Submitted on March 20, 2006
Accepted on May 29, 2006
Effects of sildenafil on hypoxic pulmonary vascular function in dogs
Pierre Fesler1, Alberto Pagnamenta2, Benoit Rondelet2, Francois Kerbaul2, and Robert Naeije2*
1 Department of Internal Medicine, Hopital Lapeyronie, Montpellier, France
2 Laboratory of Physiology, Universite Libre de Bruxelles, Brussels, Belgium
* To whom correspondence should be addressed. E-mail: rnaeije{at}ulb.ac.be.
Sildenafil has been shown to be an effective treatment of pulmonary arterial hypertension and is believed to present with pulmonary selectivity. This study was designed to precise the site of action of sildenafil compared to inhaled nitric oxide (NO) and iv sodium nitroprusside (SNP), known as selective and non selective pulmonary vasodilators. Inhaled NO 40 ppm, and maximum tolerated doses of iv SNP and sildenafil, respectively 5 µg.kg-1.min-1 and 0.1 mg.kg-1.hour-1 were administered to 8 dogs ventilated in hypoxia. Pulmonary vascular resistance (PVR) was evaluated by pulmonary arterial pressure (Ppa) minus left atrial pressure (Pla) vs flow curves, and partitioned into arterial and venous segments by the occlusion method. Right ventricular hydraulic load was defined by pulmonary arterial characteristic impedance (Zc) and elastance (Ea) calculations. Right ventricular arterial coupling was estimated by the ratio of end systolic elastance (Ees) to Ea. Decreasing the FIO2 from 0.4 to 0.1 increased Ppa-Pla at a standardized flow of 3 L.min-1.m-2 from 6±1 to 18±1 mmHg. Ppa-Pla was decreased to 9±1 by inhaled NO, 14±1 by SNP, and 14±1 mmHg by sildenafil. The partition of PVR, Zc, Ea, and Ees/Ea were not affected by the three interventions. Inhaled NO did not affect systemic arterial pressure, which was similarly decreased by sildenafil and SNP, from 115±4 to 101±4 and 98±5 mmHg, respectively. We conclude that inhaled NO inhibits hypoxic pulmonary vasoconstriction more effectively than sildenafil or SNP, and sildenafil shows no more selectivity for the pulmonary circulation than SNP.
