Ma X L, Yue T L, Lopez B L, Barone F C, Christopher T A, Ruffolo R R, Feuerstein G Z
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
J Pharmacol Exp Ther. 1996 Apr;277(1):128-36.
Oxygen-derived free radicals play a critical role in atherogenesis and reperfusion injury. The present experiment evaluated the effects of carvedilol, a new beta adrenoreceptor blocker with potent free radical-scavenging activity, on myocardial ischemia and reperfusion injury in a hypercholesterolemic rabbit model. New Zealand rabbits were fed a normal diet, a high-cholesterol diet, or a high-cholesterol diet supplemented with 1200 ppm carvedilol or propranolol. Eight weeks later, the rabbits were subjected to 60 min of myocardial ischemia followed by 60 min of reperfusion. The nontreated cholesterol-fed animals experienced greater cardiac damage after ischemia and reperfusion than rabbits fed a normal diet (necrosis 51% +/- 4% vs. 28% +/- 3% in the normal-diet group, P < .01). In addition, nontreated cholesterol-fed rabbits showed a significantly decreased vasorelaxant response to ACh in U-46619-precontracted aortic rings (56% +/- 5% vs 90% +/- 3% in the control group, P < .001). Treatment with propranolol neither preserved endothelial function after cholesterol feeding nor reduced neutrophil accumulation in ischemic-reperfused myocardial tissue. Propranolol treatment did significantly decrease HR, pressure-rate index and infarct size (necrosis 33% +/- 4%). Despite their having essentially identical effects on HR and pressure-rate index, carvedilol exerted more profound cardiac protective effects than propranolol (necrosis 19% +/- 3%). Moreover, carvedilol treatment significantly preserved aortic endothelial function and markedly reduced neutrophil accumulation in ischemic-reperfused myocardial tissue. These results indicate that in addition to its beta blocking activity, the antioxidant and endothelial protective activities of carvedilol contributed significantly to its cardiac protective effects after ischemia and reperfusion.
氧衍生的自由基在动脉粥样硬化形成和再灌注损伤中起关键作用。本实验评估了卡维地洛（一种具有强大自由基清除活性的新型β肾上腺素能受体阻滞剂）对高胆固醇血症兔模型心肌缺血和再灌注损伤的影响。将新西兰兔分为正常饮食组、高胆固醇饮食组、补充1200 ppm卡维地洛的高胆固醇饮食组或普萘洛尔组。八周后，使兔经历60分钟的心肌缺血，随后进行60分钟的再灌注。未治疗的高胆固醇饮食动物在缺血和再灌注后比正常饮食的兔遭受更大的心脏损伤（坏死率51%±4% 对比正常饮食组的28%±3%，P <.01）。此外，未治疗的高胆固醇饮食兔对U - 46619预收缩主动脉环中乙酰胆碱的血管舒张反应显著降低（56%±5% 对比对照组的90%±3%，P <.001）。普萘洛尔治疗既不能在高胆固醇饮食后保留内皮功能，也不能减少缺血再灌注心肌组织中的中性粒细胞积聚。普萘洛尔治疗确实显著降低了心率、压力 - 心率指数和梗死面积（坏死率33%±4%）。尽管卡维地洛和普萘洛尔对心率和压力 - 心率指数的影响基本相同，但卡维地洛比普萘洛尔发挥了更显著的心脏保护作用（坏死率19%±3%）。此外，卡维地洛治疗显著保留了主动脉内皮功能，并显著减少了缺血再灌注心肌组织中的中性粒细胞积聚。这些结果表明，除了其β阻断活性外，卡维地洛的抗氧化和内皮保护活性对其缺血再灌注后的心脏保护作用有显著贡献。
