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https://www.readbyqxmd.com/read/29239964/superior-efficacy-of-lipid-emulsion-infusion-over-serum-alkalinization-in-reversing-amitriptyline-induced-cardiotoxicity-in-guinea-pig
#1
Shogo Tsujikawa, Tadashi Matsuura, Kotaro Hori, Takashi Mori, Miyuki Kuno, Kiyonobu Nishikawa
BACKGROUND: Tricyclic antidepressants (TCAs) are a major cause of fatal drug poisoning due to their cardiotoxicity. Alkalinization by sodium bicarbonate (NaHCO3) administration, the first-line therapy for TCA-induced cardiotoxicity, can occasionally yield insufficient efficacy in severe cases. Because most TCAs are highly lipophilic, lipid emulsion may be more effective than alkalinization. However, it remains to be determined whether lipid emulsion is more beneficial than alkalinization in reversing amitriptyline-induced cardiotoxicity...
December 11, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29236952/impaired-cardiac-contractile-function-in-agat-knockout-mice-devoid-of-creatine-is-rescued-by-homoarginine-but-not-creatine
#2
Kiterie M E Faller, Dorothee Atzler, Debra J McAndrew, Sevasti Zervou, Hannah J Whittington, Jillian N Simon, Dunja Aksentijevic, Michiel Ten Hove, Chi-Un Choe, Dirk Isbrandt, Barbara Casadei, Jurgen E Schneider, Stefan Neubauer, Craig A Lygate
Aims: Creatine buffers cellular ATP via the creatine kinase reaction. Creatine levels are reduced in heart failure, but their contribution to pathophysiology is unclear. Arginine:glycine amidinotransferase (AGAT) in the kidney catalyses both the first step in creatine biosynthesis as well as homoarginine synthesis. AGAT-/- mice fed a creatine-free diet have a whole body creatine-deficiency. We hypothesised that AGAT-/- mice would develop cardiac dysfunction and rescue by dietary creatine would imply causality...
December 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29233660/negative-inotropic-effects-of-diadenosine-tetraphosphate-are-mediated-by-protein-kinase-c-and-phosphodiesterases-stimulation-in-the-rat-heart
#3
Nikolai Pakhomov, Ksenia Pustovit, Victoria Potekhina, Tatiana Filatova, Vladislav Kuzmin, Denis Abramochkin
Extracellular diadenosine polyphosphates (ApnA) are recently considered as an endogenous signaling compounds with transmitter-like activity which present in numerous tissues, including heart. It has been demonstrated previously that extracellular ApnA cause alteration of the heart functioning via purine receptors in different mammalian species. Nevertheless, principal intracellular pathways which underlie ApnA action in the heart remain unknown. In the present study the role of the P2Y-associated intracellular regulatory pathway in the mediation of diadenosine tetraphosphate (Ap4A) effects in the rat heart has been investigated for the first time...
December 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29218410/cardioprotective-effect-of-thyroid-hormone-is-mediated-by-at2-receptor-and-involves-nitric-oxide-production-via-akt-activation-in-mice
#4
Ivson Bezerra da Silva, Dayane Aparecida Gomes, Natalia Alenina, Michael Bader, Robson Augusto Dos Santos, Maria Luiza M Barreto-Chaves
Studies have demonstrated that thyroid hormone (T3) can precondition the heart against ischaemic injury and improve post-ischaemic recovery. This study investigated whether the AT2 receptor (AT2R) is involved in cardioprotection and the potential molecular mechanism responsible for this effect. Hyperthyroidism was induced in male wild-type (WT) and AT2R knockout (KO) mice by administering daily intraperitoneal injections of T3 (7 μg/100 g body weight) for 14 days. The mouse hearts were harvested and perfused with a Krebs-Henseleit solution at a constant flow in a Langendorff set-up...
December 7, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/29204375/modified-langendorff-technique-for-mouse-heart-cannulation-improved-heart-quality-and-decreased-risk-of-ischemia
#5
Negar Motayagheni
Oscar Langendorff introduced the first method for isolating a heart with contractile activity in 1895. Since then, the Langendorff method has remained a powerful technique in cardiac research and has led to major advances in medicine. The primary goal of the Langendorff method is to provide an isolated heart with oxygen and metabolites via a cannula inserted into the aorta. The Langendorff heart is a complex in vitro technique used primarily in pharmacological and physiological research that allows the evaluation of multiple cardiac hemodynamic parameters including, but not limited to, contractility and heart rate...
