الفهرس 
Mediators of preconditioning:Only 14 pages are availabe for public view
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Abstract
The aim of the present investigation was to study the cardioprotective effects of different non pharmacological and pharmacological preconditioning therapies in ischemia/reperfusion (I/R)-induced hemodynamic, biochemical and histological changes in rats. Two main sets of experiments were performed. The first set was carried out to determine the cardioprotective effects of different cycles or doses of various preconditioning therapies in myocardial I/R (40min/10min). These therapies were local or remote preconditioning with 1, 2, 3 and 4 cycles, oxidative preconditioning with two doses of ozone therapy and pharmacological preconditioning with nicorandil (3 or 6 mg/kg) and pioglitazone (10 or 20 mg/kg). Heart rate and ventricular arrhythmias were continuously recorded during the whole operation. At the end of reperfusion, plasma creatine kinase-MB (CK-MB) activity and total nitrate/nitrite (NOx) were determined. In addition, lactate, adenine nucleotides, thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and myeloperoxidase (MPO) activity were estimated in the heart left ventricle. The effective cycle or dose in each type of preconditioning therapy was assessed based on its protective effects on measured parameters and hence was selected to complete the second set of study. In the second set of study, descending aortic blood flow was continuously recorded during the whole operation. Moreover, plasma tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF), cytosolic calcium and myocardial caspase-3 activity were estimated. Histological examination was also performed to visualize the protective cellular effects of different pretreatments. In the first set of study, local preconditioning provided more effective cardioprotection than remote preconditioning in ameliorating the overall electrophysiological and biochemical changes associated with I/R injury. The higher dose of ozone therapy afforded more prominent cardioprotection against the biochemical changes induced by I/R. Lower doses of nicorandil and pioglitazone provided also more cardioprotection than higher doses against ventricular arrhythmias and biochemical changes associated with I/R injury. Finally, it could be concluded that local preconditioning with 3 cycles and pharmacological preconditioning with nicorandil (3 mg/kg) were more effective than other types of preconditioning therapies in ameliorating the overall electrophysiological, biochemical and histological changes associated with myocardial I/R.
Key words: ischemia/reperfusion; nicorandil; ozone; pioglitazone; preconditioning.