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Isoform-selective 5?-AMP-activated protein kinase-dependent preconditioning mechanisms to prevent postischemic leukocyte-endothelial cell adhesive interactions  

PubMed Central

We previously demonstrated that preconditioning induced by ethanol consumption at low levels [ethanol preconditioning (EPC)] or with 5-aminoimidazole-4-carboxamide 1-?-d-ribofuranoside (AICAR-PC) 24 h before ischemia-reperfusion prevents postischemic leukocyte-endothelial cell adhesive interactions (LEI) by a mechanism that is initiated by nitric oxide formed by endothelial nitric oxide synthase. Recent work indicates that 1) ethanol increases the activity of AMP-activated protein kinase (AMPK) and 2) AMPK phosphorylates endothelial nitric oxide synthase at the same activation site seen following EPC (Ser1177). In light of these observations, we postulated that the heterotrimeric serine/threonine kinase, AMPK, may play a role in triggering the development of the anti-inflammatory phenotype induced by EPC. Ethanol was administered to C57BL/6J mice by gavage in the presence or absence of AMPK inhibition. Twenty-four hours later, the numbers of rolling and adherent leukocytes in postcapillary venules of the small intestine were recorded using an intravital microscopic approach. Following 45 min of ischemia, LEI were recorded after 30 and 60 min of reperfusion or at equivalent time points in control animals. Ischemia-reperfusion induced a marked increase in LEI relative to sham-operated control mice. The increase in LEI was prevented by EPC, an effect that was lost with AMPK inhibition during the period of ethanol exposure. Studies conducted in AMPK ?1- and ?2-knockout mice suggest that the anti-inflammatory effects of AICAR are not dependent on which isoform of the catalytic ?-subunit is present because a deficiency of either isoform results in a loss of protection. In sharp contrast, EPC appears to be triggered by an AMPK ?2-isoform-dependent mechanism.

Spencer Gaskin, F.; Kamada, Kazuhiro; Zuidema, Mozow (Yusof); Jones, Allan W.; Rubin, Leona J.



Multidrug donor preconditioning prevents cold liver preservation and reperfusion injury  

Microsoft Academic Search

Purpose  Primary graft dysfunction still represents a major challenge in liver transplantation. We herein studied in an isolated rat\\u000a liver perfusion model whether a multidrug donor preconditioning (MDDP) can not only reduce but also completely prevent cold\\u000a ischemia–reperfusion injury.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  MDDP included curcumin, simvastatin, N-acetylcysteine, erythropoietin, pentoxyphylline, melatonin, glycine, and methylprednisolone. Postischemic reperfusion was\\u000a performed after 24 h cold storage in histidine–tryptophan–ketoglutarate solution

Mohammed Reza Moussavian; Claudia Scheuer; Michael Schmidt; Otto Kollmar; Matthias Wagner; Maximilian von Heesen; Martin K. Schilling; Michael D. Menger



Late phase ischemic preconditioning preserves mitochondrial oxygen metabolism and attenuates post-ischemic myocardial tissue hyperoxygenation  

PubMed Central

Aims Late phase ischemic preconditioning (LPC) protects the heart against ischemia reperfusion (I/R) injury. However, its effect on myocardial tissue oxygenation and related mechanism(s) are unknown. The aim of the current study is to determine whether LPC attenuates post-ischemic myocardial tissue hyperoxygenation through preserving mitochondrial oxygen metabolism. Main methods C57BL/6 mice were subjected to 30 min coronary ligation followed by 60 min or 24 hr reperfusion w/o LPC (3 cycles of 5 min I/5 min R): Sham, LPC, I/R, and LPC+I/R group. Myocardial tissue Po2 and redox status were measured with electron paramagnetic resonance (EPR) spectroscopy. Key findings Upon reperfusion, tissue Po2 rose significantly above the pre-ischemic level in the I/R mice (23.1 ± 2.2 vs. 12.6 ± 1.3 mmHg, p<0.01). This hyperoxygenation was attenuated by LPC in the LPC+I/R mice (11.9 ± 2.0 mmHg, p<0.01). Activities of NADH dehydrogenase (NADH-DH), succinate-cytochrome c reductase (SCR) and cytochrome c oxidase (CcO) were preserved or increased in the LPC group, significantly reduced in the I/R group, and conserved in the LPC+I/R group. Manganese superoxide dismutase (Mn-SOD) protein expression was increased by LPC in the LPC and LPC+I/R mice compared to that in the sham control (1.24 ± 0.01 and 1.23 ± 0.01, p<0.05). Tissue redox status was shifted to the oxidizing state with I/R (0.0268 ± 0.0016/min) and was corrected by LPC in the LPC+I/R mice (0.0379 ± 0.0023/min). Finally, LPC reduced the infarct size in the LPC+I/R mice (10.5 ± 0.4% vs. 33.3 ± 0.6%, p<0.05). Significance Thus, LPC preserved mitochondrial oxygen metabolism, attenuated post-ischemic myocardial tissue hyperoxygenation, and reduced I/R injury.

Li, Yuanjing; Cai, Ming; Xu, Yi; Swartz, Harold M.; He, Guanglong



Unique Transcriptional Profile of Sustained Ligand-Activated Preconditioning in Pre- and Post-Ischemic Myocardium  

PubMed Central

Background Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated genes in normoxic hearts from SLP mice (?1.3-fold change, FDR?5%). Induced genes encoded sarcomeric/contractile proteins (Myh7, Mybpc3,Myom2,Des), natriuretic peptides (Nppa,Nppb) and stress-signaling elements (Csda,Ptgds). Highly repressed genes primarily encoded chemokines (Ccl2,Ccl4,Ccl7,Ccl9,Ccl13,Ccl3l3,Cxcl3), cytokines (Il1b,Il6,Tnf) and other proteins involved in inflammation/immunity (C3,Cd74,Cd83, Cd86,Hla-dbq1,Hla-drb1,Saa1,Selp,Serpina3), together with endoplasmic stress proteins (known: Dnajb1,Herpud1,Socs3; putative: Il6, Gadd45g,Rcan1) and transcriptional controllers (Egr2,Egr3, Fos,Hmox1,Nfkbid). Biological themes modified thus related to inflammation/immunity, together with cellular/cardiovascular movement and development. SLP also modified the transcriptional response to I-R (46 genes uniquely altered post-ischemia), which may influence later infarction/remodeling. This included up-regulated determinants of cellular resistance to oxidant (Mgst3,Gstm1,Gstm2) and other forms of stress (Xirp1,Ankrd1,Clu), and repression of stress-response genes (Hspa1a,Hspd1,Hsp90aa,Hsph1,Serpinh1) and Txnip. Conclusions Protection via SLP is associated with transcriptional repression of inflammation/immunity, up-regulation of sarcomeric elements and natriuretic peptides, and modulation of cell stress, growth and development, while conventional protective molecules are unaltered.

Ashton, Kevin J.; Tupicoff, Amanda; Williams-Pritchard, Grant; Kiessling, Can J.; See Hoe, Louise E.; Headrick, John P.; Peart, Jason N.



Rock preconditioning to prevent rock bursts  

SciTech Connect

A US Bureau of Mines method to precondition rocks to prevent rock bursts is presented. The approach uses deep drill holes from a mine opening in a radial pattern in the vein and load and blast to fracture the rock prior to production mining. The method was successfully tested on a sphalerite-galena vein in a hard gangue of quartz and quartzite at the 7700 level of the Hecla Mining Company's Star Mine in Burke, Idaho. (JMT)

Not Available



Thermal preconditioning prevents peritendinous adhesions and inflammation.  


Adhesion formation is one of the foremost obstacles to a reliably good outcome in tendon and joint surgery. Thermal preconditioning has been found to reduce the inflammatory response through the induction of molecular chaperone expression, a recently described family of cytoprotective intracellular proteins. The authors analyzed the effect of thermal preconditioning on the inflammatory response to surgery, on tendon healing, and on the formation of peritendinous adhesions in 16 New Zealand White rabbits. Very significant decreases in adhesion formation and in the gliding and dimensions of tendons in animals that had thermal preconditioning were found. Tendons from these animals also showed a decreased level of adhesion formation and a significantly diminished inflammatory response on histologic examination with no biomechanically significant deleterious effect on the strength of tendon healing on testing load to failure. These findings are consistent with induction of heat shock proteins by hyperthermic pretreatment. Such prevention of peritendinous adhesions and the inflammatory response to injury and surgery without compromising healing are findings that have significant implications for tendon surgery and all surgery involving joints and soft tissues. PMID:12461382

Mulhall, Kevin J; McLaughlin, Raymond; Kay, Elaine; Kiely, Patrick; Bouchier-Hayes, David; Murray, Paraic



Late preconditioning against myocardial stunning. An endogenous protective mechanism that confers resistance to postischemic dysfunction 24 h after brief ischemia in conscious pigs.  

PubMed Central

Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3 of stage I). The recovery of systolic wall thickening (WTh) after the 10th reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating that the myocardium had become preconditioned against "stunning." 10 d after stage I, pigs underwent again a sequence of 10 2-min coronary occlusions for two consecutive days (days 1 and 2 of stage II). On day 1 of stage II, the recovery of WTh after the 10th reperfusion was similar to that noted on day 1 of stage I; on day 2 of stage II, however, the recovery of WTh was again markedly improved compared with day 1. Blockade of adenosine receptors with 8-p-sulfophenyl theophylline failed to prevent the development of preconditioning against stunning. Northern blot analysis demonstrated an increase in heat stress protein (HSP) 70 mRNA 2 h after the preconditioning ischemia; at this same time point, immunohistochemical analysis revealed a concentration of HSP70 in the nucleus and an overall increase in staining for HSP70. 24 h after the preconditioning ischemia, Western dot blot analysis demonstrated an increase in HSP70. This study indicates the existence of a new, previously unrecognized cardioprotective phenomenon. The results demonstrate that a brief ischemic stress induces a powerful, long-lasting (at least 48 h) adaptive response that renders the myocardium relatively resistant to stunning 24 h later (late preconditioning against stunning). This adaptive response disappears within 10 d after the last ischemic stress but can be reinduced by another ischemic stress. Unlike early and late preconditioning against infarction, late preconditioning against stunning is not blocked by adenosine receptor antagonists, and therefore appears to involve a mechanism different from that of other forms of preconditioning currently known. The increase in myocardial HSP70 is compatible with, but does not prove, a role of HSPs in the pathogenesis of this phenomenon. Images

Sun, J Z; Tang, X L; Knowlton, A A; Park, S W; Qiu, Y; Bolli, R



Glyburide prevents isoflurane's reducing effects on hydroxyl radical formation in the postischemic reperfused rat heart  

PubMed Central

BACKGROUND: The role of KATP channels in isoflurane’s reducing effects on oxygen free radical formation are not well known. OBJECTIVES: To investigate whether glyburide, an ATP-regulated potassium (KATP) channel blocker, abolishes isoflurane-induced cardioprotective effects and whether it affects hydroxyl radical formation in the postischemic reperfused heart. ANIMALS AND METHODS: Thirty-nine male Wistar rats were divided into four groups: group C (control, n=10), group I (isoflurane, n=9), group G (glyburide, n=10) and group GI (glyburide and isoflurane, n=10). The hearts were perfused as a Neely’s working heart model. Afterwards, global heart ischemia was induced for 15 min followed by reperfusion for 20 min. The formation of hydroxyl radicals in the coronary effluent and heart was measured with high performance liquid chromatography. RESULTS: Isoflurane alone and glyburide alone produced significant decreases in the duration of ventricular fibrillation during reperfusion (group C 452±345, group I 247±60, group G 261±135 s; P<0.05). In the presence of glyburide, isoflurane did not further decrease the duration of arrhythmia (group GI 230±48 s). Isoflurane reduced hydroxyl radical formation significantly in the coronary effluent during ischemia and reperfusion, but this was prevented by glyburide. CONCLUSION: The results suggest that isoflurane reduces hydroxyl radical formation, at least in part, through activation of KATP channels.

Yamaguchi, Toshiaki; Kashimoto, Satoshi; Oguchi, Takeshi; Kumazawa, Teruo



Adenosine in blood cardioplegia prevents postischemic dysfunction in ischemically injured hearts.  


Adenosine (ADO) is an endogenous cardioprotective autacoid that exerts receptor-mediated cardioprotection from ischemic-reperfusion injury. This study tested the hypothesis that blood cardioplegia (BCP) supplemented with ADO reduces postischemic left ventricular dysfunction in ischemically injured hearts. Twenty-one anesthetized dogs on total bypass were subjected to 30 minutes of normothermic global ischemia. Cold (4 degrees C) potassium BCP was then delivered every 20 minutes for 60 minutes of cardioplegic arrest. In 7 dogs, unsupplemented BCP was used; in 7 dogs, BCP was supplemented with 400 mumol/L ADO; and, in 7 dogs, ADO receptors were blocked with 8-p-sulfophenyltheophylline (30 mg/kg) given with 400 mumol/L ADO in BCP. Preischemic and postischemic left ventricular systolic function was assessed by the slope and volume axis intercept of the end-systolic pressure-volume (impedance catheter) relationship (ESPVR). In unsupplemented BCP, the postischemic slope of the ESPVR was significantly depressed by 42% versus the preischemic value (from 6.8 +/- 1.2 mm Hg/mL to 3.9 +/- 0.4 mm Hg/mL; p < 0.05 versus the preischemic value). In contrast, BCP supplemented with ADO was found to restore the postischemic ESPVR slope to preischemic levels (7.7 +/- 1.0 mm Hg/mL versus 7.4 +/- 1.2 mm Hg/mL, respectively). This cardioprotection was reversed by 8-p-sulfophenyltheophylline (9.9 +/- 1.5 mm Hg/mL versus 4.5 +/- 0.7 mm Hg/mL; p < 0.05 versus the preischemic value). Postischemic plasma creatinine kinase activity was elevated equally in all groups over the baseline values. We conclude that ADO in BCP attenuates postcardioplegia dysfunction in severely injured hearts through the operation of receptor-mediated mechanisms. PMID:7979728

Hudspeth, D A; Nakanishi, K; Vinten-Johansen, J; Zhao, Z Q; McGee, D S; Williams, M W; Hammon, J W



Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart  

Microsoft Academic Search

Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against

P. Abete; G. Testa; G. Galizia; F. Mazzella; D. Della Morte; D. de Santis; C. Calabrese; F. Cacciatore; G. Gargiulo; N. Ferrara; G. Rengo; V. Sica; C. Napoli; F. Rengo



A selective M1 and M3 receptor antagonist, penehyclidine hydrochloride, prevents postischemic LTP: Involvement of NMDA receptors.  


Our previous and other studies have confirmed that a selective M1 and M3 receptor antagonist, Penehyclidine hydrochloride (PHC), has neuroprotection activity in cerebral ischemia. However, the precise mechanisms of protection of PHC are still elusive. In this study we analyzed PHC-mediated neuroprotection on a model of brain ischemia (oxygen and glucose deprivation), named postischemic LTP (i-LTP). We found that the activation of NMDA receptor was required for the induction of i-LTP. Compared with scopolamine, PHC could prevent it due to selectively blocking M1 receptor, not M2 receptor, to decrease NMDAR activation. Our findings further showed that the inhibition of SK2 channels occluded the prevention of PHC on NMDAR activation. Furthermore, we confirmed that PHC exerted its roles through directly disinhibition of SK2 channels by blocking M1 receptor and subsequent restricting PKC activation. Moreover, our studies further revealed the critical roles of SK2 channels in i-LTP. Thus, the mechanisms of PHC in brain protection may be involved in suppression of NMDAR by regulation of SK2 channels. Our results obtained in effects of PHC on i-LTP further provided a better understanding of the therapy strategy during stroke and identified potential therapeutic targets to prevent development of ischemia. Synapse 67:865-874, 2013. © 2013 Wiley Periodicals, Inc. PMID:23813456

Ma, Teng-Fei; Zhou, Li; Wang, Yun; Qin, Shou-Jun; Zhang, Yuan; Hu, Bin; Yan, Jing-Zhi; Ma, Xing; Zhou, Cheng-Hua; Gu, Shu-Ling



Ischemic preconditioning at a remote site prevents acute kidney injury in patients following cardiac surgery.  


Acute kidney injury, a common complication of cardiac surgery with cardiopulmonary bypass, is associated with increased morbidity and mortality. Ischemic preconditioning at a remote site mitigates ischemia-reperfusion injury and may prevent acute kidney injury after cardiac surgery, thus providing clinical benefit. To further study this, we enrolled 120 adult patients undergoing elective cardiac surgery for whom cardiopulmonary bypass was anticipated in a randomized, single-blind, and controlled pilot trial. Patients were stratified for the type of surgery and equally assigned to a control group or to receive remote ischemic preconditioning by an automated thigh tourniquet consisting of three 5-min intervals of lower extremity ischemia separated by 5-min intervals of reperfusion. The primary end point was acute kidney injury defined as an elevation of serum creatinine of ?0.3?mg/dl or ?50% within 48?h after surgery. Fifty-nine patients in each group were analyzed on an intention-to-treat basis. Acute kidney injury occurred in 12 remote ischemic preconditioned and 28 control patients, reflecting an absolute risk reduction of 0.27 and a significantly reduced relative risk due to preconditioning of 0.43. Hence, remote ischemic preconditioning prevents acute kidney injury in patients undergoing cardiopulmonary bypass-assisted cardiac surgery. PMID:21677633

Zimmerman, Robert F; Ezeanuna, Prosperity U; Kane, Jane C; Cleland, Catherine D; Kempananjappa, Thejaswini J; Lucas, F Lee; Kramer, Robert S



Prevention of core cell damage in isolated islets of Langerhans by low temperature preconditioning  

Microsoft Academic Search

AIM: To study the core cell damage in isolated islets of Langerhans and its prevention by low temperature preconditioning (26 ). METHODS: Islets were cultured at 37 for 7-14 d after isolation, and then at 26 for 2, 4 and 7 d before additional culture at 37 for another 7 d. Core cell damage in the isolated islets was monitored

Yun-Fu Cui; Ming Ma; Gui-Yu Wang; De-En Han; Brigitte Vollmar; Michael D. Menger



Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts  

Microsoft Academic Search

INTRODUCTION: Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both

Dirk Bruegger; Markus Rehm; Matthias Jacob; Daniel Chappell; Mechthild Stoeckelhuber; Ulrich Welsch; Peter Conzen; Bernhard F Becker



Short-term ischemia usually used for ischemic preconditioning down-regulates central cannabinoid receptors in the gerbil hippocampus  

Microsoft Academic Search

Transient forebrain ischemia of 5-min duration causes delayed neuronal death (DND) of vulnerable CA1 neurons in the gerbil hippocampus, which can be prevented by “preconditioning” with a short ischemic stimulus of 2.5-min duration. While a key role of excitatory glutamate receptors for both phenomena has been widely accepted, little is known about the postischemic regulation of central cannabinoid (CB1) receptors.

Markus Schomacher; Harald D. Müller; Clemens Sommer



Morinda citrifolia fruit juice prevents ischemic neuronal damage through suppression of the development of post-ischemic glucose intolerance.  


Fruit juice of Morinda citrifolia (Noni juice) is a well-known health drink and has various pharmacological properties including antioxidant and anti-inflammatory effects. We have hitherto found the protective effect of Noni juice on brain damage caused by ischemic stress in mice. In addition, we also recently reported that regulation of post-ischemic glucose intolerance might be important for good prognosis. Here, we focused on the effect of Noni juice on the development of the post-ischemic glucose intolerance as a cerebral protective mechanism. Noni juice was obtained from the mature fruit grown in Okinawa (about 1.5 L/4 kg of fruit; 100% ONJ). Male ddY mice were given 10% ONJ in drinking water for 7 days. Then, mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Ingestion of 10% ONJ suppressed the development of neuronal damage after MCAO. Interestingly, glucose intolerance observed on the 1st day after MCAO completely disappeared after 10% ONJ administration. Furthermore, ONJ treatment significantly increased serum insulin levels much further than the control group on the 1st day, while serum adiponectin levels were not affected at all. These results suggest that ONJ could facilitate insulin secretion after ischemic stress and may attenuate the development of glucose intolerance. These mechanisms may contribute to the neuronal protective effect of ONJ against ischemic stress. PMID:20574728

Harada, Shinichi; Fujita-Hamabe, Wakako; Kamiya, Kohei; Mizushina, Yoshiyuki; Satake, Toshiko; Tokuyama, Shogo



Ischemic Preconditioning Prevents Free Radical Production and Mitochondrial Depolarization in Small-for-Size Rat Liver Grafts  

Microsoft Academic Search

Background. Ischemic preconditioning (IP) renders tissues more tolerant to subsequent longer episodes of ischemia. This study tested whether IP attenuates injury of small-for-size liver grafts by preventing free radical production and mitochondrial dysfunction. Methods. IP was induced by clamping the portal vein and hepatic artery for 9 min. Livers were harvested 5 min after releasing the clamp. Mitochondrial polarization and

Hasibur Rehman; Henry D. Connor; Venkat K. Ramshesh; Tom P. Theruvath; Ronald P. Mason; Gary L. Wright; John J. Lemasters; Zhi Zhong



Chemical preconditioning prevents paradoxical increase in glutamate release during ischemia by activating ATP-dependent potassium channels in gerbil hippocampus.  


Ischemic tolerance induced by pretreatment with a low dose of 3-nitropropionic acid (3-NPA), called chemical preconditioning, prolongs the delay to hypoxic depolarization and improves the recovery of synaptic transmission (Exp. Neurol. 166 (2000), 385-391). We studied the effect of chemical preconditioning on the presynaptic site by analyzing spontaneous excitatory postsynaptic currents (sEPSCs) and miniature EPSCs (mEPSCs) with a whole cell patch-clamp technique in gerbil hippocampal slices. The frequency of sEPSCs decreased first and then dramatically increased during ischemia (10 min in duration, low pO(2), and deprivation of glucose) up to 200-300%. This increase was apparently a paradox, since synaptic transmission evoked by electrical stimulation diminished when the sEPSC frequency started to increase. The frequency of mEPSCs also increased in the same time course. Increases in sEPSC and mEPSC frequencies were prevented by chemical preconditioning with 3-NPA (4 mg/kg) administered intraperitoneally 3 h before the preparation of brain slices. These effects of chemical preconditioning were abolished by glibenclamide (5 microM), a blocker of ATP-dependent potassium (K(ATP)) channels, applied in vitro before the ischemic insult. The application of diazoxide (500 microM), an opener of K(ATP) channels, produced the same preventive effects on sEPSC and mEPSC frequencies. These results suggested that chemical preconditioning acted on presynaptic terminals to prevent the paradoxical increase in glutamate release during ischemia through the activation of K(ATP) channels. PMID:12957501

Nakagawa, Ichiro; Ogawa, Yoichi; Noriyama, Yoshinobu; Nakase, Hiroyuki; Yamashita, Masayuki; Sakaki, Toshisuke



Postischemic administration of liposome-encapsulated luteolin prevents against ischemia-reperfusion injury in a rat middle cerebral artery occlusion model.  


Oxidative stress-induced neuronal cell death has been implicated in neurodegenerative diseases; one such disease is ischemic stroke. Using reactive oxygen species (ROS)-insulted primary neurons, we screened neuroprotectants with clinical potential and then, using ischemia/reperfusion (I/R) model, investigated the anti-ischemic potential of candidate neuroprotectants. Here, we showed that luteolin, isolated from the ripe fruit of Perilla frutescens (L.) Britt, exhibited a neuroprotective action upon the in vitro platform, thus serving as candidate for in vivo pharmacological evaluation. Liposome-encapsulated luteolin produced dramatic preventing effects on I/R-induced behavioral and histological injuries after a 13-day post-ischemic treatment. Furthermore, this phytochemical not only lowered the increased level of mitochondrial ROS but also substantially up-regulated the decreased activity of catalase and glutathione in I/R rat brains. Collectively, luteolin as a neuroprotectant acts by anti-ischemic activity likely through a rebalancing of pro-oxidant/antioxidant status. Its multitarget mechanisms implicate potential effectiveness for clinically treating ischemia stroke. PMID:21190830

Zhao, Gang; Zang, Shao-Yun; Jiang, Zhi-Hua; Chen, Yao-Yue; Ji, Xun-He; Lu, Bu-Feng; Wu, Jia-Hu; Qin, Guo-Wei; Guo, Li-He



Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats.  


Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage. PMID:23969972

Bakkal, B H; Gultekin, F A; Guven, B; Turkcu, U O; Bektas, S; Can, M



Modest actomyosin energy conservation increases myocardial postischemic function.  


We have proposed that pharmacological preconditioning, leading to PKC-epsilon activation, in hearts improves postischemic functional recovery through a decrease in actomyosin ATPase activity and subsequent ATP conservation. The purpose of the present study was to determine whether moderate PKC-independent decreases in actomyosin ATPase are sufficient to improve myocardial postischemic function. Rats were given propylthiouracil (PTU) for 8 days to induce a 25% increase in beta-myosin heavy chain with a 28% reduction in actomyosin ATPase activity. Recovery of postischemic left ventricular developed pressure (LVDP) was significantly higher in PTU-treated rat hearts subjected to 30 min of global ischemia than in control hearts: 57.9 +/- 6.2 vs. 32.6 +/- 5.1% of preischemic values. In addition, PTU-treated hearts exhibited a delayed onset of rigor contracture during ischemia and a higher global ATP content after ischemia. In the second part of our study, we demonstrated a lower maximal actomyosin ATPase and a higher global ATP content after ischemia in human troponin T (TnT) transgenic mouse hearts. In mouse hearts with and without a point mutation at F110I of human TnT, recovery of postischemic LVDP was 55.4 +/- 5.5 and 62.5 +/- 14.5% compared with 20.0 +/- 2.9% in nontransgenic mouse hearts after 35 min of global ischemia. These results are consistent with the hypothesis that moderate decreases in actomyosin ATPase activity result in net ATP conservation that is sufficient to improve postischemic contractile function. PMID:15498825

Blunt, Bradford C; Chen, Yi; Potter, James D; Hofmann, Polly A



Early Postischemic Hyperperfusion: Pathophysiologic Insights From Positron Emission Tomography  

Microsoft Academic Search

Early postischemic hyperperfusion (EPIH) has long been documented in animal stroke models and is the hallmark of efficient recanalization of the occluded artery with subsequent reperfusion of the tissue (although occasionally it may be seen in areas bordering the hypoperfused area during arterial occlusion). In experimental stroke, early reperfusion has been reported to both prevent infarct growth and aggravate edema

Gilles Marchal; Alan R. Young; Jean-Claude Baron



Early preconditioning prevents the loss of endothelial nitric oxide synthase and enhances its activity in the ischemic/reperfused rat heart.  


Cardiac ischemia may be responsible for either the loss of endothelial nitric oxide synthase (eNOS) or changes in its activity, both conditions leading to coronary dysfunction. We investigated whether early ischemic preconditioning was able to preserve eNOS protein expression and function in the ischemic/reperfused myocardium. Langendorff-perfused rat hearts were subjected to 20 min global ischemia, followed by 30 min reperfusion (I/R). A second group of hearts was treated as I/R, but preconditioned with three cycles of 5 min-ischemia/5 min-reperfusion (IP). Cardiac contractility markedly decreased in I/R, consistently with the rise of creatine kinase (CK) activity in the coronary effluent, whilst ischemic preconditioning significantly improved all functional parameters and reduced the release of CK. Western blot analysis revealed that the amount of eNOS protein decreased by 54.2% in I/R with respect to control (p < 0.01). On the other hand, NOS activity was not significantly reduced in I/R, as well as cGMP tissue levels, suggesting that a parallel compensatory stimulation of this enzymatic activity occurred during ischemia/reperfusion. Ischemic preconditioning completely prevented the loss of eNOS. Moreover, both NOS activity and cGMP tissue level were significantly higher (p < 0.05) in IP (12.7 +/- 0.93 pmol/min/mg prot and 58.1 +/- 12.2 fmol/mg prot, respectively) than I/R (7.34 +/- 2.01 pmol/min/mg prot and 21.4 +/- 4.13 fmol/mg prot, respectively). This suggest that early ischemic preconditioning may be useful to accelerate the complete recovery of endothelial function by preserving the level of cardiac eNOS and stimulating the basal production of nitric oxide. PMID:14687653

Muscari, Claudio; Bonafe', Francesca; Gamberini, Chiara; Giordano, Emanuele; Tantini, Benedetta; Fattori, Monia; Guarnieri, Carlo; Caldarera, Claudio Marcello



The GRONORUN 2 study: effectiveness of a preconditioning program on preventing running related injuries in novice runners. The design of a randomized controlled trial  

PubMed Central

Background Distance running is a popular recreational exercise. It is a beneficial activity for health and well being. However, running may also cause injuries, especially of the lower extremities. In literature there is no agreement what intrinsic and extrinsic factors cause running related injuries (RRIs). In theory, most RRIs are elicited by training errors, this too much, too soon. In a preconditioning program runners can adapt more gradually to the high mechanical loads of running and will be less susceptible to RRIs. In this study the effectiveness of a 4-week preconditioning program on the incidence of RRIs in novice runners prior to a training program will be studied. Methods/Design The GRONORUN 2 (Groningen Novice Running) study is a two arm randomized controlled trial studying the effect of a 4-week preconditioning (PRECON) program in a group of novice runners. All participants wanted to train for the recreational Groningen 4-Mile running event. The PRECON group started a 4-week preconditioning program with walking and hopping exercises 4 weeks before the start of the training program. The control (CON) and PRECON group started a frequently used 9-week training program in preparation for the Groningen 4-Mile running event. During the follow up period participants registered their running exposure, other sporting activities and running related injuries in an Internet based running log. The primary outcome measure was the number of RRIs. RRI was defined as a musculoskeletal ailment or complaint of the lower extremities or back causing a restriction on running for at least three training sessions. Discussion The GRONORUN 2 study will add important information to the existing running science. The concept of preconditioning is easy to implement in existing training programs and will hopefully prevent RRIs especially in novice runners. Trial registration The Netherlands National Trial Register NTR1906. The NTR is part of the WHO Primary Registries.



The mitochondrial origin of postischemic arrhythmias  

PubMed Central

Recovery of the mitochondrial inner membrane potential (??m) is a key determinant of postischemic functional recovery of the heart. Mitochondrial ROS-induced ROS release causes the collapse of ??m and the destabilization of the action potential (AP) through a mechanism involving a mitochondrial inner membrane anion channel (IMAC) modulated by the mitochondrial benzodiazepine receptor (mBzR). Here, we test the hypothesis that this mechanism contributes to spatiotemporal heterogeneity of ??m during ischemia-reperfusion (IR), thereby promoting abnormal electrical activation and arrhythmias in the whole heart. High-resolution optical AP mapping was performed in perfused guinea pig hearts subjected to 30 minutes of global ischemia followed by reperfusion. Typical electrophysiological responses, including progressive AP shortening followed by membrane inexcitablity in ischemia and ventricular fibrillation upon reperfusion, were observed in control hearts. These responses were reduced or eliminated by treatment with the mBzR antagonist 4?-chlorodiazepam (4?-Cl-DZP), which blocks depolarization of ??m. When applied throughout the IR protocol, 4?-Cl-DZP blunted AP shortening and prevented reperfusion arrhythmias. Inhibition of ventricular fibrillation was also achieved by bolus infusion of 4?-Cl-DZP just before reperfusion. Conversely, treatment with an agonist of the mBzR that promotes ??m depolarization exacerbated IR-induced electrophysiological changes and failed to prevent arrhythmias. The effects of these compounds were consistent with their actions on IMAC and ??m. These findings directly link instability of ??m to the heterogeneous electrophysiological substrate of the postischemic heart and highlight the mitochondrial membrane as a new therapeutic target for arrhythmia prevention in ischemic heart disease.

Akar, Fadi G.; Aon, Miguel A.; Tomaselli, Gordon F.; O'Rourke, Brian



Ozone oxidative preconditioning prevents atherosclerosis development in New Zealand White rabbits.  


Atherosclerosis is a major cause of death in the Western World. It is known that Lipofundin 20% induces atherosclerotic lesions, whereas ozone at low doses has been satisfactorily used in the prevention of oxidative stress-associated pathologies, such as coronary artery diseases. The aim of the present work was to evaluate the effects of ozone therapy on Lipofundin-induced atherosclerotic lesions in New Zealand White rabbits. Ozone (1 mg), mixed with oxygen as passive carrier, was administered by rectal insufflation during 15 sessions in 5 weeks. Then, the animals were intravenously treated with 2 mL/kg of Lipofundin, daily during 8 days. Animals were euthanized and eosin and hematoxylin staining was used for aortic histopathological analysis. The biomarkers of oxidative stress and lipid profile in serum were determined by spectrophotometric techniques. The results demonstrated that ozone induced inhibitory effects on aortic lesions formation. On the other hand, a reduction of biomolecular damage and an increase of antioxidant systems were observed at the end of the experiment. The serum lipids profiles were not modified after only 1 cycle of ozone treatment. Our results reinforced the hypotheses that antioxidant effects induced by ozone in the context of atherosclerosis demonstrate the antiatherogenic properties of the gas in the experimental conditions of this study. PMID:23222311

Delgado-Roche, Livan; Martínez-Sánchez, Gregorio; Re, Lamberto



Aging abolishes the cardioprotective effect of combination heat shock and hypoxic preconditioning in reperfused rat hearts  

Microsoft Academic Search

.   Hypoxic preconditioning (HP) does not improve post-ischemic function in the hearts of aging rats secondary to failure of\\u000a protein kinase C (PKC) activation, but the effect of heat shock (HS) or preconditioning has not been studied. We studied whether\\u000a HS increases tolerance to ischemia and whether its combination with HP would restore the cardioprotective effect in aging\\u000a rat hearts.

Yukako Honma; Masato Tani; Michiyo Takayama; Ken Yamamura; Hiroshi Hasegawa



Preconditioning Balloons  

NSDL National Science Digital Library

Students use balloons (a polymer) to explore preconditioningâa viscoelastic material behavior that is important to understand when designing biomedical devices. They improve their understanding of preconditioning by measuring the force needed to stretch a balloon to the same displacement multiple times. Students gain experience in data collection and graph interpretation.

Integrated Teaching And Learning Program


Sustained Ligand-Activated Preconditioning via ?-Opioid Receptors  

PubMed Central

We have previously described novel cardioprotection in response to sustained morphine exposure, efficacious in young to aged myocardium and mechanistically distinct from conventional opioid or preconditioning (PC) responses. We further investigate opioid-dependent sustained ligand-activated preconditioning (SLP), assessing duration of protection, opioid receptor involvement, additivity with conventional responses, and signaling underlying preischemic induction of the phenotype. Male C57BL/6 mice were treated with morphine (75-mg subcutaneous pellet) for 5 days followed by morphine-free periods (0, 3, 5, or 7 days) before ex vivo assessment of myocardial tolerance to 25-min ischemia/45-min reperfusion. SLP substantially reduced infarction (by ?50%) and postischemic contractile dysfunction (eliminating contracture, doubling force development). Cardioprotection persisted for 5 to 7 days after treatment. SLP was induced specifically by ?-receptor and not ?- or ?-opioid receptor agonism, was eliminated by ?-receptor and nonselective antagonism, and was additive with adenosinergic but not acute morphine- or PC-triggered protection. Cotreatment during preischemic morphine exposure with the phosphoinositide-3 kinase (PI3K) inhibitor wortmannin, but not the protein kinase A (PKA) inhibitor myristoylated PKI-(14-22)-amide, prevented induction of SLP. This was consistent with shifts in total and phospho-Akt during the induction period. In summary, data reveal that SLP triggers sustained protection from ischemia for up to 7 days after stimulus, is ?-opioid receptor mediated, is induced in a PI3K-dependent/PKA-independent manner, and augments adenosinergic protection. Mechanisms underlying SLP may be useful targets for manipulation of ischemic tolerance in young or aged myocardium.

Hoe, Louise E. See; Gross, Garrett J.; Headrick, John P.



Cerebral postischemic hypoperfusion is mediated by ET A receptors  

Microsoft Academic Search

Effect of ETA-receptor antagonist, BQ123, on postischemic hypoperfusion in the presence or absence of nitric oxide synthetase inhibitor,N?-nitro-l-arginine (NLA), was investigated in Mongolian gerbils. BQ123 given prior to ischemia reversed the early incomplete recovery of cerebral blood flow observed with NLA without affecting the late postischemic hypoperfusion. Additional postischemic administration of BQ123 also reversed (P ) the late postischemic hypoperfusion

Maria Spatz; Yoshihide Yasuma; Alois Strasser; Richard M. McCarron



Targeted deletion of the A3 adenosine receptor confers resistance to myocardial ischemic injury and does not prevent early preconditioning.  


We used mice with genetic disruption of the A3 adenosine receptor (AR) gene (A3AR(-/-)mice) to assess the in vivo role of the A3AR in modulating myocardial ischemia/reperfusion injury and preconditioning (PC). Surprisingly, infarct size induced by 30 min of coronary artery occlusion and 24 h of reperfusion was 35% smaller in A3AR(-/-)compared to wild-type mice (A3AR(+/+)). The reduction in infarct size was not the result of differences in heart rate, body temperature or increased cardiac expression of A1ARs. However, neutrophil infiltration within infarcted regions was less in A3AR(-/-)mice. Furthermore, ischemic PC induced by either a single episode (one 5 min occlusion) or multiple episodes (six 4 min occlusions) of ischemia produced equivalent reductions in infarct size in A3AR(-/-)and A3AR(+/+)mice. These results indicate that, in the mouse, (i) A3ARs play an injurious role during acute myocardial ischemia/reperfusion injury, possibly by exacerbating the inflammatory response, and (ii) A3ARs are not necessary for the development of the early phase of ischemic PC. PMID:11273734

Guo, Y; Bolli, R; Bao, W; Wu, W J; Black, R G; Murphree, S S; Salvatore, C A; Jacobson, M A; Auchampach, J A



Calcium-sensing receptor: a sensor and mediator of ischemic preconditioning in the heart.  


As a G protein-coupled receptor, the extracellular Ca(2+)-sensing receptor (CaSR) responds to changes not only in extracellular Ca(2+), but also to many other ligands. CaSR has been found to be expressed in the hearts and cardiovascular system. In this study, we confirmed that CaSR is expressed in mouse cardiomyocytes and showed that it is predominantly localized in caveolae. The goal of this study was to investigate whether CaSR plays a cardioprotective role in ischemic preconditioning (IPC). Hearts from C57BL/6J mice (male, 12-16 wk) were perfused in the Langendorff mode and subjected to the following treatments: 1) control perfusion; 2) perfusion with a specific CaSR antagonist, NPS2143; 3) IPC (four cycles of 5 min of global ischemia and 5 min of reperfusion); or 4) perfusion with NPS2143 before and during IPC. Following these treatments, hearts were subjected to 20 min of no-flow global ischemia and 120 min of reperfusion. Compared with control, IPC significantly improved postischemic left ventricular functional recovery and reduced infarct size. Although NPS2143 perfusion alone did not change the hemodynamic function and did not change the extent of postischemic injury, NPS2143 treatment abolished cardioprotection of IPC. Through immunoblot analysis, it was demonstrated that IPC significantly increased the levels of phosphorylated ERK1/2, AKT, and GSK-3?, which were also prevented by NPS2143 treatment. Taken together, the distribution of CaSR in caveolae along with NPS2143-blockade of IPC-induced cardioprotective signaling suggest that the activation of CaSR during IPC is cardioprotective by a process involving caveolae. PMID:20833954

Sun, Junhui; Murphy, Elizabeth



Postischemic Cerebral Blood Flow and Neuroeffector Mechanisms  

Microsoft Academic Search

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by

Robert Macfarlane; Michael A. Moskowitz; Erol Tasdemiroglu; Enoch P. Wei; Hermes A. Kontos



MicroRNAs in Postischemic Vascular Repair.  


The term angiogenesis describes the growth of endothelial sprouts from preexisting postcapillary venules. More recently, this term has been used to generally indicate the growth and remodeling process of the primitive vascular network into a complex network during development. In adulthood, angiogenesis is activated as a reparative process during wound healing and following ischemia, and it plays a key role in tumor growth and metastasis as well as in inflammatory diseases and diabetic retinopathy. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that negatively control gene expression of target mRNAs. In this paper, we aim at describing the role of miRNAs in postischemic angiogenesis. First, we will describe the regulation and the expression of miRNAs in endothelial cells. Then, we will analyze the role of miRNAs in postischemic vascular repair. Finally, we will discuss the role of circulating miRNAs as potential biomarkers in ischemic diseases. PMID:22482069

Caporali, Andrea; Emanueli, Costanza



Post-Ischemic Inflammation in the Brain  

PubMed Central

Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. In this review, we focus on the post-ischemic inflammation triggered by infiltrating immune cells, macrophages, and T lymphocytes. Brain ischemia is a sterile organ, but injury-induced inflammation is mostly dependent on Toll-like receptor (TLR) 2 and TLR4. Some endogenous TLR ligands, high mobility group box 1 (HMGB1) and peroxiredoxin family proteins, in particular, are implicated in the activation and inflammatory cytokine expression in infiltrating macrophages. Following macrophage activation, T lymphocytes infiltrate the ischemic brain and regulate the delayed phase inflammation. IL-17-producing ??T lymphocytes induced by IL-23 from macrophages promote ischemic brain injury, whereas regulatory T lymphocytes suppress the function of inflammatory mediators. A deeper understanding of the inflammatory mechanisms of infiltrating immune cells may lead to the development of novel neuroprotective therapies.

Shichita, Takashi; Sakaguchi, Ryota; Suzuki, Mayu; Yoshimura, Akihiko



MicroRNAs in Postischemic Vascular Repair  

PubMed Central

The term angiogenesis describes the growth of endothelial sprouts from preexisting postcapillary venules. More recently, this term has been used to generally indicate the growth and remodeling process of the primitive vascular network into a complex network during development. In adulthood, angiogenesis is activated as a reparative process during wound healing and following ischemia, and it plays a key role in tumor growth and metastasis as well as in inflammatory diseases and diabetic retinopathy. MicroRNAs (miRNAs) are endogenous, small, noncoding RNAs that negatively control gene expression of target mRNAs. In this paper, we aim at describing the role of miRNAs in postischemic angiogenesis. First, we will describe the regulation and the expression of miRNAs in endothelial cells. Then, we will analyze the role of miRNAs in postischemic vascular repair. Finally, we will discuss the role of circulating miRNAs as potential biomarkers in ischemic diseases.

Caporali, Andrea; Emanueli, Costanza



Towards a dynamical network view of brain ischemia and reperfusion. Part II: a post-ischemic neuronal state space  

PubMed Central

The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the “ischemic cascade”. This is the second in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ischemia. We here build the bistable network model of brain ischemia. The central concept is that of a post-ischemic state space. Ischemia, as a quantitative perturbation, is envisioned to push the brain through a series of four phenotypes as a function of the amount of ischemia: the homeostatic, preconditioned, delayed neuronal death and necrotic phenotypes. The phenotypes are meta-stable attractors in the landscape of the post-ischemic state space. The sequence of the phenotypes derives from the mutual antagonism between damage mechanisms and stress responses, each conceived as aggregate ensemble variables. The competition between damage mechanisms and stress responses is posited to have the form of a bistability. Application of bistability to brain ischemia is grounded in the incontrovertible fact that post-ischemic neurons face the mutually exclusive decision to either live or die.

DeGracia, Donald J.



Equilibrative nucleoside transporter 1 (ENT1) regulates postischemic blood flow during acute kidney injury in mice  

PubMed Central

A complex biologic network regulates kidney perfusion under physiologic conditions. This system is profoundly perturbed following renal ischemia, a leading cause of acute kidney injury (AKI) — a life-threatening condition that frequently complicates the care of hospitalized patients. Therapeutic approaches to prevent and treat AKI are extremely limited. Better understanding of the molecular pathways promoting postischemic reflow could provide new candidate targets for AKI therapeutics. Due to its role in adapting tissues to hypoxia, we hypothesized that extracellular adenosine has a regulatory function in the postischemic control of renal perfusion. Consistent with the notion that equilibrative nucleoside transporters (ENTs) terminate adenosine signaling, we observed that pharmacologic ENT inhibition in mice elevated renal adenosine levels and dampened AKI. Deletion of the ENTs resulted in selective protection in Ent1–/– mice. Comprehensive examination of adenosine receptor–knockout mice exposed to AKI demonstrated that renal protection by ENT inhibitors involves the A2B adenosine receptor. Indeed, crosstalk between renal Ent1 and Adora2b expressed on vascular endothelia effectively prevented a postischemic no-reflow phenomenon. These studies identify ENT1 and adenosine receptors as key to the process of reestablishing renal perfusion following ischemic AKI. If translatable from mice to humans, these data have important therapeutic implications.

Grenz, Almut; Bauerle, Jessica D.; Dalton, Julee H.; Ridyard, Douglas; Badulak, Alexander; Tak, Eunyoung; McNamee, Eoin N.; Clambey, Eric; Moldovan, Radu; Reyes, German; Klawitter, Jost; Ambler, Kelly; Magee, Kristann; Christians, Uwe; Brodsky, Kelley S.; Ravid, Katya; Choi, Doo-Sup; Wen, Jiaming; Lukashev, Dmitriy; Blackburn, Michael R.; Osswald, Hartmut; Coe, Imogen R.; Nurnberg, Bernd; Haase, Volker H.; Xia, Yang; Sitkovsky, Michail; Eltzschig, Holger K.



Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat  

Microsoft Academic Search

This study evaluates whether preconditioning could modulate the injurious effects of tumor necrosis factor (TNF) on liver and lung following hepatic ischemia-reperfusion (I\\/R) by inhibiting hepatic postischemic TNF release. The inhibition of hepatic TNF release from Kupffer cells with gadolinium chloride (GdCl3) previous to ischemia maintained TNF at control levels, attenuating the increases in transaminases, vascular permeability, and edema associated

Carmen Peralta; Neus Prats; Carme Xaus



Fetal brain genomic reprogramming following asphyctic preconditioning  

PubMed Central

Background Fetal asphyctic (FA) preconditioning is effective in attenuating brain damage incurred by a subsequent perinatal asphyctic insult. Unraveling mechanisms of this endogenous neuroprotection, activated by FA preconditioning, is an important step towards new clinical strategies for asphyctic neonates. Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of preconditioning. Therefore we investigated whole genome differential gene expression in the preconditioned rat brain. FA preconditioning was induced on embryonic day 17 by reversibly clamping uterine circulation. Male control and FA offspring were sacrificed 96 h after FA preconditioning. Whole genome transcription was investigated with Affymetrix Gene1.0ST chip. Results Data were analyzed with the Bioconductor Limma package, which showed 53 down-regulated and 35 up-regulated transcripts in the FA-group. We validated these findings with RT-qPCR for adh1, edn1, leptin, rdh2, and smad6. Moreover, we investigated differences in gene expression across different brain regions. In addition, we performed Gene Set Enrichment Analysis (GSEA) which revealed 19 significantly down-regulated gene sets, mainly involved in neurotransmission and ion transport. 10 Gene sets were significantly up-regulated, these are mainly involved in nucleosomal structure and transcription, including genes such as mecp2. Conclusions Here we identify for the first time differential gene expression after asphyctic preconditioning in fetal brain tissue, with the majority of differentially expressed transcripts being down-regulated. The observed down-regulation of cellular processes such as neurotransmission and ion transport could represent a restriction in energy turnover which could prevent energy failure and subsequent neuronal damage in an asphyctic event. Up-regulated transcripts seem to exert their function mainly within the cell nucleus, and subsequent Gene Set Enrichment Analysis suggests that epigenetic mechanisms play an important role in preconditioning induced neuroprotection.



Hypoxic preconditioning attenuates neuronal cell death by preventing MEK/ERK signaling pathway activation after transient global cerebral ischemia in adult rats.  


Our previous data indicated that hypoxic preconditioning (HPC) ameliorates transient global cerebral ischemia (tGCI)-induced neuronal death in hippocampal CA1 subregion of adult rats. However, the possible molecular mechanisms for neuroprotection of this kind are largely unknown. This study was performed to investigate the role of the mitogen-activated protein kinase/extra-cellular signal-regulated kinase kinase (MEK)/extra-cellular signal-regulated kinase (ERK) pathway in HPC-induced neuroprotection. tGCI was induced by applying the four-vessel occlusion method. Pretreatment with 30 min of hypoxia applied 1 day before 10 min tGCI significantly decreased the level of MEK1/2 and ERK1/2 phosphorylation in ischemic hippocampal CA1 subregion. Also, HPC decreased the expression of phosphorylated ERK1/2 in degenerating neurons and astrocytes. However, the administration of U0126, a MEK kinase inhibitor, partly blocked MEK1/2 and ERK1/2 phosphorylation induced by tGCI. Meanwhile, neuronal survival was improved, and glial cell activation was significantly reduced. Collectively, these data indicated that the MEK/ERK signaling pathway might be involved in HPC-induced neuroprotection following tGCI. Also, HPC resulted in a reduction of glial activation. PMID:23519519

Zhan, Lixuan; Yan, Hongxin; Zhou, Huarong; Sun, Weiwen; Hou, Qinghua; Xu, En



Glucose metabolism, energetics, and function of rat hearts exposed to ischemic preconditioning and oxygenated cardioplegia.  


We examined changes induced during ischemia-reperfusion on myocardial metabolism and function by oxygenated warm cardioplegia (CP) and ischemic preconditioning (IP). The postischemic hemodynamic recovery was comparable and significantly better in IP and CP groups, than in untreated hearts (e.g., LVDP recovery was threefold that of the control). The IP hearts reached a pH plateau earlier during ischemia and at considerably higher pH value (pH approximately 6) compared to the other groups (pH approximately 5.5). Postischemic phosphocreatine (PCr) and ATP recoveries were comparable and better in protected groups (approximately 72% and approximately 30% vs approximately 25% and approximately 10% in control, p < 0.0001). Preischemic glycogen was significantly reduced in IP to 49% and increased in CP hearts to 127%. However, the lactate levels at the end of ischemia were similar in all the groups, indicating glucose utilization from extracellular space during ischemia in IP hearts. Thus, similar hemodynamic protection by CP and IP is observed despite increased energy depletion during ischemia in IP. IP and CP protection is expressed through better energetic status and by higher recovery of the TCA cycle activity or enhanced mitochondria-cytosol transport of alpha-ketoglutarate on reperfusion in addition to metabolic changes during ischemia. Glycogen store recovered significantly better in IP than in CP and Control. These results exhibit similar and improved postischemic hemodynamic protection by CP and IP. Increased recovery of postischemic glycogen pool is a protective feature of IP, whereas slightly higher lactate metabolism during reperfusion is a protection component of CP. PMID:12489906

Olivson, Abira; Berman, Elisha; Houminer, Ester; Borman, Joseph B; Merin, Gideon; Karck, Matthias; Haverich, Axel; Chisin, Roland; Schwalb, Herzl


Effects of red light on postischemic myocardium during reperfusion.  


Effects of low-intensity red light on lipid peroxidation in isolated rat heart in the postischemic period were studied. It was established that both laser and wideband luminescent irradiation applied during reperfusion reduced the content of lipid peroxidation products in tissues to a near-control level. This effect is possibly associated with reactivation of antioxidant enzymes. PMID:11550016

Drugova, O V; Monich, V A; Zhitnikova, O V



Reduced matrix metalloproteinase-9 activity and cell death after global ischemia in the brain preconditioned with hyperbaric oxygen.  


Matrix metalloproteinase-9 (MMP-9) plays a deleterious role in cell death after global cerebral ischemia. Preconditioning with hyperbaric oxygen (HBO-PC) reduces neuronal damage in the post-ischemic brain; however, its effect on ischemia-induced increase in MMP-9 activity and expression remains unexplored.We investigated effects of HBO-PC on alterations in MMP-9 activity/tissue expression accompanying neuronal death after transient global cerebral ischemia.Male SD rats (300-350 g), were allocated either to non-ischemic (naive control or sham-operated) or ischemic (four-vessel occlusion, 4VO; 10 min) groups that were HBO-preconditioned (2.5 ATA, 1 h daily for 5 days; the last session 24 h before ischemia) or not. Neurobehavioral deficits were assessed prior to collection of brain tissue for gel zymography (MMP-9) and histology (MMP-9 immunofluorescence, TUNEL) at 0 (without ischemia), 6, 24, 72 h and 7 days after 4VO.Both, MMP-9 levels and cell death increased in the hippocampus at 72 h after 4VO. HBO-PC suppressed postischemic MMP-9 activity and CA1 cell damage, and improved functional performance. The increase in MMP-9 immunoreactivity in the brain was also detected after HBO-PC alone. HBO-PC suppresses MMP-9 activity and expression in the postischemic hippocampus. The mechanism of HBO preconditioning may depend on the induction of MMP-9 in the preischemic phase and may be in part mediated by exhaustion of MMP-9 stores in cerebral tissues. PMID:19812919

Ostrowski, Robert P; Jadhav, Vikram; Chen, Wanqiu; Zhang, John H



Reduced Matrix Metalloproteinase-9 Activity and Cell Death After Global Ischemia in the Brain Preconditioned with Hyperbaric Oxygen  

Microsoft Academic Search

\\u000a Matrix metalloproteinase-9 (MMP-9) plays a deleterious role in cell death after global cerebral ischemia. Preconditioning\\u000a with hyperbaric oxygen (HBO-PC) reduces neuronal damage in the post-ischemic brain; however, its effect on ischemia-induced\\u000a increase in MMP-9 activity and expression remains unexplored.\\u000a \\u000a \\u000a We investigated effects of HBO-PC on alterations in MMP-9 activity\\/tissue expression accompanying neuronal death after transient\\u000a global cerebral ischemia.\\u000a \\u000a \\u000a \\u000a Male SD

Robert P. Ostrowski; Vikram Jadhav; Wanqiu Chen; John H. Zhang


Hypoxia preconditioning protects corneal stromal cells against induced apoptosis.  


