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https://www.readbyqxmd.com/read/29046334/the-organic-anion-transporter-slco2a1-constitutes-the-core-component-of-the-maxi-cl-channel
#1
Ravshan Z Sabirov, Petr G Merzlyak, Toshiaki Okada, Md Rafiqul Islam, Hiromi Uramoto, Tomoko Mori, Yumiko Makino, Hiroshi Matsuura, Yu Xie, Yasunobu Okada
The maxi-anion channels (MACs) are expressed in cells from mammals to amphibians with ~60% exhibiting a phenotype called Maxi-Cl. Maxi-Cl serves as the most efficient pathway for regulated fluxes of inorganic and organic anions including ATP However, its molecular entity has long been elusive. By subjecting proteins isolated from bleb membranes rich in Maxi-Cl activity to LC-MS/MS combined with targeted siRNA screening, CRISPR/Cas9-mediated knockout, and heterologous overexpression, we identified the organic anion transporter SLCO2A1, known as a prostaglandin transporter (PGT), as a key component of Maxi-Cl...
October 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29045568/loss-of-protein-kinase-novel-1-pkn1-is-associated-with-mild-systolic-and-diastolic-contractile-dysfunction-increased-phospholamban-thr17-phosphorylation-and-exacerbated-ischaemia-reperfusion-injury
#2
Asvi A Francois, Kofo Obasanjo-Blackshire, James E Clark, Andrii Boguslavskyi, Mark R Holt, Peter Parker, Michael S Marber, Richard J Heads
Aims: PKN1 is a stress-responsive protein kinase acting downstream of small GTP-binding proteins of the Rho/Rac family. The aim was to determine its role in endogenous cardioprotection. Methods and Results: Hearts from PKN1 knockout (KO) or wild type (WT) littermate control mice were perfused in Langendorff mode and subjected to global ischemia and reperfusion (I/R). Myocardial infarct size was doubled in PKN1 KO hearts compared to WT hearts. PKN1 was basally phosphorylated on the activation loop Thr778 PDK1 target site which was unchanged during I/R...
October 16, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29042254/cardiac-sodium-channel-antagonism-translation-of-preclinical-in-vitro-assays-to-clinical-qrs-prolongation
#3
Stephen Jenkinson, Asser Bassyouni, Jason Cordes, Bernard Fermini, Donglin Guo, David M Potter, David S Ramirez, Jill Steidl-Nichols, Sunny Sun, Todd Wisialowski
INTRODUCTION: Cardiac sodium channel antagonists have historically been used to treat cardiac arrhythmias by preventing the reentry of the electrical impulse that could occur following myocardial damage. However, clinical studies have highlighted a significant increase in mortality associated with such treatment. Cardiac sodium channel antagonist activity is now seen as an off-target pharmacology that should be mitigated during the drug development process. The aim of this study was to examine the correlation between in vitro/ex vivo assays that are routinely used to measure Nav1...
October 14, 2017: Journal of Pharmacological and Toxicological Methods
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
#4
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/29039314/effects-of-puerarin-on-lipopolysaccharide-induced-myocardial-dysfunction-in-isolated-rat-hearts
#5
Zhang Shaojun, Xu Yanyan, Chen Jian, Zheng Xia, Fang Qiang, Jiang Saiping
Myocardial dysfunction is a serious complication induced by sepsis. Puerarin is an oriental medicine that possesses therapeutic benefits for cardiovascular diseases. The aim of this study was to evaluate the anti-myocardial dysfunction effects of puerarin in isolated rat hearts induced by lipopolysaccharide- and compare the myocardial protective effects between the different concentrations of puerarin. Isolated hearts were attached to a Langendorff apparatus and perfused with lipopolysaccharide (LPS) and different concentrations of puerarin...
