Losartan, an angiotensin II receptor blocker, fails to attenuate pulmonary dysfunction in ovine burn and smoke model

Abstract

Elevated levels of angiotensin II (AngII) in the lung have been shown in response to burn and smoke inhalation injury. AngII has been associated with increased nitric oxide levels, leading to nuclear oxidative damage in Type II lung epithelial cells. Losartan is an AngII receptor blocker, specific to AT1A receptors. Using an ovine model of acute respiratory distress, we hypothesized that blocking AngII receptors with losartan would improve the clinical conditions seen in response to the injury. Chronically prepared adult ewes received a 40% total body surface area third degree flame burn followed by 48 breaths of cotton smoke. The sheep were randomly divided into two groups: control (injury, no treatment, n=6) and treatment (injury + losartan, n= 6). Losartan was given intravenously as a bolus (50 mg) at 1hour post‐injury. All animals received 4ml/kg/%burn of Ringer's lactate and were mechanically ventilated. Control animals showed severe signs of acute lung injury evidenced by deterioration of pulmonary gas exchange (PaO2/FiO2, pulmonary shunt fraction), increased lung water content, and increased pulmonary transvascular fluid flux, and vascular permeability index. Although there was a trend for reduction of lung lymph flow and permeability index, these alterations could not be shown as statistically affected by this dosage of losartan in this 24‐hour ovine model of acute lung injury. SBI 8450, PPG 5P01GM066312