The purpose of this study, was to determine whether hypoxia preconditioning can protect corneal stromal cells from UV stress and cytokine mediated apoptosis. Two models were implemented. First, primary cultured bovine corneal fibroblasts were preconditioned with 0.5-1.5% O2 for 4 hr and stressed with UV-irradiation or stimulation of Fas receptor. Second, bovine eyes were preconditioned with 0.5% O2 for 4 hr and stressed by epithelial scraping to induce anterior keratocyte apoptosis. Cell fate was analyzed at 4 hr after stress using quantitative TUNEL or condensed nuclei assays. Cell apoptotic rates in hypoxia preconditioned groups were significantly lower (50-80%) than that of normoxia control groups. Hypoxia prevented the degradation of the transcription factor HIF-1alpha. CoCl2 (100-200 microM), a chemical inducer of HIF-1alpha, also produced strong protection against UV and Fas induced apoptosis. Moreover, hypoxia preconditioned media protected cells against UV-induced apoptosis. These findings demonstrate that hypoxia preconditioning has a generalized protective effect against stromal fibroblast and keratocyte apoptosis and suggest that HIF-1alpha mediated expression and secretion of protective factors is involved. PMID:16364292

Xing, Dongmei; Sun, Xingcai; Li, Jinhua; Cui, Miao; Tan-Allen, Kah; Bonanno, Joseph A



Hypoxia preconditioning protects corneal stromal cells against induced apoptosis  

PubMed Central

The purpose of this study, was to determine whether hypoxia preconditioning can protect corneal stromal cells from UV stress and cytokine mediated apoptosis. Two models were implemented. First, primary cultured bovine corneal fibroblasts were preconditioned with 0.5–1.5% O2 for 4 hr and stressed with UV-irradiation or stimulation of Fas receptor. Second, bovine eyes were preconditioned with 0.5% O2 for 4 hr and stressed by epithelial scraping to induce anterior keratocyte apoptosis. Cell fate was analyzed at 4 hr after stress using quantitative TUNEL or condensed nuclei assays. Cell apoptotic rates in hypoxia preconditioned groups were significantly lower (50–80%) than that of normoxia control groups. Hypoxia prevented the degradation of the transcription factor HIF-1?. CoCl2 (100–200 ?M), a chemical inducer of HIF-1?, also produced strong protection against UV and Fas induced apoptosis. Moreover, hypoxia preconditioned media protected cells against UV-induced apoptosis. These findings demonstrate that hypoxia preconditioning has a generalized protective effect against stromal fibroblast and keratocyte apoptosis and suggest that HIF-1? mediated expression and secretion of protective factors is involved.

Xing, Dongmei; Sun, Xingcai; Li, Jinhua; Cui, Miao; Tan-Allen, Kah; Bonanno, Joseph A.



Transgenic overexpression of cardiac A(1) adenosine receptors mimics ischemic preconditioning.  


The role of A(1) adenosine receptors (A(1)AR) in ischemic preconditioning was investigated in isolated crystalloid-perfused wild-type and transgenic mouse hearts with increased A(1)AR. The effect of preconditioning on postischemic myocardial function, lactate dehydrogenase (LDH) release, and infarct size was examined. Functional recovery was greater in transgenic versus wild-type hearts (44.8 +/- 3.4% baseline vs. 25.6 +/- 1.7%). Preconditioning improved functional recovery in wild-type hearts from 25.6 +/- 1.7% to 37.4 +/- 2.2% but did not change recovery in transgenic hearts (44.8 +/- 3.4% vs. 44.5 +/- 3.9%). In isovolumically contracting hearts, pretreatment with selective A(1) receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine attenuated the improved functional recovery in both wild-type preconditioned (74.2 +/- 7.3% baseline rate of pressure development over time untreated vs. 29.7 +/- 7.3% treated) and transgenic hearts (84.1 +/- 12.8% untreated vs. 42.1 +/- 6.8% treated). Preconditioning wild-type hearts reduced LDH release (from 7,012 +/- 1,451 to 1,691 +/- 1,256 U. l(-1). g(-1). min(-1)) and infarct size (from 62.6 +/- 5.1% to 32.3 +/- 11.5%). Preconditioning did not affect LDH release or infarct size in hearts overexpressing A(1)AR. Compared with wild-type hearts, A(1)AR overexpression markedly reduced LDH release (from 7,012 +/- 1,451 to 917 +/- 1,123 U. l(-1). g(-1). min(-1)) and infarct size (from 62.6 +/- 5.1% to 6.5 +/- 2.1%). These data demonstrate that murine preconditioning involves endogenous activation of A(1)AR. The beneficial effects of preconditioning and A(1)AR overexpression are not additive. Taken with the observation that A(1)AR blockade equally eliminates the functional protection resulting from both preconditioning and transgenic A(1)AR overexpression, we conclude that the two interventions affect cardioprotection via common mechanisms or pathways. PMID:10993769

Morrison, R R; Jones, R; Byford, A M; Stell, A R; Peart, J; Headrick, J P; Matherne, G P



[Plastic restructuring of cerebral cortex synapses in the postischemic period].  


Using the technique for the cerebral tissue contrasting with phosphoric-tungsten acid, synaptic architectonics of the molecular layer of the rat sensomotor cortex has been studied for 30 days of recirculation after 5 minutes' stop of the systemic circulation resulted from an acute hemorrhage. Gradation of the synapses per groups is performed according to the height of compact projections of the presynaptic network. Dynamics of the synaptic compactness changes with different height is stated to differ essentially during the postischemic period. A conclusion is made that in reconstruction of the synaptic architectonics of the neocortex during the postischemic period a leading role belongs to the change of state of specialized paramembranous microfilamentous compact projections of the presynaptic network. They make a part of the neuronal cytoskeleton and are included into a single integral complex--the system of subcytoskeleton and are included into a single integral complex--the system of subsynaptic units. PMID:3446097

Semchenko, V V; Stepanov, S S



Pharmacologic Preconditioning: Translating the Promise  

PubMed Central

A transient, ischemia-resistant phenotype known as “ischemic tolerance” can be established in brain in a rapid or delayed fashion by a preceding noninjurious “preconditioning” stimulus. Initial preclinical studies of this phenomenon relied primarily on brief periods of ischemia or hypoxia as preconditioning stimuli, but it was later realized that many other stressors, including pharmacologic ones, are also effective. This review highlights the surprisingly wide variety of drugs now known to promote ischemic tolerance, documented and to some extent mechanistically characterized in preclinical animal models of stroke. Although considerably more experimentation is needed to thoroughly validate the ability of any currently identified preconditioning agent to protect ischemic brain, the fact that some of these drugs are already clinically approved for other indications implies that the growing enthusiasm for translational success in the field of pharmacologic preconditioning may be well justified.

Gidday, Jeffrey M.



Sustained postischemic cardiodepression following magnesium-diltiazem cardioplegia  

SciTech Connect

Magnesium-diltiazem cardioplegia was evaluated in the intact, perfused rat heart to determine whether the joint administration of these agents would adversely affect myocardial contractile and high-energy phosphate recovery following intermittent, normothermic global ischemic arrest. Sequential metabolic and functional analyses were performed on isolated perfused rat hearts during each phase of the experimental protocol: control, normoxic cardioplegia, intermittent global ischemic arrest, and normoxic postischemic control reperfusion. Four different cardioplegic solutions were evaluated: 30 mM KCl, 30 mM KCl with 2 mg diltiazem/liter, 20 mM MgCl/sub 2/, and 20 mM MgCl/sub 2/ with 2 mg diltiazem/liter. Myocardial phosphatic metabolite levels and intracellular pH were analyzed nondestructively in the intact hearts by phosphorus-31 NMR spectroscopy. Corresponding measurements of peak left intraventricular pressure, rate of peak pressure development (dP/dt), and contraction frequency were performed at the midpoint during each 5-min interval of /sup 31/P NMR signal averaging. Magnesium plus diltiazem-treated hearts were distinguished from all other groups by a marked delay in postischemic functional recovery consisting of a prolonged depression in contractility (34% of control, P < 0.01) that persisted throughout the first 50 min of postischemic reperfusion. The apparent adverse interactive effects of excess magnesium and diltiazem suggest that elective ischemic arrest with magnesium cardioplegia in combination with diltiazem may be contraindicated clinically.

Wallis, D.E.; Gierke, L.W.; Scanlon, P.J.; Wolfson, P.M.; Kopp, S.J.



Cytokine mRNA expression in postischemic/reperfused myocardium.  

PubMed Central

While the role of cytokines in mediating injury during hind limb skeletal muscle ischemia followed by reperfusion has recently been described, the role of cytokines in myocardial infarction and ischemia/reperfusion have remained relatively unexplored. We hypothesize that cytokines play an important role in the regulation of postischemic myocardial inflammation. This study reports the temporal sequence of proinflammatory cytokine gene expression in postischemic/reperfused myocardium and localizes interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha)-protein by immunostaining. Rats were subjected to either permanent left anterior descending (LAD) occlusion or to 35 minutes of LAD occlusion followed by reperfusion and sacrificed up to 7 days later. Rat-specific oligonucleotide probes were used to semiquantitatively assess the relative expression of mRNA for TNF-alpha, IL-1 beta, IL-2, IL-6, interferon-gamma (IFN-gamma), and transforming growth factor-beta 1 (TGF-beta 1) utilizing the reverse transcriptase-polymerase chain reaction amplification technique. Increased cardiac mRNA levels for all cytokines except IL-6 and IFN-gamma were measurable within 15 to 30 minutes of LAD occlusion and increased levels were generally sustained for 3 hours. During early reperfusion, mRNA levels for IL-6 and TGF-beta 1 were significantly reduced compared with permanent LAD occlusion. In both groups, cytokine mRNA levels all returned to baseline levels at 24 hours, while IL-1 beta, TNF-alpha, and TGF-beta 1 mRNA levels again rose significantly at 7 days only in animals with permanent LAD occlusion. Immunostaining for IL-1 beta and TNF-alpha protein revealed two patterns of reactivity: 1) microvascular staining for both IL-1 beta and TNF-alpha protein only in postischemic reperfused myocardium in early post-reperfusion time points; and 2) staining of infiltrating macrophages in healing infarct zones which was most prominent at 7 days after permanent LAD occlusion. These results provide evidence for local expression of cytokine mRNA in postischemic myocardium and suggest that regulation of local cytokine release is altered during the postischemic period. Images Figure 1 Figure 3

Herskowitz, A.; Choi, S.; Ansari, A. A.; Wesselingh, S.



Clinical Application of Ischemic Preconditioning in the Elderly  

PubMed Central

A mild stress such as brief ischemic episodes may protect the heart from a successive and more prolonged myocardial ischemia (ischemic preconditioning). This phenomenon is considered a typical “hormetic mechanism” by which the heart is immunized from pathological insults such as myocardial ischemia. This mechanism is reduced with aging and it may be restored and/or preserved by drugs such as adenosine or nicorandil, a mitochondrial KATP channels, and lifestyle interventions such as physical activity and/or hypocaloric diet. Moreover, since the mechanisms involved in cardiac ischemic preconditioning have been established basic and clinical investigators are encouraged to test several drug in well-controlled animal and human studies in order to prevent and/or restore the age-related reduction of ischemic preconditioning.

Abete, Pasquale; Cacciatore, Francesco; Testa, Gianluca; Della-Morte, David; Galizia, Gianluigi; Ferrara, Nicola; Rengo, Franco



PKC regulation of neuronal zinc signaling mediates survival during preconditioning  

PubMed Central

Sub-lethal activation of cell death processes initiate pro-survival signaling cascades. As intracellular Zn2+ liberation mediates neuronal death pathways, we tested whether a sub-lethal increase in free Zn2+ could also trigger neuroprotection. Neuronal free Zn2+ transiently increased following preconditioning, and was both necessary and sufficient for conferring excitotoxic tolerance. Lethal exposure to NMDA led to a delayed increase in Zn2+ that contributed significantly to excitotoxicity in non-preconditioned neurons, but not in tolerant neurons, unless preconditioning-induced free Zn2+ was chelated. Thus, preconditioning may trigger the expression of Zn2+-regulating processes, which, in turn, prevent subsequent Zn2+-mediated toxicity. Indeed, preconditioning increased Zn2+-regulated gene expression in neurons. Examination of the molecular signaling mechanism leading to this early Zn2+ signal revealed a critical role for protein kinase C (PKC) activity, suggesting that PKC may act directly on the intracellular source of Zn2+. We identified a conserved PKC phosphorylation site at serine-32 (S32) of metallothionein (MT) that was important in modulating Zn2+-regulated gene expression and conferring excitotoxic tolerance. Importantly, we observed increased PKC-induced serine phosphorylation in immunopurified MT1, but not in mutant MT1(S32A). These results indicate that neuronal Zn2+ serves as an important, highly regulated signaling component responsible for the initiation of a neuroprotective pathway.

Aras, Mandar A.; Hara, Hirokazu; Hartnett, Karen A.; Kandler, Karl; Aizenman, Elias



Delayed Postischemic Hypothermia: A Six Month Survival Study Using Behavioral and Histological A ssessments of Neuroprotection  

Microsoft Academic Search

In the gerbil, brief global forebrain ischemia induces pro- found habituation and working memory impairments that stem from delayed hippocampal CA1 death. Short duration postischemic hypothermia has been shown to reduce CA1 loss, but such reports are controversial, as it is thought that protection may be transient. The purpose of this study was to investigate whether prolonged postischemic hypo- thermia

Frederick Colbourne; Dale Corbett


Thermal preconditioning protects the human internal mammary artery from hypoxia/re-oxygenation-induced damage.  


1. Preconditioning has been demonstrated to ameliorate ischaemia/reperfusion injury in several cells and tissues. Therefore, in the present study we investigated whether preconditioning of human bypass grafts, internal mammary artery (IMA) and saphenous vein (SV) induces heat shock protein (Hsp) expression and reduces apoptosis in response to subsequent hypoxia/re-oxygenation damage in both vessels. 2. Internal mammary artery and SV rings, obtained from 30 patients (median age 66.5 years) undergoing coronary artery bypass grafting, were either incubated for 30 min at 42 degrees C (preconditioned) or kept in a standard incubator at 37 degrees C (not preconditioned). Six hours later, graft segments were exposed to 90 min hypoxia followed by a 30 min re-oxygenation period. Western blot, real-time quantative polymerase chain reaction analysis and apoptosis detection by the Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling method were performed. 3. Heat-preconditioned IMA showed significantly increased protein expression of Hsp72 after hypoxia/re-oxygenation treatment compared with controls (median 9.1 vs 5.0 microg/mg total protein; P = 0.048). Expression of Hsp73 was weak and Hsp60 was not detectable in the IMA. 4. In the SV, neither protein nor mRNA expression of Hsp were significantly different between preconditioned and not preconditioned veins. 5. There were significantly fewer apoptotic cells in the intima of the preconditioned compared with not preconditioned IMA (P = 0.041) after hypoxia/re-oxygenation injury, whereas in the SV apoptosis was not significantly prevented by preconditioning. 6. Mild heat preconditioning before hypoxia/re-oxygenation injury is a stimulus for Hsp72 protein expression and a reduction in apoptosis in the human IMA. PMID:16789924

Hammerer-Lercher, Angelika; Haeusler, Christa; Prelog, Martina; Bonatti, Johannes; Hoefer, Daniel; Ruttmann, Elfriede; Laufer, Guenther; Werner, Ernst R; Dirnhofer, Stephan; Puschendorf, Bernd; Mair, Johannes



Missing data interpolation by recursive filter preconditioning  

Microsoft Academic Search

Missing data interpolation problems can be conveniently preconditioned by recursive in- verse filtering. A helix transform allows us to implement this idea in the multidimensional case. We show with examples that helix preconditioning can give a magnitude-order speedup in comparison with the older methods. In this paper, we show how recursive deconvolution can be applied for preconditioning interpolation problems. We

Sergey Fomel; Robert Clapp; Jon Claerbout



Mitochondrial function during ischemic preconditioning  

Microsoft Academic Search

Background. Ischemic preconditioning (IPC) protects the myocardium from ischemia reperfusion injury. The effect of IPC on the mitochondria is not well known. However, one of the mechanisms postulated in IPC (the opening of the mitochondrial KATP channels) is likely to result in changes in mitochondrial function. Therefore, the purpose of this study was to determine the effect of IPC on

Juan A Crestanello; Nicolai M Doliba; Andriy M Babsky; Natalia M Doliba; Koki Niibori; Mary D Osbakken; Glenn J. R Whitman



Projected Landweber method and preconditioning  

NASA Astrophysics Data System (ADS)

The projected Landweber method is an iterative method for solving constrained least-squares problems when the constraints are expressed in terms of a convex and closed set 0266-5611/13/2/016/img1. The convergence properties of the method have been recently investigated. Moreover, it has important applications to many problems of signal processing and image restoration. The practical difficulty is that the convergence is too slow. In this paper we apply to this method the so-called preconditioning which is frequently used for increasing the efficiency of the conjugate gradient method. We discuss the significance of preconditioning in this case and we show that it implies a modification of the original constrained least-squares problem. However, when the original problem is ill-posed, the approximate solutions provided by the preconditioned method are similar to those provided by the standard method if the preconditioning is suitably chosen. Moreover, the number of iterations can be reduced by a factor of 10 and even more. A few applications to problems of image restoration are also discussed.

Piana, M.; Bertero, M.



Post-ischemic vascular adhesion protein-1 inhibition provides neuroprotection in a rat temporary middle cerebral artery occlusion model.  


We examined the neuroprotective efficacy associated with post-ischemic vascular adhesion protein-1 (VAP-1) blockade in rats subjected to transient (1 h) middle cerebral artery occlusion (MCAo). We compared saline-treated control rats to rats treated with a highly selective VAP-1 inhibitor, LJP-1586 [Z-3-fluoro-2-(4-methoxybenzyl) allylamine hydrochloride]. Initial intraperitoneal LJP-1586 (or saline control) treatments were delayed until 6 h or 12 h reperfusion. At 72-h reperfusion, LJP-1586-treated rats displayed 51% and 33% smaller infarct volumes, relative to their controls, in the 6- and 12-h treatment groups, respectively. However, only in the 6-h treatment group was the infarct volume reduction significant (p < 0.05). On the other hand, we observed significantly improved neurologic functions in both 6- and 12-h treatment groups, versus their matched controls (p < 0.05). Also, the effect of 6-h LJP-1586 treatment on post-ischemic leukocyte trafficking in pial venules overlying the ischemic cortex was evaluated using intravital microscopy. These experiments revealed that: 1) LJP-1586 did not affect intravascular leukocyte (largely neutrophil) adhesion, at least out to 12-h reperfusion; and 2) the onset of neutrophil extravasation, which occurred between 6-8-h reperfusion in control rats, was prevented by LJP-1586-treatment. In conclusion, in rats subjected to transient MCAo, selective VAP-1 pharmacologic blockade provided neuroprotection, with a prolonged therapeutic window of 6-12-h reperfusion. PMID:23050649

Watcharotayangul, Jittiya; Mao, Lizhen; Xu, Haoliang; Vetri, Francesco; Baughman, Verna L; Paisansathan, Chanannait; Pelligrino, Dale A



Persistent Neuroprotection with Prolonged Postischemic Hypothermia in Adult Rats Subjected to Transient Middle Cerebral Artery Occlusion  

Microsoft Academic Search

Postischemic hypothermia provides long-lasting neuroprotection against global cerebral ischemia in adult rats and gerbils. Studies indicate that hypothermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. However, no study has examined long-term outcome following postischemic hypothermia in adult animals. Furthermore, most studies examined only brief hypothermia (e.g., 3 h).

Dale Corbett; Mark Hamilton; Frederick Colbourne



[Neuroprotective effect of ischemic postconditioning and remote preconditioning. Prospective of clinical use].  


Ischemic postconditioning enhances brain and spinal cord tolerance to ischemia and reperfusion. There are no clinical data on the neuroprotective effect of postconditioning. It was established that foregoing effect of ischemic postconditioning depended upon an activation of PKCs, ERK, Akt kinases and a decrease in the activity of JNK kinase. Superoxide dismutase, Bax, Bal-2 and HSP proteins may be the end effector of postconditioning. Postconditioning phenomenon is mimicked by norepinephrine, diazoxide, sevoflurane, isoflurane and propofol. It is unknown before whether these pharmacological agents prevent brain reperfusion injury in human. Remote preconditioning improves brain and spinal cord tolerance to ischemic and reperfusion damages. There are no data on the neuroprotective effect of remote preconditioning in human at ischemic insult. The endogenous cannabinoids, reactive oxygen species are triggers of remote preconditioning. The neuroprotective effect of preconditioning at distance is depended on the activation of p38, ERK kinases and is attributed to enhancement of HSP-70 protein synthesis. PMID:22929667

Maslov, L N; Lishmanov, Iu B



Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress.  


We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity. PMID:8024011

Powell, S R; Hall, D; Aiuto, L; Wapnir, R A; Teichberg, S; Tortolani, A J



Effect of ischemic preconditioning in skeletal muscle measured by functional magnetic resonance imaging and spectroscopy: a randomized crossover trial  

PubMed Central

Background Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects. Methods Twenty-three participants were included in two randomized crossover protocols in which the effects of IPC were measured by NMR and muscle force assessments. Leg ischemia was administered for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes in 31phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals were recorded. 3-Tesla NMR data were compared to those obtained for isometric muscular strength. Results The phosphocreatine (PCr) signal decreased robustly during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the recovery of muscular strength was slow. During post-ischemic stenosis, PCr increased only slightly. The BOLD signal intensity decreased during ischemia, ischemic exercise and post-ischemic stenosis but increased during hyperemic reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion. Conclusions Ischemic preconditioning positively influenced muscle metabolism during reperfusion; this resulted in an increase in PCr production and higher oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an impairment of energy replenishment during the low-flow reperfusion was detected in this model. Thus, functional NMR is capable of characterizing changes in reperfusion and in therapeutic interventions in vivo. Trial Registration NCT00883467



Preconditioning Techniques in Computational Fluid Dynamics  

Microsoft Academic Search

An overview of preconditioning for the steady-state compressible inviscid fluid dynamic equations is presented. Extensions to the Navier-Stokes equations are also considered. These preconditioners are necessary for many algorithms in order to have the correct behavior at low speeds and to converge to the solution of the incompressible equations as the Mach number goes to zero. In addition, the preconditioning

E. Turkel



Ischemic preconditioning and clinical scenarios  

PubMed Central

Purpose of review Ischemic preconditioning (IPC) is gaining attention as a novel neuroprotective therapy and could provide an improved mechanistic understanding of tolerance to cerebral ischemia. The purpose of this article is to review the recent work in the field of IPC and its applications to clinical scenarios. Recent findings The cellular signaling pathways that are activated following IPC are now better understood and have enabled investigators to identify several IPC mimetics. Most of these studies were performed in rodents, and efficacy of these mimetics remains to be evaluated in human patients. Additionally, remote ischemic preconditioning (RIPC) may have higher translational value than IPC. Repeated cycles of temporary ischemia in a remote organ can activate protective pathways in the target organ, including the heart and brain. Clinical trials are underway to test the efficacy of RIPC in protecting brain against subarachnoid hemorrhage. Summary IPC, RIPC, and IPC mimetics have the potential to be therapeutic in various clinical scenarios. Further understanding of IPC-induced neuroprotection pathways and utilization of clinically relevant animal models are necessary to increase the translational potential of IPC in the near future.

Narayanan, Srinivasan V.; Dave, Kunjan R.; Perez-Pinzon, Miguel A.



Genistein attenuates postischemic depressed myocardial function by increasing myofilament Ca2+ sensitivity in rat myocardium.  


The present study investigated whether genistein, a broad-spectrum tyrosine kinase inhibitor, could increase the myofilament Ca(2+) sensitivity and partially reverse postischemic depressed myocardial function. Left ventricular papillary muscles were isolated from adult Wistar rats and loaded with the Ca2+ indicator, aequorin. The use of fluorocarbon immersion with hypoxia simulated a model of ischemia. Myofilament responsiveness to Ca2+ was evaluated from force-[Ca2+]i relationship recorded during tetani in papillary muscles. Protein levels of troponin I (TnI) were measured in postischemic papillary muscles with the Western blot technique. Isometric contraction was depressed during the period of ischemia and remained low after 60 min of reoxygenation without a corresponding significant change of peak [Ca2+]i in the control group (n = 7). In contrast, the depression of isometric contraction was ameliorated during ischemia in muscle preparations in the presence of genistein (2 micro M; n = 8), and postischemic depressed myocardial contractility partially recovered after a 60-min reperfusion. The myofilament Ca2+ responsiveness was significantly increased in papillary muscles in the presence of genistein. Protein levels of TnI were reduced in postischemic papillary muscles, whereas genistein partially restored decreased protein levels of TnI. Our results reveal that genistein produces an effective attenuation of postischemic depressed myocardial function and improves myofibrillar Ca2+ responsiveness in rat myocardium. PMID:12192106

Min, Jiang-Yong; Liao, Haisun; Wang, Ju-Feng; Sullivan, Matthew F; Ito, Toshiro; Morgan, James P



Cx40 Is Required for, and Cx37 Limits, Postischemic Hindlimb Perfusion, Survival and Recovery  

PubMed Central

Background/Aims Ischemia induced by large-vessel obstruction or vascular injury induces a complex cascade of vasodilatory, remodeling and inflammatory pathways; coordination of these processes by vascular endothelium is likely to involve endothelial gap junctions. Vascular endothelium predominantly expresses two connexin (Cx) isoforms: Cx37 and Cx40. The relevance of these Cxs to postischemic limb recovery remains unclear. Methods In this study, we use a well-established, severe femoral-saphenous artery-vein pair resection model of unilateral hindlimb ischemia to test the relevance of Cx37 and Cx40 to postischemic tissue survival and recovery of limb perfusion. Results Cx40-deficient animals (Cx40–/–) experienced a severe reduction in limb perfusion relative to wild-type (WT) animals and exhibited profound and rapid failure of ischemic limb survival. By contrast, the deficit in limb perfusion was less severe in Cx37-ablated (Cx37–/–) animals compared to WT, corresponding with more rapid recovery of limb appearance and use. These results demonstrate that Cx40 is necessary for postischemic limb survival and reperfusion, whereas Cx37 deletion reduces the extent of ischemia in the same model. Conclusion In summary, we present evidence demonstrating that Cx37 and Cx40 uniquely regulate postischemic limb perfusion, altering the severity of ischemic insult and consequent postischemic survival.

Fang, Jennifer S.; Angelov, Stoyan N.; Simon, Alexander M.; Burt, Janis M.



Promotion of copper excretion from the isolated rat heart attenuates postischemic cardiac oxidative injury.  


This study examined the role of Cu as a mediator of cardiac postischemic oxidative injury. Isolated rat hearts were subjected to 20 min of normothermic global ischemia, followed by 30 min of reperfusion; after 20 min of preischemic loading with Krebs-Henseleit buffer +/- 20 or 30 microM zinc-bis-histidinate (Zn-His2), 0.5 mM deferoxamine (DEF) or 42 microM neocuproine (NEO). Postischemic developed systolic pressure and rate-pressure product were highest and postischemic end-diastolic pressure was lowest in hearts treated with 20 or 30 microM Zn-His2 and 0.5 mM DEF. Cu efflux was significantly increased by 225 and 290% (end of preischemic loading), and 325 and 375% (immediate postischemic period) of control basal rates in hearts treated with 30 microM Zn-His2 and 0.5 mM DEF, respectively. NEO did not effect any of these parameters. By the end of ischemia, protein carbonyls were lowest in Zn-His2-treated hearts and highest in DEF-treated hearts when compared with control hearts. The results of this study suggest that removal of redox-active Cu before ischemia has beneficial effects, indicating a mediatory role in postischemic cardiac oxidative injury. PMID:10484416

Powell, S R; Gurzenda, E M; Wingertzahn, M A; Wapnir, R A



An improved algorithm of fiber tractography demonstrates postischemic cerebral reorganization  

NASA Astrophysics Data System (ADS)

In vivo white matter tractography by diffusion tensor imaging (DTI) accurately represents the organizational architecture of white matter in the vicinity of brain lesions and especially ischemic brain. In this study, we suggested an improved fiber tracking algorithm based on TEND, called TENDAS, for tensor deflection with adaptive stepping, which had been introduced a stepping framework for interpreting the algorithm behavior as a function of the tensor shape (linear-shaped or not) and tract history. The propagation direction at each step was given by the deflection vector. TENDAS tractography was used to examine a 17-year-old recovery patient with congenital right hemisphere artery stenosis combining with fMRI. Meaningless picture location was used as spatial working memory task in this study. We detected the shifted functional localization to the contralateral homotypic cortex and more prominent and extensive left-sided parietal and medial frontal cortical activations which were used directly as seed mask for tractography for the reconstruction of individual spatial parietal pathways. Comparing with the TEND algorithms, TENDAS shows smoother and less sharp bending characterization of white matter architecture of the parietal cortex. The results of this preliminary study were twofold. First, TENDAS may provide more adaptability and accuracy in reconstructing certain anatomical features, whereas it is very difficult to verify tractography maps of white matter connectivity in the living human brain. Second, our study indicates that combination of TENDAS and fMRI provide a unique image of functional cortical reorganization and structural modifications of postischemic spatial working memory.

Liu, Xiao-dong; Lu, Jie; Yao, Li; Li, Kun-cheng; Zhao, Xiao-jie



Protein kinase C beta in postischemic brain mitochondria.  


PKC is implicated in the regulation of mitochondrial metabolism. We examined the association of PKC? with mitochondria and followed postischemic changes in its amount in mitochondria isolated from ischemia-vulnerable (CA1) and ischemia-resistant (CA2-4,DG) hippocampus in gerbil model of transient brain ischemia. Our observations suggest that transient ischemic episode induces a significant, rapid and long lasting increase of PKC? in mitochondria in CA2-4,DG, which may bespeak neuroprotection. In organotypic hippocampal culture (OHC) model of neurodegeneration, PKC? inhibition imposed over NMDA toxicity extended the death area beyond the CA1. These results suggest that PKC? might have a protective effect against excitotoxic damage in rat OHC. The pull-down method and LC-MS/MS analysis revealed mitochondrial proteins that can bind directly with PKC??. The proteins were parts of i) mitochondrial redox carriers forming the electron transport chain including ATP synthase and ii) MPTP: ANT and creatine kinase. PKC? acting through mitochondrial proteins could play a role in protecting the cells from death by e.g. influencing ROS and ATP production after ischemia in CA2-4,DG region of the hippocampus. PMID:21704734

Kowalczyk, Joanna E; Kawalec, Maria; Ber?sewicz, Ma?gorzata; D?bski, Janusz; Dadlez, Micha?; Zab?ocka, Barbara



NCX as a key player in the neuroprotection exerted by ischemic preconditioning and postconditioning.  


Ischemic preconditioning is a neuroprotective mechanism in which a brief non-injurious episode of ischemia protects the brain from a subsequent lethal insult. Recently, it has been reported that modified reperfusion subsequent to a prolonged ischemic episode may also confer neuroprotection, a phenomenon termed postconditioning. Mitogen-activated protein kinases (MAPK) play a key role in these two neuroprotective mechanisms. The aim of this study was to evaluate whether Na(+)/Ca(2+) exchangers (NCXs), a family of ionic transporters that contribute to the maintenance of intracellular ionic homeostasis, contribute to the neuroprotection elicited by ischemic preconditioning and postconditioning.Results of this study indicated that (1) NCX1 and NCX3 are upregulated in those brain regions protected by preconditioning, while (2) postconditioning treatment induces an upregulation only in NCX3 expression. (3) NCX1 upregulation and NCX3 upregulation are mediated by p-AKT since its inhibition reverted the neuroprotective effect of preconditioning and postconditioning and prevented NCXs overexpression. (4) The involvement of NCX in preconditioning and postconditioning neuroprotection is further supported by the results of experiments showing that a partial reversion of the protective effect induced by preconditioning was obtained by silencing NCX1 or NCX3, while the silencing of NCX3 was able to mitigate the protection induced by ischemic postconditioning.Altogether, the data presented here suggest that NCX1 and NCX3 -represent two promising druggable targets for setting on new strategies in stroke therapy. PMID:23224883

Pignataro, Giuseppe; Cuomo, Ornella; Vinciguerra, Antonio; Sirabella, Rossana; Esposito, Elga; Boscia, Francesca; Di Renzo, Gianfranco; Annunziato, Lucio



[Effects of ischemic preconditioning on the oxidative stress in small bowel autotransplantation].  


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. PMID:12474521

Ferencz, Andrea; Szántó, Zalán; Borsiczky, Balázs; Kiss, Katalin; Kalmár-Nagy, Károly; Telek, Géza; Szeberényi, József; Horváth, Ors Péter; Röth, Erzsébet



Prolonged but Delayed Postischemic Hypothermia: A Long-term Outcome Study in the Rat Middle Cerebral Artery Occlusion Model  

Microsoft Academic Search

Delayed but prolonged hypothermia persistently decreases cell death and functional deficits after global cerebral ischemia in rodents. Postischemic hypothermia also reduces infarction after middle cerebral artery occlusion (MCAO) in rat. Because initial neuroprotection is sometimes transient and may not subserve functional recovery, especially on demanding tasks, the authors examined whether postischemic cooling would persistently reduce infarction and forelimb reaching deficits

Frederick Colbourne; Dale Corbett; Zonghang Zhao; Jing Yang; Alastair M. Buchan



Preconditioned characteristic boundary conditions for solution of the preconditioned Euler equations at low Mach number flows  

NASA Astrophysics Data System (ADS)

Preconditioned characteristic boundary conditions (BCs) are implemented at artificial boundaries for the solution of the two- and three-dimensional preconditioned Euler equations at low Mach number flows. The preconditioned compatibility equations and the corresponding characteristic variables (or the Riemann invariants) based on the characteristic forms of preconditioned Euler equations are mathematically derived for three preconditioners proposed by Eriksson, Choi and Merkle, and Turkel. A cell-centered finite volume Roe's method is used for the discretization of the preconditioned system of equations on unstructured meshes. The accuracy and performance of the preconditioned characteristic BCs applied at artificial boundaries are evaluated in comparison with the non-preconditioned characteristic BCs and the simplified BCs in computing steady low Mach number flows. The two-dimensional flow over the NACA0012 airfoil and three-dimensional flow over the hemispherical headform are computed and the results are obtained for different conditions and compared with the available numerical and experimental data. The sensitivity of the solution to the size of computational domain and the variation of the angle of attack for each type of BCs is also examined. Indications are that the preconditioned characteristic BCs implemented in the preconditioned system of Euler equations greatly enhance the convergence rate of the solution of low Mach number flows compared to the other two types of BCs.

Hejranfar, Kazem; Kamali-Moghadam, Ramin



Laser thermal preconditioning enhances dermal wound repair  

NASA Astrophysics Data System (ADS)

Preconditioning tissues with an initial mild thermal stress, thereby eliciting a stress response, can serve to protect tissue from subsequent stresses. Patients at risk for impaired healing, such as diabetics, can benefit from therapeutic methods which enhance wound repair. We present a laser thermal preconditioning protocol that accelerates cutaneous wound repair in a murine model. A pulsed diode laser (? = 1.86 ?m, ?p = 2 ms, 50 Hz, H = 7.64 mJ/cm2) was used to precondition mouse skin before incisional wounds were made. The preconditioning protocol was optimized in vitro and in vivo using hsp70 expression, cell viability, and temperature measurements as benchmarks. Hsp70 expression was non-invasively monitored using a transgenic mouse strain with the hsp70 promoter driving luciferase expression. Tissue temperature recordings were acquired in real time using an infrared camera. Wound repair was assessed by measuring hsp70 expression, biomechanical properties, and wound histology for up to 24 d. Bioluminescence (BLI) was monitored with the IVIS 200 System (Xenogen) and tensile properties with a tensiometer (BTC-2000). The in vivo BLI studies indicated that the optimized laser preconditioning protocol increased hsp70 expression by 15-fold. The tensiometer data revealed that laser preconditioned wounds are ~40% stronger than control wounds at 10 days post surgery. Similar experiments in a diabetic mouse model also enhanced wound repair strength. These results indicate that 1) noninvasive imaging methods can aid in the optimization of novel laser preconditioning methods; 2) that optimized preconditioning with a 1.86 ?m diode laser enhances early wound repair.

Wilmink, Gerald J.; Carter, Terry; Davidson, Jeffrey M.; Jansen, E. Duco



Ischemic preconditioning improves maximal performance in humans  

Microsoft Academic Search

Repeated episodes of ischemia followed by reperfusion, commonly referred to as ischemic preconditioning (IPC), represent an\\u000a endogenous protective mechanism that delays cell injury. IPC also increases blood flow and improves endothelial function.\\u000a We hypothesize that IPC will improve physical exercise performance and maximal oxygen consumption. The purpose of the study\\u000a was to examine the effect of ischemic preconditioning in leg

Patricia C. E. de Groot; Dick H. J. Thijssen; Manuel Sanchez; Reinier Ellenkamp; Maria T. E. Hopman



Noradrenaline and Sensory Preconditioning in the Rat  

Microsoft Academic Search

Two experiments were performed to investigate the effect of noradrenaline (NA) depletion following systemic administration of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine ( DSP4; 50 mg\\/kg, ip) on sensory preconditioning in the rat. For sensory preconditioning, a taste (saccharin, CS 2) and a special type of drinking bottle (noisy bottle) were paired during Phase 1. During Phase 2, the noisy bottle (CS 1)

Trevor Archer; Teresa Cotic; Torbjörn U. C. Järbe



Preconditioning the hyperlipidemic myocardium: fact or fantasy?  


Ischemic heart disease is a leading cause of death worldwide. Myocardial ischemia results in reduced coronary flow, followed by diminished oxygen and nutrient supply to the heart. Reperfusion to an ischemic myocardium often augments the ischemic damage, known as ischemia-reperfusion (I/R) injury. Number of studies demonstrated that the hyperlipidemic myocardium is rather sensitive and more vulnerable to I/R-induced myocardial injury. Repeated brief ischemia and reperfusion cycles, termed as ischemic preconditioning, given before a sustained ischemia is known to reduce myocardial damage occur as a result of I/R. A plethora of evidence supports the fact that preconditioning is one of the promising interventional strategies having an ability to limit I/R-induced myocardial injury. Despite this fact, the preconditioning-mediated cardioprotection is blunted in chronic hyperlipidemic condition. This suggests that preconditioning is moderately a 'healthy heart protective phenomenon'. The mechanisms by which chronic hyperlipidemia abrogates cardioprotective effects of preconditioning are uncertain and are not completely understood. The impaired opening of mitochondrial-K(ATP) channels, eNOS uncoupling and excessive generation of superoxides in the hyperlipidemic myocardium could play a role in attenuating preconditioning-mediated myocardial protection against I/R injury. Moreover, hyperlipidemia-induced loss of cardioprotective effect of preconditioning is associated with redistribution of both sarcolemmal and mitochondrial Connexin 43. We addressed, in this review, the potential mechanisms involved in hyperlipidemia-induced impairment of myocardial preconditioning. Additionally, novel pharmacologic interventions to attenuate hyperlipidemia-associated exaggerated I/R-induced myocardial injury have been discussed. PMID:22101013

Balakumar, Pitchai; Babbar, Lalita



Epsilon PKC Increases Brain Mitochondrial SIRT1 Protein Levels via Heat Shock Protein 90 following Ischemic Preconditioning in Rats  

PubMed Central

Ischemic preconditioning is a neuroprotective mechanism whereby a sublethal ischemic exposure is protective against a subsequent lethal ischemic attack. We previously demonstrated that SIRT1, a nuclear localized stress-activated deacetylase, is vital for ischemic preconditioning neuroprotection. However, a recent study demonstrated that SIRT1 can also localize to the mitochondria. Mitochondrial localized SIRT1 may allow for a direct protection of mitochondria following ischemic preconditioning. The objective of this study was to determine whether ischemic preconditioning increases brain mitochondrial SIRT1 protein levels and to determine the role of PKC? and HSP90 in targeting SIRT1 to the mitochondria. Here we report that preconditioning rats, with 2 min of global cerebral ischemia, induces a delayed increase in non-synaptic mitochondrial SIRT1 protein levels which was not observed in synaptic mitochondria. This increase in mitochondrial SIRT1 protein was found to occur only in neuronal cells and was mediated by PKC? activation. Inhibition of HSP90, a protein chaperone involved in mitochondrial protein import, prevented preconditioning induced increases in mitochondrial SIRT1 and PKC? protein. Our work provides new insights into a possible direct role of SIRT1 in modulating mitochondrial function under both normal and stress conditions, and to a possible role of mitochondrial SIRT1 in activating preconditioning induced ischemic tolerance.

Thompson, John W.; Dave, Kunjan R.; Saul, Isabel; Narayanan, Srinivasan V.; Perez-Pinzon, Miguel A.



Pathways for ischemic cytoprotection: Role of sirtuins in caloric restriction, resveratrol, and ischemic preconditioning  

Microsoft Academic Search

Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective

Kahlilia C Morris; Hung Wen Lin; John W Thompson; Miguel A Perez-Pinzon



Effects of ischemic preconditioning on ischemia/reperfusion-induced arrhythmias by upregulatation of connexin 43 expression  

PubMed Central

Background The susceptibility of hypertrophied myocardium to ischemia-reperfusion injury is associated with increased risk of postoperative arrhythmias. We investigate the effects of ischemic preconditioning (IP) on post-ischemic reperfusion arrhythmias in hypertrophic rabbit hearts. Methods Thirty-three rabbit models of myocardial hypertrophy were randomly divided into three groups of 11 each: non-ischemia-reperfusion group (group A), ischemia-reperfusion group (group B), and ischemic preconditioning group (group C). Another ten healthy rabbits with normal myocardium served as the healthy control group. Rabbit models of myocardial hypertrophy were induced by abdominal aortic banding. Surface electrocardiogram (ECG) was recorded and Curtis-Ravingerova score was used for arrhythmia quantification. Connexin 43 (Cx43) expression was assessed by immunohistochemistry. Results Ratios of heart weight to body weight and left ventricular weight to body weight increase significantly in the three groups compared with the healthy control group (p < 0.05). Arrhythmia incidence in group C is significantly lower than group B (p < 0.05). Curtis-Ravingerova score in group C is lower than group B (p < 0.05). Cx43 expression area in group A is smaller by comparison with the healthy control group (p < 0.05). Cx43 expression area and fluorescence intensity in group B are reduced by 60.9% and 23.9%, respectively, compared with group A (p < 0.05). In group C, Cx43 expression area increases by 32.5% compared with group B (p < 0.05), and decreases by 54.8% compared with group A (p < 0.05). Conclusions The incidence of ischemia/reperfusion-induced arrhythmias in hypertrophic rabbit hearts decreases after IP, which plays an important protecting role on the electrophysiology of hypertrophied myocardium by up-regulating the expression of Cx43.




PubMed Central

This report demonstrated that mice deficient in Flt-1 failed to establish ischemic preconditioned (PC) mediated cardioprotection in isolated working buffer-perfused ischemic reperfused (IR) hearts compared to wild type (WT) subjected to same PC protocol. Wild type (WT) and Flt-1+/? mice were divided into four groups: (1) WT IR (2) WT+PC (3) Flt-1+/? IR (4) Flt-1+/?+PC. Groups 1 and 3 mice were subjected to 30 min of ischemia followed by 2 hrs of reperfusion and groups 2 and 4 mice were subjected to four episodes of 4-min global ischemia followed by 6 min of reperfusion before ischemia reperfusion. For both wild type and Flt-1+/? mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the knockout was less as compared to the WT mice even in preconditioning. The myocardial infarction and apoptosis were higher in Flt-1+/? compared to wild type I/R. Pronounced inhibition was observed in Flt-1+/? for p-AKT, p-eNOS, iNOS and most importantly HO-1 mRNA expression. Results demonstrates that Flt-1+/? mouse hearts are more susceptible to ischemia reperfusion injury and also documents preconditioning is not as effective as found in WT and therefore suggests the importance of VEGF/Flt-1 signaling in ischemic reperfused myocardium.

Thirunavukkarasu, Mahesh; Juhasz, Bela; Zhan, Lijun; Menon, Venugopal P; Tosaki, Arpad; Otani, Hajime; Maulik, Nilanjana



Neuronal Plasticity and Dendritic Spines: Effect of Environmental Enrichment on Intact and Postischemic Rat Brain  

Microsoft Academic Search

The authors compared the influence of environmental enrichment on intact and lesioned brain, and tested the hypothesis that postischemic exposure to an enriched environment can alter dendritic spine density in pyramidal neurons contralateral to a cortical infarct. The middle cerebral artery was occluded distal to the striatal branches in spontaneously hypertensive rats postoperatively housed either in a standard or in

Barbro B. Johansson; Pavel V. Belichenko



Metabolic Preconditioning of Donor Organs  

PubMed Central

Fatty liver is a significant risk factor for liver transplantation, and accounts for nearly half of the livers rejected from the donor pool. We hypothesized that metabolic preconditioning via ex vivo perfusion of the liver graft can reduce fat content and increase post-transplant survival to an acceptable range. We describe a perfusate medium containing agents that promote the defatting of hepatocytes and explanted livers. Defatting agents were screened on cultured hepatocytes made fatty by pre-incubation with fatty acids. The most effective agents were then used on fatty livers. Fatty livers were isolated from obese Zucker rats and normothermically perfused with medium containing a combination of defatting agents. This combination decreased the intracellular lipid content of cultured hepatocytes by 35% over 24 hours, and of perfused livers by 50% over 3 hours. Metabolite analysis suggests that the defatting cocktail upregulated both lipid oxidation and export. Furthermore, gene expression analysis for several enzymes and transcription factors involved in fatty acid oxidation and triglyceride clearance were elevated. We conclude that a cocktail of defatting agents can be used to rapidly clear excess lipid storage in fatty livers, thus providing a new means to recondition donor livers deemed unacceptable or marginally acceptable for transplantation.

Nagrath, Deepak; Xu, Hongzhi; Tanimura, Yoko; Zuo, Rongjun; Berthiaume, Francois; Yarmush, Martin L.



Field-trial evaluation of a Pasteurella vaccine in preconditioned and nonpreconditioned lightweight calves.  


A field-trial evaluation confirmed the efficacy of a pasteurella vaccine as a means of preventing bovine pneumonia. The vaccine was comprised of streptomycin-dependent Pasteurella multocida (type A:3) and Pasteurella haemolytica (type 1). Vaccinal efficacy was defined in terms of greater body weight gains, less severe clinical signs of pneumonia, and smaller death rates as compared with the same factors in nonvaccinated calves. During the 50-day trial, vaccinated calves gained weight faster than did nonvaccinated calves (P = 0.05). Economic advantage was not found for administering a booster dose of the vaccine (P = 0.25). Nonpreconditioned nonvaccinated calves made greater dollar profits than did preconditioned nonvaccinated calves (P = 0.16). A comparison of all preconditioned calves with all nonpreconditioned calves revealed that illness and death losses were less in the preconditioned calves (P = 0.07). An evaluation of the cost vs benefit factors revealed significant advantages for administering 1 dose of vaccine of $19.08 for a preconditioned calf (P = 0.006) and of $11.39 for a nonpreconditioned calf (P = 0.05). The data indicated that there was no economic advantage for preconditioning and that the greatest economic gain was made by the vaccinated nonpreconditioned calves. PMID:4051299

Kadel, W L; Chengappa, M M; Herren, C E



Involvement of CCR-2 chemokine receptor activation in ischemic preconditioning and postconditioning of brain in mice.  


The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors. PMID:22704692

Rehni, Ashish K; Singh, Thakur Gurjeet



Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection  

PubMed Central

Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells.



Ischaemic preconditioning: is it clinically relevant?  


Direct clinical evidence for the classical preconditioning phenomenon, with infarct size limitation as an endpoint, cannot be obtained. However, a number of patient groups have been identified in which adaptation to ischaemia has been demonstrated by enhanced recovery of function or preservation of high energy phosphates in models of repeated ischaemia, such as atrial pacing stress tests, percutaneous transluminal coronary angioplasty and aortic cross-clamping during cardiac surgery. Evidence is accumulating that mechanisms which are operative in experimental ischaemic preconditioning (infarct size limitation) are also operative in these clinical models of repeated reversible ischaemia. Insight into the mechanisms responsible for ischaemic preconditioning could potentially help to develop pharmacological agents which mimic preconditioning. This is especially attractive as several of the ischaemic episodes maybe too short or insufficiently severe to trigger preconditioning. By a synergistic or additive action, the combination of such a stimulus with a low dose of pharmacological agent might result in protective action. If these agents were also to be used for treating cardiovascular conditions, such as the K+ATP channel activator nicorandil for the treatment of angina pectoris, the cardioprotective effect could be a beneficial side effect. The currently available protein kinase C activators are oncogenic, but with the recognition and better understanding of the different subtypes possibly involved in preconditioning, new protein kinase C activators may become available without these side-effects. On the other hand, hearts of patients who regularly experience episodes of ischaemia may be in a more or less permanent state of preconditioning afforded by one of these stimuli or have developed tolerance. In this situation it is likely that (additional) protection by a pharmacological agent cannot be accomplished at that time. It is reassuring, however, that in the animal, preconditioning can be reinstated immediately after the cardioprotection is lost and that it can also be demonstrated in hearts with pathological conditions such as hypertrophy. Finally, in view of the observations that cardioprotection may also be produced by transient ischaemia in other organs, and even by some forms of stress which do not lead to myocardial ischaemia, it could be envisioned that ischaemic preconditioning is only one component of a general form of adaptation. PMID:8582377

Verdouw, P D; Gho, B C; Duncker, D J



Mitochondrial preconditioning: a potential neuroprotective strategy.  


Mitochondria have long been known as the powerhouse of the cell. However, these organelles are also pivotal players in neuronal cell death. Mitochondrial dysfunction is a prominent feature of chronic brain disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD), and cerebral ischemic stroke. Data derived from morphologic, biochemical, and molecular genetic studies indicate that mitochondria constitute a convergence point for neurodegeneration. Conversely, mitochondria have also been implicated in the neuroprotective signaling processes of preconditioning. Despite the precise molecular mechanisms underlying preconditioning-induced brain tolerance are still unclear, mitochondrial reactive oxygen species generation and mitochondrial ATP-sensitive potassium channels activation have been shown to be involved in the preconditioning phenomenon. This review intends to discuss how mitochondrial malfunction contributes to the onset and progression of cerebral ischemic stroke and AD and PD, two major neurodegenerative disorders. The role of mitochondrial mechanisms involved in the preconditioning-mediated neuroprotective events will be also discussed. Mitochondrial targeted preconditioning may represent a promising therapeutic weapon to fight neurodegeneration. PMID:20838473

Correia, Sónia C; Carvalho, Cristina; Cardoso, Susana; Santos, Renato X; Santos, Maria S; Oliveira, Catarina R; Perry, George; Zhu, Xiongwei; Smith, Mark A; Moreira, Paula I



Protein Kinase C? Mediates Salutary Effects on Electrical Coupling Induced by Ischemic Preconditioning  

PubMed Central

Background Ischemic preconditioning delays the onset of electrical uncoupling and prevents loss of the primary ventricular gap junction protein connexin43 (Cx43) from gap junctions during subsequent ischemia. Methods To test the hypothesis that these effects are mediated by protein kinase C epsilon (PKC?), we studied isolated Langendorff-perfused hearts from mice with homozygous germline deletion of PKC? (PKC?-KO). Cx43 phosphorylation and distribution were measured by quantitative immunoblotting and confocal microscopy. Changes in electrical coupling were monitored using the 4-electrode technique to measure whole-tissue resistivity. Results The amount of Cx43 located in gap junctions, measured by confocal microscopy under basal conditions, was significantly greater in PKC?-KO hearts compared to wildtype but total Cx43 content measured by immunoblotting was not different. These unanticipated results indicate that PKC? regulates subcellular distribution of Cx43 under normal conditions. Preconditioning prevented loss of Cx43 from gap junctions during ischemia in wildtype but not PKC?-KO hearts. Specific activation of PKC?, but not PKC?, also prevented ischemia-induced loss of Cx43 from gap junctions. Preconditioning delayed the onset of uncoupling in wildtype but hastened uncoupling in PKC?-KO hearts. Cx43 phosphorylation at the PKC site Ser368 increased 5-fold after ischemia in wildtype hearts and, surprisingly, by nearly 10-fold in PKC?-KO hearts. Preconditioning prevented phosphorylation of Cx43 in gap junction plaques at Ser368 in wildtype but not PKC?-KO hearts. Conclusion Taken together, these results indicate that PKC? plays a critical role in preconditioning to preserve Cx43 signal in gap junctions and delay electrical uncoupling during ischemia.

