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Titolo:
Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis
Autore:
Neviere, R; Fauvel, H; Chopin, C; Formtecher, P; Marchetti, P;
Indirizzi:
Fac Med, INSERM, U459, F-59045 Lille, France Fac Med Lille France F-59045 ac Med, INSERM, U459, F-59045 Lille, France Fac Med, Dept Physiol, Lille, France Fac Med Lille FranceFac Med, Dept Physiol, Lille, France
Titolo Testata:
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
fascicolo: 1, volume: 163, anno: 2001,
pagine: 218 - 225
SICI:
1073-449X(200101)163:1<218:CIPCDA>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
NECROSIS-FACTOR-ALPHA; MYOCARDIAL-CELL INJURY; HUMAN SEPTIC SHOCK; TNF-ALPHA; TUMOR; DEATH; ACTIVATION; ENDOTOXIN; MYOCYTES; INTERLEUKIN-1-BETA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Marchetti, P Fac Med, INSERM, U459, 1 Pl Verdun,EA 2689, F-59045 Lille, France Fac Med 1 Pl Verdun,EA 2689 Lille France F-59045 lle, France
Citazione:
R. Neviere et al., "Caspase inhibition prevents cardiac dysfunction and heart apoptosis in a rat model of sepsis", AM J R CRIT, 163(1), 2001, pp. 218-225

Abstract

Despite intensive therapy, severe septic shock is commonly associated withmyocardial dysfunction and death in humans. No new therapies have proven efficiency against cardiovascular alterations in sepsis. Here, we addressed the question of a beneficial effect of pharmacological inhibition of caspases on myocardial dysfunction following endotoxin treatment. Hearts from rats treated with endotoxin (10 mg/kg, intravenously) were isolated 4 h posttreatment for analysis. Assessment of myocardial contractility ex vivo and detection of apoptosis were performed. Hearts from endotoxin-treated rats displayed multiple caspase activities and also typical apoptosis pattern as detected by TUNEL, DNA fragmentation assays, and cytochrome c release as compared with control rats. z-VAD.fmk (3 mg/kg, intravenously), a broad spectrum caspase inhibitor (but not the irrelevant peptide z-FA.fmk), in coinjection with endotoxin, not only reduced caspase activities and nuclear apoptosis but also completely prevented endotoxin-induced myocardial dysfunction evaluated 4 h and even 14 h after endotoxin challenge. These data indicate that caspase activation plays an important role in myocardial cell dysfunction. Moreover, these results suggest that inhibitors of caspases may have important therapeutic applications in sepsis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 09:00:03