Circulation, Vol 85, 230-236, Copyright © 1992 by American Heart Association
M Carry, V Korley, JT Willerson, L Weigelt, AW Ford-Hutchinson and P Tagari
BACKGROUND. Experimental cardiac ischemia in some animal models results in
the activation of the enzyme 5-lipoxygenase and the subsequent production
of leukotrienes, potent proinflammatory lipid mediators, by the affected
myocardium. Furthermore, prototype antileukotriene drugs can show some
beneficial effects on infarct size and cardiac function in these models.
Accordingly, urinary excretion of leukotriene E4 (LTE4), the major urinary
metabolite of peptide leukotrienes in humans, was measured in patients
admitted to the hospital with evidence of acute myocardial ischemia to
assess in vivo release of 5-lipoxygenase products during and after the
ischemic episode. METHODS AND RESULTS. Urinary leukotriene excretion was
measured by reversed-phase high- performance liquid chromatography and
specific radioimmunoassay on admission with acute chest pain and again on
day 3 in the following patient groups: acute myocardial infarction (AMI),
AMI and clinical evidence of early reperfusion after treatment with
recombinant tissue- type plasminogen activator (rt-PA), diagnosis of
unstable angina (UA) based on clinical history and coronary arteriography,
controls with nonischemic chest pain who underwent coronary arteriography,
and age- matched controls and normal hospital employees. In 16 patients
with diagnosis of AMI, LTE4 excretion on admission (331 +/- 99 pg/mg
creatinine sulfate; mean +/- SEM) was considerably higher than that
measured on day 3 (195 +/- 59 pg/mg creatinine sulfate). In a subgroup of
seven subjects treated with rt-PA resulting in early reperfusion, day 1
excretion was similar (215 +/- 50 pg/mg) but had significantly declined by
day 3 (65 +/- 16 pg/mg; p less than 0.01). Urinary LTE4 excretion at
admission for chest pain was also elevated in 14 patients having unstable
angina (UA; 370 +/- 125 pg LTE4/mg creatinine sulfate). This had declined
significantly (p less than 0.05) by day 3 (at which time chest pain had
resolved) to 94 +/- 31 pg/mg creatinine sulfate, an excretion rate
comparable with that measured in eight similarly aged subjects (64 +/- 12
pg/mg creatinine). CONCLUSIONS. This study suggests that peptide
leukotrienes are released during episodes of myocardial ischemia and
provides clinical evidence for involvement of their biosynthetic enzyme,
5-lipoxygenase, during and after acute myocardial infarction and unstable
angina attacks. Thus, potent and specific orally active leukotriene
biosynthesis inhibitors may have therapeutic potential in limiting
myocardial damage and functional abnormalities after acute ischemia.
ARTICLES
Increased urinary leukotriene excretion in patients with cardiac ischemia. In vivo evidence for 5-lipoxygenase activation
H.L. and Ruth Ray Hunt Heart Center, Baylor University Medical Center, Dallas, Tex.
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