Hund, Thomas J.; Lerner, Deborah L.; Yamada, Kathryn A.; Schuessler, Richard B.; Saffitz, Jeffrey E.



Dichotomy in the Post-ischemic Metabolic and Functional Recovery Profiles of Isolated Blood versus Buffer-perfused Heart  

Microsoft Academic Search

There is evidence that buffer- and blood-perfused hearts differ in their post-ischemic functional recoveries. The present study was designed to: (i) compare ischemia-induced contracture and post-ischemic functional recovery, and (ii) investigate whether the recovery profiles were related to either the release of purines and norepinephrine or high-energy phosphate content. Rat hearts (n=8\\/group) were perfused at 37°C with buffer (60 mmHg)

Manuel Galiñanes; Palmira Bernocchi; Vincenzo Argano; Anna Cargnoni; Roberto Ferrari; David J. Hearse



[Myocardial preconditioning and its practical significance].  


The authors review the history and physiological basis of myocardial preconditioning including its receptors, signalization and effectors. The classical and delayed (second window) type of preconditioning and relations of the latter to heat shock proteins are discussed. Preconditioning as a form of endogenous adaptation effectively reduces the degree of myocardial injury during a subsequent ischaemia in experimental models and in human as well. Intentional triggering or augmentation of the condition may become a new therapeutic tool in the treatment of ischaemic diseases. Utilizing the advantages of endogen adaptation, the optimal drug or procedure to be applied in the routine clinical practice will come out in the future considering its efficacy and the safety and convenience of the patient. PMID:11963395

Hejjel, László; Röth, Erzsébet



Blood cardioplegia enhanced with nitric oxide donor SPM-5185 counteracts postischemic endothelial and ventricular dysfunction.  


This study tested the hypothesis that enhancement of blood cardioplegia with the nitric oxide donor agent SPM-5185 inhibits postischemic left ventricular and coronary endothelial dysfunction. Eighteen anesthetized dogs supported by total vented bypass were subjected to 30 minutes of normothermic ischemia followed by 4 degrees C multidose blood cardioplegia. Hearts received either standard blood cardioplegia (vehicle group; n = 6), blood cardioplegia with 1 mumol/L SPM-5185 (low-dose group; n = 6), or 10 mumol/L SPM-5185 (high-dose group; n = 6). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 60 minutes, first in the beating empty state for 30 minutes and then after discontinuation of bypass for 30 minutes. Baseline and postischemic left ventricular function was assessed by the slope of the end-systolic pressure-volume (impedance catheter) relation. Postischemic end-systolic pressure-volume relation was depressed by 53.7% of preischemic values in the vehicle group (from 8.2 +/- 1.0 to 3.8 +/- 0.3 mm Hg/ml) and by 33.7% (from 9.2 +/- 1.1 to 6.1 +/- 0.5 mm Hg/ml) in the low-dose group. In contrast, there was complete postischemic functional recovery in the high-dose group (from 7.6 +/- 1.1 to 7.2 +/- 1.2 mm Hg/ml). In coronary arteries isolated from these hearts, endothelium-dependent maximal relaxation to acetylcholine was impaired by 27% in the vehicle group and by 18% in the low-dose group, whereas the high-dose group showed complete endothelium-dependent relaxation. Myeloperoxidase activity, an index of neutrophil accumulation in postischemic myocardium, was elevated in the vehicle and low-dose groups (3.36 +/- 0.58 and 2.56 +/- 0.68 U/100 mg tissue) but was significantly reduced in the high-dose group to 1.27 +/- 0.45 U/100 mg tissue. We conclude that inclusion of 10 mumol/L nitric oxide donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly via inhibition of neutrophil-mediated damage. PMID:7776679

Nakanishi, K; Zhao, Z Q; Vinten-Johansen, J; Hudspeth, D A; McGee, D S; Hammon, J W



Acidic preconditioning protects against ischemia-induced brain injury.  


Ischemic preconditioning protects against cerebral ischemia. Recent investigations indicated that acidic preconditioning (APC) protects against ischemia-induced cardiomyocytes injury. However, it is not clear whether APC can protect against cerebral ischemia. To address this issue, C57BL/6 mice were exposed 3 times at 10-min intervals to a normoxic atmosphere containing 20% CO(2) for 5 min before being further subjected to bilateral common carotid artery occlusion. APC reversed the ischemia-induced brain injury as revealed by improved performance in passive avoidance experiments and decreased neuron loss in the hippocampal CA1 region. Consistently, both APC-treated brain slices and primary cultured neurons were more resistant to oxygen-glucose-deprivation (OGD)-induced injury, in a pH- and time-dependent manner, as revealed by reversed cell/tissue viability. In addition, the APC treatment prevented OGD-induced mitochondrial transmembrane potential loss and apoptosis, which was inhibited by the mitochondrial permeability transport pore opener atractyloside. Taken together, these findings indicated that APC protects against ischemia-induced neuronal injury. The beneficial effects may be attributed, at least in part, to decreased mitochondria-dependent neuronal apoptosis. PMID:22583767

Zhang, Chen-hui; Fan, Yan-ying; Wang, Xiao-fen; Xiong, Jia-yan; Tang, Ying-ying; Gao, Jie-qiong; Shen, Zhe; Song, Xiao-hui; Zhang, Jing-ying; Shen, Yao; Li, Qing; Zhang, Xiangnan; Chen, Zhong



AIF depletion provides neuroprotection through a preconditioning effect.  


Previous studies established a major role for apoptosis inducing factor (AIF) in neuronal cell death after acute brain injury. For example, AIF translocation from mitochondria to the nucleus determined delayed neuronal death, whereas reduced AIF expression provided neuroprotective effects in models of cerebral ischemia or brain trauma. The question remains, however, why reduced AIF levels are sufficient to mediate neuroprotection, since only very little AIF translocation to the nucleus is required for induction of cell death. Thus, the present study addresses the question, whether AIF gene silencing affects intrinsic death pathways upstream of nuclear translocation at the level of the mitochondria. Using MTT assays and real-time cell impedance measurements we confirmed the protective effect of AIF siRNA against glutamate toxicity in immortalized mouse hippocampal HT-22 neurons. Further, AIF siRNA prevented glutamate-induced mitochondrial fragmentation and loss of mitochondrial membrane potential. The protection of mitochondrial integrity was associated with preserved ATP levels, attenuated increases in lipid peroxidation and reduced complex I expression levels. Notably, low concentrations of the complex I inhibitor rotenone (20 nM), provided similar protective effects against glutamate toxicity at the mitochondrial level. These results expose a preconditioning effect as a mechanism for neuroprotection mediated by AIF depletion. In particular, they point out an association between mitochondrial complex I and AIF, which regulate each other's stability in mitochondria. Overall, these findings postulate that AIF depletion mediates a preconditioning effect protecting neuronal cells from subsequent glutamate toxicity through reduced levels of complex I protein. PMID:22865232

Öxler, Eva-Maria; Dolga, Amalia; Culmsee, C



Sound preconditioning therapy inhibits ototoxic hearing loss in mice  

PubMed Central

Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug–induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.

Roy, Soumen; Ryals, Matthew M.; Van den Bruele, Astrid Botty; Fitzgerald, Tracy S.; Cunningham, Lisa L.



Nonelectrocardiographic evidence that both ischemic preconditioning and adenosine preconditioning exist in humans  

Microsoft Academic Search

ObjectivesThe objective of this study was to use electrocardiogram (ECG)-independent parameters to determine whether preconditioning (PC) exists in humans during percutaneous transluminal coronary angioplasty (PTCA).

Massoud A Leesar; Marcus F Stoddard; Yu-Ting Xuan; Xian-Liang Tang; Roberto Bolli



Intermittent hypobaric hypoxia preconditioning induced brain ischemic tolerance by up-regulating glial glutamate transporter-1 in rats.  


Several studies showed that the up-regulation of glial glutamate transporter-1 (GLT-1) participates in the acquisition of brain ischemic tolerance induced by cerebral ischemic preconditioning or ceftriaxone pretreatment in rats. To explore whether GLT-1 plays a role in the acquisition of brain ischemic tolerance induced by intermittent hypobaric hypoxia (IH) preconditioning (mimicking 5,000 m high-altitude, 6 h per day, once daily for 28 days), immunohistochemistry and western blot were used to observe the changes in the expression of GLT-1 protein in hippocampal CA1 subfield during the induction of brain ischemic tolerance by IH preconditioning, and the effect of dihydrokainate (DHK), an inhibitor of GLT-1, on the acquisition of brain ischemic tolerance in rats. The basal expression of GLT-1 protein in hippocampal CA1 subfield was significantly up-regulated by IH preconditioning, and at the same time astrocytes were activated by IH preconditioning, which appeared normal soma and aplenty slender processes. The GLT-1 expression was decreased at 7 days after 8-min global brain ischemia. When the rats were pretreated with the IH preconditioning before the global brain ischemia, the down-regulation of GLT-1 protein was prevented clearly. Neuropathological evaluation by thionin staining showed that 200 nmol DHK blocked the protective role of IH preconditioning against delayed neuronal death induced normally by 8-min global brain ischemia. Taken together, the up-regulation of GLT-1 protein participates in the acquisition of brain ischemic tolerance induced by IH preconditioning in rats. PMID:22076500

Gong, Shu-Juan; Chen, Ling-Yu; Zhang, Min; Gong, Jian-Xue; Ma, Ya-Xian; Zhang, Jian-Mei; Wang, Yu-Jing; Hu, Yu-Yan; Sun, Xiao-Cai; Li, Wen-Bin; Zhang, Yi



Postischemic hyperthermia induces Alzheimer-like pathology in the rat brain  

Microsoft Academic Search

This study addresses the effects of induced hyperthermia on post-ischemic rat brain evaluated histologically and\\/or immunohistochemically after 7-day, 2-month or 6-month survival. Hyperthermia (38.5°-40°C) maintained (by heating the cage environment to 34-35°C) for two consecutive periods of 5 and 9 h timed, respectively, from 4- and 21-h recirculation following 10-min global ischemia (two-vessel occlusion + hypotension) induced chronic neuronal death

R. Sinigaglia-Coimbra; E. Cavalheiro; C. Coimbra



Catestatin Improves Post-Ischemic Left Ventricular Function and Decreases Ischemia/Reperfusion Injury in Heart  

PubMed Central

The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium.

Penna, Claudia; Alloatti, Giuseppe; Gallo, Maria Pia; Cerra, Maria Carmela; Levi, Renzo; Tullio, Francesca; Bassino, Eleonora; Dolgetta, Serena; Pagliaro, Pasquale



IQGAP1 Is Involved in Post-Ischemic Neovascularization by Regulating Angiogenesis and Macrophage Infiltration  

PubMed Central

Background Neovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS). IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF)-induced ROS production and migration of cultured endothelial cells (ECs); however, its role in post-ischemic neovascularization is unknown. Methodology/Principal Findings Ischemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3+ macrophages and CD31+ capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and ?-actin positive arterioles. Furthermore, IQGAP1?/? mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM)-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1?/? mice. In vitro, IQGAP1?/? BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1?/? mice. Conclusions/Significance IQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

Urao, Norifumi; Razvi, Masooma; Oshikawa, Jin; McKinney, Ronald D.; Chavda, Rupal; Bahou, Wadie F.; Fukai, Tohru; Ushio-Fukai, Masuko



Preconditioning and tolerance against cerebral ischaemia  

PubMed Central

Neuroprotection and brain repair in patients after acute brain damage are still major unfulfilled medical needs. Pharmacological treatments are either ineffective or confounded by adverse effects. Consequently, endogenous mechanisms by which the brain protects itself against noxious stimuli and recovers from damage are being studied. Research on preconditioning, also known as induced tolerance, over the past decade has resulted in various promising strategies for the treatment of patients with acute brain injury. Several of these strategies are being tested in randomised clinical trials. Additionally, research into preconditioning has led to the idea of prophylactically inducing protection in patients such as those undergoing brain surgery and those with transient ischaemic attack or subarachnoid haemorrhage who are at high risk of brain injury in the near future. In this Review, we focus on the clinical issues relating to preconditioning and tolerance in the brain; specifically, we discuss the clinical situations that might benefit from such procedures. We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated.

Dirnagl, Ulrich; Becker, Kyra; Meisel, Andreas



Physically Based Adaptive Preconditioning for Early Vision  

Microsoft Academic Search

Several problems in early vision have been formulated in the past in a regularization framework. These problems, when discretized, lead to large sparse linear systems. In this paper, we present a novel physically based adaptive preconditioning technique which can be used in conjunction with a conjugate gradient algorithm to dramatically improve the speed of convergence for solving the aforementioned linear

Shang-hong Lai; Baba C. Vemuri



Mechanisms of Ischemic Preconditioning in Skeletal Muscle  

Microsoft Academic Search

Background. Ischemic preconditioning (IP) (one or more cycles each consisting of a short period of ischemia and a short period of reperfusion, before the sustained ischemia) reduces ischemia-related organ damage in heart and skeletal muscle but the underlying mechanisms are not clear. This study was intended to assess the possible involvement of KATP channels and of adenosine receptors in IP

L. Gürke; A. Mattei; K. Chaloupka; A. Marx; P. M. Sutter; P. Stierli; F. Harder; M. Heberer



Temporary tendon strengthening by preconditioning  

Microsoft Academic Search

BackgroundTendon is frequently injured structure in sports activities. Stretching before activities has been recommended to prevent athletes from injuries. Clinical studies reported that stretching had effects to reduce passive muscle stiffness and leads to an increased range of motion. Recent biomechanical studies suggested that stretching might also temporary affect tensile property of tendon. However, the detailed information regarding optimizing this

Atsushi Teramoto; Zong-Ping Luo



Ischemic preconditioning improves maximal performance in humans.  


Repeated episodes of ischemia followed by reperfusion, commonly referred to as ischemic preconditioning (IPC), represent an endogenous protective mechanism that delays cell injury. IPC also increases blood flow and improves endothelial function. We hypothesize that IPC will improve physical exercise performance and maximal oxygen consumption. The purpose of the study was to examine the effect of ischemic preconditioning in leg skeletal muscles on cycling exercise performance in healthy individuals. Fifteen healthy, well-trained subjects performed two incremental maximal exercise tests on a bicycle ergometer. Power output, oxygen consumption, ventilation, respiratory quotient, and heart rate were measured continuously. Blood pressure and blood lactate were measured before and after the test. One exercise test was performed after the application of ischemic preconditioning, using a protocol of three series of 5-min ischemia at both legs with resting periods of 5 min in between. The other maximal cycling test served as a control. Tests were conducted in counterbalanced order, at least 1 week apart, at the same time of the day. The repeated ischemic periods significantly increased maximal oxygen consumption from 56.8 to 58.4 ml/min per kg (P = 0.003). Maximal power output increased significantly from 366 to 372 W (P = 0.05). Ischemic preconditioning had no effect on ventilation, respiratory quotient, maximal heart rate, blood pressure or on blood lactate. Repeated short-term leg ischemia prior to an incremental bicycle exercise test improves maximal oxygen consumption by 3% and power output by 1.6%. This protocol, which is suggested to mimic the effects of ischemic preconditioning, may have important implications for exercise performance. PMID:19760432

de Groot, Patricia C E; Thijssen, Dick H J; Sanchez, Manuel; Ellenkamp, Reinier; Hopman, Maria T E



The nitric oxide hypothesis of late preconditioning  

Microsoft Academic Search

Ischemic preconditioning (PC) occurs in two phases: an early phase, which lasts 2–3 h, and a late phase, which begins 12–24\\u000a h later and lasts 3–4 days. The mechanism for the late phase of PC has been the subject of intensive investigation. We have\\u000a recently proposed the “NO hypothesis of late PC”, which postulates that NO plays a prominent role

R. Bolli; B. Dawn; X.-L. Tang; Y. Qiu; P. Ping; Y.-T. Xuan; W. K. Jones; H. Takano; Y. Guo; J. Zhang



Role of uncoupling protein 3 in ischemia-reperfusion injury, arrhythmias, and preconditioning.  


Overexpression of mitochondrial uncoupling proteins (UCPs) attenuates ischemia-reperfusion (I/R) injury in cultured cardiomyocytes. However, it is not known whether UCPs play an essential role in cardioprotection in the intact heart. This study evaluated the cardioprotective efficacy of UCPs against I/R injury and characterized the mechanism of UCP-mediated protection in addition to the role of UCPs in ischemic preconditioning (IPC). Cardiac UCP3 knockout (UCP3(-/-)) and wild-type (WT) mice hearts were subjected to ex vivo and in vivo models of I/R injury and IPC. Isolated UCP3(-/-) mouse hearts were retrogradely perfused and found to have poorer recovery of left ventricular function compared with WT hearts under I/R conditions. In vivo occlusion of the left coronary artery resulted in twofold larger infarcts in UCP3(-/-) mice compared with WT mice. Moreover, the incidence of in vivo I/R arrhythmias was higher in UCP3(-/-) mice. Myocardial energetics were significantly impaired with I/R, as reflected by a decreased ATP content and an increase in the AMP-to-ATP ratio. UCP3(-/-) hearts generated more reactive oxygen species (ROS) than WT hearts during I/R. Pretreatment of UCP3(-/-) hearts with the pharmacological uncoupling agent carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone improved postischemic functional recovery. Also the protective efficacy of IPC was abolished in UCP3(-/-) mice. We conclude that UCP3 plays a critical role in cardioprotection against I/R injury and the IPC phenomenon. There is increased myocardial vulnerability to I/R injury in hearts lacking UCP3. The mechanisms of UCP3-mediated cardioprotection include regulation of myocardial energetics and ROS generation by UCP3 during I/R. PMID:23457013

Ozcan, Cevher; Palmeri, Monica; Horvath, Tamas L; Russell, Kerry S; Russell, Raymond R



Salicylate trapping of .OH as a tool for studying post-ischemic oxidative injury in the isolated rat heart.  


The use of salicylate as a chemical trap for .OH represents a simple and convenient alternative to the use of spin trapping techniques to study oxidative injury in isolated perfused organs. In these systems, salicylate is included in the perfusion buffer at concentrations ranging from 0.1 to 2 mM depending on the detection apparatus employed. In our studies, we have used a coulometric detector, which has a theoretical efficiency of 100% as compared to 1-5% for the standard glassy carbon electrode. We have been able to generate reproducible results by inclusion of only 100 microM salicylate, a concentration demonstrated not to affect pre- or post-ischemic cardiac function. In initial studies, we observed an increase in perfusate 2,5-dihydroxybenzoic acid consistent with an early post-ischemic burst of .OH, not unlike that reported using spin trapping techniques. Since then we and others have used this technique to examine possible relationships between .OH formation and treatments that alter post-ischemic cardiac functional recovery. For example, preischemic loading of hearts with copper results in increases in post-ischemic dysfunction and LDH release that were associated with an increase in 2,5-dihydroxybenzoate and by inference, .OH formation. Alternatively, we have reported that the nitroxide spin label, TEMPO, reputed to be a superoxide dismutase mimetic, decreased post-ischemic arrhythmias and 2,5-dihydroxybenzoate formation. Most recently, we have observed that preischemic loading of hearts with zinc-bis-histidinate results in improved post-ischemic cardiac function and decreased LDH release; changes that were associated with decreased 2,5-dihydroxybenzoate formation. These studies indicate that under certain conditions, salicylate is a valuable alternative to spin trapping techniques to probe the role of .OH in cardiac oxidative injury, particularly when applied to the isolated perfused heart preparation. PMID:7834050

Powell, S R


Adaptive polynomial preconditioning for hermitian indefinite linear systems  

Microsoft Academic Search

This paper explores the use of polynomial preconditioned CG methods for hermitian indefinite linear systems,Ax=b. Polynomial preconditioning is attractive for several reasons. First, it is well-suited to vector and\\/or parallel architectures. It is also easy to employ, requiring only matrix-vector multiplication and vector addition. To obtain an optimum polynomial preconditioner we solve a minimax approximation problem. The preconditioning polynomial,C(?), is

Steven F. Ashby; Thomas A. Manteuffel; Paul E. Saylor



Implicit preconditioned WENO scheme for steady viscous flow computation  

Microsoft Academic Search

A class of lower–upper symmetric Gauss–Seidel implicit weighted essentially nonoscillatory (WENO) schemes is developed for solving the preconditioned Navier–Stokes equations of primitive variables with Spalart–Allmaras one-equation turbulence model. The numerical flux of the present preconditioned WENO schemes consists of a first-order part and high-order part. For first-order part, we adopt the preconditioned Roe scheme and for the high-order part, we

Juan-Chen Huang; Herng Lin; Jaw-Yen Yang



Persistent neuroprotection with prolonged postischemic hypothermia in adult rats subjected to transient middle cerebral artery occlusion.  


Postischemic hypothermia provides long-lasting neuroprotection against global cerebral ischemia in adult rats and gerbils. Studies indicate that hypothermia must be prolonged (e.g., 24 h) to indefatigably salvage hippocampal CA1 neurons. Delayed hypothermia also reduces focal ischemic injury. However, no study has examined long-term outcome following postischemic hypothermia in adult animals. Furthermore, most studies examined only brief hypothermia (e.g., 3 h). Since previous studies may have overestimated long-term benefit and have likely used suboptimal durations of hypothermia, we examined whether prolonged cooling would attenuate infarction at a 2-month survival time following middle cerebral artery occlusion (MCAo) in rats. Adult male Wistar rats were implanted with telemetry brain temperature probes and later subjected to 30 min of normothermic MCAo (contralateral to side of probe placement) or sham operation. Ischemia was produced by the insertion of an intraluminal suture combined with systemic hypotension (60 mm Hg). Sham rats and one ischemic group controlled their own postischemic temperature while another ischemic group was cooled to 34 degrees C for 48 h starting at 30 min following the onset of reperfusion. The infarct area was quantified after a 2-month survival time. Normothermic MCAo resulted in almost complete striatal destruction (91% loss +/- 12 SD) with extensive cortical damage (36% +/- 16 SD). Delayed hypothermia treatment significantly reduced cortical injury to 10% +/- 10 SD (P < 0.001) while striatal injury was marginally reduced to 79% loss +/- 17 SD (P < 0.05). Delayed hypothermia of only 34 degrees C provided long-lasting cortical and striatal protection in adult rats subjected to a severe MCAo insult. These results strongly support the clinical assessment of hypothermia in acute stroke. PMID:10785459

Corbett, D; Hamilton, M; Colbourne, F



Epoxyeicosatrienoic acid prevents postischemic electrocardiogram abnormalities in an isolated heart model.  


Cytochrome P450 epoxygenases metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) which are in turn converted to dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH). The main objective of this study was to investigate the protective effects of EETs following ischemic injury using an ex vivo electrocardiogram (EKG) model. Hearts from C57Bl/6, transgenic mice with cardiomyocyte-specific overexpression of CYP2J2 (Tr) and wildtype (WT) littermates were excised and perfused with constant pressure in a Langendorff apparatus. Electrodes were placed superficially at the right atrium and left ventricle to assess EKG waveforms. In ischemic reperfusion experiments hearts were subjected to 20 min of global no-flow ischemia followed by 20 min of reperfusion (R20). The EKG from C57Bl/6 hearts perfused with 1 microM 14,15-EET showed less QT prolongation (QTc) and ST elevation (STE) (QTc=41+/-3, STE=2.3+/-0.3; R20: QTc=42+/-2 ms, STE=1.2+/-0.2mv) than control hearts (QTc=36+/-2, STE=2.3+/-0.2; R20: QTc=53+/-3 ms; STE=3.6+/-0.4mv). Similar results of reduced QT prolongation and ST elevation were observed in EKG recording from CYP2J2 Tr mice (QTc=35+/-1, STE=1.9+/-0.1; R20: QTc=38+/-4 ms, STE=1.3+/-0.2mv) compared to WT hearts. The putative epoxygenase inhibitor MS-PPOH (50 microM) and EET antagonist 14,15-EEZE (10 microM) both abolished the cardioprotective response, implicating EETs in this process. In addition, separate exposure to the K(ATP) channel blockers glibenclamide (1 microM) and HMR1098 (10 microM), or the PKA protein inhibitor H89 (50 nM) during reperfusion abolished the improved repolarization in both the models. Consistent with a role of PKA, CYP2J2 Tr mice had an enhanced activation of the PKAalpha regulatory II subunit in plasma membrane following IR injury. The present data demonstrate that EETs can enhance the recovery of ventricular repolarization following ischemia, potentially by facilitating activation of K(+) channels and PKA-dependent signaling. PMID:18973759

Batchu, S N; Law, E; Brocks, D R; Falck, J R; Seubert, J M



Prevention of Postischemic Tissue Injury by Controlled Reperfusion: A Preliminary Study  

Microsoft Academic Search

Restoration of arterial blood flow to severely and acutely ischemic extremities results in tissue necrosis and systemic-metabolic complications associated with multiorgan failure and death. Surgical revascularization alone (SRA) was compared with revascularization and controlled reperfusion using standard cardiopulmonary bypass (R-CPB) in 41 patients with acute lower limb ischemia and ischemia-induced neurological dysfunction. The mean ischemia time was 17 ± 10

Paul R. Vogt; Hans-Joachim Lutz; Hakan I. Akintürk; Peter Roth; Markus Schönburg; Ares K. Menon; Michael Szente Varga; Joerg Babin-Ebell; Martin Heidt



Hypoxic preconditioning alleviates ethanol neurotoxicity: the involvement of autophagy.  


Ethanol is a neuroteratogen and neurodegeneration is the most devastating consequence of developmental exposure to ethanol. A sublethal preconditioning has been proposed as a neuroprotective strategy against several central nervous system neurodegenerative diseases. We have recently demonstrated that autophagy is a protective response to alleviate ethanol toxicity. A modest hypoxic preconditioning (1 % oxygen) did not cause neurotoxicity but induced autophagy (Tzeng et al. Free Radic Biol Med 49: 839-846, 2010). We, therefore, hypothesize that the modest hypoxic preconditioning may offer a protection against ethanol-induced neurotoxicity. We showed here that the modest hypoxic preconditioning (1 % oxygen) for 8 h significantly alleviated ethanol-induced death of SH-SY5Y neuroblastoma cells. Under the normoxia condition, cell viability in ethanol-exposed cultures (316 mg/dl for 48 h) was 49 ± 6 % of untreated controls; however, with hypoxic preconditioning, cell viability in the ethanol-exposed group increased to 78 ± 7 % of the controls (p < 0.05; n = 3). Bafilomycin A1, an inhibitor of autophagosome and lysosome fusion, blocked hypoxic preconditioning-mediated protection. Similarly, inhibition of autophagic initiation by wortmannin also eliminated hypoxic preconditioning-mediated protection. In contrast, activation of autophagy by rapamycin further enhanced neuroprotection caused by hypoxic preconditioning. Taken together, the results confirm that autophagy is a protective response against ethanol neurotoxicity and the modest hypoxic preconditioning can offer neuroprotection by activating autophagic pathways. PMID:23568540

Wang, Haiping; Bower, Kimberly A; Frank, Jacqueline A; Xu, Mei; Luo, Jia



Implicit preconditioned WENO scheme for steady viscous flow computation  

NASA Astrophysics Data System (ADS)

A class of lower upper symmetric Gauss Seidel implicit weighted essentially nonoscillatory (WENO) schemes is developed for solving the preconditioned Navier Stokes equations of primitive variables with Spalart Allmaras one-equation turbulence model. The numerical flux of the present preconditioned WENO schemes consists of a first-order part and high-order part. For first-order part, we adopt the preconditioned Roe scheme and for the high-order part, we employ preconditioned WENO methods. For comparison purpose, a preconditioned TVD scheme is also given and tested. A time-derivative preconditioning algorithm is devised and a discriminant is devised for adjusting the preconditioning parameters at low Mach numbers and turning off the preconditioning at intermediate or high Mach numbers. The computations are performed for the two-dimensional lid driven cavity flow, low subsonic viscous flow over S809 airfoil, three-dimensional low speed viscous flow over 6:1 prolate spheroid, transonic flow over ONERA-M6 wing and hypersonic flow over HB-2 model. The solutions of the present algorithms are in good agreement with the experimental data. The application of the preconditioned WENO schemes to viscous flows at all speeds not only enhances the accuracy and robustness of resolving shock and discontinuities for supersonic flows, but also improves the accuracy of low Mach number flow with complicated smooth solution structures.

Huang, Juan-Chen; Lin, Herng; Yang, Jaw-Yen



Preconditioning concepts in polyacrylamide flooding in high salinity reservoirs  

SciTech Connect

Because of its salt sensitivity polyacrylamide solutions, selected for polymer flooding for economic reasons have to be prepared in fresh water, and the highly saline reservoirs have to be preconditioned. The authors discuss two methods of preconditioning: a preflush with fresh water and use of a comparatively small slug of a less salt sensitive polymer. Results of laboratory work leading to the improved preconditioning concept with polymer are described. Case histories of two projects with both preconditioning processes are presented and discussed in detail.

Sohn, W.O. (Edeleanu Gasellschaft mbH (DE)); Volz, H.; Maitin, B. (Deutsche Texaco AG (DE))



H(curl) Auxiliary Mesh Preconditioning  

SciTech Connect

This paper analyzes a two-level preconditioning scheme for H(curl) bilinear forms. The scheme utilizes an auxiliary problem on a related mesh that is more amenable for constructing optimal order multigrid methods. More specifically, we analyze the case when the auxiliary mesh only approximately covers the original domain. The latter assumption is important since it allows for easy construction of nested multilevel spaces on regular auxiliary meshes. Numerical experiments in both two and three space dimensions illustrate the optimal performance of the method.

Kolev, T V; Pasciak, J E; Vassilevski, P S



Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion.  


The neutrophil elastase inhibitor sivelestat (ONO-5046) possesses unknown mechanisms of cardioprotection when infused following global ischemia, even in the absence of neutrophils. Since myocardial ischemia-reperfusion injury is strongly associated with endothelial dysfunction and reactive oxygen species (ROS) generation during reperfusion, we have tested the hypothesis that infusion of sivelestat during postischemic low flow would preserve endothelial and contractile function and reduce infarct size through an ROS-mediated mechanism. Isolated male rat hearts, subjected to global ischemia of 25 minutes, were reperfused with low flow with or without sivelestat followed by a full flow reperfusion. Hearts treated with sivelestat showed a significant improvement of LV contractile function and a reduction in infarct size. Infusion of L-NAME (nonspecific blocker of endothelial nitric oxide synthase (eNOS)) along with sivelestat during reperfusion reversed the preservation of contractile function and infarct size. In vitro EPR spin trapping experiments showed that sivelestat treatment decreased superoxide adduct formation in bovine aortic endothelial cells (BAECs) subjected to hypoxia-reoxygenation. Similarly, dihydroethidine (DHE) staining showed decreased superoxide production in LV sections from sivelestat-treated hearts. Taken together, these results indicate that sivelestat infusion during postischemic low flow reduces infarct size and preserves vasoreactivity in association with decreased ROS formation and the preservation of nitric oxide. PMID:23766850

Aune, Sverre E; Yeh, Steve T; Kuppusamy, Periannan; Kuppusamy, M Lakshmi; Khan, Mahmood; Angelos, Mark G



Sivelestat Attenuates Myocardial Reperfusion Injury during Brief Low Flow Postischemic Infusion  

PubMed Central

The neutrophil elastase inhibitor sivelestat (ONO-5046) possesses unknown mechanisms of cardioprotection when infused following global ischemia, even in the absence of neutrophils. Since myocardial ischemia-reperfusion injury is strongly associated with endothelial dysfunction and reactive oxygen species (ROS) generation during reperfusion, we have tested the hypothesis that infusion of sivelestat during postischemic low flow would preserve endothelial and contractile function and reduce infarct size through an ROS-mediated mechanism. Isolated male rat hearts, subjected to global ischemia of 25 minutes, were reperfused with low flow with or without sivelestat followed by a full flow reperfusion. Hearts treated with sivelestat showed a significant improvement of LV contractile function and a reduction in infarct size. Infusion of L-NAME (nonspecific blocker of endothelial nitric oxide synthase (eNOS)) along with sivelestat during reperfusion reversed the preservation of contractile function and infarct size. In vitro EPR spin trapping experiments showed that sivelestat treatment decreased superoxide adduct formation in bovine aortic endothelial cells (BAECs) subjected to hypoxia-reoxygenation. Similarly, dihydroethidine (DHE) staining showed decreased superoxide production in LV sections from sivelestat-treated hearts. Taken together, these results indicate that sivelestat infusion during postischemic low flow reduces infarct size and preserves vasoreactivity in association with decreased ROS formation and the preservation of nitric oxide.

Aune, Sverre E.; Yeh, Steve T.; Kuppusamy, Periannan; Kuppusamy, M. Lakshmi; Khan, Mahmood; Angelos, Mark G.



The effect of ordering on preconditioned conjugate gradients  

Microsoft Academic Search

We investigate the effect of the ordering of the unknowns on the convergence of the preconditioned conjugate gradient method. We examine a wide range of ordering methods including nested dissection, minimum degree, and red-black and consider preconditionings without fill-in. We show empirically that there can be a significant difference in the number of iterations required by the conjugate gradient method

Iain S. Duff; Gérard A. Meurant



Analysis and design of preconditioning methods for the Euler equations  

Microsoft Academic Search

Preconditioning of a system of equations at the differential level represents a relatively new area of research in convergence acceleration of discrete schemes for the fluid dynamics equations. This technique attempts to remove the intrinsic stiffness of the equations caused by the different time scales of the dynamic problem. Specifically, for the Euler equations, preconditioning aims at equalizing the speed

Marco Rodolfo Zaccanti



Neuroprotective effect of hypoxic preconditioning: phenomenon and mechanisms.  


We developed a new model of hypoxic preconditioning improving tolerance of complete global cerebral ischemia. The role of adenosine receptors in the realization of this effect and in the mechanisms of hypoxic tolerance is demonstrated. Preconditioning decreases of body temperature, which correlates with the neuroprotective effect, but this effect does not directly result from hypothermia. PMID:12428296

Kulinskii, V I; Minakina, L N; Gavrilina, T V



Cerebral Vascular Autoregulation and CO2 Reactivity Following Onset of the Delayed Postischemic Hypoperfusion State in Dogs  

Microsoft Academic Search

Summary: A small number of animal studies have suggested that during the delayed postischemic hypoperfusion state, CO2 reactivity of the cerebral vasculature is lost whereas autoregulation is retained. These findings, however, are inconsistent with the bulk of experimental evidence which demonstrates that CO2 reactivity is more robust and may be retained in pathologic circumstances which abolish autoregulation. These opposing viewpoints

Thomas J. Christopherson; James H. Milde; John D. Michenfelder



Enhanced recovery from acute renal failure by the postischemic infusion of adenine nucleotides and magnesium chloride in rats  

Microsoft Academic Search

Enhanced recovery from acute renal failure by the postischemic infusion of adenine nucleotides and magnesium chloride in rats. Although a number of manipulations prior to or during the initiation phase of an acute renal injury will modify the degree of functional impairment, agents administered after the acute insult usually have been ineffective. In the present study, adenine nucleotides (AMP, ADP,

Norman J Siegel; Wayne B Glazier; Irshad H Chaudry; Karen M Gaudio; Bernard Lytton; Arthur E Baue; Michael Kashgarian



Involvement of reperfusion injury salvage kinases in preconditioning depends critically on the preconditioning stimulus.  


Different preconditioning stimuli can activate divergent signaling pathways. In rats, adenosine-independent pathways (triple 3-min coronary artery occlusion [3CAO3]) and adenosine-dependent pathways (one 15-min coronary artery occlusion [ICAO15]) exist, both ultimately converging at the level of the mitochondrial respiratory chain. Furthermore, while 3CAO3, 1CAO15 and exogenous adenosine (ADO) are equally cardioprotective, only 1CAO15 increases interstitial myocardial adenosine levels. Reperfusion Injury Salvage Kinase (RISK) pathway kinases have been implicated in ischemic preconditioning, but not all preconditioning stimuli activate this pathway. Consequently, we evaluated in anesthetized rats the effects of three distinctly different preconditioning stimuli (3CAO3, 1CAO15 or ADO) on infarct size (IS), signaling pathways with a special emphasis on kinases belonging to the RISK pathway (phosphatidylinositol 3-kinase-Akt-nitric oxide synthase and extracellular signal-related kinase [ERK]) and mitochondrial respiration. All three stimuli increased state-2 respiration (using succinate as complex-II substrate), thereby decreasing the respiratory control index, which was accompanied by a limitation of IS produced by a 60-min coronary artery occlusion (CAO). Nitric oxide synthase inhibition abolished the mitochondrial effects and the cardioprotection by 3CAO3, 1CAO15 or ADO. In contrast, the PI3 kinase inhibitor, wortmannin, blocked protection by 1CAO15, but did not affect protection by 3CAO3 or ADO. Western blotting confirmed that phosphorylation of Akt and ERK were increased by 1CAO15 (which was inhibited by wortmannin), but not by 3CAO3 or ADO. In conclusion, while the three cardioprotective stimuli 3CAO3, 1CAO15 and ADO afford cardioprotection via nitric oxide-mediated modulation of mitochondrial respiration, only the 1CAO15 exerts its protection via activation of kinases belonging to the RISK pathway. PMID:21680754

Manintveld, Olivier C; Sluiter, Wim; Dekkers, Dick H W; te Lintel Hekkert, Maaike; Lamers, Jos M J; Verdouw, Pieter D; Duncker, Dirk J



Preconditioning Triggered by Carbon Monoxide (CO) Provides Neuronal Protection Following Perinatal Hypoxia-Ischemia  

PubMed Central

Perinatal hypoxia-ischemia is a major cause of acute mortality in newborns and cognitive and motor impairments in children. Cerebral hypoxia-ischemia leads to excitotoxicity and necrotic and apoptotic cell death, in which mitochondria play a major role. Increased resistance against major damage can be achieved by preconditioning triggered by subtle insults. CO, a toxic molecule that is also generated endogenously, may have a role in preconditioning as low doses can protect against inflammation and apoptosis. In this study, the role of CO-induced preconditioning on neurons was addressed in vitro and in vivo. The effect of 1 h of CO treatment on neuronal death (plasmatic membrane permeabilization and chromatin condensation) and bcl-2 expression was studied in cerebellar granule cells undergoing to glutamate-induced apoptosis. CO's role was studied in vivo in the Rice-Vannucci model of neonatal hypoxia-ischemia (common carotid artery ligature +75 min at 8% oxygen). Apoptotic cells, assessed by Nissl staining were counted with a stereological approach and cleaved caspase 3-positive profiles in the hippocampus were assessed. Apoptotic hallmarks were analyzed in hippocampal extracts by Western Blot. CO inhibited excitotoxicity-induced cell death and increased Bcl-2 mRNA in primary cultures of neurons. In vivo, CO prevented hypoxia-ischemia induced apoptosis in the hippocampus, limited cytochrome c released from mitochondria and reduced activation of caspase-3. Still, Bcl-2 protein levels were higher in hippocampus of CO pre-treated rat pups. Our results show that CO preconditioning elicits a molecular cascade that limits neuronal apoptosis. This could represent an innovative therapeutic strategy for high-risk cerebral hypoxia-ischemia patients, in particular neonates.

Wider?e, Marius; Alves, Paula M.; Vercelli, Alessandro; Vieira, Helena L. A.



Preconditioning of improved and "perfect" fermion actions  

NASA Astrophysics Data System (ADS)

We construct a locally-lexicographic SSOR preconditioner to accelerate the parallel iterative solution of linear systems of equations for two improved discretizations of lattice fermions: (i) the Sheikholeslami-Wohlert scheme where a non-constant block-diagonal term is added to the Wilson fermion matrix and (ii) renormalization group improved actions which incorporate couplings beyond nearest neighbors of the lattice fermion fields. In case (i) we find the block ll -SSOR-scheme to be more effective by a factor 2 than odd-even preconditioned solvers in terms of convergence rates, at = 6.0. For type (ii) actions, we show that our preconditioner accelerates the iterative solution of a linear system of hypercube fermions by a factor of 3 to 4.

Bietenholz, W.; Eicker, N.; Frommer, A.; Lippert, Th.; Medeke, B.; Schilling, K.; Weuffen, G.



Healing the diabetic heart: does myocardial preconditioning work?  


Diabetes mellitus-associated ischemic heart disease is a major public burden in industrialized countries. Reperfusion to a previously ischemic myocardium is obligatory to reinstate its function prior to irreversible damage. However, reperfusion is considered 'a double-edged sword' as reperfusion per se could augment myocardial ischemic damage, known as myocardial ischemia-reperfusion (I/R) injury. The brief and repeated cycles of I/R given before a sustained ischemia and reperfusion are represented as ischemic preconditioning, which protects the heart from lethal I/R injury. Few studies have demonstrated preconditioning-mediated cardioprotection in the diabetic heart. In contrast, considerable number of studies suggests that myocardial defensive effects of preconditioning are abolished in the presence of chronic diabetes mellitus that raised questions over preconditioning effects in the diabetic heart. It is evidenced that chronic diabetes mellitus-associated deficit in survival pathways, impaired function of mito-K(ATP) channels, MPTP opening and high oxidative stress play key roles in paradoxically suppressed cardioprotective effects of preconditioning in the diabetic heart. These controversial results open up a new area of research to identify potential mechanisms influencing disparities on preconditioning effects in diabetic hearts. In this review, we discussed first the discrepancies on the modulatory role of diabetes mellitus in I/R-induced myocardial injury. Following this, we addressed whether preconditioning could protect the diabetic heart against I/R-induced myocardial injury. Moreover, potential mechanisms pertaining to the attenuated cardioprotective effects of preconditioning in the diabetic heart have been delineated. These are important to be understood for better exploitation of preconditioning strategies in limiting I/R-induced myocardial injury in the diabetic heart. PMID:21945408

Balakumar, Pitchai; Sharma, Nidhi Krishan



Signal pathway involved in the development of hypoxic preconditioning in rat hepatocytes  

Microsoft Academic Search

Ischemic preconditioning improves liver resistance to hypoxia and reduces reperfusion injury following transplantation. However, the intracellular signals that mediate the development of liver hypoxic preconditioning are largely unknown. We have investigated the signal pathway leading to preconditioning in freshly isolated rat hepatocytes. Hepatocytes were preconditioned by 10-minute incubation under hypoxic conditions followed by 10 minutes of reoxygenation and subsequently exposed

Rita Carini; Maria Grazia De Cesaris; Roberta Splendore; Daria Vay; Cinzia Domenicotti; Maria Paola Nitti; Dimitri Paola; Maria Adelaide Pronzato; Emanuele Albano



A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury  

Microsoft Academic Search

BACKGROUND: A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene\\/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a

Gila Moalem-Taylor; Man Li; Haydn N Allbutt; Ann Wu; David J Tracey



Effect of Delayed MK-801 (Dizocilpine) Treatment With or Without Immediate Postischemic Hypothermia on Chronic Neuronal Survival After Global Forebrain Ischemia in Rats  

Microsoft Academic Search

Summary: In contrast to intraischemic hypothermia, immediate postischemic hypothermia (30°C) has been shown to delay but not chronically protect the CA1 hippocampus from transient global forebrain ischemia. The inability of a relatively short postischemic hypothermic period to protect chronically might involve a delayed or secondary injury mechanism. We determined whether delayed treatment with the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 (dizocilpine),

W. Dalton Dietrich; Baowan Lin; Mordecai Y.-T. Globus; Edward J. Green; Myron D. Ginsberg; Raul Busto



The preconditioning of major sudden stratospheric warmings  

NASA Astrophysics Data System (ADS)

The preconditioning of major sudden stratospheric warmings (SSWs) is investigated with two long time series using reanalysis (ERA-40) and model (MAECHAM5/MPI-OM) data. Applying planetary wave analysis, we distinguish between wavenumber-1 and wavenumber-2 major SSWs based on the wave activity of zonal wavenumbers 1 and 2 during the prewarming phase. For this analysis an objective criterion to identify and classify the preconditioning of major SSWs is developed. Major SSWs are found to occur with a frequency of six and seven events per decade in the reanalysis and in the model, respectively, thus highlighting the ability of MAECHAM5/MPI-OM to simulate the frequency of major SSWs realistically. However, from these events only one quarter are wavenumber-2 major warmings, representing a low (˜0.25) wavenumber-2 to wavenumber-1 major SSW ratio. Composite analyses for both data sets reveal that the two warming types have different dynamics; while wavenumber-1 major warmings are preceded only by an enhanced activity of the zonal wavenumber-1, wavenumber-2 events are either characterized by only the amplification of zonal wavenumber-2 or by both zonal wavenumber-1 and zonal wavenumber-2, albeit at different time intervals. The role of tropospheric blocking events influencing these two categories of major SSWs is evaluated in the next step. Here, the composite analyses of both reanalysis and model data reveal that blocking events in the Euro-Atlantic sector mostly lead to the development of wavenumber-1 major warmings. The blocking-wavenumber-2 major warming connection can only be statistical reliable analyzed with the model time series, demonstrating that blocking events in the Pacific region mostly precede wavenumber-2 major SSWs.

Bancalá, S.; Krüger, K.; Giorgetta, M.



Preserving postischemic reperfusion in the kidney: a role for extracellular adenosine  

PubMed Central

Several adenosine receptor subtypes on endothelial, epithelial, mesangial, and inflammatory cells have been implicated in ischemic acute kidney injury, a life-threatening condition that frequently complicates the care of hospitalized patients. In this issue of the JCI, Grenz and coworkers provide novel insight into how preservation of postischemic renal perfusion by endothelial cell adenosine A2B receptors is antagonized by adenosine reuptake into proximal tubule cells by equilibrative nucleotide transporter 1, which can be inhibited by dipyridamole. The work suggests that adenosine A2B receptor agonists and inhibition of equilibrative nucleoside transporters by dipyridamole may have therapeutic potential in ischemic acute kidney injury, a condition for which there are currently no specific therapeutic interventions.

Weinberg, Joel M.; Venkatachalam, Manjeri A.



Opioids modulate post-ischemic progression in a rat model of stroke.  


Alterations in the opioidergic system have been found in cerebral ischemia. Neuroprotection studies have demonstrated the involvement of the opioidergic system in cerebral ischemia/reperfusion (I/R). However, the neuroprotective mechanisms remain largely unclear. This study was conducted to investigate whether intracerebroventricular administration of opioidergic agonists has a neuroprotective effect against cerebral ischemia in rats and, if this proved to be the case, to determine the potential neuroprotective mechanisms. Using a focal cerebral I/R rat model, we demonstrated that the opioidergic agents, BW373U86 (delta agonist) and Dynorphin A 1-13 (kappa agonist), but not TAPP (mu agonist), attenuated cerebral ischemic injury as manifested in the reduction of cerebral infarction and preservation of neurons. The antagonism assay showed that the neuroprotective effect of Dynorphin A was attenuated by nor-Binaltorphimine (kappa antagonist). Surprisingly, BW373U86-induced neuroprotection was not changed by Naltrindole (delta antagonist). These findings indicate that BW373U86 and Dynorphin A exerted distinct neuroprotection against ischemia via opioid-independent and -dependent mechanisms, respectively. The post-ischemic protection in beneficial treatments was accompanied by alleviations in brain edema, inflammatory cell infiltration, and pro-inflammatory cytokine interleukin 6 (IL-6) expression. In vitro cell study further demonstrated that the opioidergic agonists, delta and kappa, but not mu, attenuated IL-6 production from stimulated glial cells. Our findings indicate that opioidergic agents have a role in post-ischemic progression through both opioid-dependent and -independent mechanisms. In spite of the distinct-involved action mechanism, the potential neuroprotective effect of opioidergic compounds was associated with immune suppression. Taken together, these findings suggest a potential role for opioidergic agents in the therapeutic consideration of neuroinflammatory diseases. However, a better understanding of the mechanisms involved is necessary before this therapeutic potential can be realized. PMID:18294735

Kao, Tsung-Kuei; Ou, Yen-Chuan; Liao, Su-Lan; Chen, Wen-Ying; Wang, Chun-Chiang; Chen, Shih-Yun; Chiang, An-Na; Chen, Chun-Jung



NO-induced downregulation of HSP10 and HSP60 expression in the postischemic brain.  


Heat shock protein 60 (HSP60) and HSP10 are mitochondrial chaperonin proteins and are responsible for the folding of newly imported proteins and 13 polypeptides encoded by mitochondrial DNA. The expressions of HSP60 and HSP10 are regulated simultaneously because these genes are localized head to head on chromosome, separated by a bidirectional promoter, which harbors heat shock element (HSE), CHOP, STAT3, and SP1 binding sites. In the present study, we show that the expressions of HSP60 and HSP10 in the brain after middle cerebral artery occlusion (MCAO) are induced significantly. Interestingly, the expressions of HSP60 and HSP10 were further upregulated by the administration of aminoguanidine (AG), an inhibitor of the inducible nitric oxide synthase (iNOS), which is known to reduce ischemic damage in an animal model after MCAO. The results obtained in the present study suggest that HSP10 and HSP60 are induced in the postischemic brain, yet are downregulated by NO generated from 12 hr after MCAO/reperfusion. The downregulation of HSP60 and HSP10 by NO were confirmed in vitro, wherein HSP10 and SHP60 expressions were increased by treatment of LPS and IFN gamma (LPS/INF gamma) in C6 astroglioma cells and further upregulated by NMMA, another iNOS inhibitor. Reporter gene analysis combined with deletion and mutation studies showed that STAT3 binding site in the bidirectional promoter is responsible for LPS/INF gamma-induced upregulation and for downregulation by NO. Our results indicated that NO suppresses HSP60 and HSP10 inductions in the postischemic brain by suppressing STAT3 binding to its recognition site. PMID:17348040

Kim, Seung-Woo; Lee, Ja-Kyeong



Failure of oxygen-free radical scavengers to improve postischemic liver function.  


Previous investigations have demonstrated reduction of postischemic organ injury with improved flow rates following administration of superoxide dismutase (SOD) and catalase (CAT) just before reperfusion. Presumably these oxygen-free radical scavengers provide protection against oxygen-free radicals produced during reoxygenation, but the site of action remains unclear. The present study was designed to determine the effect of SOD/CAT on hepatic function following global ischemia independent of flow. Livers obtained from Sprague-Dawley rats fasted 24 hours were perfused with Krebs-Henseleit buffer containing 5 mM lactate for 130 minutes. Following a 30-minute control period, livers were subjected to 55 minutes of warm, global ischemia. The control group (N = 12) was reperfused under oxygenated conditions for an additional 45 minutes. Two other groups (N = 9; N = 4) were reperfused under identical conditions with administration of 150,000 U/L or 450,000 U/L of SOD/CAT 3 minutes before reperfusion. Hepatic flow returned to normal levels following ischemia, but gluconeogenic activity and bile production remained significantly depressed. No significant recovery of gluconeogenic activity or bile production was noted when SOD/CAT was administered before reperfusion. These results demonstrate that in the absence of flow augmentation SOD/CAT do not provide protection from oxygen-free radicals following global ischemia in the isolated rat liver. This implies that previously reported reductions of postischemic reperfusion injury, where blood flow improved as well, may be due to oxygen-free radical scavenging within the vascular network resulting in enhanced organ perfusion and, therefore, improved organ function. PMID:3772996

McEnroe, C S; Pearce, F J; Ricotta, J J; Drucker, W R



Hyperbaric oxygen preconditioning protects skin from UV-A damage.  


