Ezgi Özyılmaz1, Hacer Sinem Göktürk Büyüknacar2, Emine Kılıç Bağır3, Leman Sencar4, Özlem Görüroğlu Öztürk5, Ismail Cem Eray6, Yusuf Kenan Dağlıoğlu7, Oya Baydar1, Gülşah Seydaoğlu8, Ufuk Özgü Mete4, Derya Gümürdülü3, Ali Kocabaş1. 1. Department of Chest Diseases, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 2. Department of Pharmacology, Faculty of Pharmacy, Çukurova University, Balcalı, Turkey. 3. Department of Pathology, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 4. Department of Histology and Embryology, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 5. Department of Biochemistry, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 6. Department of General Surgery, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 7. Department of Microbiology, Faculty of Medicine, Çukurova University, Balcalı, Turkey. 8. Department of Biostatistics, Faculty of Medicine, Çukurova University, Balcalı, Turkey.
Abstract
BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with β-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-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α 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 preand 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 β-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of β-blockers on the endothelium may lead to a better understanding of sepsis.
BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with β-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-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α 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 preand 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 β-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of β-blockers on the endothelium may lead to a better understanding of sepsis.