Background Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning (IPC). However, the underlying molecular mechanism of SPC remains unclear. Studies confirm that hypoxia-inducible factor-1 (HIF-1) can transform cells from aerobic oxidation to anaerobic glycolysis by activating the switch protein pyruvate dehydrogenase kinase-1 (PDK-1), thus providing energy for the normal life activities of cells under hypoxic conditions. The purpose of this study was to investigate whether the cardioprotective effects of SPC are associated with activation of the HIF-1a/PDK-1 signal pathway. Methods The H9c2 cardiomyocytes hypoxia/reoxygenation model was established and treated with 2.4% sevoflurane at the end of equilibration. Lactate dehydrogenase (LDH) level, cell viability, cell apoptosis, mitochondrial membrane potential, key enzymes of glycolysis, ATP concentration of glycolysis were assessed after the intervention. Apoptosis related protein(Bcl-2, Bax), HIF-1a protein, and PDK-1 protein were assessed by western blot. Results Compared with the H/R group, SPC significantly increased the expression of HIF-1a, PDK-1, and Bcl-2 and reduced the protein expression of Bax, which markedly decreased the apoptosis ratio and Lactate dehydrogenase (LDH) level, increasing the cell viability, content of key enzymes of glycolysis, ATP concentration of glycolysis and stabilizing the mitochondrial membrane potential. However, the cardioprotective effects of SPC were disappeared by treatment with a HIF-1a selective inhibitor. Conclusion This study demonstrates that the cardioprotective effects of SPC are associated with the activation of the HIF-1a/PDK-1 signaling pathway. The mechanism may be related to increasing the content of key enzymes and ATP of glycolysis in the early stage of hypoxia.

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Abstract-This paper is based on simulation for groundwater demand and consumption system which needs heavy investigation efforts and takes long time by using traditional methods to analyze the rates of water demand and consumption. The main purpose of this paper is to estimate the water demand on the basis of population growth in Khartoum state for the coming years so as to fulfill the population needs for water. Information about water consumption and population increase has been covered, with emphasis on the problems of caused by lack of water. All methods in respect to simulation has been taken into consideration, illustrating various models with related definitions and taxonomy as well as various techniques of estimating future consumption of water and prediction for future population. Finally, the study reveals that the existing groundwater with the recharge from the Nile which was estimated to be about 100 million cubic meters per year can not suffice the population demand for water for the coming years in Khartoum state if they depend only on the groundwater. After 35 years from the simulation study year, the population demand will exceed the existing groundwater.Index Terms-VIN, the water left over in the groundwater basin at the end of the last year, VOL, the total volume, DEM, demand, diff, difference, VNET, the total volume net.