Pharmacological inhibition of leukotriene biosynthesis: effects on the heart conductance.
Leukotrienes are lipid mediators produced via 5-lipooxygenase pathway of arachidonic acid. At least two cysteinyl-leukotrienes receptors are highly expressed in the heart, including the conduction system. Coronary angiography or angioplasty is accompanied by release of cysteinyl leukotrienes into coronary circulation and into urine. We tested the hypothesis that inhibition of leukotrienes biosynthesis would affect the conductance system function. In a double-blind placebo controlled study, patients with stable angina undergoing elective coronary catheterization or angioplasty were randomly assigned to 48 hrs treatment with a 5-lipoxgenase inhibitor (n=54) or placebo (n=49). ECG Holter recording was carried out for 24 hrs before and after the procedure and urinary leukotriene E(4) measurements were done. Inhibition of 5-lipoxygenase caused 26% reduction of urinary leukotriene E(4), associated with: 1) decrease in heart rate by about 7%, 2) enhanced heart rate variability; 3) protection against depressions in atrioventricular conductance and ventricular repolarization induced by the procedure. No effects on either arrhythmias, or ECG patterns of ischemia were noted. We conclude that pharmacological inhibition of 5-lipoxygenase, shortly before percutaneous coronary intervention, reveals specific actions of leukotrienes on the heart rhythm. Inhibitors of 5-lipoxygenase might be of interest as a novel class of cardiac drugs affecting the conductive system.
Sanak
M
M
Department of Medicine, Jagiellonian University Medical College, Cracow, Poland.
Dropinski
J
J
Sokolowska
B
B
Faber
J
J
Rzeszutko
M
M
Szczeklik
A
A
D000368:Aged; D000789:Angina, Unstable / Q000188:drug therapy / Q000201:enzymology / Q000652:urine; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis; D004311:Double-Blind Method; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000201:enzymology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D017999:Leukotriene E4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000652:urine; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D017999:Leukotriene E4; D001094:Arachidonate 5-Lipoxygenase