Brunvand H, Liu G, Ma X L, Yue T L, Ruffolo R R, Feuerstein G Z
Department of Surgery, Haukeland Hospital, University of Bergen, Norway.
Eur J Pharmacol. 1998 Sep 4;356(2-3):193-8. doi: 10.1016/s0014-2999(98)00494-4.
The aim of this study was to investigate the effect of SB 211475, a metabolite of carvedilol with weak alpha1-adrenoceptor antagonism and antioxidant effect, on myocardial reperfusion injury and infarct size in anesthetized rabbits. The rabbits were subjected to 60 min of regional myocardial ischemia and 180 min of reperfusion. SB 211475 was administered either as 0.3, 1.0 or 3.0 mg/kg and compared to vehicle and carvedilol (1 mg/kg) treated animals. The lowest dose of SB 211475 (0.3 mg/kg) did not reduce infarct size compared to vehicle, whereas SB 211475 1.0 or 3.0 mg/kg reduced infarct size significantly compared to vehicle (41.2 +/- 2.2% and 40.5 +/- 2.8% vs. 59.1 +/- 3.9%, p < 0.05). Carvedilol reduced infarct size significantly more than SB 211475 1.0 and 3.0 mg/kg (28.8 +/- 3.9% vs. 41.2 +/- 2.2% and 40.5 +/- 2.7%, p < 0.05). Carvedilol and SB 211475 1.0 and 3.0 mg/kg reduced myeloperoxidase activity to the same extent, indicative of reduced inflammation. Rate-pressure product did not differ between doses of SB 211475. In conclusion, SB 211475 in the two highest doses reduced infarct size by protecting from reperfusion injury, possibly by reduced neutrophil accumulation. The superior cardiac protective effect of carvedilol over SB 211475 are most likely due to its adrenergic pharmacology including non-selective beta- and alpha1-adrenoceptor antagonism.
本研究旨在探讨卡维地洛的代谢产物SB 211475（具有微弱的α1肾上腺素能受体拮抗作用和抗氧化作用）对麻醉兔心肌再灌注损伤和梗死面积的影响。对兔进行60分钟的局部心肌缺血和180分钟的再灌注。SB 211475以0.3、1.0或3.0mg/kg的剂量给药，并与溶剂对照组和卡维地洛（1mg/kg）治疗的动物进行比较。与溶剂对照组相比，最低剂量的SB 211475（0.3mg/kg）并未减小梗死面积，而与溶剂对照组相比，SB 211475 1.0或3.0mg/kg显著减小了梗死面积（分别为41.2±2.2%和40.5±2.8%，对比59.1±3.9%，p<0.05）。卡维地洛比SB 211475 1.0和3.0mg/kg更显著地减小了梗死面积（分别为28.8±3.9%，对比41.2±2.2%和40.5±2.7%，p<0.05）。卡维地洛、SB 211475 1.0和3.0mg/kg在相同程度上降低了髓过氧化物酶活性，表明炎症减轻。不同剂量的SB 211475之间的心率-血压乘积无差异。总之，两个最高剂量的SB 211475通过预防再灌注损伤减小了梗死面积，可能是通过减少中性粒细胞聚集实现这一点。卡维地洛比SB 211475具有更优越的心脏保护作用，这很可能归因于其肾上腺素能药理学特性，包括非选择性β和α1肾上腺素能受体拮抗作用。
