Sasaki K, Ueno A, Katori M, Kikawada R
Department of Pharmacology and Medicine, Kitasato University School of Medicine, Kanagawa, Japan.
Cardiovasc Res. 1988 Feb;22(2):142-8. doi: 10.1093/cvr/22.2.142.
The main left coronary artery of rats was ligated near its origin under light ether anaesthesia and the infarction observed for 48 h. The ischaemic area was determined after an intravenous injection of pontamine sky blue dye 1 h before induction of cardiac arrest with potassium chloride. The unstained area (true ischaemic area) decreased with time to 27.1% of the left ventricle at 48 h, whereas the intensely stained area between the normal and the true ischaemic areas increased with time, suggesting that blood was flowing to the border from the normal surrounding tissue. The infarcted area, identified by its lack of triphenyltetrazolium chloride staining, became evident after 3 h and stabilised at 12 h (42% of left ventricle). The polymorphonuclear leucocyte counts in the hearts, differentiated by staining of their chloroacetate esterase, increased gradually up to 5500 cells per section at 24 h. The leukotriene B4 concentration, determined by radioimmunoassay after freezing of the beating heart in liquid nitrogen, increased to eight times that of the sham operated hearts and peaked at 8 h (9.4(0.6) ng per heart, mean(SEM) n = 5) before the leucocyte counts reached their maximum. A single oral dose of a selective 5-lipoxygenase inhibitor (AA-861, 80 mg.kg-1, 1 h before ligation) lowered the leukotriene B4 concentration to that of the sham operated hearts and decreased the leucocyte count by 49.4% and 41.2% at 12 and 24 h respectively. The inhibitor also reduced the infarct size at 48 h by 34.4%. It was concluded that leukotriene B4, generated in ischaemic cardiac tissue, may increase infarct size through migration of polymorphonuclear leucocytes.
在轻度乙醚麻醉下，将大鼠的左冠状动脉主干在其起始处附近结扎，并观察梗死情况48小时。在用氯化钾诱导心脏骤停前1小时静脉注射滂胺天蓝染料后，测定缺血区域。未染色区域（真正的缺血区域）随时间减少，在48小时时降至左心室的27.1%，而正常区域与真正缺血区域之间的深染区域随时间增加，表明血液从正常周围组织流向边界。通过缺乏氯化三苯基四氮唑染色确定的梗死区域在3小时后变得明显，并在12小时时稳定（占左心室的42%）。通过其氯乙酸酯酶染色区分的心脏中多形核白细胞计数逐渐增加，在24小时时达到每切片5500个细胞。在液氮中冷冻跳动的心脏后通过放射免疫测定法测定的白三烯B4浓度增加到假手术心脏的8倍，并在白细胞计数达到最大值之前的8小时达到峰值（每颗心脏9.4(0.6) ng，平均值(标准误)，n = 5）。在结扎前1小时单次口服一剂选择性5-脂氧合酶抑制剂（AA-861，80 mg·kg-1）可将白三烯B4浓度降低至假手术心脏的水平，并在12小时和24小时时分别使白细胞计数减少49.4%和41.2%。该抑制剂还使48小时时的梗死面积减少34.4%。得出的结论是，缺血性心脏组织中产生的白三烯B4可能通过多形核白细胞的迁移增加梗死面积。
