Selective reversal of hyperglycemia-evoked gastric myoelectric dysrhythmias by nitrergic stimulation in healthy humans.

Acute hyperglycemia disrupts gastric myoelectric rhythm in healthy humans. Defective nitrergic function is a factor in animal models of diabetic gastropathy. We tested participation of nitrergic pathways in hyperglycemia-evoked myoelectric dysrhythmias and compared their role in preventing dysrhythmic actions of experimental motion sickness. Twelve healthy volunteers underwent electrogastrography (EGG) with and without intravenous 20% dextrose to produce plasma glucoses of 250 mg/dl. EGG continued for 2 h after oral nitroglycerin (9 mg) or the cyclic GMP-specific phosphodiesterase inhibitorSildenafil Citrate (Viagra) (100 mg). In separate studies, 12 volunteers underwent circular vection (60 degrees /s) without and 90 min after nitroglycerin (9 mg) orSildenafil Citrate (Viagra) (100 mg) with concurrent EGG. Hyperglycemia decreased recording time in normal rhythm, increased tachygastria more than 3-fold, and decreased power of the dominant frequency (P < 0.05). Nitroglycerin andSildenafil Citrate (Viagra) reversed effects of hyperglycemia, improving normal rhythm, decreasing tachygastria (both P < 0.05), and blunting power decreases. Neither agent affected EGG rhythm during euglycemia. Vection decreased time in normal rhythm and increased tachygastria (P < 0.05). However, nitroglycerin andSildenafil Citrate (Viagra) did not reverse dysrhythmic effects of vection (P = N.S.). In conclusion, administration of a nitric oxide (NO) donor or an inhibitor of cyclic GMP-selective phosphodiesterase reverses the dysrhythmic effects of hyperglycemia on gastric myoelectric activity in healthy humans. These agents have no effect on dysrhythmias during motion sickness. These findings are consistent with selective impairment of nitrergic function in this model of diabetic gastropathy and suggest that NO donors and other agents that increase NO activity may be useful for treating diabetic dysrhythmias

Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study.

BACKGROUND: Animal studies have demonstrated that administration ofSildenafil Citrate (Viagra) can limit myocardial damage induced by prolonged ischemia, an effect that appears to be mediated by opening of adenosine triphosphate-sensitive potassium (K(ATP)) channels. No study has investigated whetherSildenafil Citrate (Viagra) can also prevent the impairment in endothelium-dependent vasodilatation induced by ischemia-reperfusion (IR) in humans. METHODS AND RESULTS: In a double-blind, placebo-controlled, crossover design, 10 healthy male volunteers (25 to 45 years old) were randomized to oralSildenafil Citrate (Viagra) (50 mg) or placebo. Two hours later, endothelium-dependent, flow-mediated dilatation (FMD) of the radial artery was measured before and after IR (15 minutes of ischemia at the level of the brachial artery followed by 15 minutes of reperfusion). Seven days later, subjects received the other treatment (ie, placebo or sildenafil) and underwent the same protocol. Pre-IR radial artery diameter and FMD, as well as baseline radial artery diameter after IR, were similar between visits (P=NS). After placebo administration, IR significantly blunted FMD (before IR: 7.9+/-1.1%; after IR: 1.2+/-0.7%, P<0.01). Importantly,Sildenafil Citrate (Viagra) limited this impairment in endothelium-dependent vasodilatation (before IR: 7.0+/-0.9%; after IR: 6.2+/-1.1%, P=NS; P<0.01 compared with placebo). In a separate protocol, this protective effect was completely prevented by previous administration of the sulfonylurea glibenclamide (glyburide, 5 mg), a blocker of K(ATP) channels (n=7; FMD before IR: 10.3+/-1.5%; after IR: 1.3+/-1.4%, P<0.05). CONCLUSIONS: In humans, oralSildenafil Citrate (Viagra) induces potent protection against IR-induced endothelial dysfunction through opening of K(ATP) channels. Further studies are needed to test the potential clinical implications of this finding

Immediate and long-term hemodynamic and clinical effects ofSildenafil Citrate (Viagra) in patients with pulmonary arterial hypertension receiving vasodilator therapy.

OBJECTIVE: To determine the immediate and long-term effects of adding sildenafil, a phosphodiesterase-5 inhibitor, to the medical regimen of patients with pulmonary arterial hypertension (PAH). PATIENTS AND METHODS: Thirteen patients with PAH received empirical adjunctiveSildenafil Citrate (Viagra) treatment at the Mayo Clinic in Rochester, Minn, between November 1, 2000, and August 31, 2001. All received a 25-mg dose of sildenafil, increased by 25 mg at 8-hour intervals, if tolerated, up to 100 mg during hemodynamic monitoring for 24 to 48 hours. Long-term effects on right heart hemodynamics were assessed by noninvasive right ventricular systolic pressure, right ventricular index of myocardial performance, and a 6-minute walk test. RESULTS:Sildenafil Citrate (Viagra) significantly increased cardiac output (CO) (P = .04) and decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and mean arterial pressure (P < or = .01) at peak measurements (obtained 1-2 hours after highest dose). At trough measurements (obtained 8 hours after highest dose),Sildenafil Citrate (Viagra) significantly decreased pulmonary artery systolic pressure, mean pulmonary artery pressure, and mean arterial pressure (P = .01). Ten patients discharged from the hospital were taking the highest-tolerated dose ofSildenafil Citrate (Viagra) every 8 hours. The right ventricular systolic pressure and right index of myocardial performance showed no significant improvement at follow-up (117 +/- 70 days), although concomitant treatment with epoprostenol could be tapered in 2 patients. Changes in New York Heart Association classes were inconsistent, and improvements in the 6-minute walk test were not significant. CONCLUSION:Sildenafil Citrate (Viagra) has an immediate pulmonary vasodilator effect in patients already receiving vasodilators for PAH. Its long-term effects on right heart function and functional status are equivocal. A large, prospective, well-designed study is needed to determine the effects ofSildenafil Citrate (Viagra) on PAH, both in untreated and concurrently treated patients

Potency after permanent prostate brachytherapy for localized prostate cancer.

