ENHANCED EXCRETION OF URINARY LEUKOTRIENE-E(4) IN CORONARY-ARTERY DISEASE AND AFTER CORONARY-ARTERY BYPASS-SURGERY

Background: Excretion of leukotriene (LT) E4, the major urinary metabolite of cysteinyl leukotrienes in humans, is increased in patients with unstable angina and myocardial infarction, suggesting that cysteinyl leukotrienes are released into the circulation during episodes of myocardial ischaemia. Furthermore, leukotrienes are known to induce potent vasoconstrictive effects in human atherosclerotic coronary arteries and the saphenous vein. Accordingly, we measured urinary excretion of LTE4 in patients with stable coronary artery disease both before and after coronary artery bypass surgery, and in age-matched healthy controls, to study the relation between the systemic synthesis of cysteinyl leukotrienes and stable coronary artery disease, as well as the possible changes after bypass surgery. Methods: LTE4 was isolated from urine samples by solid-phase extraction, purified by reverse-phase high-performance liquid chromatography, and subsequently quantified by radioimmunoassay. Results: In patients with coronary artery disease, preoperative urinary LTE4 levels were normally distributed on a log10 scale, with a geometric mean of 115 pmol/mmol creatinine (95% confidence interval 67-196) compared with 63.0 pmol/mmol creatinine (95% confidence interval 47.9-82.7) in healthy subjects (P<0.05). Urinary LTE4 levels increased further in patients after coronary artery bypass surgery with levels peaking on the second day after surgery (266.2 pmol/mmol creatinine, 95% confidence interval 167.2-423.9) at significantly higher than preoperative levels (P<0.02), and then decreasing by day 3. Conclusions: Levels of cysteinyl leukotrienes are raised in coronary artery disease patients both before and after coronary artery bypass surgery. As these mediators are capable of inducing potent vasoconstrictive effects on atherosclerotic coronary arteries and the saphenous vein, our results could have important clinical and possibly therapeutic implications.