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H Reperfusion (h + reperfusion)
Selected AbstractsCholestasis enhances liver ischemia/reperfusion-induced coagulation activation in ratsHEPATOLOGY RESEARCH, Issue 2 2010Jaap J. Kloek Aim:, Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods:, Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results:, Plasma AST and ALT levels were higher after I/R in cholestatic rats (P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion (P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion (P < 0.05). I/R in cholestatic rats resulted in a 12-fold vs. 7-fold (P < 0.01) increase in markers for thrombin generation and a 6-fold vs. 2-fold (P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1) during reperfusion. Conclusions:, Cholestasis significantly enhances I/R-induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis. [source] Rapid loss of motor nerve terminals following hypoxia,reperfusion injury occurs via mechanisms distinct from classic Wallerian degenerationJOURNAL OF ANATOMY, Issue 6 2008Becki Baxter Abstract Motor nerve terminals are known to be vulnerable to a wide range of pathological stimuli. To further characterize this vulnerability, we have developed a novel model system to examine the response of mouse motor nerve terminals in ex vivo nerve/muscle preparations to 2 h hypoxia followed by 2 h reperfusion. This insult induced a rapid loss of neurofilament and synaptic vesicle protein immunoreactivity at pre-synaptic motor nerve terminals but did not appear to affect post-synaptic endplates or muscle fibres. The severity of nerve terminal loss was dependent on the age of the mouse and muscle type: in 8,12-week-old mice the predominantly fast-twitch lumbrical muscles showed an 82.5% loss, whereas the predominantly slow-twitch muscles transversus abdominis and triangularis sterni showed a 57.8% and 27.2% loss, respectively. This was contrasted with a > 97% loss in the predominantly slow-twitch muscles from 5,6-week-old mice. We have also demonstrated that nerve terminal loss occurs by a mechanism distinct from Wallerian degeneration, as the slow Wallerian degeneration (Wlds) gene did not modify the extent of nerve terminal pathology. Together, these data show that our new model of hypoxia,reperfusion injury is robust and repeatable, that it induces rapid, quantitative changes in motor nerve terminals and that it can be used to further examine the mechanisms regulating nerve terminal vulnerability in response to hypoxia,reperfusion injury. [source] Regulatory proteins of eukaryotic initiation factor 2-alpha subunit (eIF2,) phosphatase, under ischemic reperfusion and toleranceJOURNAL OF NEUROCHEMISTRY, Issue 4 2007Lidia García-Bonilla Abstract Phosphorylation of the , subunit of eukaryotic translation initiation factor 2 (eIF2,), which is one of the substrates of protein phosphatase 1 (PP1), occurs rapidly during the first minutes of post-ischemic reperfusion after an episode of cerebral ischemia. In the present work, two experimental models of transient global ischemia and ischemic tolerance (IT) were used to study PP1 interacting/regulatory proteins following ischemic reperfusion. For that purpose we utilized PP1 purified by microcystin chromatography, as well as 2D DIGE of PP1, and PP1, immunoprecipitates. The highest levels of phosphorylated eIF2, found after 30 min reperfusion in rats without IT, correlated with increased levels in PP1 immunoprecipitates of the inhibitor DARPP32 as well as GRP78 and HSC70 proteins. After 4 h reperfusion, the levels of these proteins in PP1c complexes had returned to control values, in parallel to a significant decrease in eIF2, phosphorylated levels. IT that promoted a decrease in eIF2, phosphorylated levels after 30 min reperfusion induced the association of GADD34 with PP1c, while prevented that of DARPP32, GRP78, and HSC70. Different levels of HSC70 and DARPP32 associated with PP1, and PP1, isoforms, whereas GRP78 was only detected in PP1, immunoprecipitates. Here we suggest that PP1, through different signaling complexes with their interacting proteins, may modulate the eIF2, phosphorylation/dephosphorylation during reperfusion after a transient global ischemia in the rat brain. Of particular interest is the potential role of GADD34/PP1c complexes after tolerance acquisition. [source] Involvement of , protein kinase C in estrogen-induced neuroprotection against focal brain ischemia through G protein-coupled estrogen receptorJOURNAL OF NEUROCHEMISTRY, Issue 4 2005Shigeto Hayashi Abstract The neuroprotective effects of estrogen were studied in the ischemic model mice by 90 min transient unilateral middle cerebral artery occlusion (MCAO) followed by 22.5 h reperfusion. The total infarct size in C57BL/6 female mice after MCAO and reperfusion was significantly smaller than that in male mice. Intraperitoneal injection of estrogen after the start of reperfusion significantly reduced the infarct volume in the male mice. However, no significant gender difference was found in total infarct size in , protein kinase C (PKC)-knockout mice, suggesting that the neuroprotective effects of estrogen are due to the activation of a specific subtype of PKC, ,PKC, a neuron-specific PKC subtype, in the brain. We demonstrated that exogenous estrogen-induced neuroprotection was attenuated in ,PKC-knockout mice. Immunocytochemical study showed that ,PKC was translocated to nerve fiber-like structures when observed shortly after MCAO and reperfusion. We also visualized the rapid and reversible translocation of ,PKC-GFP (green fluorescent protein) by estrogen stimulation in living CHO-K1 cells. These results suggest that the activation of ,PKC through the G-protein-coupled