Dexmedetomidine preconditioning attenuates global cerebral ischemic injury following asphyxial cardiac arrest

Abstract

Background/Aims: To investigate the protection effect of dexmedetomidine preconditioning on global cerebral ischemic injury following asphyxial cardiac arrest (CA) in rats. Methods: Seventy-two rats were randomly assigned into three groups, sham group (no asphyxia), control group (asphyxia only), and dexmedetomidine preconditioned group (asphyxia + dexmedetomidine). Dexmedetomidine was administered 5 minutes before an 8 min of asphyxia. Rats were resuscitated by a standardized method. Blood O₂ and CO₂ partial pressures were, pH, base excess (BE), and blood glucose concentration measured before asphyxial CA and 1 h after resuscitation. Neurological deficit score (NDS) was measured at 12, 24, 48, and 72 h after CA. Histopathologic changes in the hippocampal region were observed by H&E staining and histopathologic damage score. Ultrastructural morphology was observed by transmission electron microscopy. HIF-1 and VEGF expression were measured by immunostaining of serial sections obtained from brain tissue. Results: Asphyxial CA -induced global cerebral ischemic decreased PaO₂, pH, BE and increased PaCO₂, blood glucose. Dexmedetomidine preconditioning improved neurologic outcome, which was associated with reduction in histopathologic injury measured by H&E staining, the histopathologic damage score and electron microscopy. Dexmedetomidine preconditioning also elevated HIF-1α and VEGF expression after global cerebral ischemia following asphyxial CA. Conclusion: Dexmedetomidine preconditioning protected against cerebral ischemic injury and was associated with upregulation of HIF-1α and VEGF expression.

KEYWORDS:

• dexmedetomidine
• global cerebral ischemia
• asphyxial cardiac arrest
• HIF-1α
• VEGF

Acknowledgment

This work was supported by the B. Braun Anesthesia Scientific Research Fund (grant no. BBF 2012-012).

Declaration of Interest

There are no ethical/legal conflicts involved in the article.

Authors’ Contributors

Ding XD carried out the behavioral testing studies, participated in the design of the study and drafted the manuscript. Zheng NN conceived of the study, and participated in its design and coordination and helped to draft the manuscript. Zhao GY carried out the immunoassays, histopathology and ultrastructural morphology. Cao YY participated in the design of the study and performed the statistical analysis. Zhao P participated in the sequence alignment. All authors read and approved the final manuscript.