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Christiane Jungen, Katharina Scherschel, Nadja I Bork, Pawel Kuklik, Christian Eickholt, Helge Kniep, Niklas Klatt, Stephan Willems, Viacheslav O Nikolaev, Christian Meyer
Since its invention in the late 19th century, the Langendorff ex vivo heart perfusion system continues to be a relevant tool for studying a broad spectrum of physiological, biochemical, morphological, and pharmacological parameters in centrally denervated hearts. Here, we describe a setup for the modulation of the intracardiac autonomic nervous system and the assessment of its influence on basic electrophysiology, arrhythmogenesis, and cyclic adenosine monophosphate (cAMP) dynamics. The intracardiac autonomic nervous system is modulated by the mechanical dissection of atrial fat pads-in which murine ganglia are located mainly-or by the usage of global as well as targeted pharmacological interventions...
May 22, 2018: Journal of Visualized Experiments: JoVE
Zhang Li, Zhenfeng Cheng, Yu Haifeng, Mengting Chen, Lifang Li
BACKGROUND: Acute myocardial infarction (AMI) is a server disease effecting a large population worldwide. The pathophysiological process of ischemic/reperfusion (I/R) plays an important role for heart tissue damage. VO-OHpic, a PTEN inhibitor, has been demonstrated to be cardiac protective in sudden cardiac arrest models, but its role in AMI remains unclear. METHODS: An isolated AMI model was induced by dissecting the rat heart in a Langendorff system. Cardiac myocytes were extracted and induced ischemia in vitro...
July 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Carol M Makepeace, Alejandro Suarez-Pierre, Evelyn M Kanter, Richard B Schuessler, Colin G Nichols, Jennifer S Lawton
BACKGROUND: Adenosine triphosphate-sensitive potassium (KATP ) channel openers have been found to be cardioprotective in multiple animal models via an unknown mechanism. Mouse models allow genetic manipulation of KATP channel components for the investigation of this mechanism. Mouse Langendorff models using 30 min of global ischemia are known to induce measurable myocardial infarction and injury. Prolongation of global ischemia in a mouse Langendorff model could allow the determination of the mechanisms involved in KATP channel opener cardioprotection...
July 2018: Journal of Surgical Research
Jan Doul, Dana Miková, Marcela Rašková, Ivana Ošťádalová, Hana Maxová, Bohuslav Ošťádal, Zuzana Charvátová
Cardioprotective effect of ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) in adult hearts is mediated by mitochondrial-K-ATP channels and nitric oxide (NO). During early developmental period, rat hearts exhibit higher resistance to ischemia-reperfusion (I/R) injury and their resistance cannot be further increased by IPC or IPoC. Therefore, we have speculated, whether mechanisms responsible for high resistance of neonatal heart may be similar to those of IPC and IPoC. To test this hypothesis, rat hearts isolated on days 1, 4, 7, and 10 of postnatal life were perfused according to Langendorff...
May 25, 2018: Molecular and Cellular Biochemistry
Emily Allen, John H Coote, Blair D Grubb, Trevor Fc Batten, Dainius H Pauza, G André Ng, Kieran E Brack
BACKGROUND: The intrinsic cardiac nervous system (ICNS) is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function. OBJECTIVE: To provide a picture of the neurotransmitter/neuromodulator profile of the rabbit ICNS and determine the action of spatially divergent ganglia on cardiac electrophysiology. METHODS: Nicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff perfused rabbit heart...
May 22, 2018: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Martin Stroethoff, Iris Christoph, Friederike Behmenburg, Annika Raupach, Sebastian Bunte, Semra Senpolat, André Heinen, Markus W Hollmann, Alexander Mathes, Ragnar Huhn
Activation of melatonin receptors induces cardioprotection. Mitochondrial potassium channels (mKCa and mKATP) are involved in the signalling cascade of preconditioning. The melatonin receptor agonist ramelteon is an approved oral medication for treatment of insomnia but nothing is known about possible cardioprotective properties. We investigated whether (1) ramelteon induces cardioprotection mediated by the melatonin receptor; (2) this effect is concentration-dependent; and (3) mKCa- and/or mKATP-channels are critically involved in ramelteon-induced cardioprotection...
May 21, 2018: Journal of Cardiovascular Pharmacology
Shiraz Ahmad, Haseeb Valli, Karan R Chadda, James Cranley, Kamalan Jeevaratnam, Christopher L-H Huang
INTRODUCTION: Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors. MATERIALS AND METHODS: Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/- ) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA...
