Linked Life Data

10980278

Source:http://linkedlifedata.com/resource/pubmed/id/10980278

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-10-26
pubmed:abstractText
The effect of N-[4-[2-N-methyl-N-[1-methyl-2-(2, 6-dimethylphenoxy)ethylamino]-ethyl]-phenyl]-methanesulfonamide. hydrochloride (GYKI-16638; 0.03 and 0.1 mg/kg, i.v.), a novel antiarrhythmic compound, was assessed and compared to that of D-sotalol (1 and 3 mg/kg, i.v.) on arrhythmias induced by 10 min of coronary artery occlusion and 10 min of reperfusion in anaesthetized rabbits. Also, its cellular electrophysiological effects were studied in rabbit right ventricular papillary muscle preparations and in rabbit single isolated ventricular myocytes. In anaesthetized rabbits, intravenous administration of 0.03 and 0.1 mg/kg GYKI-16638 and 1 and 3 mg/kg D-sotalol significantly increased survival during reperfusion (GYKI-16638: 82% and 77%, D-sotalol: 75% and 83% vs. 18% in controls, P<0.05, respectively). GYKI-16638 (0.1 mg/kg) significantly increased the number of animals that did not develop arrhythmias during reperfusion (46% vs. 0% in controls, P<0.05). In isolated rabbit right ventricular papillary muscle, 2 microM GYKI-16638, at 1 Hz stimulation frequency, lengthened the action potential duration at 50% and 90% repolarization (APD(50-90)) without influencing the resting membrane potential and action potential amplitude (APA). It decreased the maximal rate of depolarization (V(max)) in a use-dependent manner. This effect was statistically significant only at stimulation cycle lengths shorter than 700 ms. The offset kinetics of this V(max) block were relatively rapid, the corresponding time constant for recovery of V(max) was 328.2+/-65.0 ms. In patch-clamp experiments, performed in rabbit ventricular myocytes, 2 microM GYKI-16638 markedly depressed the rapid component of the delayed rectifier outward and moderately decreased the inward rectifier K(+) current without significantly altering the slow component of the delayed rectifier and transient outward K(+) currents. These results suggest that in rabbits, GYKI-16638 has an in vivo antiarrhythmic effect, comparable to that of D-sotalol, which can be best explained by its combined Class I/B and Class III actions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
404
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
181-90
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10980278-Action Potentials, pubmed-meshheading:10980278-Anesthesia, pubmed-meshheading:10980278-Animals, pubmed-meshheading:10980278-Anti-Arrhythmia Agents, pubmed-meshheading:10980278-Arrhythmias, Cardiac, pubmed-meshheading:10980278-Disease Models, Animal, pubmed-meshheading:10980278-Electrophysiology, pubmed-meshheading:10980278-Heart, pubmed-meshheading:10980278-Heart Ventricles, pubmed-meshheading:10980278-Hemodynamics, pubmed-meshheading:10980278-Male, pubmed-meshheading:10980278-Myocardial Ischemia, pubmed-meshheading:10980278-Myocardium, pubmed-meshheading:10980278-Papillary Muscles, pubmed-meshheading:10980278-Phenethylamines, pubmed-meshheading:10980278-Potassium Channels, pubmed-meshheading:10980278-Rabbits, pubmed-meshheading:10980278-Reperfusion, pubmed-meshheading:10980278-Sotalol, pubmed-meshheading:10980278-Sulfonamides, pubmed-meshheading:10980278-Time Factors, pubmed-meshheading:10980278-Ventricular Function
pubmed:year
2000
pubmed:articleTitle
Antiarrhythmic and electrophysiological effects of GYKI-16638, a novel N-(phenoxyalkyl)-N-phenylalkylamine, in rabbits.
pubmed:affiliation
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged and Research Unit of the Hungarian Academy of Sciences, Dóm tér 12, P.O. Box 427, H-6701, Szeged, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't