Viagra directly influences cardiac function in healthy humans

Researchers have demonstrated that sildenafil (viagra) directly influences cardiac function in healthy humans, suppressing b-adrenergic-stimulated systolic function with minimal effect under resting conditions.Sildenafil is an orally active inhibitor of phosphodiesterase 5 (PDE5A) - an enzyme that degrades the cellular messenger cGMP. Sildenafil is known to enhance intracellular cGMP levels and to induce vasodilation making it an effective treatment for erectile dysfunction. Recent animal studies suggest that sildenafil has potent effects on hearts stimulated by b-adrenergic or pressure overloads. Thus, Borlaug et al. conducted a randomised, double-blind, placebo-controlled study to test whether sildenafil pretreatment suppresses b-adrenergic-stimulated cardiac contractility in healthy humans. Thirty-five healthy volunteers recruited from the general population were randomised to this non-invasive, haemodynamic study, which used dobutamine stress testing before and after administration of oral sildenafil (100 mg, n = 19) or placebo (n = 16). Echo Doppler and blood pressure data yielded load-independent contractility indexes, ejection fraction, and measures of diastolic function.Analysis of baseline and sildenafil effect demonstrated a slight decline in arterial pressure and systemic vascular resistance, along with a parallel increase in ejection fraction in sildenafil-treated subjects. Contractility also rose slightly in this group. An inter-group analysis revealed no significant influence of drug treatment (sildenafil versus placebo) on baseline contractility or diastolic function changes, but only on arterial resistance, with borderline changes in diastolic arterial pressure and ejection fractions.In the initial dobutamine test, systolic and diastolic function improved similarly in both treatment groups (non-significant rise in peak power index of 80% in the placebo group and 82% in the sildenafil group). However, in subjects who then received sildenafil, their second dobutamine response was significantly blunted, with peak power, ejection fraction, and end-systolic elastane changes reduced by 32%, 66% and 56%, respectively (pThus the results of this study suggest that sildenafil directly influences cardiac function in healthy humans, suppressing b-adrenergic-stimulated systolic function with minimal effect under resting conditions. Furthermore, this effect was not dependent on after-load or cardiac preload changes.The authors stressed that these data refute the notion that PDE5A inhibitors have no effect on the human heart and reveal a significant interaction in the presence of catecholamine stimulation thus justifying studies for testing chronic effects of PDE5A inhibition on cardiac structure and function."Blunting of adrenergic stimulation might prove beneficial for other disorders in which neurohormonal stimulation is enhanced such as hypertension, left ventricular hypertrophy and heart failure," they concluded.A related editorial by Marc Semigran noted: "These observations illustrate the role of cGMP signalling in cardiomyocyte physiology and confirm the presence of PDE5 in the normal heart and its role in regulating cellular function. The identification of these effects should not alter the current practice of prescribing PDE5 inhibitors for the treatment of male erectile dysfunction, because it appears unlikely that the diminution in cardiac response to adrenergic stimulation should lead to adverse events, even in patients with coronary disease."Reference...