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1

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

2000-01-01

2

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

2002-01-01

3

Ischemic preconditioning (IP) of the liver as a safe and protective technique against ischemia/reperfusion injury (IRI).  

PubMed

The aim of the study was to evaluate safety and efficacy of IP in LT, particularly in marginal grafts. From 2007 to 2008, 75 LT donors were randomized to receive IP (IP+) or not (IP-). Considering the graft quality, we divided the main groups in two subgroups (marg+/marg-). IP was performed by 10-min inflow occlusion (Pringle maneuver utilizing a toruniquet). Donor variables considered were gender, age, AST/ALT, ischemia time and steatosis. Recipient variables were gender, age, indication to LT and MELD/CHILD/UNOS score. AST/ALT levels, INR, bilirubin, lactic acid, bile output on postoperative days 1, 3 and 7 were evaluated. Histological analysis was performed evaluating necrosis/steatosis, hepatocyte swelling, PMN infiltration and councilman bodies. Thirty patients received IP+ liver. No differences were seen between groups considering recipient and donor variables. Liver function and AST/ALT levels showed no significant differences between the main two groups. Marginal IP+ showed lower AST levels on day1 compared with untreated marginal livers (936.35 vs. 1268.23; p = 0.026). IP+ livers showed a significant reduction of moderate-severe hepatocyte swelling (33.3% vs. 65.9%; p = 0.043). IP+ patients had a significant reduction of positive early microbiological investigations (36.7% vs. 57.1%; p = 0.042). In our experience IP was safe also in marginal donors, showing a protective role against IRI. PMID:19519822

Franchello, A; Gilbo, N; David, E; Ricchiuti, A; Romagnoli, R; Cerutti, E; Salizzoni, M

2009-06-10

4

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

2005-01-01

5

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.

2013-01-01

6

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

2010-01-01

7

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

2005-01-01

8

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

9

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

2000-01-01

10

Ischemic preconditioning improves maximal performance in humans.  

PubMed

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

2009-09-18

11

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

2008-01-01

12

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

13

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

2001-01-01

14

Clinically useful cardioprotection: ischemic preconditioning then and now.  

PubMed

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

15

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

2008-01-01

16

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

17

Ischemic preconditioning alters the epigenetic profile of the brain from ischemic intolerance to ischemic tolerance.  

PubMed

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

2013-10-01

18

Ischemic preconditioning of free muscle flaps: an experimental study.  

PubMed

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

2005-01-01

19

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

2011-01-01

20

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

2006-01-01

21

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

2003-01-01

22

Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes  

Microsoft Academic Search

Whether ischemic preconditioning (IP) reduces ischemia\\/reperfusion (I\\/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological

D Degli Esposti; M Sebagh; P Pham; M Reffas; C Poüs; C Brenner; D Azoulay; A Lemoine

2011-01-01

23

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

2009-01-01

24

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

2004-01-01

25

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

2003-01-01

26

Heparin inhibits protective effect of ischemic preconditioning in ischemia/reperfusion-induced acute pancreatitis.  

PubMed

Previous studies have shown that pancreatic ischemic preconditioning or heparin, applied before induction of acute pancreatitis inhibit the development of this disease and accelerate pancreatic recovery. The aim of the study was to determine the influence of treatment with heparin on protective effect of ischemic preconditioning (IP) in ischemia/reperfusion-induced acute pancreatitis. Heparin was administered twice, before and during induction of acute pancreatitis. IP was performed by short-term clamping of celiac artery, 30 min before induction of acute pancreatitis. Acute pancreatitis was induced in rats by clamping of inferior splenic artery for 30 min followed by reperfusion. Rats were sacrificed after 6-h and 24-h reperfusion. Results: IP applied alone caused a mild pancreatic damage associated with a limited increase in plasma amylase activity, concentration of pro-inflammatory interleukin-1? and plasma level of D-dimer. Pretreatment with heparin or IP applied alone reduced the severity of acute pancreatitis. Both these procedures caused a similar reduction in plasma lipase, amylase and interleukin-1?, as well as in histological signs of pancreatic damage. These changes were associated with partial reversion of the pancreatitis-evoked fall of pancreatic blood flow and DNA synthesis. Combination of heparin plus IP reduced the protective effect of heparin or IP applied alone. It was manifested by an increase in pancreatic damage and plasma level of lipase, amylase and interleukin-1?, as well as by reduction in pancreatic DNA synthesis and plasma concentration of D-dimer and interleukin-10. Conclusions: heparin abolishes the protective effect of ischemic preconditioning in ischemia reperfusion-induced pancreatitis. This observation suggests that initial clot formation is necessary to induce pancreatic protection by IP. PMID:23070084

Warzecha, Z; Dembinski, A; Ceranowicz, P; Dembinski, M; Sendur, R; Cieszkowski, J; Sendur, P; Tomaszewska, R

2012-08-01

27

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

PubMed

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

2012-06-28

28

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

PubMed

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

2006-08-30

29

Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70  

Microsoft Academic Search

Abstract Abstract Abstract Abstract AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process.

Zygmunt Warzecha; Artur Dembinski; Piotr Ceranowicz; Stanislaw J Konturek; Marcin Dembinski; Wieslaw W Pawlik; Romana Tomaszewska; Jerzy Stachura; Beata Kusnierz-Cabala; Jerzy W Naskalski; Peter C Konturek; Konturek SJ; Pawlik WW

2005-01-01

30

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

1999-01-01

31

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

2002-01-01

32

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

1996-01-01

33

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

2003-01-01

34

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

2011-01-01

35

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

2008-01-01

36

Autophagy induced by ischemic preconditioning is essential for cardioprotection.  

PubMed

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

2010-05-11

37

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.

2010-01-01

38

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

2007-01-01

39

Pharmacologic stimulation of adenosine A2 receptor supplants ischemic preconditioning in providing ischemic tolerance in rat livers  

Microsoft Academic Search

Background: Ischemic preconditioning (IPC) is a promising strategy for conferring ischemic tolerance. We confirmed the acquisition of ischemic tolerance in the liver immediately after IPC and the role of adenosine kinetics in this process. Methods: Male Lewis rats were used. IPC was administered with a 10-minute ischemia followed by a 10-minute reperfusion. Ischemic tolerance was tested with a 45-minute ischemia.

Hiroyuki Nakayama; Yuzo Yamamoto; Makoto Kume; Kazuhiko Yamagami; Hidekazu Yamamoto; Syuji Kimoto; Yasuhide Ishikawa; Nobuhiro Ozaki; Yasuyuki Shimahara; Yoshio Yamaoka

1999-01-01

40

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

PubMed

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

41

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

2001-01-01

42

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

PubMed

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

2003-07-02

43

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.

2008-01-01

44

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

2003-01-01

45

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

2002-01-01

46

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.

2011-01-01

47

Antiarrhythmic effect of ischemic preconditioning in recent unstable angina patients undergoing coronary artery bypass grafting.  

PubMed

Coronary artery bypass grafting (CABG) for unstable angina pectoris patients results in a higher incidence of arrhythmia and higher arrhythmic cardiac mortality. Ischemic preconditioning (IP) has proved effective in suppressing ischemia reperfusion arrhythmias in animals and in humans. The purpose of the present study was to investigate whether IP protects against postoperative arrhythmias in recent unstable angina patients undergoing urgent CABG. Forty-one patients with recent unstable angina and three-vessel coronary artery disease admitted for CABG were randomized into an IP group and a control group. The IP protocol involved twice occluding the ascending aorta with a cross-clamp for 2 minutes, followed by 3 minutes of reperfusion. Twenty-four-hour continuous electrocardiography (24-h ECG) was recorded from the preoperative day to the 2nd postoperative day. The incidences of supraventricular extrasystole (SVES), ventricular extrasystole (VES), supraventricular tachycardia (SVT), and ventricular tachycardia (VT) were 95.2%, 85.7%, 26.2%, and 26.2%, respectively, before surgery and 100.0%, 100.0%, 88.1%, and 76.2%, respectively, after surgery. IP significantly reduced the incidence of VT and the severity of SVES, VES, SVT, and VT after surgery. The period of mechanical ventilation and the length of stay in the intensive care unit were significantly shorter in the IP group. In summary, rhythm disturbances are common in CABG patients with recent unstable angina. IP significantly reduces rhythm disturbances, including SVES, VES, SVT, and VT after CABG. The findings indicate that IP could constitute an additional myocardial protective strategy in recently unstable angina patients undergoing CABG. PMID:14612991

Wu, Zhong-Kai; Iivainen, Tiina; Pehkonen, Erkki; Laurikka, Jari; Tarkka, Matti R

2003-11-14

48

Elevated semicarbazide-sensitive amine oxidase (SSAO) activity in lung with ischemia–reperfusion injury: Protective effect of ischemic preconditioning plus SSAO inhibition  

Microsoft Academic Search

Ischemic preconditioning (IP) has been shown to protect the lung against ischemia–reperfusion (I\\/R) injury. Although the production of reactive oxygen species (ROS) has been postulated to play a crucial role in I\\/R injury, the sources of these radicals in I\\/R and the mechanisms of protection in IP remain unknown. Since it was postulated that deamination of endogenous and exogenous amines

Gulberk Ucar; Eda Topaloglu; H. Burak Kandilci; Bulent Gumusel

2005-01-01

49

Application of NMR-based metabonomics in the investigation of myocardial ischemia-reperfusion, ischemic preconditioning and antioxidant intervention in rabbits  

Microsoft Academic Search

NMR based metabonomics was applied in rabbit plasma samples during myocardial ischemia-reperfusion injury, with the following interventions: (1) Control (no intervention); (2) ischemic preconditioning (IpC); (3) administration of melatonin; (4) IpC+administration of melatonin; (5) treatment of the indole derivative C6458. The 1H NMR signal intensity ratio of lactate\\/glucose was found to increase in Control samples during reperfusion compared to baseline,

Maria A. Constantinou; Anna Tsantili-Kakoulidou; Ioanna Andreadou; Efstathios K. Iliodromitis; Dimitrios Th. Kremastinos; Emmanuel Mikros

2007-01-01

50

Calmodulin kinase II inhibition enhances ischemic preconditioning by augmenting ATP-sensitive K+ current.  

PubMed

Mice with genetic inhibition (AC3-I) of the multifunctional Ca(2+)/calmodulin dependent protein kinase II (CaMKII) have improved cardiomyocyte survival after ischemia. Some K(+) currents are up-regulated in AC3-I hearts, but it is unknown if CaMKII inhibition increases the ATP sensitive K(+) current (I(KATP)) that underlies ischemic preconditioning (IP) and confers resistance to ischemia. We hypothesized increased I(KATP) was part of the mechanism for improved ventricular myocyte survival during ischemia in AC3-I mice. AC3-I hearts were protected against global ischemia due to enhanced IP compared to wild type (WT) and transgenic control (AC3-C) hearts. IKATP was significantly increased, while the negative regulatory dose-dependence of ATP was unchanged in AC3-I compared to WT and AC3-C ventricular myocytes, suggesting that CaMKII inhibition increased the number of functional I(KATP) channels available for IP. We measured increased sarcolemmal Kir6.2, a pore-forming I(KATP) subunit, but not a change in total Kir6.2 in cell lysates or single channel I(KATP) opening probability from AC3-I compared to WT and AC3-C ventricles, showing CaMKII inhibition increased sarcolemmal I(KATP) channel expression. There were no differences in mRNA for genes encoding I(KATP) channel subunits in AC3-I, WT and AC3-C ventricles. The I(KATP) opener pinacidil (100 microM) reduced MI area in WT to match AC3-I hearts, while the I(KATP) antagonist HMR1098 (30 microM) increased MI area to an equivalent level in all groups, indicating that increased I(KATP) and augmented IP are important for reduced ischemic cell death in AC3-I hearts. Our study results show CaMKII inhibition enhances beneficial effects of IP by increasing I(KATP). PMID:18690039

Li, Jingdong; Marionneau, Celine; Koval, Olha; Zingman, Leonid; Mohler, Peter J; Nerbonne, Jeanne M; Anderson, Mark E

2007-12-17

51

Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes  

PubMed Central

Whether ischemic preconditioning (IP) reduces ischemia/reperfusion (I/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological and immunohistological characteristics of post-reperfusion biopsies were analyzed. Incidence of post-reperfusion necrosis was increased (10/10 versus 9/14, respectively; P<0.05) and the clinical outcome of recipients was worse for non-IP steatotic liver grafts compared with non-IP non-steatotic grafts. IP significantly lowered the transaminase values only in patients receiving a non-steatotic liver. An increased expression of beclin-1 and LC3, two pro-autophagic proteins, tended to decrease the incidence of necrosis (P=0.067) in IP steatotic livers compared with non-IP steatotic group. IP decreased the incidence of acute and chronic rejection episodes in steatotic livers (2/12 versus 6/10; P=0.07 and 2/12 versus 7/10; P<0.05, respectively), but not in non-steatotic livers. Thus, IP may induce autophagy in human steatotic liver grafts and reduce rejection in their recipients.

Degli Esposti, D; Sebagh, M; Pham, P; Reffas, M; Pous, C; Brenner, C; Azoulay, D; Lemoine, A

2011-01-01

52

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

2011-01-01

53

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

2001-01-01

54

Beneficial effects of ischemic preconditioning on pancreas cold preservation.  

PubMed

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

2012-01-01

55

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

PubMed

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

2012-01-01

56

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

2008-01-01

57

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

PubMed

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

2012-06-15

58

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.

2010-01-01

59

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

2007-01-01

60

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

2008-01-01

61

Ischemic preconditioning protects by activating prosurvival kinases at reperfusion.  

PubMed

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

2004-09-09

62

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

PubMed

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

2013-08-01

63

Ischemic preconditioning improves islet recovery after pancreas cold preservation.  

PubMed

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

64

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

PubMed

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

2012-06-09

65

Sarcolemmal Blebs and Osmotic Fragility as Correlates of Irreversible Ischemic Injury in Preconditioned Isolated Rabbit Cardiomyocytes  

Microsoft Academic Search

The hypothesis that irreversible ischemic injury is related to sub-sarcolemmal blebbing and an inherent osmotic fragility of the blebs was tested by subjecting isolated control and ischemically preconditioned (IPC) or calyculin A (CalA)-pretreated (protected) rabbit cardiomyocytes to ischemic pelleting followed by resuspension in 340, 170 or 85 mosmol medium containing trypan blue. At time points from 0–240 min, osmotic fragility

Stephen C. Armstrong; Christine L. Shivell; Charles E. Ganote

2001-01-01

66

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

PubMed

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

2004-01-16

67

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

PubMed

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

2013-01-01

68

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

PubMed

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

2009-02-25

69

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

PubMed

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

2000-02-01

70

Bilateral common carotid artery occlusion as an adequate preconditioning stimulus to induce early ischemic tolerance to focal cerebral ischemia.  

PubMed

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

2013-05-09

71

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

2007-01-01

72

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

2011-01-01

73

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

PubMed

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

2006-01-01

74

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

2013-01-01

75

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

PubMed

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

2011-06-15

76

Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice.  

PubMed

Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5min occlusion and 5min reperfusion of unilateral renal artery) 24h before global brain ischemia (20min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5mg/kg, i.p.) was injected 30min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24h after global ischemia. Apoptosis and neuronal cell density were assessed 72h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC+IR) suggesting a role for mTOR in RIPC induced hippocampal protection. PMID:23806777

Zare Mehrjerdi, Fatemeh; Aboutaleb, Nahid; Habibey, Rouhollah; Ajami, Marjan; Soleimani, Mansoureh; Arabian, Maedeh; Niknazar, Somayeh; Hossein Davoodi, Sayed; Pazoki-Toroudi, Hamidreza

2013-06-24

77

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

2004-01-01

78

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

2004-01-01

79

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

2000-01-01

80

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

2003-01-01

81

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

2010-01-01

82

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

PubMed

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

2002-10-01

83

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

2000-01-01

84

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

2001-01-01

85

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

2000-01-01

86

Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the heart.  

PubMed

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

2013-10-07

87

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

2003-01-01

88

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.

2013-01-01

89

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

2010-01-01

90

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

1999-01-01

91

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

PubMed

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

1997-01-01

92

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

93

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

2002-01-01

94

The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning  

PubMed Central

Background Pharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear. Objective To determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion. Methods COX-2 knockout (KO) mice (COX-2?/?), prostacyclin receptor KO (IP?/?) mice, and respective wildtype (WT, COX-2+/+ and IP+/+) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30-min O/24 h R. Results There were no significant differences in infarct size (IS) between non-preconditioned (non-PC) COX-2+/+, COX-2?/?, IP+/+, and IP?/? mice, indicating that neither COX-2 nor IP modulates IS in the absence of PC. When COX-2?/? or IP?/? mice were preconditioned, IS was not reduced, indicating that the protection of late PC was completely abrogated by deletion of either the COX-2 or the IP gene. Administration of the IP selective antagonist, RO3244794 to C57BL6/J (B6) mice 30 min prior to the 30-min O had no effect on IS. When B6 mice were preconditioned 24 h prior to the 30-min O, IS was markedly reduced; however, the protection of late PC was completely abrogated by pretreatment of RO3244794. Conclusions This is the first study to demonstrate that targeted disruption of the COX-2 gene completely abrogates the infarct-sparing effect of late PC, and that the IP, downstream of the COX-2/prostanoid pathway, is a key mediator of the late PC. These results provide unequivocal molecular genetic evidence for an essential role of the COX-2/PGI2 receptor axis in the cardioprotection afforded by the late PC.

Guo, Yiru; Tukaye, Deepali Nivas; Wu, Wen-Jian; Zhu, Xiaoping; Book, Michael; Tan, Wei; Jones, Steven P.; Rokosh, Gregg; Narumiya, Shuh; Li, Qianhong; Bolli, Roberto

2012-01-01

95

New insights into cardioprotection by ischemic preconditioning and other forms of stress.  

PubMed

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

1999-06-30

96

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

2010-01-01

97

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

2011-01-01

98

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

99

Regulated Production of Free Radicals by the Mitochondrial Electron Transport Chain: Cardiac Ischemic Preconditioning  

PubMed Central

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

Matsuzaki, Satoshi; Szweda, Pamela A.; Szweda, Luke I.; Humphries, Kenneth M.

2009-01-01

100

[Phytoadaptogens-induced phenomenon similar to ischemic preconditioning].  

PubMed

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

2009-04-01

101

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

PubMed

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

2011-11-12

102

Neuroprotective Effects of Ischemic Preconditioning and Postconditioning on Global Brain Ischemia in Rats through the Same Effect on Inhibition of Apoptosis.  

PubMed

Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic challenge. Therefore, we investigated the effect of ischemic preconditioning and postconditioning on neural cell apoptosis in rats. The result showed that both ischemic preconditioning and postconditioning may attenuate the neural cell death and DNA fragment in the hippocampal CA1 region. Further western blot study suggested that ischemic preconditioning and postconditioning down-regulates the protein of cleaved caspase-3, caspase-6, caspase-9 and Bax, but up-regulates the protein Bcl-2. These findings suggest that ischemic preconditioning and postconditioning have a neuroprotective role on global brain ischemia in rats through the same effect on inhibition of apoptosis. PMID:22754351

Ding, Zhe-Min; Wu, Bing; Zhang, Wei-Qiao; Lu, Xiao-Jie; Lin, Yu-Chang; Geng, Yong-Jian; Miao, Yi-Feng

2012-05-18

103

Neuroprotective Effects of Ischemic Preconditioning and Postconditioning on Global Brain Ischemia in Rats through the Same Effect on Inhibition of Apoptosis  

PubMed Central

Transient forebrain or global ischemia induces neuronal death in vulnerable CA1 pyramidal cells with many features. A brief period of ischemia, i.e., ischemic preconditioning, or a modified reperfusion such as ischemic postconditioning, can afford robust protection of CA1 neurons against ischemic challenge. Therefore, we investigated the effect of ischemic preconditioning and postconditioning on neural cell apoptosis in rats. The result showed that both ischemic preconditioning and postconditioning may attenuate the neural cell death and DNA fragment in the hippocampal CA1 region. Further western blot study suggested that ischemic preconditioning and postconditioning down-regulates the protein of cleaved caspase-3, caspase-6, caspase-9 and Bax, but up-regulates the protein Bcl-2. These findings suggest that ischemic preconditioning and postconditioning have a neuroprotective role on global brain ischemia in rats through the same effect on inhibition of apoptosis.

Ding, Zhe-Min; Wu, Bing; Zhang, Wei-Qiao; Lu, Xiao-Jie; Lin, Yu-Chang; Geng, Yong-Jian; Miao, Yi-Feng

2012-01-01

104

Heme Oxygenase 1 Is Associated with Ischemic Preconditioning-Induced Protection Against Brain Ischemia  

PubMed Central

Ischemic preconditioning (IPC) protects brain against ischemic injury by activating specific mechanisms. Our goal was to determine if the inducible heme oxygenase 1 (HO1) is required for such protection. IPC before transient or permanent ischemia reduced cortical infarct volumes by 57.4% and 33.9%, respectively at 48 h in wildtype adult mice. Interestingly, IPC failed to protect the HO1 gene deleted mice against permanent ischemic brain injury. IPC also resulted in a significant increase in HO1 protein levels in the brain and correlated with reduced neurological deficits after permanent and transient brain ischemia. Our study demonstrates that neuroprotective effects of IPC are at least partially mediated via HO1. Elucidating the physiological/cellular role by which HO1 is protective against brain ischemia may aid the development of selective drugs to treat stroke and its associated neurological disorders.

Zeynalov, Emil; Shah, Zahoor A.; Li, Rung-chi; Dore, Sylvain

2009-01-01

105

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

PubMed

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

2000-09-01

106

Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation  

PubMed Central

Inhibition of mitochondrial permeability transition pore (MPTP) opening at reperfusion is critical for cardioprotection by ischemic preconditioning (IP). Some studies have implicated mitochondrial protein phosphorylation in this effect. Here we confirm that mitochondria rapidly isolated from pre-ischemic control and IP-hearts show no significant difference in calcium-mediated MPTP opening, whereas IP inhibits MPTP opening in mitochondria isolated from IP-hearts following 30 min global normothermic ischemia or 3 min reperfusion. Analysis of protein phosphorylation in density-gradient purified mitochondria was performed using both 2D and 1D electrophoresis with detection of phosphoproteins using Pro-Q Diamond or phospho-amino specific antibodies. Several phosphoproteins were detected, including voltage-dependent anion channels isoforms 1 and 2, but none showed significant IP-mediated changes either before ischemia or during ischemia and reperfusion. Nor did either Western blotting or 2-D fluorescence difference gel electrophoresis (DIGE) detect translocation of protein kinase C (?, ? or ? isoforms), glycogen synthase kinase 3? (GSK3?), or Akt to the mitochondria following IP. In freeze-clamped hearts changes in phosphorylation of GSK3?, Akt and AMP-activated protein kinase (AMPK) were detected following ischemia and reperfusion but no IP-mediated changes correlated with MPTP inhibition or cardioprotection. However, measurement of mitochondrial protein carbonylation, a surrogate marker for oxidative stress, suggested that a reduction in mitochondrial oxidative stress at the end of ischemia and during reperfusion might account for IP-mediated inhibition of MPTP. The signalling pathways mediating this effect and maintaining it during reperfusion are discussed.

Clarke, Samantha J.; Khaliulin, Igor; Das, Manika; Parker, Joanne E.; Heesom, Kate J.; Halestrap, Andrew P.

2008-01-01

107

Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption  

PubMed Central

Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan’s Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-? (TNF-?) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-? mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-? expression.

Fang, Bo; Li, Xiao-Man; Sun, Xi-Jia; Bao, Na-Ren; Ren, Xiao-Yan; Lv, Huang-Wei; Ma, Hong

2013-01-01

108

Ischemic Preconditioning Protects against Spinal Cord Ischemia-Reperfusion Injury in Rabbits by Attenuating Blood Spinal Cord Barrier Disruption.  

PubMed

Ischemic preconditioning has been reported to protect against spinal cord ischemia-reperfusion (I-R) injury, but the underlying mechanisms are not fully understood. To investigate this, Japanese white rabbits underwent I-R (30 min aortic occlusion followed by reperfusion), ischemic preconditioning (three cycles of 5 min aortic occlusion plus 5 min reperfusion) followed by I-R, or sham surgery. At 4 and 24 h following reperfusion, neurological function was assessed using Tarlov scores, blood spinal cord barrier permeability was measured by Evan's Blue extravasation, spinal cord edema was evaluated using the wet-dry method, and spinal cord expression of zonula occluden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-? (TNF-?) were measured by Western blot and a real-time polymerase chain reaction. ZO-1 was also assessed using immunofluorescence. Spinal cord I-R injury reduced neurologic scores, and ischemic preconditioning treatment ameliorated this effect. Ischemic preconditioning inhibited I-R-induced increases in blood spinal cord barrier permeability and water content, increased ZO-1 mRNA and protein expression, and reduced MMP-9 and TNF-? mRNA and protein expression. These findings suggest that ischemic preconditioning attenuates the increase in blood spinal cord barrier permeability due to spinal cord I-R injury by preservation of tight junction protein ZO-1 and reducing MMP-9 and TNF-? expression. PMID:23685868

Fang, Bo; Li, Xiao-Man; Sun, Xi-Jia; Bao, Na-Ren; Ren, Xiao-Yan; Lv, Huang-Wei; Ma, Hong

2013-05-17

109

Both ischemic preconditioning and ghrelin administration protect hippocampus from ischemia/reperfusion and upregulate uncoupling protein-2  

PubMed Central

Background A major endogenous protective mechanism in many organs against ischemia/reperfusion (I/R) injury is ischemic preconditioning (IPC). By moderately uncoupling the mitochondrial respiratory chain and decreasing production of reactive oxygen species (ROS), IPC reduces apoptosis induced by I/R by reducing cytochrome c release from the mitochondria. One element believed to contribute to reduce ROS production is the uncoupling protein UCP2 (and UCP3 in the heart). Although its implication in IPC in the brain has been shown in vitro, no in vivo study of protein has shown its upregulation. Our first goal was to determine in rat hippocampus whether UCP2 protein upregulation was associated with IPC-induced protection and increased ROS production. The second goal was to determine whether the peptide ghrelin, which possesses anti-oxidant and protective properties, alters UCP2 mRNA levels in the same way as IPC during protection. Results After global forebrain ischemia (15 min) with 72 h reperfusion (I/R group), we found important neuronal lesion in the rat hippocampal CA1 region, which was reduced by a preceding 3-min preconditioning ischemia (IPC+I/R group), whereas the preconditioning stimulus alone (IPC group) had no effect. Compared to control, UCP2 protein labelling increased moderately in the I/R (+39%, NS) and IPC+I/R (+28%, NS) groups, and substantially in the IPC group (+339%, P < 0.05). Treatment with superoxide dismutase (10000 U/kg ip) at the time of a preconditioning ischemia greatly attenuated (-73%, P < 0.001) the increase in UCP2 staining at 72 h, implying a role of oxygen radicals in UCP2 induction. Hippocampal UCP2 mRNA showed a moderate increase in I/R (+33%, P < 0.05) and IPC+I/R (+40%, P < 0.05) groups versus control, and a large increase in the IPC group (+333%, P < 0.001). In ghrelin experiments, the I/R+ghrelin group (3 daily administrations) showed considerable protection of CA1 neurons versus I/R animals, and increased hippocampal UCP2 mRNA (+151%, P < 0.001). Conclusion We confirm that IPC causes increased expression of UCP2 protein in vivo, at a moment appropriate for protection against I/R in the hippocampus. The two dissimilar protective strategies, IPC and ghrelin administration, were both associated with upregulated UCP2, suggesting that UCP2 may often represent a final common pathway in protection from I/R.

Liu, Yajun; Chen, Lianbi; Xu, Xiaoqun; Vicaut, Eric; Sercombe, Richard

2009-01-01

110

Ischemic preconditioning modulates mitochondrial respiration, irrespective of the employed signal transduction pathway.  

PubMed

We tested in the in vivo rat heart the hypothesis that although ischemic preconditioning can employ different signal transduction pathways, these pathways converge ultimately at the level of the mitochondrial respiratory chain. Infarct size produced by a 60-min coronary artery occlusion (69%+/-2% of the area at risk) was limited by a preceding 15-min coronary occlusion (48%+/-4%). Cardioprotection by this stimulus was triggered by adenosine receptor stimulation, which was followed by protein kinase C and tyrosine kinase activation and then mitochondrial K(+)(ATP)-channel opening. In contrast, cardioprotection by 3 cycles of 3-min coronary occlusions (infarct size 27%+/-5% of the area at risk) involved the release of reactive oxygen species, which was followed by protein kinase C and tyrosine kinase activation, but was independent of adenosine receptor stimulation and K(+)(ATP)-channel activation. However, both pathways decreased respiratory control index (RCI; state-3/state-2, using succinate as complex-II substrate) from 3.1+/-0.2 in mitochondria from sham-treated hearts to 2.4+/-0.2 and 2.5+/-0.1 in hearts subjected to a single 15-min and triple 3-min coronary occlusions, respectively (both P<0.05). The decreases in RCI were due to an increase in state-2 respiration, whereas state-3 respiration was unchanged. Abolition of cardioprotection by blockade of either signal transduction pathway was paralleled by a concomitant abolition of mitochondrial uncoupling. These observations are consistent with the concept that mild mitochondrial uncoupling contributes to infarct size limitation by various ischemic preconditioning stimuli, despite using different signal transduction pathways. In conclusion, in the in vivo rat heart, different ischemic preconditioning (IPC) stimuli can activate highly different signal transduction pathways, which seem to converge at the level of the mitochondria where they increase state-2 respiration. PMID:18061124

Liem, David A; Manintveld, Olivier C; Schoonderwoerd, Kees; McFalls, Edward O; Heinen, Andre; Verdouw, Pieter D; Sluiter, Wim; Duncker, Dirk J

2007-10-29

111

STAT subtype specificity and ischemic preconditioning in mice: is STAT-3 enough?  

