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American Journal of Physiology. Heart and Circulatory Physiology

Per Martin Arvidsson, Johannes Töger, Marcus Carlsson, Katarina Steding-Ehrenborg, Gianni Pedrizzetti, Einar Heiberg, Hakan Arheden
Intracardiac blood flow is driven by hemodynamic forces that are exchanged between the blood and myocardium. Previous studies have been limited to 2D measurements or investigated only LV forces. Right ventricular forces and their mechanistic contribution to asymmetric redirection of flow in the RV have not been measured. We therefore aimed to quantify three-dimensional hemodynamic forces in both ventricles in a cohort of healthy subjects, using magnetic resonance imaging 4D flow measurements. 25 controls,14 elite endurance athletes, and two patients with left ventricular dyssynchrony were included...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Alexis V Mickelson, Sampath K Gollapudi, Murali Chandra
The present study investigated the functional consequences of the human hypertrophic cardiomyopathy (HCM) mutation, A28V, in cardiac troponin T (TnT). The A28V mutation is located within the N-terminus of TnT, a region known to be important for full activation of cardiac thin filaments. The functional consequences of the A28V mutation in TnT remain unknown. Given how α- and β-myosin heavy chain (MHC) isoforms differently alter the effect of the N-terminus of TnT, we hypothesized that the A28V-induced effects would be differently modulated by α- and β-MHC isoforms...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Shigemiki Omiya, Yosuke Omori, Manabu Taneike, Andrea Protti, Osamu Yamaguchi, Shizuo Akira, Ajay M Shah, Kazuhiko Nishida, Kinya Otsu
We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated.TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days post-operation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Marty D Spranger, Jasdeep Kaur, Javier A Sala-Mercado, Abhinav C Krishnan, Rania Abu-Hamdah, Alberto Alvarez, Tiago M Machado, Robert A Augustyniak, Donal S O'Leary
Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise is, in part, a function of muscle metaboreflex activation (MMA). As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction during mild treadmill exercise with MMA (elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Milad C El Hajj, Van K Ninh, Elia C El Hajj, Jessica M Bradley, Jason D Gardner
We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (SHAM), volume overloaded (ACF), SHAM treated with estrogen receptor antagonist, ICI 182,780 (SHAM+ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram and tissue samples were collected at 5 days and 6 weeks post-surgery...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Laura M G Meems, Hasan Mahmud, Hendrik Buikema, Jorg Tost, Sven Michel, Janny Takens, Rikst N Verkaik-Schakel, Inge Vreeswijk-Baudoin, Irene V Mateo-Leach, Torsten Plosch, Rudolf A de Boer
Vitamin D deficiency is one of the most common nutritional deficiencies worldwide. Maternal vitamin D deficiency is associated with increased susceptibility to hypertension in offspring but the reasons for this remain unknown. The aim of this study was to determine if parental vitamin D deficiency leads to altered DNA methylation in offspring that may relate to hypertension. Male and female Sprague-Dawley rats were fed a standard or vitamin D depleted diet. After 10 weeks, non-sibling rats were mated. The conceived pups received standard chow...
October 21, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Mark V Pinti, Quincy A Hathaway, John M Hollander
Heart failure (HF) is an endpoint resulting from a number of disease states. The prognosis for HF patients is poor with survival rates precipitously low. Energy metabolism is centrally linked to the development of HF and it involves the proteomic remodeling of numerous pathways, many of which are targeted to the mitochondrion. MicroRNA (miRNA) are noncoding RNAs that influence post-transcriptional gene regulation. MiRNA have garnered considerable attention for their ability to orchestrate changes to the transcriptome and ultimately the proteome, during HF...
