding, the patient was not led to expect this benefit, and there is evidence that reduced nitric oxide bioactivity plays an important role in the pathophysiology of peripheral arterial disease. Given the biological plausibility of this effect, we feel that a randomised, blinded and placebo-controlled clinical study is warranted to confirm the benefit of phosphodiesterase type-5 inhibitors in peripheral arterial disease.

Topics: Anticholesteremic Agents; Erectile Dysfunction; Exercise Therapy; Humans; Intermittent Claudication; Male; Middle Aged; Peripheral Arterial Disease; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Scotland; Sildenafil Citrate; Simvastatin; Sulfones; Treatment Outcome; Walking