Document Detail


Pharmacological inhibition of leukotriene biosynthesis: effects on the heart conductance.
MedLine Citation:
PMID:  20228415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Sanak; J Dropinski; B Sokolowska; J Faber; M Rzeszutko; A Szczeklik
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Publication Detail:
Type:  Comparative Study; Controlled Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of physiology and pharmacology : an official journal of the Polish Physiological Society     Volume:  61     ISSN:  1899-1505     ISO Abbreviation:  J. Physiol. Pharmacol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-10-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9114501     Medline TA:  J Physiol Pharmacol     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  53-8     Citation Subset:  IM    
Affiliation:
Department of Medicine, Jagiellonian University Medical College, Cracow, Poland.
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MeSH Terms
Descriptor/Qualifier:
Aged
Angina, Unstable / drug therapy,  enzymology,  urine
Arachidonate 5-Lipoxygenase / antagonists & inhibitors,  biosynthesis
Double-Blind Method
Female
Heart Conduction System / drug effects*,  enzymology
Heart Rate / drug effects*,  physiology*
Humans
Leukotriene Antagonists / pharmacology*
Leukotriene E4 / antagonists & inhibitors,  biosynthesis,  urine
Leukotrienes* / biosynthesis,  metabolism,  physiology
Lipoxygenase Inhibitors / pharmacology
Male
Middle Aged
Chemical
Reg. No./Substance:
0/Leukotriene Antagonists; 0/Leukotrienes; 0/Lipoxygenase Inhibitors; 75715-89-8/Leukotriene E4; EC 1.13.11.34/Arachidonate 5-Lipoxygenase

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