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Frank Starling

Jenna Scotcher, Oleksandra Prysyazhna, Andrii Boguslavskyi, Kornel Kistamas, Natasha Hadgraft, Eva D Martin, Jenny Worthington, Olena Rudyk, Pedro Rodriguez Cutillas, Friederike Cuello, Michael J Shattock, Michael S Marber, Maria R Conte, Adam Greenstein, David J Greensmith, Luigi Venetucci, John F Timms, Philip Eaton
The Frank-Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16-a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis...
October 26, 2016: Nature Communications
Ka Eul Kim, Hyun-Jin Tae, Petrashevskaya Natalia, Jae-Chul Lee, Ji Hyeon Ahn, Joon Ha Park, In Hye Kim, Taek Geun Ohk, Chan Woo Park, Jun Hwi Cho, Moo-Ho Won
OBJECTIVE: Combination of β1-adrenergic receptor (AR) blockade and β2-AR activation might be a potential novel therapy for treating heart failure. However, use of β-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β1- and β2-ARs (β1- and β2-AR TG mice, respectively)...
September 2016: Clin Exp Emerg Med
María S Brea, Romina G Díaz, Daiana S Escudero, Claudia I Caldiz, Enrique L Portiansky, Patricio E Morgan, Néstor G Pérez
BACKGROUND: Myocardial stretch increases force biphasically: the Frank-Starling mechanism followed by the slow force response (SFR). Based on pharmacological strategies, we proposed that epidermal growth factor (EGF) receptor (EGFR or ErbB1) activation is crucial for SFR development. Pharmacological inhibitors could block ErbB4, a member of the ErbB family present in the adult heart. We aimed to specifically test the role of EGFR activation after stretch, with an interference RNA incorporated into a lentiviral vector (small hairpin RNA [shRNA]-EGFR)...
October 15, 2016: Journal of the American Heart Association
Jia-Ling Ruan, Nathaniel L Tulloch, Maria V Razumova, Mark Saiget, Veronica Muskheli, Lil Pabon, Hans Reinecke, Michael Regnier, Charles E Murry
BACKGROUNDS: -Tissue engineering enables the generation of functional human cardiac tissue using cells derived in vitro in combination with biocompatible materials. Human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes provide a cell source for cardiac tissue engineering; however, their immaturity limits their potential applications. Here we sought to study the effect of mechanical conditioning and electrical pacing on the maturation of hiPSC-derived cardiac tissues. METHODSS: -Cardiomyocytes derived from hiPSCs were used to generate collagen-based bioengineered human cardiac tissue...
October 13, 2016: Circulation
Mithras Kuipers, Michael Richter, Daan Scheepers, Maarten A Immink, Elio Sjak-Shie, Henk van Steenbergen
The ability to adjust attentional focus to varying levels of task demands depends on the adaptive recruitment of cognitive control processes. The present study investigated for the first time whether the mobilization of cognitive control during response-conflict trials in a flanker task is associated with effort-related sympathetic activity as measured by changes in the RZ-interval at a single-trial level, thus providing an alternative to the pre-ejection period (PEP) which can only be reliably measured in ensemble-averaged data...
October 10, 2016: International Journal of Psychophysiology
Kevin L Sack, Brian Baillargeon, Gabriel Acevedo-Bolton, Martin Genet, Nuno Rebelo, Ellen Kuhl, Liviu Klein, Georg M Weiselthaler, Daniel Burkhoff, Thomas Franz, Julius M Guccione
PURPOSE: Heart failure is a worldwide epidemic that is unlikely to change as the population ages and life expectancy increases. We sought to detail significant recent improvements to the Dassault Systèmes Living Heart Model (LHM) and use the LHM to compute left ventricular (LV) and right ventricular (RV) myofiber stress distributions under the following 4 conditions: (1) normal cardiac function; (2) acute left heart failure (ALHF); (3) ALHF treated using an LV assist device (LVAD) flow rate of 2 L/min; and (4) ALHF treated using an LVAD flow rate of 4...
October 10, 2016: International Journal of Artificial Organs
Daniel Gagnon, Steven A Romero, Hai Ngo, Satyam Sarma, William K Cornwell, Paula Y S Poh, Douglas Stoller, Benjamin D Levine, Craig G Crandall
During heat stress, stroke volume is maintained in young adults despite reductions in cardiac filling pressures. This is achieved by a general augmentation of cardiac function, highlighted by a left and upward shift of the Frank-Starling relation. In contrast, healthy aged adults are unable to maintain stroke volume during heat stress. We hypothesized that this would be associated with a lack of shift in the Frank-Starling relation. Frank-Starling relations were examined in 11 aged [69 ± 4 (SD) yr, 4 men/7 women] and 12 young (26 ± 5 yr, 6 men/6 women) adults during normothermic and heat stress (1...
