Sildenafil in endotoxin-induced pulmonary hypertension: an experimental study

Abstract

Background: Sepsis and septic shock still represent great challenges in critical care medicine. Sildenafil has been largely used in the treatment of pulmonary arterial hypertension, but its effects in sepsis are unknown. The aim of this study was to investigate the hypothesis that sildenafil can attenuate endotoxin-induced pulmonary hypertension in a porcine model of endotoxemia. Methods: Twenty pigs were randomly assigned to Control group (n.ß=.ß10), which received saline solution; or to Sildenafil group (n.ß=.ß10), which received sildenafil orally (100.ßmg). After 30.ßminutes, both groups were submitted to endotoxemia with intravenous bacterial lipopolysaccharide endotoxin (LPS) infusion (4.ß..g.kg-1.h-1) for 180.ßminutes. We evaluated hemodynamic and oxygenation functions, and also lung histology and plasma cytokine (TNF.., IL-1.., IL6, and IL10) and troponin I response. Results: Significant hemodynamic alterations were observed after 30.ßminutes of LPS continuous infusion, mainly in pulmonary arterial pressure (from Baseline 19.ß...ß2.ßmmHg to LPS30 52.ß...ß4.ßmmHg, p.ß<.ß0.05). There was also a significant decrease in PaO2/FiO2 (from Baseline 411.ß...ß29 to LPS180 334.ß...ß49, p.ß<.ß0.05). Pulmonary arterial pressure was significantly lower in the Sildenafil group (35.ß...ß4.ßmmHg at LPS30, p.ß<.ß0.05). The Sildenafil group also presented lower values of systemic arterial pressure. Sildenafil maintained oxygenation with higher PaO2/FiO2 and lower oxygen extraction rate than Control group but had no effect on intrapulmonary shunt. All cytokines and troponin increased after LPS infusion in both groups similarly. Conclusion: Sildenafil attenuated endotoxin-induced pulmonary hypertension preserving the correct heart function without improving lung lesions or inflammation.

Keywords

• Phosphodiesterase V inhibitors
• Acute lung injury
• LPS
• Septic shock
• Experimental model
• Swine