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 metabo lite of cysteinyl leukotrienes in humans, is increased in patients wit h unstable angina and myocardial infarction, suggesting that cysteinyl leukotrienes are released into the circulation during episodes of myo cardial ischaemia. Furthermore, leukotrienes are known to induce poten t 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 a fter coronary artery bypass surgery, and in age-matched healthy contro ls, to study the relation between the systemic synthesis of cysteinyl leukotrienes and stable coronary artery disease, as well as the possib le changes after bypass surgery. Methods: LTE4 was isolated from urine samples by solid-phase extraction, purified by reverse-phase high-per formance liquid chromatography, and subsequently quantified by radioim munoassay. Results: In patients with coronary artery disease, preopera tive urinary LTE4 levels were normally distributed on a log10 scale, w ith a geometric mean of 115 pmol/mmol creatinine (95% confidence inter val 67-196) compared with 63.0 pmol/mmol creatinine (95% confidence in terval 47.9-82.7) in healthy subjects (P<0.05). Urinary LTE4 levels in creased further in patients after coronary artery bypass surgery with levels peaking on the second day after surgery (266.2 pmol/mmol creati nine, 95% confidence interval 167.2-423.9) at significantly higher tha n preoperative levels (P<0.02), and then decreasing by day 3. Conclusi ons: Levels of cysteinyl leukotrienes are raised in coronary artery di sease patients both before and after coronary artery bypass surgery. A s these mediators are capable of inducing potent vasoconstrictive effe cts on atherosclerotic coronary arteries and the saphenous vein, our r esults could have important clinical and possibly therapeutic implicat ions.