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langendorff heart perfusion system

Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning (RIPC) treatment strategy is a breakthrough in the field of cardiovascular pharmacology as it has the potential to attenuate myocardial ischemia-reperfusion injury. However, the underlying intracellular pathways have not been widely explored. The present study intends to explore the possible role of TRPV1 channels in mediating remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 cycles in succession) was delivered by tying the blood pressure cuff at the inguinal level of the rat...
October 17, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Justin Judd, Jonathan Lovas, Guo N Huang
Cultured cardiomyocytes can be used to study cardiomyocyte biology using techniques that are complementary to in vivo systems. For example, the purity and accessibility of in vitro culture enables fine control over biochemical analyses, live imaging, and electrophysiology. Long-term culture of cardiomyocytes offers access to additional experimental approaches that cannot be completed in short term cultures. For example, the in vitro investigation of dedifferentiation, cell cycle re-entry, and cell division has thus far largely been restricted to rat cardiomyocytes, which appear to be more robust in long-term culture...
2016: Journal of Visualized Experiments: JoVE
Sebastian Kötter, Malgorzata Kazmierowska, Christian Andresen, Katharina Bottermann, Maria Grandoch, Simone Gorressen, Andre Heinen, Jens M Moll, Jürgen Scheller, Axel Gödecke, Jens W Fischer, Joachim P Schmitt, Martina Krüger
RATIONALE: Myocardial infarction (MI) increases the wall stress in the viable myocardium and initiates early adaptive remodeling in the left ventricle to maintain cardiac output. Later remodeling processes include fibrotic reorganization that eventually leads to cardiac failure. Understanding the mechanisms that support cardiac function in the early phase post MI and identifying the processes that initiate transition to maladaptive remodeling are of major clinical interest. OBJECTIVE: To characterize MI-induced changes in titin-based cardiac myocyte stiffness and to elucidate the role of titin in ventricular remodeling of remote myocardium in the early phase after MI...
October 14, 2016: Circulation Research
Lara Testai, Alice Marino, Ilaria Piano, Vincenzo Brancaleone, Kengo Tomita, Lorenzo Di Cesare Mannelli, Alma Martelli, Valentina Citi, Maria C Breschi, Roberto Levi, Claudia Gargini, Mariarosaria Bucci, Giuseppe Cirino, Carla Ghelardini, Vincenzo Calderone
The endogenous gasotransmitter hydrogen sulphide (H2S) is an important regulator of the cardiovascular system, particularly of myocardial function. Moreover, H2S exhibits cardioprotective activity against ischemia/reperfusion (I/R) or hypoxic injury, and is considered an important mediator of "ischemic preconditioning", through activation of mitochondrial potassium channels, reduction of oxidative stress, activation of the endogenous "anti-oxidant machinery" and limitation of inflammatory responses. Accordingly, H2S-donors, i...
September 9, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Gina Sanchez, Daniela Berrios, Ivonne Olmedo, Javier Pezoa, Jaime A Riquelme, Luis Montecinos, Zully Pedrozo, Paulina Donoso
Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination...
2016: PloS One
Yingna Qiu, Ning Cong, Meng Liang, Yongqiang Wang, Jianshe Wang
In this paper, we investigated the multi-target effect of myricetin as a therapeutic for cardiovascular disease, using an acute ischemia/reperfusion-induced myocardial injury model to gain insight into its mechanism of action. The compound-target interaction profiles of myricetin were determined using a combination of text mining, chemometric and chemogenomic methods. The effect of myricetin on cardiac function was investigated by carrying out experiments in rats subjected to ischemia/reperfusion (I/R) using Langendorff retrograde perfusion technology...
August 2, 2016: Cardiovascular Toxicology
Hilbert Grievink, Galina Zeltcer, Benjamin Drenger, Eduard Berenshtein, Mordechai Chevion
Preconditioning (PC) procedures (ischemic or pharmacological) are powerful procedures used for attaining protection against prolonged ischemia and reperfusion (I/R) injury, in a variety of organs, including the heart. The detailed molecular mechanisms underlying the protection by PC are however, complex and only partially understood. Recently, an 'iron-based mechanism' (IBM), that includes de novo ferritin synthesis and accumulation, was proposed to explain the specific steps in cardioprotection generated by IPC...
2016: PloS One
Gai-Ge Chen, Jin-Bin Yan, Xu-Ming Wang, Ming-Zhi Zheng, Jian-Ping Jiang, Xin-Mei Zhou, Bin Cai, Yue-Liang Shen
In the present study, the alterations in uncoupling protein 2 (UCP2) expression following hypothermic preservation in rat hearts were investigated. Isolated rat hearts were preserved in Celsior solution for 3‑12 h followed by 60 min of reperfusion. The cardiac function was evaluated using the Langendorff perfusion system. UCP2 and silent mating type information regulation 2 homolog 1 (SIRT1) proteins were detected by western blot analysis. The ATP production and mitochondrial reactive oxygen species (ROS) levels were assessed...
