Key result
Sildenafil administration significantly reduced right ventricular systolic pressure (29.8 vs 60.7 mmHg, P<0.001) and improved cardiac diastolic function in rats with monocrotaline-induced pulmonary hypertension.
Why the study?
Does sildenafil prevent right ventricular dysfunction and reduce right ventricular systolic pressure in rats with monocrotaline-induced pulmonary arterial hypertension?
Does sildenafil prevent right ventricular dysfunction and reduce right ventricular systolic pressure in rats with monocrotaline-induced pulmonary arterial hypertension?
Absolute Event Rate: 29.8% vs 60.7%
p-value: p=<0.001
Sildenafil prevents the elevation of right ventricular systolic pressure and improves right ventricular diastolic function in a rat model of monocrotaline-induced pulmonary hypertension.
Does not support clinical use; leaves open translation of sildenafil benefits from rat PH models to patients.
The present study aimed to evaluate the preventive effect of sildenafil treatment on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Fifty-four 12-week-old male Sprague-Dawley rats were injected with MCT or saline solution (MCT-injected rats: n=36; saline: n=18). Serial echocardiography and right ventricular systolic pressure (RVSP) measurements via a cardiac catheter were performed at 2, 4 and 6 weeks after the injection. After injection of MCT, rats received oral sildenafil (MCT/sildenafil group: n=18) or no treatment (MCT group: n=18) until undergoing echocardiography and cardiac catheterization. RVSP in the MCT/sildenafil group was lower than that in the MCT group at 4 (P<0.001) and 6 weeks (P<0.001). The septal curvature was improved in the MCT/sildenafil group compared with the MCT group. This finding showed that sildenafil prevented flattening of the interventricular septum because of right ventricular pressure overload. The ratio of peak trans-tricuspid early diastolic wave velocity to active filling with atrial systolic velocity showed that sildenafil improved diastolic function. Tricuspid annular plane systolic excursion and tricuspid annular systolic velocity in the MCT/sildenafil group did not show preserved myocardial contraction after administration of sildenafil. Administration of sildenafil leads to a reduction in RVSP and improvement in cardiac function in rats with PH induced by MCT. The vasodilatory action of sildenafil improves right ventricular diastolic function, but the intrinsic, positive, inotropic effect of sildenafil is minimal.
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Yoshiyuki et al. (2016) studied Monocrotaline-induced pulmonary arterial hypertension (n=54). Sildenafil vs. No treatment (MCT group) was evaluated on Right ventricular systolic pressure (RVSP) at 6 weeks (p=<0.001). Sildenafil administration significantly reduced right ventricular systolic pressure (29.8 vs 60.7 mmHg, P<0.001) and improved cardiac diastolic function in rats with monocrotaline-induced pulmonary hypertension.
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