October 14, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Stefano Fiorucci, Angela Zampella, Giuseppe Cirino, Mariarosaria Bucci, Eleonora Distrutti
Bile acids are end product of cholesterol metabolism generated in the liver and released in the intestine. In addition to their role in nutrient absorption, bile acids are increasingly recognized as regulatory signals which exert their function beyond the intestine by activating a network of membrane and nuclear receptors. The best characterized of these bile acid activated receptors, GPBAR1 (also known as TGR5) and the Farnesosid-x-receptor (FXR) have also been detected in the vascular system and their activation mediate the vasodilatory effects of bile acids in the systemic and splanchnic circulation...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Joshua A Beckman, Allison B Goldfine, Jane A Leopold, Mark A Creager
Oxidative stress is a key driver of vascular dysfunction in diabetes mellitus. Ebselen is a glutathione-peroxidase mimetic. A single-site, randomized, double-masked, placebo-controlled crossover trial in 26 subjects with either type 1 or type 2 diabetes to evaluate effects of high-dose ebselen (150 mg orally twice daily) administration on oxidative stress and endothelium-dependent vasodilation. Treatment periods were in random order of 4 weeks duration, with a 4 week washout between. Measures of oxidative stress included nitrotyrosine, plasma 8-isoprostanes, and the ratio of reduced-to-oxidized glutathione...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Xiaodong Huang, Tae Yun Kim, Gideon Koren, Bum-Rak Choi, Zhilin Qu
The occurrence of early afterdepolarizations (EADs) and increased dispersion of repolarization are two known factors for arrhythmogenesis in long QT syndrome. However, increased dispersion of repolarization tends to suppress EADs due to the source-sink effect, and thus how the two competing factors cause initiation of arrhythmias remains incompletely understood. Here we used optical mapping and computer simulation to investigate the mechanisms underlying spontaneous initiation of arrhythmias in type 2 long QT (LQT2) syndrome...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Victor M Niemeijer, Ruud F Spee, Thijs Schoots, Pieter F F Wijn, Hareld M Kemps
The extent and speed of transient skeletal muscle deoxygenation during exercise onset in chronic heart failure (CHF) patients is related to impairments of local O2 delivery and utilization. This study examined the physiological background of submaximal exercise performance in 19 moderately impaired CHF patients (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-minute exercise tests (bout 1 and 2) with measurements of pulmonary oxygen uptake kinetics, and SmO2 using near infrared (NIR) spatially resolved spectroscopy (SRS) at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and deoxygenation overshoot characteristics...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Jay S Naik, Jessica M Osmond, Benjimen R Walker, Nancy L Kanagy
Hydrogen sulfide (H2S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtansferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H2S production and are required for H2S-induced dilation. However, the signal transduction pathway activated by H2S within EC has not been elucidated. TRPV4 and large conductance Ca(2+)-activated K channels (BK channels) are expressed in EC. H2S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
William Spencer Cheyne, Alexandra Mackenzie Williams, Megan Harper, Neil Derek Eves
COPD is associated with dynamic lung hyperinflation (DH), increased pulmonary vascular resistance (PVR) and large increases in negative intrathoracic pressure (nITP). The individual and interactive effect of these stressors on left ventricular (LV) filling, emptying and geometry, and the role of direct ventricular interaction (DVI) in mediating these interactions have not been fully elucidated. Twenty healthy subjects were exposed to the following stressors alone and in combination: 1) inspiratory resistive loading of -20 cmH2O (nITP), 2) expiratory resistive loading to cause dynamic hyperinflation (DH), and 3) normobaric-hypoxia to increase PVR (hPVR)...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Erik H Van Iterson, Courtney Gramm, Nicholas R Randall, Thomas P Olson
Although pathophysiologic links between postmenopause and healthy aging remain unclear, both factors are associated with increased blood pressure and sympathetic nerve activity (SNA) in women. Activation of polymodal musculoskeletal neural afferents originating within adventia of venules modulates SNA and blood pressure control during exercise in healthy adults. We hypothesized transient subsystolic regional circulatory occlusion (RCO) during exercise sensitizes these afferents leading to augmented systemic vascular resistance (SVR) mediated increased mean arterial pressure (MAP) in postmenopause versus premenopause...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Donal Melanaphy, Christpher D Johnson, Maxim Kustov, Connall Watson, Lyudmyla Borysova, Theodore Burdyga, Alexander V Zholos
Transient receptor potential melastatin 8 (TRPM8) is the principal cold and menthol receptor channel. Characterized primarily for its cold sensing role in sensory neurons, it is expressed and functional in several non-neuronal tissues, including vasculature. We previously demonstrated that menthol causes vasoconstriction and vasodilatation in isolated arteries, depending on vascular tone. Here we investigated calcium's role in responses mediated by TRPM8 ligands in rat tail artery myocytes using patch-clamp electrophysiology and ratiometric Ca(2+) recording...
