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A Mahalakshmi, Gino A Kurian
Earlier literature underlines that oxidative stress plays a major role in the pathology of myocardial ischemia-reperfusion (I/R) injury, diabetic cardiomyopathy (DCM), diabetes mellitus (DM), fibrosis and hypertrophy which could adversely affect the normal cardiac function. However, the contributory role of oxidative stress in I/R pathology of heart with pre-existing abnormalities or diseases like DM and DCM remains to be explored. I/R injury was induced in normal (normal diet), DM (normal diet + streptozotocin: multiple low dose of 30mg/kg) and DCM (high fat diet (40% fat) + streptozotocin: multiple low dose of 30mg/kg) rat hearts using Langendorff isolated heart perfusion apparatus...
February 17, 2018: Free Radical Biology & Medicine
Kien Tran, Alexandre Murza, Xavier Sainsily, David Coquerel, Jérôme Côté, Karine Belleville, Lounès Haroune, Jean-Michel Longpré, Robert Dumaine, Dany Salvail, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
The apelin receptor generates increasing interest as a potential target across several cardiovascular indications. However, the short half-life of its cognate ligands, the apelin peptides, is a limiting factor for pharmacological use. In this study, we systematically explored each position of apelin-13 to find the best position to cyclize the peptide, with the goal to improve its stability while optimizing its binding affinity and signaling profile. Macrocyclic analogues showed a remarkably higher stability in rat plasma (half-life > 3 h versus 24 min for Pyr-apelin-13), accompanied with improved affinity (analogue 15, Ki 0...
February 20, 2018: Journal of Medicinal Chemistry
Maryam Mahmoudabady, Milad Haghshenas, Saeed Niazmand
Background: The deleterious effect of oxidative stress on myocardial ischemia-reperfusion (I/R) has already been shown in previous studies. Since Teucrium polium has anti-oxidative and cardio-protective properties, the aim of this study was to investigate the effects of this plant on I/R injuries in the isolated rat heart. Materials and Methods: The myocardial I/R injury of rat was created by Langendorff retrograde perfusion technology. The heart was preperfused with Krebs-Henseleit (K-H) solution containing T...
2018: Advanced Biomedical Research
Hiroki Saito, Shigeo Godo, Saori Sato, Akiyo Ito, Yosuke Ikumi, Shuhei Tanaka, Tomoaki Ida, Shigemoto Fujii, Takaaki Akaike, Hiroaki Shimokawa
AIMS: Nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) play important roles in maintaining cardiovascular homeostasis. We have previously demonstrated that endothelial NO synthase (eNOS) plays diverse roles depending on vessel size, as a NO generating system in conduit arteries and an EDH-mediated system in resistance arteries, for which caveolin-1 (Cav-1) is involved. However, the physiological role of endothelial Cav-1 in microvessels remains to be elucidated. METHODS AND RESULTS: We newly generated endothelium-specific Cav-1-knockout (eCav-1-KO) mice...
February 2018: Journal of Cardiovascular Pharmacology
Qiming Duan, Yunhui Xu, Pauline V Marck, Jennifer Kalisz, Eric E Morgan, Sandrine V Pierre
Ouabain preconditioning (OPC) initiated by low concentrations of the cardiac glycoside (CG) ouabain binding to Na/K-ATPase is relayed by a unique intracellular signaling and protects cardiac myocytes against ischemia/reperfusion injury. To explore more clinically applicable protocols based on CG properties, we tested whether the FDA-approved CG digoxin could trigger cardioprotective effects comparable with those of ouabain using PC, preconditioning and PostC, postconditioning protocols in the Langendorff-perfused mouse heart subjected to global ischemia and reperfusion...
February 2018: Journal of Cardiovascular Pharmacology
Martin Lewis, Adrian Szobi, Dirki Balaska, Igor Khaliulin, Adriana Adameova, Elinor Griffiths, Clive H Orchard, M-Saadeh Suleiman
Consecutive treatment of adult rat heart with isoproterenol and adenosine (Iso/Aden), known to consecutively activate PKA/PKC signaling, is cardioprotective against ischemia and reperfusion (I/R). Whether this is cardioprotective in an immature heart is unknown. Langendorff-perfused hearts from adult and immature (60 and 14 days old) male Wistar rats were exposed to 30 min ischemia and 120 min reperfusion, with or without prior perfusion with 5 nM Iso for 3 min followed by 30 μM Aden for 5 min. Changes in hemodynamics (developed pressure and coronary flow) and cardiac injury (Lactate Dehydrogenase (LDH) release and infarct size) were measured...