estrogen receptors on the plasma membrane is involved in the estrogen-induced neuroprotection against focal brain ischemia. [source] Sphingolipids in rat model of transient focal cerebral ischemia: implication for stroke injuryJOURNAL OF NEUROCHEMISTRY, Issue 2002M. Khan Lipids are essential for signal transduction in response to trauma leading to neurodegeneration. Ceramide is an important mediator of apoptosis and cell proliferation. We studied the involvement of ceramide/sphingomyelin pathway in rat brain (stroke model) after 45 min ischemia followed by 24-h reperfusion. Ischemia was performed through occlusion of right middle cerebral artery (MCA). The level of ceramide was found increased (70,100% in ischemic side of brain v/s contralateral side of brain). Sphingomyelin levels were also decreased by 20,25% in ischemic brain v/s contralateral side of brain. Increase in ceramide and decrease in sphingomyelin were in good agreement with observed apoptotic cell loss (TUNEL assay) and decrease in the level of cardiolipin (a mitochondrian specific phospholipids) in affected ischemic brain. N-acetyl cysteine (NAC), a therapeutic agent recognized as potent antioxidant provided protective effect. Pretreatment with NAC before ischemia reduced the infarct volume size, suppressed apoptosis, restored cardiolipin level and decreased the levels of free fatty acids. However, NAC did not normalize the ceramide level. These interesting observations raise a question about the role of ceramide and its relationship with apoptosis and oxidative stress in rat brain ischemia. Acknowledgements:, Supported by NIH grants NS-40144, NS-40810, NS-22576, NS-34741 and NS-37766. [source] Siberian ginseng reduces infarct volume in transient focal cerebral ischaemia in Sprague-Dawley ratsPHYTOTHERAPY RESEARCH, Issue 2 2005Yungmin Bu Abstract Siberian ginseng, the root and stem bark of Acanthopanax senticosus Harms, has been used as a tonic and adaptogen to strengthen qi in traditional Korean medicine. The neuroprotective effects of water extracts of A. senticosus (ASW) were investigated in transient middle cerebral artery occlusion (MCAo, 90 min occlusion, 24 h reperfusion) of Sprague-Dawley rats. The infarct volume was significantly reduced by 36.6% after the peritoneal injection of ASW (100 mg[sol ]kg) compared with the control. In the immunohistochemical study, ASW markedly inhibited both cyclooxygenase-2 and OX-42 expressions in the penumbral region at 24 h after MCAo. These results suggest that A. senticosus has a neuroprotective effect by inhibiting inflammation and microglial activation in brain ischaemia. Copyright © 2005 John Wiley & Sons, Ltd. [source] Control Strategy for Biventricular Assistance with Mixed-Flow PumpsARTIFICIAL ORGANS, Issue 8 2000George Endo Abstract: A left ventricular assist device (LVAD) is an effective method to rescue severe heart failure. Although some require a biventricular assist, the control method for the biventricular assist device (BVAD) with a rotary pump is rarely shown. The objective of this study was to investigate the strategy for controlling BVAD with rotary pumps by in vivo studies. Using 5 piglets, we set a BVAD through a left thoracotomy and made global ischemia for 30 min by clamping the base of the ascending aorta. After unclamping, the analysis of pumping performance acted for 6 h reperfusion. We set the target flow of the LVAD and set the right ventricular assist device (RVAD) speed limit as less than when the atrial collapse occurs. To detect the ventricular collapse without any specific sensor, we calculated the index of current amplitude from motor current waveform and simultaneous mean current value. In all cases, over 6 h of observation was performed, and the RVAD was weaned almost automatically. [source] Attenuation of reperfusion injury by renal ischaemic preconditioning: the role of nitric oxideBJU INTERNATIONAL, Issue 9 2000M.K. Jefayri Objective To determine the effect on nitric oxide (NO) release and renal NO synthase (endothelial, eNOS and inducible, iNOS) activity of renal ischaemia-reperfusion (I/R) in vivo in an animal model, and to examine the possible involvement of NO in ischaemic preconditioning (IP) of the kidney. Materials and methods In a right-nephrectomized rat model, 42 animals were randomized in four groups: controls; IP-only (4 min of ischaemia followed by 11 min of reperfusion, total of four cycles); renal warm ischaemia (45 min) and 6 h reperfusion; ischaemia (45 min) preceded by IP pretreatment. Serum NO metabolites were assayed 2 and 6 h after ischaemia or the control equivalent. NOS expression in the kidney was detected immuno-histochemically, and damage assessed morphologically in sections stained with haematoxylin and eosin. Kidney function was assessed by the levels of serum creatinine, urea and electrolytes. Results Compared with before ischaemia, the concentration of serum NO metabolites at 6 h was increased in the IP-only animals (P = 0.016) and in the IP + I/R group (P = 0.002). There was greater eNOS expression in the IP-only group (P = 0.009) and in the IP + I/R group than in controls (P = 0.050). iNOS expression was greater in the IP-only animals than in the control group (P = 0.050). Histological assessment showed less evidence of cellular damage in IP + I/R animals than in the I/R-alone group (P = 0.020). Serum creatinine level was not significantly different between the IP-only group and the control. There were no differences after 2 h of reperfusion. Conclusion Ischaemic preconditioning has a protective effect on renal structure and function, which may be produced by increased NO release arising from increased NOS expression by 6 h after reperfusion. [source] | |||||||||||||