PubMed Central

The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/dtmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/dtmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC.

Goodman, Michael D.; Koch, Sheryl E.; Afzal, Muhammad R.

2011-01-01

112

Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury  

PubMed Central

The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide.

Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

2012-01-01

113

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.

2009-01-01

114

Remote ischemic preconditioning reduces myocardial injury after coronary artery bypass surgery with crystalloid cardioplegic arrest  

Microsoft Academic Search

Remote ischemic preconditioning (RIPC) with transient upper limb ischemia reduces myocardial injury in patients undergoing\\u000a on-pump coronary artery bypass grafting (CABG) with cross-clamp fibrillation or blood cardioplegia for myocardial protection.\\u000a Whether or not such protection is still operative when standard crystalloid cardioplegic arrest is used is uncertain. Fifty-three\\u000a consecutive, non-diabetic patients with triple-vessel disease and 64 ± 12 years of age (mean ± SD), who

Matthias Thielmann; Eva Kottenberg; Kerstin Boengler; Christoph Raffelsieper; Markus Neuhaeuser; Jürgen Peters; Heinz Jakob; Gerd Heusch

2010-01-01

115

The Sulfonylurea Glipizide Does Not Inhibit Ischemic Preconditioning in Anesthetized Rabbits  

Microsoft Academic Search

Summary  The KATP channel blocker glibenclamide inhibits cardioprotection afforded by ischemic preconditioning (IPC), raising concern about\\u000a sulfonylurea use by patients with cardiovascular disease. We examined the effects of the widely prescribed sulfonylurea glipizide\\u000a (Glucotrol XL® ) on IPC in anesthetized rabbits. Initially, in parallel studies in pentobarbital-anesthetized rabbits, we\\u000a identified doses of glipizide (GLIP, 0.17 mg\\/kg + 0.12 mg\\/kg\\/h, IV) and glibenclamide (GLIB, 0.05 mg\\/kg

David M. Flynn; Andrew H. Smith; Judith L. Treadway; Carolyn B. Levy; Walter C. Soeller; Wayne A. Boettner; Peter Wisniecki; David R. Plowchalk; Steve S. Gernhardt; W. Ross Tracey; Delvin R. Knight

2005-01-01

116

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

1999-01-01

117

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

1999-01-01

118

Changes in the spontaneous calcium oscillations for the development of the preconditioning-induced ischemic tolerance in neuron/astrocyte co-culture.  

PubMed

Spontaneous Ca(2+) oscillations are believed to contribute to the regulation of gene expression. Here we investigated whether and how the dynamics of Ca(2+) oscillations changed after sublethal preconditioning (PC) for PC-induced ischemic tolerance in neuron/astrocyte co-cultures. The frequency of spontaneous Ca(2+) oscillations significantly decreased between 4 and 8 h after the end of PC in both neurons and astrocytes. Treatment with 2-APB, an inhibitor of IP3 receptors, decreased the oscillatory frequency, induced ischemic tolerance and a down-regulation of glutamate transporter GLT-1 contributing to the increase in the extracellular glutamate during ischemia. The expression of GLT-1 is known to be up-regulated by PACAP. Treatment with PACAP38 increased the oscillatory frequency, and antagonized both the PC-induced down-regulation of GLT-1 and ischemic tolerance. These results suggested that the PC suppressed the spontaneous Ca(2+) oscillations regulating the gene expressions of various proteins, especially of astrocytic GLT-1, for the development of the PC-induced ischemic tolerance. PMID:17401678

Tanaka, Motoki; Kawahara, Koichi; Kosugi, Tatsuro; Yamada, Takeshi; Mioka, Tetsuo

2007-03-31

119

TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING  

EPA Science Inventory

Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C. Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning Craig...

120

Modification of the Hepatic Mitochondrial Proteome in Response to Ischemic Preconditioning following Ischemia-Reperfusion Injury of the Rat Liver  

Microsoft Academic Search

Background\\/Aim: Ischemic preconditioning (IPC) may reduce hepatic ischemia-reperfusion (IR) injury, but efficacy of IPC on mitochondrial proteome is not demonstrated. We investigated how IPC modifies the mitochondrial proteome after IR injury. Methods: Rats were subjected to 25 min of portal triad crossclamping (IR group, n = 8). In the IPC group (n = 8), 10 min of temporal portal triad

R. Oshima; H. Nakano; M. Katayama; J. Sakurai; W. Wu; S. Koizumi; T. Asano; T. Watanabe; T. Asakura; T. Ohta; T. Otsubo

2008-01-01

121

Using hormetic strategies to improve ischemic preconditioning and postconditioning against stroke.  

PubMed

Both ischemic preconditioning (IPreC) and ischemic postconditioning (IPostC) trigger endogenous neuroprotective mechanisms in cerebral ischemia. IPreC is defined as a brief ischemia that protects against a subsequent severe ischemia, while IPostC refers to a series of brief cerebral blood vessel occlusions performed at reperfusion following an ischemic event. Hormesis describes a biphasic dose-response relationship in toxicology, where a low dose of toxicant stimulates and a high dose inhibits biological responses. In general, any minor stress will stimulate a biological system to generate an adaptive response; in most cases, if not all, such an adaptive response to a minor stress is beneficial to the biological system. Proponents of hormesis suggest that this effect is independent of any models, either in vivo or in vitro, from animal, plant, fungi, yeast, to bacteria, by any measurement of end points, survival ratio or time, growth, tissue repair, life span, cognition, learning and memory. In this review, we examine whether IPreC and IPostC are actually sub-forms of hormesis and whether quantitative hormetic strategies can be used to study IPreC and IPostC. By integrating the concepts of IPreC and IPostC with hormesis, we aim to broaden the avenues leading to clinical translation of IPreC and IPostC in stroke treatment. PMID:23750305

Zhao, Heng; Joo, Sungpil; Xie, Weiying; Ji, Xunming

2013-05-27

122

Ischemic preconditioning alters cerebral microRNAs that are upstream to neuroprotective signaling pathways  

PubMed Central

Cerebral gene expression is known to be significantly influenced by a sublethal ischemic event (preconditioning; PC) that induces tolerance to future damaging ischemic events. Small non-coding RNAs known as microRNAs (miRNAs) were recently shown to control the mRNA translation. We currently profiled cerebral miRNAs in the cerebral cortex of rats subjected to PC. The miRNAome reacted quickly and by 6h following PC, levels of 51 miRNAs were altered (26 up- and 25 downregulated; >1.5 fold change). 20 of these stayed at the altered level even at 3 days after PC. At least 9 miRNAs showed >5 fold change at one or more time points between 6h to 3 days after PC compared to sham. Bioinformatics analysis showed 2007 common targets of the miRNAs that were up-regulated and 459 common targets of the miRNAs that were down-regulated after PC. Pathways analysis showed that MAP-kinase and mTOR signaling are the top 2 KEGG pathways targeted by the upregulated miRNAs, and Wnt and GnRH signaling are the top 2 KEGG pathways targeted by the down-regulated miRNAs after PC. We hypothesize that alterations in miRNAs and their down-stream mRNAs of signaling pathways might play a role in the induction of ischemic tolerance.

Dharap, Ashutosh; Vemuganti, Raghu

2010-01-01

123

An essential role of the JAK-STAT pathway in ischemic preconditioning  

PubMed Central

The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)–signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 ± 53%) and JAK2 (+238 ± 35%), indicating rapid activation of these two kinases. Similar results were obtained by immunoblotting with anti-pTyr-JAK1 and anti-pTyr-JAK2 antibodies. Western analysis with anti-pTyr-STAT antibodies demonstrated a marked increase in nuclear pTyr-STAT1 (+301 ± 61%) and pTyr-STAT3 (+253 ± 60%) 30 min after ischemic PC, which was associated with redistribution of STAT1 and STAT3 from the cytosolic to the nuclear fraction and with an increase in STAT1 and STAT3 ?-IFN activation site DNA-binding activity (+606 ± 64%), indicating activation of STAT1 and STAT3. No nuclear translocation or tyrosine phosphorylation of STAT2, STAT4, STAT5A, STAT5B, or STAT6 was observed. Pretreatment with the JAK inhibitor AG-490 20 min before the six occlusion/reperfusion cycles blocked the enhanced tyrosine phosphorylation of JAK1 and JAK2 and the increased tyrosine phosphorylation, nuclear translocation, and enhanced DNA-binding activity of STAT1 and STAT3. The same dose of AG-490 abrogated the protection against myocardial infarction and the concomitant up-regulation of inducible NO synthase (iNOS) protein and activity observed 24 h after ischemic PC. Taken together, these results demonstrate that ischemic PC induces isoform-selective activation of JAK1, JAK2, STAT1, and STAT3, and that ablation of this response impedes the up-regulation of iNOS and the concurrent acquisition of ischemic tolerance. This study demonstrates that the JAK-STAT pathway plays an essential role in the development of late PC. The results reveal a signaling mechanism that underlies the transcriptional up-regulation of the cardiac iNOS gene and the adaptation of the heart to ischemic stress.

Xuan, Yu-Ting; Guo, Yiru; Han, Hui; Zhu, Yanqing; Bolli, Roberto

2001-01-01

124

CBF changes associated with focal ischemic preconditioning in the spontaneously hypertensive rat.  

PubMed

Experimental stroke models exhibit robust protection after prior preconditioning (PC) insults. This study comprehensively examined cerebral blood flow (CBF) responses to permanent middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats preconditioned by noninjurious transient focal ischemia, using [(14)C]iodoantipyrine autoradiography at varied occlusion intervals. Preconditioning was produced by 10-min occlusion of the MCA and ipsilateral common carotid artery under halothane anesthesia. These vessels were permanently coagulated 24 h later in naïve, PC, and sham-operated rats. Infarct volumes were determined from hematoxylin-eosin-stained frozen sections after 1 or 3 days. Edema-corrected infarct volume was reduced from 127+/-21 in naïve rats to 101+/-31 and 52+/-28 mm(3) in sham and PC groups, respectively, at 1 day, with similar results at 3 days. All animals exhibited a consistent CBF threshold for infarction (approximately 30 mL/100 g/min). Tissue volumes below this threshold were identical in naïve and PC groups after 15-min occlusion. However, by 3 h the volume of ischemic cortex decreased in the PC group but remained unchanged in naïve rats, predicting final infarct volumes. Cerebral blood flow recovery was confirmed in brains of individual rats evaluated by repeated laser Doppler perfusion imaging during the same 3-h interval. Modest sham protection correlated with better-maintained global perfusion, detectable also in the contralateral cortex, apparently reflecting the PC effects of prior anesthesia. These results establish that timely reperfusion of penumbra, achieved by synergistic mechanisms, is a primary determinant of PC-induced protection in experimental stroke. PMID:16407854

Zhao, Liang; Nowak, Thaddeus S

2006-01-11

125

Cardiac-specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic preconditioning  

PubMed Central

Background Caveolae, lipid-rich microdomains of the sarcolemma, localize and enrich cardiac protective signaling molecules. Caveolin-3 (Cav-3), the dominant isoform in cardiac myocytes, is a determinant of caveolae formation. We hypothesized that cardiac myocyte-specific overexpression of Cav-3 would enhance the formation of caveolae and augment cardiac protection in vivo. Methods and Results Ischemic preconditioning (IPC) in vivo increased formation of caveolae. Adenovirus for Cav-3 increased caveolar formation and phosphorylation of survival kinases in cardiac myocytes. A transgenic (TG) mouse with cardiac myocyte-specific overexpression of Cav-3 (Cav-3 OE) showed enhanced formation of caveolae on the sarcolemma. Cav-3 OE mice subjected to ischemia/reperfusion injury had a significantly reduced infarct size relative to TGneg mice. Endogenous cardiac protection in Cav-3 OE mice was similar to wild-type mice undergoing IPC; no increased protection was observed in preconditioned Cav-3 OE mice. Cav-3 knockout mice did not show endogenous protection and showed no protection in response to IPC. Cav-3 OE mouse hearts had increased basal Akt and GSK3? phosphorylation comparable to wild-type mice exposed to IPC. Wortmannin, a PI3K inhibitor, attenuated basal phosphorylation of Akt and GSK3? and blocked cardiac protection in Cav-3 OE mice. Cav-3 OE mice had improved functional recovery and reduced apoptosis at 24 h of reperfusion. Conclusion Expression of caveolin-3 is both necessary and sufficient for cardiac protection, a conclusion that unites long-standing ultrastructural and molecular observations in the ischemic heart. The current results indicate that increased expression of caveolins, apparently via actions that depend on PI3K, has the potential to protect hearts exposed to ischemia-reperfusion injury.

Tsutsumi, Yasuo M.; Horikawa, Yousuke T.; Jennings, Michelle M.; Kidd, Michael W.; Niesman, Ingrid R.; Yokoyama, Utako; Head, Brian P.; Hagiwara, Yasuko; Ishikawa, Yoshihiro; Miyanohara, Atsushi; Patel, Piyush M.; Insel, Paul A.; Patel, Hemal H.; Roth, David M.

2009-01-01

126

Insulin suppresses ischemic preconditioning-mediated cardioprotection through Akt-dependent mechanisms.  

PubMed

It is believed that the diabetic myocardium is refractory to cardioprotection by ischemic preconditioning (IPC) mainly because of impaired insulin signaling to phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB or Akt). However, human as well as animal studies have clearly showed that the hearts of type 2 diabetic humans and animals may exhibit increased signaling through PI3K-Akt but yet are resistant to cardioprotection by IPC or ischemic post-conditioning. Therefore, this study was designed to determine whether activation of insulin signaling prior to IPC is detrimental for cardioprotection and to assess the role of insulin receptors (IRs) and Akt in mediating this effect. Wild-type (WT) hearts, hearts lacking IRs or hearts expressing an active form of Akt (myrAkt1) were perfused ex vivo using a Langendorff preparation and were subjected to IPC (3cycles of 5min ischemia followed by 5min reflow before 30min no flow ischemia and then by 45min reperfusion) in the presence or absence of 1nmol/L insulin. Interestingly, whereas insulin was protective against I/R (30min no flow ischemia and 45min reperfusion), it completely abolished cardioprotection by IPC in WT hearts but not in mice lacking insulin receptors (IRs) in cardiomyocytes (CIRKO) or in all cardiac cells (TIRKO). The suppression of IPC-mediated cardioprotection was mediated through downstream signaling to Akt and Gsk3?. In addition, transgenic induction of Akt in the heart was sufficient to abrogate IPC even when insulin was absent, further confirming the involvement of Akt in insulin's suppression of cardioprotection by IPC. These data provide evidence that excessive insulin signaling to Akt is detrimental for cardioprotection by IPC and could explain the failure of the diabetic myocardium to precondition. PMID:23994159

Fullmer, Tanner M; Pei, Shaobo; Zhu, Yi; Sloan, Crystal; Manzanares, Robert; Henrie, Brandon; Pires, Karla M; Cox, James E; Abel, E Dale; Boudina, Sihem

2013-08-30

127

Lovastatin interferes with the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts.  

PubMed

Statins have been shown to be cardioprotective; however, their interaction with endogenous cardioprotection by ischemic preconditioning and postconditioning is not known. In the present study, we examined if acute and chronic administration of the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor lovastatin affected the infarct size-limiting effect of ischemic preconditioning and postconditioning in rat hearts. Wistar rats were randomly assigned to the following three groups: 1) vehicle (1% methylcellulose per os for 12 days), 2) chronic lovastatin (15 mg.kg(-1).day(-1) per os for 12 days), and 3) acute lovastatin (1% methylcellulose per os for 12 days and 50 micromol/l lovastatin in the perfusate). Hearts isolated from the three groups were either subjected to a nonconditioning (aerobic perfusion followed by 30-min coronary occlusion and 120-min reperfusion, i.e., test ischemia-reperfusion), preconditioning (three intermittent periods of 5-min ischemia-reperfusion cycles before test ischemia-reperfusion), or postconditioning (six cycles of 10-s ischemia-reperfusion after test ischemia) perfusion protocol. Preconditioning and postconditioning significantly decreased infarct size in vehicle-treated hearts. However, preconditioning failed to decrease infarct size in acute lovastatin-treated hearts, but the effect of postconditioning remained unchanged. Chronic lovastatin treatment abolished postconditioning but not preconditioning; however, it decreased infarct size in the nonconditioned group. Myocardial levels of coenzyme Q9 were decreased in both acute and chronic lovastatin-treated rats. Western blot analysis revealed that both acute and chronic lovastatin treatment attenuated the phoshorylation of Akt; however, acute but not chronic lovastatin treatment increased the phosphorylation of p42 MAPK/ERK. We conclude that, although lovastatin may lead to cardioprotection, it interferes with the mechanisms of cardiac adaptation to ischemic stress. PMID:18359895

Kocsis, Gabriella F; Pipis, Judit; Fekete, Veronika; Kovács-Simon, Andrea; Odendaal, Louise; Molnár, Eva; Giricz, Zoltán; Janáky, Tamás; van Rooyen, Jacques; Csont, Tamás; Ferdinandy, Péter

2008-03-21

128

Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure.  

PubMed

Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure. PMID:21924386

Foster, Gary P; Westerdahl, Daniel E; Foster, Laura A; Hsu, Jeffrey V; Anholm, James D

2011-09-09

129

A role for tumor necrosis factor-? in ischemia and ischemic preconditioning  

PubMed Central

During cerebral ischemia, elevation of TNF-? and glutamate to pathophysiological levels may induce dysregulation of normal synaptic processes, leading ultimately to cell death. Previous studies have shown that patients subjected to a mild transient ischemic attack within a critical time window prior to a more severe ischemic episode may show attenuation in the clinical severity of the stroke and result in a more positive functional outcome. Studies with organotypic hippocampal cultures and mixed primary hippocampal cultures have shown that prior incubation with low concentrations of glutamate and TNF-? increase the resistance of neurones to a subsequent insult from glutamate, AMPA and NMDA, while co-exposure of TNF-? and for example AMPA may have neuroprotective effects compared to cultures exposed to excitotoxic agents alone. In addition our work has shown that although glutamate and TNF-? pretreatment induces analogous levels of desensitisation of the intracellular calcium dynamics of neurons under resting conditions and in response to acute glutamate stimulation, their downstream signalling pathways involved in this response do not converge. Glutamate and TNF-? would appear to have opposing effects on resting Ca2+ levels which supports the proposal that they have distinct modes of preconditioning.

2011-01-01

130

Mitogen-activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic preconditioning.  

PubMed

We previously described the phenomenon of retinal ischemic pre-conditioning (IPC) and we have shown the role of various signaling proteins in the protective pathways, including the mitogen-activated protein kinase p38. In this study we examined the role in IPC of mitogen-activated protein kinase phosphatase-1 (MKP-1), which inactivates p38. Ischemia was produced by elevation of intraocular pressure above systolic arterial blood pressure in adult Wistar rats. Preconditioning was produced by transient retinal ischemia for 5 min, 24 h prior to ischemia. Small interfering RNA (siRNA) to MKP-1 or a control non-silencing siRNA, was injected into the vitreous 6 h prior to IPC. Recovery was assessed by electroretinography (ERG) and histology. The a-and b-waves, and oscillatory potentials (OPs), measured before and 1 week after ischemia, were then normalized relative to pre-ischemic baseline, and corrected for diurnal variation in the normal non-ischemic eye. The P2, or post-photoreceptor component of the ERG (which reflects function of the rod bipolar cells in the inner retina), was derived using the Hood-Birch model. MKP-1 was localized in specific retinal cells using immunohistochemistry; levels of mitogen-activated protein kinases were measured using Western blotting. Injection of siRNA to MKP-1 significantly attenuated the protective effect of IPC as reflected by decreased recovery of the electroretinogram a and b-waves and the P2 after ischemia. The injection of siRNA to MKP-1 reduced the number of cells in the retinal ganglion cell and outer nuclear layers after IPC and ischemia. Blockade of MKP-1 by siRNA also increased the activation of p38 at 24 h following IPC. MKP-1 siRNA did not alter the levels of phosphorylated jun N-terminal kinase (JNK) or extracellular signal-regulated kinase (ERK) after IPC. The results suggest the involvement of dual-specificity phosphatase MKP-1 in IPC and that MKP-1 is involved in IPC by regulating levels of activated MAPK p38. PMID:21094639

Dreixler, John C; Bratton, Anthony; Du, Eugenie; Shaikh, Afzhal R; Savoie, Brian; Alexander, Michael; Marcet, Marcus M; Roth, Steven

2010-11-20

131

Cardioprotection by ischemic and nonischemic myocardial stress and ischemia in remote organs. Implications for the concept of ischemic preconditioning.  

PubMed

Ischemic preconditioning studies employ one or more brief total coronary artery occlusions separated by complete reperfusion to limit infarct size during a subsequent prolonged coronary artery occlusion. We now present evidence that in anesthetized pigs a partial coronary artery occlusion without intervening reperfusion between the partial and prolonged total occlusions can also precondition the myocardium provided that the reduction in coronary blood flow is sufficiently severe. Thus infarct size was reduced after a 60 min total coronary artery occlusion when the total occlusion was preceded by a partial coronary occlusion that reduced coronary blood flow by 70% but not when the flow reduction was only 30%. In this two-stage coronary occlusion model the degree of protection appears greater in the epicardial than in the endocardial half. In view of evidence that brief occlusions of a coronary artery also protect myocardium outside its perfusion territory, we subsequently investigated whether ischemia in remote organs can protect myocardium. Because of reports that development of infarct size may be temperature dependent, we also investigated whether the cardioprotection by remote organ ischemia was temperature dependent. In anesthetized rats a 15 min coronary artery occlusion was more effective in reducing infarct size produced by a subsequent 60 min total coronary artery occlusion when the experiments were performed at a body core temperature of 30-31 degrees C than at 36-37 degrees C, while infarct size of animals which were subjected to only the 60 min total coronary artery occlusion was the same for the two body core temperatures. In rats with a body core temperature of 36-37 degrees C a 15 min mesenteric artery occlusion, but not a 15 min renal artery occlusion, reduced infarct size produced by a subsequent 60 min coronary artery occlusion. When the experiments were performed at 30-31 degrees C both the mesenteric and renal artery occlusions were protective. These observations indicate the local myocardial ischemia is not required to protect the myocardium during a prolonged coronary occlusion. We further investigated whether myocardium could also be protected by a cardiac stimulus which does not produce ischemia at all. For this purpose we electrically paced the left ventricle of anesthetized pigs to produce heart rates of 200 bpm (which did not lead to ischemia as assessed by a number of functional and biochemical variables) and found that 30 min of ventricular pacing reduced myocardial infarct size produced by a subsequent 60 min coronary artery occlusion. The protection by ventricular pacing involved activation of K+ATP channels as pretreatment with glibenclamide abolished the protection by ventricular pacing. We conclude that a number of distinctly different stimuli can protect the myocardium suggesting that ischemic myocardial preconditioning could be just one feature of a more general protection phenomenon. PMID:8906153

Verdouw, P D; Gho, B C; Koning, M M; Schoemaker, R G; Duncker, D J

1996-09-30

132

Pharmacological preconditioning with hyperbaric oxygen: can this therapy attenuate myocardial ischemic reperfusion injury and induce myocardial protection via nitric oxide?  

PubMed

Ischemic reperfusion injury (IRI) is an inevitable part cardiac surgery such as coronary artery bypass graft (CABG). While ischemic hypoxia and the ensuing normoxic or hyperoxic reperfusion are critical to the initiation and propagation of IRI, conditioning myocardial cells to an oxidative stress prior to IRI may limit the consequences of this injury. Hyperbaric oxygen (HBO2) is a modality of treatment that is known to generate an oxidative stress. Studies have shown that treatment with HBO2 postischemia and reperfusion is useful in ameliorating myocardial IRI. Moreover, preconditioning the myocardium with HBO2 before reperfusion has demonstrated a myocardial protective effect by limiting the infarct size post ischemia and reperfusion. Current evidence suggests that HBO2 preconditioning may partly attenuate IRI by stimulating the endogenous production of nitric oxide (NO). As NO has the capacity to reduce neutrophil sequestration, adhesion and associated injury, and improve vascular flow, HBO2 preconditioning induced NO may play a role in providing myocardial protection during interventions that involve an inevitable episode of IRI. This current opinion review article attempts to suggest that HBO2 may be used to pharmacologically precondition and protect the myocardium from the effects of IRI that is known to occur during cardiac surgery. PMID:17996900

Yogaratnam, Jeysen Zivan; Laden, Gerard; Guvendik, Lavent; Cowen, Mike; Cale, Alex; Griffin, Steve

2007-10-11

133

Evidence for an essential role of cyclooxygenase-2 as a mediator of the late phase of ischemic preconditioning in mice  

Microsoft Academic Search

Recent studies have demonstrated that cyclooxygenase-2 (COX-2) is an essential mediator of the cardioprotective effects of\\u000a the late phase of ischemic preconditioning (PC) in rabbits. The goal of this study was to determine whether COX-2 also plays\\u000a an essential role in late PC in the mouse. B6129F2\\/J mice underwent a 30-min coronary occlusion followed by 24 h of reperfusion. Administration

Yiru Guo; Weike Bao; Wen-Jian Wu; Ken Shinmura; Xian-Liang Tang; Roberto Bolli

2000-01-01

134

Essential Role of Adenosine, Adenosine A1 Receptors, and ATP-Sensitive K^+ Channels in Cerebral Ischemic Preconditioning  

Microsoft Academic Search

Preconditioning with sublethal ischemia protects against neuronal damage after subsequent lethal ischemic insults in hippocampal neurons. A pharmacological approach using agonists and antagonists at the adenosine A1 receptor as well as openers and blockers of ATP-sensitive K^+ channels has been combined with an analysis of neuronal death and gene expression of subunits of glutamate and gamma-aminobutyric acid receptors, HSP70, c-fos,

Catherine Heurteaux; Inger Lauritzen; Catherine Widmann; Michel Lazdunski

1995-01-01

135

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

2006-01-01

136

Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog.  

PubMed

Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, no studies have addressed the possibility that EETs serve a beneficial role in IPC or POC. We tested the hypothesis that EETs may play a role in these two phenomena by preconditioning dog hearts with one 5-min period of total coronary occlusion followed by 10 min of reperfusion before 60 min of occlusion and 3 h of reperfusion or by postconditioning with three 30-s periods of reperfusion interspersed with three 30-s periods of occlusion. To test for a role of EETs in IPC and POC, the selective EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) or its derivative, 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester (14,15-EEZE-PEG), were administered 10 min before IPC, 5 min after IPC, or 5 min before POC. In a separate series, the selective EET synthesis inhibitor N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) was administered 10 min before IPC. Infarct size was determined by tetrazolium staining and coronary collateral blood flow at 30 min of occlusion and reperfusion flow at 3 h by radioactive microspheres. Both IPC and POC produced nearly equivalent reductions in IS expressed as a percentage of the area at risk (AAR) [Control 21.2 +/- 1.2%, IPC 8.3 +/- 2.2%, POC 10.1 +/- 1.8% (P < 0.001)]. 14,15-EEZE, 14,15-EEZE-PEG, and MS-PPOH markedly attenuated the cardioprotective effects of IPC and POC (14,15-EEZE and 14,15-EEZE-PEG) at doses that had no effect on IS/AAR when given alone. These results suggest a unique role for endogenous EETs in both IPC and POC. PMID:19448143

Gross, Garrett J; Gauthier, Kathryn M; Moore, Jeannine; Campbell, William B; Falck, John R; Nithipatikom, Kasem

2009-05-15

137

Evidence for role of epoxyeicosatrienoic acids in mediating ischemic preconditioning and postconditioning in dog  

PubMed Central

Cytochrome P-450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites, the epoxyeicosatrienoic acids (EETs), have been shown to produce marked reductions in infarct size (IS) in canine myocardium either given before an ischemic insult or at reperfusion similar to that produced in ischemic preconditioning (IPC) and postconditioning (POC) protocols. However, no studies have addressed the possibility that EETs serve a beneficial role in IPC or POC. We tested the hypothesis that EETs may play a role in these two phenomena by preconditioning dog hearts with one 5-min period of total coronary occlusion followed by 10 min of reperfusion before 60 min of occlusion and 3 h of reperfusion or by postconditioning with three 30-s periods of reperfusion interspersed with three 30-s periods of occlusion. To test for a role of EETs in IPC and POC, the selective EET antagonists 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) or its derivative, 14,15-epoxyeicosa-5(Z)-enoic acid 2-[2-(3-hydroxy-propoxy)-ethoxy]-ethyl ester (14,15-EEZE-PEG), were administered 10 min before IPC, 5 min after IPC, or 5 min before POC. In a separate series, the selective EET synthesis inhibitor N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) was administered 10 min before IPC. Infarct size was determined by tetrazolium staining and coronary collateral blood flow at 30 min of occlusion and reperfusion flow at 3 h by radioactive microspheres. Both IPC and POC produced nearly equivalent reductions in IS expressed as a percentage of the area at risk (AAR) [Control 21.2 ± 1.2%, IPC 8.3 ± 2.2%, POC 10.1 ± 1.8% (P < 0.001)]. 14,15-EEZE, 14,15-EEZE-PEG, and MS-PPOH markedly attenuated the cardioprotective effects of IPC and POC (14,15-EEZE and 14,15-EEZE-PEG) at doses that had no effect on IS/AAR when given alone. These results suggest a unique role for endogenous EETs in both IPC and POC.

