Effects of different inspired oxygen fractions on sildenafil-induced pulmonary anti-hypertensive effects in a sheep model of acute pulmonary embolism

Abstract

Aims: Sildenafil is a pulmonary anti-hypertensive agent whose action could be modified by different fractions of inspired oxygen (FiO2). We compared the effects of pure oxygen (FiO2 > 90%) or room air (21% FiO2) on the cardiopulmonary actions of sildenafil in sheep with acute pulmonary embolism (APE).

Main methods: Thirty-two anesthetized, mechanically ventilated sheep (34.9 ± 5.4 kg), were randomly distributed into four groups (n = 8 per group): FiO2 > 90% without intervention; APE induced by microspheres with FiO2 > 90%, followed 30 min later by placebo (Emb90); or APE followed 30 min later by intravenous sildenafil (0.7 mg/kg over 30 min) with FiO2 > 90% (Emb + Sild90) or 21% FiO2 (Emb + Sild21) [Corrected]. Variables were recorded until 30 min after the end of treatment administration.

Key findings: Microsphere injection increased (P < 0.05) mean pulmonary artery pressure (MPAP) in all embolized groups (111-140% higher than that of baseline). Compared with values recorded 30 min after induction of APE (E30), sildenafil induced greater decreases in MPAP in the Emb + Sil90 group than in the Emb + Sil21 group (23% and 14% lower than E30, respectively). Hypotension (mean arterial pressure < 60 mm Hg) was precipitated by sildenafil due to systemic vasodilation in the Emb + Sil21 group. Embolization lowered the PaO2/FiO2 ratio and increased venous admixture, but sildenafil did not alter the oxygenation impairment induced by APE.

Significance: Sildenafil induces a more consistent pulmonary anti-hypertensive effect and causes less interference with the systemic circulation with the concomitant use of pure oxygen than that with room air in the APE setting.

Keywords: Acute pulmonary embolism; Pulmonary hypertension; Sildenafil.