Hyperbaric oxygen therapy (HBOT) is used for a number of applications, including the treatment of diabetic foot ulcers and CO poisoning. However, we and others have shown that HBOT can mobilize cellular antioxidant defenses, suggesting that it may also be useful under circumstances in which tissue protection from oxidative damage is desired. To test the protective properties of hyperbaric oxygen (HBO) on a tissue level, we evaluated the ability of a preconditioning treatment regimen to protect cutaneous tissue from UV-A-induced oxidative damage. Three groups of hairless SKH1-E mice were exposed to UV-A 3 days per week for 22 weeks, with two of these groups receiving an HBO pretreatment either two or four times per week. UV-A exposure increased apoptosis and proliferation of the skin tissue, indicating elevated levels of epithelial damage and repair. Pretreatment with HBO significantly reduced UV-A-induced apoptosis and proliferation. A morphometric analysis of microscopic tissue folds also showed a significant increase in skin creasing following UV-A exposure, which was prevented by HBO pretreatment. Likewise, skin elasticity was found to be greatest in the group treated with HBO four times per week. The effects of HBO were also apparent systemically as reductions in caspase-3 activity and expression were observed in the liver. Our findings support a protective function of HBO pretreatment from a direct oxidative challenge of UV-A to skin tissue. Similar protection of other tissues may likewise be achievable. PMID:22855227

Fuller, Ashley M; Giardina, Charles; Hightower, Lawrence E; Perdrizet, George A; Tierney, Cassandra A



[Phytoadaptogens-induced phenomenon similar to ischemic preconditioning].  


The course administration (16 mg/kg per os for 5 days) of extracts of Panax ginseng or Rhodiola rosea induced a decrease in the infarction size/the area at risk (IS AAR) ratio during a 45-min local ischemia and a 2-hr reperfusion in artificially ventilated chloralose-anaesthetized rats. Single administration of ginseng or Rhodiola 24 h before ischemia did not affect the IS/AAR ratio. Chronic administration of Extracts of Eleutherococcus senticosus, Leuzea carthamoides and Aralia mandshurica had no effect on the IS/AAR ratio. Pretreatment with extract ofAralia mandshurica prevented appearance of ventricular arrhythmias during first 10 min coronary artery occlusion. Pretreatment with extract of Rhodiola rosea decreased the incidence of ventricular fibrillation during ischemia. Single administration of extracts of Panax ginseng or Rhodiola rosea in a dose of 16 mg/kg had no effect on the IS/AAR ratio. The authors conclude that extracts of ginseng or Rhodiola exhibit a powerful cardioprotective effect. Extract of Aralia exhibit a strong antiarrhythmic effect. Extracts of ginseng and Rhodiola do not mimic phenomena of ischemia preconditioning. PMID:19505042

Arbuzov, A G; Maslov, L N; Burkova, V N; Krylatov, A V; Konkovskaia, Iu N; Safronov, S M



Essential involvement of the NMDA receptor in ethanol preconditioning-dependent neuroprotection from amyloid-betain vitro.  


In several epidemiological studies, moderate ethanol consumption has been associated with reduced risks of cognitive decline or Alzheimer's dementia. Of potential relevance is that brain cultures preconditioned with moderate ethanol concentrations are resistant to neurotoxic Alzheimer's amyloid-beta (Abeta) peptides. Using rat cerebellar mixed cultures we investigated whether certain membrane receptors were early 'sensors' in moderate ethanol preconditioning (MEP). In a 6-day MEP protocol (30 mM ethanol), neuroprotection from Abeta25-35 was undiminished by antagonism during the first 3 days of either adenosine A(1) or Galpha(i/o) protein-coupled receptors. However, similar cotreatment with memantine or DL-2-amino-5-phosphono-pentanoic acid (AP-5), antagonists of NMDA receptors (NMDAR), abolished neuroprotection, indicating key early involvement of this ionotropic glutamate receptor. Also in these cultures, directly activating NMDAR using subexcitotoxic NMDA preconditioning prevented Abeta neurotoxicity. By day 2 of MEP, we observed increased levels of NMDAR subunits NR1, NR2B, and NR2C that persisted through day 6. Interestingly, memantine co-exposure blocked elevations in the obligatory NR1 subunit. Furthermore, 2 days of MEP significantly increased two indicators of synaptic NMDAR localization, NR2B phospho-Tyr1472, and post-synaptic density 95 scaffolding protein. The results indicate that ethanol preconditioning-dependent neuroprotection is associated with early increases in NR subunits concomitant with enhancement of synaptic localization and activity of NMDAR. PMID:19694907

Mitchell, Robert M; Neafsey, Edward J; Collins, Michael A



Parallel Domain Decomposition Preconditioning for Computational Fluid Dynamics.  

National Technical Information Service (NTIS)

This viewgraph presentation gives an overview of the parallel domain decomposition preconditioning for computational fluid dynamics. Details are given on some difficult fluid flow problems, stabilized spatial discretizations, and Newton's method for solvi...

T. J. Barth T. F. Chan W. P. Tang



[Postischemic reorganization of dendritic architectonics of the hippocampal CA3 region in albino rats predisposed to seizures].  


Total short term ischemia of brain was induced experimentally in albino rats (10 min long clamp of heart vascular bundle). Using Golgi Silver nitrate impregnation geometry of pyramidal neurons dendritic tree was studied in sector of hippocampus in norm, postischemic period (d 1.30 and 90) healthy animals and those predisposed to cramps. Significant reduction of dendrite volume, total length, dendrite territory, parameters of dendrite arborization were shown on the background of stable numerical density of neurons in all animals who survived brain ischemia. The extent of reduction, volume and duration of changes of parameters of dendritic tree geometry was higher in animals predisposed to cramps than in high threshold animals without cramps. Possible mechanisms of postischemic neuron "epileptization" were discussed. PMID:11210456

Semchenko, V V; Stepanov, S S; Nikel', A E; Akulinin, V A



Ischemic Preconditioning in the Younger and Aged Heart  

PubMed Central

Ischemic preconditioning is the effect of brief ischemic episodes which protect the heart from the following more prolonged ischemic episode. This mechanism is effective in younger but not in aged heart. The age-related reduction of ischemic preconditioning has been demonstrated in experimental models and in elderly patients. Preinfarction angina, a clinical equivalent of ischemic preconditioning, reduces mortality in adult but not in elderly patients with acute myocardial infarction. Physical activity or caloric restriction is partially capable to preserve the cardioprotective effect of ischemic preconditioning in the aging heart. More importantly, physical activity and caloric restriction in tandem action completely preserve the protective mechanism of ischemic preconditioning. Accordingly, the protective mechanism of preinfarction angina is preserved in elderly patients with a high grade of physical activity or a low body-mass index. Thus, both physical activity and caloric restriction are confirmed as powerful anti-aging interventions capable to restore age-dependent reduction of a critical endogenous protective mechanism such as ischemic preconditioning.

Abete, Pasquale; Testa, Gianluca; Cacciatore, Francesco; Della-Morte, David; Galizia, Gianluigi; Langellotto, Assunta; Rengo, Franco



Oxygen sensitivity of mitochondrial redox status and evoked potential recovery early during reperfusion in post-ischemic rat brain  

Microsoft Academic Search

Inspired oxygen (FiO2) was manipulated during the early reperfusion period after global cerebral ischemia (four-vessel occlusion of 20 or 30 min duration) in anesthetized rats. The goal was to determine whether oxygen availability during the early reperfusion period alters recovery of mitochondrial redox state and evoked electrical activity. The effectiveness of post-ischemic oxygen treatment was monitored at the tissue level

Zi-Cai Feng; Thomas J Sick; Myron Rosenthal



The effect of long-term post-ischemic bifemelane hydrochloride treatment on cholinergic systems in the gerbil hippocampus  

Microsoft Academic Search

Bifemelane hydrochloride (BF) is a modulator of various neurotransmitter systems. The effect of BF on the cholinergic system was studied in the gerbil hippocampus at 100 days after ischemic damage. Marked enhancement of AChE staining was noticed in the CAI of saline-treated animals at 100 (lays after ischemia, while the post-ischemic enhancement of AChE staining intensity was milder in BF-treated

Yi-Lin Huang; Hiroshi Onodera; Atsushi Takeda; Yasuto Itoyama; Kyuya Kogure



NADPH oxidase-derived overproduction of reactive oxygen species impairs postischemic neovascularization in mice with type 1 diabetes.  


We hypothesized that diabetes-induced oxidative stress may affect postischemic neovascularization. The response to unilateral femoral artery ligation was studied in wild-type or gp91(phox)-deficient control or type 1 diabetic mice or in animals treated with the anti-oxidant N-acetyl-l-cysteine (NAC) or with in vivo electrotransfer of a plasmid encoding dominant-negative Rac1 (50 microg) for 21 days. Postischemic neovascularization was reduced in diabetic mice in association with down-regulated vascular endothelial growth factor-A protein levels. In diabetic animals vascular endothelial growth factor levels and postischemic neovascularization were restored to nondiabetic levels by the scavenging of reactive oxygen species (ROS) by NAC administration or the inhibition of ROS generation by gp91(phox) deficiency or by administration of dominant-negative Rac1. Finally, diabetes reduced the ability of adherent bone marrow-derived mononuclear cells (BM-MNCs) to differentiate into endothelial progenitor cells. Treatment with NAC (3 mmol/L), apocynin (200 micromol/L), or the p38MAPK inhibitor LY333351 (10 micromol/L) up-regulated the number of endothelial progenitor cell colonies derived from diabetic BM-MNCs by 1.5-, 1.6-, and 1.5-fold, respectively (P < 0.05). In the ischemic hindlimb model, injection of diabetic BM-MNCs isolated from NAC-treated or gp91(phox)-deficient diabetic mice increased neovascularization by approximately 1.5-fold greater than untreated diabetic BM-MNCs (P < 0.05). Thus, inhibition of NADPH oxidase-derived ROS overproduction improves the angiogenic and vasculogenic processes and restores postischemic neovascularization in type 1 diabetic mice. PMID:16877369

Ebrahimian, Téni G; Heymes, Christophe; You, Dong; Blanc-Brude, Olivier; Mees, Barend; Waeckel, Ludovic; Duriez, Micheline; Vilar, José; Brandes, Ralph P; Levy, Bernard I; Shah, Ajay M; Silvestre, Jean-Sébastien



The Role of SDF-1-CXCR4/CXCR7 Axis in the Therapeutic Effects of Hypoxia-Preconditioned Mesenchymal Stem Cells for Renal Ischemia/Reperfusion Injury  

PubMed Central

In vitro hypoxic preconditioning (HP) of mesenchymal stem cells (MSCs) could ameliorate their viability and tissue repair capabilities after transplantation into the injured tissue through yet undefined mechanisms. There is also experimental evidence that HP enhances the expression of both stromal-derived factor-1 (SDF-1) receptors, CXCR4 and CXCR7, which are involved in migration and survival of MSCs in vitro, but little is known about their role in the in vivo therapeutic effectiveness of MSCs in renal ischemia/reperfusion (I/R) injury. Here, we evaluated the role of SDF-1-CXCR4/CXCR7 pathway in regulating chemotaxis, viability and paracrine actions of HP-MSCs in vitro and in vivo. Compared with normoxic preconditioning (NP), HP not only improved MSC chemotaxis and viability but also stimulated secretion of proangiogenic and mitogenic factors. Importantly, both CXCR4 and CXCR7 were required for the production of paracrine factors by HP-MSCs though the former was only responsible for chemotaxis while the latter was for viability. SDF-1? expression was upregulated in postischemic kidneys. After 24 h systemical administration following I/R, HP-MSCs but not NP-MSCs were selectively recruited to ischemic kidneys and this improved recruitment was abolished by neutralization of CXCR4, but not CXCR7. Furthermore, the increased recruitment of HP-MSCs was associated with enhanced functional recovery, accelerated mitogenic response, and reduced apoptotic cell death. In addition, neutralization of either CXCR4 or CXCR7 impaired the improved therapeutic potential of HP-MSCs. These results advance our knowledge about SDF-1-CXCR4/CXCR7 axis as an attractive target pathway for improving the beneficial effects of MSC-based therapies for renal I/R.

Xue, Wujun; Ge, Guanqun; Luo, Xiaohui



Analysis and design of preconditioning methods for the Euler equations  

NASA Astrophysics Data System (ADS)

Preconditioning of a system of equations at the differential level represents a relatively new area of research in convergence acceleration of discrete schemes for the fluid dynamics equations. This technique attempts to remove the intrinsic stiffness of the equations caused by the different time scales of the dynamic problem. Specifically, for the Euler equations, preconditioning aims at equalizing the speed of propagation of the different waves of the hyperbolic problem. This 'fix' becomes particularly useful in the incompressible limit and in the neighborhood of the sonic point. Practical examples of application of preconditioning include modern transonic supercritical airfoils, and nearly incompressible flows with embedded regions where compressibility is important (e.g., low speed combustion). This study attempts the ambitious project of reviewing most of the work done in Euler preconditioning, while at the same time extending some of the existing methods and correcting their robustness problems. Several original contributions to the theory of Euler preconditioning are given, including a thorough exposition of the symmetrizability property of the preconditioned equations, a discussion of the positive definiteness property of the preconditioning matrix, and the study of the eigenvalues for the full form of the preconditioner. Considering the numerical implementation of the preconditioned methods using the Roe flux function, a scheme based on the classical one-Riemann problem normal to the cell interface is proposed, and its advantages over other formulations found in the literature, as well as its drawbacks, are discussed. Then, the analysis of several existing preconditioning methods is conducted, and the complete eigenvector structure of the equations preconditioned with the Van Leer- Lee-Roe matrix, the Turkel matrix, the Choi-Merkle matrix, and a few others, is obtained and analyzed. A comprehensive exploration of preconditioning in one and two spatial dimensions is attempted, which allows to better understand the properties of existing preconditioners. While this investigation suggests new interesting families of one-dimensional preconditioners, for the two-dimensional case the analysis is complete only for the sparse form of the preconditioner, and shows that in this instance it is not possible to remove all of the robustness problems usually found in Euler preconditioning. When considering the full form of the preconditioning matrix the analysis is not complete, because of the formidable algebraic problem involved. Nonetheless, some specific solutions are considered, and a few general conclusions are also drawn in this case. Finally, it is shown that there exist at least two sparse preconditioners that are sufficiently robust in computing stagnation point flow, while preserving the overall effectiveness of preconditioning for low speed flow. One of these matrices is a modification of the popular Turkel method. Using this matrix in regions of low Mach number, in conjunction with the Van Leer-Lee-Roe preconditioner in the transonic and supersonic parts of the flow field, allows to achieve a very robust and efficient preconditioning procedure for the entire Mach regime.

Zaccanti, Marco Rodolfo


Nuclear Factor-?B Activation and Postischemic Inflammation Are Suppressed in CD36-Null Mice after Middle Cerebral Artery Occlusion  

PubMed Central

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-?B, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1? were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-?B activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino



Green Tea Polyphenols Precondition against Cell Death Induced by Oxygen-Glucose Deprivation via Stimulation of Laminin Receptor, Generation of Reactive Oxygen Species, and Activation of Protein Kinase C?  

PubMed Central

As the development of synthetic drugs for the prevention of stroke has proven challenging, utilization of natural products capable of preconditioning neuronal cells against ischemia-induced cell death would be a highly useful complementary approach. In this study using an oxygen-glucose deprivation and reoxygenation (OGD/R) model in PC12 cells, we show that 2-day pretreatment with green tea polyphenols (GTPP) and their active ingredient, epigallocatechin-3-gallate (EGCG), protects cells from subsequent OGD/R-induced cell death. A synergistic interaction was observed between GTPP constituents, with unfractionated GTPP more potently preconditioning cells than EGCG. GTPP-induced preconditioning required the 67-kDa laminin receptor (67LR), to which EGCG binds with high affinity. 67LR also mediated the generation of reactive oxygen species (ROS) via activation of NADPH oxidase. An exogenous ROS-generating system bypassed 67LR to induce preconditioning, suggesting that sublethal levels of ROS are indeed an important mediator in GTPP-induced preconditioning. This role for ROS was further supported by the fact that antioxidants blocked GTPP-induced preconditioning. Additionally, ROS induced an activation and translocation of protein kinase C (PKC), particularly PKC? from the cytosol to the membrane/mitochondria, which was also blocked by antioxidants. The crucial role of PKC in GTPP-induced preconditioning was supported by use of its specific inhibitors. Preconditioning was increased by conditional overexpression of PKC? and decreased by its knock-out with siRNA. Collectively, these results suggest that GTPP stimulates 67LR and thereby induces NADPH oxidase-dependent generation of ROS, which in turn induces activation of PKC, particularly prosurvival isoenzyme PKC?, resulting in preconditioning against cell death induced by OGD/R.

Gundimeda, Usha; McNeill, Thomas H.; Elhiani, Albert A.; Schiffman, Jason E.; Hinton, David R.; Gopalakrishna, Rayudu



Nanoparticle preconditioning for enhanced thermal therapies in cancer.  


Nanoparticles show tremendous promise in the safe and effective delivery of molecular adjuvants to enhance local cancer therapy. One important form of local cancer treatment that suffers from local recurrence and distant metastases is thermal therapy. In this article, we review a new concept involving the use of nanoparticle-delivered adjuvants to 'precondition' or alter the vascular and immunological biology of the tumor to enhance its susceptibility to thermal therapy. To this end, a number of opportunities to combine nanoparticles with vascular and immunologically active agents are reviewed. One specific example of preconditioning involves a gold nanoparticle tagged with a vascular targeting agent (i.e., TNF-?). This nanoparticle embodiment demonstrates preconditioning through a dramatic reduction in tumor blood flow and induction of vascular damage, which recruits a strong and sustained inflammatory infiltrate in the tumor. The ability of this nanoparticle preconditioning to enhance subsequent heat or cold thermal therapy in a variety of tumor models is reviewed. Finally, the potential for future clinical imaging to judge the extent of preconditioning and thus the optimal timing and extent of combinatorial thermal therapy is discussed. PMID:21542691

Shenoi, Mithun M; Shah, Neha B; Griffin, Robert J; Vercellotti, Gregory M; Bischof, John C



Acute postischemic seizures are associated with increased mortality and brain damage in adult mice.  


Postischemic seizures are associated with worsened outcome following stroke, but the underlying pathophysiology is poorly understood. Here we examined acute seizures in adult mice following hypoxia-ischemia (HI) via combined behavioral, electrophysiological, and histological assessments. C57BL/6 mice aged 4-9 months received a permanent occlusion of the right common carotid artery and then underwent a systemic hypoxic episode. Generalized motor seizures were observed within 72 h following HI. These seizures occurred nearly exclusively in animals with extensive brain injury in the hemisphere ipsilateral to the carotid occlusion, but their generation was not associated with electroencephalographic discharges in bilateral hippocampal and neocortical recordings. Animals exhibiting these seizures had a high rate of mortality, and post-HI treatments with diazepam and phenytoin greatly suppressed these behavioral seizures and improved post-HI animal survival. Based on these data, we conclude that these seizures are a consequence of HI brain injury, contribute to worsened outcome following HI, and that they originate from deep subcortical structures. PMID:21531782

El-Hayek, Youssef Hanna; Wu, Chiping; Chen, Rick; Al-Sharif, Abdel Rahman; Huang, Shelley; Patel, Nisarg; Du, Chao; Ruff, Crystal Ann; Fehlings, Michael G; Carlen, Peter L; Zhang, Liang



The Use of NeuroAiD (MLC601) in Postischemic Stroke Patients.  


Aim. We aimed to assess the efficacy of MLC601 on functional recovery in patients given MLC601 after an ischemic stroke. Methods. This is a retrospective cohort study comparing poststroke patients given open-label MLC601 (n = 30; 9 female) for three months and matching patients who did not receive MLC601 from our Stroke Data Bank. Outcome assessed was modified Rankin Scale (mRS) at three months and analyzed according to: (1) achieving a score of 0-2, (2) achieving a score of 0-1, and (3) mean change in scores from baseline. Results. At three months, 21 patients on MLC601 became independent as compared to 17 patients not on MLC601 (OR 1.79; 95% CI 0.62-5.2; P = 0.29). There were twice as many patients (n = 16) on MLC601 who attained mRS scores similar to their prestroke state than in the non-MLC601 group (n = 8) (OR 3.14; 95% CI 1.1-9.27; P = 0.038). Mean improvement in mRS from baseline was better in the MLC601 group than in the non-MLC601 group (-1.7 versus -0.9; mean difference -0.73; 95% CI -1.09 to -0.38; P < 0.001). Conclusion. MLC601 improves functional recovery at 3 months postischemic stroke. An ongoing large randomized control trial of MLC601 will help validate these results. PMID:23304514

Navarro, Jose C; Molina, Mark C; Baroque Ii, Alejandro C; Lokin, Johnny K



MFGE8 inhibits inflammasome-induced IL-1? production and limits postischemic cerebral injury.  


Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1? production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1? production by macrophages through mediation of integrin ?(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1? production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1? production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1? production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1? production. PMID:23454767

Deroide, Nicolas; Li, Xuan; Lerouet, Dominique; Van Vré, Emily; Baker, Lauren; Harrison, James; Poittevin, Marine; Masters, Leanne; Nih, Lina; Margaill, Isabelle; Iwakura, Yoichiro; Ryffel, Bernhard; Pocard, Marc; Tedgui, Alain; Kubis, Nathalie; Mallat, Ziad



Peptide Nanofibers Preconditioned with Stem Cell Secretome Are Renoprotective  

PubMed Central

Stem cells may contribute to renal recovery following acute kidney injury, and this may occur through their secretion of cytokines, chemokines, and growth factors. Here, we developed an acellular, nanofiber-based preparation of self-assembled peptides to deliver the secretome of embryonic stem cells (ESCs). Using an integrated in vitro and in vivo approach, we found that nanofibers preconditioned with ESCs could reverse cell hyperpermeability and apoptosis in vitro and protect against lipopolysaccharide-induced acute kidney injury in vivo. The renoprotective effect of preconditioned nanofibers associated with an attenuation of Rho kinase activation. We also observed that the combined presence of follistatin, adiponectin, and secretory leukoprotease during preconditioning was essential to the renoprotective properties of the nanofibers. In summary, we developed a designer-peptide nanofiber that can serve as a delivery platform for the beneficial effects of stem cells without the problems of teratoma formation or limited cell engraftment and viability.

Wang, Yin; Bakota, Erica; Chang, Benny H.J.; Entman, Mark; Hartgerink, Jeffrey D.



Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important?  

PubMed Central

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

Meier, J J; Gallwitz, B; Schmidt, W E; Mugge, A; Nauck, M A



Operator-Based Preconditioning of Stiff Hyperbolic Systems  

SciTech Connect

We introduce an operator-based scheme for preconditioning stiff components encoun- tered in implicit methods for hyperbolic systems of partial differential equations posed on regular grids. The method is based on a directional splitting of the implicit operator, followed by a char- acteristic decomposition of the resulting directional parts. This approach allows for solution to any number of characteristic components, from the entire system to only the fastest, stiffness-inducing waves. We apply the preconditioning method to stiff hyperbolic systems arising in magnetohydro- dynamics and gas dynamics. We then present numerical results showing that this preconditioning scheme works well on problems where the underlying stiffness results from the interaction of fast transient waves with slowly-evolving dynamics, scales well to large problem sizes and numbers of processors, and allows for additional customization based on the specific problems under study.

Daniel R. Reynolds, Ravi Samtaney, and Carol S. Woodward



40 CFR 85.2218 - Preconditioned idle test-EPA 91.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false Preconditioned idle test-EPA 91. 85.2218 Section 85.2218 ...Emission Control System Performance Warranty Short Tests § 85.2218 Preconditioned idle testâEPA 91. (a) General requirements...



p53 down-regulation: a new molecular mechanism involved in ischaemic preconditioning  

Microsoft Academic Search

Ischaemic preconditioning is associated with the activation of prosurvival mechanisms. Here we demonstrate that following a preconditioning protocol, the proapoptotic p53 is inactivated possibly via phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-murine double minute 2 (Mdm2) phosphorylation. Our data show that in preconditioned hearts Mdm2 was significantly phosphorylated, and wortmannin (a PI3K inhibitor) abrogated this effect (Western blotting). Also in preconditioned

Mihaela M Mocanu; Derek M Yellon



Experimental study of the protection of ischemic preconditioning to spinal cord ischemia  

Microsoft Academic Search

BACKGROUNDSince the advent of ischemic preconditioning in myocardium, more and more attention has been paid to ischemic preconditioning in the central nervous system (CNS). This study was designed to evaluate the protective effect of ischemic preconditioning on spinal cord ischemia.METHODSInterventional neuroradiological techniques were used to induce spinal cord ischemia in a rabbit model. Hydrogen electrode technique was used to determine

Tao Fan; Chung-Cheng Wang; Fen-Mei Wang; Fei Cheng; Hui Qiao; Shu-Lin Liu; Wei Guo; Fei-Yu Xiang



Protection of the Liver by Ischemic Preconditioning: A Review of Mechanisms and Clinical Applications  

Microsoft Academic Search

Ischemic preconditioning refers to the endogenous mechanism of protection against a sustained ischemic insult following an initial, brief ischemic stimulus. Ischemia-reperfusion injury of the liver is a major cause of morbidity and mortality in liver surgery and transplantation and ischemic preconditioning is a promising strategy for improving the outcome of liver surgery. The preconditioning phenomenon was first described in a

Rahul S. Koti; Alexander M. Seifalian; Brian R. Davidson



Preconditioning of swine heart with monophosphoryl lipid A improves myocardial preservation  

Microsoft Academic Search

Background. Ischemic preconditioning has been proven to be a powerful tool for myocardial protection in the setting of ischemia and reperfusion. A new drug to provide pharmacologic preconditioning, monophosphoryl lipid A (MLA), was administered 24 hours before an acute coronary occlusion in pigs to determine the effect on pharmacologic preconditioning.Methods. Two studies were completed. In the first, swine were distributed

Tetsuya Yoshida; Richard M Engelman; Daniel T Engelman; John A Rousou; Nilanjana Maulik; Motoaki Sato; Gary T Elliott; Dipak K Das



Cardiac gene expression and systemic cytokine profile are complementary in a murine model of post-ischemic heart failure  

PubMed Central

After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1? (3.8X) and TNF-? (6.0X). IFN-? was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.

Lachtermacher, S.; Esporcatte, B.L.B.; Montalvao, F.; Costa, P.C.; Rodrigues, D.C.; Belem, L.; Rabischoffisky, A.; Neto, H.C.C. Faria; Vasconcellos, R.; Iacobas, S.; Iacobas, D.A.; Dohmann, H.F.R.; Spray, D.C.; Goldenberg, R.C.S.; Campos-de-Carvalho, A.C.



The use of Stronger Neo-Minophagen C, a glycyrrhizin-containing preparation, in robust neuroprotection in the postischemic brain.  


Stronger Neo-Minophagen C (SNMC) is a glycyrrhizin-containing preparation that is approved in Japan for the treatment of chronic hepatic diseases and is marketed in Japan, China, Korea, Taiwan, and India. Glycyrrhizin, a triterpene present in the roots and rhizomes of licorice (Glycyrrhiza glabra) has been shown to have anti-inflammatory, anti-oxidative, and anti-viral effects. In the present study, we demonstrated the marked neuroprotective effects of SNMC in the postischemic rat brain after middle cerebral artery occlusion (MCAO). We used 1 ml/kg of SNMC, which is within the dose range used for the treatment of patients with chronic hepatic disease. The administration of SNMC intravenously at 30 minutes before or 30 minutes and 3 hours after MCAO (60 minutes) reduces mean infarct volumes to 27.0±4.2%, 37.1±12.4%, and 67.8±5.8% of that of untreated controls, respectively. This neuroprotective effect is accompanied by improvements in motor impairment and neurological deficits. The administration of SNMC is shown to suppress microglia activation and neutrophil infiltration in the postischemic brain. In addition, SNMC suppresses lipopolysaccharide-induced nitrite production and proinflammatory cytokine induction in a microglia cell line, BV2. This indicates that the neuroprotective effect of SNMC might be due, at least in part, to an anti-inflammatiory effect. Interestingly, SNMC shows significantly higher neuroprotective potency compared to an equivalent dose of pure glycyrrhizin, in terms of reducing infarct volume and improving neurological deficits. Together these results indicate that SNMC, a glycyrrhizin-containing preparation developed for chronic liver disease, has a marked neuroprotective function in the postischemic brain via its anti-inflammatory effects. PMID:22254159

Kim, Seung-Woo; Lim, Chae-Moon; Lee, Hye-Kyung; Lee, Ja-Kyeong



Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardioprotective properties in rat models  

PubMed Central

OBJECTIVE: Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs. METHODS: The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet. RESULTS: A lower early reperfusion arrhythmia score (1.50±0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33±0.71). Meanwhile, reduced infarct size was also observed (15.27±5.19% in remote perconditioning, 14.53±3.45% in remote preconditioning, and 19.84±5.85% in remote post-conditioning vs. 34.47±7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255±0.053 in remote perconditioning, 1.463±0.290 in remote preconditioning, and 1.461±0.541 in remote post-conditioning vs. 1.003±0.159 in ischemia reperfusion, p<0.05). CONCLUSION: Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia.

Zhu, Shui-Bo; Liu, Yong; Zhu, Yu; Yin, Gui-Lin; Wang, Rong-Ping; Zhang, Yu; Zhu, Jian; Jiang, Wei



Lipoxin a4 preconditioning and postconditioning protect myocardial ischemia/reperfusion injury in rats.  


This study aims to investigate the pre- and postconditioning effects of lipoxin A4 (LXA4) on myocardial damage caused by ischemia/reperfusion (I/R) injury. Seventy-two rats were divided into 6 groups: sham groups (C1 and C2), I/R groups (I/R1 and I/R2), and I/R plus LXA4 preconditioning and postconditioning groups (LX1 and LX2). The serum levels of IL-1 ? , IL-6, IL-8, IL-10, TNF- ? , and cardiac troponin I (cTnI) were measured. The content and the activity of Na(+)-K(+)-ATPase as well as the superoxide dismutase (SOD), and malondialdehyde (MDA) levels were determined. Along with the examination of myocardium ultrastructure and ventricular arrhythmia scores (VAS), connexin 43 (Cx43) expression were also detected. Lower levels of IL-1 ? , IL-6, IL-8, TNF- ? , cTnI, MDA content, and VAS and higher levels of IL-10, SOD activity, Na(+)-K(+)-ATPase content and activity, and Cx43 expression appeared in LX groups than I/R groups. Besides, H&E staining, TEM examination as well as analysis of gene, and protein confirmed that LXA4 preconditioning was more effective than postconditioning in preventing arrhythmogenesis via the upregulation of Cx43. That is, LXA4 postconditioning had better protective effect on Na(+)-K(+)-ATPase and myocardial ultrastructure. PMID:23956501

Zhao, Qifeng; Shao, Lan; Hu, Xingti; Wu, Guowei; Du, Jie; Xia, Jie; Qiu, Huixian



Critical Role of Endothelial Hydrogen Peroxide in Post-Ischemic Neovascularization  

PubMed Central

Background Reactive oxygen species (ROS) play an important role in angiogenesis in endothelial cells (ECs) in vitro and neovascularization in vivo. However, little is known about the role of endogenous vascular hydrogen peroxide (H2O2) in postnatal neovascularization. Methodology/Principal Findings We used Tie2-driven endothelial specific catalase transgenic mice (Cat-Tg mice) and hindlimb ischemia model to address the role of endogenous H2O2 in ECs in post-ischemic neovascularization in vivo. Here we show that Cat-Tg mice exhibit significant reduction in intracellular H2O2 in ECs, blood flow recovery, capillary formation, collateral remodeling with larger extent of tissue damage after hindlimb ischemia, as compared to wild-type (WT) littermates. In the early stage of ischemia-induced angiogenesis, Cat-Tg mice show a morphologically disorganized microvasculature. Vascular sprouting and tube elongation are significantly impaired in isolated aorta from Cat-Tg mice. Furthermore, Cat-Tg mice show a decrease in myeloid cell recruitment after hindlimb ischemia. Mechanistically, Cat-Tg mice show significant decrease in eNOS phosphorylation at Ser1177 as well as expression of redox-sensitive vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in ischemic muscles, which is required for inflammatory cell recruitment to the ischemic tissues. We also observed impaired endothelium-dependent relaxation in resistant vessels from Cat-Tg mice. Conclusions/Significance Endogenous ECs-derived H2O2 plays a critical role in reparative neovascularization in response to ischemia by upregulating adhesion molecules and activating eNOS in ECs. Redox-regulation in ECs is a potential therapeutic strategy for angiogenesis-dependent cardiovascular diseases.

Urao, Norifumi; Sudhahar, Varadarajan; Kim, Seok-Jo; Chen, Gin-Fu; McKinney, Ronald D.; Kojda, Georg; Fukai, Tohru; Ushio-Fukai, Masuko



40 CFR 86.132-00 - Vehicle preconditioning.  

Code of Federal Regulations, 2010 CFR

...CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may precondition a test...



40 CFR 86.132-00 - Vehicle preconditioning.  

Code of Federal Regulations, 2010 CFR

...CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New...iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may precondition a test...



40 CFR 86.132-00 - Vehicle preconditioning.  

Code of Federal Regulations, 2011 CFR

...highway, US06 or SC03 test cycles. (ii) [Reserved] (iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may precondition a test vehicle on test fuel and the US06 cycle. Upon request from a...



Endogenous neuroprotection: Mitochondria as gateways to cerebral preconditioning?  

Microsoft Academic Search

From single to multicellular organisms, protective mechanisms have evolved against endogenous and exogenous noxious stimuli. Preconditioning paradigms, in which stimulation below the threshold of injury results in subsequent protection of the brain, have played an important role in elucidating such endogenous protective mechanisms. Consequently, over the past decades numerous signaling pathways have been discovered by which the brain senses and

Ulrich Dirnagl; Andreas Meisel



Ischemic Preconditioning Attenuates Apoptotic Cell Death in the Rat Retina  

Microsoft Academic Search

PURPOSE. Ischemic preconditioning (IPC) protects the rat retina against the injury that ordinarily follows prolonged ischemia. It has been shown that release of adenosine, de novo protein synthesis, and mediators, such as protein kinase C and KATP channels, is required for IPC protection. However, the molec- ular mechanisms of neuroprotection by IPC are unknown. Retinal cells die after ischemia by

Cheng Zhang; Daniel M. Rosenbaum; Afzhal R. Shaikh; Qing Li; Pearl S. Rosenbaum; Daniel J. Pelham; Steven Roth



Ischemic Preconditioning Decreases Oxidative Stress during Reperfusion: A Chemiluminescence Study  

Microsoft Academic Search

The mechanism responsible for ischemic preconditioning (IPC) is still unknown but may involve the induction of antioxidant enzymes decreasing oxidative stress during subsequent periods of ischemia (I) and reperfusion (RP). The purpose of this study was to determine whether, in fact, an antioxidant mechanism is involved in the protection afforded by IPC. Lucigenin-enhanced chemiluminescence (LEC), a direct, continuous, nondestructive, on-line

Juan A. Crestanello; David M. Lingle; Joseph Kamelgard; John Millili; Glenn J. R. Whitman



Is ischemic preconditioning of the kidney clinically relevant?  

Microsoft Academic Search

Background. Renal ischemic preconditioning (IPC) is a phenomenon whereby a brief period of ischemia and reperfusion (I\\/R) provides tolerance to subsequent periods of ischemia. IPC has been demonstrated to protect rodent kidneys during I\\/R. The applicability to large mammals, including human beings, is unclear. The objective of this study was to determine if renal IPC has a beneficial effect in

Maciej Kosieradzki; Mary Ametani; James H. Southard; Martin J. Mangino



Evidence for the delayed effect in human ischemic preconditioning  

Microsoft Academic Search

OBJECTIVESThis study aimed to investigate prospectively the protective effect of a first preinfarction angina attack against acute myocardial infarction (AMI) in human hearts without significant collaterals.BACKGROUNDSeveral retrospective studies and the prospective studies have demonstrated the existence of the preconditioning (PC) effect in humans. However, collaterals were not examined in the prospective studies. In animal models, the PC effect on myocardial

Toshiyuki Noda; Shinya Minatoguchi; Kenshi Fujii; Masatsugu Hori; Takayuki Ito; Katsuo Kanmatsuse; Masunori Matsuzaki; Tetsuji Miura; Hiroshi Nonogi; Michihiko Tada; Masaru Tanaka; Hisayoshi Fujiwara



Preconditions of Peat Harvesting in Finnish Central-Lapland.  

National Technical Information Service (NTIS)

The aim of the study was to find out the effects of the differences in weather and geographical conditions on the preconditions of peat harvesting in the Finnish Central Lapland. The survey was done by conducting practical peat harvesting tests in three h...

E. Tapio V. Klemetti



Ischemic Preconditioning: A Novel Target for Neuroprotective Therapy  

Microsoft Academic Search

Ischemic preconditioning involves a brief exposure to ischemia in order to develop a tolerance to injurious effects of prolonged ischemia. The molecular mechanisms of neuroprotection that lead to ischemic tolerance are not yet completely understood. However, it seems that two distinct phases are involved. Firstly, a cellular defense function against ischemia may be developed by the mechanisms inherent to neurons

Miguel Blanco; Ignacio Lizasoain; Tomás Sobrino; José Vivancos; José Castillo



Autophagy induced by ischemic preconditioning is essential for cardioprotection.  


Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned hearts. In Langendorff-perfused hearts subjected to an IPC protocol of 3 x 5 min ischemia, we also observed an increase in autophagy within 10 min, as assessed by Western blotting for p62 and cadaverine dye binding. To establish the role of autophagy in IPC cardioprotection, we inhibited autophagy with Tat-ATG5(K130R), a dominant negative mutation of the autophagy protein Atg5. Cardioprotection by IPC was reduced in rat hearts perfused with recombinant Tat-ATG5(K130R). To extend the potential significance of autophagy in cardioprotection, we also assessed three structurally unrelated cardioprotective agents--UTP, diazoxide, and ranolazine--for their ability to induce autophagy in HL-1 cells. We found that all three agents induced autophagy; inhibition of autophagy abolished their protective effect. Taken together, these findings establish autophagy as an end-effector in ischemic and pharmacologic preconditioning. PMID:20559777

Huang, Chengqun; Yitzhaki, Smadar; Perry, Cynthia N; Liu, Wayne; Giricz, Zoltan; Mentzer, Robert M; Gottlieb, Roberta A



Autophagy Induced by Ischemic Preconditioning is Essential for Cardioprotection  

PubMed Central

Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with 5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned hearts. In Langendorff-perfused hearts subjected to an IPC protocol of 3?×?5 min ischemia, we also observed an increase in autophagy within 10 min, as assessed by Western blotting for p62 and cadaverine dye binding. To establish the role of autophagy in IPC cardioprotection, we inhibited autophagy with Tat-ATG5K130R, a dominant negative mutation of the autophagy protein Atg5. Cardioprotection by IPC was reduced in rat hearts perfused with recombinant Tat-ATG5K130R. To extend the potential significance of autophagy in cardioprotection, we also assessed three structurally unrelated cardioprotective agents—UTP, diazoxide, and ranolazine—for their ability to induce autophagy in HL-1 cells. We found that all three agents induced autophagy; inhibition of autophagy abolished their protective effect. Taken together, these findings establish autophagy as an end-effector in ischemic and pharmacologic preconditioning.

Huang, Chengqun; Yitzhaki, Smadar; Perry, Cynthia N.; Liu, Wayne; Giricz, Zoltan; Mentzer, Robert M.



40 CFR 86.232-94 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Vehicle preconditioning. 86.232-94 ...EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for...Year Gasoline-Fueled New Light-Duty Vehicles, New Light-Duty Trucks and New...



40 CFR 86.132-00 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Vehicle preconditioning. 86.132-00 ...EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New...



40 CFR 86.132-96 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Vehicle preconditioning. 86.132-96 ...EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New...



40 CFR 86.1232-96 - Vehicle preconditioning.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Vehicle preconditioning. 86.1232-96 ...EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Evaporative...Gas-Fueled and Methanol-Fueled Heavy-Duty Vehicles § 86.1232-96 Vehicle...



Preconditioning of PWR steam generators to reduce radiation buildup  

SciTech Connect

The purpose of the tests carried out on the CORELE loop was to determine whether preconditioning of steam generator tube surfaces could minimize the release rate of corrosion products. The test program and evaluation of the results obtained are included in this report.

Beslu, P.; Masse, F.; Anthoni, S.; Galliano, N. (CEA Centre d'Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France))



Finite difference preconditioning cubic spline collocation method of elliptic equations  

Microsoft Academic Search

Summary.   We discuss a finite difference preconditioner for the interpolatory cubic spline collocation method for a uniformly elliptic operator defined by in (the unit square) with homogeneous Dirichlet boundary conditions. Using the generalized field of values arguments, we discuss\\u000a the eigenvalues of the preconditioned matrix where is the matrix of the collocation discretization operator corresponding to , and is the

Hong Oh Kim; Sang Dong Kim; Yong Hun Lee



Metabolomic analysis of two different models of delayed preconditioning.  


Recently we described an ischemic preconditioning induced by repetitive coronary stenosis, which is induced by 6 episodes of non-lethal ischemia over 3 days, and which also resembles the hibernating myocardium phenotype. When compared with traditional second window of ischemic preconditioning using cDNA microarrays, many genes which differed in the repetitive coronary stenosis appeared targeted to metabolism. Accordingly, the goal of this study was to provide a more in depth analysis of changes in metabolism in the different models of delayed preconditioning, i.e., second window and repetitive coronary stenosis. This was accomplished using a metabolomic approach based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) techniques. Myocardial samples from the ischemic section of porcine hearts subjected to both models of late preconditioning were compared against sham controls. Interestingly, although both models involve delayed preconditioning, their metabolic signatures were radically different; of the total number of metabolites that changed in both models (135 metabolites) only 7 changed in both models, and significantly more, p<0.01, were altered in the repetitive coronary stenosis (40%) than in the second window (8.1%). The most significant changes observed were in energy metabolism, e.g., phosphocreatine was increased 4 fold and creatine kinase activity increased by 27.2%, a pattern opposite from heart failure, suggesting that the repetitive coronary stenosis and potentially hibernating myocardium have enhanced stress resistance capabilities. The improved energy metabolism could also be a key mechanism contributing to the cardioprotection observed in the repetitive coronary stenosis and in hibernating myocardium. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism". PMID:23127662

Bravo, Claudio; Kudej, Raymond K; Yuan, Chujun; Yoon, Seonghun; Ge, Hui; Park, Ji Yeon; Tian, Bin; Stanley, William C; Vatner, Stephen F; Vatner, Dorothy E; Yan, Lin



Preconditioning with Endoplasmic Reticulum Stress Mitigates Retinal Endothelial Inflammation via Activation of X-box Binding Protein 1*  

PubMed Central

Endoplasmic reticulum (ER) stress is widely implicated in various pathological conditions such as diabetes. Previously, we reported that enhanced ER stress contributes to inflammation and vascular damage in diabetic and ischemia-induced retinopathy. However, the exact role of the signaling pathways activated by ER stress in vascular inflammation remains poorly understood. In the present study, we investigated the role of X-box binding protein 1 (XBP1) in retinal adhesion molecule expression, leukostasis, and vascular leakage. Exposure of human retinal endothelial cells to low dose ER stress inducers resulted in a robust activation of XBP1 but did not affect inflammatory gene expression. However, ER stress preconditioning almost completely abolished TNF-?-elicited NF-?B activation and adhesion molecule ICAM-1 and VCAM-1 expression. Pharmaceutical inhibition of XBP1 activation or knockdown of XBP1 by siRNA markedly attenuated the effects of preconditioning on inflammation. Moreover, loss of XBP1 led to an increase in ICAM-1 and VCAM-1 expression. Conversely, overexpression of spliced XBP1 attenuated TNF-?-induced phosphorylation of IKK, I?B?, and NF-?B p65, accompanied by decreased NF-?B activity and reduced adhesion molecule expression. Finally, in vivo studies show that activation of XBP1 by ER stress preconditioning prevents TNF-?-induced ICAM-1 and VCAM-1 expression, leukostasis, and vascular leakage in mouse retinas. These results collectively indicate a protective effect of ER stress preconditioning against retinal endothelial inflammation, which is likely through activation of XBP1-mediated unfolded protein response (UPR) and inhibition of NF-?B activation.

Li, Jingming; Wang, Joshua J.; Zhang, Sarah X.



Preconditioning with endoplasmic reticulum stress mitigates retinal endothelial inflammation via activation of X-box binding protein 1.  


Endoplasmic reticulum (ER) stress is widely implicated in various pathological conditions such as diabetes. Previously, we reported that enhanced ER stress contributes to inflammation and vascular damage in diabetic and ischemia-induced retinopathy. However, the exact role of the signaling pathways activated by ER stress in vascular inflammation remains poorly understood. In the present study, we investigated the role of X-box binding protein 1 (XBP1) in retinal adhesion molecule expression, leukostasis, and vascular leakage. Exposure of human retinal endothelial cells to low dose ER stress inducers resulted in a robust activation of XBP1 but did not affect inflammatory gene expression. However, ER stress preconditioning almost completely abolished TNF-?-elicited NF-?B activation and adhesion molecule ICAM-1 and VCAM-1 expression. Pharmaceutical inhibition of XBP1 activation or knockdown of XBP1 by siRNA markedly attenuated the effects of preconditioning on inflammation. Moreover, loss of XBP1 led to an increase in ICAM-1 and VCAM-1 expression. Conversely, overexpression of spliced XBP1 attenuated TNF-?-induced phosphorylation of IKK, I?B?, and NF-?B p65, accompanied by decreased NF-?B activity and reduced adhesion molecule expression. Finally, in vivo studies show that activation of XBP1 by ER stress preconditioning prevents TNF-?-induced ICAM-1 and VCAM-1 expression, leukostasis, and vascular leakage in mouse retinas. These results collectively indicate a protective effect of ER stress preconditioning against retinal endothelial inflammation, which is likely through activation of XBP1-mediated unfolded protein response (UPR) and inhibition of NF-?B activation. PMID:21138840

Li, Jingming; Wang, Joshua J; Zhang, Sarah X



Nitric oxide preconditioning regulates endothelial monolayer integrity via the heat shock protein 90-soluble guanylate cyclase pathway.  


Large (pathological) amounts of nitric oxide (NO) induce cell injury, whereas low (physiological) NO concentrations often ameliorate cell injury. We tested the hypotheses that pretreatment of endothelial cells with low concentrations of NO (preconditioning) would prevent injury induced by high NO concentrations. Apoptosis, induced in bovine aortic endothelial cells (BAECs) by exposing them to either 4 mM sodium nitroprusside (SNP) or 0.5 mM N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1,2-ethylenediamine (spermine NONOate) for 8 h, was abolished by 24-h pretreatment with either 100 microM SNP, 10 microM spermine NONOate, or 100 microM 8-bromo-cGMP (8-Br-cGMP). Repair of BAECs following wounding, measured as the recovery rate of transendothelial electrical resistance, was delayed by 8-h exposure to 4 mM SNP, and this delay was significantly attenuated by 24-h pretreatment with 100 microM SNP. NO preconditioning produced increased association and expression of soluble guanyl cyclase (sGC) and heat shock protein 90 (HSP90). The protective effect of NO preconditioning, but not the injurious effect of 4 mM SNP, was abolished by either a sGC activity inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) or a HSP90 binding inhibitor (radicicol) and was mimicked by 8-Br-cGMP. We conclude that preconditioning with a low dose of NO donor accelerates repair and maintains endothelial integrity via a mechanism that includes the HSP90/sGC pathway. HSP90/sGC may thus play a role in the protective effects of NO-generating drugs from injurious stimuli. PMID:17012359

Antonova, Galina N; Snead, Connie M; Antonov, Alexander S; Dimitropoulou, Christiana; Venema, Richard C; Catravas, John D




PubMed Central

Isoflurane preconditioning neuroprotection in experimental stroke is male-specific. The role of androgens in the ischemic sensitivity of isoflurane preconditioned male brain and whether androgen effects are androgen receptor dependent were assessed. Male C57BL/6 mice were implanted with flutamide (androgen receptor antagonist), or castrated and implanted with testosterone, dihydrotestosterone, flutamide, letrozole (aromatase inhibitor), or vehicle 7–13 days before preconditioning. P450 estrogen aromatase wild-type and knockout mice were also evaluated. All mice were preconditioned for 4 h with 0% (sham preconditioning) or 1% isoflurane (isoflurane preconditioning) and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery occlusion and were evaluated 22 h later for infarct volume. For neurobehavioral outcomes, sham and isoflurane preconditioned castrated male±dihydrotestosterone groups underwent 1 h of middle cerebral artery occlusion followed by 9 days of reperfusion. Isoflurane preconditioning neuroprotection relative to infarct volume outcomes were testosterone and dihydrotestosterone dose-specific and androgen receptor-dependent. Relative to long-term neurobehavioral outcomes, front paw sensorimotor function improved in isoflurane preconditioned mice regardless of androgen status while androgen replacement independently improved sensorimotor function. In contrast, isoflurane preconditioning improved cognitive function in castrates lacking endogenous androgens, but this improvement was absent in androgen replaced mice. Our findings suggest that androgen availability during isoflurane preconditioning may influence infarct volume and neurobehavioral outcomes in male mice following experimental stroke.




Cerebral vascular autoregulation and CO2 reactivity following onset of the delayed postischemic hypoperfusion state in dogs.  


A small number of animal studies have suggested that during the delayed postischemic hypoperfusion state, CO2 reactivity of the cerebral vasculature is lost whereas autoregulation is retained. These findings, however, are inconsistent with the bulk of experimental evidence which demonstrates that CO2 reactivity is more robust and may be retained in pathologic circumstances which abolish autoregulation. These opposing viewpoints were therefore further evaluated in 18 dogs in which complete global ischemia was induced by cerebrospinal fluid (CSF) compression for periods of 12 (n = 12) and 18 (n = 6) min. Following 45 min of reperfusion and with onset of the delayed postischemic hypoperfusion state, autoregulation and CO2 reactivity were evaluated using a continuous measurement of CBF (by sagittal sinus outflow). CO2 reactivity was tested over a PaCO2 range of 20 to 60 mm Hg; autoregulation was tested over a blood pressure range of 60 to 140 mm Hg. Results demonstrated that after both 12 and 18 min of complete global ischemia, autoregulation and CO2 reactivity of the cerebral vasculature were both present, but attenuated. In the case of CO2 reactivity, the slope of the CBF response was decreased approximately 75%. In the case of autoregulation, the response in some dogs was incomplete as compared with their preischemic response. PMID:8436617

Christopherson, T J; Milde, J H; Michenfelder, J D



Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3? Signaling and Inhibiting Mitochondrial Permeability Transition  

PubMed Central

Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 ?mol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 ?mol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3?) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3? signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury.

Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin



Hydrogen Sulfide Preconditioning Protects Rat Liver against Ischemia/Reperfusion Injury by Activating Akt-GSK-3? Signaling and Inhibiting Mitochondrial Permeability Transition.  


Hydrogen sulfide (H2S) is the third most common endogenously produced gaseous signaling molecule, but its impact on hepatic ischemia/reperfusion (I/R) injury, especially on mitochondrial function, remains unclear. In this study, rats were randomized into Sham, I/R, ischemia preconditioning (IPC) or sodium hydrosulfide (NaHS, an H2S donor) preconditioning groups. To establish a model of segmental (70%) warm hepatic ischemia, the hepatic artery, left portal vein and median liver lobes were occluded for 60 min and then unclamped to allow reperfusion. Preconditioning with 12.5, 25 or 50 ?mol/kg NaHS prior to the I/R insult significantly increased serum H2S levels, and, similar to IPC, NaHS preconditioning decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the plasma and prevented hepatocytes from undergoing I/R-induced necrosis. Moreover, a sub-toxic dose of NaHS (25 ?mol/kg) did not disrupt the systemic hemodynamics but dramatically inhibited mitochondrial permeability transition pore (MPTP) opening and thus prevented mitochondrial-related cell death and apoptosis. Mechanistic studies revealed that NaHS preconditioning markedly increased the expression of phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3?) and B-cell lymphoma-2 (Bcl-2) and decreased the release of mitochondrial cytochrome c and cleaved caspase-3/9 levels. Therefore, NaHS administration prior to hepatic I/R ameliorates mitochondrial and hepatocellular damage through the inhibition of MPTP opening and the activation of Akt-GSK-3? signaling. Furthermore, this study provides experimental evidence for the clinical use of H2S to reduce liver damage after perioperative I/R injury. PMID:24058562

Zhang, Qingqing; Fu, Hailong; Zhang, Hao; Xu, Fengying; Zou, Zui; Liu, Meng; Wang, Quanxing; Miao, Mingyong; Shi, Xueyin



Protection of the liver by ischemic preconditioning: a review of mechanisms and clinical applications.  


