Document Detail


Inhibition of thromboxane synthetase by the imidazole derivative 3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid as a novel therapeutic approach to experimental myocardial ischemia.
MedLine Citation:
PMID:  3768069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3-(1H-imidazol-1-yl-methyl)-2-methyl-1H-indole-1-propanoic acid (UK 38.485), a novel imidazole derivative, was employed to study potential protective effects of thromboxane synthetase inhibition on ischemically stressed canine myocardium. In anaesthetized open-chest mongrel dogs (n = 5) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the left anterior descending artery. A total of 18 occlusions after therapy was analysed and compared to a total of 15 occlusions under control conditions. In each experiment 2-3 control occlusions and 3-4 occlusions under therapy were performed. The drug was applicated intravenously at a dose of 5 mg/kg body weight 30 min before the first therapy occlusion. Hemodynamics and energetics did not significantly change. The efficiency of the drug in protecting ischemically stressed myocardium was examined by the amounts of potassium, inorganic phosphate and lactate released in the first minute of reperfusion and by quantification of 02-debt and 02-repayment in the occlusion and reperfusion periods. Compared to control occlusions, premedication with UK 38.485 led to a reduced 02-debt (-39.1%; p less than 0.01) combined with a significant decrease of the release of potassium (-15.7%; p less than 0.001), inorganic phosphate (-20.2%; p less than 0.002) and lactate (-20.7%; p less than 0.01). The protective effect is suggested to be mainly due to enhanced flow to ischemic areas regarding a significant lesser reduction of myocardial blood flow and an improved oxygen uptake during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Authors:
H Korb; A Hoeft; W Wober; H G Wolpers; G Hellige
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arzneimittel-Forschung     Volume:  36     ISSN:  0004-4172     ISO Abbreviation:  Arzneimittelforschung     Publication Date:  1986 Jul 
Date Detail:
Created Date:  1986-11-03     Completed Date:  1986-11-03     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372660     Medline TA:  Arzneimittelforschung     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  1040-4     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Disease / drug therapy*,  metabolism,  physiopathology
Dogs
Energy Metabolism / drug effects
Heart / drug effects
Hemodynamics / drug effects
Imidazoles / therapeutic use*
Myocardium / metabolism
Oxygen Consumption / drug effects
Thromboxane-A Synthase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Imidazoles; 76894-77-4/dazmegrel; EC 5.3.99.5/Thromboxane-A Synthase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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