2017: MethodsX
https://www.readbyqxmd.com/read/29197997/class-effects-of-sglt2-inhibitors-in-mouse-cardiomyocytes-and-hearts-inhibition-of-na-h-exchanger-lowering-of-cytosolic-na-and-vasodilation
#6
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
December 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29196133/rapid-negative-inotropic-effect-induced-by-tnf-%C3%AE-in-rat-heart-perfused-related-to-pkc-activation
#7
B Jude, S Vetel, M A Giroux-Metges, J P Pennec
Myocardial depression, frequently observed in septic shock, is mediated by circulating molecules such as cytokines. TNF-α appears to be the most important pro-inflammatory cytokine released during the early phase of a septic shock. It was previously shown that TNF-α had a negative inotropic effect on myocardium. Now, the aim of this study was to investigate the effects of the activation of PKC by TNF-α on heart function, and to determine if this cytokine could induce a decrease of membrane excitability. Isolated rat hearts (n = 6) were perfused with Tyrode solution containing TNF-α at 20 ng/ml during 30 min by using a Langendorff technique...
November 29, 2017: Cytokine
https://www.readbyqxmd.com/read/29190815/aldose-reductase-modulates-acute-activation-of-mesenchymal-markers-via-the-%C3%AE-catenin-pathway-during-cardiac-ischemia-reperfusion
#8
Devi Thiagarajan, Karen O' Shea, Gopalkrishna Sreejit, Radha Ananthakrishnan, Nosirudeen Quadri, Qing Li, Ann Marie Schmidt, Kenneth Gabbay, Ravichandran Ramasamy
Aldose reductase (AR: human, AKR1B1; mouse, AKR1B3), the first enzyme in the polyol pathway, plays a key role in mediating myocardial ischemia/reperfusion (I/R) injury. In earlier studies, using transgenic mice broadly expressing human AKR1B1 to human-relevant levels, mice devoid of Akr1b3, and pharmacological inhibitors of AR, we demonstrated that AR is an important component of myocardial I/R injury and that inhibition of this enzyme protects the heart from I/R injury. In this study, our objective was to investigate if AR modulates the β-catenin pathway and consequent activation of mesenchymal markers during I/R in the heart...
2017: PloS One
https://www.readbyqxmd.com/read/29180358/nonclinical-cardiovascular-studies-of-prucalopride-a-highly-selective-5-hydroxytryptamine-4-receptor-agonist
#9
Kelly Conlon, Joris H De Maeyer, Chris Bruce, Jan A J Schuurkes, Lee Christie, James McRedmond, Katayoun Derakhchan, Paul R Wade
Patients with chronic constipation benefit from treatment with 5-hydroxytryptamine 4 (5-HT4) receptor agonists. However, the first-generation 5-HT4 receptor agonists cisapride and tegaserod were withdrawn from the market owing to rare cardiovascular adverse events, which were not 5-HT4-receptor-related, but due to the lack of selectivity of these drugs. Here we report the nonclinical cardiovascular profile of the selective 5-HT4 receptor agonist prucalopride. To assess its non-5-HT4 receptor-mediated effects on cardiovascular electrophysiological parameters, in vitro studies were performed in human ether-a-go-go-related gene-transfected cells, guinea pig ventricular myocytes and papillary muscle preparations, rabbit and dog Purkinje fibers, and the Langendorff rabbit heart...
November 27, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29172064/propofol-attenuates-myocardial-ischemia-reperfusion-injury-partly-through-inhibition-of-resident-cardiac-mast-cell-activation
#10
Xiaoqian Yu, Xiaotong Sun, Meng Zhao, Yonghao Hou, Jingxin Li, Jingui Yu, Yuedong Hou
Cardiac mast cell activation is involved in the process of myocardial ischemia reperfusion (I/R) injury and exacerbates myocardial infarction. Propofol, an anesthetic with antioxidant property, can reduce myocardial infarct size in I/R injury. The present study was designed to investigate whether propofol can attenuate myocardial I/R injury by inhibiting resident cardiac mast cell activation by a Langendorff model. Thirty rats were randomly assigned to 5 groups (n=6 per group): control group and four test groups (I/R, I/R+compound 48/80, I/R+propofol, I/R+compound 48/80+propofol)...