Ischemic preconditioning refers to the endogenous mechanism of protection against a sustained ischemic insult following an initial, brief ischemic stimulus. Ischemia-reperfusion injury of the liver is a major cause of morbidity and mortality in liver surgery and transplantation and ischemic preconditioning is a promising strategy for improving the outcome of liver surgery. The preconditioning phenomenon was first described in a canine model of myocardial ischemia-reperfusion injury in 1986 and since then has been shown to exist in other organs including skeletal muscle, brain, kidneys, retina and liver. In the liver, the preconditioning effect has been demonstrated in rodents and a recent study has demonstrated human clinical benefits of preconditioning during hemihepatectomies. Ischemic preconditioning has been described as an adaptive response and although the precise mechanism of hepatoprotection from preconditioning is unknown it is likely to be a receptor-mediated process. Several hypotheses have been proposed and this review assesses possible mechanisms of ischemic preconditioning and its role in hepatic surgery and liver transplantation. The future lies in defining the mechanisms of the ischemic preconditioning effect to allow drug targeting to induce the preconditioning response. PMID:12840597

Koti, Rahul S; Seifalian, Alexander M; Davidson, Brian R



Acetyl l-Carnitine selectively prevents post-ischemic LTP via a possible action on mitochondrial energy metabolism  

Microsoft Academic Search

It has been hypothesized that Acetyl-l-Carnitine (ALC) contributes to mitochondrial ATP production through maintenance of key mitochondrial proteins and protects mitochondria against oxidative stress. We have investigated the role of ALC on the expression of two forms of synaptic plasticity in the striatum: (i) the physiological long-term potentiation (LTP) and (ii) the ischemic long-term potentiation (i-LTP), an aberrant form of

Vincenza Bagetta; Ilaria Barone; Veronica Ghiglieri; Massimiliano Di Filippo; Carmelo Sgobio; Giorgio Bernardi; Paolo Calabresi; Barbara Picconi



Mechanisms of neuroprotection during ischemic preconditioning: lessons from anoxic tolerance.  


Different physiological adaptations for anoxia resistance have been described in the animal kingdom. These adaptations are particularly important in organs that are highly susceptible to energy deprivation such as the heart and brain. Among vertebrates, turtles are one of the species that are highly tolerant to anoxia. In mammals however, insults such as anoxia, ischemia and hypoglycemia, all cause major histopathological events to the brain. However, in mammals even ischemic or anoxic tolerance is found when a sublethal ischemic/anoxic insult is induced sometime before a lethal ischemic/anoxic insult is induced. This phenomenon is defined as ischemic preconditioning. Better understanding of the mechanisms inducing both anoxic tolerance in turtles or ischemic preconditioning in mammals may provide novel therapeutic interventions that may aide mammalian brain to resist the ravages of cerebral ischemia. In this review, we will summarize some of the mechanisms implemented in both models of tolerance, emphasizing physiological and biochemical similarities. PMID:17045830

Perez-Pinzon, Miguel A



Organ preconditioning: the past, current status, and related lung studies  

PubMed Central

Preconditioning (PC) has emerged as a powerful method for experimentally and clinically attenuating various types of organ injuries. In this paper related clinical and basic research issues on organ preconditioning issues were systemically reviewed. Since lung injuries, including ischemia-reperfusion and others, play important roles in many clinical results, including thromboembolism, trauma, thermal injury, hypovolemic and endotoxin shock, reimplantation response after organ transplantation, and many respiratory diseases in critical care. It is of interest to uncover methods, including the PCs, to protect the lung from the above injuries. However, related studies on pulmonary PC are relatively rare and still being developed, so we will review previous literature on experimental and clinical studies on pulmonary PC in the following paragraphs.

Luh, Shi-ping; Yang, Pan-chyr



HMC algorithm with multiple time scale integration and mass preconditioning  

NASA Astrophysics Data System (ADS)

We present a variant of the HMC algorithm with mass preconditioning (Hasenbusch acceleration) and multiple time scale integration. We have tested this variant for standard Wilson fermions at ?=5.6 and at pion masses ranging from 380 to 680 MeV. We show that in this situation its performance is comparable to the recently proposed HMC variant with domain decomposition as preconditioner. We give an update of the “Berlin Wall” figure, comparing the performance of our variant of the HMC algorithm to other published performance data. Advantages of the HMC algorithm with mass preconditioning and multiple time scale integration are that it is straightforward to implement and can be used in combination with a wide variety of lattice Dirac operators.

Urbach, C.; Jansen, K.; Shindler, A.; Wenger, U.



Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry  

PubMed Central

Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery.

Wang, Wei Zhong



Induction of tolerance in rat cortical neurons: hypoxic preconditioning  

Microsoft Academic Search

Sublethal ischemia leads to increased tolerance against subsequent prolonged cerebral ischemia in vivo. In the present study we modeled preconditioning mechanisms in a neuronal-enriched culture. Damage was significantly reduced (up to 72%) with 1.5 h of oxygen-glucose deprivation 48–72 h before 3 h oxygen-glucose deprivation. Tolerance was also elicited by Na+-K+-ATPase inhibition. No damage was observed when astroglial or endothelial

Ulrike Bruer; Markus K Weih; Nikolaj K Isaev; Andreas Meisel; Karsten Ruscher; Alexandra Bergk; George Trendelenburg; Frank Wiegand; Ilya V Victorov; Ulrich Dirnagl



Early Microcirculatory Changes after Ischemic Preconditioning and Small Bowel Autotransplantation  

Microsoft Academic Search

Background\\/Aims: Ischemia-reperfusion injury contributes to the high complication rate of small bowel transplantation (SBTX). Ischemic preconditioning (IPC) protects against reperfusion injury in several organs, but the IPC-induced microcirculatory reaction in the intestine is unknown. Methods: We examined the effects of IPC on the macrohemodynamics and graft microcirculation in a canine model of SBTX during a 4-hour reperfusion period. In group

A. Wolfárd; J. Kaszaki; S. Varga; G. Lázár; M. Boros



Is There a Place for Cerebral Preconditioning in the Clinic?  

Microsoft Academic Search

Preconditioning (PC) describes a phenomenon whereby a sub-injury-inducing stress can protect against a later injurious stress.\\u000a Great strides have been made in identifying the mechanisms of PC-induced protection in animal models of brain injury. While\\u000a these may help elucidate potential therapeutic targets, there are questions over the clinical utility of cerebral PC, primarily\\u000a because of questions over the need to

Richard F. Keep; Michael M. Wang; Jianming Xiang; Ya Hua; Guohua Xi



Pharmacological preconditioning with diazoxide slows energy metabolism during sustained ischemia  

PubMed Central

Ischemic preconditioning (PC) is associated with slower destruction of the adenine nucleotide pool (?Ad) and slower rate of anaerobic glycolysis during ischemic stress. These changes are concordant with the preconditioned state, supporting an essential role of lowered energy demand in the cardioprotective mechanism of PC. Although pharmacological PC induced by the activation of mitochondrial KATP channels also limits infarct size, its effect on energy metabolism during sustained ischemia is unknown. Using metabolite levels found at baseline and after a 15 min test episode of regional ischemia, the effect of a cardioprotective dose of diazoxide on metabolic features associated with PC was tested in barbital-anesthetized, open-chest dogs. Diazoxide (3.5 mg/kg at an intravenous rate of 1 mL/min) infused before a test episode of ischemia had no effect on baseline metabolic indices. However, during ischemic stress, treated hearts exhibited less destruction of ATP, less degradation of the ?Ad into nucleosides and bases, as well as less lactate production than control hearts subjected only to ischemic stress. Thus, diazoxide mimics the metabolic alterations observed in PC tissue. This supports the hypothesis that a reduction in energy demand, which is now equated with an increased ATP to ADP ratio in the sarcoplasm, is a critical component of the mechanism of cardioprotection in preconditioned myocardium. It is hypothesized that during PC or diazoxide treatment, the passage of the ?Ad into and out of the mitochondria is slowed, limiting the level of ATP available to the mitochondrial ATPase and preserving ATP and the total ?Ad. Altered ischemic mitochondrial metabolism plays an important role in establishing and maintaining the preconditioned state.

Schwartz, Lisa M; Reimer, Keith A; Crago, Mark S; Jennings, Robert B



Plasma preconditioning of sapphire substrate for GaN epitaxy  

Microsoft Academic Search

The crystalline quality of molecular beam epitaxy (MBE)-grown layers of GaN on sapphire strongly depends on the initial stage of film nucleation and growth. Thus, pre-conditioning of the substrate is of vital importance. In this study we use X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED) to examine in situ the case for surface cleaning and nitridation of

Christian Heinlein; Jostein Grepstad; Henning Riechert; Robert Averbeck



Cardiac preconditioning with calcium: Clinically accessible myocardial protection  

Microsoft Academic Search

Cardiac preconditioning is mediated by protein kinase C. Although endogenous calcium is a potent stimulus of protein kinase C, it remains unknown whether preischemic administration of exogenous calcium can induce protein kinase C–mediated myocardial protection against ischemia-reperfusion injury. To study this, calcium chloride was administered retrogradely through the aorta at a rate 5 nmol\\/min for 2 minutes to isolated perfused

Daniel R. Meldrum; Joseph C. Cleveland; Brett C. Sheridan; Robert T. Rowland; Anirban Banerjee; Alden H. Harken



Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction.  


We propose a preconditioned alternating projection algorithm (PAPA) for solving the maximum a posteriori (MAP) emission computed tomography (ECT) reconstruction problem. Specifically, we formulate the reconstruction problem as a constrained convex optimization problem with the total variation (TV) regularization. We then characterize the solution of the constrained convex optimization problem and show that it satisfies a system of fixed-point equations defined in terms of two proximity operators raised from the convex functions that define the TV-norm and the constrain involved in the problem. The characterization (of the solution) via the proximity operators that define two projection operators naturally leads to an alternating projection algorithm for finding the solution. For efficient numerical computation, we introduce to the alternating projection algorithm a preconditioning matrix (the EM-preconditioner) for the dense system matrix involved in the optimization problem. We prove theoretically convergence of the preconditioned alternating projection algorithm. In numerical experiments, performance of our algorithms, with an appropriately selected preconditioning matrix, is compared with performance of the conventional MAP expectation-maximization (MAP-EM) algorithm with TV regularizer (EM-TV) and that of the recently developed nested EM-TV algorithm for ECT reconstruction. Based on the numerical experiments performed in this work, we observe that the alternating projection algorithm with the EM-preconditioner outperforms significantly the EM-TV in all aspects including the convergence speed, the noise in the reconstructed images and the image quality. It also outperforms the nested EM-TV in the convergence speed while providing comparable image quality. PMID:23271835

Krol, Andrzej; Li, Si; Shen, Lixin; Xu, Yuesheng



Preconditioning the bidomain model with almost linear complexity  

NASA Astrophysics Data System (ADS)

The bidomain model is widely used in electro-cardiology to simulate spreading of excitation in the myocardium and electrocardiograms. It consists of a system of two parabolic reaction diffusion equations coupled with an ODE system. Its discretisation displays an ill-conditioned system matrix to be inverted at each time step: simulations based on the bidomain model therefore are associated with high computational costs. In this paper we propose a preconditioning for the bidomain model either for an isolated heart or in an extended framework including a coupling with the surrounding tissues (the torso). The preconditioning is based on a formulation of the discrete problem that is shown to be symmetric positive semi-definite. A block LU decomposition of the system together with a heuristic approximation (referred to as the monodomain approximation) are the key ingredients for the preconditioning definition. Numerical results are provided for two test cases: a 2D test case on a realistic slice of the thorax based on a segmented heart medical image geometry, a 3D test case involving a small cubic slab of tissue with orthotropic anisotropy. The analysis of the resulting computational cost (both in terms of CPU time and of iteration number) shows an almost linear complexity with the problem size, i.e. of type nlog?(n) (for some constant ?) which is optimal complexity for such problems.

Pierre, Charles



Effects of hypoxic preconditioning on expression of transcription factor NGFI-A in the rat brain after unavoidable stress in the "learned helplessness" model.  


We report here our immunocytochemical studies establishing that the development of a depression-like state in rats following unavoidable stress in a "learned helplessness" model is accompanied by stable activation of the expression of transcription factor NGFI-A in the dorsal hippocampus (field CA1) and the magnocellular paraventricular nucleus of the hypothalamus, along with an early wave of post-stress expression, which died down rapidly, in the ventral hippocampus (the dentate gyrus) and a long period of up to five days of high-level expression in the neocortex. In rats subjected to three sessions of preconditioning consisting of moderate hypobaric hypoxia (360 mmHg, 2 h, with intervals of 24 h), which did not form depression in these circumstances, there were significant changes in the dynamics of immunoreactive protein content in the hippocampus, with a stable increase in expression in the ventral hippocampus and only transient and delayed (by five days) expression in field CA1. In the neocortex (layer II), preconditioning eliminated the effects of stress, preventing prolongation of the first wave of NGFI-A expression to five days, while in the magnocellular hypothalamus, conversely, preconditioning stimulated a second (delayed) wave of the expression of this transcription factor. The pattern of NGFI-A expression in the hippocampus, neocortex, and hypothalamus seen in non-preconditioned rats appears to reflect the pathological reaction to aversive stress, which, rather than adaptation, produced depressive disorders. Post-stress modification of the expression of the product of the early gene NGFI-A in the brain induced by hypoxic preconditioning probably plays an important role in increased tolerance to severe psychoemotional stresses and is an important component of antidepressant mechanisms. PMID:20535567

Baranova, K A; Rybnikova, E A; Mironova, V I; Samoilov, M O



Tachycardia Preconditions Infarct Size in Dogs Role of Adenosine and Protein Kinase C  

Microsoft Academic Search

Background—Myocardial ischemic preconditioning is a well-known phenomenon, however there is scant information in regard to nonischemic preconditioning. Methods and Results—We studied in anesthetized dogs the preconditioning effect of tachycardia and the mediation of adenosine and protein kinase C in this process. In a control group the anterior descending coronary artery was occluded for 60 minutes and reperfused for 270 minutes.

Raul J. Domenech; Pilar Macho; Diego Velez; Gina Sanchez; Xueliang Liu; Naranjan Dhalla


A Preconditioned Multigrid Method for Efficient Simulation of Three-dimensional Compressible and Incompressible Flows  

Microsoft Academic Search

To develop an efficient and robust aerodynamic analysis method for numerical optimization designs of wing and complex configuration, a combination of matrix preconditioning and multigrid method is presented and investigated. The time derivatives of three-dimensional Navier-Stokes equations are preconditioned by Choi-Merkle preconditioning matrix that is originally designed for two-dimensional low Mach number viscous flows. An extension to three-dimensional viscous flow

Zhonghua Han; Fei He; Wenping Song; Zhide Qiao



Calcitonin Gene-Related Peptide-Induced Preconditioning Improves Preservation With Cardioplegia  

Microsoft Academic Search

Background. Our recent work has shown that calcitonin gene-related peptide (CGRP) may play an important role in mediation of ischemic preconditioning. Therefore, we tested the hypothesis that CGRP-induced preconditioning protects against myocardial damage after prolonged cardioplegic arrest in isolated rat hearts.Methods. Six groups were studied: the control, ischemic preconditioning, and CGRP-pretreated groups for both 4- and 8-hour hypothermic ischemia. All

Er-Xiong Lu; Chang-Fu Peng; Yuan-Jian Li; Sheng-Xi Cheng



Preconditioning concepts in polymer flooding in high-salinity reservoirs; Laboratory investigations and case histories  

SciTech Connect

In polymer-flood field projects with partially hydrolized polyacrylamide (PH PAA) solutions, the authors applied two methods of preconditioning: a preflush with fresh water and the use of a relatively small slug of a less-salt-sensitive polymer. Results of laboratory work that led to an improved preconditioning concept with polymer are described. Case histories of two projects with two different preconditioning processes are presented and discussed in detail.

Volz, H.; Maltin, B.K. (RWE-DEA AG (DE)); Sohn, W.O.



Effects of fasudil, a Rho-kinase inhibitor, on myocardial preconditioning in anesthetized rats  

Microsoft Academic Search

The aim of this study was to examine the effects of fasudil, a Rho-kinase inhibitor, on ischemic preconditioning and carbachol preconditioning in anesthetized rats. The total number of ventricular ectopic beats was markedly augmented with fasudil at 0.3 mg\\/kg and depressed with fasudil at 10 mg\\/kg. Fasudil at 10 mg\\/kg also markedly decreased the ventricular tachycardia incidence. Ischemic preconditioning, induced

?eniz Demiryürek; Ali F. Kara; Ahmet Çelik; Aydan Babül; Abdullah T. Demiryürek



Attenuation of Focal Cerebral Ischemic Injury Following Post-Ischemic Inhibition of Angiotensin Converting Enzyme (ACE) Activity in Normotensive Rat  

PubMed Central

Background Central renin angiotensin system has an important role on the cerebral microcirculation and metabolism. Our previous work showed that inhibition of angiotensin converting enzyme () activity prior to induction of ischemia protected the brain from severe ischemia/reperfusion (I/R) injuries. This study evaluated the impacts of post-ischemic inhibition of , enalapril, on brain infarction in normotensive rats. Methods Rats were anesthetized with chloral hydrate (400 mg/kg). Focal cerebral ischemia was induced by 60-min intraluminal occlusion of right middle cerebral artery (MCA). Intraperitoneal injection of enalapril (0.03 or 0.1 mg/kg) was done after MCA reopening (reperfusion). Neurological deficit score (NDS) was evaluated after 24 h and the animals randomly assigned for the assessments of infarction, absolute brain water content (ABWC) and index of brain edema Results Severe impaired motor functions (NDS = 2.78 ± 0.28), massive infarction (cortex = 214 ± 19 mm3, striatum = 86 ± 5 mm3) and edema (ABWC = 83.1 ± 0.46%) were observed in non-treated ischemic rats. Non-hypotensive dose of enalapril (0.03 mg/kg) significantly reduced NDS (1.5 ± 0.22), infarction (cortex = 102 ± 16 mm3, striatum = 38 ± 5 mm3) and edema (ABWC = 80.9 ± 0.81%). Enalapril at dose of 0.1 mg/kg significantly lowered arterial pressure could not improve NDS (2.0 ± 0.45) and reduce infarction (cortex = 166 ± 26 mm3, striatum = 71 ± 11 mm3). Conclusion Post-ischemic ACE inhibition in the normotensive rats without affecting arterial pressure protects the brain from reperfusion injuries; however, this beneficial action is masked by hypotension.

Panahpour, Hamdollah; Dehghani, Gholam Abbas



[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. II].  


It is thought that highly reactive oxygen radicals generated at the ischemia-reperfusion in case of strokes play an important role in damaging the brain. It is well known that lipid peroxidation is propagated by active oxygen radicals, and the the brain is susceptible to the lipid peroxidation. In the previous study, we found that several Chinese herbal medicines and kampo components, which were used for the attenuation of the post-ischemic brain injury, showed a free-radical (OH., O2-. and DPPH) scavenging activity. However, it is not clear whether these Chinese herbal medicines can inhibit the lipid peroxidation reaction or not. In attempting to address this question, we have used three kinds of kampo formulations (Oren-gedoku-to (Huang-Lian-Jie-Du-Tang), Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) and Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan)) to measure the suppressive effect of the lipid peroxidation on the mouse cerebrum using the TBA technique in vitro and in vivo. In vitro experiments, all these Chinese herbal medicines decreased the levels of TBA-reactive substances concentration-dependently. In vivo studies, the levels of the TBA-reactive substance of the cerebrum homogenate of mice treated with these kampo formulations by p.o. for three weeks also decreased. From these results, we suggest that the pharmacological action of Chinese herbal medicines used for the attenuation of the post-ischemic brain damage not only have a free-radical scavenging activity, but also have a suppressive effect on the generation of the lipid peroxidation. PMID:7473058

Fushitani, S; Minakuchi, K; Tsuchiya, K; Takasugi, M; Murakami, K



Activated protein C promotes neovascularization and neurogenesis in post-ischemic brain via protease activated receptor 1  

PubMed Central

Activated protein C (APC) is a serine protease with anticoagulant and direct cytoprotective activities. Early post-ischemic APC application activates the cellular protein C pathway in brain endothelium and neurons which is neuroprotective. Whether late APC administration after a transient ischemic attack is neuroprotective and whether APC influences brain repair is not known. Here, we determined safety and efficacy of late APC and tissue-plasminogen activator (tPA) administrations in a mouse model of transient brain ischemia. tPA given at 6 h after onset of ischemia killed all mice within 2 days, whereas APC given at 6 or 24 h after ischemia onset improved significantly functional outcome and reduced spread of the ischemic lesion. At 7 days post-ischemia, APC multiple-dosing (0.8 mg/kg i.p.) at 6-72 h or 72-144 h enhanced comparably cerebral perfusion in the ischemic border by about 40% as shown by in vivo lectin-FITC angiography, blocked blood-brain barrier leakage of serum proteins and increased the number of endothelial replicating cells by 4.5-4.7-fold. APC multi-dosing at 6-72 h or 72-144 h increased proliferation of neuronal progenitor cells in the subventricular zone (SVZ) by 40-50% and migration of newly formed neuroblasts from the SVZ towards the ischemic border by about 2-fold. APC's effects on neovascularization and neurogenesis were mediated by protease activated receptor-1 and were independent of APC's reduction of infarction volume. Our data show that delayed APC administration is neuroprotective and mediates brain repair, i.e., neovascularization and neurogenesis, suggesting a significant extension of the therapeutic window for APC intervention in post-ischemic brain.

Thiyagarajan, Meenakshisundaram; Fernandez, Jose A.; Lane, Steven M.; Griffin, John H.; Zlokovic, Berislav V.



Role of endogenous endothelin-1 in post-ischemic cardiac dysfunction and norepinephrine overflow in rat hearts.  


Endothelin-1 and norepinephrine are involved in myocardial ischemia/reperfusion injury. The aim of this study was to investigate the role of endogenously generated endothelin-1 in ischemia/reperfusion-induced norepinephrine overflow and cardiac dysfunction using a nonselective prototype of endothelin-converting enzyme (ECE) inhibitor, phosphoramidon, and a selective ECE inhibitor, SM-19712 (4-chloro-N-[[(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]carbonyl]benzenesulfonamide, monosodium salt). According to the Langendorff technique, isolated Sprague-Dawley rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. Phosphoramidon and SM-19712 were perfused 30 min before ischemia and during reperfusion. Endothelin-1 level in left ventricle was increased by ischemia/reperfusion. This increase in left ventricular endothelin-1 level was suppressed by treatment with SM-19712. SM-19712 significantly improved ischemia/reperfusion-induced cardiac dysfunction such as decreased left ventricular developed pressure and dP/dt(max) and increased left ventricular end diastolic pressure. In addition, this agent suppressed excessive norepinephrine overflow in the coronary effluent from the post-ischemic heart. In contrast, treatment with phosphoramidon further enhanced left ventricular endothelin-1 level and norepinephrine overflow, and significantly worsened cardiac dysfunction after ischemia/reperfusion. These responses such as exaggerated norepinephrine overflow and the cardiac dysfunction observed after ischemia/reperfusion were markedly suppressed in the presence of a selective endothelin ET(A) receptor antagonist, ABT-627 [2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid]. These findings indicate that cardiac endothelin-1 production is enhanced by ischemia/reperfusion, and this endogenously increased endothelin-1 is involved in post-ischemic norepinephrine overflow and cardiac dysfunction via the activation of endothelin ET(A) receptors. PMID:18586023

Tawa, Masashi; Fukumoto, Taiki; Ohkita, Mamoru; Matsumura, Yasuo



Post-ischemic hyperglycemia exacerbates the development of cerebral ischemic neuronal damage through the cerebral sodium-glucose transporter.  


Post-ischemic hyperglycemia may be one of the triggers of ischemic neuronal damage. However, the detailed mechanisms of this injury process are still unknown. Here, we focused on the involvement of the sodium-glucose transporter (SGLT), which transports glucose together with Na(+) ions, and generates inward currents while transporting glucose into cells, resulting in depolarization and increased excitability. The aim of this study was to determine the involvement of the SGLT in the development of cerebral ischemic stress-induced neuronal damage. Male ddY mice were subjected to 2h of middle cerebral artery occlusion (MCAO). Fasting blood glucose (FBG) was measured using the glucose pilot. Neuronal damage was estimated by histological and behavioral analyses. Phlorizin and glucose were administered by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection. Administration of phlorizin (40, 120 or 200mg/kg, i.p.) significantly and dose-dependently suppressed the elevation of FBG and ischemic neuronal damage. In contrast, phlorizin (10 or 40?g/mouse, i.c.v.) significantly and dose-dependently suppressed ischemic neuronal damage without reducing the elevation of FBG. Moreover, the development of neuronal damage was significantly and dose-dependently exacerbated following i.c.v. administration of glucose (10% or 25% (w/v)), and its exacerbation was suppressed by i.c.v. administration of phlorizin (40?g/mouse). These results suggest that cerebral SGLT is activated by post-ischemic hyperglycemia and may be involved in the exacerbation of ischemic neuronal damage. PMID:23078759

Yamazaki, Yui; Harada, Shinichi; Tokuyama, Shogo



Preconditioning with volatile anaesthetic sevoflurane in ischemic retinal lesion in rats.  


Volatile anaesthetic agents have been recognized for their neuroprotective properties since the 1960s. However, little is known regarding the potential retinoprotective effects of preconditioning by anaesthetic drugs. Retinal ischemia can be modeled by permanent bilateral common carotid artery occlusion (BCCAO). Here we studied the degree of ischemic injury with preconditioning by sevoflurane in the rat retina. During the BCCAO operation and preconditioning Wistar rats were anaesthetized with 1 MAC of sevoflurane. The oxygen, carbon dioxide, and anaesthetic vapor concentration in the anaesthetizing box was monitored with a gas analyzer. We examined 4 groups: non- and preconditioning groups in control and BCCAO animals. The duration of preconditioning period was 1 h and it was performed 1 day before BCCAO. The retinas were processed for histological evaluation after 2 weeks survival to determine the cell number in the ganglion cell layer and the thickness of the whole retina and that of all retinal layers. BCCAO-induced retinal ischemic injury was ameliorated by sevoflurane preconditioning. Retinal thickness and the cell number in the ganglion cell layer were more retained in preconditioned animals after BCCAO compared to non-preconditioned group. These results suggest that preconditioning using sevoflurane could provide a new perspective in retinoprotective strategies. PMID:22684245

Szabadfi, Krisztina; Danyadi, Bese; Kiss, Peter; Manavalan, Sridharan; Gabriel, Robert; Reglodi, Dora; Tamas, Andrea; Trasy, Domonkos; Batai, Istvan



Isoflurane preconditioning protects astrocytes from oxygen and glucose deprivation independent of innate cell sex  

PubMed Central

Isoflurane exposure can protect the mammalian brain from subsequent insults like ischemic stroke. However, this protective preconditioning effect is sexually dimorphic, with isoflurane preconditioning decreasing male while exacerbating female brain damage in a mouse model of cerebral ischemia. Emerging evidence suggests that innate cell sex is an important factor in cell death, with brain cells having sex-specific sensitivities to different insults. We used an in vitro model of isoflurane preconditioning and ischemia to test the hypothesis that isoflurane preconditioning protects male astrocytes while having no effect or even a deleterious effect in female astrocytes following subsequent oxygen and glucose deprivation (OGD). Sex-segregated astrocyte cultures derived from postnatal day 0 to 1 mice were allowed to reach confluency before being exposed to either 0% (sham preconditioning) or 3% isoflurane preconditioning for 2 hours. Cultures were then returned to normal growth conditions for 22 hours before undergoing 10 hours of OGD. Twenty-four hours following OGD, cell viability was quantified using a lactate dehydrogenase assay. Isoflurane preconditioning increased cell survival following OGD compared to sham preconditioning independent of innate cell sex. More studies are needed to determine how cell type and cell sex may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain.

Johnsen, Dustin; Murphy, Stephanie J.



A review of the Alberta certified preconditioned feeder program (1980-1987)  

PubMed Central

Data from the Alberta Certified Preconditioned Feeder Program (1980-1987) were reviewed retrospectively. Numbers of calves sold, price premiums realized, pre-and postsale performance, production and health performance of preconditioned and regular calves were examined. During the study period, the program showed marked expansion and consistently resulted in substantial premiums for preconditioned calves. Real net returns from efficient rates of gain, increased sale weights, better calf quality and improved health status (disease resistance) were realized at sale time. Feedlot data indicated that postsale morbidity and mortality were markedly reduced in groups of preconditioned calves.

Schipper, Casey; Church, Terry; Harris, Brian



[The role of oxygen free radicals in the mechanisms of local and distant ischemic myocardial preconditioning].  


The phenomenon of ischemic preconditioning consists in increase in myocardial tolerance to ischemia after short periods of ischemia and reperfusion of the myocardium (local preconditioning) or a distant organ (distant preconditioning). This study is dedicated to the role of oxygen free radicals (OFR) in the mechanisms of preconditioning; pharmacological inhibition of OFR with N-2-mercaptopropionylglycin, a synthetic anti-oxidant, was used. Mouse experiments demonstrated a reduction in the infarction-limiting effect of local preconditioning as a result of OFR inhibiting. This confirms the hypothesis according to which OFR play an important role in the mechanisms of launching and mediating the protective effect of local preconditioning. On the contrary, application of the same dose of N2-mercaptopropionylglycin does not lead to a significant weakening of the infarction-limiting effect of distant preconditioning caused by 20 min of ischemia and 15 min of reperfusion of the small intestine. Thus, it is unlikely that OFR participate in the realization of the effect of distant preconditioning caused by small intestinal ischemia. The authors discuss hypothetic molecular mechanisms of distant myocardial preconditioning. PMID:17002019

Petrishchev, N N; Shliakhto, E V; Tsyrlin, V A; Vlasov, T D; Syrenski?, A V; Galagudza, M M



Roles of thioredoxin in nitric oxide-dependent preconditioning-induced tolerance against MPTP neurotoxin  

SciTech Connect

Hormesis, a stress tolerance, can be induced by ischemic preconditioning stress. In addition to preconditioning, it may be induced by other means, such as gas anesthetics. Preconditioning mechanisms, which may be mediated by reprogramming survival genes and proteins, are obscure. A known neurotoxicant, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes less neurotoxicity in the mice that are preconditioned. Pharmacological evidences suggest that the signaling pathway of {center_dot}NO-cGMP-PKG (protein kinase G) may mediate preconditioning phenomenon. We developed a human SH-SY5Y cell model for investigating {sup {center_dot}}NO-mediated signaling pathway, gene regulation, and protein expression following a sublethal preconditioning stress caused by a brief 2-h serum deprivation. Preconditioned human SH-SY5Y cells are more resistant against severe oxidative stress and apoptosis caused by lethal serum deprivation and 1-mehtyl-4-phenylpyridinium (MPP{sup +}). Both sublethal and lethal oxidative stress caused by serum withdrawal increased neuronal nitric oxide synthase (nNOS/NOS1) expression and {sup {center_dot}}NO levels to a similar extent. In addition to free radical scavengers, inhibition of nNOS, guanylyl cyclase, and PKG blocks hormesis induced by preconditioning. S-nitrosothiols and 6-Br-cGMP produce a cytoprotection mimicking the action of preconditioning tolerance. There are two distinct cGMP-mediated survival pathways: (i) the up-regulation of a redox protein thioredoxin (Trx) for elevating mitochondrial levels of antioxidant protein Mn superoxide dismutase (MnSOD) and antiapoptotic protein Bcl-2, and (ii) the activation of mitochondrial ATP-sensitive potassium channels [K(ATP)]. Preconditioning induction of Trx increased tolerance against MPP{sup +}, which was blocked by Trx mRNA antisense oligonucleotide and Trx reductase inhibitor. It is concluded that Trx plays a pivotal role in {sup {center_dot}}NO-dependent preconditioning hormesis against MPTP/MPP{sup +}.

Chiueh, C.C. [School of Pharmacy, Taipei Medical University, Taipei 110, Taiwan (China) and Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD 20892-1264 (United States)]. E-mail:; Andoh, Tsugunobu [Department of Applied Pharmacology, Toyama Medical and Pharmaceutical University (Japan); Chock, P. Boon [Laboratory of Biochemistry, NHLBI, NIH, Bethesda, MD 20892-8012 (United States)



Preconditioning with Associated Blocking of Ca2+ Inflow Alleviates Hypoxia-Induced Damage to Pancreatic ?-Cells  

PubMed Central

Objective Beta cells of pancreatic islets are susceptible to functional deficits and damage by hypoxia. Here we aimed to characterize such effects and to test for and pharmacological means to alleviate a negative impact of hypoxia. Methods and Design Rat and human pancreatic islets were subjected to 5.5 h of hypoxia after which functional and viability parameters were measured subsequent to the hypoxic period and/or following a 22 h re-oxygenation period. Preconditioning with diazoxide or other agents was usually done during a 22 h period prior to hypoxia. Results Insulin contents decreased by 23% after 5.5 h of hypoxia and by 61% after a re-oxygenation period. Preconditioning with diazoxide time-dependently alleviated these hypoxia effects in rat and human islets. Hypoxia reduced proinsulin biosynthesis (3H-leucine incorporation into proinsulin) by 35%. Preconditioning counteracted this decrease by 91%. Preconditioning reduced hypoxia-induced necrosis by 40%, attenuated lowering of proteins of mitochondrial complexes I–IV and enhanced stimulation of HIF-1-alpha and phosphorylated AMPK proteins. Preconditioning by diazoxide was abolished by co-exposure to tolbutamide or elevated potassium (i.e. conditions which increase Ca2+ inflow). Preconditioning with nifedipine, a calcium channel blocker, partly reproduced effects of diazoxide. Both diazoxide and nifedipine moderately reduced basal glucose oxidation whereas glucose-induced oxygen consumption (tested with diazoxide) was unaffected. Preconditioning with diaxoxide enhanced insulin contents in transplants of rat islets to non-diabetic rats and lowered hyperglycemia vs. non-preconditioned islets in streptozotocin-diabetic rats. Preconditioning of human islet transplants lowered hyperglycemia in streptozotocin-diabetic nude mice. Conclusions 1) Prior blocking of Ca2+ inflow associates with lesser hypoxia-induced damage, 2) preconditioning affects basal mitochondrial metabolism and accelerates activation of hypoxia-reactive and potentially protective factors, 3) results indicate that preconditioning by K+-ATP-channel openers has therapeutic potential for islet transplantations.

Ma, Zuheng; Moruzzi, Noah; Catrina, Sergiu-Bogdan; Hals, Ingrid; Oberholzer, Jose



Preconditioned Conjugate Gradient methods for low speed flow calculations  

NASA Astrophysics Data System (ADS)

An investigation is conducted into the viability of using a generalized Conjugate Gradient-like method as an iterative solver to obtain steady-state solutions of very low-speed fluid flow problems. Low-speed flow at Mach 0.1 over a backward-facing step is chosen as a representative test problem. The unsteady form of the two dimensional, compressible Navier-Stokes equations are integrated in time using discrete time-steps. The Navier-Stokes equations are cast in an implicit, upwind finite-volume, flux split formulation. The new iterative solver is used to solve a linear system of equations at each step of the time-integration. Preconditioning techniques are used with the new solver to enhance the stability and the convergence rate of the solver and are found to be critical to the overall success of the solver. A study of various preconditioners reveals that a preconditioner based on the lower-upper (L-U)-successive symmetric over-relaxation iterative scheme is more efficient than a preconditioner based on incomplete L-U factorizations of the iteration matrix. The performance of the new preconditioned solver is compared with a conventional line Gauss-Seidel relaxation (LGSR) solver. Overall speed-up factors of 28 (in terms of global time-steps required to converge to a steady-state solution) and 20 (in terms of total CPU time on one processor of a CRAY-YMP) are found in favor of the new preconditioned solver, when compared with the LGSR solver.

Ajmani, Kumud; Ng, Wing-Fai; Liou, Meng-Sing



Clinically useful cardioprotection: ischemic preconditioning then and now.  


Ischemic preconditioning (IP) is the most effective, reproducible form of protection against myocardial cell death yet described. The mechanism of classic IP has not been identified, but recent investigations have focused on the mitochondrial permeability transition pore (mPTP). Similarly, the mechanism of the "second window of protection" (SWOP) is not known but thought to involve increased expression of important gene products. Currently, IP in the clinical arena is limited to cardiac surgery, planned angioplasty, and organ preservation protocols. To move preconditioning into a broader clinical arena will require resolution of important fundamental yet stubborn problems involving both basic and clinical science. Important unresolved issues include the mechanisms involved in the transition from reversible to irreversible injury, the amount of potential salvageable myocardium present at the onset of reperfusion, the identity and signaling of the mPTP, the optimization of protocols, the identity of end effectors (SWOP), and the identification of the best experimental model systems. From a clinical standpoint, important issues include the influence of comorbidities on cardioprotection, identification of appropriate animal models, the lack of a biologic marker of the cardioprotective state, the influence of coexistent therapeutic drugs, potential toxicity of pharmacologic mimics, and the window of opportunity for significant protection. Ischemic preconditioning has yielded promising results in other organs including the brain as well as tissue preservation for certain surgical procedures that will require definition of the underlying mechanism(s) to be fully exploited clinically. Over the past 25 years, the scientific community has learned much regarding the biology and potential mechanisms of IP and the concept has been expanded to many other organ systems in many other clinically relevant scenarios. To realize the full clinical potential will require continued investigation into the mechanism. PMID:21821524

Vander Heide, Richard


Calcium preconditioning triggers neuroprotection in retinal ganglion cells  

PubMed Central

In the mammalian retina, excitotoxicity has been shown to be involved in apoptotic retinal ganglion cell (RGC) death and is associated with certain retinal disease states including glaucoma, diabetic retinopathy and retinal ischemia. Previous studies from this lab (Wehrwein et al., 2004) have demonstrated that acetylcholine (ACh) and nicotine protects against glutamate-induced excitotoxicity in isolated adult pig RGCs through nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs in these RGCs triggers cell survival signaling pathways and inhibits apoptotic enzymes (Asomugha et al., 2010). However, the link between binding of nAChRs and activation of neuroprotective pathways is unknown. In this study, we examine the hypothesis that calcium permeation through nAChR channels is required for ACh-induced neuroprotection against glutamate-induced excitotoxicity in isolated pig RGCs. RGCs were isolated from other retinal tissue using a two step panning technique and cultured for 3 days under different conditions. In some studies, calcium imaging experiments were performed using the fluorescent calcium indicator, fluo-4, and demonstrated that calcium permeates the nAChR channels located on pig RGCs. In other studies, the extracellular calcium concentration was altered to determine the effect on nicotine-induced neuroprotection. Results support the hypothesis that calcium is required for nicotine-induced neuroprotection in isolated pig RGCs. Lastly, studies were performed to analyze the effects of preconditioning on glutamate-induced excitotoxicity and neuroprotection. In these studies, a preconditioning dose of calcium was introduced to cells using a variety of mechanisms before a large glutamate insult was applied to cells. Results from these studies support the hypothesis that preconditioning cells with a relatively low level of calcium before an excitotoxic insult leads to neuroprotection. In the future, these results could provide important information concerning therapeutic agents developed to combat various diseases involved with glutamate-induced excitotoxicity.

Brandt, Sean K.; Weatherly, Monique E.; Ware, Lillian; Linn, David M.; Linn, Cindy L.



Ischemic Preconditioning And Myocardial Infarction: An Update and Perspective  

PubMed Central

Myocardial infarction is the leading cause of mortality in Western societies with annual expenditures of $431.8 billion spent on coronary artery disease in man. Therapeutics to combat infarction from myocardial injury, based on studies of ischemic preconditioning (IPC), are currently in progress. Hence, this review provides an update on IPC, including general and molecular mechanisms responsible for IPC and the effects of IPC in models of aging or disease. A summary of therapeutics shown to possess efficacy in preclinical and clinical trials and future directions of studies regarding cardiac IPC are also discussed.

Gross, Eric R.; Gross, Garrett J.



Preconditioning of the Navier-Stokes equations with multiple constraints  

NASA Astrophysics Data System (ADS)

The Navier-Stokes equations represent a mathematical model of incompressible fluid flow. To obtain a unique solution, these need to be supplemented by a physically relevant set of boundary conditions (BCs). These BCs, such as natural outflow, no-slip, no-penetration, can be easily imposed within the finite element setting in the case of straight boundaries that are aligned with the Cartesian axes. When more general domains are considered, as in many realistic industrial applications, one practical way of imposing BCs is with Lagrange multipliers. This procedure leads to an augmented linear system at the discrete level. In this paper we discuss efficient preconditioning of such systems.

White, Raymon; Heil, Matthias; Mihajlovi?, Milan



Postischemic flap washout with hydroxyethyl starch (HAES) and its beneficial effect on the no-reflow phenomenon in rat skin island flaps  

Microsoft Academic Search

This study investigated the possible effect of hydroxyethyl starch (HAES) as a postischemic perfusion washout on survival\\u000a of skin flaps. Forty-eight, male, Sprague-Dawley rats were used in this experiment. A 46 cm unilateral island skin flap based\\u000a on the superficial inferior epigastric artery and vein was raised. The femoral neurovascular bundle supplying the flap pedicle\\u000a was also dissected free. The

S. Ak?n; M. Özcan



Influence of low-power luminescent red light on recovery of contractile function of the heart in the post-ischemic period  

NASA Astrophysics Data System (ADS)

The influence of incoherent low-power luminescent red light (Lumir) on recovery of cardiac contractile function during post-ischemic period was investigate. The method of isolated heart was used. Considerable reduce of heart rate was observe.d It is proved, that Lumir contributes to accelerated recovery of contractile function of myocardium. The physiotherapeutic procedure led also to improvement of heart rate and to stabilization of relaxation speed in post- ischemic period.

Malinovskaya, Svetlana L.; Drugova, Olga V.; Monich, Victor A.; Mukhina, Irin V.



Effects of L-carnitine and its derivatives on postischemic cardiac function, ventricular fibrillation and necrotic and apoptotic cardiomyocyte death in isolated rat hearts  

Microsoft Academic Search

The study aimed to examine whether L-carnitine and its derivatives, acetyl-L-carnitine and propionyl-L-carnitine, were equally effective and able to improve postischemic cardiac function, reduce the incidence of reperfusion-induced ventricular fibrillation, infarct size, and apoptotic cell death in ischemic\\/reperfused isolated rat hearts. There are several studies indicating that L-carnitine, a naturally occurring amino acid and an essential cofactor, can improve mechanical

Jianhua Cui; Dipak K. Das; Aldo Bertelli; Arpad Tosaki



Moderate ethanol preconditioning of rat brain cultures engenders neuroprotection against dementia-inducing neuroinflammatory proteins: possible signaling mechanisms.  


There is no question that chronic alcohol (ethanol) abuse, a leading worldwide problem, causes neuronal dysfunction and brain damage. However, various epidemiologic studies in recent years have indicated that in comparisons with abstainers or never-drinkers, light/moderate alcohol consumers have lower risks of age-dependent cognitive decline and/or dementia, including Alzheimer's disease (AD). Such reduced risks have been variously attributed to favorable circulatory and/or cerebrovascular effects of moderate ethanol intake, but they could also involve ethanol "preconditioning" phenomena in brain glia and neurons. Here we summarize our experimental studies showing that moderate ethanol preconditioning (MEP; 20-30 mM ethanol) of rat brain cultures prevents neurodegeneration due to beta-amyloid, an important protein implicated in AD, and to other neuroinflammatory proteins such as gp120, the human immunodeficiency virus 1 envelope protein linked to AIDS dementia. The MEP neuroprotection is associated with suppression of neurotoxic protein-evoked initial increases in [Ca(+2)](i) and proinflammatory mediators--e.g., superoxide anion, arachidonic acid, and glutamate. Applying a sensor --> transducer --> effector model to MEP, we find that onset of neuroprotection correlates temporally with elevations in "effector" heat shock proteins (HSP70, HSP27, and phospho-HSP27). The effector status of HSPs is supported by the fact that inhibiting HSP elevations due to MEP largely restores gp120-induced superoxide potentiation and subsequent neurotoxicity. As upstream mediators, synaptic N-methyl-d-aspartate receptors may be initial prosurvival sensors of ethanol, and protein kinase C epsilon and focal adhesion kinase are likely transducers during MEP that are essential for protective HSP elevations. Regarding human consumption, we speculate that moderate ethanol intake might counter incipient cognitive deterioration during advanced aging or AD by exerting preconditioning-like suppression of ongoing neuroinflammation related to amyloidogenic protein accumulation. PMID:20422315

Collins, Michael A; Neafsey, Edward J; Wang, Kewei; Achille, Nicholas J; Mitchell, Robert M; Sivaswamy, Sreevidya



41 CFR 102-72.68 - What preconditions must be satisfied before an Executive agency may exercise the delegated...  

Code of Federal Regulations, 2013 CFR

...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual ancillary...preconditions must be satisfied before an Executive agency may exercise the delegated authority to perform an individual...



Electroacupuncture reduces myocardial infarct size and improves post-ischemic recovery by invoking release of humoral, dialyzable, cardioprotective factors.  


Previous studies have shown that electroacupuncture (EA) can induce cardioprotection against ischemia-reperfusion (IR) injury, but its mechanisms are incompletely understood. We have previously shown that several other forms of remote preconditioning of the heart work, at least in part, via the release of circulating cardioprotective factors into the bloodstream, that can be dialyzed and subsequently shown to reduce IR injury in isolated hearts. We used the same methods to assess whether EA leads to similar humoral cardioprotection. EA rabbits were subjected to 60 min of bilateral stimulation at the Neiguan point, following which their blood was drawn, dialyzed, and used to perfuse hearts in Langendorff preparation and subsequently subjected to 60 min of global ischemia and 120 min of reperfusion. Compared to controls, dialysate from EA animals led to significant reduction in infarct size and improved functional recovery. The degree of cardioprotection was no different to that seen in animals randomized to receive remote preconditioning using transient limb ischemia (4 cycles of 5 min ischemia/5 min reperfusion). These results suggest that EA recapitulates the cardioprotection achieved by remote preconditioning, by similarly leading to release of circulating cardioprotective factors. PMID:23529221

Redington, Kathrine L; Disenhouse, Tara; Li, Jing; Wei, Can; Dai, Xiaojing; Gladstone, Rachel; Manlhiot, Cedric; Redington, Andrew N



Liver Ischemic Preconditioning Is Mediated by the Inhibitory Action of Nitric Oxide on Endothelin  

Microsoft Academic Search

The concerted involvement of both NO and endothelin in the protective effect of preconditioning against hepatic ischemia- reperfusion induced injury has been evaluated in this study. Thus hepatic ischemia-reperfusion or preconditioning plus ischemia-reperfusion was induced in rats and the effect of nitric oxide administration or inhibition with addition of the endothelin antagonist Bosentan was evaluated. Results show that the increases

C. Peralta; D. Closa; G. Hotter; E. Gelp??; N. Prats; J. Roselló-Catafau



Preconditioning method for condensate fluid and solid coupling problems in general curvilinear coordinates  

Microsoft Academic Search

A preconditioned flux-vector splitting (PFVS) scheme in general curvilinear coordinates which can be applied to condensate fluid and solid coupling problems is presented and some typical calculated results are shown to prove the availability of the present method. This method is based on the preconditioning method applied to compressible Navier–Stokes (NS) equations with additional equations and source terms for condensate

Satoru Yamamoto



40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.  

Code of Federal Regulations, 2010 CFR

...2010-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section...Tests § 85.2220 Preconditioned two speed idle testâEPA 91. (a) General requirements...section, consists of a first-chance high-speed mode followed immediately by a...



40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.  

Code of Federal Regulations, 2010 CFR

...2009-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section...Tests § 85.2220 Preconditioned two speed idle testâEPA 91. (a) General requirements...section, consists of a first-chance high-speed mode followed immediately by a...



Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain  

Microsoft Academic Search

This review will focus on inhalational anesthetic neuroprotection during cerebral ischemia and inhalational anesthetic preconditioning before ischemic brain injury. The limitations and challenges of past and current research in this area will be addressed before reviewing experimental and clinical studies evaluating the effects of inhalational anesthetics before and during cerebral ischemia. Mechanisms underlying volatile anesthetic neuroprotection and preconditioning will also

Hideto Kitano; Jeffrey R Kirsch; Patricia D Hurn; Stephanie J Murphy



40 CFR 1065.590 - PM sampling media (e.g., filters) preconditioning and tare weighing.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 false PM sampling media (e.g., filters) preconditioning and...Duty Cycles § 1065.590 PM sampling media (e.g., filters) preconditioning and...the following steps to prepare PM sampling media (e.g., filters) and equipment...



Exercise Preconditioning Provides Long-Term Protection Against Early Chronic Doxorubicin Cardiotoxicity  

Microsoft Academic Search

Acute doxorubicin (DOX) cardiotoxicity can be attenuated by exercise preconditioning, but little is known of whether this cardioprotection continues beyond 10 days post-DOX administration. The purpose of this study was to determine the effects of exercise preconditioning on early chronic DOX-induced cardiotoxicity. Male rats were randomly assigned to sedentary, treadmill, or wheel running groups. Treadmill and wheel running animals participated

David S. Hydock; Chia-Ying Lien; Brock T. Jensen; Carole M. Schneider; Reid Hayward



Investigation for the Reduction of In-plane Compressive Strength in Preconditioned Thin Composite Panels  

Microsoft Academic Search

This paper investigates the effects of precondition characteristics on the residual compressive strength (RCS) of 16-ply carbon\\/epoxy panels through the establishment of their compressive and buckling response characteristics. The preconditions of varying sizes include impact damage and embedded artificial delaminations of both circular and elliptical shapes. A sequence of prebuckling, local and global buckling, and postbuckling is found in both

G. Zhou; L. A. Rivera



Intestinal Preconditioning Is Mediated by a Transient Increase in Nitric Oxide  

Microsoft Academic Search

The effect of ischemic preconditioning on the intestine, as well the implication of nitric oxide and prostacyclin in this process has been evaluated. Thus, intestinal ischemia-reperfusion was induced in rats, and the protection conferred by previous preconditioning was evaluated. In addition, the effect of nitric oxide inhibition and the administration of nitric oxide were determined. Results show that the increases

G. Hotter; D. Closa; M. Prados; L. Fernández-Cruz; N. Prats; E. Gelp??; J. Roselló-Catafau



Effect of temperature preconditioning on catalase, peroxidase, and superoxide dismutase in chilled zucchini squash  

Microsoft Academic Search

The development of chilling injury symptoms in zucchini squash (Cucurbita pepo L., cv. ‘Elite’) stored at 5 °C was delayed by preconditioning the fruit at a temperature of 15 °C for two days. This temperature preconditioning treatment suppressed the increase in peroxidase activity and reduced the decline of catalase activity in squash during subsequent storage at 5 °C. The superoxide

Chien Yi Wang



Relationships between mixis in Brachionus plicatilis and preconditioning of culture medium by crowding  

Microsoft Academic Search

Several experiments with Brachionus plicatilis have been conducted to test the existence of chemical-mediated induction of mixis. In a first experimental set, bioassays were used to test relationships between preconditioning of culture medium to high population density and the occurrence of mixis in mass cultures with these media. The results show that a preconditioned medium has inducing properties that are

Maria José Carmona; Manuel Serra; Maria Rosa Miracle



Using the preconditioned Generalized Minimum RESidual (GMRES) method to solve the sea-ice momentum equation  

Microsoft Academic Search

We introduce the preconditioned generalized minimum residual (GMRES) method, along with an outer loop (OL) iteration to solve the sea-ice momentum equation. The preconditioned GMRES method is the linear solver. GMRES together with the OL is used to solve the nonlinear momentum equation. The GMRES method has low storage requirements, and it is computationally efficient and parallelizable. It was found

Jean-François Lemieux; Bruno Tremblay; Stephen Thomas; Jan Sedlá?ek; Lawrence A. Mysak



The relationship of hepatic tissue oxygenation with nitric oxide metabolism in ischemic preconditioning of the liver  

Microsoft Academic Search

Ischemic preconditioning (IPC) may increase the hepatic tolerance of ischemic injury during liver surgery and transplantation via nitric oxide (NO) formation. This study investigates the effect of IPC on hepatic tissue oxygenation and the role of NO stimulation and inhibition on the preconditioning effect in the rat liver. Study groups had 1) sham laparotomy; 2) 45-min lobar liver ischemia and

Rahul S. Koti; Alexander M. Seifalian; Alan G. McBride; Wenxuan Yang



40 CFR 85.2220 - Preconditioned two speed idle test-EPA 91.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Preconditioned two speed idle test-EPA 91. 85.2220 Section 85.2220...Emission Control System Performance Warranty Short Tests § 85.2220 Preconditioned two speed idle testâEPA 91. (a) General requirements...



p53 down-regulation: a new molecular mechanism involved in ischaemic preconditioning.  


