Cardioprotection Via Modulation of Calcium Homeostasis by Thiopental in Hypoxia-Reoxygenated Neonatal Rat Cardiomyocytes

Purpose: Ca 2+ homeostasis plays an important role in myocardial cell injury induced by hypoxia-reoxygenation, and prevention of intracellular Ca 2+ overload is key to cardioprotection.Even though thiopental is a frequently used anesthetic agent, little is known about its cardioprotective effects, particulary in association with Ca 2+ homeostasis.We investigated whether thiopental protects cardiomyocytes against hypoxia-reoxygenation injury by regulating Ca 2+ homeostasis.Materials and Methods: Neonatal rat cardiomyocytes were isolated.Cardiomyocytes were exposed to different concentrations of thiopental and immediately replaced in the hypoxic chamber to maintain hypoxia.After 1 hour of exposure, a culture dish was transferred to the CO2 incubator and cells were incubated at 37˚C for 5 hours.At the end of the experiments, the authors assessed cell protection using immunoblot analysis and caspase activity.The mRNA of genes involved in Ca 2+ homeostasis, mitochondrial membrane potential, and cellular Ca 2+ levels were examined.Results: In thiopental-treated cardiomyocytes, there was a decrease in expression of the proapoptotic protein Bax, caspase-3 activation, and intracellular Ca 2+ content.In addition, both enhancement of anti-apoptotic protein Bcl-2 and activation of Erk concerned with survival were shown.Furthermore, thiopental attenuated alterations of genes involving Ca 2+ regulation and significantly modulated abnormal changes of NCX and SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes.Thiopental suppressed disruption of mitochondrial membrane potential (∆Ψm) induced by hypoxia-reoxygenation.Conclusion: Thiopental is likely to modulate expression of genes that regulate Ca 2+ homeostasis, which reduces apoptotic cell death and results in cardioprotection.