Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brief ischemia before normothermic ischemia protects hearts against reperfusion injury (ischemic preconditioning, IPC), but it is unclear whether it protects against long-term moderate hypothermic ischemia. We explored in isolated guinea pig hearts 1) the influence of two 2-min periods of normothermic ischemia before 4 h, 17 degrees C hypothermic ischemia on cardiac cytosolic [Ca(2+)], mechanical and metabolic function, and infarct size, and 2) the potential role of K(ATP) channels in eliciting cardioprotection. We found that IPC before 4 h moderate hypothermia improved myocardial perfusion, contractility, and relaxation during normothermic reperfusion. Protection was associated with markedly reduced diastolic [Ca(2+)] loading throughout both hypothermic storage and reperfusion. Global infarct size was markedly reduced from 36 +/- 2 (SE)% to 15 +/- 1% with IPC. Bracketing ischemic pulses with 200 microM 5-hydroxydecanoic acid or 10 microM glibenclamide increased infarct size to 28 +/- 3% and 26 +/- 4%, respectively. These results suggest that brief ischemia before long-term hypothermic storage adds to the cardioprotective effects of hypothermia and that this is associated with decreased cytosolic [Ca(2+)] loading and enhanced ATP-sensitive K channel opening.
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PMID:Cardiac preconditioning with 4-h, 17 degrees C ischemia reduces [Ca(2+)](i) load and damage in part via K(ATP) channel opening. 1200 99

NADH increases during ischemia because O(2) shortage limits NADH oxidation at the electron transport chain. Ischemic (IPC) and anesthetic preconditioning (APC) attenuate cardiac reperfusion injury. We examined whether IPC and APC similarly alter NADH, i.e., mitochondrial metabolism. NADH fluorescence was measured at the left ventricular wall of 40 Langendorff-prepared guinea pig hearts. IPC was achieved by two 5-min periods of ischemia and APC by exposure to 0.5 or 1.3 mM sevoflurane for 15 min, each ending 30 min before 30 min of global ischemia. During ischemia, NADH initially increased in nonpreconditioned control hearts and then gradually declined below baseline levels. This increase in NADH was lower after APC but not after IPC. The subsequent decline was slower after IPC and APC. On reperfusion, NADH was less decreased after IPC or APC, mechanical and metabolic functions were improved, and infarct size was lower compared with controls. Our results indicate that IPC and APC cause distinctive changes in mitochondrial metabolism during ischemia and thus lead to improved function and tissue viability on reperfusion.
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PMID:Altered NADH and improved function by anesthetic and ischemic preconditioning in guinea pig intact hearts. 1206 74

The main goals of the current study were to assess: (a) whether a sublethal ischemic insult could protect the CA1 subregion of the hippocampus in organotypic slices against a lethal ischemic insult; and (b) whether this protection is long lasting as determined with an accurate immunohistochemical neuronal marker, NeuN. Hippocampal slice cultures were grown for 12-14 days in vitro. Slices were exposed either to oxygen/glucose deprivation (OGD) for 45 min (ischemia), or OGD for 15 min (ischemic preconditioning), 48 h prior to 45 min OGD, or were untreated (sham). Cell death was estimated by propidium iodide fluorescence 1 day after OGD and by NeuN immunohistochemistry 7 days after OGD. Image analysis was employed to measure the relative optical density of the NeuN-signal in all groups. After ischemia, damaged neurons were shrunken or lost and NeuN immunoreactivity was reduced. Relative optical density of NeuN (ROD [NeuN]) was 0.193+/-0.015 in control (sham) (n=9). In slices that underwent ischemia, ROD [NeuN] declined to 0.108+/-0.018 (n=5) in CA1 (*P<0.05 ROD [NeuN] in preconditioned slice cultures was 0.190+/-0.037 (76% higher than the ischemia group). Similar results were found after measuring PI fluorescence. In the CA1 sub-region, PI fluorescence was about 13, 47 and 17% in the sham, ischemic and IPC groups, respectively. We suggest that the immunohistochemical approach validates the dye uptake method used in slice cultures and yields quantitative data specific for neurons. We also conclude that the organotypic hippocampal slice model is useful for studying delayed ischemic preconditioning that is maintained for hours or days after the preconditioning event.
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PMID:Improvement in neuronal survival after ischemic preconditioning in hippocampal slice cultures. 1237 75