February 7, 2018: International Journal of Molecular Sciences
Alejandro Ciocci Pardo, Sergio Scuri, Luisa F González Arbeláez, Claudia Caldiz, Juliana Fantinelli, Susana M Mosca
The response to ischemia/reperfusion and the effects of ischemic post-conditioning (IPC) are sex-dependent, but the mechanisms have not been clarified. Male (M) and female (F) rat hearts isolated and perfused using the Langendorff technique were subject to 30 min of global ischemia (GI) and 60 min reperfusion (R). In IPC hearts, three cycles of 30-sec GI/30-sec R were applied at the beginning of R. Infarct size and myocardial function were assessed. Superoxide production, antioxidant systems, and expressions of phosphorylated forms of serine/threonine kinase (Akt), glycogen synthase kinase 3β (GSK-3β), protein kinase C ε (PKCε), endothelial nitric oxide synthase (eNOS), and apoptosis were measured...
December 28, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
Lin Wang, Nanhu Quan, Wanqing Sun, Xu Chen, Courtney Cates, Thomas Rousselle, Xinchun Zhou, Xuezhong Zhao, Ji Li
Aim: A longevity gene, Sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise. The objective of this study is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults. Methods and Results: Mice were subjected to ligation of left anterior descending coronary artery for in vivo ischemic models...
February 2, 2018: Cardiovascular Research
Lili Wan, Matthew J Powell-Palm, Charles Lee, Anshal Gupta, Bradley P Weegman, Mark G Clemens, Boris Rubinsky
Isochoric (constant volume) preservation at subfreezing temperatures is being investigated as a novel method for preserving cells and organs. This study is a first initial effort to evaluate the efficacy of this method for heart preservation, and to provide a preliminary outline of appropriate preservation parameters. To establish a baseline for further studies, rat hearts were preserved in a University of Wisconsin (UW) intracellular solution for one hour under isochoric conditions at: 0 °C (atmospheric pressure - 0...
January 29, 2018: Biochemical and Biophysical Research Communications
Akiko Kojima, Yutaka Fukushima, Yuki Ito, Wei-Guang Ding, Hirotoshi Kitagawa, Hiroshi Matsuura
Reperfusion of ischemic myocardium is accompanied by intracellular Ca overload, leading to cardiac dysfunction. However, the mechanisms underlying intracellular Ca overload have yet to be fully elucidated. The mechanism may involve the activation of store-operated Ca entry, which is primarily mediated through the transient receptor potential canonical (TRPC) channels. The present study was undertaken to examine the possible involvement of TRPC channels in the development of contractile dysfunction associated with reperfusion of ischemic myocardium using a mouse heart model...
January 30, 2018: Journal of Cardiovascular Pharmacology
Michal K Handzlik, Dumitru Constantin-Teodosiu, Paul L Greenhaff, Mark A Cole
The pattern of metabolic reprogramming in chronic hypoxia shares similarities with that following myocardial infarction or hypertrophy, however the response of the chronically hypoxic heart to subsequent acute injury, and the role of metabolism is not well understood. Here, we determined the myocardial tolerance of the chronically hypoxic heart to subsequent acute injury, and hypothesised that activation of a key regulator of myocardial metabolism, the pyruvate dehydrogenase complex (PDC), could improve hypoxic tolerance...
January 31, 2018: Journal of Physiology
S Plecevic, B Jakovljevic, M Savic, V Zivkovic, T Nikolic, J Jeremic, I Milosavljevic, I Srejovic, N Tasic, D Djuric, V Jakovljevic
The aim of present study was to evaluate the effects of 3- and 6-week swimming exercise on cardiodynamics and coronary flow in high salt-induced hypertensive and normotensive rats. 80 male Wistar albino rats (6 weeks old) were divided into 8 groups: hypertensive animals that swam for 3 weeks; hypertensive animals that swam for 6 weeks and their respective sedentary controls; normotensive animals that swam for 3 weeks; normotensive animals that swam for 6 weeks and their respective sedentary controls. Hypertensive animals were on high sodium (8% NaCl solution) diet for 4 weeks, and these animals did not drink tap water during the experimental protocol...
January 27, 2018: Molecular and Cellular Biochemistry
Christian Ellermann, Magdalena Sterneberg, Simon Kochhäuser, Dirk G Dechering, Michael Fehr, Lars Eckardt, Gerrit Frommeyer
Aims: Antazoline is a first-generation antihistamine with antiarrhythmic properties. This study examines potential electrophysiological effects of antazoline in short-QT-syndrome (SQTS) and long-QT-syndrome (LQTS). Methods and results: Sixty-five rabbit hearts were Langendorff-perfused. Action potential duration at 90% of repolarization (APD90), QT-interval, spatial dispersion (DISP), and effective refractory period (ERP) were measured. The IK, ATP-opener pinacidil (1 µM, n = 14) reduced APD90 (-14 ms, P < 0...