August 2016: Molecular Medicine Reports
Yanqi Zhu, Caimei Zhang, Biyi Chen, Rong Chen, Ang Guo, Jiang Hong, Long-Sheng Song
BACKGROUNDS: Low serum cholesterol levels are associated with cardiac arrhythmias and poor prognosis in patients with chronic heart failure. However, the underlying mechanisms by which decreases in cholesterol content lead to cardiac dysfunction remain unclear. Multiple studies have implicated damage to cardiac transverse (T)-tubules as a key mediator of excitation-contraction (E-C) coupling dysfunction and heart failure. Since the T-tubule membrane system is enriched in cholesterol, we hypothesized that depletion of membrane cholesterol promotes T-tubule remodeling and E-C coupling dysfunction...
August 2016: Journal of Molecular and Cellular Cardiology
Puneet Kaur Randhawa, Amteshwar Singh Jaggi
Remote ischemic preconditioning is a well reported therapeutic strategy that induces cardioprotective effects but the underlying intracellular mechanisms have not been widely explored. The current study was designed to investigate the involvement of TRP and especially TRPV channels in remote hind limb preconditioning-induced cardioprotection. Remote hind limb preconditioning stimulus (4 alternate cycles of inflation and deflation of 5 min each) was delivered using a blood pressure cuff tied on the hind limb of the anesthetized rat...
August 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Jan-Michael Abicht, Tanja Axinja Jelena Mayr, Judith Jauch, Sonja Guethoff, Stefan Buchholz, Bruno Reichart, Andreas Bauer
Background Existing large-animal, ex vivo, cardiac perfusion models are restricted in their ability to establish an ischemia/reperfusion condition as seen in cardiac surgery or transplantation. Other working heart systems only challenge one ventricle or require a substantially larger priming volume. We describe a novel biventricular cardiac perfusion system with reduced priming volume. Methods Juvenile pig hearts were cardiopleged, explanted, and reperfused ex vivo after 150 minutes of cold ischemia. Autologous whole blood was used as perfusate (minimal priming volume 350 mL)...
April 4, 2016: Thoracic and Cardiovascular Surgeon
Hui Yang, Wanqing Sun, Nanhu Quan, Lin Wang, Dongyang Chu, Courtney Cates, Quan Liu, Yang Zheng, Ji Li
AMP-activated protein kinase (AMPK) signaling pathway plays a pivotal role in intracellular adaptation to energy stress during myocardial ischemia. Notch1 signaling in the adult myocardium is also activated in response to ischemic stress. However, the relationship between Notch1 and AMPK signaling pathways during ischemia remains unclear. We hypothesize that Notch1 as an adaptive signaling pathway protects the heart from ischemic injury via modulating the cardioprotective AMPK signaling pathway. C57BL/6J mice were subjected to an in vivo ligation of left anterior descending coronary artery and the hearts from C57BL/6J mice were subjected to an ex vivo globe ischemia and reperfusion in the Langendorff perfusion system...
May 15, 2016: Biochemical Pharmacology
Virginia Perez, Veronica D'Annunzio, Laura B Valdez, Tamara Zaobornyj, Silvina Bombicino, Tamara Mazo, Nadia Longo Carbajosa, Mariela M Gironacci, Alberto Boveris, Junichi Sadoshima, Ricardo J Gelpi
AIM: We evaluated the effect of thioredoxin1 (Trx1) system on postischemic ventricular and mitochondrial dysfunction using transgenic mice overexpressing cardiac Trx1 and a dominant negative (DN-Trx1) mutant (C32S/C35S) of Trx1. Langendorff-perfused hearts were subjected to 15 min of ischemia followed by 30 min of reperfusion (R). We measured left ventricular developed pressure (LVDP, mmHg), left ventricular end diastolic pressure (LVEDP, mmHg), and t63 (relaxation index, msec). Mitochondrial respiration, SERCA2a, phospholamban (PLB), and phospholamban phosphorylation (p-PLB) Thr17 expression (Western blot) were also evaluated...
July 10, 2016: Antioxidants & Redox Signaling
Virginia Perez, Verónica D Annunzio, Tamara Mazo, Timoteo Marchini, Lourdes Caceres, Pablo Evelson, Ricardo J Gelpi
Thioredoxin-1 (Trx-1) is part of an antioxidant system that maintains the cell redox homeostasis but their role on ischemic postconditioning (PostC) is unknown. The aim of this work was to determine whether Trx-1 participates in the cardioprotective mechanism of PostC in young, middle-aged, and old mice. Male FVB young (Y: 3 month-old), middle-aged (MA: 12 month-old), and old (O: 20 month-old) mice were used. Langendorff-perfused hearts were subjected to 30 min of ischemia and 120 min of reperfusion (I/R group)...
