一氧化氮在七氟醚预处理减轻兔心肌缺血再灌注损伤中的作用

目的 评价一氧化氮在七氟醚预处理减轻兔心肌缺血再灌注损伤中的作用.方法 健康雄性新西兰大白兔40只,体重2.1～2.9 kg,随机分为5组(n=8):缺血再灌注组(IR组)、七氟醚预处理组(SEV组)、L-NAME组、七氟醚预处理+L-NAME组(SL组)和L-NAME+七氟醚预处理组(LS组).采用结扎冠状动脉前降支45 min,再灌注3 h的方法制备兔心肌缺血再灌注模型.SEV组吸入1.7%七氟醚30 min,洗脱15 min行预处理后制备模型;L-NAME组静脉注射一氧化氮合酶(NOS)抑制剂L-NAME 1 mg/kg,5 min后制备模型;SL组七氟醚预处理后,静脉注射L-NAME 1 mg/kg,5 min后制备模型;LS组静脉注射L-NAME 1 mg/kg,5 min后行七氟醚顶处理,制备模型.于模型制备前即刻(T0)、心肌缺血45 min(T1)、再灌注60 min(T2)、120 min(T3)、180 min(T4)时记录HR、MAP、左室收缩压(LVSP)和左室收缩压最大上升速率(+dp/dtmax),于T4时抽取股动脉血3 ml,测定血浆心肌肌钙蛋白T(cTnT)浓度、心肌磷酸肌酸激酶(CK-MB)和乳酸脱氢酶(LDH)活性,取心室肌组织,测定心肌缺血危险区(AAR)和梗塞区(IS)面积,并计算IS/AAR.结果 与IR组比较,SEV组缺血再灌注时+dp/dtmax升高,血浆cTnT浓度、CK-MB和LDH活性和心室肌IS/AAR降低(P<0.05),其余组上述指标差异均无统计学意义(P0.05).结论 一氧化氮参与了七氟醚预处理减轻兔心肌缺血再灌注损伤,一氧化氮可能是其保护作用中某一通路上的信号分子.

Role of nitric oxide in sevoflurane preconditioning-induced amelioration of myocardial ischemia-reperfusion injury in rabbits

Objective To evaluate the role of nitric oxide (NO) in sevoflurane preconditioning-induced amelioration of myocardial ischemia-reperfusion injury (I/R) in rabbits. Methods Forty healthy New Zealand white rabbits weighing 2.1-2.9 kg were randomly divided into 5 groups (n=8 each): group Ⅰ I/R;group Ⅱ sevoflurane preconditioning (SEV);group Ⅲ L-NAME;group Ⅳ SEV + L-NAME and group Ⅴ L-NAME + SEV. The animals were anesthetized with pentobarbital, tracheostomized, intubated and mechanically ventilated (VT=15 ml/kg, RR = 35 bpm, FiO2 = 50% ). PET CO2 was maintained at 30-35 mm Hg. MAP, HR, LVSP and +dp/dtmax were monitored. Myocardial I/R was produced by occlusion of left anterior descending branch of coronary artery for 45 min followed by 3 h reperfusion. In group SEV(group Ⅱ) 1.7% SEV was inhaled for 30 min followed by 15 min washout before myocardial I/R. In group L-NAME (group Ⅲ) L-NAME (the NOS inhibitor) 1 mg/kg was given iv 5 rain before I/R. In group Ⅳ L-NAME 1 mg/kg was given iv between SEV preconditioning and I/R and in group Ⅴ L-NAME 1 mg/kg was given iv before SEV preconditioning and I/R. MAP, HR, LVSP and + dp/dtmax were recorded at 30 min stabilization (baseline), at the end of 45 min myocardial ischemia (T1), and at 60, 120 and 180 min of reperfusion (T2-4). Blood samples were taken at 1"4 for determination of plasma concentration of cTnT, activation of CK-MB and LDH. The hearts were then removed for determination of infarct size (IS) and the area at risk of ischemia (AAR). IS/AAR was calculated.Results + dp/dtmax was significantly higher, the plasma concentration of cTnT and activity of CK-MB and LDH and IS/AAR were significantly lower at T4 in group SEV (group Ⅱ) than in group I/R (group Ⅰ) (P<0.05). There were no significant differences in the hemodynamics, plasma cTnT concentration, CK-MB and LDH activities and IS/AAR between group Ⅰ (I/R) and group Ⅲ,Ⅳ and Ⅴ (P0.05). Conclusion NO is involved in the protective effect of SEV preconditioning against I/R injury.