Gross, Garrett J.; Gauthier, Kathryn M.; Moore, Jeannine; Campbell, William B.; Falck, John R.; Nithipatikom, Kasem

2009-01-01

138

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.

2013-01-01

139

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

2004-01-01

140

ERK-MAPK Signaling Opposes Rho-Kinase to Reduce Cardiomyocyte Apoptosis in Heart Ischemic Preconditioning  

PubMed Central

We and others have reported that Rho-kinase plays an important role in the pathogenesis of heart ischemia/reperfusion (I/R) injury. Studies have also demonstrated that the activation of Rho-kinase is reversed in ischemic preconditioning (IPC). However, the mechanisms by which Rho-kinase is increased in I/R and reversed in IPC are not thoroughly understood. In female Wistar rats, we created I/R by ligating the left anterior–descending branch of the coronary artery (LAD) for 30 min and releasing the ligature for 180 min. IPC rats underwent IPC (two cycles of 5-min ligation of the LAD and 5-min reflow) before I/R. IPC caused a significant increase in extracellular signal–regulated kinase (ERK)1/2 activity and reduced Rho-kinase activity and cardiomyocyte apoptosis (P < 0.05 versus I/R). Administration of PD98059, an inhibitor of ERK–mitogen-activated protein kinase (MAPK), increased cardiomyocyte apoptosis, Caspase-3 activity and myocardial infarction size (P < 0.05 versus IPC). Western-blot analysis showed that administration of PD98059 increased Rho-kinase activity. Treatment with fasudil, an inhibitor of Rho-kinase, reversed cell apoptosis caused by treatment with PD98059 in IPC. In addition, ROCK1 (Rho-kinase 1) may be the major Rho-kinase isoform that is opposed by ERK-MAPK signaling in IPC. These results indicate that ERK-MAPK signaling is required in IPC to oppose Rho-kinase activity in cardiomyocyte apoptosis in vivo.

Juan-Zhang; Bian, Hong-Jun; Li, Xiao-Xing; Liu, Xiao-Bo; Sun, Jun-Ping; Na-Li; Yun-Zhang; Ji, Xiao-Ping

2010-01-01

141

Ischemic Preconditioning in the Animal Kidney, a Systematic Review and Meta-Analysis  

PubMed Central

Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h?=?early vs. ?24 h?=?late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.

Rovers, Maroeska; van der Vliet, J. Adam; Rongen, Gerard A.; Masereeuw, Rosalinde; Ritskes-Hoitinga, Merel; Hooijmans, Carlijn R.; Warle, Michiel

2012-01-01

142

Apolipoprotein A-I Is a Potential Mediator of Remote Ischemic Preconditioning  

PubMed Central

Background Remote ischemic preconditioning (RIPC) has emerged as an attractive strategy in clinical settings. Despite convincing evidence of the critical role played by circulating humoral mediators, their actual identities remain unknown. In this study, we aimed to identify RIPC-induced humoral mediators using a proteomic approach. Methods and Results Rats were exposed to 10-min limb ischemia followed by 5- (RIPC 5?) or 10-min (RIPC 10?) reperfusion prior to blood sampling. The control group only underwent blood sampling. Plasma samples were analyzed using surface-enhanced laser desorption and ionization - time of flight - mass spectrometry (SELDI-TOF-MS). Three protein peaks were selected for their significant increase in RIPC 10?. They were identified and confirmed as apolipoprotein A-I (ApoA-I). Additional rats were exposed to myocardial ischemia-reperfusion (I/R) and assigned to one of the following groups RIPC+myocardial infarction (MI) (10-min limb ischemia followed by 10-min reperfusion initiated 20 minutes prior to myocardial I/R), ApoA-I+MI (10 mg/kg ApoA-I injection 10 minutes before myocardial I/R), and MI (no further intervention). In comparison with untreated MI rats, RIPC reduced infarct size (52.2±3.7% in RIPC+MI vs. 64.9±2.6% in MI; p<0.05). Similarly, ApoA-I injection decreased infarct size (50.9±3.8%; p<0.05 vs. MI). Conclusions RIPC was associated with a plasmatic increase in ApoA-I. Furthermore, ApoA-I injection before myocardial I/R recapitulated the cardioprotection offered by RIPC in rats. This data suggests that ApoA-I may be a protective blood-borne factor involved in the RIPC mechanism.

Hibert, Pierre; Prunier-Mirebeau, Delphine; Beseme, Olivia; Chwastyniak, Maggy; Tamareille, Sophie; Lamon, Delphine; Furber, Alain; Pinet, Florence; Prunier, Fabrice

2013-01-01

143

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.

2013-01-01

144

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

PubMed

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

2010-09-10

145

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 ClinicalTrials.gov: NCT00883467

2011-01-01

146

Improved resistance to ischemia and reperfusion, but impaired protection by ischemic preconditioning in patients with type 1 diabetes mellitus: a pilot study  

PubMed Central

Background In patients with type 1 diabetes mellitus (T1DM), cardiovascular events are more common, and the outcome following a myocardial infarction is worse than in nondiabetic subjects. Ischemic or pharmacological preconditioning are powerful interventions to reduce ischemia reperfusion (IR)-injury. However, animal studies have shown that the presence of T1DM can limit these protective effects. Therefore, we aimed to study the protective effect of ischemic preconditioning in patients with T1DM, and to explore the role of plasma insulin and glucose on this effect. Methods 99mTechnetium-annexin A5 scintigraphy was used to detect IR-injury. IR-injury was induced by unilateral forearm ischemic exercise. At reperfusion, Tc-annexin A5 was administered, and IR-injury was expressed as the percentage difference in radioactivity in the thenar muscle between the experimental and control arm 4 hours after reperfusion. 15 patients with T1DM were compared to 21 nondiabetic controls. The patients were studied twice, with or without ischemic preconditioning (10 minutes of forearm ischemia and reperfusion). Patients were studied in either normoglycemic hyperinsulinemic conditions (n?=?8) or during hyperglycemic normoinsulinemia (n?=?7). The controls were studied once either with (n?=?8) or without (n?=?13) ischemic preconditioning. Results Patients with diabetes were less vulnerable to IR-injury than nondiabetic healthy controls (12.8?±?2.4 and 11.0?±?5.1% versus 27.5?±?4.5% in controls; p?ischemic preconditioning to reduce IR-injury, however, was lower in the patients and was even completely abolished during hyperglycemia. Conclusions Patients with T1DM are more tolerant to forearm IR than healthy controls in our experimental model. The efficacy of ischemic preconditioning to limit IR-injury, however, is reduced by acute hyperglycemia. Trial Registration The study is registered at www.clinicaltrials.gov (NCT00184821)

2012-01-01

147

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

1996-01-01

148

Inducible Nitric Oxide Synthase Modulates Cyclooxygenase2 Activity in the Heart of Conscious Rabbits During the Late Phase of Ischemic Preconditioning  

Microsoft Academic Search

Cyclooxygenase-2 (COX-2) is known to mediate the cardioprotective effects of the late phase of ischemic preconditioning (PC); however, the signaling pathways involved in COX-2 induction following ischemic PC are unknown. In addition, although inducible nitric oxide synthase (iNOS) has been identified as a co-mediator of late PC together with COX-2, the interaction between iNOS and COX-2 in the heart is

Ken Shinmura; Yu-Ting Xuan; Xian-Liang Tang; Eitaro Kodani; Hui Han; Yanqing Zhu; Roberto Bolli

149

Demonstration of Selective Protein Kinase C-Dependent Activation of Src and Lck Tyrosine Kinases During Ischemic Preconditioning in Conscious Rabbits  

Microsoft Academic Search

Abstract—Src tyrosine kinases have been shown to mediate cellular responses to stress in noncardiac cells. However, the effect of myocardial ischemia on Src tyrosine kinases is unknown. Furthermore, the identity of the tyrosine kinase(s) involved in the genesis of ischemic preconditioning (PC) remains obscure. Here, we present the first evidence that ischemic PC (6 cycles of 4-minute coronary occlusion and

Peipei Ping; Jun Zhang; Yu-Ting Zheng; Richard C. X. Li; Buddhabeb Dawn; Xian-Liang Tang; Hitoshi Takano; Zarema Balafanova; Roberto Bolli

2010-01-01

150

HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS  

EPA Science Inventory

Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection Induced by Ischemic Preconditioning of the Mouse Heart Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 , Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

151

In vitro hypoxic preconditioning of embryonic stem cells as a strategy of promoting cell survival and functional benefits after transplantation into the ischemic rat brain  

Microsoft Academic Search

Hypoxic preconditioning (HP) and stem cell transplantation have been extensively studied as individual therapies for ischemic stroke. The present investigation is an initial effort to combine these methods to achieve increased therapeutic effects after brain ischemia. Sublethal in vitro hypoxia pretreatment significantly enhanced the tolerance of neurally-differentiating embryonic stem (ES) cells and primary bone marrow mesenchymal stem cells (BMSC) to

Michelle Hedrick Theus; Ling Wei; Lin Cui; Kevin Francis; Xinyang Hu; Christine Keogh; Shan Ping Yu

2008-01-01

152

Ischemic Preconditioning Mediates Cyclooxygenase-2 Expression Via Nuclear Factor-Kappa B Activation in Mixed Cortical Neuronal Cultures  

PubMed Central

Nuclear factor-kappaB (NF-?B) activation occurs following ischemic preconditioning (IPC) in brain. However, the upstream signaling messengers and down-stream targets of NF-?B required for induction of IPC remain undefined. In a previous study, we demonstrated that epsilon protein kinase c (?PKC) was a key mediator of IPC in brain. Activation of ?PKC induced cyclooygenase-2 (COX-2) expression and conferred ischemic tolerance in the neuronal and hippocampal slice models. Here, we hypothesized that IPC-mediated COX-2 expression was mediated by NF-?B. We tested this hypothesis in mixed cortical neuron/astrocyte cell cultures. To simulate IPC or ischemia, cell cultures were exposed to 1 or 4 h of oxygen–glucose deprivation, respectively. Our results demonstrated translocation of p65 and p50 subunits of NF-?B into nucleus following IPC or ?PKC activation. NF-?B inhibition with pyrrolidine dithiocarbamate (10 ?M) abolished IPC or ?PKC activator-mediated neuroprotection indicating that NF-?B activation was involved in ischemic tolerance. In parallel studies, inhibition of either ?PKC or the extracellular signal-regulated kinase (ERK 1/2) pathway reduced IPC-induced NF-?B activation. Finally, inhibition of NF-?B blocked IPC-induced COX-2 expression. In conclusion, we demonstrated that IPC-signaling cascade comprises ?PKC activation?ERK1/2 activation?NF-?B translocation to nucleus?COX-2 expression resulting in neuroprotection in mixed neuronal culture.

Kim, Eun Joo; Raval, Ami P.; Hirsch, Nina

2010-01-01

153

Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts  

Microsoft Academic Search

Nitric oxide plays a crucial role in myocardial ischemia reperfusion injury as well as in myocardial adaptation to ischemic stress. To understand the dichotomy of nitric oxide behavior in the ischemic myocardium, isolated rat hearts were subjected to ischemia\\/reperfusion protocol. The tissue contents of sphingomyelin (SM), ceramide and sphingosine were determined by high performance thin layer chromatography (HPTLC). The myocardial

Peter Der; Jianhua Cui; Dipak K. Das

2006-01-01

154

Ischemic preconditioning-induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide-2 deficiency  

PubMed Central

The ubiquitin-proteasome system plays an important role in many cellular processes through degradation of specific proteins. Low molecular mass polypeptide 2 (LMP-2 or ?1i) is one important subunit of the immunoproteasome. Ischemic preconditioning (IPC) activates cell signaling pathways and generates cardioprotection but has not been linked to LMP-2 function previously. LMP-2 knockout mice (C57BL6 background) and wild-type C57BL6 mice were subjected to 30 min of ischemia (I-30) and 120 min of reperfusion (R-120) with or without preceding IPC (10 min of infusion and 5 min of reperfusion). IPC significantly increased left ventricular developed pressure and decreased infarct size in wild-type mice, but this protective effect of IPC was lost in LMP-2 knockout mice. IPC-mediated degradation of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and activation of the downstream protein kinase Akt were impaired in LMP-2 knockout hearts. The impairment of PTEN degradation was associated with defective immunoproteasomes and decreased proteolytic activities. When LMP-2 knockout mice were pretreated with the PTEN inhibitor bpV(HOpic), cardiac function was significantly improved, and myocardial infarct size was significantly reduced after I-30/R-120. In conclusion, LMP-2 is required for normal proteasomal function and IPC induction in the heart. Its action may be related to PTEN protein degradation.—Cai, Z. P., Shen, Z., Van Kaer, L., Becker, L. C. Ischemic preconditioning-induced cardioprotection is lost in mice with immunoproteasome subunit low molecular mass polypeptide-2 deficiency.

Cai, Zheqing P.; Shen, Zhenyun; Van Kaer, Luc; Becker, Lewis C.

2008-01-01

155

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

1999-01-01

156

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

PubMed

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

2001-04-01

157

Ischemic pre-conditioning of 5 minutes but not of 10 minutes improves lung function after warm ischemia in a canine model  

Microsoft Academic Search

Background: Protection from reperfusion injury by ischemic pre-conditioning (IPC) before prolonged ischemia has been proven for the heart and the liver. We now assess the efficacy of IPC to protect lungs from reperfusion injury.Methods: Eighteen foxhounds (25 to 30 kg) were anesthetized, intubated, and ventilated with a fraction of inspired oxygen of 0.3 at a volume-controlled mode to maintain arterial

Ivar Friedrich; Jan Spillner; Er-Xiong Lu; Babette Bartling; Markus Barnscheid; Armin Sablotzki; Ulrich Schade; J. Christoph Reidemeister; Rolf Edgar Silber; Andreas Gunther; Jochen Borgermann

2001-01-01

158

Cardioprotection During the Final Stage of the Late Phase of Ischemic Preconditioning Is Mediated by Neuronal NO Synthase in Concert With Cyclooxygenase2  

Microsoft Academic Search

The infarct-sparing effect of the late phase of ischemic preconditioning (late PC) lasts for 72 hours. Upregulation of both cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) has been shown to be essential to the protection in the initial stage of late PC (24 hours after PC); however, the mechanisms underlying the protection in the final stage of late PC (48

Yang Wang; Eitaro Kodani; Jianxun Wang; Shelley X. Zhang; Hitoshi Takano; Xian-Liang Tang; Roberto Bolli

2009-01-01

159

VEGFR1 (Flt-1+/?) GENE KNOCKOUT LEADS TO THE DISRUPTION OF VEGF MEDIATED SIGNALING THROUGH NITRIC OXIDE/HEMEOXYGENASE PATHWAY IN ISCHEMIC PRECONDITIONED MYOCARDIUM  

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

2007-01-01

160

Enriched environment preconditioning induced brain ischemic tolerance without reducing infarct volume and edema: the possible role of enrichment-related physical activity increase.  

PubMed

External stimuli, including environmental enrichment (EE) and physical activity, have been shown to significantly facilitate recovery from brain injury. However, whether EE can be used as a preconditioning method to induce cerebral ischemic tolerance has never been investigated. Furthermore, whether, and to what extent, such environmental stimuli regulate physical activity to promote neuroprotection is largely unclear. To examine the neuroprotective effects of pre-ischemic EE (PIEE) and to investigate the relationship between these effects and EE-induced physical activity, we tested neurobehavioral and morphological recovery of rats following transient focal cerebral ischemia. Our study showed that PIEE improved the recovery of motor function, spatial learning and memory without reduction in brain edema or infarct volume. We also found that PIEE robustly increased the level of physical activity of rats that positively correlated with the extent of neurobehavioral recovery. Our results suggest that PIEE may induce brain ischemic tolerance through, at least partially, increasing physical activity. PMID:23501217

Xie, Hongyu; Wu, Yi; Jia, Jie; Liu, Gang; Zhang, Feng; Zhang, Qi; Yu, Kewei; Hu, Yongshan; Bai, Yulong; Hu, Ruiping

2013-03-15

161

Dietary (n-3) long-chain polyunsaturated fatty acids inhibit ischemia and reperfusion arrhythmias and infarction in rat heart not enhanced by ischemic preconditioning.  

PubMed

Ischemic preconditioning (IPC) and (n-3) PUFA are both cardioprotective. This study compared effects of dietary fish oil, IPC, and their interactions on heart function and injury during myocardial ischemia and reperfusion. Male Wistar rats were fed diets containing 10% wt:wt fat comprising either 7% high-docosahexaenoic acid (DHA) [22:6(n-3)] tuna fish oil + 3% olive oil [(n-3) PUFA]; 5% sunflower seed oil + 5% olive oil [(n-6) PUFA]; or 7% beef tallow + 3% olive oil [saturated fat (SF)] for 6 wk. In control experiments, isolated perfused hearts were subjected to 30-min regional ischemia and reperfused for 120 min. The IPC hearts were subjected to 3 cycles of 5-min global ischemia before the ischemia and reperfusion. Control (n-3) PUFA hearts had significantly lower heart rate, coronary flow, end diastolic pressure, maximum relaxation rate, and ischemic and reperfusion arrhythmias. In reperfusion, they had greater developed pressure and maximum relaxation rate and smaller infarct (10.9 +/- 0.6% ischemic zone, n = 6) than (n-6) PUFA (47.4 +/- 0.3%, n = 6) or SF (50.3 +/- 0.3%, n = 6). Compared with control, IPC significantly improved heart function and reduced infarct in (n-6) PUFA (11.8 +/- 0.4%, n = 6) and SF hearts (13.1 +/- 0.1%, n = 6). Heart function and infarct [(n-3) PUFA 9.6 +/- 0.1%, n = 6] did not differ among dietary IPC groups. Arrhythmias, significantly reduced by IPC in (n-6) PUFA and SF hearts, were significantly lower in (n-3) PUFA IPC hearts. Dietary fish oil induces a form of preconditioning, nutritional preconditioning, limiting ischemic cardiac injury, and myocardial infarction and endows cardioprotection as powerful as IPC, which provides no additional protection in (n-3) PUFA hearts. PMID:18806099

Abdukeyum, Grace G; Owen, Alice J; McLennan, Peter L

2008-10-01

162

Myocardium tolerant to an adenosine-dependent ischemic preconditioning stimulus can still be protected by stimuli that employ alternative signaling pathways.  

PubMed

Clinical studies on cardioprotection by preinfarct angina are ambiguous, which may involve development of tolerance to repeated episodes of ischemia. Not all preconditioning stimuli use identical signaling pathways, and because patients likely experience varying numbers of episodes of preinfarct angina of different degrees and durations, it is important to know whether myocardium tolerant to a particular preconditioning stimulus can still be protected by stimuli employing alternative signaling pathways. We tested the hypothesis that development of tolerance to a particular stimulus does not affect cardioprotection by stimuli that employ different signaling pathways. Anesthetized rats underwent classical, remote or pharmacological preconditioning. Infarct size (IS), produced by a 60-min coronary artery occlusion (CAO), was determined after 120 min of reperfusion. Preconditioning by two 15-min periods of CAO (2CAO15, an adenosine-dependent stimulus) limited IS from 69 +/- 2% to 37 +/- 6%, but when 2CAO15 was preceded by 4CAO15, protection by 2CAO15 was absent (IS = 68 +/- 1%). This development of tolerance coincided with a loss of cardiac interstitial adenosine release, whereas two 15-min infusions of adenosine (200 microg/min i.v.) still elicited cardioprotection (IS = 40 +/- 4%). Furthermore, cardioprotection was produced when 4CAO15 was followed by the adenosine-independent stimulus 3CAO3 (IS = 50 +/- 8%) or the remote preconditioning stimulus of two 15-min periods of mesenteric artery occlusion (IS = 49 +/- 6%). In conclusion, development of tolerance to cardioprotection by an adenosine-dependent preconditioning stimulus still allows protection by pharmacological or ischemic stimuli intervention employing different signaling pathways. PMID:15486028

Liem, David A; te Lintel Hekkert, Maaike; Manintveld, Olivier C; Boomsma, Frans; Verdouw, Pieter D; Duncker, Dirk J

2004-10-14

163

Neuroprotection of preconditioning against ischemic brain injury in rat hippocampus through inhibition of the assembly of GluR6—PSD95—mixed lineage kinase 3 signaling module via nuclear and non-nuclear pathways  

Microsoft Academic Search

Our previous studies showed that the assembly of the GluR6–PSD95–mixed lineage kinase 3 (MLK3) signaling module played an important role in rat ischemic brain injury. In this study, we aimed to elucidate whether ischemic preconditioning could downregulate the assembly of the GluR6–PSD95–MLK3 signaling module and suppress the activation of MLK3, MKK4\\/7, and c-Jun N-terminal kinase (JNK). As a result, ischemic

Y. Du; C. Li; W.-W. Hu; Y.-J. Song; G.-Y. Zhang

2009-01-01

164

Phosphorylated MAPK/ERK1/2 may not always represent its kinase activity in a rat model of focal cerebral ischemia with or without ischemic preconditioning  

PubMed Central

The ERK 1/2 protein require a dual phosphorylation at conserved threonine and tyrosine residues to be fully activated under normal physiological conditions. Thus, ERK1/2 kinase activity is often defined by the quantity of phosphorylated kinase. However, this may not accurately represent its true activity under certain pathological conditions. We investigated whether ERK1/2 kinase activity is proportional to its phosphorylation state in a rat focal ischemia model with and without rapid ischemic preconditioning. We showed that phosphorylated-ERK1/2 protein levels were increased 2.6±0.07 fold, and ERK1/2 kinase activity was increased 10.6±1.9 fold in animals receiving ischemic preconditioning alone without test ischemia compared with sham group (P<0.05, n=6/group), suggesting that phosphorylated-ERK1/2 protein levels represent its kinase activity under these conditions. However, preconditioning plus test ischemia robustly blocked ERK1/2 kinase activity, while it increased phosphorylated-ERK1/2 protein levels beyond those receiving test ischemia alone, suggesting that phosphorylated-ERK1/2 protein levels were not representative of actual kinase activity in this pathological condition. In conclusion, protein phosphorylation levels of ERK1/2 do not always correspond to kinase activity, thus, measuring the true kinase activity is essential.

Takahashi, Tetsuya; Steinberg, Gary K.; Zhao, Heng

2012-01-01

165

Remote ischemic preconditioning confers late protection against myocardial ischemia-reperfusion injury in mice by upregulating interleukin-10  

PubMed Central

Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia-reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. Mice were exposed to lower limb RIPC or sham ischemia. After 24 h, mice with RIPC demonstrated decreased myocardial infarct size and improved cardiac contractility following 30-min ischemia and 120-min reperfusion (I-30/R-120). These effects of RIPC were completely blocked by anti-IL-10 receptor antibodies. In IL-10 knockout mice, RIPC cardioprotection was lost, but it was mimicked by exogenous IL-10. Administration of IL-10 to isolated perfused hearts increased phosphory-lation of the protein kinase Akt and limited infarct size after I-30/R-120. In wild-type mice, RIPC increased plasma and cardiac IL-10 protein levels and caused activation of Akt and endothelial nitric oxide synthase in the heart at 24 h, which was also blocked by anti-IL-10 receptor antibodies. In the gastrocnemius muscle, RIPC resulted in immediate inactivation of the phosphatase PTEN and activation of Stat3, with increased IL-10 expression 24 h later. Myocyte-specific PTEN inactivation led to increased Stat3 phosphorylation and IL-10 protein expression in the gastrocnemius muscle. Taken together, these results suggest that RIPC induces late protection against myocardial IR injury by increasing expression of IL-10 in the remote muscle, followed by release of IL-10 into the circulation, and activation of protective signaling pathways in the heart. This study provides a scientific basis for the use of RIPC to confer systemic protection against IR injury.

Parajuli, Nirmal; Zheng, Xiaoxu; Becker, Lewis

2013-01-01

166

The alpha1 isoform of soluble guanylate cyclase regulates cardiac contractility but is not required for ischemic preconditioning  

PubMed Central

Nitric oxide (NO)-dependent soluble guanylate cyclase (sGC) activation is an important component of cardiac signal transduction pathways, including the cardioprotective signaling cascade induced by ischemic preconditioning (IPC). The sGC? subunit, which binds to the common sGC?1 subunit, exists in two different isoforms, sGC?1 and sGC?2, but their relative physiological roles remain unknown. In the present study, we studied Langendorff-perfused isolated hearts of genetically engineered mice lacking functional sGC?1 (sGC?1KO mice), which is the predominant isoform in the heart. Our results show that the loss of sGC?1 has a positive inotropic and lusitropic effect on basal cardiac function, indicating an important role for sGC?1 in regulating basal myocardial contractility. Surprisingly, IPC led to a similar 35–40% reduction in infarct size and concomitant protein kinase C? (PKC?) phosphorylation in both wild-type (WT) and sGC?1KO hearts subjected to 40 min of global ischemia and reperfusion. Inhibition of the activation of all sGC isoforms by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, 10 ?mol/L) completely abolished the protection by IPC in WT and sGC?1KO hearts. NO-stimulated cGMP production was severely attenuated in sGC?1KO hearts compared to WT hearts, indicating that the sGC?2 isoform only produces minute amounts of cGMP after NO stimulation. Taken together, our results indicate that although sGC?1 importantly regulates cardiac contractility, it is not required for cardioprotection by IPC. Instead, our results suggest that possibly only minimal sGC activity, which in sGC?1KO hearts is provided by the sGC?2 isoform, is sufficient to transduce the cardioprotective signal induced by IPC via phosphorylation of PKC?.

Sips, Patrick Y.; Brouckaert, Peter; Ichinose, Fumito

2012-01-01

167

Effect of Remote Ischemic Preconditioning on Phosphorylated Protein Signaling in Children Undergoing Tetralogy of Fallot Repair: A Randomized Controlled Trial  

PubMed Central

Background Our previous randomized controlled trial demonstrated cardiorespiratory protection by remote ischemic preconditioning (RIPC) in children before cardiac surgery. However, the impact of RIPC on myocardial prosurvival intracellular signaling remains unknown in cyanosis. RIPC may augment phosphorylated protein signaling in myocardium and circulating leukocytes during tetralogy of Fallot (ToF) repair. Methods and Results Children (n=40) undergoing ToF repair were double?blind randomized to RIPC (n=11 boys, 9 girls) or control (sham RIPC: n=9 boys, 11 girls). Blood samples were taken before, immediately after, and 24 hours after cardiopulmonary bypass. Resected right ventricular outflow tract muscle and leukocytes were processed for protein expression and mitochondrial respiration. There was no difference in age (7.1±3.4 versus 7.1±3.4 months), weight (7.7±1.8 versus 7.5±1.9 kg), or bypass or aortic cross?clamp times between the groups (control versus RIPC, mean±SD). No differences were seen between the groups for an increase in the ratio of phosphorylated to total protein for protein kinase B, p38 mitogen activated protein kinase, signal transducer and activator of transcription 3, glycogen synthase kinase 3?, heat shock protein 27, Connexin43, or markers associated with promotion of necrosis (serum cardiac troponin I), apoptosis (Bax, Bcl?2), and autophagy (Parkin, Beclin?1, LC3B). A high proportion of total proteins were in phosphorylated form in control and RIPC myocardium. In leukocytes, mitochondrial respiration and assessed protein levels did not differ between groups. Conclusions In patients with cyanotic heart disease, a high proportion of proteins are in phosphorylated form. RIPC does not further enhance phosphorylated protein signaling in myocardium or circulating leukocytes in children undergoing ToF repair. Clinical Trial Registration URL: (http://www.anzctr.org.au/trial_view.aspx?id=335613. Unique identifier: Australian New Zealand Clinical Trials Registry number ACTRN12610000496011.

Pepe, Salvatore; Liaw, Norman Y.; Hepponstall, Michele; Sheeran, Freya L.; Yong, Matthew S.; d'Udekem, Yves; Cheung, Michael M.; Konstantinov, Igor E.

2013-01-01

168

Transcriptome analysis of renal ischemia/reperfusion injury and its modulation by ischemic pre-conditioning or hemin treatment.  

