Myocardial protection provided by chronic skeletal muscle ischemia is not further enhanced by ischemic pre- or postconditioning: comparative effects on intracellular signaling.
J Cardiovasc Pharmacol Ther
; 19(2): 220-7, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24177336
ABSTRACT
Chronic skeletal muscle ischemia protects the ischemic heart by preserving coronary flow and inducing arterioangiogenesis. We sought to determine the effect and the underlying molecular mechanisms of preconditioning (PreC) and postconditioning (PostC), applied in a model of chronic skeletal muscle ischemia. Male rabbits were divided into 3 series. In each series, the animals were subjected either to severe hind limb (HL) ischemia, by excision of the femoral artery, or to sham operation (SHO). After 4 weeks, all the animals underwent 30 minutes of regional heart ischemia and 3 hours reperfusion. The animals of the first series received no further intervention (HL and SHO groups), those of the second series underwent PreC (HL + PreC and SHO + PreC), and of the third series PostC (HL + PostC and SHO + PostC). Infarct size (I) and risk zones (R) were determined, and their ratio was calculated in percentage. Three additional series of experiments were performed with respective interventions up to the 10th minute of reperfusion, where sample tissue was obtained for assessment of protein kinase B (Akt), endothelial nitric oxide synthase (eNOS), glycogen synthase kinase 3ß (GSK3ß), p44/42, signal transducer and activator of transcription (STAT) 3, and STAT5. All groups demonstrated significantly smaller percentage of I/R compared with the SHO group (HL 14.4% ± 3.7%, HL + PreC 13.1% ± 1.0%, SHO + PreC 21.3% ± 1.6%, HL + PostC 18.0% ± 1.1%, and SHO + PostC 24.3% ± 1.7%, P < .05 vs 35.7% ± 4.4% in SHO). The PreC and PostC did not further reduce the infarct size in HL groups. The Akt, eNOS, GSK3ß, p44/42, and STAT3 were activated in all PreC or PostC groups regardless of the infarct size reduction. The STAT5 was activated only in the HL groups compared with the SHO groups. In conclusion, chronic skeletal muscle ischemia results in effective cardioprotection, which is not further enhanced with application of PreC or PostC. The Akt, eNOS, GSK3ß, p44/42, and STAT3 may only be considered as indicators of the intracellular changes taking place during protection. Activation of STAT5 is possibly the end effector, which is responsible for infarct size reduction provided by chronic skeletal muscle ischemia.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Músculo Esquelético
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Precondicionamento Isquêmico Miocárdico
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Líquido Intracelular
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Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article