Early propranolol treatment ameliorates endothelial dysfunction in experimental septic lung

Abstract

PubMedID: 29969202Background. Recent reports have indicated an improved prognosis in sepsis with beta blocker agents; however, the underlying action mechanism is still under debate. Objectives. The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. Material and methods. The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. Results. Serum tumor necrosis factor alpha (TNF-?) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-? scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the pre- and post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. Conclusions. These results suggest that the improved outcome with beta blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of beta blockers on the endothelium may lead to a better understanding of sepsis. © 2019 by Wroclaw Medical University