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Role of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase-3 beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning in isolated human right atria.
Lemoine, Sandrine; Zhu, Lan; Beauchef, Gallic; Lepage, Olivier; Babatasi, Gérard; Ivascau, Caline; Massetti, Massimo; Galera, Philippe; Gérard, Jean-Louis; Hanouz, Jean-Luc.
Afiliação
  • Lemoine S; Laboratory of Experimental Anesthesiology and Cellular Physiology EA3212, Institut Fédératif de Recherche ICORE146 Université de Caen Basse Normandie, Caen, France.
Anesthesiology ; 112(6): 1355-63, 2010 Jun.
Article em En | MEDLINE | ID: mdl-20460998
ABSTRACT

BACKGROUND:

Desflurane during early reperfusion has been shown to postcondition human myocardium. Whether it involves "reperfusion injury salvage kinase" pathway remains incompletely studied. The authors tested the involvement of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, glycogen synthase kinase (GSK)-3beta, and mitochondrial permeability transition pore in desflurane-induced postconditioning.

METHODS:

The authors recorded isometric contraction of human right atrial trabeculae suspended in an oxygenated Tyrode's solution (34 degrees C, stimulation frequency 1 Hz). After a 30-min hypoxic period, desflurane 6% was administered during the first 5 min of reoxygenation. Desflurane was administered alone or with pretreatment of rapamycin, a 70-kDa ribosomal protein S6 kinase inhibitor, NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, and atractyloside, the mitochondrial permeability transition pore opener. GSK-3beta inhibitor VII was administered during the first few minutes of reoxygenation alone or in the presence of desflurane 6%, rapamycin, NG-nitro-L-arginine methyl ester, and atractyloside. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). Phosphorylation of GSK-3beta was measured using blotting.

RESULTS:

Desflurane 6% (84 +/- 4% of baseline) enhanced the recovery of force after 60 min of reoxygenation when compared with the control group (54 +/- 4%, P < 0.0001). Rapamycin (68 +/- 8% of baseline), NG-nitro-L-arginine methyl ester (57 +/- 8%), atractyloside (52 +/- 7%) abolished desflurane-induced postconditioning (P < 0.001). GSK-3beta inhibitor-induced postconditioning (84 +/- 5%, P < 0.0001 vs. control) was not modified by desflurane (78 +/- 6%), rapamycin (81 +/- 6%), and NG-nitro-L-arginine methyl ester (82 +/- 10%), but it was abolished by atractyloside (49 +/- 6%). Desflurane increased the phosphorylation of GSK-3beta (3.30 +/- 0.57-fold increase in desflurane vs. control; P < 0.0001).

CONCLUSIONS:

In vitro, desflurane-induced postconditioning protects human myocardium through the activation of 70-kDa ribosomal protein S6 kinase, nitric oxide synthase, inhibition, and phosphorylation of GSK-3beta, and preventing mitochondrial permeability transition pore opening.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Função do Átrio Direito / Óxido Nítrico Sintase / Quinase 3 da Glicogênio Sintase / Proteínas Quinases S6 Ribossômicas 70-kDa / Proteínas de Transporte da Membrana Mitocondrial / Isoflurano Limite: Humans Idioma: En Revista: Anesthesiology Ano de publicação: 2010 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 1_ASSA2030 / 2_ODS3 Base de dados: MEDLINE Assunto principal: Função do Átrio Direito / Óxido Nítrico Sintase / Quinase 3 da Glicogênio Sintase / Proteínas Quinases S6 Ribossômicas 70-kDa / Proteínas de Transporte da Membrana Mitocondrial / Isoflurano Limite: Humans Idioma: En Revista: Anesthesiology Ano de publicação: 2010 Tipo de documento: Article