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Myocardial ischemia and glucose

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https://www.readbyqxmd.com/read/29154687/pyruvate-enhancement-of-cardiac-performance-cellular-mechanisms-and-clinical-application
#1
Robert T Mallet, Albert H Olivencia-Yurvati, Rolf Bünger
Cardiac contractile function is adenosine-5'-triphosphate (ATP)-intensive, and the myocardium's high demand for oxygen and energy substrates leaves it acutely vulnerable to interruptions in its blood supply. The myriad cardioprotective properties of the natural intermediary metabolite pyruvate make it a potentially powerful intervention against the complex injury cascade ignited by myocardial ischemia-reperfusion. A readily oxidized metabolic substrate, pyruvate augments myocardial free energy of ATP hydrolysis to a greater extent than the physiological fuels glucose, lactate and fatty acids, particularly when it is provided at supra-physiological plasma concentrations...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29148291/effectiveness-and-safety-of-anti-ischemic-trimetazidine-in-patients-with-stable-angina-pectoris-and-type-2-diabetes
#2
Zsófia Meiszterics, Attila Kónyi, Gábor Hild, Zsolt Sárszegi, Balázs Gaszner
Aim & methods: This 6-month prospective, observational, noninterventional, open-label clinical study assessed the effectiveness/safety of trimetazidine in 737 patients with stable angina pectoris and Type 2 diabetes mellitus (OGYI/51534-1/2014). RESULTS: Trimetazidine-based therapy was effective in stable coronary artery disease, with significant improvements from baseline (p < 0.05) in: number of angina attacks/week (2.9 ± 2.4 vs 1.1 ± 1.6), angina severity (Canadian Cardiovascular Society Classification 1...
November 17, 2017: Journal of Comparative Effectiveness Research
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#3
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29130958/propofol-through-upregulating-caveolin-3-attenuates-post-hypoxic-mitochondrial-damage-and-cell-death-in-h9c2-cardiomyocytes-during-hyperglycemia
#4
Fan Deng, Shuang Wang, Liangqing Zhang, Xiang Xie, Shuyun Cai, Haobo Li, Gui-Ling Xie, Hui-Lai Miao, Changmin Yang, Xin Liu, Zhengyuan Xia
BACKGROUND/AIMS: Hearts from diabetic subjects are susceptible to myocardial ischemia reperfusion (I/R) injury. Propofol has been shown to protect against myocardial I/R injury due to its antioxidant properties while the underlying mechanism remained incompletely understood. Thus, this study aimed to determine whether or not propofol could attenuate myocardial I/R injury by attenuating mitochondrial dysfunction/damage through upregulating Caveolin (Cav)-3 under hyperglycemia. METHODS: Cultured rat cardiomyocyte H9C2 cells were subjected to hypoxia/reoxygenation (H/R) in the absence or presence of propofol under high glucose (HG), and cell viability, lactate dehydrogenase (LDH) and mitochondrial viability as well as creatine kinase-MB (CK-MB), cardiac troponin I (cTnI) and intracellular adenosine triphosphate (ATP) content were measured with colorimetric Enzyme-Linked Immunosorbent Assays...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29121919/effects-of-hypoglycemia-on-myocardial-susceptibility-to-ischemia-reperfusion-injury-and-preconditioning-in-hearts-from-rats-with-and-without-type-2-diabetes
#5
Kim B Pælestik, Nichlas R Jespersen, Rebekka V Jensen, Jacob Johnsen, Hans Erik Bøtker, Steen B Kristiansen
BACKGROUND: Hypoglycemia is associated with increased mortality rate in patients with diabetes. The underlying mechanisms may involve reduced myocardial tolerance to ischemia and reperfusion (IR) or reduced capacity for ischemic preconditioning (IPC). As IPC is associated with increased myocardial glucose uptake (MGU) during reperfusion, cardioprotection is linked to glucose metabolism possibly by O-linked β-N-acetylglucosamine (O-GlcNAc). We aimed to investigate the impact of hypoglycemia in hearts from animals with diabetes on myocardial IR tolerance, on the efficacy of IPC and whether modulations of MGU and O-GlcNAc levels are involved in the underlying mechanisms...