PubMed

Ischemia/reperfusion injury (IRI) is a leading cause of acute renal failure. The definition of the molecular mechanisms involved in renal IRI and counter protection promoted by ischemic pre-conditioning (IPC) or Hemin treatment is an important milestone that needs to be accomplished in this research area. We examined, through an oligonucleotide microarray protocol, the renal differential transcriptome profiles of mice submitted to IRI, IPC and Hemin treatment. After identifying the profiles of differentially expressed genes observed for each comparison, we carried out functional enrichment analysis to reveal transcripts putatively involved in potential relevant biological processes and signaling pathways. The most relevant processes found in these comparisons were stress, apoptosis, cell differentiation, angiogenesis, focal adhesion, ECM-receptor interaction, ion transport, angiogenesis, mitosis and cell cycle, inflammatory response, olfactory transduction and regulation of actin cytoskeleton. In addition, the most important overrepresented pathways were MAPK, ErbB, JAK/STAT, Toll and Nod like receptors, Angiotensin II, Arachidonic acid metabolism, Wnt and coagulation cascade. Also, new insights were gained about the underlying protection mechanisms against renal IRI promoted by IPC and Hemin treatment. Venn diagram analysis allowed us to uncover common and exclusively differentially expressed genes between these two protective maneuvers, underscoring potential common and exclusive biological functions regulated in each case. In summary, IPC exclusively regulated the expression of genes belonging to stress, protein modification and apoptosis, highlighting the role of IPC in controlling exacerbated stress response. Treatment with the Hmox1 inducer Hemin, in turn, exclusively regulated the expression of genes associated with cell differentiation, metabolic pathways, cell cycle, mitosis, development, regulation of actin cytoskeleton and arachidonic acid metabolism, suggesting a pleiotropic effect for Hemin. These findings improve the biological understanding of how the kidney behaves after IRI. They also illustrate some possible underlying molecular mechanisms involved in kidney protection observed with IPC or Hemin treatment maneuvers. PMID:23166714

Correa-Costa, Matheus; Azevedo, Hátylas; Amano, Mariane Tami; Gonçalves, Giselle Martins; Hyane, Meire Ioshie; Cenedeze, Marcos Antonio; Renesto, Paulo Guilherme; Pacheco-Silva, Alvaro; Moreira-Filho, Carlos Alberto; Câmara, Niels Olsen Saraiva

2012-11-14

169

Ischemic preconditioning negatively regulates plenty of SH3s–mixed lineage kinase 3–Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt  

Microsoft Academic Search

Activation of Akt\\/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immunoprecipitation analysis reveals that Akt physically interacts with Rac1,

Q.-G. Zhang; D. Han; J. Xu; Q. Lv; R. Wang; X.-H. Yin; T.-L. Xu; G.-Y. Zhang

2006-01-01

170

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

1999-01-01

171

Reduced expression of mitochondrial electron transport chain proteins from hibernating hearts relative to ischemic preconditioned hearts in the second window of protection.  

PubMed

Although protection against necrosis has been observed in both hibernating (HIB) and ischemic preconditioned hearts in the second window of protection (SWOP), a comparison of the mitochondrial proteome between the two entities has not been previously performed. Anesthetized swine underwent instrumentation with a fixed constrictor around the LAD artery and were followed for 12 weeks (HIB; N=7). A second group of anesthetized swine underwent ischemic preconditioning by inflating a balloon within the LAD artery 10 times for 2 min, each separated by 2 min reperfusion and were sacrificed 24h later (SWOP; N=7). Myocardial blood flow and high-energy nucleotides were obtained in the LAD region and normalized to remote regions. Post-sacrifice, protein content as measured with iTRAQ was compared in isolated mitochondria from the LAD area of a Sham heart. Basal regional blood flow in the LAD region when normalized to the remote region was 0.86±0.04 in HIB and 1.02±0.02 in SWOP tissue (P<0.05). Despite reduced regional blood flows in HIB hearts, ATP content in the LAD region, when normalized to the remote region was similar in HIB versus SWOP (1.06±0.06 and 1.02±0.05 respectively; NS) as was the transmural phosphocreatine (PCr) to ATP ratio (2.1±0.2 and 2.2±0.2 respectively; NS). Using iTRAQ, 64 common proteins were identified in HIB and SWOP hearts. Compared with SWOP, the relative abundance of mitochondrial proteins involved with electron transport chain (ETC) were reduced in HIB including NADH dehydrogenase, Cytochrome c reductase and oxidase, ATP synthase, and nicotinamide nucleotide transhydrogenase. Within chronically HIB heart tissue with reduced blood flow, the relative abundance of mitochondrial ETC proteins is decreased when compared with SWOP tissue. These data support the concept that HIB heart tissue subjected to chronically reduced blood flow is associated with a down-regulation in the expression of key mitochondrial proteins involved in electron transport. PMID:23562790

Cabrera, Jesús A; Butterick, Tammy A; Long, Eric K; Ziemba, Elizabeth A; Anderson, Lorraine B; Duffy, Cayla M; Sluiter, Willem; Duncker, Dirk J; Zhang, Jianyi; Chen, Yingjie; Ward, Herbert B; Kelly, Rosemary F; McFalls, Edward O

2013-04-02

172

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.

2010-01-01

173

Effects of ischemic preconditioning on vascular reactivity and calcium sensitivity after hemorrhagic shock and their relationship to the RhoA–Rho-kinase pathway in rats.  

PubMed

We investigated the effect of ischemic preconditioning (IPC) on vascular reactivity and calcium sensitivity after hemorrhagic shock and its relationship to the RhoA–Rho-kinase pathway. Using hemorrhagic-shock rats (40 mm Hg for 3 hours) and isolated rings of the superior mesenteric artery (SMA), the effects of IPC (abdominal aorta occlusion applied 2 hours before shock) on the pressor effect of norepinephrine (3 ?g/kg), vascular reactivity and calcium sensitivity of SMA, and the activity and role of RhoA and Rho-kinase were investigated. IPC with 1-minute occlusion plus 5-minute loosening of aneurysm clips thrice significantly increased survival time and prevalence of survival at 24 hours of hemorrhagic-shock rats. This IPC condition also significantly increased the pressor response of norepinephrine and significantly improved the vascular reactivity and calcium sensitivity of the SMA. The activity of Rho-kinase and RhoA in the SMA decreased after hemorrhagic shock, but increased after IPC. Y-27632 (Rho-kinase antagonist) and C3 Transferase (RhoA antagonist) significantly decreased IPC-induced increase in vascular reactivity and calcium sensitivity. These results suggested that IPC can improve shock-induced vascular hyporeactivity and calcium desensitization. The RhoA–Rho-kinase pathway played an important part in this process. These findings suggested that the RhoA–Rho-kinase pathway may be a potential target to treat vascular hyporeactivity in severe trauma, shock, or multiple-organ dysfunction syndrome. PMID:21107281

Hu, Yi; Li, Tao; Tang, Xiao Feng; Chen, Ken; Liu, Liangming

2011-02-01

174

Preconditioning and post-treatment with cobalt chloride in rat model of perinatal hypoxic-ischemic encephalopathy.  

PubMed

Background: Hypoxia-ischemia (HI)-induced perinatal encephalopathy is a major cause of acute mortality and chronic neurologic morbidities such as cerebral palsy, mental retardation, and epilepsy. As the essential transcription factor for the activation of hypoxia-inducible genes, hypoxia-inducible factor 1 alpha (HIF-1?) plays an important role in the pathophysiological response to the stress of HI brain damage. Whether HIF-1? activation promotes neuroprotection in HI tissues is controversial. Methods: The left common carotid artery of rats aged 7days was ligated under anesthesia. The pups were then exposed to hypoxia in a normobaric chamber filled with 8% oxygen and 92% nitrogen for 2.5h. In the sham control group, the left common carotid artery was exposed but was not ligated or exposed to hypoxia. To assess the time window for effective treatment, the HIF-1? inducer cobalt chloride (CoCl2) was injected subcutaneously 1day before surgery, immediately or 1day after surgery. The brain tissues were harvested from the pups of each groups at 1, 2 and 7days after insult for HIF-1? protein ant its target genes expression and for investigating the injury. Morris water maze tests were performed at postnatal 7weeks. Results: HIF-1? protein levels and its target genes vascular endothelial growth factor, heme oxygenase-1, and insulin-like growth factor 1 were markedly increased after intraperitoneal injection of CoCl2 (60mg/kg). The target gene inducible nitric oxide synthase exhibited a biphasic time course. HI caused apoptosis and reduced capillary density, which were ameliorated by CoCl2. Both preconditioning with CoCl2 24h before HI and administration of CoCl2 24h after HI improved long-term reference memory compared with that in vehicle-injected littermate controls. Administration of CoCl2 immediately after HI did not improve spatial working memory. Conclusions: CoCl2 activates HIF-1? and protects against brain damage in vivo. The time of administration could be used to manipulate the activity of HIF-1? pathways and promote recovery. PMID:23694759

Dai, Ying; Li, Wendi; Zhong, Min; Chen, Jie; Liu, Youxue; Cheng, Qian; Li, Tingyu

2013-05-18

175

Reappraisal of H2S/sulfide concentration in vertebrate blood and its potential significance in ischemic preconditioning and vascular signaling.  

PubMed

Hydrogen sulfide (H(2)S) is rapidly emerging as a biologically significant signaling molecule. Studies published before 2000 report low or undetectable H(2)S (usually as total sulfide) levels in blood or plasma, whereas recent work has reported sulfide concentrations between 10 and 300 microM, suggesting it acts as a circulating signal. In the first series of experiments, we used a recently developed polarographic sensor to measure the baseline level of endogenous H(2)S gas and turnover of exogenous H(2)S gas in real time in blood from numerous animals, including lamprey, trout, mouse, rat, pig, and cow. We found that, contrary to recent reports, H(2)S gas was essentially undetectable (<100 nM total sulfide) in all animals. Furthermore, exogenous sulfide was rapidly removed from blood, plasma, or 5% bovine serum albumin in vitro and from intact trout in vivo. To determine if blood H(2)S could transiently increase, we measured oxygen-dependent H(2)S production by trout hearts in vitro and in vivo. H(2)S has been shown to mediate ischemic preconditioning (IPC) in mammals. IPC is present in trout and, unlike mammals, the trout myocardium obtains its oxygen from relatively hypoxic systemic venous blood. In vitro, myocardial H(2)S production was inversely related to Po(2), whereas we failed to detect H(2)S in ventral aortic blood from either normoxic or hypoxic fish in vivo. These results provide an autocrine or paracrine mechanism for myocardial coupling of hypoxia to H(2)S in IPC, i.e., oxygen sensing, but they fail to provide any evidence that H(2)S signaling is mediated by the circulation. PMID:18417642

Whitfield, Nathan L; Kreimier, Edward L; Verdial, Francys C; Skovgaard, Nini; Olson, Kenneth R

2008-04-16

176

Liver Ischemic Preconditioning (IPC) Improves Intestinal Microbiota Following Liver Transplantation in Rats through 16s rDNA-Based Analysis of Microbial Structure Shift  

PubMed Central

Background Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-?. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-? decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”.

Lu, Haifeng; Chen, Xinhua; Jiang, Jianwen; Liu, Hui; He, Yong; Ding, Songming; Hu, Zhenhua; Wang, Weilin; Zheng, Shusen

2013-01-01

177

Essential role of nitric oxide in acute ischemic preconditioning: S-nitros(yl)ation versus sGC/cGMP/PKG signaling?  

PubMed

Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection. PMID:22989471

Sun, Junhui; Aponte, Angel M; Kohr, Mark J; Tong, Guang; Steenbergen, Charles; Murphy, Elizabeth

2012-09-16

178

Influence of ischemic preconditioning and nitric oxide on microcirculation and the degree of rat liver injury in the model of ischemia and reperfusion.  

PubMed

The aim of this study was to assess the influence of ischemic preconditioning (IPC) on parenchymal liver blood flow during the early phase of reperfusion after 60 minutes of ischemia, additionally modified by adding N-nitro-L-arginine methyl ester (L-NAME). Our research involved 4 groups of rats (10 animals in each group), which underwent liver ischemia and 24 hours of reperfusion. Group I, ischemia/reperfusion (IR) was performed; group II, IPC, 10 minutes of ischemia and 10 minutes of reperfusion, and IR after that; group III, L-NAME (10 mg/kg intravenous [iv]), 10 minutes before IR; and group IV, L-NAME before IPC + IR. Activity of APAT, ALAT, GGTP, and FA was marked in serum in 90 minutes and 24 hours of reperfusion. In the liver biopsies at 24 hours of reperfusion, we analyzed reaction on adenosine-3-phosphatase stimulated by Mg++ and performed histological examination. The parenchymal perfusion was measured using a laser-doppler blood flowmeter (model PeriFlux System5000, Perimed Inc., United Kingdom). IPC during reperfusion led to minor injuries of the organ, with statistically significant normalization of enzymes compared with group 1, and a better reaction to the adenosine-3-phosphatase IPC produced faster and full return of perfusion to the 68.3 value at 24 hours (59.1 in the 60 minutes). In groups III and IV at 60 minutes, the perfusion was not statistically different from that in group 1. IPC causes full and faster blood return in the early phase of reperfusion and minor injury of liver parenchyma and liver sinus. The protective effect observed, especially in the first 60 minutes of reperfusion, was limited by L-NAME and was influenced by the action of nitric oxide. PMID:16504701

Caban, A; Oczkowicz, G; Abdel-Samad, O; Cierpka, L

179

Deletion of the Innate Immune NLRP3 Receptor Abolishes Cardiac Ischemic Preconditioning and Is Associated with Decreased Il-6/STAT3 Signaling  

PubMed Central

Objective Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those for cardiac ischemia-reperfusion (I/R) and ischemic preconditioning (IPC), we explored the possibility that the NLRP3 inflammasome is involved in IPC and acute I/R injury of the heart. Principal Findings Baseline cardiac performance and acute I/R injury were investigated in isolated, Langendorff-perfused hearts from wild-type (WT), ASC?/? and NLRP3?/? mice. Deletion of NLRP3 inflammasome components ASC?/? or NLRP3?/? did not affect baseline performance. The deletions exacerbated I/R-induced mechanical dysfunction, but were without effect on I/R-induced cell death. When subjected to IPC, WT and ASC?/? hearts were protected against I/R injury (improved function and less cell death). However, IPC did not protect NLRP3?/? hearts against I/R injury. NLRP3?/? hearts had significantly decreased cardiac IL-6 levels with a trend towards lower IL-1? levels at end reperfusion, suggesting abrogation of IPC through diminished IL-6 and/or IL-1? signaling. Subsequent experiments showed that neutralising IL-6 using an antibody against IL-6 abrogated IPC in WT hearts. However, inhibition of the IL-1r receptor with the IL-1 receptor inhibitor Anakinra (100 mg/L) did not abrogate IPC in WT hearts. Analysis of survival kinases after IPC demonstrated decreased STAT3 expression in NLRP3?/? hearts when compared to WT hearts. Conclusions The data suggest that the innate immune NLRP3 protein, in an NLRP3-inflammasome-independent fashion, is an integral component of IPC in the isolated heart, possibly through an IL-6/STAT3 dependent mechanism.

Eerbeek, Otto; Koeman, Anneke; Pulskens, Wilco P.; Butter, Loes M.; Leemans, Jaklien C.; Hollmann, Markus W.

2012-01-01

180

Vector-free and transgene-free human iPS cells differentiate into functional neurons and enhance functional recovery after ischemic stroke in mice.  

PubMed

Stroke is a leading cause of human death and disability in the adult population in the United States and around the world. While stroke treatment is limited, stem cell transplantation has emerged as a promising regenerative therapy to replace or repair damaged tissues and enhance functional recovery after stroke. Recently, the creation of induced pluripotent stem (iPS) cells through reprogramming of somatic cells has revolutionized cell therapy by providing an unlimited source of autologous cells for transplantation. In addition, the creation of vector-free and transgene-free human iPS (hiPS) cells provides a new generation of stem cells with a reduced risk of tumor formation that was associated with the random integration of viral vectors seen with previous techniques. However, the potential use of these cells in the treatment of ischemic stroke has not been explored. In the present investigation, we examined the neuronal differentiation of vector-free and transgene-free hiPS cells and the transplantation of hiPS cell-derived neural progenitor cells (hiPS-NPCs) in an ischemic stroke model in mice. Vector-free hiPS cells were maintained in feeder-free and serum-free conditions and differentiated into functional neurons in vitro using a newly developed differentiation protocol. Twenty eight days after transplantation in stroke mice, hiPS-NPCs showed mature neuronal markers in vivo. No tumor formation was seen up to 12 months after transplantation. Transplantation of hiPS-NPCs restored neurovascular coupling, increased trophic support and promoted behavioral recovery after stroke. These data suggest that using vector-free and transgene-free hiPS cells in stem cell therapy are safe and efficacious in enhancing recovery after focal ischemic stroke in mice. PMID:23717557

Mohamad, Osama; Drury-Stewart, Danielle; Song, Mingke; Faulkner, Ben; Chen, Dongdong; Yu, Shan Ping; Wei, Ling

2013-05-23

181

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

2001-01-01

182

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

183

Preconditioning the hyperlipidemic myocardium: fact or fantasy?  

PubMed

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

2011-11-09

184

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

1986-01-01

185

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

2000-01-01

186

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

1996-01-01

187

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

2005-01-01

188

Lipopolysaccharide preconditioning attenuates neuroapoptosis and improves functional recovery through activation of Nrf2 in traumatic spinal cord injury rats.  

PubMed

The previous studies suggested that low-dose lipopolysaccharide (LPS) provides neuroprotection against subsequent challenge with ischemic/reperfusion injury in the brain. But there were few reports about the neuroprotective effects of low-dose LPS against spinal cord injury (SCI). In this study, we evaluated the effect of low-dose LPS preconditioning on neuroapoptosis status after traumatic SCI (TSCI), using a standardized contusion model (NYU, New York University, impactor). SCI-induced rats were randomly divided into three groups: sham operation, control (receiving only normal saline) and LPS preconditioning (0.2 mg/kg, ip; 72 hours before injury). Neurologic function was assessed by the Basso, Beattie and Bresnahan (BBB) score at 6, 12, 24, 48 and 72 hours after TSCI. Rats were sacrificed at 72 hours postinjury. Histological changes were studied using Nissl staining. Apoptotic neural cells were assessed using the TdT-mediated dUTP Nick End Labeling (TUNEL) assay. Nuclear factor erythroid 2-related factor 2 (Nrf2) and caspase-3 were detected with immunohistochemistry and Western blot. LPS preconditioning reduced neuron apoptosis, improved neurologic outcome and actived Nrf2 expression. Moreover, Histological changes and the number of apoptotic cells were correlated with Nrf2 expression after the rats suffered the SCI. Our results suggest that LPS preconditioning exerted a neuroprotective effect against TSCI in rats, and activation of Nrf2 was believed to be one of the contributing mechanisms. PMID:23215850

Li, Wei-Chao; Jiang, Dian-Ming; Hu, Ning; Qi, Xiao-Tong; Qiao, Bo; Luo, Xiao-Ji

2013-01-29

189

Mitochondrial preconditioning: a potential neuroprotective strategy.  

PubMed

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

2010-08-26

190

Healing the diabetic heart: does myocardial preconditioning work?  

PubMed

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

2011-09-16

191

Transient Ischemic Attack Before Nonlacunar Ischemic Stroke in the Elderly  

PubMed Central

Background: Several studies suggest transient ischemic attack (TIA) may be neuroprotective against ischemic stroke analogous to preinfarction angina's protection against acute myocardial infarction. However, this protective ischemic preconditioning-like effect may not be present in all ages, especially among the elderly. The purpose of this study was to determine the neuroprotective effect of TIAs (clinical equivalent of cerebral ischemic preconditioning) to neurologic damage after cerebral ischemic injury in patients over 65 years of age. Methods: We reviewed the medical charts of patients with ischemic stroke for presence of TIAs within 72 hours before stroke onset. Stroke severity was evaluated by the National Institutes of Health Stroke Scale and disability by a modified Rankin scale. Results: We evaluated 203 patients (?65 years) with diagnosis of acute ischemic stroke and categorized them according to the presence (n = 42, 21%) or absence (n = 161, 79%) of TIAs within 72 hours of stroke onset. Patients were monitored until discharged from the hospital (length of hospital stay 14.5 ± 4.8 days). No significant differences in the National Institutes of Health Stroke Scale and modified Rankin scale scores were observed between those patients with TIAs and those without TIAs present before stroke onset at admission or discharge. Conclusion: These results suggest that the neuroprotective mechanism of cerebral ischemic preconditioning may not be present or functional in the elderly.

Morte, David Della; Abete, Pasquale; Gallucci, Ferdinando; Scaglione, Anna; D'Ambrosio, Daniele; Gargiulo, Gaetano; De Rosa, Giovanna; Dave, Kunjan R.; Lin, Hung Wen; Cacciatore, Francesco; Mazzella, Francesca; Uomo, Generoso; Rundek, Tanja; Perez-Pinzon, Miguel A.; Rengo, Franco

2009-01-01

192

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

1998-01-01

193

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

194

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

1996-01-01

195

Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases.  

PubMed

Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34(+) EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases. PMID:23896001

Yoo, Chae Hwa; Na, Hee-Jun; Lee, Dong-Seol; Heo, Soon Chul; An, Yuri; Cha, Junghwa; Choi, Chulhee; Kim, Jae Ho; Park, Joo-Cheol; Cho, Yee Sook

2013-07-26

196

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

2010-01-01

197

ISOFLURANE PRECONDITIONING NEUROPROTECTION IN EXPERIMENTAL FOCAL STROKE IS ANDROGEN-DEPENDENT IN MALE MICE  

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.

ZHU, W.; WANG, L.; ZHANG, L.; PALMATEER, J. M.; LIBAL, N. L.; HURN, P. D.; HERSON, P. S.; MURPHY, S. J.

2010-01-01

198

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.

2011-01-01

199

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

2007-01-01

200

Protective preconditioning by transient global ischemia in the rat: components of delayed injury progression and lasting protection distinguished by comparisons of depolarization thresholds for cell loss at long survival times  

Microsoft Academic Search

Robust ischemic preconditioning has been shown in rodent brain, but there are concerns regarding the persistence of neuron protection. This issue was examined in rat hippocampus following 4-vessel occlusion (4-VO) ischemia, using DC shifts characteristic of ischemic depolarization to reproducibly define insult severity. Preconditioning ischemia producing 2 to 3.5 mins depolarization was followed at intervals of 2, 5, or 7

Masayuki Ueda; Thaddeus S Nowak

2005-01-01

201

Impaired mitochondrial function in chronically ischemic human heart.  

PubMed

Chronic ischemic heart disease is associated with myocardial hypoperfusion. The resulting hypoxia potentially inflicts damage upon the mitochondria, leading to a compromised energetic state. Furthermore, ischemic damage may cause excessive production of reactive oxygen species (ROS), producing mitochondrial damage, hereby reinforcing a vicious circle. Ischemic preconditioning has been proven protective in acute ischemia, but the subject of chronic ischemic preconditioning has not been explored in humans. We hypothesized that mitochondrial respiratory capacity would be diminished in chronic ischemic regions of human myocardium but that these mitochondria would be more resistant to ex vivo ischemia and, second, that ROS generation would be higher in ischemic myocardium. The aim of this study was to test mitochondrial respiratory capacity during hyperoxia and hypoxia, to investigate ROS production, and finally to assess myocardial antioxidant levels. Mitochondrial respiration in biopsies from ischemic and nonischemic regions from the left ventricle of the same heart was compared in nine human subjects. Maximal oxidative phosphorylation capacity in fresh muscle fibers was lower in ischemic compared with nonischemic myocardium (P < 0.05), but the degree of coupling (respiratory control ratio) did not differ (P > 0.05). The presence of ex vivo hypoxia did not reveal any chronic ischemic preconditioning of the ischemic myocardial regions (P > 0.05). ROS production was higher in ischemic myocardium (P < 0.05), and the levels of antioxidant protein expression was lower. Diminished mitochondrial respiration capacity and excessive ROS production demonstrate an impaired mitochondrial function in ischemic human heart muscle. No chronic ischemic preconditioning effect was found. PMID:23542918

Stride, Nis; Larsen, Steen; Hey-Mogensen, Martin; Hansen, Christina N; Prats, Clara; Steinbrüchel, Daniel; Køber, Lars; Dela, Flemming

2013-03-29

202

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

2002-01-01

203

Metabolomic analysis of two different models of delayed preconditioning.  

PubMed

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

2012-11-02

204

Mobile IP Using Private IP Addresses  

Microsoft Academic Search

The mobile IP data communication is widely spreading. Accordingly, it is pointed out that the number of IP addresses in IPv4 will be short if every mobile terminal has its IP address. In order to solve this address starvation problem, we propose an approach to realize mobile IP protocol by assigning a private IP address to a mobile terminal. It

Toshihiko Kato; Akira Idoue; Hidetoshi Yokota

2001-01-01

205

In Vitro Ischemic Tolerance Involves Upregulation of Glutamate Transport Partly Mediated by the TACE\\/ADAM17Tumor Necrosis Factor  Pathway  

Microsoft Academic Search

A short ischemic event (ischemic preconditioning (IPC)) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance). Although tumor necrosis factor- (TNF-) contributes to the brain damage found after cerebral ischemia, its expression and neuroprotective role in models of IPC have also been described. Regarding the role of TNF- convertase (TACE\\/ADAM17), we have recently shown its upregulation in

Cristina Romera; Olivia Hurtado; Sofia H. Botella; Ignacio Lizasoain; Antonio Cardenas; Paz Fernandez-Tome; Juan C. Leza; Pedro Lorenzo; Maria A. Moro

2004-01-01

206

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: chiueh@tmu.edu.tw; 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)

2005-09-01

207

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

PubMed

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

2011-06-16

208

IP switching for scalable IP services  

Microsoft Academic Search

Internet protocol (IP) switching is emerging as a critical technology for improving the speed and scalability of the Internet. This paper discusses IP Navigator, a form of IP switching developed specifically for use in core network backbones, such as Internet service provider networks and major corporate backbones. IP Navigator combines the high speed and quality of service capabilities of asynchronous

HASSAN M. AHMED; R. Gallon; ANDREW G. MALIS; JOHN MOY

1997-01-01

209

Ischemic Tolerance  

Microsoft Academic Search

A brief period of cerebral ischemia confers transient tolerance to a subsequent ischemic challenge in the brain. This phenomenon of ischemic tolerance has been confirmed in various animal models of forebrain ischemia and focal cerebral ischemia. Since the ischemic tolerance afforded by preceding ischemia can bring about robust protection of the brain, the mechanism of tolerance induction has been extensively

Takaaki Kirino

2002-01-01

210

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.

2011-01-01

211

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

1997-01-01

212

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

1999-01-01

213

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

2001-01-01

214

Relationship between the activation of cyclic AMP responsive element binding protein and ischemic tolerance in the penumbra region of rat cerebral cortex.  

PubMed

Application of a brief period of ischemia, i.e. preconditioning treatment of the middle cerebral artery territory, has been known to produce ischemic tolerance, reducing cerebral infarction volume in the penumbra region after lethal ischemia. However, little is known about the molecular mechanisms responsible for preconditioning-induced ischemic tolerance. In the present study, we examined the difference in the phosphorylation pattern of cyclic AMP responsive element binding protein (CREB) after 1 h of focal cerebral ischemia between preconditioned and non-preconditioned rats by immunohistochemistry and Western blotting. The phosphorylation of CREB in the penumbra region was more rapidly enhanced in the preconditioned rats than in the non-preconditioned rats after 1 h of ischemia. The result suggested that the immediate enhancement in the phosphorylation of CREB in the penumbra region prevented the spread of infarction in the preconditioned rats. PMID:12359312

Nakajima, Takayuki; Iwabuchi, Sadahiro; Miyazaki, Hiroyuki; Okuma, Yasunobu; Inanami, Osamu; Kuwabara, Mikinori; Nomura, Yasuyuki; Kawahara, Koichi

2002-10-01

215

The Role of a Common Adenosine Monophosphate Deaminase (AMPD)-1 Polymorphism in Outcomes of Ischemic and Nonischemic Heart Failure  

Microsoft Academic Search

BackgroundA common variant of the adenosine monophosphate deaminase (AMPD)-1 gene (C34T) results in enzymatic inactivity and may increase adenosine in cardiac muscle and confer cardioprotection through ischemic preconditioning.

Matthew J. Kolek; John F. Carlquist; Surai Thaneemit-Chen; Laura C. Lazzeroni; Bryant M. Whiting; Benjamin D. Horne; Joseph B. Muhlestein; Philip Lavori; Jeffrey L. Anderson

2005-01-01

216

Resveratrol pretreatment protects rat brain from cerebral ischemic damage via a sirtuin 1–uncoupling protein 2 pathway  

Microsoft Academic Search

Resveratrol is a natural polyphenol found in grapes and wine and has been associated with protective effects against cardiovascular diseases. In vitro, both resveratrol preconditioning (RPC) and ischemic preconditioning (IPC) require activation of sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, to induce neuroprotection against cerebral ischemia. In the present study, we tested two hypotheses: (a) that neuroprotection against

D. Della-Morte; K. R. Dave; R. A. DeFazio; Y. C. Bao; A. P. Raval; M. A. Perez-Pinzon

2009-01-01

217

Ischemic colitis  

Microsoft Academic Search

Ischemic colitis represents the most common form of gastrointestinal ischemia. The presumed etiologies are numerous; however, it typically develops “spontaneously,” in the absence of major vasculature occlusion, and in the presence of viable intestine elsewhere. It is most usefully classified into gangrenous and nongangrenous forms, the latter of which may be subdivided into transient and chronic types. Ischemic colitis may

Sanjiv K. Gandhi; Morin M. Hanson; Anthony M. Vernava; Donald L. Kaminski; Walter E. Longo

1996-01-01

218

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

1997-01-01

219

Hypoxia Preconditioned Mesenchymal Stem Cells Improve Vascular and Skeletal Muscle Fiber Regeneration After Ischemia Through a Wnt4-dependent Pathway  

Microsoft Academic Search

Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow

Lionel Leroux; Betty Descamps; Nancy F Tojais; Benjamin Séguy; Pierre Oses; Catherine Moreau; Danièle Daret; Zoran Ivanovic; Jean-Michel Boiron; Jean-Marie D Lamazière; Pascale Dufourcq; Thierry Couffinhal; Cécile Duplàa

2010-01-01

220

The PKC Activator PMA Preconditions Rabbit Heart in the Presence of Adenosine Receptor Blockade: Is 5?Nucleotidase Important?  