October 1, 2016: Journal of Applied Physiology
Boon C Ng, Peter A Smith, Frank Nestler, Daniel Timms, William E Cohn, Einly Lim
The successful clinical applicability of rotary left ventricular assist devices (LVADs) has led to research interest in devising a total artificial heart (TAH) using two rotary blood pumps (RBPs). The major challenge when using two separately controlled LVADs for TAH support is the difficulty in maintaining the balance between pulmonary and systemic blood flows. In this study, a starling-like controller (SLC) hybridized with an adaptive mechanism was developed for a dual rotary LVAD TAH. The incorporation of the adaptive mechanism was intended not only to minimize the risk of pulmonary congestion and atrial suction but also to match cardiac demand...
August 19, 2016: Annals of Biomedical Engineering
Hannah C Pulcastro, Peter O Awinda, Mei Methawasin, Henk Granzier, Wenji Dong, Bertrand C W Tanner
Titin is a giant protein spanning from the Z-disk to the M-band of the cardiac sarcomere. In the I-band titin acts as a molecular spring, contributing to passive mechanical characteristics of the myocardium throughout a heartbeat. RNA Binding Motif Protein 20 (RBM20) is required for normal titin splicing, and its absence or altered function leads to greater expression of a very large, more compliant N2BA titin isoform in Rbm20 homozygous mice (Rbm20 (ΔRRM) ) compared to wild-type mice (WT) that almost exclusively express the stiffer N2B titin isoform...
2016: Frontiers in Physiology
Abdelaziz Beqqali, Ilse A E Bollen, Torsten B Rasmussen, Maarten M van den Hoogenhof, Hanneke W M van Deutekom, Sebastian Schafer, Jan Haas, Benjamin Meder, Keld E Sørensen, Ralph J van Oort, Jens Mogensen, Norbert Hubner, Esther E Creemers, Jolanda van der Velden, Yigal M Pinto
AIM: Mutations in the RS-domain of RNA-binding motif protein 20 (RBM20) have recently been identified to segregate with aggressive forms of familial dilated cardiomyopathy (DCM). Loss of RBM20 in rats results in missplicing of the sarcomeric gene titin (TTN). The functional and physiological consequences of RBM20 mutations outside the mutational hotspot of RBM20 have not been explored to date. In this study, we investigated the pathomechanism of DCM caused by a novel RBM20 mutation in human cardiomyocytes...
October 2016: Cardiovascular Research
Christopher N Toepfer, Timothy G West, Michael A Ferenczi
KEY POINTS: Regulatory light chain (RLC) phosphorylation has been shown to alter the ability of muscle to produce force and power during shortening and to alter the rate of force redevelopment (ktr ) at submaximal [Ca(2+) ]. Increasing RLC phosphorylation ∼50% from the in vivo level in maximally [Ca(2+) ]-activated cardiac trabecula accelerates ktr . Decreasing RLC phosphorylation to ∼70% of the in vivo control level slows ktr and reduces force generation. ktr is dependent on sarcomere length in the physiological range 1...
September 15, 2016: Journal of Physiology
Marco Cirillo, Marco Campana, Federico Brunelli, Margherita Dalla Tomba, Zean Mhagna, Antonio Messina, Emmanuel Villa, Giuseppe Natalini, Giovanni Troise
OBJECTIVE: The history of left ventricular reconstruction has demonstrated that the full spectrum of recoverable physiologic parameters is essential for a good functional result. We report the long-term outcome of a new surgical technique that arranges myocardial fibers in a near-normal disposition, also recovering left ventricular twisting. METHODS: Between May 2006 and October 2013, 29 consecutive patients with previous anterior myocardial infarction and heart failure symptoms underwent physiologic left ventricular reconstruction surgery and coronary revascularization...
August 2016: Journal of Thoracic and Cardiovascular Surgery
Nathaniel Huebsch, Peter Loskill, Nikhil Deveshwar, C Ian Spencer, Luke M Judge, Mohammad A Mandegar, Cade B Fox, Tamer M A Mohamed, Zhen Ma, Anurag Mathur, Alice M Sheehan, Annie Truong, Mike Saxton, Jennie Yoo, Deepak Srivastava, Tejal A Desai, Po-Lin So, Kevin E Healy, Bruce R Conklin
Tissue engineering approaches have the potential to increase the physiologic relevance of human iPS-derived cells, such as cardiomyocytes (iPS-CM). However, forming Engineered Heart Muscle (EHM) typically requires >1 million cells per tissue. Existing miniaturization strategies involve complex approaches not amenable to mass production, limiting the ability to use EHM for iPS-based disease modeling and drug screening. Micro-scale cardiospheres are easily produced, but do not facilitate assembly of elongated muscle or direct force measurements...
