The effect of sildenafil on right ventricular contractility in hypoxic exercise is unknown, whereas reports have shown that sildenafil is associated with a smaller increase in pulmonary vascular resistance and right ventricular systolic pressure (RVSP) with exercise at high altitude. The present study evaluates the changes induced by controlled hypoxia on right ventricular pressure and performance with and without sildenafil administration. Tricuspid annular isovolumic acceleration (IVA) and annular velocities were measured in 14 healthy subjects at rest and after maximal exercise in a cross-over, double blind placebo controlled trial in three situations: normoxia, normobaric hypoxia with, and normobaric hypoxia without the administration of 100 mg sildenafil. RVSP, assessed by Doppler echocardiography, was determined from the peak tricuspid regurgitation pressure gradient. RVSP during rest increased from 26.9 ± 2.3 mmHg in normoxia to 37.8 ± 6.9 mmHg in hypoxia, p < 0.01; sildenafil administration reduced RVSP in hypoxia to 30.5 ± 5.6, p < 0.01. Compared to normoxia at rest, IVA increased similarly with peak exercise in normoxia and hypoxiasildenafil (by 2.37 and 1.90 m/s2, respectively), but the observed increase in IVA during exercise was smaller (0.86 m/s2, p < 0.05) in hypoxiaplacebo. Right ventricular contractility, as estimated by IVA at peak exercise is increased with the administration of sildenafil as compared to placebo, and is not different from the values seen during exercise in normoxia. This effect seems independent of the effect of sildenafil on RVSP.
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Acknowledgments Study coordinators Minelle Hulsebus and Kathy O’Malley are thanked for their devoted work to the recruitment and data collection, and sonographer Jo-Ellen Ehrsam RDCS is acknowledged for her efforts in acquiring the echocardiographic images. This work was supported by American Heart Association, grants no. AHA0410073Z and AHA05-25727Z-01; and Mayo Clinic CTSA Clinical Research Unit, NCRR/NIH # M01-RR00585, and Pfizer Inc. The Danish Heart Foundation supported the research fellowship of Dr. Kjaergaard, grant no. 04-10-B109-A166-22192.
- Phosphodiesterase-5 inhibition
- Pulmonary hypertension
- Right ventricular function