November 9, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29118818/folic-acid-prevents-cardiac-dysfunction-and-reduces-myocardial-fibrosis-in-a-mouse-model-of-high-fat-diet-induced-obesity
#6
Wei Li, Renqiao Tang, Shengrong Ouyang, Feifei Ma, Zhuo Liu, Jianxin Wu
Background: Folic acid (FA) is an antioxidant that can reduce reactive oxygen species generation and can blunt cardiac dysfunction during ischemia. We hypothesized that FA supplementation prevents cardiac fibrosis and cardiac dysfunction induced by obesity. Methods: Six-week-old C57BL6/J mice were fed a high-fat diet (HFD), normal diet (ND), or an HFD supplemented with folic acid (FAD) for 14 weeks. Cardiac function was measured using a transthoracic echocardiographic exam...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29062465/nlrp3-inflammasome-activation-mediated-pyroptosis-aggravates-myocardial-ischemia-reperfusion-injury-in-diabetic-rats
#7
Zhen Qiu, Shaoqing Lei, Bo Zhao, Yang Wu, Wating Su, Min Liu, Qingtao Meng, Bin Zhou, Yan Leng, Zhong-Yuan Xia
The reactive oxygen species- (ROS-) induced nod-like receptor protein-3 (NLRP3) inflammasome triggers sterile inflammatory responses and pyroptosis, which is a proinflammatory form of programmed cell death initiated by the activation of inflammatory caspases. NLRP3 inflammasome activation plays an important role in myocardial ischemia/reperfusion (MI/R) injury. Our present study investigated whether diabetes aggravated MI/R injury through NLRP3 inflammasome-mediated pyroptosis. Type 1 diabetic rat model was established by intraperitoneal injection of streptozotocin (60 mg/kg)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29061061/metabolic-disturbances-induce-malignant-heart-arrhythmias-in-rats
#8
B Liptak, V Knezl, Z Gasparova
OBJECTIVES: Metabolic disturbances are considered to condition the occurrence of malignant heart arrhythmias and negatively influence the chances of a patient to survive. To test this assumption, a model of metabolic syndrome was selected in which rats were receiving a diet resembling that of the westernized population. BACKGROUND: Metabolic syndrome is a comorbidity of major cardiovascular risk factors (dyslipidemia, hypertension, impaired glucose tolerance or insulin resistance, diabetes mellitus, and obesity), all facilitating cardiovascular complications leading to morbidity and mortality of patients...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29057797/oxidative-stress-responsive-apoptosis-inducing-protein-oraip-plays-a-critical-role-in-high-glucose-induced-apoptosis-in-rat-cardiac-myocytes-and-murine-pancreatic-%C3%AE-cells
#9
Takako Yao, Tsutomu Fujimura, Kimie Murayama, Ko Okumura, Yoshinori Seko
We previously identified a novel apoptosis-inducing humoral factor in the conditioned medium of hypoxic/reoxygenated-cardiac myocytes. We named this novel post-translationally-modified secreted-form of eukaryotic translation initiation factor 5A Oxidative stress-Responsive Apoptosis-Inducing Protein (ORAIP). We confirmed that myocardial ischemia/reperfusion markedly increased plasma ORAIP levels and rat myocardial ischemia/reperfusion injury was clearly suppressed by neutralizing anti-ORAIP monoclonal antibodies (mAbs) in vivo...
October 18, 2017: Cells
https://www.readbyqxmd.com/read/29042932/cardioprotective-effect-of-notch-signaling-on-the-development-of-myocardial-infarction-complicated-by-diabetes-mellitus
#10
Fang Wu, Bo Yu, Xu Zhang, Yuelan Zhang
The present study aimed to elucidate the role of Notch signaling in the development of myocardial infarction (MI) concomitant with diabetes in vivo and in vitro and evaluated the therapeutic effect of the Notch signaling in vitro. Streptozotocin-induced diabetic rats were subjected to 25 min of ischemia and 2 h of reperfusion. Cardiac troponin T (cTnT) and creatine kinase-MB (CK-MB) isoenzyme levels were detected. Infarct size was measured by 2,3,5-triphenyltetrazolium chloride staining. Myocardial apoptosis and fibrosis were examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and Masson Trichrome staining, respectively...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29040168/failure-of-isoflurane-cardiac-preconditioning-in-obese-type-2-diabetic-mice-involves-aberrant-regulation-of-microrna-21-endothelial-nitric-oxide-synthase-and-mitochondrial-complex-i
#11
Zhi-Dong Ge, Yingchuan Li, Shigang Qiao, Xiaowen Bai, David C Warltier, Judy R Kersten, Zeljko J Bosnjak, Mingyu Liang
BACKGROUND: Diabetes impairs the cardioprotective effect of volatile anesthetics, yet the mechanisms are still murky. We examined the regulatory effect of isoflurane on microRNA-21, endothelial nitric-oxide synthase, and mitochondrial respiratory complex I in type II diabetic mice. METHODS: Myocardial ischemia/reperfusion injury was produced in obese type 2 diabetic (db/db) and C57BL/6 control mice ex vivo in the presence or absence of isoflurane administered before ischemia...