PURPOSE: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy ofSildenafil Citrate (Viagra) were studied. METHODS AND MATERIALS: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated withSildenafil Citrate (Viagra) were evaluated as to its efficacy. RESULTS: The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response toSildenafil Citrate (Viagra) was significantly better in those patients not treated with NAAD (p = 0.04). CONCLUSIONS: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who receivedSildenafil Citrate (Viagra) exhibited improved potency in a majority of cases

Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension.

Only a small percentage of patients with chronic thromboembolic pulmonary hypertension are eligible for pulmonary thrombendarterectomy. We investigated the effects of oralSildenafil Citrate (Viagra) on hemodynamics and exercise capacity in 12 nonoperable chronic thromboembolic pulmonary hypertension patients. All patients were in disease progression despite sufficient long-term anticoagulation and the best supportive care and suffered from severe pulmonary hypertension (pulmonary vascular resistance index 1,935 +/- 228 dyn. s. cm-5. m2, cardiac index 2.0 l. min-1. m-2, 6-minute walking distance 312 +/- 30 m). After approximately 6 months ofSildenafil Citrate (Viagra) treatment, pulmonary hemodynamics and exercise capacity improved significantly (pulmonary vascular resistance index 1,361 +/- 177 L. min-1. m2, p = 0.004, cardiac index 2.4 +/- 0.2 L. min-1. m-2, p = 0.009, 6-minute walking distance 366 +/- 28 m, p = 0.02). Therefore, oralSildenafil Citrate (Viagra) may offer a new option for medical treatment of this devastating disease

Combining programmed intracavernous PGE1 injections andSildenafil Citrate (Viagra) on demand to salvageSildenafil Citrate (Viagra) nonresponders.

In a prospective, placebo-controlled, one group crossover design study, we tested whether adding programmed intracavernous PGE1 injections (IC-PGE1) can improve the effectiveness ofSildenafil Citrate (Viagra) in Erectile Dysfunction (ED) patients unresponsive to monotherapy with this drug. In all, 40 ED patients who had experienced unsatisfactory erections with both the 50 and 100 mgSildenafil Citrate (Viagra) doses were treated with four bi-weekly 20 mug IC-PGE1 injections given in the clinic and provided with either placebo or 50 mgSildenafil Citrate (Viagra) capsules for the next 4 weeks. Thereafter, they were crossed over to the other oral treatment for an additional 4-week period. The IIEF-Erectile Function domain score (IIEF-EFS), the main outcome measure, was found considerably higher (P<0.001) with the combined IC-PGE1-50 mgSildenafil Citrate (Viagra) treatment than with IC-PGE1-placebo orSildenafil Citrate (Viagra) alone (50 or 100 mg) in a subset of 26 subjects (65%). They thus shifted from the 'severe' or 'moderate' to the 'mild' grading of ED classification.International Journal of impotence Research advance online publication, 10 February 2005; doi:10.1038/sj.ijir.3901290

The effect ofSildenafil Citrate (Viagra) on electrostimulation-induced erection in the rat model.

This study was conducted to show the effect ofSildenafil Citrate (Viagra) on electrostimulation-induced erection in the rat model. Fifteen 12-week-old male Wistar Kyoto rats were used. The intracavernous pressure and arterial blood pressure were simultaneously monitored through electric cavernous nerve stimulation before and after the administration ofSildenafil Citrate (Viagra) (2 mg/kg). Statistical analysis was performed on maximal intracavernous pressure (MIP), mean arterial blood pressure (MAP), the MIP/MAP and detumescence time. MAP decreased significantly by about 20 mmHg afterSildenafil Citrate (Viagra) administration. The MIP/MAP increased significantly afterSildenafil Citrate (Viagra) administration. The effect ofSildenafil Citrate (Viagra) on the MIP/MAP was marked especially at lower (2-3 Hz) frequencies. The detumescence time significantly increased afterSildenafil Citrate (Viagra) administration. We have shown thatSildenafil Citrate (Viagra) is effective for enhancing erection at lower frequencies and prolonging penile erection in rats. After the administration of sildenafil, penile erection would be induced by weak stimuli that will not cause penile erection under normal conditions

Cardioprotection with sildenafil, a selective inhibitor of cyclic 3',5'-monophosphate-specific phosphodiesterase 5.

The effects of Sildenafil Citrate (Viagra), a specific inhibitor of phosphodiesterase 5, on ischemic myocardium was examined using an isolated rat heart model. Rats were pretreated withSildenafil Citrate (Viagra) at doses ranging from 0.001 mg to 0.5 mg/kg body weight. After 60 min, isolated hearts were subjected to ischemia for 30 min followed by 2 h of reperfusion. The results demonstrated that at 0.05 mg/kg (and to some extent at 0.01 mg/kg),Sildenafil Citrate (Viagra) provided significant cardioprotection as evidenced by improved ventricular recovery, a reduced incidence of ventricular fibrillation and decreased myocardial infarction. At higher doses, it caused a significant increase in the incidence of ventricular fibrillation while at very low doses it had no effect on cardiac function. As expected,Sildenafil Citrate (Viagra) increased cyclic 3',5'-monophosphate (cGMP) content in the heart. The results demonstrate for the first time that within a narrow dose range,Sildenafil Citrate (Viagra) can protect the heart from ischemia/reperfusion injury, probably through a cGMP-signaling pathway