November 21, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29160855/effects-of-red-palm-oil-on-myocardial-antioxidant-enzymes-nitric-oxide-synthase-and-heart-function-in-spontaneously-hypertensive-rats
#11
Emma Katengua-Thamahane, Barbara Szeiffova Bacova, Iveta Bernatova, Matus Sykora, Vladimir Knezl, Jacques Van Rooyen, Narcis Tribulova
The purpose of this study was to investigate the effect of antioxidants rich red palm oil (RPO) supplementation on cardiac oxidative stress known as crucial factor deteriorating heart function in hypertension. 3-month-old, male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were fed standard rat chow without or with RPO (0.2 mL/day/5 weeks). General characteristic of rats were registered. Left ventricular tissue (LV) was used to determine expression of superoxide dismutases (SOD1, SOD2) and glutathione peroxidases (Gpx) as well as activity of nitric oxide synthase (NOS)...
November 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29159980/role-of-pi3k-in-myocardial-ischaemic-preconditioning-mapping-pro-survival-cascades-at-the-trigger-phase-and-at-reperfusion
#12
Xavier Rossello, Jaime A Riquelme, Sean M Davidson, Derek M Yellon
The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro-survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K-Akt, its negative regulator PTEN and other pro-survival proteins such as ERK and STAT3 in the context of IPC, C57BL/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion...
November 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29156723/effects-of-pharmacological-gap-junction-and-sodium-channel-blockade-on-s1s2-restitution-properties-in-langendorff-perfused-mouse-hearts
#13
Gary Tse, Tong Liu, Guangping Li, Wendy Keung, Jie Ming Yeo, Yin Wah Fiona Chan, Bryan P Yan, Yat Sun Chan, Sunny Hei Wong, Ronald A Li, Jichao Zhao, William K K Wu, Wing Tak Wong
Gap junctions and sodium channels are the major molecular determinants of normal and abnormal electrical conduction through the myocardium, however, their exact contributions to arrhythmogenesis are unclear. We examined conduction and recovery properties of regular (S1) and extrasystolic (S2) action potentials (APs), S1S2 restitution and ventricular arrhythmogenicity using the gap junction and sodium channel inhibitor heptanol (2 mM) in Langendorff-perfused mouse hearts (n=10). Monophasic action potential recordings obtained during S1S2 pacing showed that heptanol increased the proportion of hearts showing inducible ventricular tachycardia (0/10 vs...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155786/isolation-and-cultivation-of-adult-rat-cardiomyocytes
#14
Franziska Nippert, Rolf Schreckenberg, Klaus-Dieter Schlüter
In an intact heart, adjacent cells influence adult cardiomyocytes. With the method of isolation and cultivation of adult cardiomyocytes, a precise investigation of the behavior of these cells under specific treatments and environments is possible. This manuscript presents a protocol for successful isolation and cultivation of adult rat ventricular cardiomyocytes (ARVC). The rat is sacrificed by cervical dislocation under deep anesthesia. Then, the heart is extracted and the aorta is uncovered. Subsequently, perfusion on the Langendorff perfusion system with calcium depletion and collagenase treatment is performed...
October 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29151278/tetrahydrobiopterin-bh4-targeting-endothelial-nitric-oxide-synthase-as-a-potential-therapy-for-pulmonary-hypertension
#15
Bahaa N Francis, Maram Salameh, Rola Khamisy-Farah, Raymond Farah
PURPOSE: Pulmonary Hypertension (PH) is complex disease which is associated with endothelial and cardiac dysfunction. Tetrahydrobiopterin (BH4 ) regulates endothelial nitric oxide synthase (eNOS) to produce nitric oxide rather than superoxide which maintains normal endothelial and cardiac function. This study explores the therapeutic potential of BH4 in experimental PH. METHODS: Monocrotaline-induced PH in rats and Hph-1 deficiency in mice were used for animal experiments...
