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Journal of Cardiovascular Pharmacology

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https://www.readbyqxmd.com/read/28817484/levosimendan-in-acute-and-advanced-heart-failure-an-appraisal-of-the-clinical-database-and-evaluation-of-its-therapeutic-applications
#1
J Altenberger, F Gustafsson, V-P Harjola, K Karason, D Kindgen-Milles, M Kivikko, G Malfatto, Z Papp, J Parissis, P Pollesello, G Pölzl, C Tschöpe
The use of inotropes for correcting haemodynamic dysfunction in patients with congestive heart failure has been described over many decades. However, negative or insufficient data have been collected regarding the effects of cardiac glycosides, catecholamines and phosphodiesterase inhibitors on quality of life and survival. More recently, the calcium sensitizer and potassium channel-opener levosimendan has been proposed as a safer inodilator than traditional agents in some heart failure settings, such as Advanced Heart Failure...
August 15, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817483/time-course-study-on-left-ventricular-function-in-a-rabbit-model-of-ischemia-reperfusion-injury-with-morphine-preconditioning
#2
Baihua Zhao, Chengxiao Liu, Darong Pu, Shi Zeng, Xi Dai, Minghui Liu
AIMS: The study aimed to analyze the left ventricular longitudinal function in a rabbit model of myocardial ischemia-reperfusion with morphine preconditioning through strain rate imaging and evaluate the effect of morphine preconditioning. METHODS: A myocardial ischemia-reperfusion model was induced by occlusion and recanalization of the coronary artery in forty male New Zealand white rabbits, which were divided into a sham group, morphine group, and vehicle control group...
August 15, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817487/inhibiting-protein-tyrosine-phosphatase-1b-to-improve-regenerative-functions-of-endothelial-cells
#3
Yuan Wang, Feng Yan, Wenjing Zhang, Shu Pang, Fan Jiang
Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor- and vascular endothelial growth factor receptor-dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration, and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817486/overcoming-clopidogrel-resistance-three-promising-novel-antiplatelet-drugs-developed-in-china
#4
Hong-Guang Xie, Yu-Meng Jia, Ting Tai, Jin-Zi Ji
Clopidogrel is one of the most frequently prescribed drugs worldwide; however, the presence of clopidogrel resistance and high susceptibility to genetic variations and drug interactions are facilitating the development of other antiplatelet drugs. To overcome clopidogrel resistance, several promising clopidogrel analogues have been developed in China, such as vicagrel (and its deuterated analogues), PLD-301, and W1. These novel chemical analogues are all characterized by much faster and more efficient bioconversion to clopidogrel thiolactone (or 2-oxo-clopidogrel, the precursor of clopidogrel active metabolite) in the intestine than clopidogrel through bypassing the first-step P450-mediated oxidation of clopidogrel in the liver...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28817485/anti-diabetic-drug-alogliptin-protects-the-heart-against-ischemia-reperfusion-injury-via-glp-1-receptor-dependent-and-independent-pathways-involving-no-production-in-rabbits
#5
Shinya Baba, Masamitsu Iwasa, Kenshi Higashi, Shingo Minatoguchi, Yoshihisa Yamada, Hiromitsu Kanamori, Masanori Kawasaki, Kazuhiko Nishigaki, Shinya Minatoguchi
GLP-1 has been reported to be cardioprotective against ischemia-reperfusion injury. We aimed to examine the effect of alogliptin, which may produce GLP-1, on ischemia-reperfusion injury and its mechanisms. Rabbits were fed a normal chow (control group) and a chow containing alogliptin (2 mg/kg/day: alogliptin-L group, and 20 mg/kg/day: alogliptin-H group) for 7 days. The rabbits underwent 30 min of coronary occlusion and 48 h of reperfusion. Exendin (9-39) (5 or 50μg/kg, i.v., alogliptin-H+exendin (9-39)-L group and alogliptin-H+exendin (9-39)-H group) or L-NAME(10 mg/kg, i...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28777256/the-p-407-induced-mouse-model-of-dose-controlled-hyperlipidemia-and-atherosclerosis-twenty-five-years-later
#6
Thomas P Johnston, Tatyana A Korolenko, Amirhossein Sahebkar
The poloxamer 407 (P-407) non-genetic, non-diet-induced mouse model of dose-controlled hyperlipidemia and atherosclerosis was first introduced in 1992. Dyslipidemia is produced in C57BL/6 mice of either sex following the intraperitoneal administration of P-407, which is a polyether-based nonionic surface-active-agent. Aortic atherosclerotic lesions begin to form after 1 month of repeated P-407 administration and obtain maximum size, numerical density, and human-like pathological features by 4 months. Our laboratory published a review of this model in 2004, although an update would seem both appropriate and timely based on new findings since 2004...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28777255/endogenous-and-agonist-induced-opening-of-mitochondrial-big-vs-small-ca2-sensitive-k-channels-on-cardiac-cell-and-mitochondrial-protection