May 12, 2018: Mechanisms of Ageing and Development
Felix Mayer, Martin Falk, Ragnar Huhn, Friederike Behmenburg, Stefanie Ritz-Timme
Matrixmetalloproteinases (MMP) 2 and 9 as well as tissue inhibitor of metalloproteinases (TIMP) 1 were tested as markers of myocardial early ischemia/infarctions. Experiments with an animal model, the isolated Langendorff heart, and analysis of human tissue samples drawn during autopsies were performed. Results of the experiments with the Langendorff model implied that the detectable amount of the markers might increase early after the onset of ischemia, in less than one hour, under ideal conditions. The results of the examined human cases showed that MMP-2 is constantly detectable in human myocardial tissue with an increased amount in case of an infarction with longer survival times...
April 27, 2018: Forensic Science International
Rebeca E Nuñez, Sabzali Javadov, Nelson Escobales
Angiotensin II preconditioning (APC) involves an angiotensin II type 1 receptor (AT1-R)-dependent translocation of PKCε and survival kinases to the mitochondria leading to cardioprotection after ischemia-reperfusion (IR). However, the role that mitochondrial AT1-Rs and angiotensin II type 2 receptors (AT2-Rs) play in APC is unknown. We investigated whether pretreatment of Langendorff-perfused rat hearts with losartan (L, AT1-R blocker), PD 123,319 (PD, AT2-R blocker), or their combination (L + PD) affects mitochondrial AT1-R, AT2-R, PKCε, PKCδ, Akt, PKG-1, MAPKs (ERK1/2, JNK, p38), mitochondrial respiration, cardiac function, and infarct size (IS)...
May 10, 2018: Pflügers Archiv: European Journal of Physiology
Beihua Zhong, Jack Rubinstein, Shuangtao Ma, Donna H Wang
BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) channels in sensory nerves have anti-oxidative properties and counteract obesity and diabetes that are associated with diastolic dysfunction with preserved ejection fraction. We tested the hypothesis that TRPV1 knockout exacerbates high-fat diet (HFD)-induced glucose intolerance and diastolic dysfunction. METHOD: Trpv1-/- and wild-type (WT) mice were fed chow diet or HFD for 20 weeks. Then, we performed the intraperitoneal glucose tolerance test, measured the heart function through transthoracic echocardiography and Langendorff heart perfusion system, analyzed cardiac histology, and measured the myocardial superoxide production and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases...
May 3, 2018: Cardiovascular & Hematological Disorders Drug Targets
Gui-Zhen Yang, Fu-Shan Xue, Ya-Yang Liu, Hui-Xian Li, Qing Liu, Xu Liao
INTRODUCTION: The available evidence shows that perioperative oral thyroid hormone can significantly attenuate the postoperative decline in the serum hormone level and improve postoperative hemodynamic and prognostic parameters. However, there has been no study assessing the effects of preoperative oral different-dose thyroid hormone on serum hormone levels and myocardial ischemia-reperfusion injury (IRI) after cardiac surgery. METHODS: Forty-eight healthy Wistar rats, aged 35 days, were randomly allocated into six groups: Group BC, Group C and four pretreatment groups in which the rats were given levothyroxine-sodium of 10 μg, 20 μg, 40 μg and 80 μg/100 g...
April 1, 2018: Perfusion
Somayeh Javidanpour, Mahin Dianat, Mohammad Badavi, Seyyed Ali Mard
The incidence of arrhythmias is the main cause of high mortality after myocardial infarction (AMI). The aim of the present study was to determine whether the rosmarinic acid (RA) could reduce the stretch-induced arrhythmias (SIAs) related to overexpression of NCX1 after AMI. Adult male Sprague-Dawley rats were randomly allocated into six groups: Sham, MI (100 mg/kg of isoproterenol (Iso), subcutaneously, on two consecutive days), RA (30 mg/kg, orally, 14 days), and RA (10, 15 and 30 mg/kg, 14 days) + I...
March 30, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Zhengjiang Liu, Hua Liu, Zhi Huan Zeng
Background: The aim of this study was to investigate the potential mechanisms by which chronic unpredictable mild stress (CMS) might induce cardiovascular disease. Methods: Twenty male Sprague-Dawley rats (weighing 180-250 g) were divided into the CMS group (CMS for 3 weeks) and control group ( n = 10/group). Sucrose solution consumption, sucrose solution preference rate, and the open field test (horizontal and vertical movements) were used to confirm the establishment of the CMS model...
