异丙酚对离体大鼠心脏再灌注损伤后冠脉儿茶酚胺浓度的影响

Effect of propofol on concentration of catecholamine in coronary outflow of isolated contracting rat heart after ischemiar-rperfusion injury

目的 通过建立离体大鼠工作心脏灌注模型,测定冠脉流出液儿茶酚胺浓度,研究异丙酚对离体大鼠心脏缺血/再灌注损伤后左室功能及心肌代谢的保护机制。方法 雄性SD大鼠40只,随机分为4组(每组10只),对照组、异丙酚10μmol/L组、50μmol/L组、100μmol/L组。建立工作心脏模型后,所有心脏全心缺血25 min,再灌注30 min。在缺血前5 min、0 min,再灌注后5、10、15、20、25和30 min分别观察心率(HR)、左室发展压与心率乘积(LVDP×HR)、冠脉流量(CF)、心排出量(CO)等心功能指标,并留取冠脉流出液测量肌酸激酶(CK)、儿茶酚胺含量。结果 缺血前,异丙酚组CO、HR、LVPSP及LVDP×HR均显著低于对照组(P<0.05);4组CK值无显著变化(P>0.05),儿茶酚胺测不出。再灌注时,异丙酚组CF、CO、HR、LVEDP、LVPSP及LVDP×HR在相应时点均比对照组恢复明显(P<0.05);异丙酚组CK值显著低于对照组(P<0.05);再灌注后,异丙酚组肾上腺素和去甲肾上腺素显著低于对照组(P<0.05);各组多巴胺含量差别不显著(P>0.05)。结论 异丙酚对离体大鼠心肌缺血/再灌注损伤具有保护作用,其机制之一可能是由于异丙酚抑制心肌缺血再灌注损伤后儿茶酚胺的释放。

Objective The normothermic isolated contracting rat heart model was used to investigate the mechanism of protective effect of propofol on left ventricular function and myocardial metabolism against ischemia-reperfusion injury by determination of the catecholamme concentration in the coronary outflow. Methods forty healthy male SD rats weighing 310-450 g were randomly divided into 4 groups of each 10 animals: control group, propofol 10μmol/L (P10), 50μmol/L (P50) and 100μmol/L (P100). The animal were sacrificed by knock-out and the heart was immediately removed. The aorta was connected to a Larigendorff apparatus and retrogradely perfused with oxygenated (95% O, and 5% CO2) Krebs-Henseleit buffer (KHB) for 5 min. Then the left ventricle was perfused through a cannula inserted in pulmonary vein at a constant pressure of 12.5 cm H2O (preload). The pressure at aorta outflow was 90 cm H2O (afterload). Different concentrations of propofol in KHB were prepared. Global ischemia of the heart was induced by suspension of perfusion for 25 min followed by 30 min reperfusion. Coronary flow (CF), aortic flow (AF), cardiac output (CO = AF + CF), HR, left ventricular peak systolic pressure (LVPSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP = LVPSP-LVEDP) and the product of LVDP and HR were measured and recorded 5 min and immediately before ischemia and 5, 10, 15, 20, 25 and 30 min following reperfusion. Coronary outflow was collected for determination of creatine kinase (CK) and catecholamine ( epinephrine, norepinephrine and dopamine) concentrations.Results Before ischemia CF was significantly higher and CO, HR, LVPSP and LVDP × HR were significantly lower in the 3 propofol groups in comparison with the controls. During reperfusion CF, CO, HR, LVPSP and LVEDP recovered much better in the propofol groups than those in control group. In group P50 LVDP × HR reached 88.7% of the pre-ischemic value while in control group only 56.3% . The CK and catecholamine concentrations were not significantly different among the 4 groups before ischemia. During reperfusion CK, epinephrine and noeepinepherine concentrations were significantly lower in propofol groups than in control group (P < 0.05), while dopamine concentration was not significantly different. Conclusion Our results show that propofol may protect heart from ischemia-reperfusion injury through suppression of catecholamine release following ischemia-reperfusion.