November 19, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29151120/biomechanical-stress-in-myocardial-infarctions-can-endothelin-1-and-growth-differentiation-factor-15-serve-as-immunohistochemical-markers
#16
M Falk, R Huhn, F Behmenburg, St Ritz-Timme, F Mayer
Myocardial infarctions go along with biomechanical stress, i.e. stretching of muscle fibres, and the expression of certain marker molecules. We tested if two of those markers, endothelin-1 (ET-1) and growth differentiation factor 15 (GDF-15), can be used as immunohistochemical markers for myocardial ischaemia/infarctions. The study included experiments with an animal model, the isolated perfused Langendorff heart, as well as the investigation of human tissue samples drawn during autopsies. The overall picture of our results showed that GDF-15 is very sensitive and expressed very fast, not only as a consequence of ischaemia/infarctions, but also under other circumstances...
November 18, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/29147482/combined-postconditioning-with-ischemia-and-cyclosporine-a-restore-oxidative-stress-and-histopathological-changes-in-reperfusion-injury-of-diabetic-myocardium
#17
Reza Badalzadeh, Seyed Mahmoud Tabatabaei, Mustafa Mohammadi, Arash Khaki, Dariush Mohammadnezhad
Objectives: Chronic diabetes impedes cardioprotection in reperfusion injury and hence protecting the diabetic heart would have important outcomes. In this study, we evaluated whether combined postconditioning with ischemia and cyclosporine-A can restore oxidative stress and histopathological changes in reperfusion injury of the diabetic myocardium. Materials and Methods: Streptozocin-induced diabetic hearts and nondiabetic controls in eight subgroups (with or without receiving ischemic-postconditioning (IPostC), cyclosporine-A, an inhibitor of mitochondrial permeability transition, or both of them) suffered from 30 min regional ischemia followed by 45 min reperfusion on an isolated-heart Langendorff system...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29130663/-capsaicin-alleviate-myocardial-ischemia-reperfusion-injury-through-attenuating-mitochondrial-oxidative-stress
#18
Juan-Xia Zhu, Ling-Heng Kong, Chao-Feng Zhang, Na Sun, Jin-Rui Chang, Yan Xu
OBJECTIVE: To investigate the role of capsaicin (CAP) in myocardial ischemia reperfusion injury and its underlying mechanisms. METHODS: Twentyfour adult male SD rats were randomized into 4 groups,namely the control group,ischemia reperfusion group,ischemia reperfusion with CAP group,and ischemia reperfusion with CAPZ and CAP group. Isolated rat hearts underwent Langendorff perfusion. Left ventricular enddiastolic pressure (LVEDP) andleft ventricular developed pressure (LVDP) was calculated to evaluate myocardial performance at 30 min of reperfusion...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29123207/atropine-augments-cardiac-contractility-by-inhibiting-camp-specific-phosphodiesterase-type-4
#19
Ruwan K Perera, Thomas H Fischer, Michael Wagner, Matthias Dewenter, Christiane Vettel, Nadja I Bork, Lars S Maier, Marco Conti, Juergen Wess, Ali El-Armouche, Gerd Hasenfuß, Viacheslav O Nikolaev
Atropine is a clinically relevant anticholinergic drug, which blocks inhibitory effects of the parasympathetic neurotransmitter acetylcholine on heart rate leading to tachycardia. However, many cardiac effects of atropine cannot be adequately explained solely by its antagonism at muscarinic receptors. In isolated mouse ventricular cardiomyocytes expressing a Förster resonance energy transfer (FRET)-based cAMP biosensor, we confirmed that atropine inhibited acetylcholine-induced decreases in cAMP. Unexpectedly, even in the absence of acetylcholine, after G-protein inactivation with pertussis toxin or in myocytes from M2- or M1/3-muscarinic receptor knockout mice, atropine increased cAMP levels that were pre-elevated with the β-adrenergic agonist isoproterenol...
November 9, 2017: Scientific Reports
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
#20
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
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