2018: BioMed Research International
Mariko Omatsu-Kanbe, Kengo Yoshioka, Ryo Fukunaga, Hironori Sagawa, Hiroshi Matsuura
The aim of this study was to establish a simple and reproducible antegrade perfusion method for isolating single viable mouse heart cells and to determine the standard practical protocols that are appropriate for mice of various ages. Antegrade perfusion was performed by injecting perfusate from near the apex of the left ventricle of the excised heart, the aorta of which was clamped, using an infusion pump. This could thoroughly perfuse the myocardium through the coronary circulation. All procedures were carried out on a prewarmed heater mat under a microscope, which allows for the processes of injection and perfusion to be monitored...
May 2018: Physiological Reports
Zhen Zhou, Shuang Ma, Jie Liu, Qiao-Rong Ji, Cheng-Zhu Cao, Xiao-Na Li, Feng Tang, Wei Zhang
The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected...
April 25, 2018: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Jum-Suk Ko, Shuai Guo, Jonathan Hassel, Patricia Celestino-Soper, Ty C Lynnes, James E Tisdale, James J Zheng, Stanley E Taylor, Tatiana Foroud, Michael D Murray, Richard J Kovacs, Xiaochun Li, Shien-Fong Lin, Zhenhui Chen, Matteo Vatta, Peng-Sheng Chen, Michael Rubart
The apamin-sensitive, small conductance, calcium-activated potassium (SK) current ( IKAS ) is encoded by KCNN genes. IKAS importantly contributes to cardiac repolarization in conditions associated with reduced repolarization reserve. To test the hypothesis that IKAS inhibition contributes to drug-induced long QT (diLQT) syndrome, we (1) screened for KCNN variants among patients with diLQT, (2) determined the properties of heterologously expressed wildtype and variant KCNN channels, and (3) determined if the 5-HT3 receptor antagonist ondansetron blocks IKAS ...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Takamitsu Tanaka, Masao Saotome, Hideki Katoh, Terumori Satoh, Prottoy Hasan, Hayato Ohtani, Hiroshi Satoh, Hideharu Hayashi, Yuichiro Maekawa
Accumulating evidence has revealed pivotal roles of glycogen synthase kinase-3β (GSK3β) inactivation on cardiac protection. Because the precise mechanisms of cardiac protection against ischemia/reperfusion (I/R) injury by GSK3β-inactivation remain elusive, we investigated the relationship between GSK3β-mediated mitochondrial hexokinase II (mitoHK-II; a downstream target of GSK3β) dissociation and mitochondrial permeability transition pore (mPTP) opening. In Langendorff-perfused hearts, GSK3β inactivation by SB216763 improved the left ventricular-developed pressure and retained mitoHK-II binding after I/R...
April 18, 2018: Journal of Physiological Sciences: JPS
Jila Haghi, Tahereh Eteraf-Oskouei, Moslem Najafi
Purpose: In the present study, postconditioning effect of fructose against ischemia/reperfusion (I/R)-induced arrhythmias and infarct size were investigated in isolated rat heart. Methods: The isolated hearts were divided into 7 groups, mounted on a Langendorff apparatus at constant pressure then subjected to 30 min zero flow global ischemia followed by 120 min reperfusion. In the control group, normal Krebs-Henseleit (K/H) solution was perfused into the hearts throughout the experiment. In two separate sets of experiments, the treatment groups received 12, 24 and 48 mM of fructose with/without normal glucose in K/H solution for 20 min at the beginning of reperfusion...
March 2018: Advanced Pharmaceutical Bulletin
Bin Qian, Yang Yang, Yusheng Yao, Yanling Liao, Ying Lin
Purpose: Sevoflurane preconditioning (SPC) can provide myocardial protective effects similar to ischemic preconditioning. However, the exact mechanism of SPC remains unclear. Previous studies indicate that vascular endothelial growth factor receptor 1 (VEGFR-1) is involved in ischemic preconditioning-mediated cardioprotection. This study was designed to determine the significance of VEGFR-1 signaling in SPC-mediated cardioprotection. Materials and methods: Myocardial ischemia-reperfusion (I/R) rat model was established using the Langendorff isolated heart perfusion apparatus...
2018: Drug Design, Development and Therapy
Xavier Rossello, Zhenhe He, Derek M Yellon
PURPOSE: To accurately estimate the effect size of both local or classic ischaemic preconditioning (IPC) and remote ischaemic preconditioning (RIPC) using a pooling data set of 91 animals. METHODS: We combined all the available mouse data collected from our Institute over the last 3 years regarding (i) local IPC (4 cycles of 5 min of global ischaemia/reperfusion injury, IRI, followed by 35-min ischaemia and 2-h reperfusion) in the Langendorff-isolated perfused mouse heart model and (ii) RIPC (3 cycles of 5 min of limb occlusion followed by 40-min ischaemia and 2-h reperfusion) in the in vivo mouse model...
April 2018: Cardiovascular Drugs and Therapy
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