Effect of free radical scavenger on cardiovascular system in sepsis

本研究的目的是确定尼卡拉芬对脂多糖（LPS）诱导的脓毒症心功能和细胞因子产生的影响。本议定书经我们的机构委员会批准。大鼠（330 ~ 350 g）行动、静脉插管和气管造口术后，戊巴比妥麻醉，控制模式机械通气（TV = 12 ml/kg, RR = 40 rpm）。在基线测量后，大鼠（n = 20）给予LPS （10 mg/kg，静脉注射），并随机分为两组：尼卡拉文组（3 mg/kg/min，静脉注射）和对照组（生理盐水）。每隔1 h用压导导管测量左室血压和容积。心功能包括心输出量（CO）、射血分数（EF）和左心室最大弹性（E_<max>）。术后每2小时采集大鼠血液，离心（2000g, 15min， × 2）， -80℃保存，采用酶联免疫吸附测定试剂盒测定血浆中TNF-α、il - 1-β和巨噬细胞迁移抑制因子（MIF）的浓度。动脉血气分析和乳酸浓度测定。资料采用重复测量方差分析。尼加拉瓜文组的CO显著高于对照组（p < 0.05）。尼加拉瓜文组的EF和E_<max>也显著高于对照组（p < 0.05）。尼卡拉芬组动脉乳酸、TNF-α、il - 1-β、MIF显著低于对照组（P < 0.05）。综上所述，本研究表明，尼加拉瓜文治疗可以保持心脏功能，降低血浆细胞因子浓度，改善脓毒症模型的乳酸酸中毒。

The purposes of present study were to determine the effects of nicaraven on cardiac function and cytokine production in lipopolysaccharide (LPS) induced sepsis.This protocol was approved by our institutional committee. Following arterial and venous cannulation and tracheostomy, rats (330-350 g) were anesthetized with pentobarbital, and mechanically ventilated with a control mode (TV = 12 ml/kg, RR = 40 rpm). After baseline measurements, rats (n = 20) were administrated with LPS (10 mg/kg, intravenously) and randomly assigned to following two groups : the nicaraven group treated with nicaraven (3 mg/kg/min, intravenously) and the control group treated with saline. The left ventricular, pressure and volume were measured with the pressure and conductance catheter every one hour. Cardiac function, including cardiac output (CO), ejection fraction (EF), and maximal elastance of left ventricle (E_<max>) were analyzed with a computer soft. Blood was collected, centrifuged (2000g, 15 min, x 2), and stored (-80 c) from rats every 2 hours after operation to measure plasma concentration of TNF-α, IL1-β and macrophage migration inhibitory factor (MIF) using enzyme-linked immunosorbent assays kits. Arterial blood gas analysis and lactate concentration were also measured. Data were analyzed by repeated measure ANOVA.The CO in the nicaraven group was kept significantly higher than the control group (p < 0.05). The EF and E_<max> in the nicaraven group were also kept significantly higher than the control group (p < 0.05). Arterial lactate, TNF-α, IL1-β and MIF were significantly lower in the nicaraven group versus the control group (P < 0.05).In conclusion, the current study indicates that the treatment with nicaraven preserves cardiac function and reduces plasma concentration of cytokine, and improves lactic acidosis in septic model.