April 2016: Molecular and Cellular Biochemistry
Jiyoung Park, Yeon A Kim, Jeong Yeol Han, Sangkyu Jin, Seong-Ho Ok, Ju-Tae Sohn, Heon-Keun Lee, Young-Kyun Chung, Il-Woo Shin
BACKGROUND: Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. METHODS: We measured hemodynamic effects using a digital analysis system after Intralipid® and Lipofundin® MCT/LCT were infused into hearts hanging in a Langendorff perfusion system...
February 2016: Korean Journal of Anesthesiology
Eva Calderón-Sánchez, Ignacio Díaz, Antonio Ordóñez, Tarik Smani
AIMS: Urocortin-1 (Ucn-1) is an endogenous peptide that protects heart from ischemia and reperfusion (I/R) injuries. Ucn-1 is known to prevent cardiac cell death, but its role in the transcription of specific genes related to survival signaling pathway has not been fully defined. The aim of this study was to investigate the molecular signaling implicated in the improvement of cardiac myocytes survival induced by Ucn-1. METHODS AND RESULTS: Ucn-1 administration before ischemia and at the onset of reperfusion, in rat hearts perfused in Langendorff system, fully recovered heart contractility and other hemodynamic parameters...
2016: PloS One
Chao Yang, Honglai Xu, Lanjun Cai, Xiaoxiao Du, Yinan Jiang, Yong Zhang, Hongmin Zhou, Zhonghua Klaus Chen
OBJECTIVES: Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy metabolism and has been shown to be protective in ischaemia/reperfusion injury (IRI). We hypothesized that preactivation of AMPK with an activator before donor heart procurement could protect heart grafts from cold IRI. METHODS: Donor Sprague-Dawley rats were injected intravenously with AMPK activator 5-amino-imidazole-4-carboxamide ribonucleotide (AICAR) or vehicle 30 min before heart procurement...
May 2016: European Journal of Cardio-thoracic Surgery
Olivier Van Caenegem, Christophe Beauloye, Luc Bertrand, Sandrine Horman, Sophie Lepropre, Grégory Sparavier, Jonathan Vercruysse, Noëlla Bethuyne, Alain J Poncelet, Pierre Gianello, Peter Demuylder, Eric Legrand, Gwen Beaurin, Françoise Bontemps, Luc M Jacquet, Jean-Louis Vanoverschelde
OBJECTIVES: Cardiac transplantation using hearts from donors after circulatory death (DCD) is critically limited by the unavoidable warm ischaemia and its related unpredictable graft function. Inasmuch as hypothermic machine perfusion (MP) has been shown to improve heart preservation, we hypothesized that MP could enable the use of DCD hearts for transplantation. METHODS: We recovered 16 pig hearts following anoxia-induced cardiac arrest and cardioplegia. Grafts were randomly assigned to two different groups of 4-h preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il)...
May 2016: European Journal of Cardio-thoracic Surgery
M Germana Sanna, Kevin P Vincent, Emanuela Repetto, Nhan Nguyen, Steven J Brown, Lusine Abgaryan, Sean W Riley, Nora B Leaf, Stuart M Cahalan, William B Kiosses, Yasushi Kohno, Joan Heller Brown, Andrew D McCulloch, Hugh Rosen, Pedro J Gonzalez-Cabrera
The molecular pharmacology of the G protein-coupled receptors for sphingosine 1-phosphate (S1P) provides important insight into established and new therapeutic targets. A new, potent bitopic S1P3 antagonist, SPM-354, with in vivo activity, has been used, together with S1P3-knockin and S1P3-knockout mice to define the spatial and functional properties of S1P3 in regulating cardiac conduction. We show that S1P3 is a key direct regulator of cardiac rhythm both in vivo and in isolated perfused hearts. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol in vivo and S1P in isolated hearts induced a spectrum of cardiac effects, ranging from sinus bradycardia to complete heart block, as measured by a surface electrocardiogram in anesthetized mice and in volume-conducted Langendorff preparations...
January 2016: Molecular Pharmacology
M Kalbitz, M Huber-Lang, F Gebhard, P Ward
INTRODUCTION: In sepsis myocardial dysfunction is correlated with high mortality rates. Damage associated molecular patterns are released from cells during sepsis. Furthermore, the complement activation product C5a resulted in murine cardiomyocyte in defective contractility and relaxation, suggesting that interaction of C5a with its receptors is involved in the development of septic cardiomyopathy. We hypothesized that during sepsis interaction of C5a with its receptors contribute to cardiac dysfunction...
October 2015: Shock
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