One determining factor in intestinal transplantation is the bowel's extreme sensitivity to ischemia-reperfusion injury. This study was meant to investigate the effect of ischemic preconditioning prior to autotransplantation. Total orthotopic intestinal autotransplantation was performed in 40 mongrel dogs. Four groups (GI-GIV) were established. In GI and GII grafts were stored in 4 degrees C Euro Collins and University of Wisconsin solutions. In GIII and GIV before preservation IPC was induced by 4 cycles (5-min ischemia + 10-min reperfusion). Three hours of preservation was followed by 1 hour of reperfusion. We determined oxidative stress markers in bowel tissue [reduced glutathione (GSH), superoxide dismutase (SOD)], oxygen free radicals (OFRs) (confocal microscopy), NF-kappa B (gel electrophoretic mobility shift assay), DNA damage (TUNEL). Cold preservation could not prevented against oxidative stress and resulted decrease of SOD activity significantly during reperfusion. In the preconditioned groups the elevated GSH and better preserved SOD activity indicated development of protection. Production of OFRs increased during reperfusion in non-preconditioned groups. Activation of NF-kappa beta was peaking by 1-3 hours following preconditioning. We detected more cells suffered DNA strand breaks in preconditioned groups. Our findings confirm that ischemic preconditioning prior to preservation can moderate the severity of oxidative stress and activate the endogenous celluar adaptation in bowel tissue.
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PMID:[Effects of ischemic preconditioning on the oxidative stress in small bowel autotransplantation]. 1247 21

Recent studies demonstrated that brief period of Ca2+ depletion and repletion (Ca2+ preconditioning, CPC) has strong protective effects against ischemia in a rat heart. CPC and classic preconditioning (IPC) were compared in relation with infarct size and protein kinase C (PKC) isozymes. Isolated Langendorff-perfused rabbit hearts were subjected to 45-min ischemia (Isc) followed by 120-min reperfusion (R) with or without IPC, induced by 5-min Isc and 10-min R. In the CPC hearts, 5-min Ca2+ depletion and 10-min repletion (CPC) were given before 45-min Isc, with or without concurrent PKC inhibition (calphostin C, 200 nmol/L). IPC enhanced recovery of LV function, while CPC did not. Infarct size was significantly reduced by both CPC and IPC (p < 0.05 vs. ischemic control). Membrane PKC was significantly increased from 2.53 +/- 0.07 (baseline, nmol/g tissue) to 3.11+/-0.07, 3.34 +/- 0.11, 3.15 +/- 0.09, and 3.06 +/- 0.08 by IPC, IPC and 45-min Isc, CPC and 45-min Isc, respectively (p < 0.01). Immunoblots of membrane PKC were increased by IPC, IPC and 45-min Isc, and CPC. These effects were abolished by PKC inhibition. Thus, activation of PKC may have trigger role in the mechanism of cardioprotective effect by CPC.
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PMID:Infarct size-limiting effect of calcium preconditioning in rabbit hearts. 1280 18

The objective of the present study was to investigate the differential activation of protein kinase C between ischemic (IPC) and pharmacological preconditioning (PPC) in the rabbit heart. Control, IPC, diazoxide (Diaz), and chelerythrine (Chel)+IPC groups underwent prolonged coronary artery occlusion (CAO) for 30 minutes followed by 180 minutes' reperfusion (protocol I). In protocol II, sham, IPC-only, Diaz-only, and Chel+IPC-only groups did not undergo prolonged CAO. IPC was induced with 4 cycles of 5-min regional ischemia and 10-min reperfusion before prolonged CAO. Diaz (5 mg/kg) was administered 30 min before prolonged CAO. Chel (5 mg/kg) was administered 5 min before the IPC procedure. Infarct size was determined by tetrazolium staining. Assessment of protein kinase C (PKC) isoforms from a left ventricular (LV) sample was conducted by western blotting. Apoptosis in situ was determined by TUNEL assay. The infarction area in the IPC (11.6 +/- 1.0%) and Diaz (19.5 +/- 3.8%) groups was reduced significantly (p< 0.01, p< 0.05) relative to the control group (40.0 +/- 3.8%). The reduction by IPC was abolished by pretreatment with Chel. Apoptosis was significantly decreased (p< 0.01) in the IPC and diazoxide groups compared with the control and Chel+IPC groups (control: 4.78 +/- 0.56% vs. IPC: 2.00 +/- 0.38% vs. Diaz: 2.20 +/- 0.32% vs. Chel+IPC: 4.32 +/- 0.41%) and DNA laddering was attenuated in the IPC and Diaz groups. Membrane PKC-epsilon levels in the IPC and Diaz groups increased significantly relative to the control and Chel+IPC groups. Membrane PKC-epsilon levels in the IPC-only group showed greater increases than the Diaz-only and Chel+IPC-only groups. These findings suggest that whereas PPC suppresses apoptosis when diazoxide opens mitochondrial K(ATP) channels and then activates PKC-epsilon through ischemia-reperfusion, IPC activates PKC-epsilon in the particulate fraction prior to continuous ischemia-reperfusion. We concluded that the difference between IPC and PPC appears to consist in the difference in the timing of PKC-epsilon activation, though both IPC and PPC provide the cardioprotection in ischemia-reperfusion injury.
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PMID:Differential activation of protein kinase C between ischemic and pharmacological preconditioning in the rabbit heart. 1452 78

