sildenafil-citrate and Peripheral-Vascular-Diseases

Sildenafil citrate is a highly effective erectogenic agent. However, predicting which patients will respond to this agent is often difficult. While the patient response to this agent is dependent on the nitric oxide-guanylate cyclase-cyclic guanosine monophosphate cascade, the integrity of penile arterial flow and venocclusive mechanism is also important. Duplex Doppler penile ultrasonography can reliably document penile hemodynamics. This study aimed at defining response rates based on degree of penile vascular sufficiency.. This study enrolled patients who met strict criteria for sildenafil citrate response who had also undergone penile ultrasound. Correlation was drawn between the nature and the severity of the vascular insufficiency and the response rate to sildenafil citrate.. The distribution of vascular diagnoses was arteriogenic 64%, venogenic 6%, mixed vascular insufficiency 18%, and normal 12%. The best response was seen in those men with normal vascular studies, 80% responding. Fifty-three percent of all men with any abnormality on penile ultrasound responded; 65% of men with arteriogenic erectile dysfunction (ED), 25% of patients with venogenic ED, and 6% of men with a mixed vascular insufficiency were responders. There was a correlation between the degree of vascular impairment and the response rate. All men with venogenic ED who responded had mild leak.. These data demonstrate a correlation between the nature and severity of penile vascular disease and the ability to respond to sildenafil citrate. These data may be useful to the sexual medicine practitioner when counseling patients regarding oral erectogenic therapy.

Topics: Erectile Dysfunction; Hemodynamics; Humans; Male; Middle Aged; Penis; Peripheral Vascular Diseases; Piperazines; Purines; Regional Blood Flow; Sildenafil Citrate; Sulfones; Treatment Outcome; Ultrasonography, Doppler, Duplex; Vasodilator Agents

We report the case of a 37-year-old woman who developed critical upper limb ischemia caused by a cervical rib. Because the malformation was initially undiagnosed, a vascular bypass was performed, and failure occurred. Following a 6-month therapy with sildenafil, revascularization of the arm was successful and amputation was avoided. A 6-year follow-up shows a rich collateral network at the compression site and normal values of digital plethysmography. Because hand surgeons often see patients with digital ulcerations and other manifestations of peripheral vascular pathology, therapy of ischemia with sildenafil could be an effective treatment option in patients not responding to classic drugs.

Topics: Adult; Arm; Female; Humans; Ischemia; Necrosis; Peripheral Vascular Diseases; Sildenafil Citrate; Skin Ulcer; Thoracic Outlet Syndrome; Vasodilator Agents

Peripheral artery disease (PAD) is a prevalent cardiovascular disorder that results in tissue ischemia which can progress to critical limb ischemia. Restoration of tissue perfusion in the setting of chronic ischemia through stimulation of arteriogenesis and angiogenesis remains a key therapeutic target for PAD. However, experimental therapeutics, including growth factor and gene therapy, have had little clinical success indicating the need for a better understanding of molecular pathways required for therapeutic angiogenesis.. Here we report that phosphodiesterase-5 inhibition by sildenafil significantly increases vascular perfusion, tissue blood flow, and vascular density during chronic ischemia of the mouse hind limb. Importantly, sildenafil therapy did not alter any of these parameters in nonischemic limbs. Sildenafil increased tissue cGMP levels independently of increases in nitric oxide production, and sildenafil therapy stimulated angiogenesis in ischemic limbs of eNOS-/- and iNOS-/- mice. Lastly, sildenafil-mediated angiogenic activity was blocked by inhibition of protein kinase G using the PKG antagonist DT-3.. These data demonstrate that sildenafil therapy results in increased angiogenic activity through a PKG-dependent pathway that is independent of nitric oxide production or NOS activity and identify the angiogenic therapeutic potential of sildenafil for critical limb ischemia.

Topics: Animals; Cyclic GMP-Dependent Protein Kinases; Disease Models, Animal; Hindlimb; Ischemia; Male; Mice; Neovascularization, Physiologic; Peripheral Vascular Diseases; Phosphodiesterase Inhibitors; Piperazines; Purines; Regional Blood Flow; Signal Transduction; Sildenafil Citrate; Sulfones