Galiè N, Guarnieri C, Ussia G P, Zimarino M, Traini A M, Parlangeli R, Vaona I, Branzi A, Magnani B
Institute of Cardiovascular Diseases, University of Bologna, Italy.
J Cardiovasc Pharmacol. 1995 Sep;26(3):477-84. doi: 10.1097/00005344-199509000-00019.
Nicorandil is a compound with hybrid properties of nitrates and adenosine triphosphate (ATP)-sensitive potassium channel (KATP) opening. The effects of nicorandil and isosorbide dinitrate (ISDN) were investigated in a model of 60-min coronary occlusion/180-min reperfusion in open chest pigs. Three groups of 10 pigs were randomly assessed to receive saline or equihypotensive doses of nicorandil or ISDN. Drug infusion was started at 30 min of ischemia and continued throughout reperfusion. Area at risk (AAR) and infarcted area (IA) were assessed by monastral blue dye-triphenyltetrazolium dual staining technique and calculated by planimetry. Myeloperoxidase concentration (MPO) in the non-ischemic area and in the IA was assessed as an index of presence of neutrophils. Measurements of reduced glutathione (GSH), oxidized glutathione (GSSG), lipofuscine, and malondialdehyde were performed on coronary vein blood as indexes of oxidative stress. IA, as a percentage of AAR, was 78 +/- 10% after saline, 61 +/- 12% after N (p < 0.05 vs. saline), and 69 +/- 14% after ISDN (not significant vs. saline). Cardiac output and left ventricular dP/dt were depressed during coronary occlusion in all groups and their recovery during reperfusion was earlier in the nicorandil group. In the saline group, MPO was increased in the IA compared to the nonischemic area (78 +/- 63 vs. 21 +/- 21 micrograms/mg prot, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
尼可地尔是一种具有硝酸盐和三磷酸腺苷（ATP）敏感性钾通道（KATP）开放双重特性的化合物。在开胸猪60分钟冠状动脉闭塞/180分钟再灌注模型中研究了尼可地尔和硝酸异山梨酯（ISDN）的作用。将三组各10头猪随机评估以接受生理盐水或等降压剂量的尼可地尔或ISDN。在缺血30分钟时开始药物输注，并在整个再灌注过程中持续。通过亚甲蓝染料-三苯基四氮唑双重染色技术评估危险区域（AAR）和梗死区域（IA），并通过平面测量法计算。评估非缺血区域和IA中的髓过氧化物酶浓度（MPO）作为中性粒细胞存在的指标。对冠状静脉血进行还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）、脂褐素和丙二醛的测量，作为氧化应激指标。IA占AAR的百分比，生理盐水组后为78±10%，尼可地尔组后为61±12%（与生理盐水组相比，p<0.05），ISDN组后为69±14%（与生理盐水组相比无显著差异）。所有组在冠状动脉闭塞期间心输出量和左心室dP/dt均降低，尼可地尔组在再灌注期间恢复较早。在生理盐水组中，IA中的MPO相比于非缺血区域增加（78±63对21±21微克/毫克蛋白，p = 0.02）。（摘要截断于250字）