Ischaemic preconditioning is associated with the activation of prosurvival mechanisms. Here we demonstrate that following a preconditioning protocol, the proapoptotic p53 is inactivated possibly via phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-murine double minute 2 (Mdm2) phosphorylation. Our data show that in preconditioned hearts Mdm2 was significantly phosphorylated, and wortmannin (a PI3K inhibitor) abrogated this effect (Western blotting). Also in preconditioned hearts p53 was shown to be bound to phospho-Mdm2 (co-immunoprecipitation). Furthermore, pifithrin alpha (a p53 inhibitor), administered to isolated perfused hearts prior to ischaemia, significantly attenuated the infarction. In conclusion our results suggest that p53 is implicated in ischaemia/reperfusion injury and that preconditioning counterbalances this effect via PI3K-Akt-Mdm2 phosphorylation. PMID:14644432

Mocanu, Mihaela M; Yellon, Derek M



Ischemic preconditioning of free muscle flaps: an experimental study.  


The aim of this study was to apply the hypothesis of ischemic preconditioning (IP) on free skeletal muscle (rat thigh flap). Five groups of Sprague-Dawley rats (n = 6) were used. In group A (control group), standard free autologous flap transfers were performed. Flaps in groups B and C underwent 4 and 6 h, respectively, of ischemia before transfer. In groups D and E, muscle flaps were preconditioned (3 x 10 min ischemia interrupted by 10 min of reperfusion, clip applied on the dissected artery of the flap) and subjected to 4 and 6 h, respectively, of ischemia before transfer. After 48 h of reperfusion, the muscle flaps were evaluated macroscopically as well as by histological and immunohystochemical staining. In group A, the viability was 100%, whereas in groups D and E the viability was 83.3% and 100%, respectively. Groups B and C had undergone macroscopically parceled to total necrosis, further confirmed by histological findings (fragmentation and disappearance of muscle striations, combined with tissue necrosis and intravascular thrombosis). The beneficial effect of IP demonstrated in the heart, liver, and small bowel extends to skeletal muscle, which can be used in free-flap transfers, if the transfer includes a long period of predictable ischemia. PMID:16184525

Marian, Claudiu F; Jiga, Lucian P; Ionac, Mihai



Physics-Based Preconditioning for a Radially Compressed FRC Model  

NASA Astrophysics Data System (ADS)

SEL is a parallel code for solving initial-boundary value problems for coupled nonlinear fluid equations, using high-order spectral elements for discretization in 2 spatial dimensions, and a fully-implicit time step. Efficient parallel operation requires a scalable method for solving large, sparse matrices. In previous work, a framework for such a solver has been developed, separated into general-purpose modules for all applications and problem-specific code for each application. The heart of the method is physics-based preconditioning, which reduces the order and enhances the diagonal dominance of the linear systems to be solved. Approximations introduced at this stage are eliminated by matrix-free Newton-Krylov iteration on the full nonlinear system. The details of the approach depend on the coupling of the various physical variables. It has been successfully tested for ideal MHD waves in a doubly periodic plane. The purpose of this presentation is to describe the development and testing of physics-based preconditioning for a more interesting test case, modeling a radially compressed FRC with extend MHD.

Glasser, A. H.; Lukin, V. S.



Nutritional preconditioning by dietary (n-3) long chain polyunsaturated fatty acids protects the heart against ischemic damage  

Microsoft Academic Search

Ischaemic preconditioning is a powerful cardioprotective phenomenon. Cardioprotection afforded by (n-3) polyunsaturated fatty acids (PUFA) also suggests preconditioning-like effects. This study examined the effects of dietary fish oil on heart function and injury during myocardial ischemia and reperfusion and interactions between diet and ischemic preconditioning (IP). Male Wistar rats were fed diets containing 10% fat by weight including either 7%

G. G. Abdukeyum; A. J. Owen; P. L. McLennan



Ischemic preconditioning maintains cardioprotection in aging normotensive and spontaneously hypertensive rats.  


We determined whether ischemic preconditioning could reduce infarct size and improve cardiac function in both aging normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The left anterior descending coronary artery was occluded for 1h followed by 3 h reperfusion in aging ( approximately 16 months old) SHR rats and age-matched WKY rats. Hearts were either preconditioned or not (control group) prior to 1h of coronary artery occlusion. The preconditioning regimen consisted of three cycles of 3 min occlusion followed by 5 min reperfusion applied prior to the subsequent 1h occlusion. In WKY (n=12 each group), the risk zone was similar in the control (51+/-2%) and preconditioned group (46+/-2%; p=0.1). Preconditioning significantly reduced infarct size (as a percentage of the ischemic risk zone) (24+/-6%) compared to controls (51+/-5%; p=0.0026). In SHR rats (n=9 each group), the risk zone was smaller in the preconditioning group (41+/-3%) than in the control group (51+/-3%; p=0.035). Infarct size (as % of ischemic risk zone) was also significantly reduced in the preconditioned group (13+/-4%) compared to controls (62+/-5%; p<0.0001). For both WKY and SHR rats, for any sized risk zone the infarct size was smaller in preconditioned hearts compared with the control hearts. Preconditioning improved aspects of LV function during ischemia and reperfusion phase in SHR rats, but these benefits were not observed in the WKY rats. Preconditioning maintains powerful cardioprotection in aging normotensive hearts as well as aging hypertrophied hearts. PMID:19248825

Dai, Wangde; Simkhovich, Boris Z; Kloner, Robert A



Tolerance to nitroglycerin-induced preconditioning of the endothelium: a human in vivo study.  


Damage and dysfunction of the vascular endothelium critically influence clinical outcomes after ischemia and reperfusion (I/R). Brief exposure to organic nitrates can protect the vascular endothelium from I/R injury via a mechanism that is similar to ischemic preconditioning and is independent of hemodynamic changes. The clinical relevance of these protective effects clearly depends on whether they can be sustained over time. Twenty-four healthy (age 25-32) male volunteers were randomized to receive 1) transdermal nitroglycerin (GTN; 0.6 mg/h) administered for 2 h on 1 day only, 2) transdermal GTN for 2 h/day for 7 days, or 3) continuous therapy with transdermal GTN for 7 days. Eight volunteers underwent continuous GTN therapy followed by intra-arterial infusion of the antioxidant vitamin C. Finally, five additional subjects underwent no therapy and served as controls. Endothelial function measurements were performed before and after induction of I/R of the arm. I/R caused a significant blunting of the flow responses to acetylcholine in the control group (P < 0.01 vs. before I/R). A single 2-h GTN dosage, given 24 h before I/R, prevented I/R-induced endothelial dysfunction [P = not significant (NS) vs. before I/R], but this protective effect was completely lost after 1 wk of GTN administration 2 h/day (P < 0.05 vs. before I/R; P = NS vs. control). In subjects who received continuous GTN, endothelial responses were blunted before I/R, and I/R did not cause further endothelial dysfunction. Finally, vitamin C normalized acetylcholine responses and prevented the loss of preconditioning associated with prolonged GTN. In a separate experimental model using isolated human endothelial cells, short-term incubation with GTN caused upregulation of heme oxygenase, an effect that was lost after prolonged GTN administration. Although a single administration of GTN is able to protect the endothelium from I/R-induced endothelial dysfunction, this protection is lost upon prolonged exposure, likely via an oxidative mechanism. PMID:19933412

Gori, Tommaso; Dragoni, Saverio; Di Stolfo, Giuseppe; Sicuro, Silvia; Liuni, Andrew; Luca, Mary Clare; Thomas, George; Oelze, Matthias; Daiber, Andreas; Parker, John D



Post-ischemic continuous infusion of erythropoeitin enhances recovery of lost memory function after global cerebral ischemia in the rat  

PubMed Central

Background Erythropoietin (EPO) and its covalently modified analogs are neuroprotective in various models of brain damage and disease. We investigated the effect on brain damage and memory performance, of a continuous 3-day intravenous infusion of EPO, starting 20 min after a transient 10 minute period of global cerebral ischemia in the rat. Results We found no effect on selective neuronal damage in the CA1 region of the hippocampus, neocortical damage and damage to the striatum assessed at 7 days after ischemia. Also, no differences were observed in sensori-motor scores between EPO treated and saline treated ischemic animals. In contrast, memory performance was significantly improved in the EPO treated group. Saline treated injured animals (n?=?7) failed in a test assessing recovery of spatial memory (6/6 and 5/6), while EPO treated animals had few and none failures (0/7 and 1/7). Conclusion We conclude that although post-ischemic treatment with EPO is not neuroprotective in a model of cardiac arrest brain ischemia, its markedly positive effect on brain plasticity and recovery of memory function warrants consideration as treatment of cardiac arrest patients.



The protective effect of M40401, a superoxide dismutase mimetic, on post-ischemic brain damage in Mongolian gerbils  

PubMed Central

Background Overproduction of free radical species has been shown to occur in brain tissues after ischemia-reperfusion injury. However, most of free radical scavengers known to antagonize oxidative damage (e.g. superoxide dismutase, catalase), are unable to protect against ischemia-reperfusion brain injury when given in vivo, an effect mainly due to their difficulty to gain access to brain tissues. Here we studied the effect of a low molecular weight superoxide dismutase mimetic (M40401) in brain damage subsequent to ischemia-reperfusion injury in Mongolian gerbils. Results In animals undergoing ischemia-reperfusion injury, neuropathological and ultrastructural changes were monitored for 1–7 days either in the presence or in the absence of M40401 after bilateral common carotid artery occlusion (BCCO). Administration of M40401 (1–40 mg/kg, given i.p. 1 h after BCCO) protected against post-ischemic, ultrastructural and neuropathological changes occurring within the hippocampal CA1 area. The protective effect of M40401 was associated with a significant reduction of the levels of malondialdehyde (MDA; a marker of lipid peroxidation) in ischemic brain tissues after ischemia-reperfusion. Conclusion Taken together, these results demonstrate that M40401 provides protective effects when given early after the induction of ischemia-reperfusion of brain tissues and suggest the possible use of such compounds in the treatment of neurological dysfunction subsequent to cerebral flow disturbances.

Mollace, Vincenzo; Iannone, Michelangelo; Muscoli, Carolina; Palma, Ernesto; Granato, Teresa; Modesti, Andrea; Nistico, Robert; Rotiroti, Domenicantonio; Salvemini, Daniela



In vitro cultured progenitors and precursors of cardiac cell lineages from human normal and post-ischemic hearts.  


The demonstration of the presence of dividing primitive cells in damaged hearts has sparked increased interest about myocardium regenerative processes. We examined the rate and the differentiation of in vitro cultured resident cardiac primitive cells obtained from pathological and normal human hearts in order to evaluate the activation of progenitors and precursors of cardiac cell lineages in post-ischemic human hearts. The precursors and progenitors of cardiomyocyte, smooth muscle and endothelial lineage were identified by immunocytochemistry and the expression of characteristic markers was studied by western blot and RT-PCR. The amount of proteins characteristic for cardiac cells (alpha-SA and MHC, VEGFR-2 and FVIII, SMA for the precursors of cardiomyocytes, endothelial and smooth muscle cells, respectively) inclines toward an increase in both alpha-SA and MHC. The increased levels of FVIII and VEGFR2 are statistically significant, suggesting an important re-activation of neoangiogenesis. At the same time, the augmented expression of mRNA for Nkx 2.5, the trascriptional factor for cardiomyocyte differentiation, confirms the persistence of differentiative processes in terminally injured hearts. Our study would appear to confirm the activation of human heart regeneration potential in pathological conditions and the ability of its primitive cells to maintain their proliferative capability in vitro. The cardiac cell isolation method we used could be useful in the future for studying modifications to the microenvironment that positively influence cardiac primitive cell differentiation or inhibit, or retard, the pathological remodeling and functional degradation of the heart. PMID:18162457

Di Meglio, F; Nurzynska, D; Castaldo, C; Arcucci, A; De Santo, L; de Feo, M; Cotrufo, M; Montagnani, S; Giordano-Lanza, G


Nitrite as a mediator of ischemic preconditioning and cytoprotection  

PubMed Central

Ischemia/reperfusion (IR) injury is a central component in the pathogenesis of several diseases and is a leading cause of morbidity and mortality in the western world. Subcellularly, mitochondrial dysfunction, characterized by depletion of ATP, calcium-induced opening of the mitochondrial permeability transition pore, and exacerbated reactive oxygen species (ROS) formation, plays an integral role in the progression of IR injury. Nitric oxide (NO) and more recently nitrite (NO2-) are known to modulate mitochondrial function, mediate cytoprotection after IR and have been implicated in the signaling of the highly protective ischemic preconditioning (IPC) program. Here, we review what is known about the role of NO and nitrite in cytoprotection after IR and consider the putative role of nitrite in IPC. Focus is placed on the potential cytoprotective mechanisms involving NO and nitrite-dependent modulation of mitochondrial function.

Murillo, Daniel; Kamga, Christelle; Mo, Li; Shiva, Sruti



Is There A Place For Cerebral Preconditioning In The Clinic?  

PubMed Central

Preconditioning (PC) describes a phenomenon whereby a sub-injury inducing stress can protect against a later injurious stress. Great strides have been made in identifying the mechanisms of PC-induced protection in animal models of brain injury. While these may help elucidate potential therapeutic targets, there are questions over the clinical utility of cerebral PC, primarily because of questions over the need to give the PC stimulus prior to the injury, narrow therapeutic windows and safety. The object of this review is to address the question of whether there may indeed be a clinical use for cerebral PC and to discuss the deficiencies in our knowledge of PC that may hamper such clinical translation.

Keep, Richard F.; Wang, Michael M.; Xiang, Jianming; Hua, Ya; Xi, Guohua



Effect of cyclic preconditioning on the tensile properties of human quadriceps tendons and patellar ligaments.  


Preconditioning of soft tissues has become a common procedure in tensile testing to assess the history dependence of these viscoelastic materials. To our knowledge, this is the first study comparing tensile properties of soft tissues-before and after cyclic preconditioning with high loads. Sixteen quadriceps tendon-bone (QT-B) complexes and 16 patellar ligament-bone (PL-B) complexes from a young population (mean age 24.9 +/- 4.4 years) were loaded to failure with a deformation rate of 1 mm/s. Half of the QT-B and the PL-B complexes underwent 200 uniaxial preconditioning cycles from 75 to 800 N at 0.5 Hz before ultimate failure loading. High-load preconditioning was made possible by the development of a highly reliable and easy-to-use cryofixation device to attach the free tendon end. PL-B complexes were more influenced by preconditioning than the QT-B complexes. Ultimate failure load, stiffness at 200 N and stiffness at 800 N were significantly higher for PL-B complexes after preconditioning, while the structural properties of QT-B complexes exhibited no significant alterations. The values of the mechanical properties like Young's modulus at 200 N and 800 N were much higher for both preconditioned specimen groups. In addition, ultimate stress was augmented by preconditioning for PL-B complexes. Hysteresis and creep effects were highest during the first few loading cycles. More than 160 cycles were needed to reach a steady state. Beyond 160 cycles there was no further creep, and hysteresis was almost constant. Creep values were 2.2% of the initial testing length for the QT-B and 3.2% of the initial testing length for the PL-B complexes. The effect of cyclic preconditioning seems to be caused by progressive fiber recruitment and by alterations of the interstitial fluid milieu. PMID:9608465

Schatzmann, L; Brunner, P; Stäubli, H U



Effect of Heat Preconditioning by Microwave Hyperthermia on Human Skeletal Muscle After Eccentric Exercise  

PubMed Central

The purpose of this study was to clarify whether heat preconditioning results in less eccentric exercise-induced muscle damage and muscle soreness, and whether the repeated bout effect is enhanced by heat preconditioning prior to eccentric exercise. Nine untrained male volunteers aged 23 ± 3 years participated in this study. Heat preconditioning included treatment with a microwave hyperthermia unit (150 W, 20 min) that was randomly applied to one of the subject’s arms (MW); the other arm was used as a control (CON). One day after heat preconditioning, the subjects performed 24 maximal isokinetic eccentric contractions of the elbow flexors at 30°·s-1 (ECC1). One week after ECC1, the subjects repeated the procedure (ECC2). After each bout of exercise, maximal voluntary contraction (MVC), range of motion (ROM) of the elbow joint, upper arm circumference, blood creatine kinase (CK) activity and muscle soreness were measured. The subjects experienced both conditions at an interval of 3 weeks. MVC and ROM in the MW were significantly higher than those in the CON (p < 0.05) for ECC1; however, the heat preconditioning had no significant effect on upper arm circumference, blood CK activity, or muscle soreness following ECC1 and ECC2. Heat preconditioning may protect human skeletal muscle from eccentric exercise-induced muscle damage after a single bout of eccentric exercise but does not appear to promote the repeated bout effect after a second bout of eccentric exercise. Key pointsThere have been few studies about the effects of heat preconditioning on muscle damage caused by eccentric exercise and the repeated bout effect after a second bout of eccentric exercise.Heat preconditioning with microwave hyperthermia may attenuate eccentric exercise-induced muscle damage.Heat preconditioning does not enhance the repeated bout effect.

Saga, Norio; Katamoto, Shizuo; Naito, Hisashi



Ischemic preconditioning protects by activating prosurvival kinases at reperfusion.  


Pharmacological activation of the prosurvival kinases Akt and ERK-1/2 at reperfusion, after a period of lethal ischemia, protects the heart against ischemia-reperfusion injury. We hypothesized that ischemic preconditioning (IPC) protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion. In isolated perfused Sprague-Dawley rat hearts subjected to 35 min of lethal ischemia, the phosphorylation states of Akt, ERK-1/2, and p70 S6 kinase (p70S6K) were determined after 15 min of reperfusion, and infarct size was measured after 120 min of reperfusion. IPC induced a biphasic response in Akt and ERK-1/2 phosphorylation during the preconditioning and reperfusion phases after the period of lethal ischemia. IPC induced a fourfold increase in Akt, ERK-1/2, and p70S6K phosphorylation at reperfusion and reduced the infarct risk-to-volume ratio (56.9 +/- 5.7 and 20.9 +/- 3.6% for control and IPC, respectively, P < 0.01). Inhibiting the IPC-induced phosphorylation of Akt, ERK-1/2, and p70S6K at reperfusion with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002 or the MEK-1/2 inhibitor PD-98059 abrogated IPC-induced protection (46.3 +/- 5.8, 49.2 +/- 4.0, and 20.9 +/- 3.6% for IPC + LY-294002, IPC + PD-98059, and IPC, respectively, P < 0.01), demonstrating that the phosphorylation of these kinases at reperfusion is required for IPC-induced protection. In conclusion, we demonstrate that the reperfusion phase following sustained ischemia plays an essential role in mediating IPC-induced protection. Specifically, we demonstrate that IPC protects the heart by phosphorylating the prosurvival kinases Akt and ERK-1/2 at reperfusion. PMID:15358610

Hausenloy, Derek J; Tsang, A; Mocanu, Mihaela M; Yellon, Derek M



Preconditioning the diabetic heart: the importance of Akt phosphorylation.  


Conflicting evidence exists whether diabetic myocardium can be protected by ischemic preconditioning (IPC). The phosphatidylinositol 3-kinase (PI3K)-Akt pathway is important in IPC. However, components of this cascade have been found to be defective in diabetes. We hypothesize that IPC in diabetic hearts depends on intact signaling through the PI3K-Akt pathway to reduce myocardial injury. Isolated perfused Wistar (normal) and Goto-Kakizaki (diabetic) rat hearts were subjected to 1) 35 min of regional ischemia and 120 min of reperfusion with infarct size determined; 2) preconditioning (IPC) using 5 min of global ischemia followed by 10 min of reperfusion performed one, two, or three times before prolonged ischemia; or 3) determination of Akt phosphorylation after stabilization or after one and three cycles of IPC. In Wistar rats, one, two, and three cycles of IPC reduced infarct size 44.7 +/- 3.8% (P < 0.05), 31.4 +/- 4.9% (P < 0.01), and 34.3 +/- 6.1% (P < 0.01), respectively, compared with controls (60.7 +/- 4.5%). However, in diabetic rats only three cycles of IPC significantly reduced infarction to 20.8 +/- 2.6% from 46.6 +/- 5.2% in controls (P < 0.01), commensurate with significant Akt phosphorylation after three cycles of IPC. To protect the diabetic myocardium, it appears necessary to increase the IPC stimulus to achieve the threshold for cardioprotection and a critical level of Akt phosphorylation to mediate myocardial protection. PMID:16046302

Tsang, Andrew; Hausenloy, Derek J; Mocanu, Mihaela M; Carr, Richard D; Yellon, Derek M



Preconditioned GMRES methods with incomplete Givens orthogonalization method for large sparse least-squares problems  

NASA Astrophysics Data System (ADS)

We propose to precondition the GMRES method by using the incomplete Givens orthogonalization (IGO) method for the solution of large sparse linear least-squares problems. Theoretical analysis shows that the preconditioner satisfies the sufficient condition that can guarantee that the preconditioned GMRES method will never break down and always give the least-squares solution of the original problem. Numerical experiments further confirm that the new preconditioner is efficient. We also find that the IGO preconditioned BA-GMRES method is superior to the corresponding CGLS method for ill-conditioned and singular least-squares problems.

Yin, Jun-Feng; Hayami, Ken



Mechanisms of the Beneficial Actions of Ischemic Preconditioning on Subcellular Remodeling in Ischemic-Reperfused Heart  

PubMed Central

Cardiac function is compromised by oxidative stress which occurs upon exposing the heart to ischemia reperfusion (I/R) for a prolonged period. The reactive oxygen species (ROS) that are generated during I/R incur extensive damage to the myocardium and result in subcellular organelle remodeling. The cardiac nucleus, glycocalyx, myofilaments, sarcoplasmic reticulum, sarcolemma, and mitochondria are affected by ROS during I/R injury. On the other hand, brief periods of ischemia followed by reperfusion, or ischemic preconditioning (IPC), have been shown to be cardioprotective against oxidative stress by attenuating the cellular damage and alterations of subcellular organelles caused by subsequent I/R injury. Endogenous defense mechanisms, such as antioxidant enzymes and heat shock proteins, are activated by IPC and thus prevent damage caused by oxidative stress. Although these cardioprotective effects of IPC against I/R injury are considered to be a consequence of changes in the redox state of cardiomyocytes, IPC is considered to promote the production of NO which may protect subcellular organelles from the deleterious actions of oxidative stress. The article is intended to focus on the I/R-induced oxidative damage to subcellular organelles and to highlight the cardioprotective effects of IPC. In addition, the actions of various endogenous cardioprotective interventions are discussed to illustrate that changes in the redox state due to IPC are cardioprotective against I/R injury to the heart.

Muller, By Alison L; Dhalla, Naranjan S



Ozone oxidative preconditioning: a protection against cellular damage by free radicals.  

PubMed Central

There is some anecdotal evidence that oxygen-ozone therapy may be beneficial in some human diseases. However so far only a few biochemical and pharmacodynamic mechanisms have been elucidated. On the basis of preliminary data we postulated that controlled ozone administration would promote an oxidative preconditioning preventing the hepatocellular damage mediated by free radicals. Six groups of rats were classified as follows: (1) negative control, using intraperitoneal sunflower oil; (2) positive control using carbon tetrachloride (CCl4) as an oxidative challenge; (3) oxygen-ozone, pretreatment via rectal insufflation (15 sessions) and after it, CCl4; (4) oxygen, as group 3 but using oxygen only; (5) control oxygen-ozone, as group 3, but without CCl4; group (6) control oxygen, as group 5, but using oxygen only. We have evaluated critical biochemical parameters such as levels of transaminase, cholinesterase, superoxide dismutase, catalase, phospholipase A, calcium dependent ATPase, reduced glutathione, glucose 6 phosphate dehydrogenase and lipid peroxidation. Interestingly, in spite of CCl4 administration, group 3 did not differ from group 1, while groups 2 and 4 showed significant differences from groups 1 and 3 and displayed hepatic damage. To our knowledge these are the first experimental results showing that repeated administration of ozone in atoxic doses is able to induce an adaptation to oxidative stress thus enabling the animals to maintain hepatocellular integrity after CCl4 poisoning.

Leon, O S; Menendez, S; Merino, N; Castillo, R; Sam, S; Perez, L; Cruz, E; Bocci, V



Parvalbumin is overexpressed in the late phase of pharmacological preconditioning in skeletal muscle.  


Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K(+) channel openers such as diazoxide, provides protection against ischemia in cardiac muscle, skeletal muscle, and other tissues. Effects on Ca(2+) homeostasis during the late phase of PPC have been described in cardiomyocytes, but no information is available regarding intracellular Ca(2+) changes in skeletal muscle fibers during late PPC. Intracellular Ca(2+) signals were measured in single fibers of adult mouse skeletal muscle, with fluorescent probes, 48 h after the administration of diazoxide. Parvalbumin levels in the myofibers were quantitated by Western blot. Diazoxide induction of late PPC was confirmed by partial protection of muscles from peroxide-induced damage. Late PPC was associated with a significant decrease in the duration of Ca(2+) signals during single twitches and tetanus with no changes in peak values. This effect was prevented by the reactive oxygen species (ROS) scavenger tiron. Late PPC was accompanied by a 30% increase in parvalbumin levels, and this effect was also blocked by tiron. Our data show, for the first time, a role of parvalbumin in late PPC in skeletal muscle. PMID:24117265

Solis, Rosario; Carrillo, Elba D; Hernández, Ascención; García, María C; Sánchez, Jorge A



Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil  

Microsoft Academic Search

The effectiveness of defibrotide, a single-stranded polydeoxyribonucleotide compound, in preventing damage caused by cerebral ischemia was studied. Global ischemia was induced in anesthetized gerbils by bilateral carotid artery occlusion for 10 min. Defibrotide (100 mg\\/kg) or saline was injected, i.v., immediately after reperfusion. The following parameters were evaluated simultaneously: (1) electroencephalographic (EEG) spectral power, recorded before, during and after the

Mariaelvina Sala; Maria Primula Leone; Paola Lampugnani; Luigi Matturri; Enzo Gori



Protein tyrosine nitration of the flavin subunit is associated with oxidative modification of mitochondrial complex II in the post-ischemic myocardium.  


Increased O(2)* and NO production is a key mechanism of mitochondrial dysfunction in myocardial ischemia/reperfusion injury. A crucial segment of the mitochondrial electron transport chain is succinate ubiquinone reductase (SQR or Complex II). In SQR, oxidative impairment and deglutathionylation of the 70-kDa flavin protein occurs in the post-ischemic heart ( Chen, Y. R., Chen, C. L., Pfeiffer, D. R., and Zweier, J. L. (2007) J. Biol. Chem. 282, 32640-32654 ). To gain insights into the oxidative modification of the 70-kDa protein in the post-ischemic myocardium, we used the identified S-glutathionylated peptide ((77)AAFGLSEAGFNTACVTK(93)) of the 70-kDa protein as a chimeric epitope incorporating a "promiscuous" T cell epitope to generate a high titer polyclonal antibody, AbGSC90. Purified AbGSC90 showed a high binding affinity to isolated SQR. Antibodies of AbGSC90 moderately inhibited the electron transfer and superoxide generation activities of SQR. To test for protein nitration, rats were subjected to 30 min of coronary ligation followed by 24 h of reperfusion. Tissue homogenates were immunoprecipitated with AbGSC90 and probed with antibodies against 3-nitrotyrosine. Enhancement of protein tyrosine nitration was detected in the post-ischemic myocardium. Isolated SQR was subjected to in vitro protein nitration with peroxynitrite, leading to site-specific nitration at the 70-kDa polypeptide and impairment of SQR electron transfer activity. Protein nitration of SQR further impaired its protein-protein interaction with Complex III. Liquid chromatography/tandem mass spectrometry analysis indicated that Tyr-56 and Tyr-142 were involved in protein tyrosine nitration. When the isolated SQR was subjected to in vitro S-glutathionylation, oxidative modification and impairment mediated by peroxynitrite were significantly decreased, thus confirming the protective effect of S-glutathionylation from the oxidative damage of nitration. PMID:18682392

Chen, Chwen-Lih; Chen, Jingfeng; Rawale, Sharad; Varadharaj, Saradhadevi; Kaumaya, Pravin P T; Zweier, Jay L; Chen, Yeong-Renn



Formation of Hydrogen Peroxide and Reduction of Peroxynitrite via Dismutation of Superoxide at Reperfusion Enhances Myocardial Blood Flow and Oxygen Consumption in Postischemic Mouse Heart  

PubMed Central

Reactive oxygen/nitrogen species suppress myocardial oxygen consumption. In this study, we determined that endogenous hydrogen peroxide through dismutation of superoxide enhances postischemic myocardial blood perfusion and oxygen consumption. Electron paramagnetic resonance oximetry was applied to monitor in vivo tissue Po2 in mouse heart subjected to regional ischemia reperfusion. Heart rate, arterial blood pressure, blood flow, infarction, and activities of mitochondrial NADH dehydrogenase and cytochrome c oxidase were measured in six groups of wild-type (WT) and endothelial nitric-oxide synthase knock-out (eNOS?/?) mice treated with phosphate-buffered saline (PBS), superoxide dismutase mimetic (SODm) M40403 [a manganese(II)-bis(cyclohexylpyridine)-substituted macrocyclic superoxide dismutase mimetic, C21H35Cl2MnN5], 10006329 EUK 134 [EUK134, manganese 3-methoxy N,N1-bis(salicyclidene)ethylenediamine chloride], and SODm plus glibenclamide to study the protective effect of hydrogen peroxide via dismutation of superoxide on the activation of sarcolemmal potassium channels. In the PBS group, there was an overshoot of tissue Po2 after reperfusion. Treatment with SODm, EUK134, and SODm + glibenclamide protected mitochondrial enzyme activities, reduced infarct size, and suppressed the post-ischemic hyperoxygenation. In particular, in the SODm-treated group, there was a transient peak of tissue Po2 at 9 min after reperfusion, which was dependent on endogenous hydrogen peroxide but not nitric oxide formation as it appeared in both WT and eNOS?/? mice. Blood flow and rate pressure product were higher in the SODm group than in other groups, which contributed to the transient oxygen peak. Thus, SOD mimetics protected mouse heart from superoxide-induced reperfusion injury. With treatment of different SOD mimetics, it is concluded that endogenous hydrogen peroxide via dismutation of superoxide at reperfusion enhances postischemic myocardial blood perfusion and mitochondrial oxygen consumption, possibly through activation of sarcolemmal ATP-sensitive potassium channels.

Xu, Yi; Liu, Bin; Zweier, Jay L.; He, Guanglong



Protective Effects of Deferoxamine Mesylate Preconditioning on Pancreatic Tissue in Orthotopic Liver Autotransplantation in Rats  

Microsoft Academic Search

BackgroundDeferoxamine mesylate is known to ameliorate tissue ischemia–reperfusion injury. This study was designed to explore the impact of deferoxamine mesylate preconditioning (DMP) on pancreatic tissue and its possible effects during orthotopic liver autotransplantation.

Y. Li; P.-J. Zhang; C. Jin; B. Zhou; X.-Y. Liu; L.-D. Tao; M. Feng



The effect of Allium sativum on ischemic preconditioning and ischemia reperfusion induced cardiac injury  

PubMed Central

In the present study, the effect of garlic (Allium sativum) extract on ischemic preconditioning and ischemia-reperfusion induced cardiac injury has been studied. Hearts from adult albino rats of Wistar strain were isolated and immediately mounted on Langendorff's apparatus for retrograde perfusion. After 15 minutes of stabilization, the hearts were subjected to four episodes of 5 min ischemia, interspersed with 5 min reperfusion (to complete the protocol of ischemic preconditioning), 30 min global ischemia, followed by 120 min of reperfusion. In the control and treated groups, respective interventions were given instead of ischemic preconditioning. The magnitude of cardiac injury was quantified by measuring Lactate Dehydrogenase and creatine kinase concentration in the coronary effluent and myocardial infarct size by macroscopic volume method. Our study demonstrates that garlic extract exaggerates the cardio protection offered by ischemic preconditioning and per se treatment with garlic extract also protects the myocardium against ischemia reperfusion induced cardiac injury.

Bhatti, Rajbir; Singh, Kushlinder; Ishar, M.P.S.; Singh, Jatinder



Toward Efficient Implementations of PCCG (Preconditioned Conjugate Gradient) Methods on Vector Supercomputers.  

National Technical Information Service (NTIS)

The authors considers large, sparse linear systems which result from the discretization of partial differential equations on regular and irregular domains, and he focuses on the application of the preconditioned conjugate gradient (PCCG) method to the sol...

R. Melhem



40 CFR 85.2219 - Idle test with loaded preconditioning-EPA 91.  

Code of Federal Regulations, 2013 CFR

... 2013-07-01 2013-07-01 false Idle test with loaded preconditioning-EPA 91. 85.2219...Emission Control System Performance Warranty Short Tests § 85.2219 Idle test with loaded preconditioningâEPA 91. (a)...



Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice  

PubMed Central

Background Classical and delayed preconditioning are powerful endogenous protection mechanisms against ischemia-reperfusion damage. However, it is still uncertain whether delayed preconditioning can effectively salvage myocardium in patients with co-morbidities, such as diabetes and the metabolic syndrome. We investigated delayed preconditioning in mice models of type II diabetes and the metabolic syndrome and investigated interventions to optimize the preconditioning potential. Methods Hypoxic preconditioning was induced in C57Bl6-mice (WT), leptin deficient ob/ob (model for type II diabetes) and double knock-out (DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome). Twenty-four hours later, 30 min of regional ischemia was followed by 60 min reperfusion. Left ventricular contractility and infarct size were studied. The effect of 12 weeks food restriction or angiotensin-converting enzyme inhibition (ACE-I) on this was investigated. Differences between groups were analyzed for statistical significance by student’s t-test or one-way ANOVA followed by a Fisher’s LSD post hoc test. Factorial ANOVA was used to determine the interaction term between preconditioning and treatments, followed by a Fisher’s LSD post hoc test. Two-way ANOVA was used to determine the relationship between infarct size and contractility (PRSW). A value of p<0.05 was considered significant. Results Left ventricular contractility is reduced in ob/ob compared with WT and even further reduced in DKO. ACE-I improved contractility in ob/ob and DKO mice. After ischemia/reperfusion without preconditioning, infarct size was larger in DKO and ob/ob versus WT. Hypoxic preconditioning induced a strong protection in WT and a partial protection in ob/ob mice. The preconditioning potential was lost in DKO. Twelve weeks of food restriction or ACE-I restored the preconditioning potential in DKO and improved it in ob/ob. Conclusion Delayed preconditioning is restored by food restriction and ACE-I in case of type II diabetes and the metabolic syndrome.



Post-ischemic early acidosis in cardiac postconditioning modifies the activity of antioxidant enzymes, reduces nitration, and favors protein S-nitrosylation  

Microsoft Academic Search

Postconditioning (PostC) modifies the early post-ischemic pH, redox environment, and activity of enzymes. We hypothesized\\u000a that early acidosis in PostC may affect superoxide dismutase (SOD) and catalase (CAT) activities, may reduce 3-nitrotyrosine\\u000a (3-NT) protein levels, and may increase S-nitrosylated (SNO) protein levels, thus deploying its protective effects. To verify\\u000a this hypothesis, we studied the early (7th min) and late (120th

Claudia Penna; Maria-Giulia Perrelli; Francesca Tullio; Francesca Moro; Maria Laura Parisella; Annalisa Merlino; Pasquale Pagliaro


Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels  

PubMed Central

BACKGROUND AND PURPOSE Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K+ (mitoKATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca2+ homeostasis during PPC, particularly changes in Ca2+ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca2+ channels. EXPERIMENTAL APPROACH PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca2+ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the ?1c subunit of L-type channels in the cellular membrane were measured by Western blot. KEY RESULTS PPC was accompanied by a 50% reduction in ?1c subunit levels, and by a reversible fall in L-type current amplitude and Ca2+ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoKATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the ?1c subunit and Ca2+ channel function were prevented in part by the protease inhibitor leupeptin. CONCLUSIONS AND IMPLICATIONS PPC downregulated the ?1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca2+ channel, which in turn reduced Ca2+ influx, which may attenuate Ca2+ overload during reperfusion.

Gonzalez, G; Zaldivar, D; Carrillo, ED; Hernandez, A; Garcia, MC; Sanchez, JA



Post-filtering of IC2-factors for load balancing in parallel preconditioning  

NASA Astrophysics Data System (ADS)

A modification is proposed for the second order incomplete Cholesky decomposition (IC2). It makes possible to design a preconditioning procedure for the conjugate gradient method (CGM) with a controllable fill-in in the preconditioner. The modified algorithm is used to develop a load-balancing parallel preconditioning for CGM as applied to linear systems with symmetric positive definite matrices. Numerical results obtained using a multiprocessor computer system are presented.

Kaporin, I. E.; Kon'shin, I. N.



Ischemic preconditioning involves dual cardio-protective axes with p38MAPK as upstream target  

Microsoft Academic Search

The existing literature indicates a crucial role of p38 MAP (mitogen-activated protein) kinase (p38MAPK) and its downstream target MAPKAP kinase 2 (MK2) in ischemic preconditioning (IPC). Accordingly, deletion of MK2 gene should abolish the cardioprotective ability of IPC. Interestingly, we were able to partially precondition the hearts from MK2?\\/? knockout mice suggesting the existence of an as yet unknown alternative

Norbert Nagy; Keisuke Shiroto; Gautam Malik; Chi-Kuang Huang; Mathias Gaestel; Maha Abdellatif; Arpad Tosaki; Nilanjana Maulik; Dipak K. Das



Hypoxia preconditioning protection of corneal stromal cells requires HIF1? but not VEGF  

PubMed Central

Purpose Hypoxia preconditioning protects corneal stromal cells from stress-induced death. This study determined whether the transcription factor HIF-1? (Hypoxia Inducible Factor) is responsible and whether this is promulgated by VEGF (Vascular Endothelial Growth Factor). Methods Cultured bovine stromal cells were preconditioned with hypoxia in the presence of cadmium chloride, a chemical inhibitor of HIF-1?, and HIF-1? siRNA to test if HIF-1? activity is needed for hypoxia preconditioning protection from UV-irradiation induced cell death. TUNEL assay was used to detect cell apoptosis after UV-irradiation. RT-PCR and western blot were used to detect the presence of HIF-1? and VEGF in transcriptional and translational levels. Results During hypoxia (0.5% O2), 5 ?M cadmium chloride completely inhibited HIF-1? expression and reversed the protection by hypoxia preconditioning.  HIF-1? siRNA (15 nM) reduced HIF-1? expression by 90% and produced a complete loss of protection provided by hypoxia preconditioning.  Since VEGF is induced by hypoxia, can be HIF-1? dependent, and is often protective, we examined the changes in transcription of VEGF and its receptors after 4 h of hypoxia preconditioning.  VEGF and its receptors Flt-1 and Flk-1 are up-regulated after hypoxia preconditioning.  However, the transcription and translation of VEGF were paradoxically increased by siHIF-1?, suggesting that VEGF expression in stromal cells is not down-stream of HIF-1?. Conclusions These findings demonstrate that hypoxia preconditioning protection in corneal stromal cells requires HIF-1?, but that VEGF is not a component of the protection.

Xing, Dongmei



That Which Does Not Kill You Makes You Stronger: A Molecular Mechanism for Preconditioning  

NSDL National Science Digital Library

Preconditioning by sublethal stress can protect a cell from subsequent injury and apoptosis through a mechanism that has been unclear. Many such stresses stimulate the formation of stress granules: transient cytoplasmic foci that contain heat shock protein as well as translationally stalled mRNA and various mRNA-binding proteins. Recent research suggests that sequestration in stress granules of TRAF2, an adaptor protein that is required for tumor necrosis factor receptor 1 signaling, may underlie preconditioning by sublethal stresses.

Jonathan E. McDunn (Washington University School of Medicine;Cellular Injury and Adaptation Laboratory, Departments of Surgery and Genetics REV); J. Perren Cobb (Washington University School of Medicine;Cellular Injury and Adaptation Laboratory, Departments of Surgery and Genetics REV)



Hypoxia tolerance and preconditioning are not additive in the trout (Oncorhynchus mykiss) heart.  


Research has shown that the trout heart is normally hypoxia-sensitive, and that it can be preconditioned. However, we have identified a group of rainbow trout Oncorhynchus mykiss that shows a surprising degree of myocardial hypoxia tolerance. In this study, we used in situ hearts from these fish as a comparative model to examine whether the cardioprotective effects afforded by hypoxic adaptation and preconditioning are additive. In situ trout hearts were exposed to severe hypoxia (perfusate PO2 5-10 mmHg) in the absence and presence of a transient hypoxic pre-exposure (preconditioning). The four groups studied were: (1) control (no hypoxia); (2) 5 min of severe hypoxia; (3) 30 min of severe hypoxia; and (4) 5 min of severe hypoxia (hypoxic preconditioning) followed 20 min later by 30 min of severe hypoxia. 30 min of severe hypoxia significantly decreased maximum cardiac output and stroke volume by 15-30%. However, hypoxic preconditioning failed to confer any protection against post-hypoxic myocardial dysfunction. This work shows that the protection afforded by inherent myocardial hypoxia tolerance and preconditioning are not additive in this population of trout, and strongly suggests that the relationship between hypoxic adaptation and preconditioning in fishes resembles that of the neonatal/immature, not adult, mammalian heart. Further, our results (1) indicate that stretch (volume loading) and chronic exposure to low levels of adrenaline (15 nmol l(-1)) do not confer any protection against hypoxia-related myocardial dysfunction in this population, and (2) validate the use of the in situ trout heart as a comparative model for studying aspects of myocardial hypoxia tolerance and preconditioning in vertebrates. PMID:15184521

Gamperl, A Kurt; Faust, Heather A; Dougher, Bekah; Rodnick, Kenneth J



A preconditioning strategy for the solution of linear boundary element systems using the GMRES method  

Microsoft Academic Search

In this paper a novel preconditioning strategy is presented that is designed to improve the convergence rates of the Generalized Minimal Residual (GMRES) method when applied to dense linear systems of boundary element equations of the form Hx = c. The GMRES method is applied to the preconditioned system (D+L)?1?Hx = (D+L)?1?c, where D = diag(H), L is the strictly

K. Davey; S. Bounds



The Role of Erythropoetin in Ischemic Preconditioning, Postconditioning, and Regeneration of the Brain after Ischemia  

Microsoft Academic Search

Analysis of published data shows that erythropoietin plays an important role in controlling the tolerance of the brain to\\u000a the actions of ischemia and reperfusion. This cytokine has a role in ischemic preconditioning of the brain and can imitate\\u000a the phenomena of preconditioning and postconditioning. However, it is unclear whether endogenous erythropoietin is involved\\u000a in postconditioning of the brain. Erythropoetin

L. N. Maslov



Preconditioned C\\/GMRES algorithm for nonlinear receding horizon control of hovercrafts connected by a string  

Microsoft Academic Search

This paper describes preconditioning methods for real-time algorithm of nonlinear receding horizon control. Nonlinear receding horizon control requires a solution of a finite-horizon optimal control problem at each sampling time. Although the problem can be solved by a fast algorithm called C\\/GMRES, calculation may fail for some stiff systems. By introducing preconditioning methods such as block Jacobi or ILU preconditioner

Takuma Tanida; Toshiyuki Ohtsuka



The Effect of Ischemic Preconditioning on Long-term Prognosis in Acute Myocardial Infarction  

Microsoft Academic Search

Background and Objectives:The brief repetitive periods of ischemia and reperfusion before a myocardial infarction appears to precondition the heart, making it more resistant to subsequent longer periods of ischemia. This phenomenon is known as ischemic preconditioning (IP). We studied the long-term effects of IP in patients with acute myocardial infarction. Subjects and Methods:Between January 1991 and August 1993, we examined,

Cheol Hong Kim; Kyu Hyung Ryu; Jin Won Jo; Ji Hyun Hong; Seong Woo Han; Sang Jin Han; Yung Lee


Low-diffusion preconditioning scheme for numerical simulation of low-speed flows past airfoil  

Microsoft Academic Search

The preconditioning technique can address the stiffness of a low Mach number flow, while its stability is poor. Based on the\\u000a conventional preconditioning method of Roe's scheme, a low-diffusion scheme is proposed. An adjustable parameter is introduced\\u000a to control numerical dissipation, especially over the dissipation in the boundary layer and extremely in a low speed region.\\u000a Numerical simulations of the

Qian Xiang; Song-ping Wu; Chun-hian Lee; Ning cao



Inhalational anesthetics as neuroprotectants or chemical preconditioning agents in ischemic brain  

PubMed Central

This review will focus on inhalational anesthetic neuroprotection during cerebral ischemia and inhalational anesthetic preconditioning before ischemic brain injury. The limitations and challenges of past and current research in this area will be addressed before reviewing experimental and clinical studies evaluating the effects of inhalational anesthetics before and during cerebral ischemia. Mechanisms underlying volatile anesthetic neuroprotection and preconditioning will also be examined. Lastly, future directions for inhalational anesthetics and ischemic brain injury will be briefly discussed.

Kitano, Hideto; Kirsch, Jeffrey R; Hurn, Patricia D; Murphy, Stephanie J



[Biochemical and pharmacological mechanisms of different types of hypoxic preconditioning in cerebral ischemia in mice].  


Different types of hypoxic preconditioning (hypoxic, circulatory, hemic and tissue hypoxia) increase the tolerance to complete global cerebral ischemia at early terms (hours). Biochemico-pharmacological analysis with the use of selective agonists and antagonists showed the importance of adenosine A1-receptors and K+(ATP)-channels in the mechanisms of the neuroprotective effect and natural tolerance. The general scheme of the investigated mechanisms of different types of hypoxic preconditioning has been proposed. PMID:16898589

Kulinski?, V I; Gavrilina, T V; Minakina, L N; Kovtun, V Iu


Chronic Valproate Treatment Enhances Post-ischemic Angiogenesis and Promotes Functional Recovery in a Rat Model of Ischemic Stroke  

PubMed Central

Background and Purpose Enhanced angiogenesis facilitates neurovascular remodeling processes and promotes brain functional recovery after stroke. Previous studies from our laboratory demonstrated that valproate (VPA), a histone deacetylase (HDAC) inhibitor, protects against experimental brain ischemia. The present study investigated whether VPA could enhance angiogenesis and promote long-term functional recovery after ischemic stroke. Methods Male rats underwent middle cerebral artery occlusion (MCAO) for 60 minutes followed by reperfusion for up to 14 days. Assessed parameters were: locomotor function via rotarod test; infarct volume via T2-weighted magnetic resonance imaging; microvessel density via immunohistochemistry; relative cerebral blood flow (rCBF) via perfusion-weighted imaging; protein levels of pro-angiogenic factors via Western blotting; and matrix metalloproteinase (MMP)-2/9 activities via gelatin zymography. Results Post-ischemic VPA treatment robustly improved the rotarod performance of MCAO rats on days 7 and 14 after ischemia, and significantly reduced brain infarction on day 14. Concurrently, VPA markedly enhanced microvessel density, facilitated endothelial cell proliferation, and increased rCBF in the ipsilateral cortex. The transcription factor hypoxia-inducible factor (HIF)-1? and its downstream pro-angiogenic factors, vascular endothelial growth factor (VEGF) and MMP-2/9, were upregulated after MCAO and significantly potentiated by VPA in the ipsilateral cortex. Acetylation of histone-H3 and H4 was robustly increased by chronic VPA treatment. The beneficial effects of VPA on rotarod performance and microvessel density were abolished by HIF-1? inhibition. Conclusions Chronic VPA treatment enhances angiogenesis and promotes functional recovery after brain ischemia. These effects may involve HDAC inhibition and upregulation of HIF-1? and its downstream pro-angiogenic factors VEGF and MMP-2/9.

Wang, Zhifei; Tsai, Li-Kai; Munasinghe, Jeeva; Leng, Yan; Fessler, Emily Bame; Chibane, Fairouz; Leeds, Peter; Chuang, De-Maw



Decreased long-chain fatty acid oxidation impairs postischemic recovery of the insulin-resistant rat heart.  


Diabetic patients with acute myocardial infarction are more likely to die than nondiabetic patients. In the present study we examined the effect of insulin resistance on myocardial ischemia tolerance. Hearts of rats, rendered insulin resistant by high-sucrose feeding, were subjected to ischemia/reperfusion ex vivo. Cardiac power of control hearts from chow-fed rats recovered to 93%, while insulin-resistant hearts recovered only to 80% (P<0.001 vs. control). Unexpectedly, impaired contractile recovery did not result from an impairment of glucose oxidation (576±36 vs. 593±42 nmol/min/g dry weight; not significant), but from a failure to increase and to sustain oxidation of the long-chain fatty acid oleate on reperfusion (1878±56 vs. 2070±67 nmol/min/g dry weight; P<0.05). This phenomenon was due to a reduced ability to transport oleate into mitochondria and associated with a 38-58% decrease in the mitochondrial uncoupling protein 3 (UCP3) levels. Contractile function was rescued by replacing oleate with a medium-chain fatty acid or by restoring UCP3 levels with 24 h of food withdrawal. Lastly, the knockdown of UCP3 in rat L6 myocytes also decreased oleate oxidation by 13-18% following ischemia. Together the results expose UCP3 as a critical regulator of long-chain fatty acid oxidation in the stressed heart postischemia and identify octanoate as an intervention by which myocardial metabolism can be manipulated to improve function of the insulin-resistant heart.-Harmancey, R., Vasquez, H. G., Guthrie, P. H., Taegtmeyer, H. Decreased long-chain fatty acid oxidation impairs postischemic recovery of the insulin-resistant rat heart. PMID:23825227

Harmancey, Romain; Vasquez, Hernan G; Guthrie, Patrick H; Taegtmeyer, Heinrich



Preconditioned 70S30C bioactive glass foams promote osteogenesis in vivo.  


Bioactive glass scaffolds (70S30C; 70% SiO2 and 30% CaO) produced by a sol-gel foaming process are thought to be suitable matrices for bone tissue regeneration. Previous in vitro data showed bone matrix production and active remodelling in the presence of osteogenic cells. Here we report their ability to act as scaffolds for in vivo bone regeneration in a rat tibial defect model, but only when preconditioned. Pretreatment methods (dry, pre-wetted or preconditioned without blood) for the 70S30C scaffolds were compared against commercial synthetic bone grafts (NovaBone® and Actifuse®). Poor bone ingrowth was found for both dry and wetted sol-gel foams, associated with rapid increase in pH within the scaffolds. Bone ingrowth was quantified through histology and novel micro-CT image analysis. The percentage bone ingrowth into dry, wetted and preconditioned 70S30C scaffolds at 11weeks were 10±1%, 21±2% and 39±4%, respectively. Only the preconditioned sample showed above 60% material-bone contact, which was similar to that in NovaBone and Actifuse. Unlike the commercial products, preconditioned 70S30C scaffolds degraded and were replaced with new bone. The results suggest that bioactive glass compositions should be redesigned if sol-gel scaffolds are to be used without preconditioning to avoid excess calcium release. PMID:23891811

Midha, Swati; Kim, Taek Bo; van den Bergh, Wouter; Lee, Peter D; Jones, Julian R; Mitchell, Christopher A



Proteomic analysis of the mice hippocampus after preconditioning induced by N-methyl-D-aspartate (NMDA).  


Preconditioning induced by N-methyl-D-aspartate (NMDA) has been used as a therapeutic tool against later neuronal insults. NMDA preconditioning affords neuroprotection against convulsions and cellular damage induced by the NMDA receptor agonist, quinolinic acid (QA) with time-window dependence. This study aimed to evaluate the molecular alterations promoted by NMDA and to compare these alterations in different periods of time that are related to the presence or lack of neuroprotection. Putative mechanisms related to NMDA preconditioning were evaluated via a proteomic analysis by using a time-window study. After a subconvulsant and protective dose of NMDA administration mice, hippocampi were removed (1, 24 or 72 h) and total protein analyzed by 2DE gels and identified by MALDI-TOF. Differential protein expression among the time induction of NMDA preconditioning was observed. In the hippocampus of protected mice (24 h), four proteins: HSP70(B), aspartyl-tRNA synthetase, phosphatidylethanolamine binding protein and creatine kinase were found to be up-regulated. Two other proteins, HSP70(A) and V-type proton ATPase were found down-regulated. Proteomic analysis showed that the neuroprotection induced by NMDA preconditioning altered signaling pathways, cell energy maintenance and protein synthesis and processing. These events may occur in a sense to attenuate the excitotoxicity process during the activation of neuroprotection promoted by NMDA preconditioning. PMID:23001814

do Amaral e Silva Müller, Gabrielle; Vandresen-Filho, Samuel; Tavares, Carolina Pereira; Menegatti, Angela C O; Terenzi, Hernán; Tasca, Carla Inês; Severino, Patricia Cardoso



Influence of laser preconditioning on the capacity of optical films to resist laser-induced damage  

NASA Astrophysics Data System (ADS)

As a technique to improve the ability of optical films to resist laser-induced damage (ARLID), laser preconditioning has been investigated broadly. In this paper, the laser preconditioning effect has been analyzed based on the defect-initialized damage mechanism that the author had put forward previously. Theoretical results show that an energy density scope (PEDS) exists in which the preconditioning laser can effectively improve the ARLID of optical films. In addition, when the energy density of the testing laser pulse is altered, the boundary of PEDS will change accordingly. Experimental results have verified these theoretical assumptions. PEDS will also become wider if the critical energy density of the preconditioning laser that can induce films’ micro-damage increases, or the critical energy density of the preconditioning laser that can cause laser annealing decreases. In these cases, it is relatively easy to improve the ARLID of optical films. Results of the current work show great significance in enhancing the ARLID of optical films through the laser preconditioning technique.

