Lipoxygenase inhibitor nafazatrom fails to attenuate postischaemic ventricular dysfunction.
Lipoxygenase inhibitor nafazatrom fails to attenuate postischaemic ventricular dysfunction.
复制标题
脂氧合酶抑制剂 nafazatrom 不能减轻缺血后心室功能障碍。
DOI：
10.1093/cvr/21.10.755
复制
发表时间：
1987
影响因子：
10.8
通讯作者：
Bolli,R
中科院分区：
文献类型：
--
作者：
O'Neill,PG;Charlat,ML;Kim,HS;Pocius,J;Michael,LH;Hartley,CJ;Zhu,WX;Roberts,R;Bolli,R
在开胸犬中研究了脂氧合酶激活在缺血后心肌功能障碍发生中的作用，该犬经历了15分钟的左前降支动脉闭塞，随后再灌注4小时。治疗组动物（n=9）在阻断前4 h口服一种有效的脂氧合酶抑制剂萘扎特龙（nafazatrom）10 mg·kg-1，随后在阻断前15 min和再灌注前1 min分别静脉推注1.5 mg·kg-1和0.5 mg·kg-1。对照动物（n=10）接受生理盐水。药物未产生明显的血液动力学效应。对照组缺血区（放射性微球）的侧支血流量为0.14（0.02）ml·min-1·g-1，治疗组为0.16（0.05）ml·min-1·g-1。通过死后灌注确定的闭塞床尺寸为对照组左心室的25.5（0.8）%，治疗组为24.3（1.3）%。组织学检查显示，萘扎曲姆治疗动物的非缺血心肌中性粒细胞浸润减少，再灌注心肌中性粒细胞浸润程度较低，表明脂氧合酶抑制。使用心外膜脉冲多普勒探头评估心外膜壁增厚（局部功能指标）。两组在基线条件下表现出相当的收缩期增厚。尽管治疗组动物在冠状动脉闭塞期间表现出较少的运动障碍（p<0.05），但功能恢复并没有比对照组增强，并且在两组中，再灌注心肌在4 h时仍然存在运动障碍。因此，萘唑仑未能改善缺血后心室功能障碍，表明白三烯对这种现象没有重要作用。
The role of lipoxygenase activation in the genesis of postischaemic myocardial dysfunction was investigated in open chest dogs undergoing a 15 min occlusion of the left anterior descending artery followed by 4 h of reperfusion. Treated animals (n=9) received nafazatrom, a potent lipoxygenase inhibitor, 10 mg·kg−1orally 4 h before occlusion followed by intravenous boluses of 1.5 mg·kg−1and 0.5 mg·kg−15 min before occlusion and 1 min before reperfusion respectively. Control animals (n=10) received saline. No discernible haemodynamic effects were produced by the drug. Collateral flow to the ischaemic zone (radioactive microspheres) was 0.14(0.02) ml·min−1·g−1in the control group and 0.16(0.05) ml·min−1·g−1in the treated group. The size of the occluded bed as determined by postmortem perfusion was 25.5(0.8)% of the left ventricle in the control and 24.3(1.3)% in the treated group. Histological examination showed a decrease in neutrophil infiltration of the non-ischaemic myocardium and, to a lesser extent, of the reperfused myocardium in nafazatrom treated animals, suggesting lipoxygenase inhibition. Systolic wall thickening (an index of regional function) was assessed using an epicardial pulsed Doppler probe. The two groups exhibited comparable systolic thickening under baseline conditions. Though treated animals showed less dyskinesis during coronary occlusion (p<0.05), recovery of function was not enhanced over controls and in both groups the reperfused myocardium was still dyskinetic at 4 h. Thus nafazatrom failed to improve postischaemic ventricular dysfunction, suggesting that leukotrienes do not contribute importantly to this phenomenon.