October 7, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Sofia-Iris Bibli, I Andreadou, Constantinos Glynos, Athanasia Chatzianastasiou, Dimitrios Toumpanakis, Spyros G Zakynthinos, Theodoros Vassilakopoulos, Efstathios K Iliodromitis, Andreas Papapetropoulos
Cigarette smoking is one of the risk factors for coronary artery disease. Although conditioning decreases infarct size in hearts from healthy animals, co-morbidities may render it ineffective. We investigated the effects of cigarette smoke (CS) exposure on intracellular myocardial signaling, infarct size after ischemia/reperfusion and the potential interference with ischemic conditioning. Exposure of mice to CS increased blood pressure, caused cardiac hypertrophy and up regulated the NOS/sGC/cGMP pathway. To test the effect of CS exposure on the endogenous cardioprotective mechanisms, mice were subjected to regional myocardial ischemia and reperfusion with no further intervention or application of preconditioning (PreC) or postconditioning (PostC)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Antoine Heni Chaanine, Erik Kohlbrenner, Scott I Gamb, Adam J Guenzel, Katherine A Klaus, Ahmed U Fayyaz, K Sreekumaran Nair, Roger J Hajjar, Margaret M Redfield
The Forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy and cell death in post-mitotic cells. Its role in regulating mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BNIP3, modulates mitochondrial morphology and function in HF. We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE) stressed adult cardiac myocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant-negative FOXO3a (AAV9...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Daniel R Machin, Heather L Clifton, Ryan S Garten, Jayson R Gifford, Russell S Richardson, D Walter Wray, Tracy M Frech, Anthony John Donato
Systemic sclerosis (SSc) is a rare, auto-immune disease characterized by debilitating fibrosis and vascular dysfunction, however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP), were determined at rest and during progressive static-intermittent handgrip exercise...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Rinku Pal, Qingen Ke, German A Pihan, Ayce Yesilaltay, Marsha L Penman, Li Wang, Chandramohan Chitraju, Peter M Kang, Monty Krieger, Olivier Kocher
The HDL receptor SR-BI mediates the transfer of cholesteryl esters from HDL to cells and controls HDL abundance and structure. Depending on the genetic background, loss of SR-BI causes hypercholesterolemia, anemia, reticulocytosis, splenomegaly, thrombocytopenia, female infertility and fatal coronary heart disease (CHD). The C-terminus of SR-BI (505QEAKL509) must bind to the cytoplasmic adaptor PDZK1 for normal hepatic -but not steroidogenic cell- expression of SR-BI protein. To determine if SR-BI's C-terminus is also required for normal protein levels in steroidogenic cells, we introduced into SR-BI's gene a 507Ala/STOP mutation that produces a truncated receptor (SR-BIΔCT)...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Sinead T J McDonagh, Anni Vanhatalo, Jonathan Fulford, Lee J Wylie, Stephen J Bailey, Andrew M Jones
We tested the hypothesis that dietary nitrate-rich beetroot juice (BR) supplementation could partially offset deteriorations in O(2) transport and utilization, and exercise tolerance, after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following the withdrawal of ~450 mL of whole blood. Before donation, all subjects consumed 7 x 70 mL of nitrate-depleted beetroot juice shots (PL) in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed 7 shots of either BR (each containing 6...
September 30, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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