Microsoft Academic Search

While there is good evidence that both protein kinase C (PKC) and adenosine are involved in ischemic preconditioning, their sequence in the intracellular signaling cascade is in dispute. One hypothesis proposes that PKC activation causes release of adenosine which then protects the heart, while the other proposes that adenosine stimulates PKC which in turn causes protection. Accordingly, we studied the

Efstathios K. Iliodromitis; Takayuki Miki; Guang S. Liu; James M. Downey; Michael V. Cohen; Dimitrios T. Kremastinos

1998-01-01

221

From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia.  

PubMed

Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain ischemia, preconditioning is a sublethal insult performed in advance of brain ischemia, and postconditioning, which conventionally refers to a series of brief occlusions and reperfusions of the blood vessels, is conducted after ischemia/reperfusion. In this article, we first briefly review the history of preconditioning, including the experimentation that initially uncovered its neuroprotective effects and later revealed its underlying mechanisms-of-action. We then discuss how preconditioning research evolved into that of postconditioning--a concept that now represents a broad range of stimuli or triggers, including delayed postconditioning, pharmacological postconditioning, remote postconditioning--and its underlying protective mechanisms involving the Akt, MAPK, PKC and K(ATP) channel cell-signaling pathways. Because the concept of postconditioning is so closely associated with that of preconditioning, and both share some common protective mechanisms, we also discuss whether a combination of preconditioning and postconditioning offers greater protection than preconditioning or postconditioning alone. PMID:22204317

Zhao, Heng; Ren, Chuancheng; Chen, Xingmiao; Shen, Jiangang

2012-02-01

222

Cardioprotection techniques: preconditioning, postconditioning and remote con-ditioning (basic science).  

PubMed

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. The major pathological consequences of IHD arise from the detrimental effects of acute ischemia-reperfusion injury (IRI) on the myocardium. Therefore, in order to improve clinical outcomes in patients with IHD, novel therapeutic strategies are required to protect the myocardium from acute IRI and preserve cardiac function (cardioprotection). In this regard, endogenous cardioprotective strategies such as ischemic preconditioning (IPC), ischemic postconditioning (IPost) and remote ischemic conditioning (RIC) may provide novel approaches for protecting the heart in clinical settings in which the patient experiences acute myocardial IRI. In this review article, we provide an overview of these endogenous cardioprotective strategies with respect to the pre-clinical experimental literature, exploring their major characteristics and underlying signaling mechanisms. The application of these therapeutic strategies in the clinical setting for potential patient benefit is reviewed in another article in this special issue. PMID:23270554

Hausenloy, Derek J

2013-01-01

223

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.

1997-04-01

224

[Role of receptor transactivation in the cardioprotective effects of preconditioning and postconditioning].  

PubMed

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

2012-03-01

225

Epsilon Protein Kinase C Mediated Ischemic Tolerance Requires Activation of the Extracellular Regulated Kinase Pathway in the Organotypic Hippocampal Slice  

Microsoft Academic Search

Ischemic preconditioning (IPC) promotes brain tolerance against subsequent ischemic insults. Using the organotypic hippocampal slice culture, we conducted the present study to investigate (1) the role of adenosine A1 receptor (A1AR) activation in IPC induction, (2) whether epsilon protein kinase C (?PKC) activation after IPC is mediated by the phosphoinositol pathway, and (3) whether ?PKC protection is mediated by the

Christian Lange-Asschenfeldt; Ami P. Raval; Kunjan R. Dave; Daria Mochly-Rosen; Thomas J. Sick; Miguel A Pérez-Pinzón

2004-01-01

226

Direct Evidence That Protein Kinase C Plays an Essential Role in the Development of Late Preconditioning against Myocardial Stunning in Conscious Rabbits and That e Is the Isoform Involved  

Microsoft Academic Search

Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning (PC) against stunning). The mechanism of this powerful protec- tive effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC against infarction, it is un- known whether it triggers late PC against stunning. In addi- tion, the entire PKC hypothesis of ischemic

Yumin Qiu; Peipei Ping; Xian-Liang Tang; Srinivas Manchikalapudi; Ali Rizvi; Jun Zhang; Hitoshi Takano; Wen-Jian Wu; Steffi Teschner; Roberto Bolli

227

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

2002-01-01

228

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

2006-01-01

229

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

2010-01-01

230

Delayed Preconditioning-Mimetic Action of Nitroglycerin in Patients Undergoing Coronary Angioplasty  

Microsoft Academic Search

Background—Experimental studies suggest that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked pharmacologically. However, to date, no drug has been tested with respect to its ability to elicit a late PC effect in humans. As a consequence, clinical exploitation of the powerful anti-stunning and anti-infarct actions of late PC has been elusive thus far.

Massoud A. Leesar; Marcus F. Stoddard; Buddhadeb Dawn; Venu G. Jasti; Ronald Masden; Roberto Bolli

2010-01-01

231

Preconditioning with adenosine leads to concentration-dependent infarct size reduction in the isolated rabbit heart  

Microsoft Academic Search

Adenosine (ADO) has a cardioprotective effect in ischemia-reperfusion injury when administered both prior to ischemia and during reperfusion. ADO has also been implicated in the mechanism of ischemic pre-conditioning. The aim of this study was to investigate whether there was a concentration-response between the administration of ADO prior to ischemia-reperfusion and reduction in subsequent infarct size. Rabbit isolated perfused hearts

R. G. Woolfson; V. C. Patel; D. M. Yellon

1996-01-01

232

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

PubMed

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

2007-02-22

233

Voice over IP Calculator  

NSDL National Science Digital Library

The Voice over IP Calculator Web site actually consists of four free online tools that can be used to estimate bandwidth requirements and voice paths for a planned VoIP system. The four tools are: Lines and IP Bandwidth Calculator, Erlangs and Bandwidth Calculator, Minutes and Lines Calculator, and Erlangs and Lines Calculator. Each utility is very easy to use, but is mainly intended for experienced IT workers.

2008-02-12

234

Voice over IP forensics  

Microsoft Academic Search

With the tremendous growth in popularity and bandwidth of the Internet, VoIP technology has emerged that allows phone calls to be routed over Internet infrastructure rather than the traditional Public Switched Telephone Network (PSTN) infrastructure. The issues faced by law enforcement authorities concerning VoIP are very different from that of traditional telephony. Wiretapping is not applicable to VoIP calls and

Jill Slay; Matthew Simon

2008-01-01

235

Photonic IP routing  

Microsoft Academic Search

A photonic Internet protocol (IP) routing is proposed in which the IP address, mapped onto optical code, is recognized by performing optical correlation in the time domain in a parallel manner. Preliminary experiment shows that it can process 6.5×109 packets per second. It will help overcome the bottleneck in current electrical IP routers; i.e., the time it takes to look

K.-I. Kitayama; N. Wada

1999-01-01

236

Systemic chemokine levels, coronary heart disease, and ischemic stroke events  

PubMed Central

Objectives: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-?-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. Methods: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. Results: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05–2.74), IP-10 (HR = 1.53; 95% CI 1.06–2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02–2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68–1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). Conclusions: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors.

Canoui-Poitrine, F.; Luc, G.; Mallat, Z.; Machez, E.; Bingham, A.; Ferrieres, J.; Ruidavets, J.-B.; Montaye, M.; Yarnell, J.; Haas, B.; Arveiler, D.; Morange, P.; Kee, F.; Evans, A.; Amouyel, P.; Ducimetiere, P.

2011-01-01

237

Voice over IP  

Microsoft Academic Search

The authors begin by discussing the components of voice over IP (VoIP). They go on to consider SS7, H.323, SIP (session initiation protocol), voice coders, ITU-T specifications, RTP (real time transport protocol), gateway control, wireless networks, quality of service, packet loss, jitter, latency and bit rate

Princy Mehta; Sanjay Udani

2001-01-01

238

Acidic preconditioning protects against ischemia-induced brain injury.  

PubMed

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

2012-05-11

239

Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning.  

PubMed

In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic preconditioning (PC), postconditioning (PostC) and their mimetic agents have been shown to reduce infarct size in experiments using healthy animals. However, a variety of pharmacological agents have failed to demonstrate infarct size limitation in clinical trials. One of the possible reasons for the discrepancy between the results of animal experiments and clinical trials is that co-morbidities, including DM, modified myocardial responses to ischemia/reperfusion and to cardioprotective agents. Here we summarize observations of the effects of DM on myocardial infarct size and ischemic PC and PostC and discuss perspectives for protection of DM hearts. PMID:22694800

Miki, Takayuki; Itoh, Takahito; Sunaga, Daisuke; Miura, Tetsuji

2012-06-13

240

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

1999-01-01

241

Collateral recruitment and “warm-up” after first exercise in ischemic heart disease  

Microsoft Academic Search

Background Proposed mechanisms for “warm-up” after angina on first exercise include ischemic preconditioning and collateral recruitment. The aim of this study was to determine whether patients with ischemic heart disease and well-developed coronary collateral vessels have a greater warm-up response than those with no visible collateral vessels. Methods And Results Fifteen patients with a total coronary occlusion and collateral vessels

I. Patrick Kay; John Kittelson; Ralph A. H. Stewart

2000-01-01

242

The warm-up effect protects against ischemic left ventricular dysfunction in patients with angina  

Microsoft Academic Search

OBJECTIVESThe goal of this study was to investigate whether the “warm-up” effect in angina protects against ischemic left ventricular (LV) dysfunction.BACKGROUNDAfter exercise, patients with coronary disease demonstrate persistent myocardial dysfunction, which may represent stunning, as well as warm-up protection against further angina, which may represent ischemic preconditioning. The effect of warm-up exercise on LV function during subsequent exercise has not

Andrew D Kelion; Terence P Webb; Maureen A Gardner; Oliver J. M Ormerod; Adrian P Banning

2001-01-01

243

IP-SOFC Model  

Microsoft Academic Search

The Integrated Planar-Solid Oxide Fuel Cell (IP-SOFC) [1] is a proprietary solid oxide fuel cell design currently developed\\u000a by Rolls-Royce Fuel Cell Systems Ltd (RRFCS) for integration into an SOFC-gas turbine hybrid system. The IP-SOFC is substantially\\u000a a cross between tubular and planar geometries, seeking to combine the thermal compliance qualities of the former and the low-cost\\u000a component fabrication and

Simone Grosso; Laura Repetto; Paola Costamagna

244

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA  

PubMed Central

We have shown that the cellular process of macroautophagy plays a protective role in HL-1 cardiomyocytes subjected to simulated ischemia/reperfusion (sI/R) (Hamacher-Brady et al. in J Biol Chem 281(40):29776–29787). Since the nucleoside adenosine has been shown to mimic both early and late phase ischemic preconditioning, a potent cardioprotective phenomenon, the purpose of this study was to determine the effect of adenosine on autophagosome formation. Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes. We investigated the effect of adenosine receptor agonists on autophagy and cell survival following sI/R in GFP-LC3 infected HL-1 cells and neonatal rat cardiomyocytes. The A1 adenosine receptor agonist 2-chloro-N(6)-cyclopentyl-adenosine (CCPA) (100 nM) caused an increase in the number of autophagosomes within 10 min of treatment; the effect persisted for at least 300 min. A significant inhibition of autophagy and loss of protection against sI/R measured by release of lactate dehydrogenase (LDH), was demonstrated in CCPA-pretreated cells treated with an A1 receptor antagonist, a phospholipase C inhibitor, or an intracellular Ca(+2) chelator. To determine whether autophagy was required for the protective effect of CCPA, autophagy was blocked with a dominant negative inhibitor (Atg5K130R) delivered by transient transfection (in HL-1 cells) or protein transduction (in adult rat cardiomyocytes). CCPA attenuated LDH release after sI/R, but protection was lost when autophagy was blocked. To assess autophagy in vivo, transgenic mice expressing the red fluorescent autophagy marker mCherry-LC3 under the control of the alpha myosin heavy chain promoter were treated with CCPA 1 mg/kg i.p. Fluorescence microscopy of cryosections taken from the left ventricle 30 min after CCPA injection revealed a large increase in the number of mCherry-LC3-labeled structures, indicating the induction of autophagy by CCPA in vivo. Taken together, these results indicate that autophagy plays an important role in mediating the cardioprotective effects conferred by adenosine pretreatment.

Yitzhaki, Smadar; Huang, Chengqun; Liu, Wayne; Lee, Youngil; Gustafsson, Asa B.; Mentzer, Robert M.

2013-01-01

245

Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA.  

PubMed

We have shown that the cellular process of macroautophagy plays a protective role in HL-1 cardiomyocytes subjected to simulated ischemia/reperfusion (sI/R) (Hamacher-Brady et al. in J Biol Chem 281(40):29776-29787). Since the nucleoside adenosine has been shown to mimic both early and late phase ischemic preconditioning, a potent cardioprotective phenomenon, the purpose of this study was to determine the effect of adenosine on autophagosome formation. Autophagy is a highly regulated intracellular degradation process by which cells remove cytosolic long-lived proteins and damaged organelles, and can be monitored by imaging the incorporation of microtubule-associated light chain 3 (LC3) fused to a fluorescent protein (GFP or mCherry) into nascent autophagosomes. We investigated the effect of adenosine receptor agonists on autophagy and cell survival following sI/R in GFP-LC3 infected HL-1 cells and neonatal rat cardiomyocytes. The A(1) adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) (100 nM) caused an increase in the number of autophagosomes within 10 min of treatment; the effect persisted for at least 300 min. A significant inhibition of autophagy and loss of protection against sI/R measured by release of lactate dehydrogenase (LDH), was demonstrated in CCPA-pretreated cells treated with an A(1) receptor antagonist, a phospholipase C inhibitor, or an intracellular Ca(+2) chelator. To determine whether autophagy was required for the protective effect of CCPA, autophagy was blocked with a dominant negative inhibitor (Atg5(K130R)) delivered by transient transfection (in HL-1 cells) or protein transduction (in adult rat cardiomyocytes). CCPA attenuated LDH release after sI/R, but protection was lost when autophagy was blocked. To assess autophagy in vivo, transgenic mice expressing the red fluorescent autophagy marker mCherry-LC3 under the control of the alpha myosin heavy chain promoter were treated with CCPA 1 mg/kg i.p. Fluorescence microscopy of cryosections taken from the left ventricle 30 min after CCPA injection revealed a large increase in the number of mCherry-LC3-labeled structures, indicating the induction of autophagy by CCPA in vivo. Taken together, these results indicate that autophagy plays an important role in mediating the cardioprotective effects conferred by adenosine pretreatment. PMID:19242639

Yitzhaki, Smadar; Huang, Chengqun; Liu, Wayne; Lee, Youngil; Gustafsson, Asa B; Mentzer, Robert M; Gottlieb, Roberta A

2009-02-26

246

Transient Ischemic Attack  

MedlinePLUS

NINDS Transient Ischemic Attack Information Page Synonym(s): Mini Stroke Table of Contents (click to jump to sections) What is Transient Ischemic ... Trials Organizations Additional resources from MedlinePlus What is Transient Ischemic Attack? A transient ischemic attack (TIA) is a transient ...

247

The role of HIF in cobalt-induced ischemic tolerance.  

PubMed

Understanding the endogenous survival pathways induced by ischemic tolerance may yield targets for neuroprotection from stroke. One well-studied pathway reported to be evoked by preconditioning stimuli is the transcription factor HIF (hypoxia-inducible factor). However, whether HIF induction by ischemic insults is neuroprotective or toxic is still unclear. We examined the ability of three prolyl-hydroxylase inhibitors, which induce HIF, to protect hippocampal cultures from oxygen-glucose deprivation. Hippocampal cultures were exposed to ischemic preconditioning or various concentrations of cobalt chloride, deferoxamine (DFO) or dimethyloxylalyglycine (DMOG), prior to lethal oxygen-glucose deprivation (OGD). Cell survival of neurons and astrocytes was determined with dual-label immunocytochemistry. The induction of HIF targets was assessed in mixed as well as astrocyte-enriched cultures. Ischemic preconditioning, as well as low concentrations of cobalt and DFO, enhanced the survival of neurons following OGD. However, DMOG exacerbates OGD-induced neuronal death. At low concentrations, all three prolyl-hydroxylase (PHD) inhibitors increased the survival of astrocytes. Neuroprotective concentrations of cobalt induced the transcription of the cytokine erythropoietin (EPO) in astrocyte cultures. In addition, pretreatment with recombinant human erythropoietin (rH-EPO) also protected neurons from OGD. Our data suggest that HIF-induced EPO, released from astrocytes, protects neurons from OGD. However, the three PHD inhibitors each exhibited different neuroprotective profiles at low concentrations, suggesting that not all PHD inhibitors are created equal. The protective effects at low doses is reminiscent of HIF involvement in ischemic tolerance, in which sub-lethal insults induce HIF pathways resulting in neuroprotection, whereas the high-dose toxicity suggests that over-activation of HIF is not always protective. Therefore, the choice of inhibitor and dose may determine the clinical utility of these compounds. Deferoxamine exhibited little toxicity even at higher doses, and therefore appears a promising candidate for clinical use. PMID:23916558

Jones, S M; Novak, A E; Elliott, J P

2013-08-03

248

Preconditioning Strategies to Enhance Physical Performance on the Day of Competition.  

PubMed

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

2013-05-20

249

Strategies to promote donor cell survival: combining preconditioning approach with stem cell transplantation  

PubMed Central

Stem cell transplantation has emerged as a potential modality in cardiovascular therapeutics due to their inherent characteristics of self-renewal, unlimited capacity for proliferation and ability to cross lineage restrictions and adopt different phenotypes. Constrained by extensive death in the unfriendly milieu of ischemic myocardium, the results of heart cell therapy in experimental animal models as well as clinical studies have been less than optimal. Several factors which play a role in early cell death after engraftment in the ischemic myocardium include; absence of survival factors in the transplanted heart, disruption of cell-cell interaction coupled with loss of survival signals from matrix attachments, insufficient vascular supply and elaboration of inflammatory cytokines resulting from ischemia and/or cell death. This article reviews various signaling pathways involved in triggering highly complex forms of cell death and provides critical appreciation of different novel anti-death strategies developed from the knowledge gained from using an ischemic preconditioning approach. The use of pharmacological preconditioning for up-regulation of pro-survival proteins and cardiogenic markers in the transplanted stem cells will be discussed.

Haider, Husnain Kh; Ashraf, Muhammad

2008-01-01

250

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

2012-06-01

251

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

2008-03-01

252

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.

2013-01-01

253

Mild activation of poly(ADP-ribose) polymerase (PARP) is neuroprotective in rat hippocampal slice models of ischemic tolerance.  

PubMed

Ischemic tolerance is a phenomenon in which exposure to a mild preconditioning stress results in resistance to a subsequent lethal ischemic insult. Here we investigated the role of poly(ADP-ribose) polymerase (PARP) in the development of ischemic tolerance by using organotypic rat hippocampal slices exposed to 30 min oxygen-glucose deprivation (OGD), which leads to selective injury of the CA1 subregion 24 h later. We developed models of pharmacological preconditioning by exposing slices to subtoxic concentrations of either N-methyl-D-aspartate (NMDA) or (S)-3,5-dihydroxyphenylglycine (DHPG) and then, 24 h later, to 30 min OGD. Under these conditions, we observed a significant reduction in OGD-induced CA1 damage. Exposure of slices to the PARP-1 and -2 inhibitors TIQ-A, PJ-34 and UPF 1069 during preconditioning prevented the development of OGD tolerance in a concentration-dependent manner. NMDA and DHPG preconditioning increased the activity of PARP, as detected by immunoblots using antibodies against the poly(ADP-ribose) polymer product, but was not associated with consumption of cellular NAD(+) or ATP. Neuroprotection induced by preconditioning was also prevented by the caspase inhibitor Z-VAD-FMK. The modest but significant increase in caspase-3/7 induced by preconditioning, however, was not associated with PARP-1 cleavage, as occurred with staurosporine. Finally, TIQ-A prevented the activation of ERK1/2 and Akt induced by NMDA preconditioning, suggesting that the protective mechanism evoked by PARP requires activation of these prosurvival mediators. Our results suggest that preconditioning with appropriate pharmacological stimuli may promote neuroprotective mechanisms triggered by the sublethal activation of two otherwise deleterious executioners such as PARP and caspase-3/7. PMID:22639866

Gerace, Elisabetta; Scartabelli, Tania; Formentini, Laura; Landucci, Elisa; Moroni, Flavio; Chiarugi, Alberto; Pellegrini-Giampietro, Domenico E

2012-05-28

254

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.

2009-01-01

255

Preconditioning the diabetic heart: the importance of Akt phosphorylation.  

PubMed

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

2005-08-01

256

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.

2011-01-01

257

Voice Over IP Curriculum  

NSDL National Science Digital Library

The Convergence Technology Center has made Voice over IP curriculum available online. The site includes a syllabus and learning activities related to the topic. If you are an educator who would like to gain full access to the complete curriculum, you may email convergence_technology@collin.edu (further instructions for access are available on the site).

2012-10-02

258

Remote ischemic postconditioning promotes the survival of retinal ganglion cells after optic nerve injury.  

PubMed

Ischemic conditioning, the application of a mild ischemic stimulus to an ischemia-sensitive structure like the heart or brain either before (preconditioning) or after (postconditioning) its exposure to a lethal ischemic insult, is known to switch on endogenous protective mechanisms. However, most studies of its neuroprotective effect in the central nervous system (CNS) have focused on ischemic damage or related conditions like hypoxia, while its potential in treating other neural diseases remains uncertain. In particular, the recent discovery of remote ischemic postconditioning whereby mild ischemia applied to a region remote from the target after the main ischemic insult also confers protection offers an attractive paradigm to study its potential in other types of neural injury. Retinal ganglion cells damaged by optic nerve transection undergo extensive cell death. However, application of a series of mild ischemic/reperfusion cycles to the hind limb (limb remote ischemic postconditioning) at 10 min or 6 h after optic nerve cut was found to promote ganglion cell survival at 7 days post-injury, with the 10 min postconditioning still exerting protection at 14 days post-injury. Concomitant with the increased ganglion cell survival, 51 % more ganglion cells expressed the small heat shock protein HSP27, when remote ischemic postconditioning was performed at 10 min post-injury, as compared to the sham conditioning group. Our results highlight the potential of using remote ischemic postconditioning as a noninvasive neuroprotective strategy in different CNS disorders like spinal cord and traumatic brain injury. PMID:23733254

Liu, Xia; Sha, Ou; Cho, Eric Y P

2013-06-05

259

CXCL10/IP-10  

PubMed Central

OBJECTIVE Interferon (IFN)-? inducible protein, CXCL10/IP-10, is a member of the CXC chemokine family with pro-inflammatory and anti-angiogenic properties. This chemokine has been proposed to be a key link between inflammation and angiogenesis. The aim of this study was to determine whether preeclampsia and delivery of a small for gestational age (SGA) neonate are associated with changes in maternal serum concentration of CXCL10/IP-10. STUDY DESIGN This cross-sectional study included patients in the following groups: (1) non pregnant women (N=49); (2) women with normal pregnancies (N=89); (3) patients with preeclampsia (N=100); and (4) patients who delivered an SGA neonate (N=78). SGA was defined as birth weight below the 10th percentile. Maternal serum concentrations of CXCL10/IP-10 were measured by sensitive immunoassay. Non-parametric statistics were used for analysis. RESULTS (1) Patients with normal pregnancies had a significantly higher median serum concentration of CXCL10/IP-10 than non-pregnant women (median: 116.1 pg/mL, range: 40.7-1314.3 vs. median: 90.3 pg/mL, range: 49.2-214.7, respectively; p=0.002); (2) no significant correlation was found between maternal serum concentration of CXCL10/IP-10 and gestational age (between 19 and 38 weeks); (3) there were no differences in median serum CXCL10/IP-10 concentrations between patients who delivered an SGA neonate and those with normal pregnancies (median: 122.4 pg/mL, range: 37.3-693.5 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p>0.05); (4) patients with preeclampsia had a higher median serum concentration of CXCL10/IP-10 than normal pregnant women (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 116.1 pg/mL, range: 40.7-1314.3, respectively; p<0.05); (5) patients with preeclampsia had a higher median concentration of CXCL10/IP-10 than those who delivered an SGA neonate (median: 156.4 pg/mL, range: 47.4-645.9 vs. median: 122.4 pg/mL, range: 37.3-693.5, respectively; p<0.05). CONCLUSIONS Patients with preeclampsia have significantly higher serum concentrations of CXCL10/IP-10 than both normal pregnant women and mothers who have SGA neonates. These results are likely to reflect an anti-angiogenic state as well as an enhanced systemic inflammatory response in patients with preeclampsia. Alternatively, since preeclampsia and SGA share several mechanisms of disease, it is possible that a higher concentration of this chemokine may contribute to the clinical presentation of preeclampsia in patients with a similar intrauterine insult.

Gotsch, Francesca; Romero, Roberto; Friel, Lara; Kusanovic, Juan Pedro; Espinoza, Jimmy; Erez, Offer; Than, Nandor Gabor; Mittal, Pooja; Edwin, Samuel; Yoon, Bo Hyun; Kim, Chong Jai; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.

2008-01-01

260

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

PubMed

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

2003-09-01

261

Hypoxic Preconditioning Improves Survival of Cardiac Progenitor Cells: Role of Stromal Cell Derived Factor-1?-CXCR4 Axis  

PubMed Central

Background Cardiac progenitor cells (CPCs) have been shown to be suitable in stem cell therapy for resurrecting damaged myocardium, but poor retention of transplanted cells in the ischemic myocardium causes ineffective cell therapy. Hypoxic preconditioning of cells can increase the expression of CXCR4 and pro-survival genes to promote better cell survival; however, it is unknown whether hypoxia preconditioning will influence the survival and retention of CPCs via the SDF-1?/CXCR4 axis. Methods and Results CPCs were isolated from adult mouse hearts and purified by magnetic activated cell sorting using c-kit magnetic beads. These cells were cultured at various times in either normoxic or hypoxic conditions, and cell survival was analyzed using flow cytometry and the expression of hypoxia-inducible factor-1? (HIF-1?), CXCR4, phosphorylated Akt and Bcl-2 were measured by Western blot. Results showed that the expression of pro-survival genes significantly increased after hypoxia treatment, especially in cells cultured in hypoxic conditions for six hours. Upon completion of hypoxia preconditioning from c-kit+ CPCs for six hours, the anti-apoptosis, migration and cardiac repair potential were evaluated. Results showed a significant enhancement in anti-apoptosis and migration in vitro, and better survival and cardiac function after being transplanted into acute myocardial infarction (MI) mice in vivo. The beneficial effects induced by hypoxia preconditioning of c-kit+ CPCs could largely be blocked by the addition of CXCR4 selective antagonist AMD3100. Conclusions Hypoxic preconditioning may improve the survival and retention of c-kit+ CPCs in the ischemic heart tissue through activating the SDF-1?/CXCR4 axis and the downstream anti-apoptosis pathway. Strategies targeting this aspect may enhance the effectiveness of cell-based cardiac regenerative therapy.

Yan, Fengdi; Yao, Yuyu; Chen, Lijuan; Li, Yefei; Sheng, Zulong; Ma, Genshan

2012-01-01

262

Ischaemic preconditioning: is it clinically relevant?  

PubMed

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

1995-09-01

263

Continuously Connected With Mobile IP.  

National Technical Information Service (NTIS)

Cisco Systems developed Cisco Mobile Networks, making IP devices mobile. With this innovation, a Cisco router and its connected IP devices can roam across network boundaries and connection types. Because a mobile user is able to keep the same IP address w...

2002-01-01

264

Distance learning using IP multicast  

Microsoft Academic Search

Summary: As the Internet and Internet technologies storm the world of communications, economic forces are driving IP to provide services well beyond what was originally intended. The simple flexible IP service model and the avoidance of the burdensome regulatory\\/contractual legacy of telephony have resulted in ubiquitous reach and greater economies. IP multicast promises to bring the same to group communications.

Björn Brynjúlfsson; Ólafur Ragnar Helgason; Heimir Þór Sverrisson; Gísli Hjálmtýsson

265

[Myocardial preconditioning and its practical significance].  

PubMed

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

2002-03-24

266

Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase.  

PubMed

Adenosine and acetylcholine (ACh) trigger preconditioning by different signaling pathways. The involvement of phosphatidylinositol 3-kinase (PI3-kinase), a protein tyrosine kinase, and Src family tyrosine kinase in preconditioning was evaluated in isolated rabbit hearts. Either wortmannin (PI3-kinase blocker), genistein (tyrosine kinase blocker), lavendustin A (tyrosine kinase blocker), or 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2; Src family tyrosine kinase blocker) was given for 15 min to bracket a 5-min infusion of either adenosine or ACh (trigger phase). The hearts then underwent 30 min of regional ischemia. Infarct size for ACh alone was 9.3 +/- 3.5% of the risk zone versus 34.3 +/- 4.1% in controls. All four inhibitors blocked ACh-induced protection. When wortmannin or PP2 was infused only during the 30-min ischemic period (mediator phase), ACh-induced protection was not affected (7.4 +/- 2.1% and 9.7 +/- 1.7% infarction, respectively). Adenosine-triggered protection was not blocked by any of the inhibitors. Therefore, PI3-kinase and at least one protein tyrosine kinase, probably Src kinase, are involved in the trigger phase of ACh-induced, but not adenosine-induced, preconditioning. Neither PI3-kinase nor Src kinase is a mediator of the protection of ACh. PMID:12388236

Qin, Qining; Downey, James M; Cohen, Michael V

2002-10-17

267

Involvement of Akt in preconditioning-induced tolerance to ischemia in PC12 cells  

PubMed Central

The serine–threonine protein kinase Akt has been identified as an important mediator of cell survival able to counteract apoptotic stimuli. However, hibernation, a model of natural tolerance to cerebral ischemia, is associated with downregulation of Akt. We previously established a model of ischemic tolerance in a PC12 cell line and using this model we now addressed the question whether ischemic tolerance also downregulates Akt in PC12 cells. Kinetic studies showed decreased Akt phosphorylation in tolerized cells. Similarly, phosphorylated levels of three major targets of Akt and well-known proapoptotic factors, the glycogen synthase kinase 3 (GSK-3), a Forkhead family member, FoxO4, and the protein murine double minute 2 (MDM2), all inactivated upon phosphorylation by Akt, were decreased in preconditioned cells. In addition, pharmacological blockade of the phosphoinositide 3-kinase (PI3K)/Akt pathway reduced cell death induced by oxygen and glucose deprivation (OGD) and increased the protective effect of preconditioning (PC). Furthermore, decreasing availability of P-Akt by transfecting PC12 cells with constructs of inactive Akt also resulted in protection against OGD and potentiation of the protective effect of PC. Depending on the environment, GSK-3, FOXO-4, and MDM2 can trigger apoptotic responses or cell cycle arrest, and thus, in a situation of reduced energy, driving the cells into a state of quiescence might be neuroprotective. This work suggests that in the context of tolerance downregulation of Akt is beneficial.

