Hyperglycemia attenuates myocardial preconditioning of remifentanil
Hyun Soo Kim ; So Yeon Kim ; Yon Hee Shim ; Ki Chul Hwang ; Young Lan Kwak
Journal of Surgical Research, Vol.174(2) : 231~237, 2012
Journal of Surgical Research
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.