October 17, 2017: Anesthesiology
https://www.readbyqxmd.com/read/29035826/effects-of-gallic-acid-on-hemodynamic-parameters-and-infarct-size-after-ischemia-reperfusion-in-isolated-rat-hearts-with-alloxan-induced-diabetes
#12
Fatemeh Ramezani-Aliakbari, Mohammad Badavi, Mahin Dianat, Seyed Ali Mard, Akram Ahangarpour
Diabetic rats are more susceptible to myocardial ischemia-reperfusion injury than control rats. The aim of the present study was to evaluate the cardioprotective effect of gallic acid (GA) on isolated rat hearts with alloxan-induced diabetes mellitus. Adult male Sprague-Dawley rats were divided randomly into three groups: control, untreated diabetic and diabetic animals treated with (GA, 25mg/kg). Diabetes was induced by 120mg/kg alloxan injection. Eight weeks after GA administration, the hearts were isolated and exposed to myocardial ischemia-reperfusion...
October 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29032506/differential-effects-of-amp-activated-protein-kinase-in-isolated-rat-atria-subjected-to-simulated-ischemia-reperfusion-depending-on-the-energetic-substrates-available
#13
Romina Hermann, Victoria Evangelina Mestre Cordero, María de Las Mercedes Fernández Pazos, Federico Joaquín Reznik, Débora Elisabet Vélez, Enrique Alberto Savino, María Gabriela Marina Prendes, Alicia Varela
AMP-activated protein kinase (AMPK) is a serine-threonine kinase that functions primarily as a metabolic sensor to coordinate anabolic and catabolic processes in the cell, via phosphorylation of multiple proteins involved in metabolic pathways, aimed to re-establish energy homeostasis at a cell-autonomous level. Myocardial ischemia and reperfusion represents a metabolic stress situation for myocytes. Whether AMPK plays a critical role in the metabolic and functional responses involved in these conditions remains uncertain...
October 14, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29023410/long-term-osmotic-mini-pump-treatment-with-alpha-msh-improves-myocardial-function-in-zucker-diabetic-fatty-rats
#14
Miklos Szokol, Daniel Priksz, Mariann Bombicz, Balazs Varga, Arpad Kovacs, Gabor Aron Fulop, Tamas Csipo, Aniko Posa, Attila Toth, Zoltan Papp, Zoltan Szilvassy, Bela Juhasz
The present investigation evaluates the cardiovascular effects of the anorexigenic mediator alpha-melanocyte stimulating hormone (MSH), in a rat model of type 2 diabetes. Osmotic mini pumps delivering MSH or vehicle, for 6 weeks, were surgically implanted in Zucker Diabetic Fatty (ZDF) rats. Serum parameters, blood pressure, and weight gain were monitored along with oral glucose tolerance (OGTT). Echocardiography was conducted and, following sacrifice, the effects of treatment on ischemia/reperfusion cardiac injury were assessed using the isolated working heart method...
October 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29021296/lactate-promotes-synthetic-phenotype-in-vascular-smooth-muscle-cells
#15
Libang Yang, Ling Gao, Thomas Nickel, Jing Yang, Jingyi Zhou, Adam Gilbertsen, Zhaohui Geng, Caitlin Johnson, Bernice Young, Craig Henke, Glenn R Gourley, Jianyi Zhang
RATIONALE: The phenotypes of vascular smooth muscle cells (vSMCs) comprise a continuum bounded by predominantly contractile and synthetic cells. Some evidence suggests that contractile vSMCs can assume a more synthetic phenotype in response to ischemic injury, but the mechanisms that activate this phenotypic switch are poorly understood. OBJECTIVE: To determine whether lactate, which increases in response to regional ischemia, may promote the synthetic phenotype in vSMCs...
