Effects of Aprotinin on Acute Lung Injury by Endotoxin in Rabbits / 대한마취과학회지

BACKGROUND: Aprotinin, a serine protease inhibitor, has an anti-inflammatory and hemostatic effect and has been used to reduce perioperative blood loss and lung injury after cardiopulmonary bypass in cardiac surgery. Acute respiratory distress syndrome (ARDS), which results in clinical manifestations due to non-cardiogenic permeability edema is a fatal condition associated with a mortality rate of 50 to 80%. The purpose of this study was to evaluate the effects of aprotinin on acute lung injury induced by bacterial endotoxin in rabbits. METHODS: Nineteen rabbits were anesthetized with intravenous xylazine, Ketamine and vecuronium and ventilated with a Harvard apparatus maintaining normocapnea. In 7 rabbits, 2 mg/Kg of lipopolysaccharide from E. coli was infused intravenously for 30 min (Toxin group) and in another 7 rabbits aprotonin loading with 200,000 KIU/Kg followed by a continuous infusion of 50,000 KIU/Kg/hr was performed 30 min before the endotoxin infusion throughout the experiment (Aprotinin group). At 1, 2, 3, and 4 hours after endotoxin infusion, arterial blood gas, blood cell count, prothrombin time, activated partial thromboplastin time, fibrinogen, and hemodynamic profiles were checKed. At four hours, the animals were dissected at which time the lungs were divided into three regions for wet/dry weight ratio (WW/DW), myeloperoxidase activity and microscopic examination. RESULTS: In the Aprotinin group, pulmonary vascular resistance, arterial oxygen partial pressure and coagulation function were well preserved compared with the Toxin group. Furthermore, lung WW/DW, myeloperoxidase activity, and inflammatory responses also increased less in the Aprotinin group. CONCLUSIONS: The results of the current data showed that aprotinin has prophylactic effects against acute lung injury and coagulation impairment induced by bacterial endotoxin in rabbits.

Role of Nitric Oxide in Lipopolysaccharide-Induced Acute Lung Injury and Lipid Peroxidation in Rats / 대한마취과학회지

BACKGROUND: Nitric oxide (NO) may act as an oxygen radical scavenger or as an antioxidant, and inhibit neutrophil superoxide anion production. In contrast, NO combines with superoxide to form peroxynitrite, a very damaging material whose decomposition RESULTS in the generation of a hydroxyl radical. This study was designed to determine the role of NO in the development of acute lung injury and lipid peroxidation induced by lipopolysaccharide (LPS) in rats. METHODS: Male Sprague-Dawley rats (200 - 250 g) were given one of the following treatments; intraperitoneal normal saline 0.5 ml, intraperitoneal E. coli LPS (5 mg/kg) in 0.5 ml normal saline, 4 mg/kg L-N(6)-(1-iminoethyl)lysine (L-NIL) + LPS, or L-arginine (80 mg/kg) + LPS. Four hours after treatment, the rats were killed by an intraperitoneal pentobarbital injection (100 mg/kg) and plasma nitrate/nitrite concentration (Griess reagents) and lipid peroxide (LPO) concentration of the lung (Yagi's method) were measured (n = 8). In the other sets of experiments, myeloperoxidase activity of the lung (n = 5) and protein concentration of the bronchoalveolar lavage (BAL) fluid (BCA protein assay reagents, n = 4) were assayed. RESULTS: LPS treatment increased plasma nitrate/nitrite concentrations approximately 6 times (20.9 1.8nM, P < 0.01) compared with the control group (3.6 +/- 0.7nM), and L-NIL treatment prevented this increase. L-NIL plus LPS treatment resulted in greater increase of LPO concentrations of the lung compared with the control (P < 0.05). Myeloperoxidase activity and protein concentrations of BAL fluids were higher in LPS and L-NIL plus LPS treatment groups than the control group. CONCLUSIONS: These results suggest that inhibition of the increase of NO by selective inducible NO synthase inhibitor L-NIL may increase lipid peroxidation in septic rats.