Cardiovascular effects of leukotoxin (9,10-epoxy-12-octadecenoate) and free fatty acids in dogs

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·dr1 from 2040(205) to 1140(217) mmHg·s−1, and aortic pressure from 106(7. l)/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.l)/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.