November 10, 2017: Circulation Research
https://www.readbyqxmd.com/read/29021167/high-density-lipoprotein-delivered-after-myocardial-infarction-increases-cardiac-glucose-uptake-and-function-in-mice
#16
Sarah E Heywood, Adele L Richart, Darren C Henstridge, Karen Alt, Helen Kiriazis, Claire Zammit, Andrew L Carey, Helene L Kammoun, Lea M Delbridge, Medini Reddy, Yi-Ching Chen, Xiao-Jun Du, Christoph E Hagemeyer, Mark A Febbraio, Andrew L Siebel, Bronwyn A Kingwell
Protecting the heart after an acute coronary syndrome is a key therapeutic goal to support cardiac recovery and prevent progression to heart failure. A potential strategy is to target cardiac glucose metabolism at the early stages after ischemia when glycolysis is critical for myocyte survival. Building on our discovery that high-density lipoprotein (HDL) modulates skeletal muscle glucose metabolism, we now demonstrate that a single dose of reconstituted HDL (rHDL) delivered after myocardial ischemia increases cardiac glucose uptake, reduces infarct size, and improves cardiac remodeling in association with enhanced functional recovery in mice...
October 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28993734/osmotin-protects-h9c2-cells-from-simulated-ischemia-reperfusion-injury-through-adipor1-pi3k-akt-signaling-pathway
#17
Jianhua Liu, Hua Sui, Jianlin Zhao, Yan Wang
Objective: This study aimed to investigate the effect of osmotin on myocardial ischemia/reperfusion (I/R), as well as the underlying mechanisms. Methods:In vitro I/R injury model was established on rat cardiac myoblast H9c2 cells by oxygen and glucose deprivation followed by reperfusion (OGD/R). Cells were administrated with osmotin, and transfected with small interfering RNAs (siRNAs) which specifically target adiponectin receptor 1 or 2 (AdipoR1/2). Besides, the cells were incubated with or without LY294002 as inhibitor of phosphatidylinositol 3-kinase (PI3K) under OGD/R condition...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28967097/chronic-treatment-with-novel-nanoformulated-micelles-of-rapamycin-rapatar-protects-diabetic-heart-against-ischemia-reperfusion-injury
#18
Arun Samidurai, Fadi N Salloum, David Durrant, Olga B Chernova, Rakesh C Kukreja, Anindita Das
BACKGROUND: Enhanced mammalian target of rapamycin (mTOR) signaling contributes to the pathogenesis of diabetes and plays a critical role in myocardial ischemia/reperfusion (I/R) injury. Rapatar is a novel nanoformulated micellar of rapamycin, a putative inhibitor of mTOR, that have been rationally designed to increase water solubility of rapamycin in order to facilitate oral administration and enhance bioavailability. We examined the effect of Rapatar in improving metabolic status and protection against myocardial I/R injury in type 2 diabetic (T2D) mice...
October 1, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28965151/sodium-thiosulfate-preconditioning-ameliorates-ischemia-reperfusion-injury-in-rat-hearts-via-reduction-of-oxidative-stress-and-apoptosis
#19
Sriram Ravindran, Sri Rahavi Boovarahan, Karthi Shanmugam, Ramalingam C Vedarathinam, Gino A Kurian
PURPOSE: Sodium thiosulfate (STS) has of late been proven efficacious in models of urolithiasis and vascular calcification. However, its cardiovascular effects on ischemia reperfusion injury (IR) have not been revealed. Being an antioxidant and calcium chelator, it is assumed to play a vital role in IR as ROS production and calcium overload are major perpetrators of IR injury. METHODS: The cardioprotective effect of STS was evaluated in vitro using H9C2 cardiomyocytes and in vivo using both isolated rat heart and intact left anterior descending artery (LAD) occlusion models of ischemia reperfusion injury...
September 30, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28951984/remote-ischemic-preconditioning-protects-human-neural-stem-cells-from-oxidative-stress
#20
Ayako Motomura, Mikiko Shimizu, Akira Kato, Kazuya Motomura, Akane Yamamichi, Hiroko Koyama, Fumiharu Ohka, Tomohide Nishikawa, Yusuke Nishimura, Masahito Hara, Tetsuya Fukuda, Yasuhiko Bando, Toshihide Nishimura, Toshihiko Wakabayashi, Atsushi Natsume
In previous clinical trials, we showed that remote ischemic preconditioning (rIPC) reduced myocardial damage in children undergoing treatment for congenital heart defects and postoperative renal failure in patients undergoing abdominal aortic aneurysm surgery. In rabbit experiments, pre-treatment with plasma and plasma dialysate (obtained using 15-kDa cut-off dialysis membrane) from donor rabbits subjected to rIPC similarly protected against cardiac infarction. However, the protective substances containing in rIPC plasma have been unknown...
November 2017: Apoptosis: An International Journal on Programmed Cell Death
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