Fukushima A, Hayakawa M, Sugiyama S, Ajioka M, Ito T, Satake T, Ozawa T
Department of Internal Medicine, Faculty of Medicine, University of Nagoya, Japan.
Cardiovasc Res. 1988 Mar;22(3):213-8. doi: 10.1093/cvr/22.3.213.
Leukotoxin (9,10-epoxy-12-octadecenoate) biosynthesised from linoleate by neutrophils is highly toxic to cellular function. Its cardiovascular effects were studied in dogs together with the effects of various fatty acids. Aortic flow, left ventricular peak dP.dt-1, and aortic pressure were measured in 60 anaesthetised dogs, which were divided into 10 groups of six animals each--namely, control group (10 ml of physiological saline), three leukotoxin groups (5, 10, and 50 mg.kg-1), two linoleic acid groups (10 and 50 mg.kg-1), two oleic acid groups (10 and 50 mg.kg-1), and two stearic acid groups (10 and 50 mg.kg-1). Leukotoxin injected intravenously depressed cardiac function in a dose dependent manner. Administration of leukotoxin 5 mg.kg-1 showed no significant cardiotoxic effect. However, 10 mg.kg-1 of leukotoxin significantly decreased aortic flow from 0.74(0.04) to 0.40(0.07) litre.min-1 (mean(SEM], left ventricular peak dP.dt-1 from 2040(205) to 1140(217) mmHg.s-1, and aortic pressure from 106(7.1)/67(6.3) to 75(9.2)/48(6.5) mmHg 5 min after injection. Dogs given leukotoxin 50 mg.kg-1 showed more pronounced cardiodepressive effects; aortic flow was decreased to 0.19(0.06), left ventricular dP.dt-1 to 560(134), and aortic pressure to 72(15.1)/41(10.6) 5 min after injection. All dogs in this group were dead within 45 min. Administration of 10 mg.kg-1 of linoleic acid, oleic acid, or stearic acid caused no significant haemodynamic changes. Administration of linoleic acid 50 mg.kg-1 had cardiotoxic effects, but the effect was less than that of leukotoxin. Since leukotoxin appears to be a potent cardiodepressive agent it may be an important factor in the development of heart failure observed in patients with severe burns.
中性粒细胞由亚油酸生物合成的白细胞毒素（9,10-环氧-12-十八碳烯酸）对细胞功能具有高度毒性。在犬类中研究了其心血管效应以及各种脂肪酸的效应。对60只麻醉犬测量主动脉血流量、左心室dp/dt最大值和主动脉压力，这些犬被分为10组，每组6只动物，即对照组（10ml生理盐水）、三个白细胞毒素组（5、10和50mg·kg-1）、两个亚油酸组（10和50mg·kg-1）、两个油酸组（10和50mg·kg-1）以及两个硬脂酸组（10和50mg·kg-1）。静脉注射白细胞毒素会以剂量依赖的方式抑制心脏功能。注射5mg·kg-1白细胞毒素未显示出明显的心脏毒性作用。然而，注射10mg·kg-1白细胞毒素后5分钟，主动脉血流量从0.74（0.04）显著降至0.40（0.07）升·分钟-1（平均值（标准误）），左心室dp/dt最大值从2040（205）降至1140（217）mmHg·秒-1，主动脉压力从106（7.1）/67（6.3）降至75（9.2）/48（6.5）mmHg。注射50mg·kg-1白细胞毒素的犬表现出更明显的心脏抑制作用；注射后5分钟，主动脉血流量降至0.19（0.06），左心室dp/dt降至560（134），主动脉压力降至72（15.1）/41（10.6）。该组所有犬在45分钟内死亡。注射10mg·kg-1亚油酸、油酸或硬脂酸未引起明显的血流动力学变化。注射50mg·kg-1亚油酸具有心脏毒性作用，但作用小于白细胞毒素。由于白细胞毒素似乎是一种强效的心脏抑制剂，它可能是重度烧伤患者发生心力衰竭的一个重要因素。
