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find Keyword "Diazoxide" 4 results
  • Role of Cyclic Adenosine Monophosphate Signaling Pathway in Myocardial Protection by Diazoxide Preconditioning: Experiment with Isolated Rat Hearts

    Abstract: Objective To study the changes of the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) expression of isolated rat hearts after diazoxide preconditioning (DPC), and to explore the possible mechanism of cAMP signaling pathway in myocardial protection by DPC. Methods Isolated working heart Langendorff perfusion models of 40 Wistar rats were set up and were divided randomly into four groups. For the ischemia reperfusion injury(I/R) group (n=10), 30 min of equilibrium perfusion was followed by a 60 min reperfusion of KrebsHenseleit (K-H) fluid. The DPC group (n=10) had a 10 min equilibrium perfusion and two cycles of 5 min of 100 μmol/L diazoxide perfusion followed by a 5 min diazoxidefree period before the 30 min ischemia and the 60 min reperfusion of K-H fluid. The blank control group (control group, n=10) and the Dimethyl Sulphoxide(DMSO) group (n=10) were perfused with the same treatment as in the DPC group except that diazoxide was replaced by natriichloridum and DMSO respectively. The activity of creatine kinase (CK) in coronary outflow, the activity of malonyldialdehyde (MDA) and superoxide dismutase (SOD) in myocardium were detected. And the scope of myocardial infarction and the concentrations of myocardial cAMP and PKA were also assessed. Results Compared with the I/R group, the level of MDA for the DPC group decreased significantly (8.28±2.04 nmol/mg vs. 15.52±2.18 nmol/mg, q=11.761,Plt;0.05), the level of SOD increased significantly (621.39±86.23 U/mg vs. 477.48±65.20 U/mg, q=5.598,Plt;0.05). After a 30 min reperfusion, compared with the I/R group, the content of CK decreased significantly (82.55±10.08 U/L vs. 101.64±19.24 U/L, q=5.598, Plt;0.05) and the infarct size reduced significantly (5.63%±9.23% vs.17.58%±5.76%, q=6.176,Plt;0.05) in the DPC group. The cAMP concentration in the DPC group was much higher than that in the I/R group (0.64±0.07 pmol/g vs. 0.34±0.05 pmol/g, q=14.738,Plt;0.05), and PKA concentration was also much higher than that in the I/R group [17.13±1.57 pmol/(L·min·mg) vs. 12.85±2.01 pmol/(L·min·mg), Plt;0.05]. However, there were no significant differences between the I/R group, DMSO group and the control group in the above indexs (Pgt;0.05). Conclusion DPC significantly improves the releasing of cAMP and PKA, decreases oxygen free radicals, and relieves myocardial ischemia reperfusion injury. The cAMP signaling pathway may be involved in triggering the process of myocardial protection mechanisms of DPC.

    Release date:2016-08-30 06:02 Export PDF Favorites Scan
  • Protective Effects of Diazoxide-preconditioning on Myocardial Ischemia-reperfusion Injury of Rats

    Objective To observe the protective effects of diazoxide-preconditioning on myocardial ischemiareperfusion injury of rats and discuss its possible mechanisms. Methods Fourteen healthy SD rats were randomly divided into two groups(7 each group),In diazoxide-preconditioning group diazoxide was injected with the dosage of 12.5mg/kg through the vein,and in control group the media with the same amount was only given before ischemia. The left anterior descending branch was ligated for 2 hours. The heart was quickly excised after 2 hours reperfusion to be used for measurement of the quantity of malondialdehyde(MDA), the activity of superoxide dismutase (SOD), the size of myocardial infarct area, and the cell apoptosis and ultrastructure in ischemic area. Results Compared with the control group, the quantity of MDA,the percentage of the weight of myocardial infarct area/ischemic area, and the rate of cell apoptosis in the diazoxide-preconditioning group were greatly reduced (P〈0.05, 0. 01). The damage of cell uhrastructure was obviously alleviated,Conclusion Diazoxide-preconditioning provides evident cardioprotective effect on the myocardial ischemia-reperfusion injury of rats.

    Release date:2016-08-30 06:04 Export PDF Favorites Scan
  • Protective Effects of Diazoxide-preconditioning on Myocardial Ischemia-reperfusion Injury of Rats

    Objective To observe the protective effects of diazoxide-preconditioning on myocardial ischemiareperfusion injury of rats and discuss its possible mechanisms. Methods Fourteen healthy SD rats were randomly divided into two groups(7 each group),In diazoxide-preconditioning group diazoxide was injected with the dosage of 12.5mg/kg through the vein,and in control group the media with the same amount was only given before ischemia. The left anterior descending branch was ligated for 2 hours. The heart was quickly excised after 2 hours reperfusion to be used for measurement of the quantity of malondialdehyde(MDA), the activity of superoxide dismutase (SOD), the size of myocardial infarct area, and the cell apoptosis and ultrastructure in ischemic area. Results Compared with the control group, the quantity of MDA,the percentage of the weight of myocardial infarct area/ischemic area, and the rate of cell apoptosis in the diazoxide-preconditioning group were greatly reduced (P〈0.05, 0. 01). The damage of cell uhrastructure was obviously alleviated,Conclusion Diazoxide-preconditioning provides evident cardioprotective effect on the myocardial ischemia-reperfusion injury of rats.

    Release date:2016-08-30 06:26 Export PDF Favorites Scan
  • Preservative Effect of Diazoxide Cardioplegic Solution on the Reduction of Apoptotic Cardiomyocytes of Donor Heart

    Objective To investigate the effects of diazoxide (DIA)cardioplegic solution on the reduction of donor cardiomyocyte apoptosis, Methods In a Krebs-Henseleit (KH) solution perfused isolated rabbit heart Langendorff model, 32 rabbit hearts were divided into four groups with simple random sampling (8 rabbits in each group ): DIA group (50μmol/L diazoxide mixed in KH solution),STH group (ST, Thomas' solution), 5-HD group (50μmol/L diazoxide and 100μmol/L 5-hydroxydecanoic acid mixed in KH solution), KH group (KH solution), The rabbit hearts of each group underwent 6 hours of hypothermic (4 C) storage in the corresponding cardioplegic solution. Left ventricular developed pressure (LVDP), maximal values of positive rate of left ventricular pressure (+dp/dtmax) were measured before and after storage, The post-storage values of LVDP and +dp/dtmax were expressed as the percentage of pre-storage control values. Apoptotic cardiomyocytes were detected by the TdT- mediated dUTP-biotin nick end labeling (TUNEL). Malonaldehyde (MDA) contents and adenosine triphosphate (ATP) contents were also measured after storage. Results Recovery rates of LVDP, +dp/dtmax, and ATP contents in DIA group were higher than those of other 3 groups respectively(P〈0. 05), Cardiomyocytes apoptosis percentage and MDA content were lower than other 3 groups respectively(P〈0. 05), Conclusions Diazoxide cardioplegic solution can protect the isolated hearts and this may be relates to opening selective mitochondrial KATP channels. The selective mitochondrial KATP channel antagonist 5-hydroxydecanoic acid can block the cardioprotective effect of diazoxide.

    Release date:2016-08-30 06:26 Export PDF Favorites Scan
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