The American journal of cardiology
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Randomized Controlled Trial Clinical Trial
Effects of sildenafil citrate on human hemodynamics.
Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO-cGMP pathway also plays an important role in mediating blood pressure. ⋯ Sildenafil was well tolerated by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
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Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), which has been shown to be a clinically effective treatment for erectile dysfunction. Its action results from increased levels of cyclic guanosine monophosphate (cGMP), which is normally degraded by PDE5. This cyclic nucleotide is a second messenger for nitric oxide, which is involved in the regulation of numerous functions, including vascular smooth muscle tone. ⋯ Human platelets were found to contain PDE5, which was inhibited by 50% (IC50) by sildenafil at a concentration of 6.3 nM, consistent with the IC50 value in the corpus cavernosum. Sildenafil alone had no direct effect on platelet function, but it potentiated the in vitro antiaggregatory activity of sodium nitroprusside on rabbit and human platelets. The pharmacodynamic and adverse event profiles observed in clinical trials with sildenafil are consistent with the in vitro profile of the tissue distribution of PDE5 and its known mechanism of action as a selective inhibitor of PDE5.
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Mitral regurgitation (MR) is a significant complication after atrioventricular septal defect (AVSD) surgery. The relation of the valve leaflet morphology and the MR mechanism remains a conundrum. Two-dimensional echocardiography depicts leaflet edges, whereas volume-rendered 3-dimensional echocardiography provides direct visualization of the surface areas of the mitral valve leaflets. ⋯ The area ratios of the mural leaflet were 28 +/- 5% in group 1 and 21 +/- 5% in group 2 (p = 0.007). The superior leaflet area ratio was not different in groups 1 and 2, 40 +/- 9% and 41 +/- 6%, respectively. Three-dimensional echocardiography provides new insight into the anatomic determinants of MR following AVSD surgery.
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In selected patients, atrial fibrillation (AF) converts to atrial flutter (AFI) due to treatment with class IC antiarrhythmic drugs. In this study, we prospectively investigated the effects of AFI ablation and continuation of drug therapy in patients with AF who developed AFI due to long-term administration of class IC antiarrhythmic drugs. The study population consisted of 187 patients from an AF registry with paroxysmal AF who were orally treated with flecainide (n = 96) or propafenone (n = 91). ⋯ Eight additional patients (42.1%) had ongoing paroxysmal AF, however, with a significantly lower incidence of AF episodes than before therapy (2.3 +/- 1.6 per year vs 11.5 +/- 5.0 per year, p <0.001). In the remaining 4 patients (14.7%), no beneficial effect of AFI ablation was found. It is concluded that in patients with AF who develop typical AFI due to administration of class IC antiarrhythmic agents, a combined therapy with catheter ablation of AFI and continuation of drug treatment is highly effective in reducing occurrence and duration of atrial tachyarrhythmias.
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Previous studies have demonstrated that left ventricular (LV) filling pressures can be estimated from transmitral Doppler recording in patients in sinus rhythm who have a broad spectrum of cardiac diseases. However, the correlation between pulmonary wedge pressure (PWP) and mitral Doppler profile has not yet been clearly defined in patients with atrial fibrillation, particularly in the presence of severe LV systolic dysfunction. The aim of this study was to evaluate the correlations between PWP and transmitral Doppler variables in patients with atrial fibrillation and chronic heart failure due to dilated cardiomyopathy. ⋯ However, by stepwise multivariate analysis, deceleration time emerged as the sole independent predictor of PWP (r2 = 0.95, F = 590). The analysis led to the following equation: PWP = 51 - 0.26 (deceleration time). Our data suggest that mitral Doppler echocardiography is a useful tool for predicting PWP in heart failure patients with severe LV dysfunction even in the presence of atrial fibrillation.