Hyperglycemia attenuates myocardial preconditioning of remifentanil

Hyun Soo Kim, So Yeon Kim, Young Lan Kwak, Ki Chul Hwang, Yon Hee Shim

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Hyperglycemia attenuates cardioprotection by remifentanil-preconditioning in ischemia-reperfusion in vivo in diabetic rats. However, the effects of hyperglycemia in cultured ventricular myocytes remains unknown. Therefore, we examined the in vitro effects of hyperglycemia on hypoxia-reoxygenation (H/R) and cardioprotection from remifentanil- preconditioning in isolated neonatal rat ventricular myocytes (NRVMs), including effects on apoptotic signaling pathways and Ca 2+ homeostasis. Materials and Methods: NRVMs were cultured in medium with 5.5 mM (normoglycemia) or 25.5 mM glucose for one day. Then, NRVMs in H/R groups were exposed to 1 h of hypoxia and 5 h of reoxygenation with or without remifentanil-preconditioning at 1 μM. Cell viability, apoptosis, and Ca 2+ homeostasis were assessed by MTT assay, caspase-3 assay, confocal microscopy and immunoblots. Results: In normoglycemia, remifentanil-preconditioning improved the viability of cardiomyocytes (P < 0.01) and prevented the increase of caspase-3 activity and Ca 2+ overload after H/R injury (P < 0.05). In addition, decrease in Akt, ERK1/2, and Bcl-2, and the increase in Bax by H/R was attenuated by remifentanil-preconditioning (P < 0.05). However, in hyperglycemia, the viability was partially impaired after H/R but not improved by remifentanil-preconditioning. Apoptotic activity, Ca 2+ concentration, and apoptotic kinases except Akt were not affected by either H/R or remifentanil-preconditioning under hyperglycemia. Akt phosphorylation was decreased by H/R but not restored by remifentanil preconditioning. Conclusions: Remifentanil preconditioning under normoglycemia renders NRVMs resistant to H/R injury by reducing apoptosis and intracellular Ca 2+ concentrations. The mechanism appears to be modulation of apoptotic signaling. However, hyperglycemia mitigates H/R injury in NRVMs, and may reduce the protective effect of remifentanil-preconditioning that may be associated with the Akt pathways.

Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalJournal of Surgical Research
Volume174
Issue number2
DOIs
Publication statusPublished - 2012 May 15

All Science Journal Classification (ASJC) codes

  • Surgery

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