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Ischemic tolerance

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https://www.readbyqxmd.com/read/27913766/myocardial-cytochrome-oxidase-activity-increases-with-age-and-hypoxemia-in-patients-with-congenital-heart-disease
#1
Michael Onwugbufor, Richard J Levy, David Zurakowski, Richard A Jonas, Pranava Sinha
BACKGROUND: Myocardial tolerance to ischemia is influenced by age and preoperative cyanosis through unknown mechanisms and significantly affects postoperative outcomes. Cytochrome c oxidase (CcOx), the terminal enzyme of the mitochondrial electron transport chain, may play a role in the susceptibility to ischemic-reperfusion (IR) injury. Our study aimed at investigating changes in human myocardial CcOx activity based on age and preoperative oxygen saturation to understand its role in transition from neonatal to mature myocardium and hypoxic conditions...
December 1, 2016: Perfusion
https://www.readbyqxmd.com/read/27899277/protective-role-of-hypoxia-inducible-factor-1%C3%AE-dependent-cd39-and-cd73-in-fulminant-acute-liver-failure
#2
Eunyoung Tak, Dong-Hwan Jung, Seok-Hwan Kim, Gil-Chun Park, Dae Young Jun, Jooyoung Lee, Bo-Hyun Jung, Varvara A Kirchner, Shin Hwang, Gi-Won Song, Sung-Gyu Lee
Acute liver failure (ALF) is a severe life-threatening disease which usually arises in patients with-irreversible liver illnesses. Although human ectonucleotide triphosphate diphosphohydrolase-1, E-NTPDase1 (CD39) and ecto-5'-nucleotidase, Ecto5'NTase (CD73) are known to protect tissues from ALF, the expression and function of CD39 and CD73 during ALF are currently not fully investigated. We tested whether CD39 and CD73 are upregulated by hypoxia inducible factor (HIF)-1α, and improve ischemic tolerance to ALF...
November 26, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27894810/na-ca-2-exchanger-1-inhibition-abolishes-ischemic-tolerance-induced-by-ischemic-preconditioning-in-different-cardiac-models
#3
Pasqualina Castaldo, Maria Loredana Macrì, Vincenzo Lariccia, Alessandra Matteucci, Marta Maiolino, Santo Gratteri, Salvatore Amoroso, Simona Magi
Ca(2+)-handling disturbances play an important role in the genesis of myocardial ischemia/reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a powerful strategy to induce tolerance against subsequent ischemic episodes. IPC signaling pathways may be triggered by Ca(2+) ion. Since Na(+)/Ca(2+) exchanger 1 (NCX1) participates in modulating intracellular Ca(2+) homeostasis, here we further defined its role in I/R and investigated its potential involvement in IPC-induced cardioprotection. In isolated ventricular cardiomyocytes, perfused rat heart and H9c2 cardiomyoblasts, I/R produceda significant cellinjury, assessed by measuring extracellular lactate dehydrogenase (LDH) and, for the whole heart, also by estimating myocardialinfarct size area...
November 25, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27888904/-anti-pcsk9-antibodies-in-type-2-diabetes-and-secondary-prevention-of-cardiovascular-diseases
#4
José López-Miranda, Xavier Pintó
Patients with type 2 diabetes are considered to have the same cardiovascular risk as patients with ischemia. However, the degree of lipid control in diabetic and ischemic patients remains highly deficient. The availability of new agents, such as anti-PCSK9 monoclonal antibodies, could represent a notable advance in meeting this unmet need. Alirocumab and evolucumab, followed by bococizumab, are currently under the advanced phase of research. A growing database has demonstrated a relationship between glucose metabolism, body weight and PCSK9 function, but the clinical implications of this relationship have not been well defined...
May 2016: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/27881559/safety-and-tolerability-of-csl112-a-reconstituted-infusible-plasma-derived-apolipoprotein-a-i-after-acute-myocardial-infarction-the-aegis-i-trial-apoa-i-event-reducing-in-ischemic-syndromes-i
#5
C Michael Gibson, Serge Korjian, Pierluigi Tricoci, Yazan Daaboul, Megan Yee, Purva Jain, John H Alexander, P Gabriel Steg, A Michael Lincoff, John J P Kastelein, Roxana Mehran, Denise M D'Andrea, Lawrence I Deckelbaum, Bela Merkely, Maciej Zarebinski, Ton Oude Ophuis, Robert A Harrington
BACKGROUND: -Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction...
