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Reperfusion Phase (reperfusion + phase)
Selected AbstractsPost-ischaemic activation of kinases in the pre-conditioning-like cardioprotective effect of the platelet-activating factorACTA PHYSIOLOGICA, Issue 3 2009C. Penna Abstract Aim:, Platelet-activating factor (PAF) triggers cardiac pre-conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre-conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF-induced pre-conditioning. Methods:, Langendorff-perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10,11 m); groups 3,5 hearts were co-infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10,6 m) or the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (5 × 10,5 m) and atractyloside (2 × 10,5 m), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKC,, PKB/A,t, GSK-3, and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined. Results:, PAF pre-treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre-treatment enhanced the phosphorylation/activation of PKC,, PKB/A,t and the phosphorylation/inactivation of GSK-3, at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct-sparing effect and post-ischaemic functional improvement induced by PAF pre-treatment were abolished by post-ischaemic infusion of either chelerythrine, LY294002 or atractyloside. Conclusions:, The cardioprotective effect exerted by PAF pre-treatment involves activation of PKC and PI3K in post-ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK-3, inactivation. [source] Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury,HEPATOLOGY, Issue 3 2006Laura Llacuna The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling. Hepatic ceramide levels transiently increased after the reperfusion phase of the ischemic liver in mice, because of an early activation of acidic sphingomyelinase (ASMase) followed by acid ceramidase stimulation. In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation. ASMase-induced ceramide generation activated JNK resulting in BimL phosphorylation and translocation to mitochondria, as the inhibition of ASMase by imipramine prevented these events. In contrast, blockade of ceramide catabolism by N-oleyolethanolamine (NOE), a ceramidase inhibitor, enhanced ceramide levels and potentiated I/R injury compared with vehicle-treated mice. Pentoxifylline treatment prevented TNF upregulation and ASMase activation. Furthermore, 9 of 11 mice treated with imipramine survived 7 days after total liver ischemia, compared with 4 of 12 vehicle-treated mice, whereas 8 of 8 NOE-treated mice died within 2 days of total liver ischemia. In conclusion, ceramide generated from ASMase plays a key role in I/R-induced liver damage, and its modulation may be of therapeutic relevance. (HEPATOLOGY 2006.) [source] Protective effects of glucagon-like peptide 2 on intestinal ischemia-reperfusion ratsMICROSURGERY, Issue 4 2008Wei Zhang Ph.D. Our objective was to evaluate the protective effects of glucagon-like peptide 2 (GLP-2) on intestinal ischemia/reperfusion (I/R) rats. Thirty-two rats were randomly assigned to four experimental groups, each of 8: Group A, sham rats underwent laparotomy only, without superior mesenteric artery (SMA) occlusion; Group B, I/R animals underwent laparotomy and occlusion of the SMA for 60 minutes followed by 120 minutes of reperfusion; Group C, I/R animals underwent intestinal I/R, and received pretreatment with GLP-2 for 3 days preoperatively; and Group D, I/R animals underwent intestinal I/R, received pretreatment with GLP-2 as above, and during the reperfusion phase were injected intravenously with GLP-2. After the reperfusion of intestinal ischemia, samples of intestinal mucosa, mesenteric lymph nodes (MLN) and blood were prepared for determination. In the pretreatment rats with GLP-2 (group C), Chiu's scores, bacterial colony counts, serum D -lactate, intestinal mucosal MDA and ET-1, and serum endotoxin, TNF-, and IL-6 were significantly reduced compared with intestinal I/R rats (group B). Administration of GLP-2 during the reperfusion phase following pretreatment (group D) showed further protective effects in comparison with the pretreatment rats (group C). We conclude that treatment with GLP-2 attenuates intestinal I/R injury, reduces bacterial translocation, inhibits the release of oxygen free radicals and ET-1, and may well inhibit the production of proinflammatory cytokines. © 2008 Wiley-Liss, Inc. Microsurgery, 2008. [source] Neurological outcome after experimental cardiopulmonary resuscitation: a result of delayed and potentially treatable neuronal injury?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2002X. L. Liu Background: In experimental cardiopulmonary resuscitation (CPR) aortic balloon occlusion, vasopressin, and hypertonic saline dextran administration improve cerebral blood flow. Free radical scavenger ,-phenyl-N-tert-butyl-nitrone (PBN) and cyclosporine-A (CsA) alleviate neuronal damage after global ischemia. Combining these treatments, we investigated neurological outcome after experimental cardiac arrest. Methods: Thirty anesthetized piglets, randomly allocated into three groups, were subjected to 8 min of ventricular fibrillation followed by 5 min of closed-chest CPR. The combined treatment (CT) group received all the above-mentioned modalities; group B was treated with balloon occlusion and epinephrine; and group C had sham balloon occlusion with epinephrine. Indicators of oxidative stress (8-iso-PGF2,), inflammation (15-keto-dihydro-PGF2,), energy crisis (hypoxanthine and xanthine), and anoxia/hypoxia (lactate) were monitored in jugular bulb venous blood. Neurological outcome was evaluated 24 h after CPR. Results: Restoration of spontaneous circulation (ROSC) was more rapidly achieved and neurological outcome was significantly better in the CT group, although there was no difference in coronary perfusion pressure between groups. The jugular venous PCO2 and cerebral oxygen extraction ratio were lower in the CT group at 5,15 min after ROSC. Jugular venous 8-iso-PGF2, and hypoxanthine after ROSC were correlated to 24 h neurological outcome Conclusions: A combination of cerebral blood flow promoting measures and administration of ,-phenyl-N-tert-butyl-nitrone and cyclosporine-A improved 24 h neurological outcome after 8 min of experimental normothermic cardiac arrest, indicating an ongoing neuronal injury in the reperfusion phase. [source] The Ginkgo biloba extract, EGb 761, fails to reduce brain infarct size in rats after transient, middle cerebral artery occlusion in conditions of unprevented, ischemia-induced feverPHYTOTHERAPY RESEARCH, Issue 6 2006Keli Carina Miltus de Lima Abstract There is much biochemical evidence, but very few studies in animal models of stroke in vivo, to suggest that Ginkgo biloba (EGb 761) may offer neuroprotection against regional, ischemic brain damage; additional investigations are needed to ensure future clinical trials. This study reports the effects of EGb 761 given acutely or chronically before ischemia. Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h and the brain infarct size was assessed 24 h later. Dipyrone (100 mg/kg, i.p.) was injected 30 min before ischemia, and 2.5 and 5.5 h after ischemia, to reduce ischemia-induced fever. EGb 761 (Tebonin®) was given acutely (200 mg/kg, p.o., 60 min before ischemia) or chronically (100 mg/kg, p.o., once daily, for 14 days before ischemia). Acute or chronic treatment with EGb 761, either alone or in combination with dipyrone, did not reduce the infarct size compared with saline alone (p > 0.05). Dipyrone failed to prevent ischemia-induced fever during the intra-ischemic period (p > 0.05 vs saline; p < 0.001 vs sham). In the reperfusion phase, dipyrone reduced fever to normothermic levels in the group treated acutely with EGb 761 (p < 0.01 vs saline, p > 0.05 vs sham) but not after chronic EGb 761 (p < 0.01 vs sham), indicating possible pharmacokinetic interaction. In conclusion, within the context of unprevented, ischemia-induced fever, the present results demonstrate that EGb 761 has no significant effect on brain infarct size. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||