Recent evidence suggests that the mitochondrial K(ATP) channels may be involved as a subcellular mediator in cardioprotection afforded by ischemic and pharmacological preconditioning by K(ATP) activators. The present study investigated the effects of administration of non-hypotensive doses of ATP-sensitive K(+) channel (K(ATP)) openers, nicorandil (NIC) and pinacidil (PIN), and specific blockers of mitochondrial (5-hydroxydecanoate) and sarcolemmal (1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methyl-thiourea, HMR 1883) K(ATP) channels prior to and during coronary occlusion and post-ischemic reperfusion on survival rate, ischemia- and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized rabbits. In Group I, myocardial ischemia-induced arrhythmias were provoked by tightening a ligature over the left main coronary artery for 30 min. In Group II, arrhythmias were induced by reperfusion following a 20 min ligation of the same artery. Both in Group I and Group II, early iv administration of NIC (0.47 mg/kg), PIN (0.1 mg/kg), HMR 1883 (3 mg/kg)/NIC and HMR 1883/PIN just prior to and during ischemia increased survival rate (75%, 86%, 75% and 75%, respectively, vs. 55% in the control in Group I; 75%, 75%, 75% and 67%, respectively, vs. 50% in the control in Group II), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late iv administration of NIC or PIN just prior to reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects were abolished by pretreating rabbits with 5-hydroxy-decanoate (5 mg/kg, iv bolus). In the present study, higher levels of malondialdehyde and lower levels of reduced glutathione and superoxide dismutase in necrotic zone of myocardium in all subgroups in Group II suggest little anti-free radical property of NIC and PIN. Therefore, it may be assumed that mitochondrial K(ATP) channel opening leads to mitochondrial generation and release of ROS providing for IPC and antiarrhythmic activity. The mitochondrial rather than sarcolemmal K(ATP) channel may represent a potential site of cardioprotection and antiarrhythmic activity.
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PMID:Cardiomyocyte mitochondrial KATP channels participate in the antiarrhythmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabbit model. 1470 74

Previously, we have demonstrated a late phase protection of ischemic preconditioning in the microcirculation of cremaster muscle. This microvascular protection was blocked by a non-specific NOS inhibitor. The purpose of present study was to evaluate endothelial function in the terminal arteriole of cremaster muscle after 24-h of ischemic preconditioning followed by 4-h warm ischemia and to evaluate eNOS and iNOS gene and protein expression at 24 h after ischemic preconditioning in the cremaster muscle. A vascular pedicle isolated cremaster muscle in male SD rats underwent 45-min of ischemic preconditioning and 24 h later, 4-h of warm ischemia followed by reperfusion. Endothelial-dependent and -independent vasodilatation was evaluated on day 2 after 4-h ischemia and 60-min of reperfusion. Cremaster muscles were harvested at 24 h after ischemic preconditioning for measuring of eNOS and iNOS gene expression by reverse transcriptase polymerase chain reaction (RT-PCR) and protein expression by western blotting analysis. We found that IPC significantly attenuated endothelial dysfunction induced by 4-h warm ischemia and reperfusion. The expression of eNOS and iNOS mRNA shown a 229% and 135% increase respectively in IPC treated cremaster muscles as compared to normal cremaster muscles (P<0.05). The expression of eNOS and iNOS protein exhibited a 133% and 148% increase respectively in IPC treated cremaster muscles as compared to normal cremaster muscles (P<0.05). There was no statistically significant difference between normal cremaster muscle and sham IPC treated cremaster muscle. The results suggest that IPC preventing vascular endothelial dysfunction from ischemia/reperfusion injury may be due to the enhanced NOS expression. These results combined with the results from our previous studies suggest that IPC-induced microvascular protection in the skeletal muscle may act through a NOS-dependent mechanism.
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PMID:NOS upregulation attenuates vascular endothelial dysfunction in the late phase of ischemic preconditioning in skeletal muscle. 1509 38