Hillion, Joelle A; Li, YiXin; Maric, Dragan; Takanohashi, Asako; Klimanis, Dace; Barker, Jeffrey L; Hallenbeck, John M

2007-01-01

268

Pharmacologic preconditioning induced by beta-adrenergic stimulation is mediated by activation of protein kinase C.  

PubMed

Ischemic preconditioning (I-PC) occurs via activation of protein kinase C (PKC). This study was undertaken to determine whether pharmacologic preconditioning by beta-adrenergic stimulation (beta-PC) is mediated by PKC activation. Isolated rat hearts were subjected to 40-min ischemia and 30-min reperfusion. Beta-PC was induced by 0.25 microM isoproterenol pretreatment for 2 min followed by 10-min normoxic perfusion. Beta-PC enhanced the recovery of rate-pressure product of the ischemic/reperfused heart (79.1 +/- 8.4% vs. 12.4 +/- 1.6% of initial for Non-PC group, n = 6) and attenuated the release of creatine kinase during 30-min reperfusion (30.2 +/- 2.2 vs. 59.8 +/- 6.1 nmol/min/g wet wt for Non-PC group, n = 6), similar to an I-PC stimulus of 5-min ischemia and 5-min reperfusion. Treatment with 50 microM polymyxin B, a PKC inhibitor, abolished the cardioprotection of both beta-PC and I-PC. Furthermore, similar changes in subcellular distribution of PKC were induced by both beta-PC and I-PC. The changes in subcellular distribution of PKC-delta suggested its translocation from cytosol to membrane fraction, a marker of PKC activation. These results suggest that the cardioprotection induced by beta-PC, like I-PC, is mediated by PKC activation. PMID:9869502

Yabe, K; Ishishita, H; Tanonaka, K; Takeo, S

1998-12-01

269

Protective mechanisms during ischemic tolerance in skeletal muscle.  

PubMed

The purpose of this study was to test specific mechanisms of protection afforded the rat extensor digitorum longus (EDL) muscle during ischemic tolerance. Two days following five cycles of 10 min ischemia and 10 min reperfusion, heme oxygenase (HO) and calcium-dependent nitric oxide synthase (cNOS) activities were increased 2- and 2.5-fold (p <.05), respectively. Interestingly, calcium-independent NOS (iNOS) activity was completely downregulated (p <.05). The levels of superoxide dismutase (SOD) and catalase were increased 2-fold (p <.05), while glutathione peroxidase activity remained unchanged from non-preconditioned controls. Using intravital microscopy combined with chromium mesoporphyrin (CrMP), a selective HO inhibitor, and l-NAME, a NOS inhibitor, the roles of HO and cNOS were evaluated. Ischemic tolerance in the EDL muscle, 48 h after the preconditioning stimulus, was characterized by complete protection from both microvascular perfusion deficits and tissue injury after a 2-h period of ischemia. Removal of NOS activity completely removed the benefit afforded microvascular perfusion, while inhibition of HO activity prevented the parenchymal protection. These data suggest that ischemic tolerance within skeletal muscle is associated with the upregulation of specific cytoprotective proteins and that the benefits afforded by cNOS and HO activity are spatially discrete to the microvasculature and parenchyma, respectively. PMID:15036356

Badhwar, Amit; Bihari, Aurelia; Dungey, Alison A; Scott, Jeffrey R; Albion, Caroline D; Forbes, Thomas L; Harris, Kenneth A; Potter, Richard F

2004-02-01

270

Chronic lower extremity ischemia: a human model of ischemic tolerance  

PubMed Central

Background Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. Patients and methods Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aorto-bifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. Results Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. Conclusions Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.

Badhwar, Amit; Forbes, Thomas L.; Lovell, Marge B.; Dungey, Alison A.; McCarter, Sarah D.; Scott, Jeffrey R.; DeRose, Guy; Harris, Kenneth A.; Potter, Richard F.

2004-01-01

271

CANOPEN Controller IP Core  

NASA Astrophysics Data System (ADS)

This paper will describe the activities performed by Thales Alenia Space Italia supported by the European Space Agency in the definition of a CAN bus interface to be used on Exomars. The final goal of this activity is the development of an IP core, to be used in a slave node, able to manage both the CAN bus Data Link and Application Layer totally in hardware. The activity has been focused on the needs of the EXOMARS mission where devices with different computational performances are all managed by the onboard computer through the CAN bus.

Caramia, M.; Montagna, M.; Furano, G.; Winton, A.

2010-08-01

272

Pharmacologically induced preconditioning with diazoxide: a novel approach to brain protection 3 1 The Thoracic Surgery Directors Association (TSDA) Resident Research Award, sponsored by Medtronic, Inc, was established in 1990 to encourage resident research in cardiothoracic surgery. Abstracts submitted to The Society of Thoracic Surgeons (STS) Program Committee representing research performed by residents were forwarded to the TSDA to be considered for this award. The abstracts were reviewed by the TSDA Executive Committee, consisting of Gordon N. Olinger, President, Edward D. Verrier, President-Elect, Jeffrey P. Gold, Secretary\\/Treasurer, and Richard Shemin, Councillor-at-Large. 3 2 The eleventh TSDA Resident Research Award was given to Jay G. Shake, MD, a general surgery resident, in the Department of Surgery, Johns Hopkins Hospital, Baltimore, MD. He received a monetary award of $2,500 and an engraved desktop award. 3 3 The TSDA, with support by Medtronic, Inc, makes this award ann  

Microsoft Academic Search

Background. Ischemic preconditioning is an endogenous mechanism whereby brief periods of ischemia render neurons resistant to subsequent lethal insults. This protection appears to alter cellular apoptosis and can be induced by potassium channel openers acting on the inner membrane of the mitochondria (mitoKATP). To test the hypothesis that pharmacologic preconditioning could provide neuroprotection, the mitoKATP opener diazoxide was used in

Jay G Shake; Eric A Peck; Eduardo Marban; Vincent L Gott; Michael V Johnston; Juan C Troncoso; J. Mark Redmond; William A Baumgartner

2001-01-01

273

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

1995-01-01

274

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

2009-01-01

275

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

1997-01-01

276

[Myocardial reperfusion: salvation or danger for the heart muscle? Stunning, hibernation and preconditioning: the states of endogenous cardiac protection against ischemia].  

PubMed

During most of our decade myocardial ischemia was regarded as an all-or-nothing phenomenon, either resulting in myocardial necrosis in case of severe and prolonged ischemia, or in negligible changes when ischemia was transient and mild. This view has been challenged in the wake of new discoveries during the last 15 years which indicate that depressed myocardial contractility with preserved viability may exist during or following ischemic insults. The clinical and pathophysiologic characteristics of these ischemic myocardial syndromes--stunning, hibernation and preconditioning--are discussed in the present overview. PMID:9490468

Atar, D

1997-11-29

277

Hyperthermic preconditioning protects astrocytes from ischemia/reperfusion injury by up-regulation of HIF-1 alpha expression and binding activity.  

PubMed

It has been demonstrated that hypoxia-inducible factor-1 alpha (HIF-1 alpha) mediates ischemic tolerance induced by hypoxia/ischemia or pharmacological preconditioning. In addition, preconditioning stimuli can be cross-tolerant, safeguarding against other types of injury. We therefore hypothesized HIF-1 alpha might also be associated with ischemic tolerance induced by hyperthermic preconditioning. In the present study, we demonstrated for the first time that 6 h of hyperthermia (38°C or 40°C) could induce a characteristic "reactive" morphology and a significant increase in the expression of bystin in astrocytes. We also showed that pre-treatment with 6 h of hyperthermia resulted in a significant increase in cell viability and a remarkable decrease in lactate dehydrogenase (LDH) release and apoptosis development in the astrocytes that were exposed to 24 h of ischemia and a subsequent 24 h of reperfusion. Analysis of mechanisms showed that hyperthermia could lead to a significant increase in HIF-1 alpha expression and also the HIF-1 binding activity in the ischemia/reperfusion astrocytes. The data provide evidence to our hypothesis that the up-regulation of HIF-1 alpha is associated with the protective effects of hyperthermic preconditioning on astrocytes against ischemia/reperfusion injury. PMID:20599612

Du, Fang; Zhu, Li; Qian, Zhong-Ming; Wu, Xiao-Mei; Yung, Wing-Ho; Ke, Ya

2010-06-25

278

Hypoxia-preconditioned adipose tissue-derived mesenchymal stem cell increase the survival and gene expression of engineered neural stem cells in a spinal cord injury model  

Microsoft Academic Search

Hypoxic preconditioning (HP) is a novel strategy to make stem cells resistant to the ischemic environment they encounter after transplantation into injured tissue; this strategy improves survival of both the transplanted cells and the host cells at the injury site. Using both in vitro and in vivo injury models, we confirmed that HP-treated adipose tissue-derived mesenchymal stem cells (HP-AT-MSCs) increased

Jin Soo Oh; Yoon Ha; Sung Su An; Momin Khan; William A. Pennant; Hyo Jin Kim; Do Heum Yoon; Minhyung Lee; Keung Nyun Kim

2010-01-01

279

Cardiomyocyte overexpression of the ?1a-adrenergic receptor in the rat phenocopies second but not first window preconditioning  

PubMed Central

We examined ?1A-adrenergic receptor (AR) mediation of preconditioning in a novel ?1A-AR cardiac transgenic (TG) rat model (?1A-TG). Compared with nontransgenic littermates (NTLs), in conscious ?1A-TG rats, heart rate was reduced, contractility [left ventricle (LV) +dP/dt, ejection fraction, end-systolic elastance] was significantly enhanced, and triple product (LV systolic wall stress × LV +dP/dt × heart rate) was unchanged. However, infarct size (IS)/area at risk (AAR) in response to ischemia-reperfusion (30 min coronary occlusion/3 h reperfusion) was reduced to 35 ± 4.6% in ?1A-TGs vs. 52 ± 2.2% in NTLs (P < 0.05). Second window preconditioning reduced IS/AAR in NTLs to 29 ± 2.7% but did not afford further protection in ?1A-TGs. In contrast, with first window preconditioning, IS/AAR was reduced to similar levels in both ?1A-TGs (12 ± 1.4%) and NTLs (10 ± 1.1%). In untreated ?1A-TGs, cardioprotection was associated with enhanced myocardial phosphorylated (p)-mitogen/extracellular signal-regulated kinase (MEK), p-extracellular signal-regulated kinase (ERK), and inducible nitric oxide synthase (iNOS) at the protein level, along with a 1.3-fold increase in total nitric oxide synthase activity like in second window preconditioning. Affymetrix microarrays revealed that few genes (4.6% of 3,172 upregulated; 8.8% of 3,498 downregulated) showed directionally similar changes in ?1A-TGs vs. NTLs subjected to second window preconditioning. Thus, second, but not first, window cardioprotection is evident in ?1A-TGs in the absence of ischemic preconditioning and is mediated by iNOS activation associated with MEK/ERK phosphorylation. Transcriptionally, however, second window preconditioning is considerably more complex than ?1A-TG preconditioning, with the alteration of thousands of additional genes affording no further protection than that already available in ?1A-TG rats.

Zhao, Xin; Park, Jiyeon; Ho, David; Gao, Shumin; Yan, Lin; Ge, Hui; Iismaa, Siiri; Lin, Lin; Tian, Bin; Vatner, Dorothy E.; Graham, Robert M.

2012-01-01

280

[Association between ethanol intake and ischemic heart disease].  

PubMed

Most world populations consume alcoholic beverages. Ethanol may have both protective and harmful effects on health depending on the amount and way of consumption. An extensive body of data shows concordant J or U-shaped associations between alcohol intake and a variety of adverse health outcomes, including coronary heart disease, diabetes, hypertension, congestive heart failure, stroke, and all-cause mortality. In particular, moderate ethanol consumption is associated with cardioprotective benefits such as lower cardiovascular risk and mortality, probably mediated by beneficial effects on inflammation, lipids, and coagulation. In contrast, binge and/or heavy drinking results in proportional worsening of outcomes, increasing cardiovascular events and mortality. This harmful effect has been recently associated with the blockade of ischemic preconditioning mediated by high doses of ethanol. In this review, we highlight the recent epidemiological and experimental evidences regarding the specific benefits and risks of ethanol in the setting of ischemic heart disease. PMID:19209541

Niccoli, Giampaolo; Bacà, Marco; Cosentino, Nicola; Fabretti, Alessandro; Crea, Filippo

2008-11-01

281

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

PubMed

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

2010-01-01

282

All preconditioning-related G protein-coupled receptors can be demonstrated in the rabbit cardiomyocyte.  

PubMed

G protein-coupled receptors for adenosine (A(1), A(3), A(2A), and A(2B)), bradykinin (B(1)) and opioids (?) are all involved in the mechanism of ischemic preconditioning. Although the heart is comprised of many tissue types, it has been assumed that preconditioning's protective signaling occurs in the cardiomyocyte. We critically tested that hypothesis by testing for the presence of each of these receptors in isolated adult rabbit ventricular myocytes that had been transfected with cyclic nucleotide-gated (CNG) ion channels. Because subsarcolemmal cyclic adenosine monophosphate (cAMP) opens the CNG channels, we could monitor cAMP levels within a single cardiomyocyte by measuring channel current with a patch pipette. The presence of a receptor would be confirmed if we could alter cAMP in the cell with a selective agonist to the receptor being studied. Superfusion with the ?-adrenergic G(s)-coupled receptor agonist isoproterenol (50 nmol/L) transiently increased cAMP levels and, therefore, channel current. Pretreatment with selective agonists to A(1) or A(3) adenosine receptors (ARs) that are G(i)-coupled markedly attenuated the response to isoproterenol, indicating inhibition of adenylyl cyclase by increased G(i) activity. Agonists to bradykinin or ?-opioid receptors also attenuated isoproterenol's response. A(2A)AR and A(2B)AR are G(s)-coupled. The A(2A)AR-selective agonist CGS21680 increased current through CNG channels but only in the presence of phosphodiesterase (PDE) inhibitors, indicating low surface receptor activity and high intracellular PDE activity. As we previously reported, BAY 60-6583, an A(2B)AR-selective agonist which mimics preconditioning's protection in rabbit heart, neither increased nor decreased membrane current in transfected cardiomyocytes, suggesting the absence or a markedly limited number of A(2B)AR in the sarcolemma. However, reverse transcription polymerase chain reaction (RT-PCR) of purified cardiomyocytes yielded an A(2B)AR band, implying that rabbit cardiomyocytes do indeed express A(2B)AR. These data reveal that all receptors reported to be involved in ischemic preconditioning do exist on or within the cardiomyocyte. PMID:21828281

Xin, Wenkuan; Yang, Xiulan; Rich, Thomas C; Krieg, Thomas; Barrington, Robert; Cohen, Michael V; Downey, James M

2011-08-09

283

Essential Role of the Redox Sensitive Kinase p66shc in Determining Energetic and Oxidative Status and Cell Fate in Neuronal Preconditioning  

PubMed Central

Ischemic preconditioning is a phenomenon in which low level stressful stimuli upregulate endogenous defensive programs resulting in subsequent resistance to otherwise lethal injuries. We previously observed that signal transduction systems typically associated with neurodegeneration such as caspase activation are requisite events for the expression of tolerance and induction of HSP70. In this work, we sought to determine the extent and duration of oxidative and energetic dysfunction as well as the role of effector kinases on metabolic function in preconditioned cells. Using an in vitro neuronal culture model, we observed a robust increase in Raf and p66Shc activation within 1h of preconditioning. Total ATP content decreased by 25% 3h after preconditioning but returned to baseline by 24h. Use of a free radical spin trap or p66shc inhibitor increased ATP content whereas a Raf inhibitor had no effect. Phosphorylated p66shc rapidly relocalized to the mitochondria and in the absence of activated p66shc, autophagic processing increased. The constitutively expressed chaperone HSC70 relocalized to autophagosomes. Preconditioned cells experience significant total oxidative stress measured by F2-isoprostanes and neuronal stress evaluated by F4-neuroprostane measurement. Neuroprostane levels were enhanced in the presence of Shc inhibitors. Finally, we found that inhibiting either p66shc or Raf blocked neuroprotection afforded by preconditioning as well as upregulation of HSP70 suggesting both kinases. This is the first work to demonstrate the essential role of p66shc in mediating requisite mitochondrial and energetic compensation following preconditioning and suggests a mechanism by which protein and organelle damage mediated by ROS can increase HSP70.

Brown, Jacquelynn E.; Zeiger, Stephanie L.H.; Hettinger, Jane C.; Brooks, Joshua D.; Holt, Benjamin; Morrow, Jason D.; Musiek, Erik S.; Milne, Ginger; McLaughlin, BethAnn

2010-01-01

284

Hash-based IP traceback  

Microsoft Academic Search

The design of the IP protocol makes it difficult to reliably identify the originator of an IP packet. Even in the absence of any deliberate attempt to disguise a packet's origin, wide-spread packet forwarding techniques such as NAT and encapsulation may obscure the packet's true source. Techniques have been developed to determine the source of large packet flows, but, to

Alex C. Snoeren; Craig Partridge; Luis A. Sanchez; Christine E. Jones; Fabrice Tchakountio; Stephen T. Kent; W. Timothy Strayer

2001-01-01

285

Single-packet IP traceback  

Microsoft Academic Search

The design of the IP protocol makes it difficult to reliably identify the originator of an IP packet. Even in the absence of any deliberate attempt to disguise a packet's origin, widespread packet forwarding techniques such as NAT and encapsulation may obscure the packet's true source. Techniques have been developed to determine the source of large packet flows, but, to

Alex C. Snoeren; Craig Partridge; Luis A. Sanchez; Christine E. Jones; Fabrice Tchakountio; Beverly Schwartz; Stephen T. Kent; W. Timothy Strayer

2002-01-01

286

SN2009ip: Dimming Rapidly  

NASA Astrophysics Data System (ADS)

ATEL #4412 (Smith & Mauerhan) recently suggested that supernova impostor SN2009ip has re-brightened as a true supernova. ATEL #4414 (Margutti et al.) reported Swift observations indicating that SN2009ip is declining in magnitude and not a true supernova. We obtained V and R observations with the 20-inch telescope at the Henry R. Barber Astronomical Observatory (University of Illinois Springfield).

Martin, J. C.; O'Brien, J.; Hubbell-Thomas, J.

2012-09-01

287

IP Addresses in Email Clients  

Microsoft Academic Search

Abstract. IP addresses are an important tool for fighting spam, used for safe lists, blackhole lists, anti-spoofing and related purposes. While it is trivial to find the sender's IP address in most email server software, it turns out to be surprisingly di cult to do so in email client software: we explain why. This implies that either alternative approaches are

Joshua Goodman

2004-01-01

288

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

1981-05-01

289

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

290

Thermal preconditioning prevents peritendinous adhesions and inflammation.  

PubMed

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

2002-12-01

291

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

PubMed

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

2012-10-15

292

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

1989-01-01

293

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

2009-01-01

294

Hypoxic preconditioning alleviates ethanol neurotoxicity: the involvement of autophagy.  

PubMed

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

2013-04-09

295

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

2009-02-01

296

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))

1988-01-01

297

Increased superoxide formation induced by irradiation preconditioning triggers kidney resistance to ischemia-reperfusion injury in mice.  

PubMed

One of the obstacles in irradiation therapy is cytoresistance, acquired by activation of self-defense systems, such as antioxidant or molecular chaperone systems, to cope with stress. We investigated whether irradiation preconditioning (IP) rendered resistance of the kidney against subsequent ischemia-reperfusion (I/R) and attempted to elucidate any such protective mechanisms. Mice were irradiated with a total of 4, 6, or 8 Gy using a cesium-137 source irradiator and then, 6 days later, were subjected to 28 min of bilateral renal ischemia followed by reperfusion. Eight Gy of IP significantly attenuated the increases in plasma creatinine (PCr) and blood urea nitrogen (BUN) concentration, structural damage, lipid peroxidation, superoxide formation, expression and activity of NADPH oxidase (NOX)-2, nitrotyrosine level, and hydrogen peroxide production after I/R in kidney tissues, indicating that IP protects the kidneys from I/R injury. IP markedly increased the activity of NOX, resulting in increased superoxide formation, manganese superoxide dismutase (MnSOD) activity and expression, and heat shock protein (HSP)-27 expression in kidneys. However, it did not change expressions of catalase, copper-zinc superoxide dismutase (CuZnSOD), and HSP-72. To investigate whether the protection afforded by IP was associated with increases in MnSOD and HSP-27 expression triggered by increased superoxide formation after IP, we administered manganese (III) tetrakis(1-methyl-4-pyridyl)porphyrin, a superoxide scavenger, to IP mice. This administration blocked superoxide formation and subsequent increases in MnSOD and HSP-27 expression and accelerated the post-I/R increases in PCr and BUN. In conclusion, IP renders kidney resistance to I/R injury, and this resistance is mediated by increased superoxide formation, which activates MnSOD activity and expression as well as HSP-27 expression. PMID:19193722

Kim, Jinu; Park, Jeen-Woo; Park, Kwon Moo

2009-02-04

298

Ischemic postconditioning mediates cardioprotection via PI3K/GSK-3?/?-catenin signaling pathway in ischemic rat myocardium.  

PubMed

Previous studies have shown that PI3K/GSK-3?/?-catenin signaling pathway plays a vital role in ischemic preconditioning. The present study attempts to evaluate whether PI3K/GSK-3?/?-catenin signaling pathway might be responsible for the cardioprotection in ischemic postconditioning. Male Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery occlusion and 2 h of reperfusion. One hundred twenty rats were randomized into six groups: sham, ischemia/reperfusion (I/R), ischemic postconditioning (Post), 15 ?g · kg wortmannin (PI3K inhibitor) plus ischemic postconditioning (Wort + Post), wortmannin plus I/R (Wort + I/R), and 0.6 mg · kg SB216763 (GSK-3? inhibitor) plus I/R (SB + I/R). Wortmannin and SB216763 were administered, respectively, 10 and 5 min before reperfusion. Myocardial infarct size; number of apoptotic cardiomyocytes; total Akt, GSK-3?; phosphorylated Akt, GSK-3?; ?-catenin in cytosol and nucleus; and Bcl-2 protein were assessed. It was found that Post and SB + I/R reduced infarct size (32.3% [SD, 2.8%], 32.7% [SD, 2.1%], vs. 53.4% [SD, 3.2%], respectively, P < 0.05) and apoptotic index of cardiomyocytes (23.2% [SD, 1.8%], 23.8% [SD, 1.8%], vs. 47.3% [SD, 5.8%], respectively, P < 0.05); compared with I/R, wortmannin abolished the cardioprotection of ischemic postconditioning. Post and SB + I/R increased phosphorylated Akt, phosphorylated GSK3?, ?-catenin in cytosol and nucleus, and Bcl-2 expression versus I/R. These results indicate that ischemic postconditioning could induce myocardial protection via PI3K/GSK-3?/?-catenin signaling pathway, activation of which results in accumulation of ?-catenin and upregulation of its target genes Bcl-2. PMID:22576003

Wu, Qiao-Ling; Shen, Tu; Shao, Li-Li; Ma, Hong; Wang, Jun-Ke

2012-08-01

299

Transient Ischemic Attack  

MedlinePLUS

A transient ischemic attack (TIA) is a stroke that comes and goes quickly. It happens when the blood supply to part of the brain stops briefly. Symptoms of a TIA are like other stroke symptoms, but do not ...

300

Lubiprostone induced ischemic colitis.  

PubMed

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

2013-01-14

301

Lubiprostone induced ischemic colitis  

PubMed Central

Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

2013-01-01

302

Sites of action of adenosine in interorgan preconditioning of the heart.  

PubMed

The mechanism underlying interorgan preconditioning of the heart remains elusive, although a role for adenosine and activation of a neurogenic pathway has been postulated. We tested in rats the hypothesis that adenosine released by the remote ischemic organ stimulates local afferent nerves, which leads to activation of myocardial adenosine receptors. Preconditioning with a 15-min mesenteric artery occlusion (MAO15) reduced infarct size produced by a 60-min coronary artery occlusion (60-min CAO) from 68 +/- 2% to 48 +/- 4% (P < 0.05). Pretreatment with the ganglion blocker hexamethonium or 8-(p-sulfophenyl)theophylline (8-SPT) abolished the protection by MAO15. Intramesenteric artery (but not intraportal vein) infusion of adenosine (10 microg/min) was as cardioprotective as MAO15, which was also abolished by hexamethonium. Whereas administration of hexamethonium at 5 min of reperfusion following MAO15 had no effect, 8-SPT at 5 min of reperfusion abolished the protection. Permanent reocclusion of the mesenteric artery before the 60-min CAO enhanced the cardioprotection by MAO15 (30 +/- 5%), but all protection was abolished when 8-SPT was administered after reocclusion of the mesenteric artery. Together, these findings demonstrate the involvement of myocardial adenosine receptors. We therefore conclude that locally released adenosine during small intestinal ischemia stimulates afferent nerves in the mesenteric bed during early reperfusion, initiating a neurogenic pathway that leads to activation of myocardial adenosine receptors. PMID:12063271

Liem, David A; Verdouw, Pieter D; Ploeg, Harald; Kazim, Shahla; Duncker, Dirk J

2002-07-01

303

Broadcast quality video over IP  

Microsoft Academic Search

Abstract—We consider the problem of designing systems for the transmission of video signals of the quality found in current television broadcasts, over high-speed segments of the public IP network. Our most important contribution is the definition of a network\\/coder interface for IP networks which gathers channel state information, and then sets parameters of the video coder to maximize the quality

Sergio D. Servetto; Klara Nahrstedt

2001-01-01

304

IP Version 6, Online Version  

NSDL National Science Digital Library

This page offers five videos of lectures from Sam Bowne's IP Version 6 course. Each video varies in length from ten minutes to an hour. These materials would be most useful for individuals with some experience with IP technology; the end goal of the course was for individuals enrolled to gain IPv6 certification and be able to set up IPv6 on a router. Flash is required to view the videos.

Bowne, Sam

2012-10-17

305

How dynamic are IP addresses?  

Microsoft Academic Search

This paper introduces a novel method, UDmap, to identify dy- namically assigned IP addresses and analyze their dynamics pat- tern. UDmap is fully automatic, and relies only on application-level server logs that are already available today. We applied UDmap to a month-long Hotmail user-login trace and identified a significant number of dynamic IP addresses - more than 102 million. This

Yinglian Xie; Fang Yu; Kannan Achan; Eliot Gillum; Moisés Goldszmidt; Ted Wobber

2007-01-01

306

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

2006-08-31

307

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

1989-01-01

308

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

1999-01-01

309

Neuroprotective effect of hypoxic preconditioning: phenomenon and mechanisms.  

PubMed

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

2002-02-01

310

Hypoxia Preconditioned Mesenchymal Stem Cells Improve Vascular and Skeletal Muscle Fiber Regeneration After Ischemia Through a Wnt4-dependent Pathway  

PubMed Central

Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow and vascular formation compared to injected nonpreconditioned MSC (NormMSC). These observed effects were correlated with an increase in HypMSC engraftment and a putative role in necrotic skeletal muscle fiber clearance. Moreover, HypMSC transplantation resulted in a large increase in Wnt4 (wingless-related MMTV integration site 4) expression and we demonstrate its functional significance on MSC proliferation and migration, endothelial cell (EC) migration, as well as myoblast differentiation. Furthermore, suppression of Wnt4 expression in HypMSC, abrogated the hypoxia-induced vascular regenerative properties of these cells in the mouse hindlimb ischemia model. Our data suggest that hypoxic preconditioning plays a critical role in the functional capabilities of MSC, shifting MSC location in situ to enhance ischemic tissue recovery, facilitating vascular cell mobilization, and skeletal muscle fiber regeneration via a paracrine Wnt-dependent mechanism.