Xia, Zhilin; Zhao, Yuan'An; Huang, Caihua; Xue, Yiyu; Guo, Peitao



Spectral analysis of electrocorticographic activity during pharmacological preconditioning and seizure induction by intrahippocampal domoic acid.  


Previously we have shown that low-dose domoic acid (DA) preconditioning produces tolerance to the behavioral effects of high-dose DA. In this study, we used electrocorticography (ECoG) to monitor subtle CNS changes during and after preconditioning. Young adult male Sprague-Dawley rats were implanted with a left cortical electrode, and acute recordings were obtained during preconditioning by contralateral intrahippocampal administration of either low-dose DA (15 pmoles) or saline, followed by a high-dose DA (100 pmoles) challenge. ECoG data were analyzed by fast Fourier transformation to obtain the percentage of baseline power spectral density (PSD) for delta to gamma frequencies (range: 1.25-100 Hz). Consistent with previous results, behavioral analysis confirmed that low-dose DA preconditioning 60 min before a high-dose DA challenge produced significant reductions in cumulative seizure scores and high level seizure behaviors. ECoG analysis revealed significant reductions in power spectral density across all frequency bands, and high-frequency/high-amplitude spiking in DA preconditioned animals, relative to saline controls. Significant correlations between seizure scores and ECoG power confirmed that behavioral analysis is a reliable marker for seizure analysis. The reduction of power in delta to gamma frequency bands in contralateral cortex does not allow a clear distinction between seizure initiation and seizure propagation, but does provide objective confirmation that pharmacological preconditioning by DA reduces network seizure activity. PMID:19714566

Sawant, P M; Mountfort, D O; Kerr, D S



Human sensory preconditioning in a flavor preference paradigm.  


This experiment adapted a sensory preconditioning (SPC) procedure using human participants to determine if conditioning (Cond) to one flavor (the conditioned flavor) will enhance liking for another flavor (the SPC flavor) associated with it prior to training. Participants in one of three groups (N=40 per group) consumed and rated plain or sweetened cherry and grape kool-aids in four phases. In baseline and SPC phase, ratings for a plain cherry, grape, and cherry-grape mixture were similar. In training, one flavor was sweetened (SPC+Cond and Cond Only groups) or unsweetened (SPC Only group) and ratings increased only for the flavor that was sweetened. In test, Group SPC+Cond rated the conditioned flavor and the SPC flavor as more liked and tasting sweeter. Group Cond Only rated only the conditioned flavor as more liked and tasting sweeter. Group SPC Only showed no change in ratings from baseline to test. These are the first data to show SPC learning using a flavor preference paradigm with human participants. PMID:22721907

Privitera, Gregory J; Mulcahey, Colleen P; Orlowski, Cassandra M



Positive Indian Ocean Dipole events precondition southeast Australia bushfires  

NASA Astrophysics Data System (ADS)

The devastating “Black Saturday” bushfire inferno in the southeast Australian state of Victoria in early February 2009 and the “Ash Wednesday” bushfires in February 1983 were both preceded by a positive Indian Ocean Dipole (pIOD) event. Is there a systematic pIOD linkage beyond these two natural disasters? We show that out of 21 significant bushfires seasons since 1950, 11 were preceded by a pIOD. During Victoria's wet season, particularly spring, a pIOD contributes to lower rainfall and higher temperatures exacerbating the dry conditions and increasing the fuel load leading into summer. Consequently, pIODs are effective in preconditioning Victoria for bushfires, more so than El Niño events, as seen in the impact on soil moisture on interannual time scales and in multi-decadal changes since the 1950s. Given that the recent increase in pIOD occurrences is consistent with what is expected from global warming, an increased bushfire risk in the future is likely across southeast Australia.

Cai, W.; Cowan, T.; Raupach, M.



Ischemic preconditioning improves islet recovery after pancreas cold preservation.  


Increasing evidence supports the beneficial effects of ischemic preconditioning (IPC) of organs on subsequent ischemia. The aim of this study was to assess the effects of IPC of the pancreas on islet cell recovery after cold preservation using a rat model. The pancreas was deprived of perfusion (celiac artery and superior mesenteric artery occlusion) for 10 minutes followed by 10 minutes of reperfusion. Islet isolation was performed after 18 hours of cold ischemia. Glands undergoing IPC yielded significantly greater numbers of islets than controls. Following overnight culture, a significantly greater proportion of islets was recovered from IPC-treated pancreata. Microarray genomic analysis of pancreatic tissue revealed a significant differential expression of approximately 600 unique mRNA strands within IPC pancreata compared to only <100 unique mRNA strands within non-IPC pancreata (>2-fold change; P < .05). Proteomic analysis revealed significant differential expression of at least 5 proteins >1.5-fold change; P < .05) within the IPC vs control group. Our data indicated that IPC of the pancreas prior to cold preservation was associated with improved islet cell recovery after cold ischemia. IPC of the pancreas may represent a viable therapeutic intervention to increase islet transplantation success from a single donor and to maximize organ utilization. PMID:19249556

Hogan, A R; Doni, M; Ribeiro, M M; Molano, R D; Cobianchi, L; Molina, J; Zahr, E; Ricordi, C; Pastori, R L; Pileggi, A


Arnoldi preconditioning for solving large linear biomedical systems.  


Simulations of biomedical systems often involve solving large, sparse, linear systems of the form Ax = b. In initial value problems, this system is solved at every time step, so a quick solution is essential for tractability. Iterative solvers, especially preconditioned conjugate gradient, are attractive since memory demands are minimized compared to direct methods, albeit at a cost of solution speed. A proper preconditioner can drastically reduce computation and remains an area of active research. In this paper, we propose a novel preconditioner based on system order reduction using the Arnoldi method. Systems of orders up to a million, generated from a finite element method formulation of the elliptic portion of the bidomain equations, are solved with the new preconditioner and performance is compared with that of other preconditioners. Results indicate that the new method converges considerably faster, often within a single iteration. It also uses less memory than an incomplete LU decomposition (ILU). For solving a system repeatedly, the Arnoldi transformation must be continually recomputed, unlike ILU, but this can be done quickly. In conclusion, for solving a system once, the Arnoldi preconditioner offers a greatly reduced solution time, and for repeated solves, will still be faster than an ILU preconditioner. PMID:17282853

Deo, Makarand; Vigmond, Edward



What Happened if Various Kinds of Postconditioning Working on the Preconditioned Ischemic Skin Flaps  

PubMed Central

Objective: Ischemic pre-conditioning and post-conditioning are useful manipulations to reduce the undesirable effects of ischemia-reperfusion skin flap each. But the impact of post-conditioning on the pre-conditioning skin flap is not manifested. Here we investigated the influence of ischemic post-conditioning in a preconditioned axial pattern skin flap model. Method: We used the skin flap in 40 rabbits and divided them into 5 groups randomly. At first we induced the ischemic pre-conditioning of the flap which was applied by 2 periods of 15 minutes of ischemia/15 minutes of reperfusion cycle. Next post-conditioning was performed by 6 cycles of 10 seconds of repeated ischemia/reperfusion periods at different times of just after the reperfusion,5 minutes after the reperfusion,10 minutes after the reperfusion. The animals were allocated into 5 groups: group 1 (Ischemia Group); group 2: (Pre-conditioning Group); group 3: (Pre-conditioning+ Post-conditioning Group); group 4 (Pre-conditioning+ Post-conditioning 5 minutes later Group); group5 (Pre-conditioning+ Post-conditioning 10 minutes later). The neutrophil count was assessed with histologic analysis before the dissection of the skin flap. Flap viability was assessed 1 week after the operation, and surviving flap area was recorded as a percentage of the whole flap area. LSD test was used for statistical analysis among different groups to evaluate the effects of ischemic pre-conditioning against ischemia. Result: Among the varying groups, the neutrophil count varied: Group 1 was50.12±5.91; Group 2, 30.00±2.00, and Group 3, 18.87±3; Group 4, 22.50±1.92; Group 5, 30.12±1.88.The mean± SD surviving areas of the flaps for groups 1, 2, 3, 4 and 5 were 31.76±4.59, 51.26±3.24,82.18±5.28,66.85±3.87 and 51.13±2.90 respectively. Spearman correlation analysis shows an increase relation between neutrophil count and flap survival rate in the different groups (P <0.05). Conclusion: Ischemic post-conditioning has protective effect on ischemic preconditioned skin flaps, but the post-conditioning should be performed within 5 minutes after the end of ischemia.

Huang, Lin



Numerical investigation on a new local preconditioning method for solving the incompressible inviscid, non-cavitating and cavitating flows  

Microsoft Academic Search

A locally power-law preconditioning algorithm is developed. This is applied to compute incompressible inviscid, steady-state, non-cavitating and cavitating flows. The preconditioning parameters are adapted automatically from the pressure of computational domain. This method suggests better convergence rates rather than the standard artificial compressibility and the standard preconditioning method. Single-fluid Euler equations, cast in their conservative form, along with the barotropic

Vahid Esfahanian; Pooria Akbarzadeh



Preconditioning Prevents the Inhibition of Na+,K+ATPase Activity after Brain Ischemia  

Microsoft Academic Search

Application of single transient forebrain ischemia (ISC) in adult Wistar rats, lasting 2 or 10 min, caused inhibition of Na+,K+-ATPase activity in cytoplasmic membrane fractions of hippocampus and cerebral cortex immediately after the event. In the 2-min ISC group followed by 60 min of reperfusion, the enzyme inhibition was maintained in the cortex, while there was an increase in hippocampal

AngelaTerezinha de Souza Wyse; EmílioLuiz Streck; Paulo Worm; André Wajner; Fabiana Ritter; CarlosAlexandre Netto



Retinal cell type-specific prevention of ischemia-induced damages by LPS-TLR4 signaling through microglia.  


Reprogramming of toll-like receptor 4 (TLR4) by brief ischemia or lipopolysacharide (LPS) contributes to superintending tolerance against destructive ischemia in brain. However, beneficial roles of TLR4 signaling in ischemic retina are not well known. This study demonstrated that preconditioning with LPS 48 h prior to the retinal ischemia prevents the cellular damage in morphology with hematoxylin and eosin (H&E) staining and functions of retina with electroretinogram (ERG), while post-ischemia treatment deteriorated it. The preventive effects of LPS preconditioning showed the cell type-specificity of retinal cells. There was complete rescue of ganglion cells, partial rescue of bipolar and photoreceptor cells or no rescue of amacrine cells, respectively. LPS treatment caused the proliferation and migration of retinal microglia and its preconditioning prevented the ischemia-induced microglial activation. Preventive actions from cell damages following LPS preconditioning prior to retinal ischemia were abolished in TLR4 knock-out mice, and by pre-treatments with anti-TLR4 antibody or minocycline, a microglia inhibitor, which themselves had no effects on the retinal ischemia-induced damages or microglia activation. Thus, this study revealed that TLR4 mediates the LPS preconditioning-induced preventive effects through microglial activation in the retinal ischemia model. PMID:23574143

Halder, Sebok K; Matsunaga, Hayato; Ishii, Ken J; Akira, Shizuo; Miyake, Kensuke; Ueda, Hiroshi



Preconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats  

PubMed Central

Background Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3) to prevent I/R renal injury. Methodology/Principal Findings The rats were divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T3- treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of T3 (100 ?g/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T3 group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T3 groups. Conclusions This study demonstrates that preconditioning rats with a single dose of T3 improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury.

Ferreyra, Carla; Vargas, Felix; Rodriguez-Gomez, Isabel; Perez-Abud, Rocio; O'Valle, Francisco; Osuna, Antonio



Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats.  


Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-? levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. PMID:22915786

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa



Daily Ischemic Preconditioning Provides Sustained Protection From Ischemia-Reperfusion Induced Endothelial Dysfunction: A Human Study  

PubMed Central

Background It is well established that acute ischemic preconditioning (IPC) protects against ischemia–reperfusion (IR) injury; however, the effectiveness of repeated IPC exposure has not been extensively investigated. We aimed to determine whether daily IPC episodes provide continued protection from IR injury in a human forearm model, and the role of cyclooxygenase?2 in these responses. Methods and Results Thirty healthy volunteers were randomized to participate in 2 of 3 protocols (IR alone, 1?day IPC, 7?day IPC) in an operator?blinded, crossover design. Subjects in the IR alone protocol underwent flow?mediated dilation (FMD) measurements pre? and post?IR (15? upper?arm ischemia and 15? reperfusion). The 1?day IPC protocol involved FMD measurements before and after 1 episode of IPC (3 cycles of 5? upper?arm ischemia and 5? reperfusion) and IR. Day 7 of the 7?day IPC protocol was identical to the 1?day IPC protocol but was preceded by single daily episodes of IPC for 6 days prior. During each protocol, subjects received a 7?day treatment of either the cyclooxygenase?2 inhibitor celecoxib or placebo. Pre?IR FMD was similar between groups. IR alone reduced FMD post?IR (placebo, ?FMD: ?4.4±0.7%; celecoxib, ?FMD: ?5.0±0.5%). One?day IPC completely prevented this effect (placebo, ?FMD: ?1.1±0.6%; celecoxib, ?FMD: 0.0±0.7%; P<0.0001). Similarly, 7?day IPC demonstrated persistent endothelial protection post?IR (placebo, ?FMD: ?0.9±0.9%; celecoxib, ?FMD: 0.0±0.8%; P<0.0001, P<0.0001 for ANOVA effect of IPC protocol). Celecoxib did not alter responses to IR in any protocol. Conclusions Daily episodes of IPC provide sustained protection from IR?induced endothelial dysfunction in humans through a mechanism that appears cyclooxygenase?2?independent.

Luca, Mary Clare; Liuni, Andrew; McLaughlin, Kelsey; Gori, Tommaso; Parker, John D.



Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats  

PubMed Central

Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-? levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity.

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa



[Role of stress in myocardial protection of ischemic preconditioning].  


Objective: To determine the role of stress in myocardial protection of ischemic preconditioning (IPC). Methods: Thirty rabbits were randomly divided into an IPC group, an etomidate (Etom) group, an ischemic/reperfusion (IR) group, a methylprednisolone (MP) group and a sham group. The ratio of infarction size versus risk area (infarct/risk) was calculated. The elevations of the serum creatine kinase (CK) activity and cardiac troponin I (cTnI) concentrations as well as the serum cortisol concentrations were measured. Results: The percentages of infarct/risk in the IPC group, the MP group, the IR group, and the Etom group were (5.86±2.81)%, (11.28±3.62)%, (26.79±4.53)%, and (18.19±3.72)%, respectively. The elevations of the serum CK activity in the IPC group, the MP group, the IR group, and the Etom group were (255±89), (314±160), (855±371), and (768±404) U/L, respectively. The elevations of serum cTnI concentrations in the IPC group, the MP group, the IR group, and the Etom group were (3.6±0.6),(6.1±2.2), (8.1±3.6), and (6.4±1.6) ?g/L, respectively. Those indicators among the groups were significantly different (P<0.05). Cortisol reaction was markedly diminished in the Etom group. Conclusion: A blunted cortisol reaction can markedly reduce the benefit of IPC while methylprednisolone shows cardioprotective effects, suggesting that stress might be involved in the myocardial protection of IPC. PMID:23981998

Xu, Huashan; Chen, Shengxi; Luo, Wanjun; Jiang, Haihe



Beneficial effects of ischemic preconditioning on pancreas cold preservation.  


Ischemic preconditioning (IPC) confers tissue resistance to subsequent ischemia in several organs. The protective effects are obtained by applying short periods of warm ischemia followed by reperfusion prior to extended ischemic insults to the organs. In the present study, we evaluated whether IPC can reduce pancreatic tissue injury following cold ischemic preservation. Rat pancreata were exposed to IPC (10 min of warm ischemia followed by 10 min of reperfusion) prior to ~18 h of cold preservation before assessment of organ injury or islet isolation. Pancreas IPC improved islet yields (964 ± 336 vs. 711 ± 204 IEQ/pancreas; p = 0.004) and lowered islet loss after culture (33 ± 10% vs. 51 ± 14%; p = 0.0005). Islet potency in vivo was well preserved with diabetes reversal and improved glucose clearance. Pancreas IPC reduced levels of NADPH-dependent oxidase, a source of reactive oxygen species, in pancreas homogenates versus controls (78.4 ± 45.9 vs. 216.2 ± 53.8 RLU/?g; p = 0.002). Microarray genomic analysis of pancreata revealed upregulation of 81 genes and downregulation of 454 genes (greater than twofold change) when comparing IPC-treated glands to controls, respectively, and showing a decrease in markers of apoptosis and oxidative stress. Collectively, our study demonstrates beneficial effects of IPC of the pancreas prior to cold organ preservation and provides evidence of the key role of IPC-mediated modulation of oxidative stress pathways. The use of IPC of the pancreas may contribute to increasing the quality of donor pancreas for transplantation and to improving organ utilization. PMID:22305457

Hogan, Anthony R; Doni, Marco; Molano, R Damaris; Ribeiro, Melina M; Szeto, Angela; Cobianchi, Lorenzo; Zahr-Akrawi, Elsie; Molina, Judith; Fornoni, Alessia; Mendez, Armando J; Ricordi, Camillo; Pastori, Ricardo L; Pileggi, Antonello



Glaciations in response to climate variations preconditioned by evolving topography.  


Landscapes modified by glacial erosion show a distinct distribution of surface area with elevation (hypsometry). In particular, the height of these regions is influenced by climatic gradients controlling the altitude where glacial and periglacial processes are the most active, and as a result, surface area is focused just below the snowline altitude. Yet the effect of this distinct glacial hypsometric signature on glacial extent and therefore on continued glacial erosion has not previously been examined. Here we show how this topographic configuration influences the climatic sensitivity of Alpine glaciers, and how the development of a glacial hypsometric distribution influences the intensity of glaciations on timescales of more than a few glacial cycles. We find that the relationship between variations in climate and the resulting variation in areal extent of glaciation changes drastically with the degree of glacial modification in the landscape. First, in landscapes with novel glaciations, a nearly linear relationship between climate and glacial area exists. Second, in previously glaciated landscapes with extensive area at a similar elevation, highly nonlinear and rapid glacial expansions occur with minimal climate forcing, once the snowline reaches the hypsometric maximum. Our results also show that erosion associated with glaciations before the mid-Pleistocene transition at around 950,000 years ago probably preconditioned the landscape--producing glacial landforms and hypsometric maxima--such that ongoing cooling led to a significant change in glacial extent and erosion, resulting in more extensive glaciations and valley deepening in the late Pleistocene epoch. We thus provide a mechanism that explains previous observations from exposure dating and low-temperature thermochronology in the European Alps, and suggest that there is a strong topographic control on the most recent Quaternary period glaciations. PMID:23302860

Pedersen, Vivi Kathrine; Egholm, David Lundbek



Analysis and modeling of neural processes underlying sensory preconditioning.  


Sensory preconditioning (SPC) is a procedure to demonstrate learning to associate between relatively neutral sensory stimuli in the absence of an external reinforcing stimulus, the underlying neural mechanisms of which have remained obscure. We address basic questions about neural processes underlying SPC, including whether neurons that mediate reward or punishment signals in reinforcement learning participate in association between neutral sensory stimuli. In crickets, we have suggested that octopaminergic (OA-ergic) or dopaminergic (DA-ergic) neurons participate in memory acquisition and retrieval in appetitive or aversive conditioning, respectively. Crickets that had been trained to associate an odor (CS2) with a visual pattern (CS1) (phase 1) and then to associate CS1 with water reward or quinine punishment (phase 2) exhibited a significantly increased or decreased preference for CS2 that had never been paired with the US, demonstrating successful SPC. Injection of an OA or DA receptor antagonist at different phases of the SPC training and testing showed that OA-ergic or DA-ergic neurons do not participate in learning of CS2-CS1 association in phase 1, but that OA-ergic neurons participate in learning in phase 2 and memory retrieval after appetitive SPC training. We also obtained evidence suggesting that association between CS2 and US, which should underlie conditioned response of crickets to CS2, is formed in phase 2, contrary to the standard theory of SPC assuming that it occurs in the final test. We propose models of SPC to account for these findings, by extending our model of classical conditioning. PMID:23380289

Matsumoto, Yukihisa; Hirashima, Daisuke; Mizunami, Makoto



A Preconditioning Strategy for Fully Implicit Newton-Krylov Simulations of Resistive Magnetohydrodynamics  

NASA Astrophysics Data System (ADS)

Computational MHD of tokamak plasmas poses severe challenges due to its wide range of spatio-temporal scales, strong anisotropy and nonlinearity. Additionally, resistive MHD experiences increased ill-conditioning as the spatial meshes are refined to resolve diffusive layers. We present a fully implicit Jacobian-Free Newton-Krylov method for resistive MHD. Within this strategy, we present a preconditioning approach efficiently solve the linear system during the Krylov stage. The preconditioning stragegy is based on operator splitting in which the hyperbolic and diffusive sub-systems of the equations are separately preconditioned. The hyperbolic or ideal MHD part is preconditioned by an eigenmode decomposition, similar to those employed in upwind methods, and considering the fast and/or Alfvén waves. The diffusive sub-system of the equations is preconditioned using a multigrid technique. We demonstrate that such an approach grows increasingly necessary for efficient solution strategies as the spatial mesh is refined. We demonstrate our method with examples from MHD wave propagation, and magnetic reconnection.

Reynolds, Daniel; Samtaney, Ravi; Woodward, Carol



Avoidance but not aversion following sensory preconditioning with flavors: a challenge to stimulus substitution.  


After two neutral stimuli have been paired (AB), directly conditioning a response to one of them (A) will also be reflected in a change in responding to the other (B). Standard accounts of this sensory preconditioning effect assume that it is mediated by a memory involving the stimulus that was directly conditioned (i.e., A). The reliance on this shared pathway implies that sensory preconditioning (involving B) and direct conditioning (involving A) should support qualitatively similar patterns of responding. In three experiments, directly pairing A with lithium chloride (LiCl) delivery resulted in both a reduction in consumption of A (i.e., avoidance) and a reduction in the size of licking clusters it elicits (i.e., aversion). In contrast, the sensory preconditioning effect resulted in a reduction in the consumption of B but no change in the nature of the licking response that it elicited; and a similar dissociation was observed after trace conditioning. These dissociations involving direct conditioning and sensory preconditioning, observed over a range of flavor concentrations and different doses of LiCl, undermine standard accounts of sensory preconditioning that are based on the assumption of stimulus substitution. PMID:22984921

Dwyer, D M; Burgess, K V; Honey, R C



Role of K+ATP channels in ischemic preconditioning and cardioprotection.  


Since the phenomenon of ischemic preconditioning was first described some 15 years ago, interest in strategies aimed at reducing infarct size has increased. During the past 10 years, investigations into the mechanism of ischemic preconditioning have clearly demonstrated the cardioprotective effect of K+ATP channel opening. Thus, K+ATP channel activation has been shown to be involved in cardioprotection by a variety of stimuli, including a brief period of complete ischemia (classical ischemic preconditioning) or a partial coronary artery occlusion. In addition, ischemia in remote organs and nonischemic stimuli in the heart such as ventricular pacing, stretch, and heat stress also confer protection via K+ATP channel activation. Pharmacological agents that open K+ATP channels reduce infarct size, but K+ATP channel opening must occur prior to or early during the sustained infarct-producing coronary artery occlusion, while the degree and memory of cardioprotection are less than those produced by classical ischemic preconditioning. Although the exact mechanism by which K+ATP channel activation protects is still incompletely understood, recent studies indicate a role for the mitochondrial K+ATP channels. Before K+ATP channel opening can be employed in patients at increased risk of developing myocardial infarction (e.g., unstable angina), it is mandatory to determine whether tolerance (tachyphylaxia) occurs with repeated administration of K+ATP channel openers in a fashion similar to what occurs with ischemic preconditioning. PMID:10755195

Duncker, D J; Verdouw, P D



Neuroprotective effects of the dopamine D2/D3 agonist pramipexole against postischemic or methamphetamine-induced degeneration of nigrostriatal neurons.  


We have examined the neuroprotective efficacy of the selective dopamine (DA) D2/D3 receptor agonist pramipexole in two models of nigrostriatal (NS) degeneration. The first involves the delayed (28-day) postischemic retrograde NS degeneration that takes place in gerbils following a 10-min episode of bilateral carotid arterial occlusion-induced forebrain ischemia. In vehicle (40% hydroxypropyl cyclodextrin)-treated male gerbils, there was a 40-45% loss of NS cell bodies in the pars compacta and pars reticulata (TH immunohistochemistry and Cresyl violet histochemistry) by 28 days after ischemia/reperfusion. Daily postischemic oral dosing (1 mg/kg p.o., b.i.d., beginning at 1 h after insult) decreased the 28-day postischemic loss of NS DA neurons by 36% (P < 0.01 vs. vehicle-treated). The effect was specific for dopamine neurons since no significant salvage of hippocampal CA1 neurons was observed. In a second model, pramipexole's effects were examined on methamphetamine-induced (10 mg/kg, i.p. X 4, each 2 h apart) NS degeneration in male Swiss-Webster mice. In vehicle-treated mice, there was a 40% loss of NS neurons by day 5. In contrast, pramipexole dosing (1 mg/kg, p.o., 1 h after the last methamphetamine dose, plus daily) attenuated the NS degeneration from 40% to only 8% (P < 0.00001 vs. vehicle). We postulated that pramipexole acts in both of these models to reduce the elevated DA turnover and the associated elevation in hydroxyl radical production secondary to increased MAO activity that could be responsible for oxidative damage to the NS neurons. Indeed, in the gerbil ischemia model, we documented by HPLC-ECD a 135% postreperfusion increase in DA turnover (DOPAC + HVA/DA) at 5 min after reperfusion. Pramipexole at the 1 mg/kg, p.o., dose level was able to significantly reduce the increased DA turnover, but by only 16%. Thus, it is conceivable that other mechanisms may also contribute to pramipexole's dopaminergic neuroprotection. Based on a preliminary examination of pramipexole's oxidation potential, it appears that the compound may possess significant intrinsic antioxidant properties that might contribute to its neuroprotective effects. PMID:9117424

Hall, E D; Andrus, P K; Oostveen, J A; Althaus, J S; VonVoigtlander, P F



Antidepressant effect of hypoxic preconditioning is associated with modification of expression of transcription factor c-Fos in rat brain in response to unavoidable stress.  


Development of post-stress depression in rats was accompanied by long-term moderate activation of the expression of transcription factor c-Fos in the neocortex, hippocampus, and paraventricular nucleus of the hypothalamus. Hypoxic preconditioning preventing depressive state in rats under conditions of unavoidable stress considerably enhanced c-Fos expression in the studied brain regions during the early stages of stress response (days 1-5) and promoted its normalization at later terms (10 days). Disturbances in the wavy dynamics of c-Fos expression can contribute to the pathogenic mechanisms of depression, in particular and induce hyperproduction of hypothalamic neurohormone corticoliberin, whereas potentiation of early expression of this factor in response to stress is obviously necessary for prevention of post-stress disorders. PMID:22803133

Baranova, K A; Rybnikova, E A; Samoilov, M O



Antidepressant-like effects of mild hypoxia preconditioning in the learned helplessness model in rats.  


The effects of preconditioning using mild repetitive hypobaric hypoxia (360 Torr for 2 h each of 3 days) have been studied in the learned helplessness model of depression in rats. Male Wistar rats displayed persistent depressive symptoms (depressive-like behaviour in open field, increased anxiety levels in elevated plus maze, ahedonia, elevated plasma glucocorticoids and impaired dexamethasone test) following the exposure to unpredictable and inescapable footshock in the learned helplessness paradigm. Antidepressant treatment (ludiomil, 5 mg/kg i.p.) augmented the development of the depressive state. The hypoxic preconditioning had a clear antidepressive action returning the behavioural and hormonal parameters to the control values and was equally effective in terms of our study as the antidepressant. The findings suggest hypoxic preconditioning as an effective tool for the prophylaxis of post-stress affective pathologies in humans. PMID:17379404

Rybnikova, Elena; Mironova, Vera; Pivina, Svetlana; Tulkova, Ekaterina; Ordyan, Natalia; Vataeva, Ludmila; Vershinina, Elena; Abritalin, Eugeny; Kolchev, Alexandr; Nalivaeva, Natalia; Turner, Anthony J; Samoilov, Michail



Simulation of conformational preconditioning strategies for electrophoretic stretching of DNA in a microcontraction  

PubMed Central

We have used Brownian dynamics-finite element method to examine two conformational preconditioning approaches for improving DNA stretching in a microcontraction for the purpose of direct gene analysis. The newly proposed “pre-stretching” strategy is found to significantly improve the degree of DNA extension at the exit of the contraction. On the other hand, applying an oscillating extensional field to DNA yields no preconditioning effect. Detailed analysis of the evolution of DNA extension and conformation reveals that the success of our “pre-stretching” strategy relies on the “non-local” effect that cannot be predicted using simple kinematics analysis. In other words, accurate prediction can only be obtained using detailed simulations. Comparing to the existing preconditioning strategies, our “pre-stretching” method is easy to implement while still providing a very good performance. We hope that the insight gained from this study can be useful for future design of biomicrofluidic devices for DNA manipulation.

Hsieh, Chih-Chen; Lin, Tsung-Hsien



Growth factor preconditioning increases the function of diabetes-impaired mesenchymal stem cells.  


Bone marrow-derived mesenchymal stem cells (MSCs) possess multilineage differentiation potential and can be used for the treatment of diabetic heart failure. However, hyperglycemia can affect the function of MSCs adversely and merits the requirement for a strategy to correct this anomaly. MSCs were isolated from the tibias and femurs of C57BL/6 wild-type mice at 60 days after induction of diabetes by streptozotocin. MSCs were characterized by flow cytometry for CD44 (97.7%), CD90 (95.4%), and CD105 (92.3%) markers and were preconditioned with insulin-like growth factor-1 (IGF-1) (50?ng/mL) and fibroblast growth factor-2 (FGF-2) (50?ng/mL) in combination for 1?h in serum-free Iscove's modified Dulbecco's medium. This was followed by hypoxic and high glucose insults to mimic diabetic heart microenvironment and to study the effect of preconditioning. Diabetic MSCs after treatment showed upregulation of IGF-1, FGF-2, Akt, GATA-4, and Nkx 2.5 and downregulation of p16(INK4a), p66(shc), p53, Bax, and Bak. Under hypoxic stress, preconditioned diabetic MSCs showed high superoxide dismutase activity (52.3%) compared with untreated cells (36.9%). This was concomitant with low numbers of annexin-V-positive cells, high in vitro tube-forming ability, and high chemotactic mobility to stromal cell-derived factor-1? after preconditioning in diabetic MSCs. Upregulation of Ang-I and VEGF and downregulation of p16(INK4a) were also observed in preconditioned cells under conditions of high glucose insult. Therefore, preconditioning with IGF-1 and FGF-2 in combination represents a novel strategy to augment MSC function affected by diabetes and holds significance for future strategies to treat diabetic heart failure. PMID:20446810

Khan, Mohsin; Akhtar, Shoaib; Mohsin, Sadia; N Khan, Shaheen; Riazuddin, Sheikh



A geometric theory for preconditioned inverse iteration III: A short and sharp convergence estimate for generalized eigenvalue problems  

Microsoft Academic Search

In two previous papers by Neymeyr (Linear Algebra Appl. 322 (1-3) (2001) 61; 322 (1- 3) (2001) 87), a sharp, but cumbersome, convergence rate estimate was proved for a simple preconditioned eigensolver, which computes the smallest eigenvalue together with the corre- sponding eigenvector of a symmetric positive definite matrix, using a preconditioned gradient minimization of the Rayleigh quotient. In the

Andrew V. Knyazev; Klaus Neymeyr



PKC Is Required for the Induction of Tolerance by Ischemic and NMDA-Mediated Preconditioning in the Organotypic Hippocampal Slice  

Microsoft Academic Search

Glutamate receptors and calcium have been implicated as triggering factors in the induction of tolerance by ischemic preconditioning (IPC) in the brain. However, little is known about the signal transduction pathway that ensues after the IPC induction pathway. The main goals of the present study were to determine whether NMDA induces preconditioning via a calcium pathway and promotes translocation of

Ami P. Raval; Kunjan R. Dave; Daria Mochly-Rosen; Thomas J. Sick; Miguel A. Perez-Pinzon


Mitochondrial-mediated suppression of ROS production upon exposure of neurons to lethal stress: Mitochondrial targeted preconditioning  

Microsoft Academic Search

Preconditioning represents the condition where transient exposure of cells to an initiating event leads to protection against subsequent, potentially lethal stimuli. Recent studies have established that mitochondrial-centered mechanisms are important mediators in promoting development of the preconditioning response. However, many details concerning these mechanisms are unclear. The purpose of this review is to describe the initiating and subsequent intracellular events

David W. Busija; Tamas Gaspar; Ferenc Domoki; Prasad V. Katakam; Ferenc Bari



Sensory preconditioning in newborn rabbits: from common to distinct odor memories.  


This study evaluated whether olfactory preconditioning is functional in newborn rabbits and based on joined or independent memory of odorants. First, after exposure to odorants A+B, the conditioning of A led to high responsiveness to odorant B. Second, responsiveness to B persisted after amnesia of A. Third, preconditioning was also functional with two overlapping pairs of odorants (A+B and B+C) and amnesia of one odorant did not affect memory of the others. Thus, incidental pairing of odorants allows reinforcement of one odorant to implicitly reinforce the others, the bond then vanishes, and the memory of each element becomes independent. PMID:23950192

Coureaud, Gérard; Tourat, Audrey; Ferreira, Guillaume



Accelerated Block Preconditioned Gradient method for large scale wave functions calculations in Density Functional Theory  

NASA Astrophysics Data System (ADS)

An Accelerated Block Preconditioned Gradient (ABPG) method is proposed to solve electronic structure problems in Density Functional Theory. This iterative algorithm is designed to solve directly the non-linear Kohn-Sham equations for accurate discretization schemes involving a large number of degrees of freedom. It makes use of an acceleration scheme similar to what is known as RMM-DIIS in the electronic structure community. The method is illustrated with examples of convergence for large scale applications using a finite difference discretization and multigrid preconditioning.

Fattebert, J.-L.



Ethical considerations in the application of preconditioning to solid organ transplantation  

PubMed Central

The shortage of organs for transplantation has led researchers to look for new techniques to expand the donor pool. Preconditioning strategies have the potential to protect organs from transplant associated injury or may improve the function of substandard organs so that they become suitable for transplantation. Translating this type of technology to the clinical setting raises ethical issues, particularly relating to the deceased donor. It is important that society has the opportunity to discuss the issues raised by implementation of preconditioning strategies before they are implemented rather than as a reaction to them.

McNally, S; Harrison, E; Wigmore, S




SciTech Connect

A robust numerical method called the Preconditioned Bi-Conjugate Gradient (Pre-BiCG) method is proposed for the solution of the radiative transfer equation in spherical geometry. A variant of this method called Stabilized Preconditioned Bi-Conjugate Gradient (Pre-BiCG-STAB) is also presented. These are iterative methods based on the construction of a set of bi-orthogonal vectors. The application of the Pre-BiCG method in some benchmark tests shows that the method is quite versatile, and can handle difficult problems that may arise in astrophysical radiative transfer theory.

Anusha, L. S.; Nagendra, K. N. [Indian Institute of Astrophysics, Koramangala, Bangalore 560 034 (India); Paletou, F.; Leger, L. [Laboratoire d'Astrophysique de Toulouse-Tarbes, Universite de Toulouse, CNRS, 14 Ave. E. Belin, 31400 Toulouse (France)



Effects of condition number on preconditioning for low Mach number flows  

NASA Astrophysics Data System (ADS)

The effects of the condition number on convergence characteristics and solution quality for the preconditioned Navier-Stokes equations are studied. A general approach to the construction of preconditioning parameters is proposed to account for the effects of the condition number on these parameters. To verify this technique, laminar flows past a circular cylinder at Reynolds numbers of 20 and 40, and laminar flows past a NACA0012 airfoil at Reynolds numbers of 2500 and 5000 are solved. It is shown that the condition number has effects on the convergence characteristics and solution qualities, and also that a condition number exists that optimizes the convergence characteristics and solution quality.

Lee, Sang-Hyeon



Solving nonlinear heat conduction problems with multigrid preconditioned Newton-Krylov methods  

SciTech Connect

Our objective is to investigate the utility of employing multigrid preconditioned Newton-Krylov methods for solving initial value problems. Multigrid based method promise better performance from the linear scaling associated with them. Our model problem is nonlinear heat conduction which can model idealized Marshak waves. Here we will investigate the efficiency of using a linear multigrid method to precondition a Krylov subspace method. In effect we will show that a fixed point nonlinear iterative method provides an effective preconditioner for the nonlinear problem.

Rider, W.J.; Knoll, D.A.



Type 2 Diabetes Restricts Multipotency of Mesenchymal Stem Cells and Impairs Their Capacity to Augment Postischemic Neovascularization in db/db Mice  

PubMed Central

Background This study tested the hypothesis that type 2 diabetes restricts multipotency of db/db mesenchymal stem cells (MSCs), promotes their terminal differentiation into adipocytes rather than endothelial cells, thereby promotes adipocytic infiltration into ischemic muscles, and reduces their capacity to participate in postischemic neovascularization. Methods and Results To test this hypothesis, we transplanted MSCs from db/db or wild-type (WT) mice into WT recipients after induction of hind limb ischemia. WT recipients of db/db MSCs demonstrated adipocyte infiltration of ischemic muscle and impaired neovascularization; WT recipients of WT MSCs showed no intramuscular adipocyte infiltration and had significantly enhanced neovascularization (P<0.05; n=6). Confocal microscopy showed that the percentage of MSCs that differentiated into an adipocyte phenotype was greater and into an endothelial cell was less in WT recipients transplanted with db/db MSCs than those transplanted with WT MSCs (P<0.05; n=6). In vitro, db/db MSCs exhibited greater oxidant stress, greater adipocyte differentiation, and less endothelial differentiation than WT MSCs, and these differences were reversed by treatment with N-acetylcysteine or Nox4 siRNA (P<0.05; n=6). Insulin increased Nox4 expression, oxidant stress, and adipocyte differentiation in WT MSCs, and these insulin-induced effects were reversed by Nox4 siRNA (P<0.05; n=6). Reversal of db/db MSC oxidant stress by in vivo pretreatment with Nox4 siRNA before transplantation reversed their impaired capacity to augment postischemic neovascularization. Conclusions Type 2 diabetes–induced oxidant stress restricts the multipotency of MSCs and impairs their capacity to increase blood flow recovery after the induction of hind-limb ischemia. Reversal of MSC oxidant stress might permit greater leverage of the therapeutic potential of MSC transplantation in the setting of diabetes.

Yan, Jinglian; Tie, Guodong; Wang, Shouying; Messina, Katharine E.; DiDato, Sebastian; Guo, Sujuan; Messina, Louis M.



CX43 change in LPS preconditioning against apoptosis of mesenchymal stem cells induced by hypoxia and serum deprivation is associated with ERK signaling pathway.  


This study was designed to investigate the effect and mechanism of lipopolysaccharide (LPS) preconditioning on survival and connexin 43 (CX43) expression in rat bone marrow mesenchymal stem cells (bMSCs) under hypoxia and serum deprivation (Hypoxia/SD) conditions. Whole marrow cells were obtained from the femora and tibiae of SD rats, and bMSCs were isolated by density gradient centrifugation and attachment culture. Surface antigens were determined by FACS before the experiment using antibodies conjugated directly against anti-rat CD34, anti-CD45, anti-CD29, and anti-CD44. Passage 3 bMSCs were used for all experiments. The effect of LPS preconditioning on bMSCs apoptosis in response to Hypoxia/SD was investigated by an Annexin V-FITC/PI binding assay and a mitochondrial membrane potential (??m) assay. Cyc-c released into the cytosol from mitochondria and CX43 in bMSCs was determined by Western blot before and after LPS preconditioning. Subsequently, extracellular signal-regulated kinase (ERK) was inhibited with PD98059 to analyze the role of ERK in modulating CX43 expression after LPS preconditioning. The bMSCs surface antigen profiles obtained by flow cytometry were positive for CD29 and CD44 and negative for CD34 and CD45. The Hypoxia/SD conditions induced significant apoptosis of bMSCs. Compared with the Hypoxia/SD group, cells treated with LPS prevented ??m from falling significantly. LPS inhibited Hypoxia/SD-induced Cyc-c release. These results were consistent with the total analysis of apoptosis of MSCs. Compared with the control group, the level of CX43 expression in the Hypoxia/SD group and LPS + Hypoxia/SD group decreased significantly at each time point. The level of CX43 expression in the Hypoxia/SD group was lower than that in the LPS + Hypoxia/SD group, while the difference was not significant between the PD98059 + LPS + Hypoxia/SD group and the PD98059 + Hypoxia/SD group (P > 0.05). Compared with the LPS + Hypoxia/SD group, CX43 level in the PD98059 + LPS + Hypoxia/SD group and PD98059 + Hypoxia/SD group decreased significantly (P < 0.05). These results demonstrated that Hypoxia/SD conditions could induce apoptosis of bMSCs markedly. Low-dose LPS preconditioning may preserve the mitochondrial function by maintaining the mitochondrial transmembrane potential and inhibiting Cyc-c release in Hypoxia/SD-induced bMSCs apoptosis. LPS preconditioning also had a stabilizing effect on the cell membrane by inhibiting the decrease of CX43, and this modulating mechanism may be related to the ERK signaling pathway. PMID:23712704

Wang, Jun; Li, Zhi; Zhang, Yangyang; Liu, Xiang; Chen, Liang; Chen, Yijiang



40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.  

Code of Federal Regulations, 2010 CFR

...preconditioning; refueling test. 86.153-98...HIGHWAY VEHICLES AND ENGINES Emission...Heavy-Duty Vehicles; Test Procedures ...(b) Seal test. The...Non-integrated system seal testing shall...exhaust emission test. The Administrator...seconds after the engine starts,...



40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.  

Code of Federal Regulations, 2010 CFR

...preconditioning; refueling test. 86.153-98...HIGHWAY VEHICLES AND ENGINES Emission...Heavy-Duty Vehicles; Test Procedures ...(b) Seal test. The...Non-integrated system seal testing shall...exhaust emission test. The Administrator...seconds after the engine starts,...



Preconditioning patellar tendon autografts in arthroscopic anterior cruciate ligament reconstruction: a prospective randomized study.  


This prospective randomized evaluated the effect of preconditioning patellar tendon autografts before implantation and fixation during anterior cruciate ligament (ACL) reconstruction. Fifty-three patients with a unilateral ACL rupture were included in the study. One group of patients had their patellar tendon autograft preconditioned by passive stretching at a constant load of 39 N for 10 min immediately prior to implantation (group P). The other group underwent no preconditioning before the implantation of the graft (group NP). The follow-up examination was performed by independent observers after 26 months (23-29) in group P and after 25 months (23-30) in group NP (n.s.). At follow-up the KT-1000 laxity test revealed a total side-to-side difference of 2.5 mm (-1.5 to +8.5) in group P and 3.0 mm (-7 to +6.5) in group NP (n.s.). The Lysholm score was 86 points (47-100) in group P and 94 points (44-100) in group NP (n.s.). The Tegner activity level was 6 (2-9) in group P and 7 (3-9) in group NP (n.s.). There was no significant difference between the study groups regarding IKDC classification. Patients who underwent ACL reconstruction using a preconditioned patellar tendon autograft had no advantages in terms of restoration of laxity or clinical outcome at 2-year follow-up. PMID:11269585

Ejerhed, L; Kartus, J; Köhler, K; Sernert, N; Brandsson, S; Karlsson, J



Signal Transduction Mechanisms Involved in Ischemic Preconditioning in the Rat Retina in vivo  

Microsoft Academic Search

Ischemic preconditioning (IPC) protects the rat retina against the injury that ordinarily follows severe ischemia. We showed previously that release of adenosine and de novo protein synthesis were required for IPC protection. The mechanisms of IPC were studied in the rat retina by examining the signal transduction mediators responsible, in particular, those theorized to be downstream of adenosine receptors. In

Bing Li; Christopher Yang; Daniel M Rosenbaum; Steven Roth



Myocardial Ischemic Preconditioning in Rodents Is Dependent on Poly (ADP-ribose) Synthetase  

Microsoft Academic Search

Background: Activation of the nuclear enzyme poly (ADP-ribose) synthetase (PARS) in response to oxidant- mediated DNA injury has been shown to play an impor- tant role in the pathogenesis of reperfusion injury. Here we investigated the role of PARS in myocardial ischemic preconditioning (IPC). Materials and Methods: Mice with or without genetic disruption of PARS and rats in the absence

Lucas Liaudet; Zequan Yang; El-Bachir Al-Affar; CsabaSzabó



Attenuation of Ischemic Brain Edema and Cerebrovascular Injury After Ischemic Preconditioning in the Rat  

Microsoft Academic Search

Ischemic preconditioning (IPC) induces neuroprotection to subsequent severe ischemia, but its effect on the cerebrovasculature has not been studied extensively. This study evaluated the effects of IPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebral ischemia in the rat. Transient (15 minute) middle cerebral artery occlusion (MCAO) was used for IPC. Three days after

Tetsuya Masada; Ya Hua; Guohua Xi; Steven R Ennis; Richard F Keep



Does protein kinase C play a pivotal role in the mechanisms of ischemic preconditioning?  


This communication reviews the evidence for the pivotal role of protein kinase C in ischemic myocardial preconditioning. It is believed that several intracellular signalling pathways via receptor-coupled phospholipase C and its "cross-talk" with phospholipase D converge to activation of protein kinase C isotypes which is followed by phosphorylation of until now (a number of) unknown target proteins which produce the protective state of ischemic preconditioning. After briefly introducing the general biochemical properties of protein kinase C, its isotypes and the limitations of the methodology used to investigate the role of protein kinase C, studies are discussed in which pharmacological inhibition and activation and (immunore) activity and/or isotypes measurements of protein kinase C isotypes were applied to assess the role of activation of protein kinase C in ischemic myocardial preconditioning. It is concluded that definitive proof for the involvement of protein kinase C in preconditioning requires future studies which must focus on the isotype(s) of protein kinase C that are activated, the duration of action, cellular translocation sites and the identity and stability (of covalently bound phosphate) of phosphorylated substrate proteins. PMID:9110122

Gho, B C; Eskildsen-Helmond, Y E; de Zeeuw, S; Lamers, J M; Verdouw, P D



Hierarchical Two-level Preconditioning of MLFMA Algorithm for Electromagnetic Wave Scattering Problems  

Microsoft Academic Search

A set of higher order hierarchical basis functions is proposed for expansion of the current in electrical field integral equations (EFIE) solved by multilevel fast multipole algorithm (MLFMA). The hierarchical two-level spectral preconditioning technique is developed to solve EFIE in radar cross section (RCS) calculations. This newly constructed hierarchical two-level spectral preconditioner is used to speed up the restarted GMRES

S. S. Li; Y. Yang; R. S. Chen; T. Ke



Benign focal ischemic preconditioning induces neuronal Hsp70 and prolonged astrogliosis with expression of Hsp27  

Microsoft Academic Search

We have established a focal preconditioning (PC) paradigm that produces significant and prolonged ischemic tolerance (IT) of the brain to subsequent permanent middle cerebral artery occlusion (MCAO). PC using 10 min of MCAO induces brain tolerance at 1–7 days of reperfusion that requires active protein synthesis. The protective protein(s) involved are unknown. In these studies the increased transcription and translation

R. William Currie; Julie A Ellison; Ray F White; Giora Z Feuerstein; Xinkang Wang; Frank C Barone



Enhanced cell volume regulation: a key protective mechanism of ischemic preconditioning in rabbit ventricular myocytes  

Microsoft Academic Search

Accumulation of osmotically active metabolites, which create an osmotic gradient estimated at ~60 mOsM, and cell swelling are prominent features of ischemic myocardial cell death. This study tests the hypothesis that reduction of ischemic swelling by enhanced cell volume regulation is a key mechanism in the delay of ischemic myocardial cell death by ischemic preconditioning (IPC). Experimental protocols address whether: (i)

Michelle Batthish



Efficient Large-eddy Simulations of Low Mach Number Flows Using Preconditioning and Multigrid  

Microsoft Academic Search

In the present paper, an implicit time accurate approach combined with multigrid, preconditioning and residual smoothing is used for the large-eddy simulation (LES) of low Mach number flow. In general, due to the restriction imposed on the time step by the physics of the flow, the advantage of an implicit method over an explicit one for LES is not obvious.

Bamdad Lessani; Jan Ramboer; Chris Lacor



Thermal preconditioning of coal\\/water mixtures for gas turbine applications  

Microsoft Academic Search

Thermal preconditioning of coal\\/water mixtures (CWM) is a process proposed for use with stationary gas turbine engines. The CWM is heated before delivery to the combustor to vaporize the water and to pyrolyze and devolatilize the coal prior to injection. The process offers a number of potential advantages. Engines can be started without the use of an auxiliary fuel system,

G. Roffe; G. Miller



Pharmacological induction of ischemic tolerance in hippocampal slices by sarcosine preconditioning.  


Brain ischemic tolerance is a protective mechanism induced by a preconditioning stimulus, which prepare the tissue against harmful insults. Preconditioning with N-methyl-d-aspartate (NMDA) agonists induces brain tolerance and protects it against glutamate excitotoxicity. Recently, the glycine transporters type 1 (GlyT-1) have been shown to potentiate glutamate neurotransmission through NMDA receptors suggesting an alternative strategy to protect against glutamate excitotoxicity. Here, we evaluated the preconditioning effect of sarcosine pre-treatment, a GlyT-1 inhibitor, in rat hippocampal slices exposed to ischemic insult. Sarcosine (300 mg/kg per day, i.p.) was administered during seven consecutive days before induction of ischemia in hippocampus by oxygen/glucose deprivation (OGD). To access the damage caused by an ischemic insult, we evaluated cells viability, glutamate release, nitric oxide (NO) production, lactate dehydrogenase (LDH) levels, production of reactive oxygen species (ROS), and antioxidant enzymes as well as the impact of oxidative stress in the tissue. We observed that sarcosine reduced cell death in hippocampus submitted to OGD, which was confirmed by reduction on LDH levels in the supernatant. Cell death, glutamate release, LDH levels and NO production were reduced in sarcosine hippocampal slices submitted to OGD when compared to OGD controls (without sarcosine). ROS production was reduced in sarcosine hippocampal slices exposed to OGD, although no changes were found in antioxidant enzymes activities. This study demonstrates that preconditioning with sarcosine induces ischemic tolerance in rat hippocampal slices submitted to OGD. PMID:22750492

Pinto, Mauro Cunha Xavier; Mourão, Flávio Afonso Gonçalves; Binda, Nancy Scardua; Leite, Hércules Ribeiro; Gomez, Marcus Vinícius; Massensini, Andre Ricardo; Gomez, Renato Santiago



Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioningB  

Microsoft Academic Search

Objective: Connexin 43 (Cx43) is involved in infarct size reduction by ischemic preconditioning (IP); the underlying mechanism of protection, however, is unknown. Since mitochondria have been proposed to be involved in IP's protection, the present study analyzed whether Cx43 is localized at mitochondria of cardiomyocytes and whether such localization is affected by IP. Methods and results: Western blot analysis on

Kerstin Boengler; Giuliano Dodoni; Antonio Rodriguez-Sinovas; Alberto Cabestrero; Marisol Ruiz-Meana; Petra Gres; Ina Konietzka; Carmen Lopez-Iglesias; David Garcia-Dorado; Gerd Heusch; Rainer Schulz


Role of Inducible Nitric Oxide Synthase in Pharmacological “Preconditioning” with Monophosphoryl Lipid A  

Microsoft Academic Search

Pretreatment with monophosphoryl lipid A (MLA) can pharmacologically mimic the second window of ischemic preconditioning (SWOP) to protect the heart from prolonged ischemia and reperfusion injury. Based on the delayed time course for development of MLA associated cardioprotection, this study was designed to test if MLA's cardioprotective effect is mediated by signalling through production of inducible nitric oxide synthase (iNOS),

Lin Zhao; Patricia A. Weber; Jerry R. Smith; Malissa L. Comerford; Gary T. Elliott



How to Heat Up From the Cold: Examining the Preconditions for (Unconscious) Mood Effects  

Microsoft Academic Search

What are the necessary preconditions to make people feel good or bad? In this research, the authors aimed to uncover the bare essentials of mood induction. Several induction techniques exist, and most of these techniques demand a relatively high amount of cognitive capacity. Moreover, to be effective, most techniques require conscious awareness. The authors proposed that the common and defining

Kirsten I. Ruys; Diederik A. Stapel



Protein Kinase C- ? is Responsible for the Protection of Preconditioning in Rabbit Cardiomyocytes  

Microsoft Academic Search

The role of protein kinase C (PKC) in the protection of ischemic preconditioning (PC) is still controversial, partly because of the multiple isozymes of PKC and the inability to directly measure PKC activity in vivo. In this study we have used novel peptide inhibitors which correspond to part of the amino acid sequence from the isozyme-specific RACK-binding site on the

Guang S. Liu; Michael V. Cohen; Daria Mochly-Rosen; James M. Downey



No Involvement of Endogenous Nitric Oxide In Classical Ischemic Preconditioning in Swine  

Microsoft Academic Search

Endogenous nitric oxide (NO) is involved in the protection by classical ischemic preconditioning (IP) against ischemia-induced arrhythmias in anesthetized dogs. Furthermore, NO triggers and mediates protection against infarction and stunning in delayed IP in conscious rabbits. Up to now it is unclear whether or not endogenous NO is also involved in the protection against infarction by classical IP in vivo.

