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Titolo:
THE EFFECTS OF BARIUM, DOFETILIDE AND LF-AMINOPYRIDINE (4-AP) ON VENTRICULAR REPOLARIZATION IN NORMAL AND HYPERTROPHIED RABBIT HEART
Autore:
GILLIS AM; GEONZON RA; MATHISON HJ; KULISZ E; LESTER WM; DUFF HJ;
Indirizzi:
UNIV CALGARY,DEPT MED,CARDIOVASC RES GRP,3330 HOSP DR NW CALGARY AB T2N 4N1 CANADA UNIV CALGARY,DEPT PATHOL,CARDIOVASC RES GRP CALGARY AB T2N 4N1 CANADA
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 285, anno: 1998,
pagine: 262 - 270
SICI:
0022-3565(1998)285:1<262:TEOBDA>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSIENT OUTWARD CURRENT; SUDDEN CARDIAC DEATH; RECTIFIER K+-CURRENT; MECHANOELECTRICAL FEEDBACK; ACTION-POTENTIALS; POTASSIUM CURRENTS; PRESSURE-OVERLOAD; MYOCYTES; FAILURE; MYOCARDIUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
50
Recensione:
Indirizzi per estratti:
Citazione:
A.M. Gillis et al., "THE EFFECTS OF BARIUM, DOFETILIDE AND LF-AMINOPYRIDINE (4-AP) ON VENTRICULAR REPOLARIZATION IN NORMAL AND HYPERTROPHIED RABBIT HEART", The Journal of pharmacology and experimental therapeutics, 285(1), 1998, pp. 262-270

Abstract

The density of potassium channels, including the inward rectifying current (I-K1), the delayed rectifying current and the transient outwardcurrent have been reported to be decreased in cardiac hypertrophy. However, it is not known whether the effects of specific ionic channel blockers are altered in this setting. The effects of barium chloride, which inhibits I-K1, of dofetilide, which inhibits the rapidly activating component of the delayed rectifying current, and 4-aminopyridine, which inhibits the transient outward current, were studied in isolated perfused working rabbit hearts. Cardiac hypertrophy was induced in rabbits by aortic banding. Hearts were removed 43 +/- 8 days after surgery, and electrophysiologic parameters were measured at low (30 cm H2O) and high (100 cm H2O) afterload at base line and during perfusion of barium, dofetilide or 4-aminopyridine. The hearts from banded rabbits weighed more (13.0 +/- 2.3 g) than those from the sham controls (10.0 +/- 1.6 g; P < .001). The action potential duration at 90% repolarization (APD(90)) was greater in hypertrophied hearts (198 +/- 16 msec) at base line than in control hearts (182 +/- 20 msec; P < .01). Barium (0.025 mM) caused greater prolongation of APD(90) in hypertrophied hearts than in control hearts at both low afterload (214 +/- 9 msec vs. 195+/- 20 msec) and high afterload (200 +/- 10 msec vs. 166 +/- 22 msec,P < .01). This interaction of barium's effects on APD(90) and hypertrophy was highly statistically significant (P < .001). In contrast, dofetilide (15 nM) and 4-aminopyridine (1.0 mM) caused similar changes inAPD(90) in hypertrophied hearts and in control hearts at low afterload and high afterload (P = NS). In isolated ventricular myocytes, I-K1 and transient outward densities, but not the rapidly activating component of the delayed rectifying current were decreased in hypertrophied cells compared with control cells (P < .05). Thus the increased effects of barium on prolongation of APD in hypertrophy are probably due to the decreased density of I-K1 in hypertrophy and perhaps, in part, to a change in the balance of repolarizing currents that occurs in hypertrophy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/12/20 alle ore 13:54:01