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Titolo:
MS-551 PROTECTS AGAINST VENTRICULAR-FIBRILLATION IN A CHRONIC CANINE MODEL OF SUDDEN CARDIAC DEATH
Autore:
FRIEDRICHS GS; CHI L; GRALINSKI MR; BLACK SC; BASLER GC; MU DX; PEWITT SR; JOHNSON CR; LUCCHESI BR;
Indirizzi:
UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,1301 MED SCI RES BLDG III,1500 WMED CTR DR ANN ARBOR MI 48109
Titolo Testata:
Journal of cardiovascular pharmacology
fascicolo: 2, volume: 25, anno: 1995,
pagine: 314 - 323
SICI:
0160-2446(1995)25:2<314:MPAVIA>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
III ANTIARRHYTHMIC AGENT; TORSADES-DE-POINTES; MYOCARDIAL-INFARCTION; CORONARY DEATH; ORAL SOTALOL; TACHYCARDIA; RABBIT; DRUG; ARRHYTHMIAS; EFFICACY;
Keywords:
MS-551; CLASS III ANTIARRHYTHMIC; SUDDEN DEATH; K+ CHANNEL BLOCKER; CONSCIOUS DOGS; VENTRICULAR FIBRILLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
G.S. Friedrichs et al., "MS-551 PROTECTS AGAINST VENTRICULAR-FIBRILLATION IN A CHRONIC CANINE MODEL OF SUDDEN CARDIAC DEATH", Journal of cardiovascular pharmacology, 25(2), 1995, pp. 314-323

Abstract

We studied the electrophysiologic and antifibrillatory properties of MS-551 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 surgicallyinduced myocardial infarction (MI:2-h occlusion of the left anterior descending coronary artery, LAD), animals were subjected to programmedelectrical 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 apredrug 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.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/11/20 alle ore 19:35:34