#7
David F Stowe, Meiying Yang, James S Heisner, Amadou K S Camara
Both big (BKCa) and small (SKCa) conductance Ca-sensitive K channels are present in mammalian cardiac cell mitochondria (m). We used pharmacological agonists and antagonists of BKCa and SKCa channels to examine the importance of endogenous opening of these channels and the relative contribution of either or both of these channels to protect against contractile dysfunction and reduce infarct size after ischemia reperfusion (IR) injury through a mitochondrial protective mechanism. Following global cardiac IR injury of ex vivo perfused guinea pig hearts we found the following: both agonists NS1619 (for BKCa) and DCEB (for SKCa) improved contractility; BKCa antagonist paxilline (PAX) alone or with SKCa antagonist NS8593 worsened contractility and enhanced infarct size; both antagonists PAX and NS8593 obliterated protection by their respective agonists; BKCa and SKCa antagonists did not block protection afforded by SKCa and BKCa agonists, respectively; and all protective effects by the agonists were blocked by scavenging superoxide anions (O2) with TBAP...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28777254/t-type-and-l-type-calcium-channel-blockers-for-the-treatment-of-cardiac-iron-overload-an-update
#8
Sirinart Kumfu, Siriporn C Chattipakorn, Nipon Chattipakorn
In thalassemia patients iron overload cardiomyopathy is a major cause of cardiac dysfunction and mortality. Despite many advances in the development of new iron chelating agents, heart failure still occurs in some patients and can lead to an increase in mortality rate. Recently, potential novel therapeutic strategies in the treatment of these patients have focused on L-type and T-type calcium channel blockers. These two channels have been reported as being the main routes for cardiac iron uptake under conditions of iron overload...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28777253/mir-30e-attenuates-isoproterenol-induced-cardiac-fibrosis-through-suppressing-snai1-tgf%C3%AE-signaling
#9
Zhang Wenqi, Chang Hong, Zhang Hexun, Zhang Lei
BACKGROUND: MicroRNAs (miRNAs) are a class of small RNA molecules that inhibit protein expression through either degradation of mRNA or interference with protein translation. Our previous work suggested an involvement of miR-30e in myocardial fibrosis; however, the exact role of miR-30e in the pathogenesis of cardiac fibrosis and the underlying mechanisms are not known. METHODS: Male Sprague Dawley rats were treated with isoproterenol to induce cardiac remodeling and fibrosis and treated with either miR-30e agomir (AG) or antagomir and respective controls...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28777252/n-methyl-d-aspartate-receptor-nmdar-driven-calcium-influx-potentiates-the-adverse-effects-of-myocardial-ischemia-reperfusion-injury-ex-vivo
#10
Zi-You Liu, Shou Hu, Qin-Wen Zhong, Cheng-Nan Tian, Hou-Mou Ma, Jun-Jian Yu
BACKGROUND: Despite the adverse effects of N-methyl-D-aspartate receptor (NMDAR) activity in cardiomyocytes, no study has yet examined the effects of NMDAR activity under ex vivo ischemic-reperfusion (I/R) conditions. Therefore, our aim was to comprehensively evaluate the effects of NMDAR activity through an ex vivo myocardial I/R rat model. METHODS: Isolated rat hearts were randomly segregated into six groups (n=20 in each group): (i) an untreated control group; (ii) a NMDA-treated control group; (iii) an untreated I/R group; (iv) an I/R+NMDA group treated with NMDA; (v) an I/R+NMDA+MK-801 group treated with NMDA and the NMDAR inhibitor MK-801; and (vi) an I/R+NMDA+[Ca]-free group treated with NMDA and [Ca]-free buffer...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28731891/white-wine-consumption-influences-inflammatory-phase-of-repair-following-myocardial-infarction-in-rats
#11
Nikola Ključević, Ana Marija Milat, Mia Grga, Ivana Mudnić, Mladen Boban, Ivica Grković
Effects of white wine consumption on the expression of inflammatory markers/mediators (MMP-2, MMP-9, NF-ĸB p65 and TGF-β1) in myocardial tissue following experimentally induced permanent myocardial ischemia was investigated. Male Sprague-Dawley rats were given either a combination of white wine and water or water only, for 28 days. After coronary ligation, animals were left to survive for 24 hours. Three representative areas: infarct/ischemic, peri-infarct/border zone and control/non-ischemic zones were analysed for expression of immunoreactivity by measuring threshold area % of signal density...