November 15, 2016: Circulation
https://www.readbyqxmd.com/read/27857725/blood-micrornas-as-potential-diagnostic-and-prognostic-markers-in-cerebral-ischemic-injury
#6
REVIEW
Bridget Martinez, Philip V Peplow
MicroRNAs are a family of small, genome-encoded endogenous RNAs that are transcribed but are not translated into proteins. They serve essential roles in virtually every aspect of brain function, including neurogenesis, neural development, and cellular responses leading to changes in synaptic plasticity. They are also implicated in neurodegeneration and neurological disorders, in responses to hypoxia and ischemia, and in ischemic tolerance induced by ischemic preconditioning. In recent developments, miRNA expression profiling has been examined in stroke, and these studies indicate that miRNAs have emerged as key mediators in ischemic stroke biology...
September 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27856497/intravenous-allogeneic-mesenchymal-stem-cells-for-non-ischemic-cardiomyopathy-safety-and-efficacy-results-of-a-phase-ii-a-randomized-trial
#7
Javed Butler, Stephen E Epstein, Stephen J Greene, Arshed A Quyyumi, Sergey Sikora, Raymond J Kim, Allen S Anderson, Jane E Wilcox, Nikolai I Tankovich, Michael J Lipinski, Yi-An Ko, Kenneth B Margulies, Robert T Cole, Hal A Skopicki, Mihai Gheorghiade
RATIONALE: Potential benefits of mesenchymal stem cell (MSC) therapy in heart failure (HF) may be related to paracrine properties and systemic effects, including anti-inflammatory activities. If this hypothesis is valid, intravenous administration of MSCs should improve outcomes in HF, an entity in which excessive chronic inflammation may play a pivotal role. OBJECTIVE: To assess the safety and preliminary efficacy of intravenously administered ischemia tolerant MSCs (itMSCs) in patients with non-ischemic cardiomyopathy...
November 16, 2016: Circulation Research
https://www.readbyqxmd.com/read/27846623/paracrine-mechanisms-of-intravenous-bone-marrow-derived-mononuclear-stem-cells-in-chronic-ischemic-stroke
#8
Ashu Bhasin, M V Padma Srivastava, Sujata Mohanty, Sivasubramaniam Vivekanandhan, Sakshi Sharma, Senthil Kumaran, Rohit Bhatia
BACKGROUND: The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF)...
October 19, 2016: Cerebrovascular Diseases Extra
https://www.readbyqxmd.com/read/27844035/intravenous-thrombolysis-in-acute-ischemic-stroke-after-dabigatran-reversal-with-idarucizumab-a-case-report
#9
Johannes Sebastian Mutzenbach, Slaven Pikija, Ferdinand Otto, Ursula Halwachs, Friedrich Weymayr, Johann Sellner
Much excitement has been generated with the approval of idarucizumab, a humanized monoclonal antigen-binding antibody fragment that is capable of reversing the anticoagulant activity of dabigatran. Here, we describe our initial experience of using tissue plasminogen activator (tPA) in an acute posterior circulation ischemic stroke after dabigatran reversal with idarucizumab. Both treatments were well tolerated and no hemorrhagic or procoagulatory complications were observed. We propose that the option of dabigatran reversal needs to be considered for contemporary treatment concepts of acute ischemic stroke...
November 2016: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/27826106/differential-spread-of-anoxic-depolarization-contributes-to-the-pattern-of-neuronal-injury-after-oxygen-and-glucose-deprivation-ogd-in-the-substantia-nigra-in-rat-brain-slices
#10
Rashika N Karunasinghe, Angus C Grey, Ravindra Telang, Srdjan M Vlajkovic, Janusz Lipski
Anoxic depolarization (AD) is an acute event evoked by brain ischemia, involving a profound loss of cell membrane potential and swelling that spreads over susceptible parts of the gray matter. Its occurrence is a strong predictor of the severity of neuronal injury. Little is known about this event in the Substantia Nigra, a midbrain nucleus critical for motor control. We tested the effects of oxygen and glucose deprivation (OGD), an in vitro model of brain ischemia, in rat midbrain slices. AD developed within 4min from OGD onset and spread in the Substantia Nigra pars reticulata (SNr), but not through the Substantia Nigra pars compacta (SNc)...
