Learn More
Brief intermittent episodes of ischemia and reperfusion, at the onset of reperfusion after a prolonged period of ischemia, confer cardioprotection, a phenomenon termed "ischemic postconditioning" (Postcond). We hypothesized that this phenomenon may just represent a modified form of reperfusion that activates the reperfusion injury salvage kinase (RISK)(More)
OBJECTIVES Recruitment of the survival kinase cascades, PI3K-Akt and Raf-MEK1/2-Erk1/2, at the time of reperfusion, following a lethal ischemic insult, may mediate the protection associated with ischemic preconditioning (IPC). The exact interplay between these two kinase cascades in mediating this effect is not clear. We examine the 'cross-talk' between(More)
Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely(More)
BACKGROUND The sulfonylurea glibenclamide (Glib) abolishes the cardioprotective effect of ischemic preconditioning (IP), presumably by inhibiting mitochondrial K(ATP) channel opening in myocytes. Glimepiride (Glim) is a new sulfonylurea reported to affect nonpancreatic K(ATP) channels less than does Glib. We examined the effects of Glim on IP and on the(More)
Cardiomyocytes are vulnerable to hypoxia in the adult, but adapted to hypoxia in utero. Current understanding of endogenous cardiac oxygen sensing pathways is limited. Myocardial oxygen consumption is determined by regulation of energy metabolism, which shifts from glycolysis to lipid oxidation soon after birth, and is reversed in failing adult hearts,(More)
BACKGROUND The dipeptidyl peptidase-4 (DPP-4) inhibitors Sitagliptin and Vildagliptin lower blood glucose by augmenting endogenous levels of glucagon-like peptide-1 (GLP-1), an incretin which also confers cardioprotection. As such, we hypothesized that treatment with DPP-4 inhibitors are also cardioprotective. METHODS In ex vivo experiments: Male(More)
AIMS Old age and diabetes are risk factors that often coexist increasing the vulnerability of the heart to the lethal effects of ischaemia-reperfusion injury (IRI). However, to our knowledge, no investigations have examined IRI and cardioprotective signalling in animal models bearing these co-morbidities concomitantly. The ability of the heart to recover(More)
OBJECTIVES Mutations in PTEN inducible kinase-1 (PINK1) induce mitochondrial dysfunction in dopaminergic neurons resulting in an inherited form of Parkinson's disease. Although PINK1 is present in the heart its exact role there is unclear. We hypothesized that PINK1 protects the heart against acute ischemia reperfusion injury (IRI) by preventing(More)
Diabetes mellitus is a major risk factor for ischemic heart disease (IHD). Patients with diabetes and IHD experience worse clinical outcomes, suggesting that the diabetic heart may be more susceptible to ischemia-reperfusion injury (IRI). In contrast, the animal data suggests that the diabetic heart may be either more, equally, or even less susceptible to(More)