For the first time the involvement of C-Reactive protein (CRP) in early (acute) and delayed ischemic (IPC) and pharmacological (chemical) preconditioning (CPC) in an in vivo model of rat myocardial infarction was presented. Acute IPC was produced by three 5 minute occlusion (ischemia) periods interspersed with 5 minute reperfusion, followed by 30 minute occlusion of the left coronary artery and 2 hour reperfusion injury. Acute CPC was produced by a k-opioid receptor agonist U50488H (5 mg/kg) applied i.v. 15 minutes before 30 minute ischemia/ 2 hour reperfusion. Delayed preconditioning was produced by 30 minute ischemia/ 2 hour reperfusion, induced 24 hour after either ischemic or pharmacological preconditioning. The myocardial ischemia/reperfusion injury was evaluated on the basis of total and cardiac creatine kinase isoenzyme activity, functional recovery of the heart (ECG), infarct size (% IS/RA) and mortality at the end of the experiments. The results obtained showed that: k-opioid receptor agonist U50488H mimics both the acute and delayed IPC in the above experimental protocol; Both acute IPC and most probably CPC act by opening of K(ATP) channels (the effects were blocked by nonspecific ATP-sensitive K channel blocker glybenclamide), and via activation of protein kinase C (a selective protein kinase C inhibitor chelerythrine blocked the efects); C-reactive protein (CRP) was significantly elevated by 54% in non-preconditioned acute ischemia/reperfusion injury. The elevation was more pronounced (82% increase) 24 hour after non-preconditioned ischemia/reperfusion injury. It reflected very well the increase in cardiac isoenzymes, infarct size and mortality of the rats, and can be used as a marker of the severity of myocardial injury in this model; The increase of CRP was prevented by both IPC and CPC in early, and especially in late preconditioning. This confirms the involvement of CRP as a marker in cardiac ischemic/reperfusion injury. It was concluded that in addition to the established involvement of adenosine, bradykinin, opioid and other receptors, a suppression of myocardial CRP/complement production might be involved in the biological mechanism of preconditioning. This could be a promising perspective in clinical interventions against ischemia/reperfusion injuries of the heart.
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PMID:The role of C-reactive protein in ischemia/reperfusion injury and preconditioning in a rat model of myocardial infarction. 1519 50

The objective of this study was to evaluate the effect of ischemic preconditioning upon lesions produced by ischemia-reperfusion of the small intestine. Thirty EPM-1 Wistar rats were randomly distributed into three groups: ischemic preconditioning (IPC; n = 12), ischemia-reperfusion (I/R; n = 12), and control (C; n = 6). Laparotomy permitted isolation of the mesenteric artery for clamping. The animals were heparinized and hydrated. IPC was induced by: 10 minutes of ischemia followed by 10 minutes of reperfusion and then 50 minutes ischemia followed by another 30 minutes reperfusion. Group I/R was submitted to the same protocol except for the 20 minutes of preconditioning. Group C animals underwent only laparotomy for 100 minutes. After reperfusion small intestine fragments were examined histologically. Blood samples were obtained to measure LDH and lactate prior to euthanasia. Lactate values were significantly lower in the IPC as compared to I/R group, 39 versus 67 mg/dL, respectively (P < or =.05). However, neither IPC (grade 3) lesions of the mucosa versus I/R (grade 4) nor LDH values (PCI = 680, I/R = 873 U/L) were statistically different. Thus No morphological evidence of protection was observed following ischemic preconditioning.
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PMID:Biochemical and morphological evaluation of ischemia-reperfusion injury in rat small bowel modulated by ischemic preconditioning. 1519 94


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