November 5, 2016: Neuroscience
https://www.readbyqxmd.com/read/27811363/resveratrol-post-treatment-protects-against-neonatal-brain-injury-after-hypoxia-ischemia
#11
Shulin Pan, Songlin Li, Yingying Hu, Hao Zhang, Yanlong Liu, Huai Jiang, Mingchu Fang, Zhengmao Li, Kebin Xu, Hongyu Zhang, Zhenlang Lin, Jian Xiao
Neonatal hypoxic-ischemic brain injury is a devastating disease with limited treatment options. Preventive treatment with resveratrol has indicated to be well tolerated and has lower toxicity in both experimental models and human patients. However, whether resveratrol administration post-hypoxic-ischemic protects against neonatal hypoxic-ischemic injury is not known. Here we reported that post-treatment with resveratrol significantly reduced brain damage at 7-day after the injury. We found that resveratrol reduced the expression levels of key inflammatory factors at the mRNA and protein levels, and at least partially via inhibiting microglia activation...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27805502/cell-therapy-in-solid-organ-transplant
#12
Hassan Argani
In solid-organ transplant, cell therapy is used as an immunomodulation therapy or as a functioning graft (bioengineering medicine). Before such treatment can be more accepted among transplant societies, some uncertainties should be clarified. These include: why is such therapy mandatory? What are the indications for this therapy, and what are the mechanism(s) of actions? What types of cells are involved and what are their routes of actions? Finally, what is known about the safety? In general, the risks associated with intravenous administration of immunoregulatory cell products are similar to those encountered with conventional blood transfusions...
November 2016: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/27803392/selecting-patients-for-intra-arterial-therapy-in-the-context-of-a-clinical-trial-for-neuroprotection
#13
Patrick Lyden, Sara Weymer, Chris Coffey, Merit Cudkowicz, Samantha Berg, Sarah O'Brien, Marc Fisher, E Clarke Haley, Pooja Khatri, Jeff Saver, Steven Levine, Howard Levy, Marilyn Rymer, Lawrence Wechsler, Ashutosh Jadhav, Elizabeth McNeil, Salina Waddy, Kent Pryor
BACKGROUND AND PURPOSE: The advent of intra-arterial neurothrombectomy (IAT) for acute ischemic stroke opens a potentially transformative opportunity to improve neuroprotection studies. Combining a putative neuroprotectant with recanalization could produce more powerful trials but could introduce heterogeneity and adverse event possibilities. We sought to demonstrate feasibility of IAT in neuroprotectant trials by defining IAT selection criteria for an ongoing neuroprotectant clinical trial...
November 1, 2016: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/27799254/phosphodiesterase-2-protects-against-catecholamine-induced-arrhythmia-and-preserves-contractile-function-after-myocardial-infarction
#14
Christiane Vettel, Marta Lindner, Matthias Dewenter, Kristina Lorenz, Constanze Schanbacher, Merle Riedel, Simon Lämmle, Simone Meinecke, Fleur E Mason, Samuel Sossalla, Andreas Geerts, Michael Hoffmann, Frank Wunder, Fabian J Brunner, Thomas Wieland, Hind Mehel, Sarah Karam, Patrick Lechêne, Jérôme Leroy, Grégoire Vandecasteele, Michael Wagner, Rodolphe Fischmeister, Ali El-Armouche
RATIONALE: Phosphodiesterase 2 (PDE2) is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyses cAMP. Myocardial PDE2 is upregulated in human heart failure (HF), but its role in the heart is unknown. OBJECTIVE: To explore the role of PDE2 in cardiac function, propensity to arrhythmia and in myocardial infarction. METHODS AND RESULTS: Pharmacological inhibition of PDE2 (BAY 60-7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor (β-AR) activation in healthy mice...
October 31, 2016: Circulation Research
https://www.readbyqxmd.com/read/27796011/long-term-window-of-ischemic-tolerance-an-evolutionarily-conserved-form-of-metabolic-plasticity-regulated-by-epigenetic-modifications
#15
Nathalie Khoury, Kevin B Koronowski, Miguel A Perez-Pinzon
In the absence of effective neuroprotective agents in the clinic, ischemic and pharmacological preconditioning are gaining increased interest in the field of cerebral ischemia. Our lab recently reported that resveratrol preconditioning affords tolerance against a focal cerebral ischemic insult in mice that can last for at least 14 days in vivo making it the longest window of ischemic tolerance discovered to date by a single administration of a pharmacological agent. The mechanism behind this novel extended window of ischemic tolerance remains elusive...