Leroux, Lionel; Descamps, Betty; Tojais, Nancy F; Seguy, Benjamin; Oses, Pierre; Moreau, Catherine; Daret, Daniele; Ivanovic, Zoran; Boiron, Jean-Michel; Lamaziere, Jean-Marie D; Dufourcq, Pascale; Couffinhal, Thierry; Duplaa, Cecile

2010-01-01

311

Transplantation of Hypoxia Preconditioned Bone Marrow Mesenchymal Stem Cells Enhances Angiogenesis and Neurogenesis after Cerebral Ischemia in Rats  

PubMed Central

Hypoxic preconditioning of stem cells and neural progenitor cells has been tested for promoting cell survival after transplantation. The present investigation examined the hypothesis that hypoxic preconditioning of bone marrow mesenchymal stem cells (BMSCs) could not only enhance their survival but also reinforce regenerative properties of these cells. BMSCs from eGFP engineered rats or pre-labeled with BrdU were pre-treated with normoxia (20% O2, N-BMSCs) or sublethal hypoxia (0.5% O2. H-BMSCs). The hypoxia exposure up-regulated HIF-1? and trophic/growth factors in BMSCs, including brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) and its receptor FIK-1, erythropoietin (EPO) and its receptor EPOR, stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). Meanwhile, many pro-inflammatory cytokines/chemokines were downregulated in H-BMSCs. N-BMSCs or H-BMSCs were intravenously injected into adult rats 24 hrs after 90-min middle cerebral artery occlusion. Comparing to N-BMSCs, transplantation of H-BMSCs showed greater effect of suppressing microglia activity in the brain. Significantly more NeuN-positive and Glut1-positive cells were seen in the ischemic core and peri-infarct regions of the animals received H-BMSC transplantation than that received N-BMSCs. Some NeuN-positive and Glut-1-positive cells showed eGFP or BrdU immunoflourescent reactivity, suggesting differentiation from exogenous BMSCs into neuronal and vascular endothelial cells. In Rota-rod test performed 15 days after stroke, animals received H-BMSCs showed better locomotion recovery compared with stroke control and N-BMSC groups. We suggest that hypoxic preconditioning of transplanted cells is an effective means of promoting their regenerative capability and therapeutic potential for the treatment of ischemic stroke.

Wei, Ling; Fraser, Jamie L.; Zhong-Yang, Lu; Hu, Xinyang; Yu, Shan Ping

2012-01-01

312

Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats.  

PubMed

Hypoxic preconditioning of stem cells and neural progenitor cells has been tested for promoting cell survival after transplantation. The present investigation examined the hypothesis that hypoxic preconditioning of bone marrow mesenchymal stem cells (BMSCs) could not only enhance their survival but also reinforce regenerative properties of these cells. BMSCs from eGFP engineered rats or pre-labeled with BrdU were pre-treated with normoxia (20% O(2), N-BMSCs) or sub-lethal hypoxia (0.5% O(2). H-BMSCs). The hypoxia exposure up-regulated HIF-1? and trophic/growth factors in BMSCs, including brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) and its receptor FIK-1, erythropoietin (EPO) and its receptor EPOR, stromal derived factor-1 (SDF-1) and its CXC chemokine receptor 4 (CXCR4). Meanwhile, many pro-inflammatory cytokines/chemokines were down-regulated in H-BMSCs. N-BMSCs or H-BMSCs were intravenously injected into adult rats 24h after 90-min middle cerebral artery occlusion. Comparing to N-BMSCs, transplantation of H-BMSCs showed greater effect of suppressing microglia activity in the brain. Significantly more NeuN-positive and Glut1-positive cells were seen in the ischemic core and peri-infarct regions of the animals received H-BMSC transplantation than that received N-BMSCs. Some NeuN-positive and Glut-1-positive cells showed eGFP or BrdU immunoflourescent reactivity, suggesting differentiation from exogenous BMSCs into neuronal and vascular endothelial cells. In Rotarod test performed 15days after stroke, animals received H-BMSCs showed better locomotion recovery compared with stroke control and N-BMSC groups. We suggest that hypoxic preconditioning of transplanted cells is an effective means of promoting their regenerative capability and therapeutic potential for the treatment of ischemic stroke. PMID:22426403

Wei, Ling; Fraser, Jamie L; Lu, Zhong-Yang; Hu, Xinyang; Yu, Shan Ping

2012-03-09

313

Running TCP/IP over ATM Networks.  

ERIC Educational Resources Information Center

Discusses Internet protocol (IP) and subnets and describes how IP may operate over asynchronous transfer mode (ATM). Topics include TCP (transmission control protocol), ATM cells and adaptation layers, a basic architectural model for IP over ATM, address resolution, mapping IP to a subnet technology, and connection management strategy. (LRW)

Witt, Michael

1995-01-01

314

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

2013-01-01

315

Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells.  

PubMed

Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor engraftment in vivo. Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1? and hypoxia-inducible factor-1?), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell-matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification. PMID:21262528

Bhang, Suk Ho; Cho, Seung-Woo; La, Wan-Geun; Lee, Tae-Jin; Yang, Hee Seok; Sun, Ah-Young; Baek, Sang-Hong; Rhie, Jong-Won; Kim, Byung-Soo

2011-01-22

316

Global mobility approach with Mobile IP in \\  

Microsoft Academic Search

The purpose of the document is to describe how the EURESCOM project P1013 FIT-MIP evaluates the use of Mobile IP in an IP core network, acting as a mobility management protocol federating heterogeneous access network technologies such as PSTN, WLAN or GPRS. The aim is to provide a wide IP environment with an always-on access to IP applications (VoIP, VPN,

L. Morand; S. Tessier

2002-01-01

317

Astrocytes and ischemic injury  

PubMed Central

Ischemic injury is traditionally viewed from an axiomatic perspective of neuronal loss. Yet the ischemic infarct encompasses all cell types, including astrocytes. This review will discuss the idea that astrocytes play a fundamental role in the pathogenesis of ischemic neuronal death. It is proposed that stroke injury is primarily a consequence of the failure of astrocytes to support the essential metabolic needs of neurons. This ‘gliocentric view’ of stroke injury predicts that pharmacological interventions specifically targeting neurons are unlikely to succeed, because it is not feasible to preserve neuronal viability in an environment that fails to meet essential metabolic requirements. Neuroprotective efforts targeting the functional integrity of astrocytes may constitute a superior strategy for future neuroprotection.

Takano, Takahiro; Oberheim, NancyAnn; Cotrina, Maria Luisa; Nedergaard, Maiken

2008-01-01

318

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.

1999-06-01

319

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

2011-01-01

320

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.

2012-02-01

321

Reactive oxygen species are not a required trigger for exercise-induced late preconditioning in the rat heart.  

PubMed

Reactive oxygen species (ROS) have been reported to play a primary role in triggering the cardioprotective adaptations by some preconditioning procedures, but whether they are required for exercise-induced preconditioning is unclear. Thus in this study we used the free radical scavenger N-(2-mercaptopropionyl)glycine (MPG) to test the hypothesis that ROS is the trigger for exercise-induced preconditioning of the heart against ischemia-reperfusion injury. Male F344 rats were assigned to four groups: sedentary (SED, n = 7), SED/MPG (100 mg/kg ip daily for 2 days, n = 12), exercised on a treadmill for 2 days at 20 m/min, 6° grade, for 60 min (RUN, n = 7), and RUN/MPG with 100 mg/kg MPG injected 15 min before exercise (n = 10). Preliminary experiments verified that MPG administration maintained myocardial redox status during the exercise bout. Twenty-four hours postexercise or MPG treatment isolated perfused working hearts were subjected to global ischemia for 22.5 min followed by reperfusion for 30 min. Recovery of myocardial external work (percentage of preischemic systolic pressure times cardiac output) for SED (50.4 ± 4.5) and SED/RUN (54.7 ± 6.6) was similar and improved in both exercise groups (P < 0.05) to 77.9 ± 3.0 in RUN and 76.7 ± 4.5 in RUN/MPG. A 2 × 2 ANOVA also revealed that exercise decreased lactate dehydrogenase release from the heart during reperfusion (marker of cell damage) without MPG effects or interactions. Expression of the cytoprotective protein inducible heat shock protein 70 increased by similar amounts in the left ventricles of RUN and RUN/MPG compared with sedentary groups (P < 0.05). We conclude that ROS are not a necessary trigger for exercise-induced preconditioning in rats. PMID:22955056

Taylor, Ryan P; Starnes, Joseph W

2012-09-05

322

iPS cell sheets created by a novel magnetite tissue engineering method for reparative angiogenesis  

PubMed Central

Angiogenic cell therapy represents a novel strategy for ischemic diseases, but some patients show poor responses. We investigated the therapeutic potential of an induced pluripotent stem (iPS) cell sheet created by a novel magnetite tissue engineering technology (Mag-TE) for reparative angiogenesis. Mouse iPS cell-derived Flk-1+ cells were incubated with magnetic nanoparticle-containing liposomes (MCLs). MCL-labeled Flk-1+ cells were mixed with diluted extracellular matrix (ECM) precursor and a magnet was placed on the reverse side. Magnetized Flk-1+ cells formed multi-layered cell sheets according to magnetic force. Implantation of the Flk-1+ cell sheet accelerated revascularization of ischemic hindlimbs relative to the contralateral limbs in nude mice as measured by laser Doppler blood flow and capillary density analyses. The Flk-1+ cell sheet also increased the expressions of VEGF and bFGF in ischemic tissue. iPS cell-derived Flk-1+ cell sheets created by this novel Mag-TE method represent a promising new modality for therapeutic angiogenesis.

Kito, Tetsutaro; Shibata, Rei; Ishii, Masakazu; Suzuki, Hirohiko; Himeno, Tatsuhito; Kataoka, Yoshiyuki; Yamamura, Yumiko; Yamamoto, Takashi; Nishio, Naomi; Ito, Sachiko; Numaguchi, Yasushi; Tanigawa, Tohru; Yamashita, Jun K.; Ouchi, Noriyuki; Honda, Hiroyuki; Isobe, Kenichi; Murohara, Toyoaki

2013-01-01

323

IP Address Passing for VANETs  

Microsoft Academic Search

In Vehicular Ad-hoc Networks (VANETs), vehicles can gain short connections to the Internet by using wireless ac- cess points (AP). A significant part of the connection time is the time required for acquiring an IP address via Dynamic Host Configuration Protocol (DHCP). Depending on a ve- hicle's speed and the AP coverage area, DHCP can con- sume up to 100

Todd Arnold; Wyatt Lloyd; Jing Zhao; Guohong Cao

2008-01-01

324

Compositional Control of IP Media  

Microsoft Academic Search

In many IP media services, the media channels are point-to-point, dynamic, and set up with the participation of one or more application servers, even thou the media packets themselves travel directly between media endpoints. The application servers must be programmed so that media behavior is globally correct, even though the servers may attempt to manipulate the same media channels concurrently

Pamela Zave; Eric Cheung

2009-01-01

325

Ischemic right ventricular dysfunction  

Microsoft Academic Search

Summary For many years ischemic heart disease involving the right ventricle had received little attention. During the last 15 years, the initial works of Cohn, Isner, and others spawned a number of clinical and experimental studies that extended the understanding of the pathophysiology of ischemia in the right ventricle. Most of the work has been done in the setting of

José López-Sendón; Esteban López de Sá; Juán Luís Delcán

1994-01-01

326

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

1998-01-01

327

iPS Cell Intervention Rescues Wall Motion Disparity Achieving Biological Cardiac Resynchronization Post-Infarction.  

PubMed

Dyssynchronous myocardial motion aggravates cardiac pump function. Cardiac resynchronization using pacing devices is a standard-of-care in the management of heart failure. Post-infarction, however, scar tissue formation impedes the efficacy of device-based therapy. The present study tests a regenerative approach aimed at targeting the origin of abnormal motion to prevent dyssynchronous organ failure. Induced pluripotent stem (iPS) cells harbor a reparative potential, and were here bioengineered from somatic fibroblasts reprogrammed with the stemness factors OCT3/4, SOX2, KLF4, and c-MYC. In a murine infarction model, within 30-min after coronary ligation, iPS cells were delivered to mapped infarcted areas. Focal deformation and dysfunction underlying progressive heart failure was resolved prospectively using speckle-tracking imaging. Tracked at high temporal and spatial resolution, regional iPS cell transplantation restored, within 10 days post-infarction, the contractility of targeted infarcted foci and nullified conduction delay in adjacent non-infarcted regions. Local iPS cell therapy, but not delivery of parental fibroblasts or vehicle, prevented or normalized abnormal strain patterns correcting the decrease in peak strain, disparity of time-to-peak strain, and pathological systolic stretch. Focal benefit of iPS cell intervention translated into improved left ventricular conduction and contractility, reduced scar, and reversal of structural remodeling, protecting from organ decompensation. Thus, in ischemic cardiomyopathy targeted iPS cell transplantation synchronized failing ventricles, offering a regenerative strategy to achieve biological resynchronization. PMID:23568891

Yamada, Satsuki; Nelson, Timothy; Kane, Garvan; Martinez-Fernandez, Almudena; Crespo-Diaz, Ruben J; Ikeda, Yasuhiro; Terzic, Carmen; Terzic, Andre

2013-05-13

328

Rapid tolerance to focal cerebral ischemia in rats is induced by preconditioning with electroacupuncture: window of protection and the role of adenosine.  

PubMed

The aim of the present study was to investigate the first protective window of preconditioning with electroacupuncture (EA) against focal cerebral ischemia, and to explore whether adenosine is involved in the rapid tolerance phenomenon. Sixty-four male Sprague-Dawley rats were randomly assigned to eight groups (n=8 in each). Animals in the control group received no treatment, and animals in EA1-EA4 groups received EA at 0.5, 1, 2 and 3 h before induction of focal cerebral ischemia, respectively. Rats in DPCPX group were intraperitoneally injected with 1 mg kg-1 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 3 h before induction of focal cerebral ischemia. Animals in vehicle group and EA+DPCPX group were pretreated with 1 ml kg-1 dimethyl sulfoxide (DMSO, the solvent of DPCPX) and 1 mg kg-1 DPCPX 30 min before preconditioning with EA, respectively. All rats were anesthetized with 40 mg kg-1 pentobarbital sodium intraperitoneally. Animals that required EA preconditioning, received EA with intensity of 1 mA and frequency of 15 Hz at the Baihui acupoint (GV 20) for 30 min. The focal cerebral ischemia was produced by the right middle cerebral artery occlusion (MCAO) for 120 min. The neurologic deficit scores (NDS) and brain infarct volumes were evaluated at 24 h after reperfusion. All rats survived until 24 h after reperfusion. Preconditioning with EA at 2 h before induction of focal cerebral ischemia improved neurologic outcome (P<0.05 versus control) and reduced the infarct volume (P<0.01 versus control) at 24 h after reperfusion. These beneficial effects were reversed by pretreatment with 1 mg kg-1 DPCPX, whereas this agent itself did not affect the NDS and volume in drug-ischemic controls after ischemia. The results show that preconditioning with single EA session induces rapid tolerance to focal cerebral ischemia. The rapid ischemic tolerance appears at 2 h (but not at 0.5, 1, or 3 h) after preconditioning, and is possibly mediated through an adenosine A1 receptor-related mechanism. PMID:15882809

Wang, Qiang; Xiong, Lize; Chen, Shaoyang; Liu, Yanhong; Zhu, Xiaoling

2005-03-02

329

Hypoxia preconditioning protects corneal stromal cells against induced apoptosis.  

PubMed

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

2005-12-20

330

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.

2011-01-01

331

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

332

Past, Present and Future of IP Telephony  

Microsoft Academic Search

Since the late 90's IP telephony, commonly referred to as Voice over IP (VoIP), has been presented as a revolution on communications enabling the possibility to converge historically separated voice and data networks, reducing costs, and integrating voice, data and video on applications. This paper presents a study over the standard VoIP protocols H.323, session initiation protocol (SIP), media gateway

V. N. G. Soares; P. A. C. Neves; J. J. P. Rodrigues

2008-01-01

333

Voice over IP with JVOIPLIB and JRTPLIB  

Microsoft Academic Search

Voice over IP (VoIP) can be used in a wide variety of applications, all having different requirements. We present JVOIPLIB and JRTPLIB, a VoIP library and an RTP library respectively. Together they make it possible to easily add VoIP to various types of applications. Both libraries are written in an object-oriented style in C++, are open-source and are both very

Jori Liesenborgs; Wim Lamotte; Frank Van Reeth

2001-01-01

334

VoIP in a Campus Environment  

ERIC Educational Resources Information Center

Internet Protocol (IP) Telephony, or voice-over IP (VoIP), has proved to be a wise decision for many organizations. This technology crosses the boundaries of public and private networks, enterprise and residential markets, voice and data technologies, as well as local and long-distance services. The convergence of voice and data into a single,…

Young, Dan

2005-01-01

335

Open Source VoIP Traffic Monitoring  

Microsoft Academic Search

These days voice over IP (VoIP) is quite popular as it is a cost effective ay to reduce telephony costs using the Internet. Although many projects are focusing on developing tools and solutions for building the voice infrastructure, there is very little available in terms of tools and metrics for measuring the impact of VoIP on a network. This paper

Luca Deri

336

Approaches for resolving dynamic IP addressing  

Microsoft Academic Search

Knowledge of the Internet Protocol (IP) address is essential for connection establishment in certain classes of synchronous distributed applications, such as Internet telephony and video-conferencing systems. A problem of dynamic IP addressing arises when the connection to the Internet is through an Internet service provider, since the IP address is dynamically allocated only at connection time. Proposes and draws a

Schubert Foo; Siu Cheung Hui; See Wai Yip; Yulan He

1997-01-01

337

Observed structure of addresses in IP traffic  

Microsoft Academic Search

This paper investigates the structure of addresses contained in IP traffic. Specifically, we analyze the structural characteristics of destination IP addresses seen on Interuet links, considered as a subset of the address space. These characteristics may have implications for algorithms that deal with IP address aggregates, such as routing lookups and aggregatebased congestion control. We find that address structures are

Eddie Kohler; Jinyang Li; Vern Paxson; Scott Shenker

2002-01-01

338

Securing IP backbones in building automation networks  

Microsoft Academic Search

The use of IP networks as common backbone is becoming of increased interest in today's building automation systems (BAS). With the use of IP also new attack scenarios that threaten the overall security of BAS are introduced. Due to the absence of native security mechanisms in IP and because of its long standing and pervasive use in the IT world,

Wolfgang Granzer; Daniel Lechner; Fritz Praus; Wolfgang Kastner

2009-01-01

339

Challenges in Securing Voice over IP  

Microsoft Academic Search

Although VoIP offers lower cost and greater flexibility, it can also introduce significant risks and vulnerabilities. This article explains the challenges of VoIP security and outlines steps for helping to secure an organization's VoIP network.

Thomas J. Walsh; D. Richard Kuhn

2005-01-01

340

VoIP in a Campus Environment  

ERIC Educational Resources Information Center

|Internet Protocol (IP) Telephony, or voice-over IP (VoIP), has proved to be a wise decision for many organizations. This technology crosses the boundaries of public and private networks, enterprise and residential markets, voice and data technologies, as well as local and long-distance services. The convergence of voice and data into a single,…

Young, Dan

2005-01-01

341

On Service Level Agreements for IP Networks  

Microsoft Academic Search

Many corporate WAN architects are considering migrating from costly leased line circuits to 'private IP' services. In order to do so IP service providers must provide Service Level Agreements (SLAs) that offer robust assurances that cover service availability and performance. The industry direction is to model IP SLAs after those offered by frame relay networks. The reality however is that

Jim Martin; Arne A. Nilsson

2002-01-01

342

Effects of ozone oxidative preconditioning on liver regeneration after partial hepatectomy in rats.  

PubMed

ABSTRACT Aim: Similar protective effect of ischemic and ozone oxidative preconditioning (OzoneOP) in hepatic ischemia-reperfusion (I/R) injury was demonstrated, providing evidences that both preconditioning settings shared similar biochemical mechanisms of protection. We investigated the effects of OzoneOP on liver regeneration after 70% partial hepatectomy (PHx) in rats. Methods: Rats were divided into three groups: PHx, I/R + PHx, and OzoneOP + I/R + PHx groups. Ozone (intraperitoneal, 1.2 mg/kg) was given to rats subjected to I/R and 70% hepatectomy daily five times before operation. At 24 hr and 48 hr after resection, samples were collected for the measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-?), and interleukin-6 (IL-6). Moreover, liver regeneration rate, proliferating cell nuclear antigen (PCNA) labeling index, mitotic index, and histopathological examination were evaluated. Results: OzoneOP reduced liver injury determined by liver histology and serum transaminases. There was a rise in serum TNF-? and IL-6 levels in the I/R + PHx group whereas OzoneOP significantly decreased the rise in the level of TNF-? but not IL-6 on the 24 hr and 48 hr of reperfusion. Moreover, liver regeneration in OzoneOP + PHx group, as assessed by the regenerated liver weight, mitotic, and PCNA-labeling index, was significantly improved when compared to I/R + PHx group. Conclusion: These results suggest that OzoneOP ameliorates the hepatic injury associated with I/R and has a stimulatory effect on liver cell regeneration that may make it valuable as a hepatoprotective modality. PMID:23514050

Gultekin, Fatma Ayca; Cakmak, Guldeniz Karadeniz; Turkcu, Ummuhani Ozel; Yurdakan, Gamze; Demir, F Ebru Ofluoglu; Comert, Mustafa

2013-03-20

343

Glutamate transporter type 3 mediates isoflurane preconditioning-induced acute phase of neuroprotection in mice.  

PubMed

A pre-exposure to isoflurane reduces ischemic brain injury in rodents (isoflurane preconditioning). This neuroprotection has acute and delayed phases. Our previous in vitro studies suggest that the acute phase may involve excitatory amino acid transporters (EAATs). We determine whether this protection involves EAAT3, the major neuronal EAAT. Adult male EAAT3 knockout mice and their wild-type littermates were exposed or were not exposed to 1.5% isoflurane for 30min. Sixty minutes later, they were subjected to a 90- or 60-min middle cerebral arterial occlusion (MCAO). Their neurological outcomes were evaluated 24h after the MCAO. In another experiment, cerebral cortex was harvested for Western blotting at 30min after animals were exposed to 1.5% isoflurane for 30min. Here, we showed that isoflurane reduced brain infarct volumes and improved neurological functions of wild-type mice after a 90-min MCAO. However, isoflurane pre-exposure did not change the neurological outcome of EAAT3 knockout mice no matter whether the MCAO was for 90min or 60min. Isoflurane increased phospho-Akt, a survival-promoting protein, in the wild-type mice but not in the EAAT3 knockout mice. The isoflurane-induced neuroprotection in the wild-type mice was abolished by LY294004, an Akt activation inhibitor. LY294004 alone did not affect the neurological outcome of the wild-type or EAAT3 knockout mice after focal brain ischemia. These results suggest that the isoflurane preconditioning-induced acute phase of neuroprotection involves EAAT3. The downstream event includes Akt activation. PMID:23827345

Li, Liaoliao; Deng, Jiao; Zuo, Zhiyi

2013-07-01

344

Causes of Ischemic Stroke  

Microsoft Academic Search

\\u000a Ischemic stroke is a heterogeneous disease and occurs due to a multitude of underlying pathologic processes. The brain is\\u000a such an exquisitely sensitive reporting system that small infarctions, well below the size that causes clinical signs in other\\u000a organ systems, can cause major disability in the brain. About 85% of all strokes are due to ischemia, and in the majority

Gisele S. Silva; Walter J. Koroshetz; R. Gilberto González; Lee H. Schwamm

345

Ischemic neuronal damage.  

PubMed

Knowledge of the molecular mechanisms that underlie neuron death following stroke is important to allow the development of effective neuroprotective strategies. Since studies in human stroke are extremely limited due to the inability of collecting post mortem tissue at time points after the onset of stroke where neuronal death occurs, brain ischemia research focuses on information derived from animal models of ischemic injury. The two principal models for human stroke are induced in rodents either by global or focal ischemia. In both cases, blood flow disruptions limit the delivery of oxygen and glucose to neurons causing ATP reduction and energy depletion, initiating excitotoxic mechanisms that are deleterious for neurons. These include activation of glutamate receptors and release of excess glutamate in the extracellular space inducing neuron depolarisation and dramatic increase of intracellular calcium that in turn activates multiple intracellular death pathways. The notion that excitotoxicity leads only to neuron necrosis has been abandoned, as ultrastructural and biochemical analysis have shown signs of apoptotic and autophagic cell death in ischemic neurons and this has been further confirmed in neurons subjected to in vitro ischemia models. Both in vitro and in vivo studies, targeting a single death mechanism either by the inhibition of death-inducing molecules or the overexpression of antiapoptotic components in neurons, have shown tremendous neuroprotective potential. Despite their effectiveness in preclinical studies, a large number of neuroprotectants have failed in clinical trials for stroke suggesting that we still lack essential knowledge on the triggers and mediators of ischemic neuron death. In this review evidence will be presented on how ischemic injury occurs, what death mechanisms are activated and how these can be manipulated to induce neuroprotection. PMID:19075733

Taoufik, Era; Probert, Lesley

2008-01-01

346

Temperature preconditioning of isolated rat hearts - a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore  

PubMed Central

We investigate whether temperature preconditioning (TP), induced by short-term hypothermic perfusion and rewarming, may protect hearts against ischaemic/reperfusion injury like ischaemic preconditioning (IP). Isolated rat hearts were perfused for 40 min, followed by 25 min global ischaemia and 60 min reperfusion (37°C). During pre-ischaemia, IP hearts underwent three cycles of 2 min global ischaemia and 3 min reperfusion at 37°C, whereas TP hearts received three cycles of 2 min hypothermic perfusion (26°C) interspersed by 3 min normothermic perfusion. Other hearts received a single 6 min hypothermic perfusion (SHP) before ischaemia. Both IP and TP protocols increased levels of high energy phosphates in the pre-ischaemic heart. During reperfusion, TP improved haemodynamic recovery, decreased arrhythmias and reduced necrotic damage (lactate dehydrogenase release) more than IP or SHP. Measurements of tissue NAD+ levels and calcium-induced swelling of mitochondria isolated at 3 min reperfusion were consistent with greater inhibition of the mitochondrial permeability transition at reperfusion by TP than IP; this correlated with decreased protein carbonylation, a surrogate marker for oxidative stress. TP increased protein kinase C? (PKC?) translocation to the particulate fraction and pretreatment with chelerythrine (PKC inhibitor) blocked the protective effect of TP. TP also increased phosphorylation of AMP-activated protein kinase (AMPK) after 5 min index ischaemia, but not before ischaemia. Compound C (AMPK inhibitor) partially blocked cardioprotection by TP, suggesting that both PKC and AMPK may mediate the effects of TP. The presence of N-(2-mercaptopropionyl) glycine during TP also abolished cardioprotection, indicating an involvement of free radicals in the signalling mechanism.

Khaliulin, Igor; Clarke, Samantha J; Lin, Hua; Parker, Joanna; Suleiman, M-Saadeh; Halestrap, Andrew P

2007-01-01

347

IP Profiling via Service Cluster Membership Vectors  

SciTech Connect

This study investigates the feasibility of establishing and maintaining a system of compact IP behavioral profiles as a robust means of computer anomaly definition and detection. These profiles are based upon the degree to which a system's (IP's) network traffic is distributed among stable characteristic clusters derived of the aggregate session traffic generated by each of the major network services. In short, an IP's profile represents its degree of membership in these derived service clusters. The goal is to quantify and rank behaviors that are outside of the statistical norm for the services in question, or present significant deviation from profile for individual client IPs. Herein, we establish stable clusters for accessible features of common session traffic, migrate these clusters over time, define IP behavior profiles with respect to these clusters, migrate individual IP profiles over time, and demonstrate the detection of IP behavioral changes in terms of deviation from profile.

Bartoletti, A

2009-02-23

348

Cardiac Protection by Preconditioning Is Generated via an Iron-Signal Created by Proteasomal Degradation of Iron Proteins  

PubMed Central

Ischemia associated injury of the myocardium is caused by oxidative damage during reperfusion. Myocardial protection by ischemic preconditioning (IPC) was shown to be mediated by a transient ‘iron-signal’ that leads to the accumulation of apoferritin and sequestration of reactive iron released during the ischemia. Here we identified the source of this ‘iron signal’ and evaluated its role in the mechanisms of cardiac protection by hypoxic preconditioning. Rat hearts were retrogradely perfused and the effect of proteasomal and lysosomal protease inhibitors on ferritin levels were measured. The iron-signal was abolished, ferritin levels were not increased and cardiac protection was diminished by inhibition of the proteasome prior to IPC. Similarly, double amounts of ferritin and better recovery after ex vivo ischemia-and-reperfusion (I/R) were found in hearts from in vivo hypoxia pre-conditioned animals. IPC followed by normoxic perfusion for 30 min (‘delay’) prior to I/R caused a reduced ferritin accumulation at the end of the ischemia phase and reduced protection. Full restoration of the IPC-mediated cardiac protection was achieved by employing lysosomal inhibitors during the ‘delay’. In conclusion, proteasomal protein degradation of iron-proteins causes the generation of the ‘iron-signal’ by IPC, ensuing de-novo apoferritin synthesis and thus, sequestering reactive iron. Lysosomal proteases are involved in subsequent ferritin breakdown as revealed by the use of specific pathway inhibitors during the ‘delay’. We suggest that proteasomal iron-protein degradation is a stress response causing an expeditious cytosolic iron release thus, altering iron homeostasis to protect the myocardium during I/R, while lysosomal ferritin degradation is part of housekeeping iron homeostasis.

Bulvik, Baruch E.; Berenshtein, Eduard; Meyron-Holtz, Esther G.

2012-01-01

349

Nanoparticle preconditioning for enhanced thermal therapies in cancer.  

