Flumazenil Cardioprotection Pathway

Flumazenil is a benzodiazepine receptor antagonist. It is used clinically to reverse the effects of benzodiazepines in conscious sedation, general anesthesia, and management of suspected benzodiazepine overdose. Kochs and colleagues reported that flumazenil might be beneficial in protecting against cerebral ischemia. Rapid administration of flumazenil produced minimal coronary and left ventricular hemodynamic responses. Thus this agent may be a potential candidate for clinical application in patients with ischemic heart diseases if it can mimic preconditioning to protect the heart. The study by Zhang and Yao indicates that flumazenil mimics preconditioning in cardiomyocytes via the generation of H2O2 as the reactive oxygen species (ROS). H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via protein kinase C-epsilon in cardiomyocytes inducing ischemic preconditioning. This signal transduction and preconditioning protects ischemic cardiomyocytes. Zhang et al. indicate that the potential beneficial effects of Allitridum appear to mimic the same effects as flumazenil, to precondition cardiomyocytes, via the stimulation of PKC. Allitridum is an extract of garlic taken as a medicine in China for over 3000 years. (NCI Thesaurus/BIOCARTA)

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