Heiner Post; Rainer Schulz; Matthias Behrends; Petra Gres; Christian Umschlag; Gerd Heusch



A class of explicit preconditioned conjugate gradient methods for solving large finite element systems  

Microsoft Academic Search

A class of Explicit Preconditioned Conjugate Gradient (EPCG) methods for solving large sparse linear systems of algebraic equations resulting from the Finite Element discretization of Elliptic and Parabolic PDE's is introduced. The EPCG methods are based on explicit Approximate Inverse Matrix techniques and are particularly suitable for solving numerically initial\\/boundary-value problems on multiprocessor systems. The application of the new methods

Elias A. Lipitakis; George A. Gravvanis



40 CFR 86.153-98 - Vehicle and canister preconditioning; refueling test.  

Code of Federal Regulations, 2013 CFR

...2013-07-01 2013-07-01 false Vehicle and canister preconditioning; refueling...EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Emission Regulations for 1977 and Later Model Year New Light-Duty Vehicles and New Light-Duty Trucks and New...



Nitroglycerin Induces Late Preconditioning Against Myocardial Infarction in Conscious Rabbits Despite Development of Nitrate Tolerance  

Microsoft Academic Search

Background—Recent studies suggest that the late phase of ischemic preconditioning (PC) can be mimicked by pretreatment with NO donors. The ability of clinically relevant NO donors to induce PC against infarction, however, has not been evaluated. Furthermore, it is unknown whether tolerance to the hemodynamic actions of nitrates also extends to their PC effects. Methods and Results—Conscious rabbits underwent a

Michael Hill; Hitoshi Takano; Xian-Liang Tang; Eitaro Kodani; Gregg Shirk; Roberto Bolli



Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart.  


Both preclinical and clinical studies suggest that brief cycles of ischemia and reperfusion in the arm or leg may protect the heart against injury following prolonged coronary artery occlusion and reperfusion, a phenomenon known as remote ischemic preconditioning. Recent studies in mice indicate that increased plasma interleukin-10 (IL-10) levels play an important role in remote ischemic preconditioning induced by clamping the femoral artery for 5 min followed by 5 min of reperfusion for a total of three cycles. In this study, we demonstrate that remote ischemic preconditioning increases plasma IL-10 levels and decreases myocardial infarct size in wild-type mice but not in littermates that are heterozygous for a knockout allele at the locus encoding hypoxia-inducible factor (HIF) 1?. Injection of a recombinant adenovirus encoding a constitutively active form of HIF-1? into mouse hind limb muscle was sufficient to increase plasma IL-10 levels and decrease myocardial infarct size. Exposure of C2C12 mouse myocytes to cyclic hypoxia and reoxygenation rapidly increased levels of IL-10 mRNA, which was blocked by administration of the HIF-1 inhibitor acriflavine or by expression of short hairpin RNA targeting HIF-1? or HIF-1?. Chromatin immunoprecipitation assays demonstrated that binding of HIF-1 to the Il10 gene was induced when myocytes were subjected to cyclic hypoxia and reoxygenation. Taken together, these data indicate that HIF-1 activates Il10 gene transcription and is required for remote ischemic preconditioning. PMID:24101519

Cai, Zheqing; Luo, Weibo; Zhan, Huiwang; Semenza, Gregg L



Preconditioned pseudo-compressibility methods for incompressible Navier-Stokes equations  

NASA Astrophysics Data System (ADS)

This paper investigates the pseudo-compressibility method for the incompressible Navier-Stokes equations and the preconditioning technique for accelerating the time marching for stiff hyperbolic equations, and derives and presents the eigenvalues and eigenvectors of the Jacobian matrix of the preconditioned pseudo-compressible Navier-Stokes equations in generally cur-vilinear coordinates. Based on the finite difference discretization the cored for efficiently solving incompressible flows numerically is established. The reliability of the procedures is demonstrated by the application to the inviscid flow past a circular cylinder, the laminar flow over a flat plate, and steady low Reynolds number viscous incompressible flows past a circular cylinder. It is found that the solutions to the present algorithm are in good agreement with the exact solutions or experimental data. The effects of the pseudo-compressibility factor and the parameter brought by preconditioning in convergence characteristics of the solution are investigated systematically. The results show that the upwind Roe’s scheme is superior to the second order central scheme, that the convergence rate of the pseudo-compressibility method can be effectively improved by preconditioning and that the self-adaptive pseudo-compressibility factor can modify the numerical convergence rate significantly compared to the constant form, without doing artificial tuning depending on the specific flow conditions. Further validation is also performed by numerical simulations of unsteady low Reynolds number viscous incompressible flows past a circular cylinder. The results are also found in good agreement with the existing numerical results or experimental data.

Qian, Zhansen; Zhang, Jingbai; Li, Chunxuan



Changes in Eucalyptus camaldulensis essential oil composition as response to drought preconditioning  

Microsoft Academic Search

Water deficit, a common constraint in forestry, is the main cause of plant stress during plantation. The survival and growth of seedlings is also compromised by herbivory during establishment. The potential of nursery preconditioning to enhance survival chances of future trees by reducing palatability or attracting beneficial insects as a result of changes in chemical defences may be an answer

Silvia R. Leicach; Ana M. Garau; Ana B. Guarnaschelli; Margarita A. Yaber Grass; Norberto D. Sztarker; Analia Dato



Toward a Sustainable FTAA: Does Latin America Meet the Necessary Financial Preconditions?  

Microsoft Academic Search

This paper focuses on identifying preconditions that will ensure the sustainability of a Free Trade Area of the Americas (FTAA). It argues that the macro, micro, and political conditions advanced in the literature to measure a country's ability to compete internationally, while necessary, are not sufficient to ensure the success and permanence of a free trade agreement. Instead, two additional

Liliana Rojas-Suarez



Towards a Sustainable FTAA: DOes Latin America Meet the Necessary Financial Preconditions?  

Microsoft Academic Search

This paper focuses on identifying preconditions that will ensure the sustainability of a Free Trade Area of the Americas (FTAA). It argues that the macro, micro, and political conditions advanced in the literature to measure a country's ability to compete internationally, while necessary, are not sufficient to ensure the success and permanence of a free trade agreement. Instead, two additional

Liliana Rojas-Suarez



Isoform-Specific Membrane Translocation of Protein Kinase C After Ischemic Preconditioning  

Microsoft Academic Search

Mild cerebral anoxic\\/ischemic\\/stress insults promote ‘tolerance’ and thereby protect the brain from subsequent ‘lethal’ anoxic\\/ischemic insults. We examined whether specific activation of PKC a, d, ?, or ? isoforms is associated with ischemic preconditioning (IPC) in rat brain. IPC was produced by a 2-minute global cerebral ischemia. Membrane and cytosolic fractions of the hippocampi were immunoblotted using specific antibodies for

Kaisa Kurkinen; Raul Busto; Gundars Goldsteins; Jari Koistinaho; Miguel A. Pérez-Pinzón



Sarcolemmal Versus Mitochondrial ATP-Sensitive K1 Channels and Myocardial Preconditioning  

Microsoft Academic Search

Ischemic preconditioning (IPC) is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the heart against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of stunning, or incidence of cardiac arrhythmias. Although a number of substances and signaling pathways have been proposed to

Garrett J. Gross; Ryan M. Fryer



Ischemic preconditioning reduces the severity of ischemia\\/reperfusion-induced pancreatitis  

Microsoft Academic Search

In various organs, including heart, kidneys, brain, liver and stomach, preconditioning by brief exposure to ischemia protects the organ against damage evoked by subsequent severe ischemia. This study has been undertaken to check whether two brief ischemic periods protect the pancreas against severe ischemia\\/reperfusion-induced pancreatitis and, if so, what is the role of sensory and vagal nerves in this phenomenon.

Artur Dembi?ski; Zygmunt Warzecha; Piotr Ceranowicz; Romana Tomaszewska; Marcin Dembi?ski; Ma Pabia?czyk; Jerzy Stachura; Stanis Konturek



Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbitq  

Microsoft Academic Search

Objective: Brain death (BD) abolishes the infarct-limiting effect of ischemic preconditioning (IP) in rabbits. We wished to define the role of the norepinephrine storm in this observation. Methods: Rabbits were randomized into six groups of ten animals each. In control group (CTRL), anaesthetized rabbits were subjected to 30 min left coronary marginal branch occlusion and 90 min reperfusion. In CTRL

Fadi Farhat; Daniel Loisance; Jean-Pierre Garnier; Matthias Kirsch


Norepinephrine release after acute brain death abolishes the cardioprotective effects of ischemic preconditioning in rabbit  

Microsoft Academic Search

Objective: Brain death (BD) abolishes the infarct-limiting effect of ischemic preconditioning (IP) in rabbits. We wished to define the role of the norepinephrine storm in this observation. Methods: Rabbits were randomized into six groups of ten animals each. In control group (CTRL), anaesthetized rabbits were subjected to 30 min left coronary marginal branch occlusion and 90 min reperfusion. In CTRL+IP

Fadi Farhat; Daniel Loisance; Jean-Pierre Garnier; Matthias Kirsch



Thermal preconditioning protects rat cardiac muscle cells from doxorubicin-induced apoptosis  

Microsoft Academic Search

Doxorubicin (DOX=adriamycine), an effective chemotherapeutic agents for cancers, has severe cardiotoxicity. In the paresent study, we examined the protective effect of thermal preconditioning (TP) against apoptosis of rat cardiac muscle cells induced by DOX. Treatment with DOX (10 ?M) for 24 hrs resulted in apoptosis of cardiac muscle cells, which was evaluated by examining “DNA ladder” formation and TUNEL staining.

Hiroshi Ito; Takashi Shimojo; Hiroyuki Fujisaki; Mimi Tamamori; Shigeru Ishiyama; Susumu Adachi; Shinji Abe; Fumiaki Marumo; Michiaki Hiroe



An anisotropic preconditioning for the Wilson fermion matrix on the lattice  

SciTech Connect

A preconditioning for the Wilson fermion matrix on the lattice is defined which is particularly suited to the case when the temporal lattice spacing is much smaller than the spatial one. Details on the implementation of the scheme are given. The method is tested in numerical studies of QCD on anisotropic lattices.

Balint Joo, Robert G. Edwards, Michael J. Peardon




Microsoft Academic Search

A fast solver method called the multigrid preconditioned conjugate gradient method is proposed for the mechanical analysis of heterogenous materials on the mesoscale. Even small samples of a heterogeneous material such as concrete show a complex geometry of different phases. These materials can be modeled by projection onto a uniform, orthogonal grid of el- ements. As one major problem the



Microsoft Academic Search

In the preconditioned iterative method based on nonoverlapping domain decompo- sitions, the preconditioner is usually of block diagonal type. To calculate its action on a residual vector, it is required to solve a linear system of algebraic equations with the coecient matrix being the Schur complement block corresponding to the interface. To reduce the computational cost, the Schur complement blocks


Preconditioning-induced cytoprotection in hepatocytes requires Ca 2+ -dependent exocytosis of lysosomes  

Microsoft Academic Search

A short period of hypoxia reduces the cytotoxicity produced by a subsequent prolonged hypoxia in isolated hepatocytes. This phenomenon, termed hypoxic preconditioning, is mediated by the activation of adenosine A2A-receptor and is associated with the attenuation of cellular acidosis and Na + overload normally occurring during hypoxia. Bafilomycin, an inhibitor of the vacuolar H + \\/ATPase, reverts the latter effects

Rita Carini; Roberta Castino; Maria Grazia De Cesaris; Roberta Splendore; Marina Démoz; Emanuele Albano; Ciro Isidoro; A. Avogadro



Ischemic preconditioning alters the epigenetic profile of the brain from ischemic intolerance to ischemic tolerance.  


Ischemic preconditioning is an innate neuroprotective mechanism in which a sub-injurious ischemic exposure increases the brain's ability to withstand a subsequent, normally injurious ischemic insult. Part of ischemic preconditioning neuroprotection stems from an epigenetic reprogramming of the brain to a phenotype of ischemic tolerance, which results in a gene expression profile different from that observed in the non-injured and ischemia-injured brains. Such neuroprotective reprograming, activated by ischemic preconditioning, requires specific changes in DNA accessibility coordinated with activation of transcriptional activator and repressor proteins, which allows for expression of specific neuroprotective proteins despite a general repression of gene expression. In this review we examine the effects of injurious ischemia and ischemic preconditioning on the regulation of DNA methylation, histone post-translational modifications, and non-coding RNA expression. There is increasing interest in the role of epigenetics in disease pathobiology, and whether and how pharmacological manipulation of epigenetic processes may allow for ischemic neuroprotection. Therefore, a better understanding of the epigenomic determinants underlying the modulation of gene expression that lead to ischemic tolerance or cell death offers the promise of novel neuroprotective therapies that target global reprograming of genomic activity versus individual cellular signaling pathways. PMID:23868468

Thompson, John W; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A



Preconditioning multichannel adaptive filtering algorithms using EVD- and SVD-based signal prewhitening and system decoupling  

NASA Astrophysics Data System (ADS)

It is well known that the convergence rate of multichannel LMS-based algorithms is limited by the correlation properties of the reference signals and the cross-coupling within the plant dynamics. These factors give rise to excessive eigenvalue spread and slow convergence rate of a gradient descent algorithm. A preconditioning technique is developed in this study for the multichannel LMS algorithm so as to improve its convergence rate. Signal prewhitening and system decoupling are the two key elements of the proposed techniques. Preconditioning filters are first formulated in the frequency domain by using eigenvalue decomposition and singular value decomposition. These filters are then transformed into the time domain with causality taken into account. The preconditioning filters are incorporated into a multichannel LMS algorithm, where the reference signals are prewhitened and the plants are decoupled prior to the adaptation process. Simulations for a two-channel/one listener cross-talk cancellation problem illustrate the effectiveness of the preconditioning technique in improving the convergence rate of the adaptive algorithms.

Bai, M. R.; Elliott, S. J.



Preconditioning multichannel adaptive filtering algorithms using EVD- and SVD-based signal prewhitening and system decoupling  

Microsoft Academic Search

It is well known that the convergence rate of multichannel LMS-based algorithms is limited by the correlation properties of the reference signals and the cross-coupling within the plant dynamics. These factors give rise to excessive eigenvalue spread and slow convergence rate of a gradient descent algorithm. A preconditioning technique is developed in this study for the multichannel LMS algorithm so

M. R. Bai; S. J. Elliott



Myocardial energy metabolism in ischemic preconditioning and cardioplegia: A metabolic control analysis  

Microsoft Academic Search

For both, cardioplegia (CP) and ischemic preconditioning (IP), increased ischemic tolerance with reduction in infarct size is well documented. These cardioprotective effects are related to a limitation of high energy phosphate (HEP) depletion. As CP and IP have to be assumed to act by different mechanisms, their effects on myocardial HEP metabolism cannot be assumed to be identical. Therefore, a

Achim M. Vogt; Albrecht Elsässer; Anja Pott-Beckert; Cordula Ackermann; Sven Y. Vetter; Murat Yildiz; Wolfgang Schoels; David A. Fell; Hugo A. Katus; Wolfgang Kübler



Preconditioning stimuli do not benefit the myocardium of hypoxia-tolerant rainbow trout ( Oncorhynchus mykiss)  

Microsoft Academic Search

In many vertebrates, a short episode of oxygen lack protects against myocardial necrosis during a subsequent, longer period of oxygen deprivation. This protective effect, termed preconditioning, also improves the functional recovery. Improved functional recovery has been reported for hypoxia-sensitive, in situ perfused rainbow trout hearts, but appears absent in another strain of rainbow trout that has a more hypoxia-tolerant heart.

Johannes Overgaard; Jonathan A. W. Stecyk; Hans Gesser; Tobias Wang; A. Kurt Gamperl; Anthony P. Farrell



Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties.  


Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia-ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress. PMID:21722095

Sen, Ellora; Basu, Anirban; Willing, Lisa B; Uliasz, Tracy F; Myrkalo, Jaimie L; Vannucci, Susan J; Hewett, Sandra J; Levison, Steven W



Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties  

PubMed Central

Hypoxic preconditioning reprogrammes the brain's response to subsequent H/I (hypoxia–ischaemia) injury by enhancing neuroprotective mechanisms. Given that astrocytes normally support neuronal survival and function, the purpose of the present study was to test the hypothesis that a hypoxic preconditioning stimulus would activate an adaptive astrocytic response. We analysed several functional parameters 24 h after exposing rat pups to 3 h of systemic hypoxia (8% O2). Hypoxia increased neocortical astrocyte maturation as evidenced by the loss of GFAP (glial fibrillary acidic protein)-positive cells with radial morphologies and the acquisition of multipolar GFAP-positive cells. Interestingly, many of these astrocytes had nuclear S100B. Accompanying their differentiation, there was increased expression of GFAP, GS (glutamine synthetase), EAAT-1 (excitatory amino acid transporter-1; also known as GLAST), MCT-1 (monocarboxylate transporter-1) and ceruloplasmin. A subsequent H/I insult did not result in any further astrocyte activation. Some responses were cell autonomous, as levels of GS and MCT-1 increased subsequent to hypoxia in cultured forebrain astrocytes. In contrast, the expression of GFAP, GLAST and ceruloplasmin remained unaltered. Additional experiments utilized astrocytes exposed to exogenous dbcAMP (dibutyryl-cAMP), which mimicked several aspects of the preconditioning response, to determine whether activated astrocytes could protect neurons from subsequent excitotoxic injury. dbcAMP treatment increased GS and glutamate transporter expression and function, and as hypothesized, protected neurons from glutamate excitotoxicity. Taken altogether, these results indicate that a preconditioning stimulus causes the precocious differentiation of astrocytes and increases the acquisition of multiple astrocytic functions that will contribute to the neuroprotection conferred by a sublethal preconditioning stress.

Sen, Ellora; Basu, Anirban; Willing, Lisa B; Uliasz, Tracy F; Myrkalo, Jaimie L; Vannucci, Susan J; Hewett, Sandra J; Levison, Steven W



Protection of rat renal vitamin E levels by ischemic-preconditioning  

PubMed Central

Background During renal transplantation, the kidney remains without blood flow for a period of time. The following reperfusion of this ischemic kidney causes functional and structural injury. Formation of oxygen-derived free radicals (OFR) and subsequent lipid peroxidation (LP) has been implicated as the causative factors of these injuries. Vitamin E is known to be the main endogenous antioxidant that stabilizes cell membranes by interfering with LP. The present study was designed to examine the role of ischemic-preconditioning (repeated brief periods of ischemia, IPC) in prevention of renal injury caused by ischemia-reperfusion (IR) in rats. Methods IPC included sequential clamping of the right renal artery for 5 min and release of the clamp for another 5 min for a 3 cycles. IR was induced by 30 min ischemia followed by 10 min reperfusion. Four groups of male rats were used: Control, IPC, IR and IPC-IR. Vitamin E, an endogenous antioxidant and as an index of LP, was measured by HPLC and UV detection in renal venous plasma and tissue. Renal function was assessed by serum creatinine and BUN levels. Renal damage was assessed in sections stained with Haematoxylin and Eosin. Results In the IR group, there was a significant decrease in vitamin E in plasma and tissue compared to a control group (p,0.05). In the IPC-IR group, vitamin E concentration was significantly higher than in the IR group (p,0.01). The results showed that 30 min ischemia in the IR group significantly (p,0.05) reduced renal function demonstrated by an increase in serum creatinine levels as compared with the control group. These results in the IPC group also showed a significant difference with the IR group but no significant difference in serum BUN and creatinine between IR and IPC-IR group were detected. Histological evaluation showed no structural damage in the IPC group and an improvement in the IPC-IR group compared to IR alone. Conclusions In this study, IPC preserved vitamin E levels, but it could not markedly improve renal function in the early phase (1–2 h) of reperfusion. IPC may be a useful method for antioxidant preservation in organ transplantation.

Kadkhodaee, Mehri; Aryamanesh, Simin; Faghihi, Mahdieh; Zahmatkesh, Maryam



The in vitro preconditioning of myoblasts to enhance subsequent survival in an in vivo tissue engineering chamber model.  


The effects of in vitro preconditioning protocols on the ultimate survival of myoblasts implanted in an in vivo tissue engineering chamber were examined. In vitro testing: L6 myoblasts were preconditioned by heat (42 °C; 1.5 h); hypoxia (<8% O(2); 1.5 h); or nitric oxide donors: S-nitroso-N-acetylpenicillamine (SNAP, 200 ?M, 1.5 h) or 1-[N-(2-aminoethyl)-N-(2-aminoethyl)amino]-diazen-1-ium-1,2-diolate (DETA-NONOate, 500 ?M, 7 h). Following a rest phase preconditioned cells were exposed to 24 h hypoxia, and demonstrated minimal overall cell loss, whilst controls (not preconditioned, but exposed to 24 h hypoxia) demonstrated a 44% cell loss. Phosphoimmunoblot analysis of pro-survival signaling pathways revealed significant activation of serine threonine kinase Akt with DETA-NONOate (p < 0.01) and heat preconditioning (p < 0.05). DETA-NONOate also activated ERK 1/2 signaling (p < 0.05). In vivo implantation: 100,000 preconditioned (heat, hypoxia, or DETA-NONOate) myoblasts were implanted in SCID mouse tissue engineering chambers. 100,000 (not preconditioned) myoblasts were implanted in control chambers. At 3 weeks, morphometric assessment of surviving myoblasts indicated myoblast percent volume (p = 0.012) and myoblasts/mm(2) (p = 0.0005) overall significantly increased in preconditioned myoblast chambers compared to control, with DETA-NONOate-preconditioned myoblasts demonstrating the greatest increase in survival (p = 0.007 and p = 0.001 respectively). DETA-NONOate therefore has potential therapeutic benefits to significantly improve survival of transplanted cells. PMID:22369961

Tilkorn, Daniel J; Davies, E Michele; Keramidaris, Effie; Dingle, Aaron M; Gerrand, Yi-Wen; Taylor, Caroline J; Han, Xiao Lian; Palmer, Jason A; Penington, Anthony J; Mitchell, Christina A; Morrison, Wayne A; Dusting, Gregory J; Mitchell, Geraldine M



Postischemic temperature as a modulator of the stress response in brain: dissociation of heat shock protein 72 induction from ischemic tolerance after bilateral carotid artery occlusion in the gerbil  

Microsoft Academic Search

Brief ischemia induces tolerance to subsequent more severe insults, and induction of the 70 kDa heat shock\\/stress protein, hsp72, has been suggested to play a role. This study tested the requirement for hsp72 expression in a gerbil tolerance model in which postischemic temperature was varied to modulate the level of hsp72 induction. Gerbils were subjected to 2 min bilateral common

Hiroshi Abe; Thaddeus S Nowak Jr



Isoflurane preconditioning protects neurons from male and female mice against oxygen and glucose deprivation and is modulated by estradiol only in neurons from female mice  

PubMed Central

The volatile anesthetic, isoflurane, can protect the brain if administered before an insult such as an ischemic stroke. However, this protective “preconditioning” response to isoflurane is specific to males, with females showing an increase in brain damage following isoflurane preconditioning and subsequent focal cerebral ischemia. Innate cell sex is emerging as an important player in neuronal cell death but its role in the sexually dimorphic response to isoflurane preconditioning has not been investigated. We used an in vitro model of isoflurane preconditioning and ischemia (oxygen and glucose deprivation, OGD) to test the hypotheses that innate cell sex dictates the response to isoflurane preconditioning and that 17?-estradiol attenuates any protective effect from isoflurane preconditioning in neurons via nuclear estrogen receptors. Sex-segregated neuron cultures derived from postnatal day 0 to 1 mice were exposed to either 0% or 3% isoflurane preconditioning for 1 hour. In separate experiments, 17?-estradiol and the non-selective estrogen receptor antagonist ICI 182,780 were added 24 hours before preconditioning and then removed at the end of the preconditioning period. Twenty-three hours after preconditioning, all cultures underwent 2 hours of OGD. Twenty-four hours following OGD, cell viability was quantified using calcein-AM fluorescence. We observed that isoflurane preconditioning increased cell survival following subsequent OGD regardless of innate cell sex, but that the presence of 17?-estradiol before and during isoflurane preconditioning attenuated this protection only in female neurons independent of nuclear estrogen receptors. We also found that independent of preconditioning treatment, female neurons were less sensitive to OGD compared to male neurons and that transient treatment with 17?-estradiol protected both male and female neurons from subsequent OGD. More studies are needed to determine how cell type, cell sex and sex steroids like 17?-estradiol may impact on anesthetic preconditioning and subsequent ischemic outcomes in the brain.

Johnsen, Dustin; Murphy, Stephanie J.



Vertical Cells Driven by Vortices - A Possible Mechanism for the Preconditioning of Open-Ocean Deep Convection.  

National Technical Information Service (NTIS)

The occurrence of open-ocean deep convection requires a background cyclonic circulation and a preconditioning. Both conditions reduce the stratification of the water column within the cyclonic gyre, which will then become eligible for convection if the su...

P. C. Chu



Bilateral common carotid artery occlusion as an adequate preconditioning stimulus to induce early ischemic tolerance to focal cerebral ischemia.  


There is accumulating evidence, that ischemic preconditioning - a non-damaging ischemic challenge to the brain - confers a transient protection to a subsequent damaging ischemic insult. We have established bilateral common carotid artery occlusion as a preconditioning stimulus to induce early ischemic tolerance to transient focal cerebral ischemia in C57Bl6/J mice. In this video, we will demonstrate the methodology used for this study. PMID:23685461

Speetzen, Lukas Julius; Endres, Matthias; Kunz, Alexander



The p38 MAPK inhibitor, SB203580, abrogates ischaemic preconditioning in rat heart but timing of administration is critical  

Microsoft Academic Search

There is debate concerning the involvement of p38 mitogen activated protein kinase (MAPK) in the mediation of ischaemic preconditioning.\\u000a Pharmacological inhibition of p38 MAPK with SB203580 has been reported to block preconditioning in some studies but not in\\u000a others. We hypothesised that this divergence could be due to differences in the timing of inhibitor administration. Isolated\\u000a rat hearts were perfused

Mihaela M. Mocanu; Gary F. Baxter; Yuankun Yue; Stuart D. Critz; Derek M. Yellon



PI3 Kinase and not p42\\/p44 Appears to be Implicated in the Protection Conferred by Ischemic Preconditioning  

Microsoft Academic Search

M. M. Mocanu, R. M. Bell and D. M. Yellon. PI3 Kinase and not p42\\/p44 Appears to be Implicated in the Protection Conferred by Ischemic Preconditioning. Journal of Molecular and Cellular Cardiology (2002) 34, 661–668. Ischemic preconditioning results in an immediate phase of protection against lethal ischemia\\/reperfusion injury that is comprised of both irreversible necrosis and programmed cell death, apoptosis.

Mihaela M. Mocanu; Robert M. Bell; Derek M. Yellon



Dinitrophenol, cyclosporin A, and trimetazidine modulate preconditioning in the isolated rat heart: support for a mitochondrial role in cardioprotection  

Microsoft Academic Search

Background: Recent studies have postulated that mitochondrial ATP-sensitive potassium (mitoK ) channel activation may modulate ATP mitochondrial function with the resultant induction of a preconditioning phenotype in the heart. We hypothesized that the modulation of mitochondrial homeostasis might confer preconditioning-like cardioprotection. Methods: We used a model of regional ischemia in Langendorff-perfused isolated rat hearts. Short-term administration of 2,4-dinitrophenol (DNP), an

Jan Minners; Ewout J. van den Bos; Derek M. Yellon; Herzl Schwalb; Lionel H. Opie; Michael N. Sack


The Late Phase of Ischemic Preconditioning Is Abrogated by Targeted Disruption of the Inducible NO Synthase Gene  

Microsoft Academic Search

The goal of this study was to interrogate the role of inducible NO synthase (iNOS) in the late phase of ischemic preconditioning (PC) in vivo. A total of 321 mice were used. Wild-type mice preconditioned 24 h earlier with six cycles of 4-min coronary occlusion\\/4-min reperfusion exhibited a significant (P<0.05) increase in myocardial iNOS protein content, iNOS activity (assessed as

Yiru Guo; W. Keith Jones; Yu-Ting Xuan; Xian-Liang Tang; Weike Bao; Wen-Jian Wu; Hui Han; Victor E. Laubach; Peipei Ping; Zequan Yang; Yumin Qiu; Roberto Bolli



Ischemic Preconditioning Increases iNOS Transcript Levels in Conscious Rabbits via a Nitric Oxide-dependent Mechanism  

Microsoft Academic Search

Recent studies implicate iNOS as the mediator of the late phase of ischemic preconditioning (PC). However, it is unknown whether induction of iNOS activity is mediated by transcriptional, post-transcriptional, translational, or post-translational mechanisms. To address this issue, we isolated and sequenced a partial iNOS cDNA expressed in preconditioned rabbit myocardium. Using a rabbit-specific probe generated from this sequence, we measured

W. Keith Jones; Michael P. Flaherty; Xian-Liang Tang; Hitoshi Takano; Yumin Qiu; Supratim Banerjee; Traci Smith; Roberto Bolli



Preconditioning of the Euler and Navier-Stokes equations in low-velocity flow simulation on unstructured grids  

NASA Astrophysics Data System (ADS)

Low-velocity inviscid and viscous flows are simulated using the compressible Euler and Navier-Stokes equations with finite-volume discretizations on unstructured grids. Block preconditioning is used to speed up the convergence of the iterative process. The structure of the preconditioning matrix for schemes of various orders is discussed, and a method for taking into account boundary conditions is described. The capabilities of the approach are demonstrated by computing the low-velocity inviscid flow over an airfoil.

Volkov, K. N.



On Physics-Based Preconditioning of the Navier-Stokes Equations  

SciTech Connect

An new and more ecient all-speed flow algorithm is developed. The governing hy- drodynamic equations, in conservative form, are solved implicitly using Jacobian- free Newton-Krylov methods. To overcome numerical stiffness caused by the dis- parity between acoustic and advective modes, the governing hydrodynamic equa- tions are transformed to the primitive variable form in a preconditioning step. This transformation enables implicit treatment of distinct physics using traditional semi- implicit and physics-based splitting approaches without a loss of consistency be- tween the original and preconditioned systems. The resulting algorithm is capable of solving slow natural circulations (M ~ 10^-4) with signicant heat flux as well as the high-speed (M ~ 1) flows effciently by following dynamical time scales.

HyeongKae Park; Robert R. Nourgaliev; Richard C. Martineau; Dana A. Knoll



[Role of receptor transactivation in the cardioprotective effects of preconditioning and postconditioning].  


Analysis of published data indicates that the activity of receptors for adenosine, opioids, bradykinin, calcitonin-gene related peptides (CGRP) and epidermal growth factor (EGF) play important role in triggering the cardioprotective effects of ischemic preconditioning. Cannabinoids mimic the infarct-sparing effects of preconditioning. Endogenous adenosine, opioids, bradykinin and CGRP have also been implicated in infarct-reduction with ischemic postconditioning. Again, cannabinoids also mimic the protective effect of postconditioning. Recent works support heterodimerization of G-protein coupled receptors (GPCRs), and GPCR transactivation of EGF receptors. It was found that cross-talk between delta(j)-opioid receptors and adenosine A(1)-receptors is essential to cardiac protection. Furthermore, evidence implicates EGF receptor transactivation in cardioprotective effect of multiple GPCrs including adenosine, acetylcholine, bradykinin, and opioid receptors. Such findings support a convergent pathway in which multiple GPCRs may interact (or function independently) to transactivate EGF receptor-dependent kinase signaling and cytoprotection. PMID:22645939

Maslov, L N; Headrick, J P; Mechoulam, R; Krylatov, A V; Lishmanov, A Iu; Barzakh, E I; Naruzhnaia, N V; Zhang, Y



New insights into cardioprotection by ischemic preconditioning and other forms of stress.  


Ischemic preconditioning has not only received wide attention in heart research, but has also been a topic of extensive studies involving other organs. In several of these studies, it has been shown that in spite of differences in the endpoints used to assess protection, the same mediators as in myocardial ischemic preconditioning may be involved. However, several of the putative mediators do not require ischemia to become activated. This has guided us and others to investigate whether the myocardium can also be protected by brief ischemia in other organs and whether other non-pharmacological forms of stress, which do not produce ischemia but are capable of activating these potential mediators, are also cardioprotective. PMID:10415531

de Zeeuw, S; Van den Doel, M A; Duncker, D J; Verdouw, P D



Solving the eigenvalue equations of correlated vibrational structure methods: Preconditioning and targeting strategies  

NASA Astrophysics Data System (ADS)

Various preconditioners and eigenvector targeting strategies in combination with the Davidson and Olsen methods are presented for solving eigenvalue equations encountered in vibrational configuration interaction, its response generalization, and vibrational coupled cluster response theory. The targeting methods allow significant flexibility and robustness in computing selected vibrational states, which are particularly important in the often occurring but nontrivial cases of near degeneracies. We have investigated the effect of a mode-excitation level-based generally applicable preconditioning scheme aiming to improve the robustness of the more standard diagonal preconditioning method. Although increasing convergence rates may be achieved in general through a hierarchy of these preconditioners, the strategy is not always beneficial in terms of CPU time. Features of the methods are demonstrated in calculations of the overtone vibrational states of formaldehyde and the fundamental states of vinyl fluoride, vinyl chloride, vinyl bromide, and naphthalene.

Gy?Rffy, W.; Seidler, P.; Christiansen, O.



Preconditioning Strategies to Enhance Physical Performance on the Day of Competition.  


Sports Scientists and Strength & Conditioning professionals spend the majority of the competition season trying to ensure that their athletes training and recovery strategies are appropriate to ensure optimal performance on competition day. However, there is an additional window on the day of competition where performance can be acutely enhanced with a number of pre-conditioning strategies. These strategies include appropriately designed warm-up, passive heat maintenance, post-activation potentiation (PAP), remote ischemic pre-conditioning (RIPC), and more recently, prior exercise and hormonal priming. The aim of this review is to explore the potential practical use of these strategies and propose a theoretical timeline outlining how they may be incorporated into athlete's pre competition routine to enhance performance. For the purpose of this review we are going to confine the discussion to strategies that may enhance performance of short duration, high intensity sports (e.g. sprinting, jumping, throwing). PMID:23689163

Kilduff, Liam P; Finn, Charlotte V; Baker, Julien S; Cook, Christian J; West, Daniel J



Three-dimensional source reconstruction for bioluminescence tomography using the LSQR method with preconditioning  

NASA Astrophysics Data System (ADS)

As a novel optical molecular imaging modality, Bioluminescence Tomography (BLT) aims at quantitative reconstruction of the bioluminescent source distribution inside the biological tissue from the optical signals measured on the living animal surface, which is a highly ill-posed inverse problem. In this paper, with the finite element method solving the diffusion equation, an iterative regularization algorithm, referred to as least square QR-factorization (LSQR), is applied to the inverse problem in BLT. The affect of the preconditioning strategy on the LSQR method (PLSQR) for BLT is also investigated. The Simulations with a heterogeneous mouse chest phantom demonstrate that by incorporating a priori knowledge of the permissible source region, the LSQR method can reconstruct the source accurately and stably. Moreover, by employing preconditioning strategy, PLSQR outperforms LSQR in terms of source power density and convergence speed.

Yu, Jingjing; Liu, Fang; Jiao, Licheng; He, Xiaowei



Technological man-made disaster precondition phase model for major accidents  

Microsoft Academic Search

Major hazard organizations are dealing with hazardous material exceeding the threshold quantity. Major hazard organizations are relatively secure areas and cannot fail from single error. However, failure of an organization to control hazardous material usually results in a technological man-made disaster. The conditions preceding the onset of technological man-made disaster are collectively called the technological man-made disaster precondition phase “incubation

Ibrahim M. Shaluf; Fakharul-razi Ahmadun; Aini Mat Said; Sa’ari Mustapha; Rashid Sharif



A parallel nonlinear additive Schwarz preconditioned inexact Newton algorithm for incompressible Navier–Stokes equations  

Microsoft Academic Search

A nonlinear additive Schwarz preconditioned inexact Newton method (ASPIN) was introduced recently for solving large sparse highly nonlinear systems of equations obtained from the discretization of nonlinear partial differential equations. In this paper, we discuss some extensions of ASPIN for solving steady-state incompressible Navier–Stokes equations with high Reynolds numbers in the velocity–pressure formulation. The key idea of ASPIN is to

Feng-Nan Hwang; Xiao-Chuan Cai



Preconditioning by isoflurane as a volatile anesthetic in elective coronary artery bypass surgery  

PubMed Central

BACKGROUND Some pharmacological preconditioning approaches are utilized as an effective adjunct to myocardial protection, particularly following cardiac procedures. The current study addressed the potential clinical implications and protective effects of isoflurane as an anesthetic most applicable on postoperative myocardial function measured by cardiac biomarkers. METHODS 46 patients were included in the study. In 23 of them, preconditioning was elicited after the onset of cardiopulmonary bypass via a 5-minute exposure to isoflurane (2.5 minimum alveolar concentration), followed by a 10-minute washout before aortic cross clamping and cardioplegic arrest. 23 case-matched control patients underwent an equivalent period (15 minutes) of pre-arrest isoflurane-free bypass. Outcome measurements included creatine phosphokinase (CPK) and creatine kinase-MB (CK-MB) levels until 24 hours after the surgery. RESULTS None of the differences in enzyme levels at baseline and 24 hours after surgery between the two groups reached the threshold of statistical significance. The level of CPK was significantly reduced 24 hours after surgery compared with the baseline in the two groups. However, the postoperative release of CPK was consistently smaller in the isoflurane-preconditioned group than in the control group. The release of CK-MB displayed a statistically similar pattern. Multivariate linear regression analysis showed the effect of isoflurane regimen on reducing CPK level within the 24 hours after surgery compared with placebo. CONCLUSION Our study supports the cardio protective effect of isoflurane and the role of pharmacological preconditioning of the human heart by this volatile anesthetic during elective coronary artery bypass surgery.

Kiani, Amjad; Mirmohammad Sadeghi, Mohsen; Gharipour, Mojgan; Farahmand, Niloofar; Hoveida, Laleh



Induction of ischemic tolerance in rat cortical neurons by 3-nitropropionic acid: chemical preconditioning  

Microsoft Academic Search

Sublethal ischemia leads to increased tolerance against subsequent ischemia. We investigated whether tolerance could also be elicited by mild respiratory-chain inhibition (chemical hypoxia) in a rat neuronal-cell enriched culture system. 3-Nitropropionic acid (3-NPA) caused a concentration-dependent inhibition of succinate-dehydrogenase. Two hours preconditioning with 3-NPA 24–48 h before oxygen-glucose deprivation (OGD) reduced neuronal damage morphologically and reduced lactate deydrogenase (LDH) release

Markus Weih; Alexandra Bergk; Nikolaj K Isaev; Karsten Ruscher; Dirk Megow; Mathias Riepe; Andreas Meisel; IIya V Victorov; Ulrich Dirnagi



Ischemic Preconditioning in Pigs: A Graded Phenomenon Its Relation to Adenosine and Bradykinin  

Microsoft Academic Search

Background—A threshold concept for ischemic preconditioning (IPc) has been proposed. It is unclear, however, whether IPc, above a certain threshold, is an all-or-nothing or a graded phenomenon. Methods and Results—In 71 enflurane-anesthetized swine, severe left anterior descending coronary artery hypoperfusion for 90 minutes followed by 2 hours of reperfusion resulted in an infarct size (IS, by triphenyltetrazolium chloride) of 16.763.4%

Rainer Schulz; Heiner Post; Christian Vahlhaus; Gerd Heusch



Absence of robust ischemic preconditioning by five 1-minute total umbilical cord occlusions in fetal sheep  

Microsoft Academic Search

OBJECTIVE: To determine to what extent a series of five 1-minute total umbilical cord occlusions, intended to induce ischemic preconditioning (IP), affects the physiologic responses to a 10-minute total umbilical cord occlusion (damaging insult [DI]) 1 hour later and provides cardio- and neuroprotection. METHODS: In 14 chronically catheterized late gestation fetal sheep (127-131 days' gestation), we performed a 10-minute total

F. K. Lotgering; J. M. Bishai; P. C. Struijk; A. B. Blood; C. J. Hunter; K. C. Oberg; G. G. Power; L. D. Longo



Hyperbaric oxygen preconditioning promotes angiogenesis in rat liver after partial hepatectomy  

Microsoft Academic Search

Hyperbaric oxygen preconditioning (HBO-PC) increases the level of HIF-1? (hypoxia inducible factor-1?) and its target gene VEGF (vascular endothelial growth factor) which is involved in angiogenesis. Liver regeneration is an angiogenesis-dependent process. We hypothesized that HIF-1? and VEGF mediated the angiogenesis effect of HBO-PC on regenerating rat liver. Male Sprague Dawley rats received HBO-PC followed by 70% partial hepatectomy. Proliferation

Ping Ren; ZhiMing Kang; GuoJun Gu; Yun Liu; WeiGang Xu; HengYi Tao; John H. Zhang; XueJun Sun; Hui Ji



Multiple scattering among vias in planar waveguides using preconditioned SMCG method  

Microsoft Academic Search

Full-wave modeling for cylindrical vias in planar waveguides is formulated using Foldy-Lax multiple scattering equations. Recently, a sparse-matrix canonical-grid method based on fast Fourier transform and an iterative algorithm was proposed to solve a large-scale via problem. In this paper, we further improve computational efficiency by a preconditioning scheme based on the dominant information contained in the near field. We

Chung-Chi Huang; Leung Tsang; Chi Hou Chan; Kung-Hau Ding



Cardiac Remote Ischemic Preconditioning in Coronary Stenting (CRISP Stent) Study A Prospective, Randomized Control Trial  

Microsoft Academic Search

Background—Myocyte necrosis as a result of elective percutaneous coronary intervention (PCI) occurs in approximately one third of cases and is associated with subsequent cardiovascular events. This study assessed the ability of remote ischemic preconditioning (IPC) to attenuate cardiac troponin I (cTnI) release after elective PCI. Methods and Results—Two hundred forty-two consecutive patients undergoing elective PCI with undetectable prepro- cedural cTnI

Stephen P. Hoole; Patrick M. Heck; Linda Sharples; Sadia N. Khan; Rudolf Duehmke; Cameron G. Densem; Sarah C. Clarke; Leonard M. Shapiro; Peter M. Schofield; Michael O'Sullivan; David P. Dutka



Remote ischaemic preconditioning protects against cardiopulmonary bypass-induced tissue injury: a preclinical study  

Microsoft Academic Search

Objectives: To test the hypothesis that remote ischaemic preconditioning (rIPC) reduces injury after cardiopulmonary bypass (CPB).Design: Randomised study with an experimental model of CPB (3 h CPB with 2 h of cardioplegic arrest). Twelve 15 kg pigs were randomly assigned to control or rIPC before CPB and followed up for 6 h.Intervention: rIPC was induced by four 5 min cycles

R K Kharbanda; J Li; I E Konstantinov; M M H Cheung; P A White; H Frndova; J Stokoe; P Cox; M Vogel; G Van Arsdell; R MacAllister; A N Redington



Neuroprotection by Hypoxic Preconditioning Requires Sequential Activation of Vascular Endothelial Growth Factor Receptor and Akt  

Microsoft Academic Search

Hypoxic preconditioning provides protection against ischemic brain lesions in animal models of cerebral ischemia-hypoxia. To analyze the underlying molecular mechanisms, we developed an in vitro model of hypoxic neuroprotection in cerebellar gran- ule neurons (CGN) by reducing the oxygen tension to 1-5% for 1-24 hr. Exposure to 5% O2 for 9 hr resulted in reduction of cell death after potassium

Antje Wick; Wolfgang Wick; Johannes Waltenberger; Michael Weller; Johannes Dichgans; Jorg B. Schulz



Cross-talk between the survival kinases during early reperfusion: its contribution to ischemic preconditioning  

Microsoft Academic Search

Objectives: Recruitment of the survival kinase cascades, PI3K-Akt and Raf-MEK1\\/2-Erk1\\/2, at the time of reperfusion, following a lethal ischemic insult, may mediate the protection associated with ischemic preconditioning (IPC). The exact interplay between these two kinase cascades in mediating this effect is not clear. We examine the 'cross-talk' between these kinase cascades in their contribution to IPC- induced protection. Methods

Derek J. Hausenloy; Mihaela M. Mocanu; Derek M. Yellon



Iterative solution of panel method discretizations for potential flow problems. The modal multipolar preconditioning  

Microsoft Academic Search

The iterative solution of linear systems arising from panel method discretization of three-dimensional (3D) exterior potential problems coming mainly from aero-hydrodynamic engineering problems, is discussed. An original preconditioning based on an approximate eigenspace decomposition is proposed, which corrects bad conditioning arising from a pair of surfaces that are very close to each other, which is a very common situation in

J. D'Elía; M. Storti; S. Idelsohn



Navier-Stocks Computations of Wind-Turbine Airfoil using Low Mach Number Preconditioning  

Microsoft Academic Search

Wind turbine airfoil is numerical simulated by using the governing equations of compressible fluids in this paper. The Reynolds averaged Navier-Stokes computations are combined with low Mach preconditioning and implicit matrix-free lower-upper symmetric Gauss-Seidel (LUSGS) iteration on unstructured meshes, and the results are improved at the very low velocity speeds which are representative of the flow field around a wind

Wu Qing; Zhong Yicheng; Hu Jun; Yu Shaozhi



Finite element preconditioning on high-order element methods based on CGL-, LGL-nodes  

Microsoft Academic Search

The high-order finite element methods for discretizations to solve a second-order uniformly el- liptic partial differential equation leads to a linear equation b Sh2N2U = F which needs efficient iterative methods such as Schwarz-based methods, preconditioning methods related to multi- level methods, multigrid methods. This is because such linear systems have large condition numbers usually dependent on degrees of high-order

Seon Hee Kim; Sang Dong Kim


Heat-shock protein 70 is involved in hyperbaric oxygen preconditioning on decompression sickness in rats.  


Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-l-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and -9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects. PMID:23479759

Ni, Xiao-Xiao; Ni, Ming; Fan, Dan-Feng; Sun, Qiang; Kang, Zhi-Min; Cai, Zhi-Yu; Liu, Yun; Liu, Kan; Li, Run-Ping; Xu, Wei-Gang



Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo  

Microsoft Academic Search

During myocardial ischemia, connexin 43 (Cx43) is dephosphorylated in vitro, and the subsequent opening of gap junctions formed by two opposing Cx43 hexamers was suggested to propagate ischemia\\/reperfusion injury. Reduction of infarct size (IS) by ischemic preconditioning (IP) involves activation of protein kinase C (PKC) and p38 mitogen activated protein kinase (MAPK), both of which can phosphorylate Cx43. We now

Rainer Schulz; Petra Gres; Andreas Skyschally; Alexej Duschin; Sergej Belosjorow; Ina Konietzka; Gerd Heusch



The role of peroxynitrite in chemical preconditioning with 3-nitropropionic acid in rat hearts  

Microsoft Academic Search

Objectives: 3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, has been shown to protect against ischemic injury in the brain and in the heart via a preconditioning-like effect; however, the cellular mechanism is not known. The aim of the present study was to investigate if 3-NP pretreatment reduces infarct size and if altered metabolism of nitric oxide and reactive

Nilufer Turan; Csaba Csonka; Tamas Csont; Zoltan Giricz; Gabriella Fodor; Peter Bencsik; Mariann Gyongyosib; Iclal Cakici



Ischemic preconditioning fails to improve microcirculation but increases apoptotic cell death in experimental pancreas transplantation  

Microsoft Academic Search

Brief periods of warm ischemia and subsequent short reperfusion before either long-term cold or warm ischemic insult (ischemic preconditioning, IPC) have proven to ameliorate ischemia\\/reperfusion (I\\/R) injury in various organs, such as the liver and lung. The aim of this study was to examine the effect of IPC on pancreatic cell apoptosis and microcirculatory impairments in experimental pancreas transplantation. Male

Oliver Drognitz; Xuemei Liu; Robert Obermaier; Hannes Neeff; Ernst von Dobschuetz; Ulrich Theodor Hopt; Stefan Benz



Nitric Oxide Synthase Is the Mediator of Late Preconditioning Against Myocardial Infarction in Conscious Rabbits  

Microsoft Academic Search

Background—Despite intense investigation, the effector of the infarct-limiting protection observed during the late phase of ischemic preconditioning (PC) remains unknown. The goal of this study was to test the hypothesis that late PC against myocardial infarction is mediated by the activity of nitric oxide synthase (NOS). Methods and Results—Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of

Hitoshi Takano; Srinivas Manchikalapudi; Xian-Liang Tang; Yumin Qiu; Ali Rizvi; Asad K. Jadoon; Qin Zhang; Roberto Bolli



Bifunctional Role of Protein Tyrosine Kinases in Late Preconditioning Against Myocardial Stunning in Conscious Rabbits  

Microsoft Academic Search

Abstract—Although protein tyrosine kinases (PTKs) have been implicated in late preconditioning (PC) against infarction, their role in late PC against stunning is unknown. Furthermore, it is unknown whether PTK signaling is necessary only to trigger late PC on day 1 or also to mediate it on day 2. Thus, conscious rabbits underwent a sequence of six 4-minute coronary occlusion\\/4-minute reperfusion

Buddhadeb Dawn; Yu-Ting Xuan; Yumin Qiu; Hitoshi Takano; Xian-Liang Tang; Peipei Ping; Supratim Banerjee; Michael Hill; Roberto Bolli


Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning  

Microsoft Academic Search

Aldose reductase (AR), a member of the aldo-keto reductase superfamily, has been shown to metabolize toxic aldehydes generated by lipid peroxidation, suggesting that it may serve as an antioxidant defense. To investigate its role in the late phase of ischemic preconditioning (PC), conscious rabbits underwent 6 cycles of 4-minute coronary occlusion\\/4-minute reperfusion. Twenty-four hours later, there was a marked increase

Ken Shinmura; Roberto Bolli; Si-Qi Liu; Xian-Liang Tang; Eitaro Kodani; Yu-ting Xuan; Sanjay Srivastava; Aruni Bhatnagar


Cyclooxygenase2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits  

Microsoft Academic Search

We examined the role of cyclooxygenase-2 (COX-2) in the late phase of ischemic preconditioning (PC). A total of 176 conscious rabbits were used. Ischemic PC (six cycles of 4-min coronary occlusions\\/4-min reperfusions) resulted in a rapid increase in myocardial COX-2 mRNA levels (+231 ± 64% at 1 h; RNase protection assay) followed 24 h later by an increase in COX-2

Ken Shinmura; Xian-Liang Tang; Yang Wang; Yu-Ting Xuan; Si-Qi Liu; Hitoshi Takano; Aruni Bhatnagar; Roberto Bolli



Delphi-research exploring essential components and preconditions for case management in people with dementia  

PubMed Central

Background Case management programmes for home-dwelling people with dementia and their informal carers exist in multiple forms and shapes. The aim of this research was to identify the essential components of case management for people with dementia as well as the preconditions for an effective delivery of case management services. Method The method used to carry out the research was a modified four-phase Delphi design. First, a list of potentially essential components and preconditions for the provision of case management was drawn up on the basis of a literature review and a subsequent focus group interview. The list was then validated by experts in a first Delphi survey round, following which the researchers translated the list items into 75 statements. In the second Delphi survey, the experts rated the statements; in the third Delphi round, they rated 18 statements on which no consensus had been reached in the second round. Results The experts were able to build consensus on 61 of the 75 statements. Essential components of case management for people with dementia are: information, support and counsell