PubMed

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

2011-04-01

350

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

2009-01-01

351

VoIP Secure Communication Protocol satisfying Backward Compatibility  

Microsoft Academic Search

Several VoIP security protocols have been standardized for preventing many VoIP threats. But since several VoIP carriers have different VoIP protocols, end-to-end VoIP secure communication can not be possible. Also when initiator using secure VoIP phone wants a secure communication with responder using non-VoIP phone such as PSTN phone, or cellular phone, etc, so does it. Therefore, we propose VoIP

Joongman Kim; Seokung Yoon; Yoojae Won; Jaeil Lee

2007-01-01

352

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.

2011-01-01

353

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

2004-01-01

354

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

2009-02-09

355

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.

2011-01-01

356

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...

2013-07-01

357

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

2003-01-01

358

[Neyromidin in ischemic stroke].  

PubMed

An aim of the study was to evaluate the therapeutic effect of neyromidin in patients with ischemic stroke. Forty patients with acute carotid artery stroke were enrolled into the study. The diagnosis was made on the basis of general clinical methods as well as the neurological examination, CT or MRI scans of the head, investigation of hemodynamic parameters, ECG, ultrasound dopplerography of major brain arteries. Neurological deficit was measured using the Scandinavian Scale. According to the TOAST classification, 14 (35%) of the patients suffered from large vessel disease, 16 (40%) patients were diagnosed with cardioembolic disease and 10 (25%) with the small vessel disease. Patients were randomized to the study and control groups (n=20 patients). All patients received standard treatment. Patients of the study group were treated with neyromidin. The study duration was 80 days. Clinical examinations were performed in the acute phase, on 21st and 80th days after stroke. Better recovery of neurological functions was identified in patients treated with neyromidin compared to control patients. No side-effects of neyromidin was found. Neyromidin is recommended for complex treatment of patients in the acute stage of ischemic stroke of carotid origin. PMID:23612408

Maksimova, M Iu; Korobkova, D Z; Sineva, N A; Vodop'ianov, N P; Mikhal'chenko, V N

2013-01-01

359

Voice over IP: Risks, Threats and Vulnerabilities  

Microsoft Academic Search

Voice over IP (VoIP) and Internet Multimedia Subsystem (IMS) technologies are rapidly being adopted by consumers, enterprises, governments and militaries. These tech- nologies offer higher flexibility and more features than tra ditional telephony (PSTN) infrastructures, as well as the potential for lower cost through equipment consolidation and, for the con- sumer market, new business models. However, VoIP\\/IMS systems also represent

Angelos D. Keromytis

360

Towards Stateless Single-Packet IP Traceback  

Microsoft Academic Search

The current Internet architecture allows malicious nodes to disguise their origin during denial-of-service attacks with IP spoofing. A well-known solution to identify these nodes is IP traceback. In this paper, we intro- duce and analyze a light-weight single-packet IP trace- back system that does not store any data in the network core. The proposed system relies on a novel data

Rafael P. Laufer; Pedro B. Velloso; Daniel De Oliveira Cunha; Igor M. Moraes; Marco D. D. Bicudo; Marcelo D. D. Moreira; Otto Carlos Muniz Bandeira Duarte

2007-01-01

361

IP traffic grooming over WDM optical networks  

Microsoft Academic Search

IP over WDM has emerged as a winning network architecture to facilitate today's IP centric Internet. Although the total amount of bandwidth demands keeps increasing, there still exists a huge gap between the increasing full-wavelength capacity and the existing low-rate IP traffic. Efficiently grooming low-rate traffic stream to high-capacity lightpaths helps to alleviate the bandwidth mismatch, effectively improve the network

Jing Fang; Arun K. Somani

2005-01-01

362

The impact of experimental preconditioning using vascular endothelial growth factor in stroke and subarachnoid hemorrhage.  

PubMed

Vascular endothelial growth factor (VEGF) stimulating angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular diseases. The goal of the present study was to examine whether transfection of VEGF before occurrence of major stroke (part I) and cerebral vasospasm after experimental subarachnoid hemorrhage (SAH; part II) develops neuroprotective qualities. A total of 25 (part I) and 26 (part II) brains were analyzed, respectively. In part one, a significant reduction of infarct volume in the VEGF-treated stroke animals (43% reduction, P < 0.05) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups (P < 0.02). Analyzing microperfusion, a significant higher amount of perfused vessels could be detected (P < 0.01), whereas no significant effect could be detected towards macroperfusion. Histologically, no infarctions were observed in the VEGF-treated SAH group and the sham-operated group. Minor infarction in terms of vasospasm-induced small lesions could be detected in the control vector transduced group (P = 0.05) and saline-treated group (P = 0.09). The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH. PMID:23634319

Eicker, Sven Oliver; Hoppe, Moritz; Etminan, Nima; Macht, Stephan; Perrin, Jason; Steiger, Hans-Jakob; Hänggi, Daniel

2013-03-24

363

HMGB1 in renal ischemic injury  

PubMed Central

Factors that initiate cellular damage and trigger the inflammatory response cascade and renal injury are not completely understood after renal ischemia-reperfusion injury (IRI). High-mobility group box-1 protein (HMGB1) is a damage-associated molecular pattern molecule that binds to chromatin, but upon signaling undergoes nuclear-cytoplasmic translocation and release from cells. Immunohistochemical and Western blot analysis identified HMGB1 nuclear-cytoplasmic translocation and release from renal cells (particularly vascular and tubular cells) into the venous circulation after IRI. Time course analysis indicated HMGB1 release into the venous circulation progressively increased parallel to increased renal ischemic duration. Ethyl pyruvate (EP) treatment blocked H2O2 (oxidative stress)-induced HMGB1 release from human umbilical vein endothelial cells in vitro, and in vivo resulted in nuclear retention and significant blunting of HMGB1 release into the circulation after IRI. EP treatment before IRI improved short-term serum creatinine and albuminuria, proinflammatory cyto-/chemokine release, and long-term albuminuria and fibrosis. The renoprotective effect of EP was abolished when exogenous HMGB1 was injected, suggesting EP's therapeutic efficacy is mediated by blocking HMGB1 translocation and release. To determine the independent effects of circulating HMGB1 after injury, exogenous HMGB1 was administered to healthy animals at pathophysiological dose. HMGB1 administration induced a rapid surge in systemic circulating cyto-/chemokines (including TNF-?, eotaxin, G-CSF, IFN-?, IL-10, IL-1?, IL-6, IP-10, and KC) and led to mobilization of bone marrow CD34+Flk1+ cells into the circulation. Our results indicate that increased ischemic duration causes progressively enhanced HMGB1 release into the circulation triggering damage/repair signaling, an effect inhibited by EP because of its ability to block HMGB1 nuclear-cytoplasmic translocation.

Rabadi, May M.; Ghaly, Tammer; Goligorksy, Michael S.

2012-01-01

364

HMGB1 in renal ischemic injury.  

PubMed

Factors that initiate cellular damage and trigger the inflammatory response cascade and renal injury are not completely understood after renal ischemia-reperfusion injury (IRI). High-mobility group box-1 protein (HMGB1) is a damage-associated molecular pattern molecule that binds to chromatin, but upon signaling undergoes nuclear-cytoplasmic translocation and release from cells. Immunohistochemical and Western blot analysis identified HMGB1 nuclear-cytoplasmic translocation and release from renal cells (particularly vascular and tubular cells) into the venous circulation after IRI. Time course analysis indicated HMGB1 release into the venous circulation progressively increased parallel to increased renal ischemic duration. Ethyl pyruvate (EP) treatment blocked H(2)O(2) (oxidative stress)-induced HMGB1 release from human umbilical vein endothelial cells in vitro, and in vivo resulted in nuclear retention and significant blunting of HMGB1 release into the circulation after IRI. EP treatment before IRI improved short-term serum creatinine and albuminuria, proinflammatory cyto-/chemokine release, and long-term albuminuria and fibrosis. The renoprotective effect of EP was abolished when exogenous HMGB1 was injected, suggesting EP's therapeutic efficacy is mediated by blocking HMGB1 translocation and release. To determine the independent effects of circulating HMGB1 after injury, exogenous HMGB1 was administered to healthy animals at pathophysiological dose. HMGB1 administration induced a rapid surge in systemic circulating cyto-/chemokines (including TNF-?, eotaxin, G-CSF, IFN-?, IL-10, IL-1?, IL-6, IP-10, and KC) and led to mobilization of bone marrow CD34+Flk1+ cells into the circulation. Our results indicate that increased ischemic duration causes progressively enhanced HMGB1 release into the circulation triggering damage/repair signaling, an effect inhibited by EP because of its ability to block HMGB1 nuclear-cytoplasmic translocation. PMID:22759395

Rabadi, May M; Ghaly, Tammer; Goligorksy, Michael S; Ratliff, Brian B

2012-07-03

365

A Distributed Key-Changing Mechanism for Secure Voice Over IP (VoIP) Service  

Microsoft Academic Search

Voice over IP (VoIP) has experienced tremendous growth in recent years due to its low cost and flexible service enhancement. However, it is vulnerable to security attack. The most popular solution to providing secure VoIP service is based on the advanced encryption standard (AES). The practice for AES-based solution is to adopt a common secret key negotiated during a VoIP

Chia-hui Wang; Mei-wen Li; Wanjiun Liao

2007-01-01

366

IP-based base stations and soft handoff in all-IP wireless networks  

Microsoft Academic Search

The Internet protocol (IP) can potentially become the universal network-layer protocol over all wireless systems as it already is for wireline packet networks. Such an all-IP wireless and wireline network can bring the proven advantages of IP networking to mobile users. However, realizing an all-IP wireless network introduces many challenges, among which is soft handoff. Two major problems need to

TAO ZHANG; PRATHIMA AGRAWAL; JYIH-CHENG CHEN

2001-01-01

367

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...

2009-07-01

368

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...

2010-07-01

369

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...

2011-07-01

370

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

2008-01-01

371

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

1987-01-01

372

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...

2013-07-01

373

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...

2013-07-01

374

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...

2013-07-01

375

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...

2013-07-01

376

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))

1992-08-01

377

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

1997-01-01

378

[Cerebrolysin for acute ischemic stroke].  

PubMed

The review discusses existing evidence of benefits and risks of cerebrolysin--a mixture of low-molecular-weight peptides and amino acids derived from pigs' brain tissue with proposed neuroprotective and neurotrophic properties, for acute ischemic stroke. The review presents results of systematic search and analysis of randomised clinical trials comparing cerebrolysin with placebo in patients with acute ischemic stroke. Only one trial was selected as meeting quality criteria. No difference in death and adverse events between cerebrolysin and placebo was established. The authors conclude about insufficiency of evidence to evaluate the effect of cerebrolysin on survival and dependency in people with acute ischemic stroke. PMID:23805635

iganshina, L E; Abakumova, T R

2013-01-01

379

VoIP to the Rescue  

ERIC Educational Resources Information Center

Voice over Internet Protocol (VoIP) is everywhere. The technology lets users make and receive phone calls over the Internet, transporting voice traffic alongside data traffic such as instant messages (IMs) and e-mail. While the number of consumer customers using VoIP increases every week, the technology is finding its way into K-12 education as…

Milner, Jacob

2005-01-01

380

Approaches for Resolving Dynamic IP Addressing.  

ERIC Educational Resources Information Center

|A problem with dynamic Internet protocol (IP) addressing arises when the Internet connection is through an Internet provider since the IP address is allocated only at connection time. This article examines a number of online and offline methods for resolving the problem. Suggests dynamic domain name system (DNS) and directory service look-up are…

Foo, Schubert; Hui, Siu Cheung; Yip, See Wai; He, Yulan

1997-01-01

381

Secure and Mobile VoIP  

Microsoft Academic Search

The rapid growth of computing, the Internet and telecommunications systems have resulted in a broad range of ways to communicate and access information. voice over Internet protocol (VoIP) is a computer telephony integration (CTI) solution that transports voice traffic over a data network as an alternative to the plain old telephone service (POTS). VoIP products promise converged telecommunications and data

Alex Talevski; Elizabeth Chang; Tharam Dillon

2007-01-01

382

Voice over IP security and law enforcement  

Microsoft Academic Search

Voice over IP is one of the fastest growing Internet based application in today's networking world. As more and more enterprises are moving towards IP based voice network, the payload security has become an important issue. The voice traffic is exposed to the same threats as the normal data traffic. However, with voice traffic, the security and accessibility requirements are

N. Thanthry; R. Pendse; K. Namuduri

2005-01-01

383

IP Traceback in a Switched Ethernet Network  

Microsoft Academic Search

IP traceback is the generic term given to systems that allow the tracing of IP packets back to their originating machine. A common shortcoming shared by existing traceback proposals is that they are able to identify the source network, but not the source host. Our work extends the traceback process by allowing the tracing of frames within the origi- nating

Marios S. Andreou; Aad van Moorsel

2007-01-01

384

IP Fault Localization Via Risk Modeling  

Microsoft Academic Search

Automated, rapid, and effective fault management is a central goal of large operational IP networks. Today's networks suffer from a wide and volatile set of failure modes, where the underlying fault proves difficult to de- tect and localize, thereby delaying repair. One of the main challenges stems from operational reality: IP rout- ing and the underlying optical fiber plant are

Ramana Rao Kompella; Jennifer Yates; Albert G. Greenberg; Alex C. Snoeren

2005-01-01

385

IP Address Handoff in the MANET  

Microsoft Academic Search

When compared with a fixed host that is connected to a hardwired network, a mobile node in the MANET may change its IP address more frequently due to the deployment of autoconfiguration, global connectivity, and hierarchical addressing schemes. When an IP address changes, the performance of unicast routing protocols and real-time communications may degrade, and privacy may be compromised within

Hongbo Zhou; Matt W. Mutka; Lionel M. Ni

2004-01-01

386

Guidelines for Management of IP Address Space  

Microsoft Academic Search

This document has been reviewed by the Federal Engineering Task Force (FEPG) on behalf of the Federal Networking Council (FNC), the co- chairs of the International Engineering Planning Group (IEPG), and the Reseaux IP Europeens (RIPE). There was general consensus by those groups to support the recommendations proposed in this document for management of the IP address space.

E. Gerich

1992-01-01

387

A Fast IP Routing Lookup Scheme  

Microsoft Academic Search

Abstract—A major issue in router design for the next genera- tion Internet is the fast IP address lookup mechanism. The existing scheme by Huang et al. performs the IP address lookup in hard- ware in which the forwarding table can be compressed to fit into reasonable-size SRAM, and a lookup can be accomplished in three memory accesses. In this letter,

Pi-chung Wang; Yaw-chung Chen; Chia-tai Chan

2000-01-01

388

Nymble: Anonymous IP-Address Blocking  

Microsoft Academic Search

Anonymizing networks such as Tor allow users to access Internet ser- vices privately using a series of routers to hide the client's IP address from the server. Tor's success, however, has been limited by users employing this anonymity for abusive purposes, such as defacing Wikipedia. Website administrators rely on IP- address blocking for disabling access to misbehaving users, but this

Peter C. Johnson; Apu Kapadia; Patrick P. Tsang; Sean W. Smith

2007-01-01

389

Integrating global wireless systems with IP  

Microsoft Academic Search

We propose several algorithms for total IP based wireless networks. This includes any cellular system from TDMA, GSM to CDMA. Solutions for associated improvements come with the new architecture are also discussed. One area is the IP internetworking among different cellular systems (GSM to GSM, GSM to CDMA, TDMA to GSM). First, an easy and fast mean of deploying a

David J. Y. Lee; William C. Y. Lee

2000-01-01

390

Security Patterns for Voice over IP Networks  

Microsoft Academic Search

Voice over IP (VoIP) has had a strong effect on global communications by allowing human voice and fax information to travel over existing packet data networks along with traditional data packets. The convergence of voice and data in the same network brings both benefits and constraints to users. Among the several issues that need to be addressed when deploying this

Eduardo B. Fernández; Juan C. Pelaez; María M. Larrondo-petrie

2007-01-01

391

Seven myths about voice over IP  

Microsoft Academic Search

Voice over Internet Protocol (VoIP) is one of the fastest growing and most misunderstood technologies in the world at the moment. Confusion, outdated beliefs and urban mythology reign over such simple issues as how it works, the quality of the calls, and, of course, how much it costs. This paper examines seven existing myths about VoIP. These myths are that:

S. Cherry

2005-01-01

392

VoIP to the Rescue  

ERIC Educational Resources Information Center

|Voice over Internet Protocol (VoIP) is everywhere. The technology lets users make and receive phone calls over the Internet, transporting voice traffic alongside data traffic such as instant messages (IMs) and e-mail. While the number of consumer customers using VoIP increases every week, the technology is finding its way into K-12 education as…

Milner, Jacob

2005-01-01

393

HPC Access Using 'KVM over IP'.  

National Technical Information Service (NTIS)

A persistent challenge in the High-Performance Computing (HPC) community is how to provide remote visualization capability to its users. A dynamic and economical solution is a KVM-over-IP technology, which uses a pre- existing TCP/IP network to transmit K...

D. Kedziorek G. P. Czerniak

2007-01-01

394

Protective Effect of Grape Seed Proanthocyanidins against Liver Ischemic Reperfusion Injury: Particularly in Diet-Induced Obese Mice  

PubMed Central

Background: Hepatic ischemia and reperfusion injury (IRI) is a major complication in liver surgery, and hepatic steatosis is a primary factor aggravating cellular injury during IRI. Both pro-inflammatory cytokines and reactive oxygen species (ROS) are key mediators of hepatic IRI. Ischemic preconditioning (IpreC), remote ischemia preconditioning (RIPC) and ischemic postconditioning (IpostC) have offered protections on hepatic IRI, but all these methods have their own shortcomings. Grape seed proanthocyanidins (GSP) has a broad spectrum of pharmacological properties against oxidative stress. Thus, GSP has potential protective effects against hepatic IRI. Methods: C57BL/6 mice suffering 30mins hepatic ischemia process were sacrificed after 1h reperfusion to build murine warm hepatic IRI model. The mice were injected GSP intraperitoneally 10, 20, 40mg/kg/day for 3 weeks as pharmacological preconditioning. Obese mice fed with high-fat diet for 24 weeks before used. Three pathways related to IRI, including ROS elimination, pro-inflammatory cytokines release and hypoxia responses were examined. Results: Our data show that GSP could significantly reduce hepatic IRI by protecting hepatocyte function and increasing the activity of ROS scavengers, as well as decreasing cytokines levels. At the same time, GSP also enhance the hypoxia tolerance response. Combined GSP and postconditioning can provided synergistic protection. In the obese mice suffering hepatic IRI group, GSP was more effective than postconditioning on protecting liver against IRI, and the combined strategy was obviously superior to the solo treatment. Conclusion: GSP could protect liver against IRI: particularly in high-fat diet induced obese mice. GSP used as pharmacological preconditioning and combined with other protocols have huge potential to be used in clinical.

Song, Xiaoyu; Xu, Hongde; Feng, Yanling; Li, Xiaoman; Lin, Meina; Cao, Liu

2012-01-01

395

Tabled logic programming based IP matching tool using forced simulation  

Microsoft Academic Search

Abstract Automatic IP (Intellectual Property) matching is a key to reuse of IP cores. This paper presents a new tabled logic programming-based IP matching algorithm that can check whether a given programmable IP can be adapted to match a given specification. When such adaptation is possible, the algorithm also generates a device driver (an interface) to adapt the IP. Though

P. S. Roop; A. Sowmya; S. Ramesh; Haifeng Guo

2004-01-01

396

[Risk factors of ischemic stroke].  

PubMed

The article contains data on modern methods of ischemic stroke diagnosis. Instrumental tests and their diagnostic yield in determining the pathogenetic mechanism of stroke especially in patients with atrial fibrillation have been analysed. Holter monitoring of electrocardiography and blood pressure has specific significance in patients with rhythm disorders in acute period of ischemic stroke for determining pathogenesis of dysrhythmias and disturbances of central and cerebral hemodynamics. PMID:23373394

Shkliaieva, O P

2012-01-01

397

Subcortical ischemic cerebrovascular dementia.  

PubMed

It has become increasingly apparent, especially with the advent of MRI brain scanning, that a large number of patients develop signal intensity changes in the subcortical white matter and periventricular region as they age. This appears to be accelerated by risk factors for small vessel cerebrovascular disease such as hypertension, smoking, diabetes mellitus and hyperlipidemia. The major question becomes when such changes become clinically significant. It is obvious that subcortical lacunar-type infarction can be identified by the clinical presentation. For example, typical examples of so-called "lacunar syndrome" include pure motor hemiparesis, pure sensory stroke, sensorimotor stroke, clumsy hand-dysarthria, and hemiataxia-hemiparesis. The issue becomes a measure of impact on functional ability. This is influenced by several factors. Baseline IQ and educational level, as well as expectations of age, certainly play a role. A person who develops cognitive impairment and long tract signs in their 50s or 60s is certainly going to be recognized as more impaired than an 80 year old individual who is retired and primarily is engaged in recreational activity. It would be expected that a person born with limited intellectual capacity and/or limited educational opportunity would be less likely to be identified as impaired than a person who has achieved substantial economic achievement through their innate talents. The concept of tissue loss or lesion load becomes important when determining how pronounced the ischemic cerebrovascular changes translate into functional impairment. Correlative pathology may include cortical atrophy and ventricular dilatation. Loss of either cortical or subcortical tissue function is expected to be related to functional compromise. In addition, there are potential features such as the coexistence of small vessel cerebrovascular disease and Alzheimer's disease. Small vessel cerebrovascular disease might also play a contributing factor in patients susceptible to Dementia with Lewy Bodies or patients susceptible to fronto-temporal dementia or any other dementing process. Thus, the concept of tissue loss or lesion burden of disease becomes increasingly important as we recognize the potential for multifactorial issues, including genetic factors, to contribute to the phenotypic expression. The relationships between cognitive impairment, dementia and subcortical vascular lesions are poorly understood. There have been several papers on the different aspects of cerebral insults and their impact on cognition, the various kinds of dementia and different methods of analyzing the impact of the various insults to the brain. This chapter is an attempt to review all pertinent information currently available on the poorly understood condition of "subcortical ischemic cerebrovascular dementia." PMID:19501711

Menon, Uma; Kelley, Roger E

2009-01-01

398

Role of IP? receptor in development.  

PubMed

IP? receptor is a Ca(2+) release channel localized on the endoplasmic reticulum. IP(3) receptor is composed of three isoforms, which are expressed in various cells and tissues, and play variety of roles throughout development. I here describe the role of IP? receptor from oogenesis, meiotic maturation and fertilization. I also describe the Ca(2+) signaling at meiosis and mitosis, and especially the role in early embryogenesis to determine dorso-ventral axis formation. Loss of function mutation of type 1 IP? receptor in mouse, both by gene targeting and spontaneous mutations shows severe ataxia and other phenotypes. Interestingly, double knockouts of type 1 and type 2 exhibit cardiogenesis arrest and that of type 2 and type 3 results in exocrine secretion deficit. IP?R of Drosophila or Caenorhabditis elegans is single gene and mutation results severe phenotype of behavior. All the data described here show that IP?Rs are essential for life and abnormality of IP(3)Rs results in severe abnormality in its structure and function of organism. PMID:21596434

Mikoshiba, Katsuhiko

2011-05-18

399

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

PubMed

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

2009-11-20

400

Uniform communications software using TCP/IP  

SciTech Connect

Data acquisition applications at Fermilab require a reliable, distributed communication system for downloading, diagnostics, control, and data distribution. TCP/IP over Ethernet was chosen because of its uniform user interface and commercial availability for a number of processors and operating systems. This paper describes our software and hardware support for TCP/IP on VAX/VMS, VME/pSOS, FASTBUS/pSOS, and Unix systems. It includes plans to provide a portable, hardware independent implementation of TCP/IP based on Berkeley BSD software. 8 refs., 3 figs.

Bernett, M.; Oleynik, G.

1989-05-01

401

Uniform communications software using TCP/IP  

SciTech Connect

Data acquisition applications at Fermilab require a reliable, distributed communication system for downloading, diagnostics, control, and data distribution. TCP/IP over Ethernet was chosen because of its uniform user interface and commercial availability for a number of processors and operating systems. This paper describes the authors software and hardware support for TCP/IP on VAX/VMS, VME/rhoSOS, FASTBUS/rhoSOS, and Unix systems. It includes plans to provide a portable, hardware independent implementation of TCP/IP based on Berkeley BSD software.

Bernett, M.; Oleynik, G. (Fermi National Accelerator Lab., Batavia, IL (USA))

1989-10-01

402

Scalable architecture for VoIP privacy  

NASA Astrophysics Data System (ADS)

An access network for Voice over IP (VoIP) clients (e.g. DOCSIS-based HFC network) often provides a privacy service. However, such a privacy service is limited only to that access network. When VoIP packets are carried over an open IP network or over a network with some connections to the Internet, it is desirable to provide an end-to-end privacy service where each VoIP packet is encrypted at the source and decrypted at the terminating endpoint. Clearly, public key encryption cannot be applied to each voice packet; the performance would be unacceptable regardless of the choice of a public key algorithm. The only alternative is for the two VoIP endpoints to negotiate a shared symmetric key. Since VoIP connections are established only for duration of a phone call, the end-to-end key negotiation needs to occur during each call setup. And it should not noticeably delay the call setup phase. In order to provide end-to-end privacy, it is not sufficient to encrypt all messages between the two endpoints. It is important that the two endpoints authenticate each other - validate each other's identity. Without authentication an adversary might trick two VoIP clients to negotiate keys with her and then sit in the middle of their conversation and record each VoIP packet, before forwarding it to the intended destination. However, direct authentication of the two VoIP endpoints is not always possible in telephony networks - in particular when caller ID blocking services are enabled. To support such anonymity services, it may be sufficient to authenticate not the identity of the caller but the fact that it is a valid subscriber and that all subsequent signaling and voice traffic will be coming from the same source. The PacketCable specifications provide an example of a VoIP architecture with end-to-end privacy that meets the above stated criteria. This paper describes the PacketCable end-to-end privacy approach and suggests additional mechanisms that may be used to further strengthen VoIP privacy under the PacketCable architecture.

Medvinsky, Alexander

2001-07-01

403

Ischemic penumbra in acute stroke: Demonstration by PET with fluorine-18 fluoromisonidazole  

SciTech Connect

Ischemic penumbra (IP) in acute stroke has gained clinical interest since tissue functions may be recovered if perfusion can be reestablished. However, such therapeutic intervention is {open_quotes}blind{close_quotes} since clinical examination can not distinguish IP from developing infarction. In vivo demonstration of IP may have significance for stroke patient management. This study was a preliminary evaluation of detecting IP in vivo by F-18 fluoromisonidazole ([F-18]-FMISO), a hypoxic imaging agent. Static PET imaging was performed after IV injection of 370 MBq of [F-18]-FMISO at 20 and 120 min. Tomograms were reconstructed and evaluated visually in correlation with CT or MR scans. In acute stroke, patients (pts) were called back for the second PET study one month after the initial study. CT was used for confirming infarction. In 6 pts with acute cerebral infarction, three of them had intense [F-18]-FMISO retention in the penumbra surrounding the central, eclipse-like zone of absent radio-activity (infarction) at 2 hr in the acute state, and the penumbra disappeared in association with increased area of infarction on CT in one case in the chronic state. In five pts with chronic infarction, all had no penumbra of [F-18]-FMISO retention. In summary, our preliminary results demonstrate the feasibility of using [F-18]-FMISO PET to detect ischemic penumbra in vivo.

Yeh, S.H.; Liu, R.S.; Hu, H.H. [National Yang-Ming Medical College (Taiwan, Province of China)] [and others

1994-05-01

404

ChIP-PED enhances the analysis of ChIP-seq and ChIP-chip data  

PubMed Central

Motivation: Although chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) or tiling array hybridization (ChIP-chip) is increasingly used to map genome-wide–binding sites of transcription factors (TFs), it still remains difficult to generate a quality ChIPx (i.e. ChIP-seq or ChIP-chip) dataset because of the tremendous amount of effort required to develop effective antibodies and efficient protocols. Moreover, most laboratories are unable to easily obtain ChIPx data for one or more TF(s) in more than a handful of biological contexts. Thus, standard ChIPx analyses primarily focus on analyzing data from one experiment, and the discoveries are restricted to a specific biological context. Results: We propose to enrich this existing data analysis paradigm by developing a novel approach, ChIP-PED, which superimposes ChIPx data on large amounts of publicly available human and mouse gene expression data containing a diverse collection of cell types, tissues and disease conditions to discover new biological contexts with potential TF regulatory activities. We demonstrate ChIP-PED using a number of examples, including a novel discovery that MYC, a human TF, plays an important functional role in pediatric Ewing sarcoma cell lines. These examples show that ChIP-PED increases the value of ChIPx data by allowing one to expand the scope of possible discoveries made from a ChIPx experiment. Availability: http://www.biostat.jhsph.edu/?gewu/ChIPPED/ Contact: hji@jhsph.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Wu, George; Yustein, Jason T.; McCall, Matthew N.; Zilliox, Michael; Irizarry, Rafael A.; Zeller, Karen; Dang, Chi V.; Ji, Hongkai

2013-01-01

405

An Introduction to Voice over the IP: Laboratory Exercise  

NSDL National Science Digital Library

This document provides a sample laboratory exercise which may be used in classes studying Voice over IP. The exercise includes three parts: 1. Configure the classroom network; 2. Simulate VoIP calls; and 3. VoIP Network configuration.

Cherri, Mona

2011-09-19

406

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

2006-01-01

407

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.

2006-01-01

408

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

1997-01-01

409

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

2010-01-01

410

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

1997-01-01

411

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

1996-01-01

412

Preconditioned Alternating Projection Algorithms for Maximum a Posteriori ECT Reconstruction.  

PubMed

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 conve