2016: Journal of Neurology & Neuromedicine
https://www.readbyqxmd.com/read/27794566/transient-ischemic-attacks-preceding-acute-lacunar-infarction
#16
Jae Guk Kim, Hanna Choi, Sung-Yeon Sohn, Do-Hyung Kim, Soo Joo Lee
BACKGROUND: It has been reported that some patients with lacunar infarction have transient ischemic attacks (TIAs) before stroke. This study was aimed at evaluating the factors and prognostic value related to TIAs preceding acute lacunar stroke. METHODS: A total of 1,424 patients were admitted to the hospital for first-ever ischemic stroke. Of which 314 patients with acute lacunar infarction were enrolled for this study. The patients were divided into 2 groups based on the occurrence of TIAs before stroke...
2016: European Neurology
https://www.readbyqxmd.com/read/27793534/plasmin-human-administration-in-acute-middle-cerebral-artery-ischemic-stroke-phase-1-2a-open-label-dose-escalation-safety-study
#17
Peter J Mitchell, Bernard Yan, Miroslav Brozman, Marc Ribo, Victor Marder, Kecia L Courtney, Jeffrey L Saver
BACKGROUND: This phase 1/2a, open-label, multicenter, dose-escalation, safety study describes the first evaluation of plasmin as an intracranial thrombolytic treatment for acute ischemic stroke in the middle cerebral artery. The rationale for intrathrombus administration is that plasmin would bind fibrin inside the targeted clot, protecting it from circulating inhibitors. METHODS: Plasmin was given in escalating doses within 9 hours of stroke onset, and treatment efficacy was determined in 5 patient cohorts (N = 40): cohort 1 (20 mg, ...
October 25, 2016: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/27784628/advances-in-bone-marrow-stem-cell-therapy-for-retinal-dysfunction
#18
REVIEW
Susanna S Park, Elad Moisseiev, Gerhard Bauer, Johnathon D Anderson, Maria B Grant, Azhar Zam, Robert J Zawadzki, John S Werner, Jan A Nolta
The most common cause of untreatable vision loss is dysfunction of the retina. Conditions, such as age-related macular degeneration, diabetic retinopathy and glaucoma remain leading causes of untreatable blindness worldwide. Various stem cell approaches are being explored for treatment of retinal regeneration. The rationale for using bone marrow stem cells to treat retinal dysfunction is based on preclinical evidence showing that bone marrow stem cells can rescue degenerating and ischemic retina. These stem cells have primarily paracrine trophic effects although some cells can directly incorporate into damaged tissue...
October 23, 2016: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/27783319/expecting-the-holistic-regulation-from-chinese-medicine-based-on-the-solar-system-hypothesis-of-ischemic-heart-disease
#19
Jing Luo, An-Lu Wang, Hao Xu, Da-Zhuo Shi, Ke-Ji Chen
Stenosis of the coronary artery has been considered as an essential component of ischemic heart disease (IHD). Consequently, revascularization [e.g., percutaneous coronary intervention (PCI) and coronary artery bypass] has been the primary therapeutic approach to IHD. Such strategy has indeed revolutionized the management of IHD patients. However, not all patients with myocardial ischemia have visible coronary stenosis. Moreover, cardiovascular events occur in nearly 20% patients with stable coronary artery disease who have undergone PCI...
November 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/27777279/reductions-in-atherogenic-lipids-and-major-cardiovascular-events-a-pooled-analysis-of-10-odyssey-trials-comparing-alirocumab-to-control
#20
Kausik K Ray, Henry N Ginsberg, Michael H Davidson, Robert Pordy, Laurence Bessac, Pascal Minini, Robert H Eckel, Christopher P Cannon
BACKGROUND: -A continuous relationship between reductions in low-density lipoprotein cholesterol (LDL-C) and major adverse cardiovascular events (MACE) has been observed in statin and ezetimibe outcomes trials, down to achieved levels of 54 mg/dL. However, it is uncertain whether this relationship extends to LDL-C levels <50 mg/dL. We assessed the relationship between additional LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B100 (apoB) reductions and MACE among patients within the ODYSSEY trials that compared alirocumab versus controls (placebo/ezetimibe), mainly as add on to maximally tolerated statin...
October 24, 2016: Circulation
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