July 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29038355/isolated-heart-model-demonstrates-evidence-of-contractile-and-diastolic-dysfunction-in-right-ventricles-from-rats-with-sugen-hypoxia-induced-pulmonary-hypertension
#6
Evandro M Neto-Neves, Andrea L Frump, Alexandra Vayl, Jeffrey A Kline, Tim Lahm
Although extensively used for the study of left ventricular function, limited experience exists with the isolated heart model in the evaluation of right ventricular (RV) function. In particular, no published experience exists with this tool in sugen/hypoxia-induced pulmonary hypertension (SuHx-PH), a frequently used model of severe and progressive PH We sought to characterize markers of RV contractile and diastolic function in SuHx-PH and to establish their relationship with markers of maladaptive RV remodeling...
October 2017: Physiological Reports
https://www.readbyqxmd.com/read/29034199/cardioprotective-effects-of-achillea-wilhelmsii-on-the-isolated-rat-heart-in-ischemia-reperfusion
#7
M Mahmoudabady, M Lashkari, S Niazmand, M Soukhtanloo
CONTEXT: There are some reports about protective effects of Achillea on the heart. OBJECTIVE: We investigated the effect of Achillea wilhelmsii extract on cardiac function during ischemia-reperfusion (I/R) injury in the isolated rat heart. MATERIALS AND METHODS: 60 male Wistar rats were randomly divided into 6 groups; 1: Control group, 2: Control-ischemia (CI) 3: vitamin C (10 mg/kg), 4-6: Extract groups (E 100, E 200 and E 400 mg/kg). The animals received normal saline, vitamin C or A...
October 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29027245/epac-induced-ryanodine-receptor-type-2-activation-inhibits-sodium-currents-in-atrial-and-ventricular-murine-cardiomyocytes
#8
Haseeb Valli, Shiraz Ahmad, Sujan Sriharan, Lydia D Dean, Andrew A Grace, Kamalan Jeevaratnam, Hugh R Matthews, Christopher L-H Huang
Acute RyR2 activation by exchange protein directly activated by cAMP (Epac) reversibly perturbs myocyte Ca(2+) homeostasis, slows myocardial action potential conduction, and exerts pro-arrhythmic effects. Loose patch-clamp studies, preserving in vivo extracellular and intracellular conditions, investigated Na(+) current in intact cardiomyocytes in murine atrial and ventricular preparations following Epac activation. Depolarising steps to varying test voltages activated typical voltage-dependent Na(+) currents...
October 12, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29016731/electrical-coupling-between-ventricular-myocytes-and-myofibroblasts-in-the-infarcted-mouse-heart
#9
Michael Rubart, Wen Tao, Xiao-Long Lu, Simon J Conway, Sean P Reuter, Shien-Fong Lin, Mark H Soonpaa
Aims: Recent studies have demonstrated electrotonic coupling between scar tissue and the surrounding myocardium in cryoinjured hearts. However, the electrical dynamics occurring at the myocyte-nonmyocyte interface in the fibrotic heart remain undefined. Here, we sought to develop an assay to interrogate the nonmyocyte cell type contributing to heterocellular coupling and to characterize, on a cellular scale, its voltage response in the infarct border zone of living hearts. Methods and results: We used two-photon laser scanning microscopy in conjunction with a voltage-sensitive dye to record transmembrane voltage changes simultaneously from cardiomyocytes and adjoined nonmyocytes in Langendorff-perfused mouse hearts with healing myocardial infarction...
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29016714/low-energy-defibrillation-with-nanosecond-electric-shocks
#10
Frency Varghese, Johanna U Neuber, Fei Xie, Jonathan M Philpott, Andrei G Pakhomov, Christian W Zemlin
Aims: Reliable defibrillation with reduced energy deposition has long been the focus of defibrillation research. We studied the efficacy of single shocks of 300 nanosecond duration in defibrillating rabbit hearts as well as the tissue damage they may cause. Methods and Results: New Zealand white rabbit hearts were Langendorff-perfused and two planar electrodes were placed on either side of the heart. Shocks of 300 nanosecond duration and 0.3-3 kV amplitude were generated with a transmission line generator...
