Losartan protects the lung from chronic cellular damage induced by fat embolism (LB512)

Abstract

In a model of triolein‐induced fat embolism (FE) in the rat, we have reported that the acute pulmonary histopathological changes were ameliorated by losartan (Los). The chronic pulmonary changes of FE persisted at 6 weeks and symptoms were exacerbated by a “second hit” at that time using LPS. The present experiment extended FE study to 10 weeks and examined whether the FE effects plus LPS would continue to be blocked by Los. Groups of rats were given FE (triolein i.v. or i.v. saline controls) followed 6 weeks later by LPS (3 mg/kg i.p). One‐hour after LPS rats were treated with saline or Los (2 mg/kg i.p. and then 0.1 mg/ml Los in the drinking water for 4 more weeks). In confirmation of our previous results, the FE group showed normal weight gain both at 6 and 10 weeks and appeared to be in no distress. However the lungs showed reduced lumen patency at 10 weeks, accompanied by inflammatory and fibrotic changes that were greater than what had been found previously at 6 weeks whether or not LPS was added. These changes were reduced or blocked by Los. In addition pulmonary arteries of all Los‐treated animals had increased lumen patency compared to their respective controls. The data suggest that the effect of FE continues to progress at 10 weeks. The involvement of the renin‐angiotensin system in the pathology of FE is supported by the action of the type 1 receptor blocker, Los. In addition, the enhanced effect of LPS on FE (second hit) was also blocked by Los. These results support the possibility of using angiotensin blockade in clinical situations where fat embolism is suspected .Grant Funding Source: Supported by Geldmacher Foundation