Inhibition of mitochondrial permeability transition pore restores the cardioprotection by postconditioning in diabetic hearts.

Autor: Najafi M; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Farajnia S; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Mohammadi M; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Badalzadeh R; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran ; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Ahmadi Asl N; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran., Baradaran B; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran., Amani M; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Jazyk: angličtina
Zdroj: Journal of diabetes and metabolic disorders [J Diabetes Metab Disord] 2014 Nov 18; Vol. 13 (1), pp. 106. Date of Electronic Publication: 2014 Nov 18 (Print Publication: 2014).
DOI: 10.1186/s40200-014-0106-1
Abstrakt: Background: Cardiovascular risk factors, including diabetes mellitus may attenuate the cardioprotection by postconditioning. This study aimed to investigate the cardioprotective effect of ischemic-postconditioning (IPostC) against ischemia/reperfusion injury in normal and chronically type-1 diabetic rats and the effect of mitochondrial permeability transition pore (mPTP) inhibition in this field.
Methods: Diabetes was induced by a single intra-peritoneal injection of streptozotocin (50 mg/kg) in Wistar male rats (250-300 g). After 8 weeks, the hearts of control and diabetic animals were isolated and mounted on a constant-pressure Langendorff apparatus. All hearts were subjected to 30 min regional ischemia followed by 45 min reperfusion (by occluding and re-opening of LAD coronary artery, respectively). At the end of ischemia, the hearts received IPostC, cyclosporine-A, or both or none of them. Myocardial creatine-kinase (CK) release as an index of tissue injury was measured spectrophotometery in coronary effluent in reperfusion phase. Infarct size was identified by triphenyltetrazolium chloride staining. Heart rate, left ventricular end-diastolic pressure (LVEDP), LV systolic pressure (LVSP), rate-pressure product (RPP) and coronary flow were recorded throughout the experiment.
Results: IPostC, applied at the onset of reperfusion, failed to improve myocardial LVEDP and RPP, or reduce tissue damage indicated by infarct size and CK release in diabetic hearts, while it significantly recovered these parameters toward the pre-ischemic values in control hearts (P < 0.05). In contrast, with simultaneous inhibition of mPTP using cyclosporine-A, the cardioprotective effects of IPostC on myocardial hemodynamics, infarct size and CK release were significantly restored in diabetic hearts (P < 0.05).
Conclusions: The loss of cardioprotection by IPostC in diabetic state can be overcome by increasing the potency of protective IPostC through its co-application with mPTP inhibition.
Databáze: MEDLINE
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