Document Detail


Antiarrhythmic, metabolic and hemodynamic effects of Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) after coronary flow reduction in pigs.
MedLine Citation:
PMID:  633069     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The antiarrhythmic activity of the aminosteroid Org 6001 was investigated in young pigs (20-28 kg). Ventricular arrhythmias were induced by restriction of the flow in the left anterior descending coronary artery (LAD) to 25% of its control value during a period of 30 minutes. Nine out of 30 control animals died in this period due to ventricular fibrillation. None of the 19 animals treated with Org 6001 (5-10 mg/kg) or the 12 animals treated with lidocaine (2.75-3.50 mg/kg) fibrillated. Moreover, the number of premature ventricular beats was greatly reduced in pretreated groups compared with the untreated group (P less than .001). The first derivative of left ventricular pressure decreased with 25% (P less than 0.001) after administration of Org 6001. However, during 30 minutes of LAD flow reduction to 25% of control, the adverse effects of Org 6001 were less than those of lidocaine. Myocardial lactate production indicated some delay in onset of ischemia. However, there was no indication that this beneficial effect was long-lasting. When after 30 minutes of LAD flow reduction to 25% of control, the LAD was completely occluded between its second and third branch, all untreated animals fibrillated within 120 minutes, whereas 4 of the 19 animals treated with Org 6001 and 3 of the 12 treated with lidocaine survived. It is concluded that Org 6001 has antiarrhythmic properties in the ischemic pig heart which compare favorably with those of lidocaine.
Authors:
P D Verdouw; H C Schamhardt; W J Remme; J W De Jong
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  204     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1978 Mar 
Date Detail:
Created Date:  1978-05-24     Completed Date:  1978-05-24     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  634-44     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
17-Ketosteroids / pharmacology
Androstanes / pharmacology*
Animals
Anti-Arrhythmia Agents*
Blood Gas Analysis
Coronary Disease / metabolism,  physiopathology*
Hemodynamics / drug effects*
Lactates / metabolism
Lidocaine / pharmacology
Myocardium / metabolism*
Potassium / metabolism
Swine
Chemical
Reg. No./Substance:
0/17-Ketosteroids; 0/Androstanes; 0/Anti-Arrhythmia Agents; 0/Lactates; 137-58-6/Lidocaine; 7440-09-7/Potassium

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


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