August 29, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28988521/the-cardioprotective-effect-of-rosmarinic-acid-on-acute-myocardial-infarction-and-genes-involved-in-ca-2-homeostasis
#11
Somayeh Javidanpour, Mahin Dianat, Mohammad Badavi, Seyyed Ali Mard
Acute myocardial infarction (AMI) is a common cause of hospitalization and high mortality due to lethal arrhythmias. Sarcoplasmic reticulum Ca(2+) ATPase (sarcoplasmic reticulum Ca(2+) ATPase (SERCA)2) and ryanodine receptor (ryanodine receptor (RyR)2) regulate the cytosolic Ca(2+) ion concentration. Rosmarinic acid (RA) is one of the most common caffeic esters in Rosmarinus officinalis. The present study was conducted to test the hypothesis whether RA can protect cardiac function against AMI and arrhythmias induced by isoproterenol through the regulatory effect of SERCA2 and RyR2 gene expression...
October 8, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28971696/hydrogen-sulfide-ameliorated-l-name-induced-hypertensive-heart-disease-by-the-akt-enos-no-pathway
#12
Sheng Jin, Xu Teng, Lin Xiao, Hongmei Xue, Qi Guo, Xiaocui Duan, Yuhong Chen, Yuming Wu
Reductions in hydrogen sulfide (H2S) production have been implicated in the pathogenesis of hypertension; however, no studies have examined the functional role of hydrogen sulfide in hypertensive heart disease. We hypothesized that the endogenous production of hydrogen sulfide would be reduced and exogenous hydrogen sulfide would ameliorate cardiac dysfunction in N(ω)-nitro- L-arginine methyl ester ( L-NAME)-induced hypertensive rats. Therefore, this study investigated the cardioprotective effects of hydrogen sulfide on L-NAME-induced hypertensive heart disease and explored potential mechanisms...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28970285/calcium-dependent-arrhythmogenic-foci-created-by-weakly-coupled-myocytes-in-the-failing-heart
#13
Di Lang, Daisuke Sato, Yan Jiang, Kenneth S Ginsburg, Crystal M Ripplinger, Donald M Bers
Rationale: Intercellular uncoupling and Ca mishandling can initiate triggered ventricular arrhythmias. Spontaneous Ca release activates inward current which depolarizes membrane potential (Vm) and can trigger action potentials in isolated myocytes. However, cell-cell coupling in intact hearts limits local depolarization and may protect hearts from this arrhythmogenic mechanism. Traditional optical mapping lacks the spatial resolution to assess coupling of individual myocytes. Objective: We investigate local intercellular coupling in Ca-induced depolarization in intact hearts, using confocal microscopy to measure local Vm and intracellular [Ca(2+)] ([Ca]i) simultaneously...
October 2, 2017: Circulation Research
https://www.readbyqxmd.com/read/28967097/chronic-treatment-with-novel-nanoformulated-micelles-of-rapamycin-rapatar-protects-diabetic-heart-against-ischemia-reperfusion-injury
#14
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/28965207/phoenixin-14-detection-and-novel-physiological-implications-in-cardiac-modulation-and-cardioprotection
#15
C Rocca, F Scavello, M C Granieri, T Pasqua, N Amodio, S Imbrogno, A Gattuso, R Mazza, Maria Carmela Cerra, Tommaso Angelone
Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood-brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R)...
