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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1995-6-22
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pubmed:abstractText |
We studied the electrophysiologic and antifibrillatory properties of MS-551 (1,3-dimethyl-6-((2-[N-hydroxy-ethyl)-3-(4-nitrophenyl) propylamino] ethylamino) 2,4(1H,3H) pyrimidinedione hydrochloride) in a conscious canine model of sudden cardiac death. Three to 5 days after surgically induced myocardial infarction (MI: 2-h occlusion of the left anterior descending coronary artery, LAD), animals were subjected to programmed electrical stimulation (PES) to identify those at risk for sudden cardiac death. MS-551 was administered (2.0, 3.0, or 4 x 2.0 mg/kg intravenously, i.v.). Vehicle-treated animals received 0.9% sodium chloride solution for injection. MS-551 (multiple-dose regimen) increased ventricular effective refractory period (VERP) from 112 +/- 4 to 137 +/- 4 ms (p < 0.05) as compared with vehicle treatment, which did not alter VERP (125 +/- 6 to 121 +/- 5 ms). MS-551 prolonged QTc interval from a predrug value of 293 +/- 8 to 333 +/- 18 ms postdrug. The size of surgically induced MI did not differ among groups: 2.0 mg/kg, 23 +/- 4%; 3.0 mg/kg, 28 +/- 2%; 4 x 2.0 mg/kg, 25 +/- 3%; and vehicle, 28 +/- 3% of the left ventricle. Single bolus administration of MS-551 (2.0 or 3.0 mg/kg i.v.) did not confer significant protection against sudden cardiac death. However, repeated administration of MS-551 protected against sudden cardiac death in 8 of 10 dogs as compared with 2 of 12 in the vehicle-treated group (p < 0.05). The data indicate that a multiple-dose regimen of MS-551 provides protection against ischemia-induced ventricular fibrillation (VF) in the postinfarcted heart. The mechanism by which MS-551 achieves its antifibrillatory effect most likely depends on its ability to prolong VERP of myocardium without altering ventricular conduction velocity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0160-2446
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
314-23
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7752658-Animals,
pubmed-meshheading:7752658-Anti-Arrhythmia Agents,
pubmed-meshheading:7752658-Chromatography, High Pressure Liquid,
pubmed-meshheading:7752658-Death, Sudden, Cardiac,
pubmed-meshheading:7752658-Disease Models, Animal,
pubmed-meshheading:7752658-Dogs,
pubmed-meshheading:7752658-Dose-Response Relationship, Drug,
pubmed-meshheading:7752658-Electric Stimulation,
pubmed-meshheading:7752658-Electrocardiography,
pubmed-meshheading:7752658-Electrophysiology,
pubmed-meshheading:7752658-Male,
pubmed-meshheading:7752658-Myocardial Infarction,
pubmed-meshheading:7752658-Pyrimidinones,
pubmed-meshheading:7752658-Random Allocation,
pubmed-meshheading:7752658-Ventricular Fibrillation
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pubmed:year |
1995
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pubmed:articleTitle |
MS-551 protects against ventricular fibrillation in a chronic canine model of sudden cardiac death.
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pubmed:affiliation |
University of Michigan Medical School, Department of Pharmacology, Ann Arbor 48109-0632, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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