July 19, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28731890/metformin-exposure-during-pregnancy-and-lactation-did-not-cause-vascular-reactivity-alteration-in-adult-male-offspring
#12
Daniella R B S Novi, Simone Forcato, Camila B Vidigal, Guilherme H Loiola, Daniela C C Gerardin, Graziela S Ceravolo
Metformin has been used for the treatment of some metabolic diseases during gestation and the beneficial effects of metformin to the vascular system have been described in diabetic and obese animal models. Nevertheless, the long term consequences to the vascular system of offspring maternally exposed to metformin have not yet been characterized. Therefore, we want to test the hypothesis that gestational and lactational exposure to metformin would be safe for the vascular reactivity of male adult offspring. Wistar female rats were treated with metformin 293mg/kg/day, by gavage, from gestational day (GD) 0 to GD 21 (METG) or GD 0 until post natal day (PND) 21 (METGL)...
July 19, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28708714/sleep-medications-containing-melatonin-can-potentially-induce-ventricular-arrhythmias-in-structurally-normal-hearts-a-two-patient-report
#13
L J de Vries, T Géczy, T Szili-Torok
Idiopathic ventricular arrhythmias (IVAs) are relatively common in the general population and usually have a good prognosis. However, frequent PVCs can lower quality of life (in symptomatic cases) and can cause cardiomyopathy and sudden cardiac death. In this report, we demonstrate a novel trigger for IVAs. Melatonin use for treating sleep-disorders has increased significantly in recent years. We provide here the first human evidence of its pro-arrhythmic effect by presenting two patients (with normal myocardium) with symptomatic PVCs, while on melatonin...
July 13, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28708713/platelet-aggregation-in-direct-oral-factor-xa-inhibitors-treated-patients-with-atrial-fibrillation-a-pilot-study
#14
Peter Bánovčin, Ingrid Škorňová, Matej Samoš, Martin Schnierer, Tomáš Bolek, František Kovář, Ján Staško, Peter Kubisz, Marián Mokáň
BACKGROUND: Activated factor X (factor Xa) plays an important role in regulation of platelets. The aim of this study was to test the effect of direct oral factor Xa inhibitors - rivaroxaban and apixaban - on platelet aggregation in patients with non-valvular atrial fibrillation (NV-AF). PATIENTS AND METHODS: This single-centre pilot study enrolled 21 factor Xa inhibitors-treated (9 rivaroxaban-treated and 12 apixaban-treated) patients with NV-AF. The trough and peak samples of these patients were tested for adenosinediphosphate-induced (ADP), epinephrine-induced, and collagen-induced platelet aggregation with light transmission aggregometry (LTA), and with factor Xa-calibrated anti-Xa chromogenic analysis...
July 13, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28708712/extended-second-window-of-protection-of-sevoflurane-induced-preconditioning
#15
Friederike Behmenburg, Yvonne Boekholt, Patrick van Caster, Marianne Dorsch, André Heinen, Markus W Hollmann, Ragnar Huhn
Late preconditioning (LPC) can be induced by volatile anesthetics and initiates cardioprotection against ischemia/reperfusion injury for three to four days. We investigated the possibility to extend the time window of sevoflurane-induced LPC by repeated sevoflurane administration. An in vivo rat model of regional myocardial ischemia/reperfusion injury was used. Myocardial infarct size was determined by TTC staining at the end of the experiment. In the first series of experiments, male Wistar rats were randomized to five groups (each n=8)...
