Science.gov

Sample records for cardiac pumping function

  1. Modeling the relation between cardiac pump function and myofiber mechanics.

    PubMed

    Arts, T; Bovendeerd, P; Delhaas, T; Prinzen, F

    2003-05-01

    Complexity of the geometry and structure of the heart hampers easy modeling of cardiac mechanics. The modeling can however be simplified considerably when using the hypothesis that in the normal heart myofiber structure and geometry adapt, until load is evenly distributed. A simple and realistic relationship is found between the hemodynamic variables cavity pressure and volume, and myofiber load parameters stress and strain. The most important geometric parameter in the latter relation is the ratio of cavity volume to wall volume, while actual geometry appears practically irrelevant. Applying the found relationship, a realistic maximum is set to left ventricular pressure after chronic pressure load. Pressures exceeding this level are likely to cause decompensation and heart failure. Furthermore, model is presented to simulate left and right ventricular pump function with left-right interaction.

  2. [Interrelation between cardiac pump function disturbances and cardiac contractility after beta-adrenergic hyperstimulation of the heart in rats].

    PubMed

    Kuz'menko, M O; Pavliuchenko, V B; Tumanovs'ka, L V; Dosenko, V Ie; Moĭbenko, O O

    2011-01-01

    The complex of structural and functional changes of myocardium was investigated in experiments with rats with chronic beta-adrenergic activation for 1 month. We observed substantial attenuation of myocardial pump function, particularly reduction of stroke volume by 38.50% (P < 0.01), cardiac output by 42.38% (P < 0.01), and ejection fraction by 35.61% (P < 0.01). Furthermore, 2-fold increase of end-diastolic left ventricular pressure (P < 0.01) and rise of active relaxation constant Tau by 12.91% (P < 0.05) were observed. This indicates on an impaired diastolic function of the heart that is associated with accumulation of connective tissue elements in myocardium and increase of its end-diastolic stiffness that finally leads to cardiac pump function disturbances. Surprisingly, myocardial contractility was considerably augmented not only after the treatment with beta-adrenergic agonist but also on the 26th day after drug cessation. This phenomenon is associated with elevation of dP/dt(max) by 49.9% (P < 0.01), 2.5-fold increase of end-systolic elastance (P < 0.01) as well as maximal myocardial elastance by 42.53% (P < 0.05). It can be explained by compensatory influence of increased contractility that nevertheless failed to maintain adequate cardiac pump function and furthermore it may result in depletion of cardiac energy resource.

  3. Evaluation of cardiac function during left ventricular assist by a centrifugal blood pump.

    PubMed

    Kikugawa, D

    2000-08-01

    In this study, the effects on varying cardiac function during a left ventricular (LV) bypass from the apex to the descending aorta using a centrifugal blood pump were evaluated by analyzing the left ventricular pressure and the motor current of the centrifugal pump in a mock circulatory loop. Failing heart models (preload 15 mm Hg, afterload 40 mm Hg) and normal heart models (preload 5 mm Hg, afterload 100 mm Hg) were simulated by adjusting the contractility of the latex rubber left ventricle. In Study 1, the bypass flow rate, left ventricular pressure, aortic pressure, and motor current levels were measured in each model as the centrifugal pump rpm were increased from 1,000 to 1,500 to 2,000. In Study 2, the pump rpm were fixed at 1,300, 1,500, and 1,700, and at each rpm, the left ventricular peak pressure was increased from 40 to 140 mm Hg by steps of 20 mm Hg. The same measurements as in Study 1 were performed. In Study 1, the bypass flow rate and mean aortic pressure both increased with the increase in pump rpm while the mean left ventricular pressure decreased. In Study 2, a fairly good correlation between the left ventricular pressure and the motor current of the centrifugal pump was obtained. These results suggest that cardiac function as indicated by left ventricular pressure may be estimated from a motor current analysis of the centrifugal blood pump during left heart bypass.

