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Titolo:
USE OF CHLORIDE BLOCKERS - A NOVEL-APPROACH FOR CARDIOPROTECTION AGAINST ISCHEMIA-REPERFUSION DAMAGE
Autore:
TANAKA H; MATSUI S; KAWANISHI T; SHIGENOBU K;
Indirizzi:
TOHO UNIV,SCH PHARMACEUT SCI,DEPT PHARMACOL,2-2-1 MIYAMA FUNABASHI CHIBA 274 JAPAN NATL INST HLTH SCI,DIV BIOL CHEM & BIOL TOKYO JAPAN
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 278, anno: 1996,
pagine: 854 - 861
SICI:
0022-3565(1996)278:2<854:UOCB-A>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
INTRACELLULAR SODIUM ACTIVITY; EARLY CONTRACTILE FAILURE; CYTOSOLIC FREE CALCIUM; PIG VENTRICULAR CELLS; NA+-H+ EXCHANGE; ADENOSINE-TRIPHOSPHATE; RAT-HEART; ANTIARRHYTHMIC APPROACH; SARCOPLASMIC-RETICULUM; INORGANIC-PHOSPHATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
64
Recensione:
Indirizzi per estratti:
Citazione:
H. Tanaka et al., "USE OF CHLORIDE BLOCKERS - A NOVEL-APPROACH FOR CARDIOPROTECTION AGAINST ISCHEMIA-REPERFUSION DAMAGE", The Journal of pharmacology and experimental therapeutics, 278(2), 1996, pp. 854-861

Abstract

We examined whether the chloride channel blockers anthracene-9-carboxylic acid (9-AC) and cetamide-4'-isothiocyanatostilbene-2,2'-disulfonic acid (SITS) exert protective effects against myocardial ischemia-reperfusion damage. In isolated guinea pig ventricular cells, 9-AC (200 mu M), but not SITS (100 mu M), inhibited the chloride current induced by isoproterenol. Electrical and mechanical activities and intracellular pH of arterially perfused guinea pig right ventricular preparationswere recorded with an intracellular microelectrode, a force transducer and a pH-sensitive fluorescent probe, respectively. The preparationswere subjected to 30 min of no-flow ischemia, with or without 9-AC (100 mu M) or SITS (10 mu M), followed by reperfusion. No-flow ischemia produced decreases in action potential amplitude and duration, and thecontractile force was completely abolished. Although the changes in electrical parameters were reversed upon reperfusion, the contractile force recovered only to about 50% of preischemic values. 9-AC and SITS had no inhibitory effect on contractile force under normal conditions and during ischemia but significantly improved the recovery of contractile force upon reperfusion to about 80% of preischemic values. Both 9-AC and SITS showed significant inhibition of the ischemia-induced abbreviation of action potential duration. Other parameters were not affected by 9-AC or SITS. During ischemia, intracellular pH showed a transient small increase followed by a sustained decrease, which was completely recovered upon reperfusion. The decrease in pH during ischemia was attenuated by 80% in SITS-but not 9-AC-treated preparations. Thus, we demonstrated that the chloride channel blockers 9-AC and SITS, whichhave no cardiosuppressive effects, exert protective effects against myocardial ischemia-reperfusion damage.

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Documento generato il 01/12/20 alle ore 09:44:28