January 25, 2018: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
Alejandro Ciocci Pardo, Romina G Díaz, Luisa F González Arbeláez, Nestor G Perez, Erik Richard Swenson, Susana M Mosca, Bernardo V Alvarez
During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CA) leads to myocardial intracellular Ca2+ increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R). Langendorff perfused isolated rat hearts were subjected to 30 min of global ischemia and 60 min of reperfusion. Other hearts were treated with BZ (5 μM) during the initial 10 min of reperfusion or perfused with acid solution (AR, pH 6...
December 21, 2017: Journal of Applied Physiology
Mahvash Hesari, Dareuosh Shackebaei, Atefeh Asadmobini
OBJECTIVE: Doxorubicin (DOX) induces cardiac dysfunction. Paracetamol (APAP) has also been established as an effective cardioprotective agent during ischemia/reperfusion. Therefore, this study aims to evaluate the effect of APAP on DOX-induced cardiotoxicity in ischemia/reperfused isolated rat heart. METHODS: A total of 36 rats were equally divided into four groups: control, DOX (30 min, 20 µM DOX perfusion), APAP (15 min before and after ischemia, 0.35 mM APAP perfusion), and DOX+APAP (perfused with the same protocol in DOX and APAP groups)...
January 19, 2018: Anatolian Journal of Cardiology
Xingxing Liu, Haibo Song, Jun Yang, Cheng Zhou, Yi Kang, Linghui Yang, Jin Liu, Wensheng Zhang
OBJECTIVE: (R)-2-methoxyethyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate hydrochloride (ET-26 HCl) is a novel etomidate analogue. The purpose of this study was to characterize whether ET-26 HCl could retain the superior myocardial performance of etomidate in vivo and in vitro. METHODS: In vivo, the influence of ET-26 HCl and etomidate on the cardiac function of dogs was confirmed using echocardiography and electrocardiogram. In vitro, a Langendorff preparation was used to examine direct myocardial performance in isolated rat hearts, and a whole-cell patch-clamp technique was used to study effects on the human ether-a-go-go-related gene (hERG) channel...
2018: PloS One
Friederike Behmenburg, Lara Trefz, Marianne Dorsch, Martin Ströthoff, Alexander Mathes, Annika Raupach, André Heinen, Markus W Hollmann, Marc M Berger, Ragnar Huhn
OBJECTIVES: Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced postconditioning involves activation of mBKCa channels in the rat heart in vitro. DESIGN: Randomized, prospective, blinded laboratory investigation. SETTING: Experimental laboratory...
November 29, 2017: Journal of Cardiothoracic and Vascular Anesthesia
Xiao-Xue Jiang, Guan-Yu Liu, Han Lei, Zuo-Ling Li, Qing-Ping Feng, Wei Huang
Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel and a molecular integrator of noxious stimuli. TRPV1 activation confers cardiac protection against ischemia/reperfusion (I/R) injury. The present study aimed to investigate whether the cardioprotective effects of TRPV1 were associated with the inhibition of apoptosis via the phosphatidylinositol 3‑kinase (PI3K)/protein kinase B (Akt) and extracellular signal‑regulated protein kinase 1/2 (ERK1/2) signaling pathways. Briefly, the hearts of TRPV1 knockout (TRPV1‑/‑) or wild‑type (WT) mice were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion in a Langendorff apparatus in the presence or absence of the PI3K inhibitor, LY294002...
December 21, 2017: International Journal of Molecular Medicine
Yingxin Li, Xiaoxiao Zhang, Chen Zhang, Xiaoying Zhang, Ying Li, Zhao Qi, Christopher Szeto, Mingxin Tang, Yizhi Peng, Jeffery D Molkentin, Steven R Houser, Mingxing Xie, Xiongwen Chen
OBJECTIVE: Cav3.1 (α1G ) T-type Ca2+ channel (TTCC) is expressed in mouse sinoatrial node cells (SANCs) and atrioventricular nodal (AVN) cells and contributes to heart rate genesis and AV conduction. However, its role in heart rate (HR) regulation and AV conduction acceleration by the β-adrenergic system (SAS) is unclear, which is the topic of this study. METHODS AND RESULTS: L- (ICa-L ) and T-type (ICa-T ) Ca2+ currents were recorded in SANCs from Cav3.1 transgenic (TG) and knockout (KO), and control mice...
December 23, 2017: Journal of Physiology
Liming Xin, Bryan Gellner, Roberto Vanin Pinto Ribeiro, Giulia Maria Ruggeri, David Banner, Massimiliano Meineri, Vivek Rao, Jean Zu, Mitesh V Badiwala
Ex vivo heart perfusion has been shown to be an effective means of facilitating the resuscitation and assessment of donor hearts for cardiac transplantation. Over the last ten years however, only a few ex vivo perfusion systems have been developed for this application. While results have been promising, a system capable of facilitating multiple perfusion strategies on the same platform has not yet been realized. In this paper, the design, development and testing of a novel and modular ex vivo perfusion system is described...
December 23, 2017: Journal of Medical Systems
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