July 13, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28704306/reversal-of-ticagrelor-induced-arrhythmias-and-cheyne-stokes-respiration-with-aminophylline-infusion
#16
Lorenzo Conte, Nicola Riccardo Pugliese, Alberto Giannoni
Dyspnea and bradyarrhythmias are frequent adverse effects (AEs) of ticagrelor. AEs commonly occur within the first week of therapy, are dose related and usually mild, but sometimes they may cause drug discontinuation. Currently, the exact mechanisms of ticagrelor-related AEs have not been definitively explained. In addition to the prevalent theory of adenosine overload, other reasonable mechanisms like a direct central stimulation hypothesis was suggested. We present a case of incessant Cheyne-Stokes respiration associated with heart rate instability in patient with congestive heart failure (HF) and non-ST-segment elevation myocardial infarction (NSTEMI), supporting the use of aminophylline as a potential reversal agent of ticagrelor-related AEs...
July 12, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28662005/camkii-activation-promotes-cardiac-electrical-remodeling-and-increases-the-susceptibility-to-arrhythmia-induction-in-high-fat-diet-fed-mice-with-hyperlipidemia-conditions
#17
Peng Zhong, Dajun Quan, Yan Huang, He Huang
BACKGROUND: Obesity/hyperlipidemia is closely related to both atrial and ventricular arrhythmias. CaMKII, a multifunctional serine/threonine kinase, has been involved in cardiac arrhythmias of different etiology. However, its role in obesity/hyperlipidemia-related cardiac arrhythmia is unexplored. The aim of the present study was to determine the involvement of CaMKII in the process. METHODS: Adult male APOE-/- mice were fed a high-fat diet (HFD), administrated with KN93 (10mg/kg/2d), a specific inhibitor of CaMKII...
July 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28654510/late-ina-inhibition-as-an-antiarrhythmic-strategy
#18
Alexander Burashnikov
Late sodium channel current (late INa) is considered to be an anti-arrhythmic target. The prime anti-arrhythmic mechanisms of late INa inhibition have been suggested to be 1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (via reduction of Cai secondary to the decrease of intracellular sodium [Nai]) and 2) normalization of repolarization. Endogenous late INa is a small current and acceleration of heart rate decreases late INa density. Late INa influx may significantly contribute to Nai loading, but it appears to largely occur in the combined conditions of augmented late INa density, bradycardia, and prolonged repolarization...
June 22, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28654509/pi3ks-in-diabetic-cardiomyopathy
#19
Mingchuan Li, Alessandra Murabito, Alessandra Ghigo, Emilio Hirsch
Diabetic cardiomyopathy is a heart disease in diabetic patients, identified as ventricular dysfunction in the absence of coronary artery disease and hypertension. The molecular mechanisms underlying diabetic cardiomyopathy are still poorly understood. The protein and lipid kinase phosphoinositide 3-kinases (PI3Ks) have been suggested to regulate cardiac injury during diabetes. In this review, we will summarize the role of different PI3K isoforms and of their downstream signaling in the pathogenesis of diabetic cardiomyopathy, including the regulation of cardiac metabolism, contractility, hypertrophy, myocardial cell death and inflammation...
June 22, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28640039/levosimendan-prevents-and-reverts-right-ventricular-failure-in-experimental-pulmonary-arterial-hypertension
#20
Mona Sahlholdt Hansen, Asger Andersen, Sarah Holmboe, Jacob Gammelgaard Schultz, Steffen Ringgaard, Ulf Simonsen, Chris Happé, Harm Jan Bogaard, Jens Erik Nielsen-Kudsk
BACKGROUND: We investigated whether chronic levosimendan treatment can prevent and revert right ventricular (RV) failure and attenuate pulmonary vascular remodelling in a rat model of pulmonary arterial hypertension (PAH). METHODS AND RESULTS: PAH was induced in rats by exposure to SU5416 and hypoxia (SuHx). The rats were randomized to levosimendan (3 mg/kg/day) initiated before SuHx (n=10, PREV), levosimendan started 6 weeks after SuHx (n=12, REV), or vehicle treatment (n=10, VEH)...
June 19, 2017: Journal of Cardiovascular Pharmacology
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