2016: Scientific Reports
John Jeshurun Michael, Murali Chandra
BACKGROUND: We hypothesized that the functional effects of R206L-a rat analog of the dilated cardiomyopathy (DCM) mutation R205L in human cardiac troponin T (TnT)-were differently modulated by myosin heavy chain (MHC) isoforms and T204E, a protein kinase C (PKC) phosphomimic of TnT. Our hypothesis was based on two observations: (1) α- and β-MHC differentially influence the functional effects of TnT; and (2) PKC isoforms capable of phosphorylating TnT are upregulated in failing human hearts...
March 2016: Journal of the American Heart Association
King-Lun Li, Nazanin Bohlooli Ghashghaee, R John Solaro, Wenji Dong
Sarcomere length dependent activation (LDA) of myocardial force development is the cellular basis underlying the Frank-Starling law of the heart, but it is still elusive how the sarcomeres detect the length changes and convert them into altered activation of thin filament. In this study we investigated how the C-domain of cardiac troponin I (cTnI) functionally and structurally responds to the comprehensive effects of the Ca(2+), crossbridge, and sarcomere length of chemically skinned myocardial preparations...
July 1, 2016: Archives of Biochemistry and Biophysics
George G S Sandor
In this article the utility of echocardiographic tests of left ventricular (LV) function in pediatric cardiology is reviewed. These indices are derived from the basic concepts of cardiac physiology, namely the Frank-Starling curve, pressure volume loops, and the force frequency relation and, to some extent, are all governed by these general principles. Thus, they are prone to be load-dependent and their utility variable. Methods that use formulas for calculating LV volume are a problem in congenital heart disease in which LV geometry is frequently abnormal...
October 2016: Canadian Journal of Cardiology
Adriana V Klein, Francisco J Teixeira-Neto, Natache A Garofalo, Angie P Lagos-Carvajal, Miriely S Diniz, Diana R Becerra-Velásquez
OBJECTIVE: To compare changes in pulse pressure variation (PPV) and plethysmographic variability index (PVI) induced by hemorrhage followed by volume replacement (VR) in isoflurane-anesthetized dogs. ANIMALS: 7 healthy adult dogs. PROCEDURE: Each dog was anesthetized with isoflurane and mechanically ventilated. End-tidal isoflurane concentration was adjusted to maintain mean arterial pressure (MAP) at 60 to 70 mm Hg before hemorrhage. Controlled hemorrhage was initiated and continued until the MAP decreased to 40 to 50 mm Hg, then autologous blood removed during hemorrhage was retransfused during VR...
March 2016: American Journal of Veterinary Research
Ranganath Mamidi, Kenneth S Gresham, Sujeet Verma, Julian E Stelzer
Cardiac myosin binding protein-C (cMyBP-C) phosphorylation is an important regulator of contractile function, however, its contributions to length-dependent changes in cross-bridge (XB) kinetics is unknown. Therefore, we performed mechanical experiments to quantify contractile function in detergent-skinned ventricular preparations isolated from wild-type (WT) hearts, and hearts expressing non-phosphorylatable cMyBP-C [Ser to Ala substitutions at residues Ser273, Ser282, and Ser302 (i.e., 3SA)], at sarcomere length (SL) 1...
2016: Frontiers in Physiology
Younss Ait-Mou, Karen Hsu, Gerrie P Farman, Mohit Kumar, Marion L Greaser, Thomas C Irving, Pieter P de Tombe
The Frank-Starling mechanism of the heart is due, in part, to modulation of myofilament Ca(2+) sensitivity by sarcomere length (SL) [length-dependent activation (LDA)]. The molecular mechanism(s) that underlie LDA are unknown. Recent evidence has implicated the giant protein titin in this cellular process, possibly by positioning the myosin head closer to actin. To clarify the role of titin strain in LDA, we isolated myocardium from either WT or homozygous mutant (HM) rats that express a giant splice isoform of titin, and subjected the muscles to stretch from 2...
February 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Younss Ait Mou, Christian Bollensdorff, Olivier Cazorla, Yacoub Magdi, Pieter P de Tombe
The heart is subject to multiple sources of stress. To maintain its normal function, and successfully overcome these stresses, heart muscle is equipped with fine-tuned regulatory mechanisms. Some of these mechanisms are inherent within the myocardium itself and are known as intrinsic mechanisms. Over a century ago, Otto Frank and Ernest Starling described an intrinsic mechanism by which the heart, even ex vivo, regulates its function on a beat-to-beat basis. According to this phenomenon, the higher the ventricular filling is, the bigger the stroke volume...
2015: Global Cardiology Science & Practice
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