September 30, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28960529/pro-arrhythmic-atrial-phenotypes-in-incrementally-paced-murine-pgc1%C3%AE-hearts-effects-of-age
#16
Haseeb Valli, Shiraz Ahmad, James A Fraser, Kamalan Jeevaratnam, Christopher L-H Huang
Atrial arrhythmias, most commonly manifesting as atrial fibrillation (AF), represent a major clinical problem. AF incidences increase with both age and conditions associated with energetic dysfunction. Atrial arrhythmic phenotypes were compared in young (12-16 week) and aged (>52 week), WT and peroxisome proliferator receptor gamma co-activator 1β-deficient (Pgc-1β(-/-) ), Langendorff-perfused hearts, previously used to model mitochondrial energetic disorder. Electrophysiological explorations were performed using simultaneous whole-heart electrocardiogram and intracellular atrial action potential (AP) recordings...
September 27, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28958063/efficacy-of-esmolol-cardioplegia-during-hypothermic-ischaemia
#17
Dai Nishina, David J Chambers
OBJECTIVES: Cardioplegic arrest using a polarizing solution has been shown to have beneficial advantages for cardioprotection compared with depolarizing (potassium-based) arrest; most studies, however, have looked at normothermic ischaemia with short infusion intervals (every 10-15 min). This study examines the protective efficacy of an esmolol-based cardioplegia during hypothermic arrest, together with a prolonged infusion interval (30 min) for increased clinical feasibility. METHODS: Isolated Langendorff-perfused hearts were subjected to arrest with St Thomas' Hospital cardioplegia (STH2), or esmolol cardioplegia (single- or multidose infusion at 32°C) for 60-min, 90-min or 120-min global ischaemia at 32°C, and recovery of function (left ventricular developed pressure) measured...
September 2, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28955390/remote-ischemic-conditioning-by-effluent-collected-from-a-novel-isolated-hindlimb-model-reduces-infarct-size-in-an-isolated-heart-model
#18
Young Jin Youn, Byung-Su Yoo, Jung-Woo Son, Jun-Won Lee, Min-Soo Ahn, Sung Gyun Ahn, Jang-Young Kim, Seung-Hwan Lee, Junghan Yoon, Young Woo Eom, Ji-Eun Oh, Seong-Kyung Choi
BACKGROUND AND OBJECTIVES: Experimental protocols for remote ischemic conditioning (RIC) utilize models in which a tourniquet is placed around the hindlimb or effluent is collected from an isolated heart. In analyzing the humoral factors that act as signal transducers in these models, sampled blood can be influenced by systemic responses, while the effluent from an isolated heart might differ from that of the hindlimb. Thus, we designed a new isolated hindlimb model for RIC and tested whether the effluent from this model could affect ischemia/reperfusion (IR) injury and if the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways are involved in RIC...
September 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28947080/electromechanical-optical-mapping
#19
REVIEW
J Christoph, J Schröder-Schetelig, S Luther
Optical mapping is a widely used imaging technique for investigating cardiac electrophysiology in intact, Langendorff-perfused hearts. Mechanical contraction of cardiac tissue, however, may result in severe motion artifacts and significant distortion of the fluorescence signals. Therefore, pharmacological uncoupling is widely used to reduce tissue motion. Recently, various image processing algorithms have been proposed to reduce motion artifacts. We will review these technological developments. Furthermore, we will present a novel approach for the three-dimensional, marker-free reconstruction of contracting Langendorff-perfused intact hearts under physiological conditions...
September 22, 2017: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/28942508/role-of-inducible-nitric-oxide-synthase-in-myocardial-ischemia-reperfusion-injury-in-sleep-deprived-rats
#20
Sajad Jeddi, Asghar Ghasemi, Alireza Asgari, Amir Nezami-Asl
INTRODUCTION: REM sleep deprivation (SD) decreases tolerance of the rat heart to ischemia-reperfusion (IR) injury; the underlying mechanisms, however, are unknown. This study aimed at determining whether changes in iNOS, Bax, and Bcl-2 gene expression are involved in this detrimental effect. METHOD: SD was induced by flowerpot technique for a period of 4 days. This method is simple and able to induce sleep fragmentation which occurs as one of the sleep disorder symptoms in clinical conditions...
September 23, 2017: Sleep & Breathing, Schlaf & Atmung
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