  4. Assessing cardiac pumping capability by exercise testing and inotropic stimulation.

    PubMed Central

    Tan, L B; Bain, R J; Littler, W A

    1989-01-01

    In heart failure both functional capacity and prognosis are primarily determined by the degree of pump dysfunction. Although data on haemodynamic function at rest may indicate impaired cardiac function, they do not assess the capacity of the heart to respond to stress. Maximal bicycle ergometry and incremental intravenous inotropic stimulation in 31 patients with moderately severe heart failure were evaluated as methods of stressing the heart to determine cardiac pumping capability, which is defined as the cardiac power obtained during maximal stimulation. There was good agreement between the cardiac pumping capabilities assessed by these two methods. Maximal cardiac power output was better than maximal cardiac output and left ventricular stroke work index in representing cardiac pumping capability, because it was less dependent on the type of stimulation used during evaluation. Inotropic challenge is at least as effective as exercise testing in assessing cardiac pumping capability in heart failure, and may be a better method in patients who find physical exercise difficult. PMID:2757870

  5. Assessing cardiac pumping capability by exercise testing and inotropic stimulation.

    PubMed

    Tan, L B; Bain, R J; Littler, W A

    1989-07-01

    In heart failure both functional capacity and prognosis are primarily determined by the degree of pump dysfunction. Although data on haemodynamic function at rest may indicate impaired cardiac function, they do not assess the capacity of the heart to respond to stress. Maximal bicycle ergometry and incremental intravenous inotropic stimulation in 31 patients with moderately severe heart failure were evaluated as methods of stressing the heart to determine cardiac pumping capability, which is defined as the cardiac power obtained during maximal stimulation. There was good agreement between the cardiac pumping capabilities assessed by these two methods. Maximal cardiac power output was better than maximal cardiac output and left ventricular stroke work index in representing cardiac pumping capability, because it was less dependent on the type of stimulation used during evaluation. Inotropic challenge is at least as effective as exercise testing in assessing cardiac pumping capability in heart failure, and may be a better method in patients who find physical exercise difficult.

  6. Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis.

    PubMed

    Lumens, Joost; Arts, Theo; Broers, Bernard; Boomars, Karin A; van Paassen, Pieter; Prinzen, Frits W; Delhaas, Tammo

    2009-12-01

    In pulmonary arterial hypertension (PAH), duration of myofiber shortening is prolonged in the right ventricular (RV) free wall (RVfw) compared with that in the interventricular septum and left ventricular free wall. This interventricular mechanical asynchrony eventually leads to right heart failure. We investigated by computer simulation whether, in PAH, early RVfw pacing may improve interventricular mechanical synchrony and, hence, cardiac pump function. A mathematical model of the human heart and circulation was used to simulate left ventricular and RV pump mechanics and myofiber mechanics. First, we simulated cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and blood vessels were adapted so that mechanical tissue load was normalized. Second, compensated PAH was simulated by increasing mean pulmonary artery pressure to 32 mmHg while applying load adaptation. Third, decompensated PAH was simulated by increasing mean pulmonary artery pressure further to 79 mmHg without further adaptation. Finally, early RVfw pacing was simulated in severely decompensated PAH. Time courses of circumferential strain in the ventricular walls as simulated were similar to the ones measured in healthy subjects (uniform strain patterns) and in PAH patients (prolonged RVfw shortening). When simulating pacing in decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber work, and most homogeneous distribution of workload over the ventricular walls. Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve RV pump function and may homogenize workload over the ventricular walls.

  7. Effects of left ventricular assist device on cardiac function: experimental study of relationship between pump flow and left ventricular diastolic function.

    PubMed

    Saito, A; Shiono, M; Orime, Y; Yagi, S; Nakata, K I; Eda, K; Hattori, T; Funahashi, M; Taniguchi, Y; Negishi, N; Sezai, Y

    2001-09-01

    The left ventricular assist device (LVAD) with centrifugal pump has two characteristics. One is a pump flow wave of the centrifugal pump, consisting of the pulsatile flow of the native heart and the nonpulsatile flow of the centrifugal pump. The other is that the centrifugal pump fills from the native heart not only in the systolic phase, but also in the diastolic phase. In the case of the apex outlet LVAD with centrifugal pump, blood flows from the left atrium through the left ventricle to the pump. Pump flow is regulated by preload, and preload is regulated by diastolic hemodynamics. The aim of this study is to analyze the relationship between pump flow and the diastolic hemodynamics of the native heart. Ten anesthetized intact pigs were studied after placement of an LVAD. Data were recorded with the LVAD off (control) and the LVAD on. The assist rate was changed to 25%, 50%, and 75%. The indexes of left ventricular (LV) diastolic function included LV myocardial relaxation (time constant of isovolumic pressure decay [Tau] and maximum negative dP/dt [LV dP/dt min]) and LV filling (peak filling rate [PFR], time to peak filling rate [tPFR], and diastolic filling time [DFT]). Stroke volume decreased significantly in 75% assist. LV end-systolic pressure decreased significantly in 50% and 75% assist. LV end-diastolic volume decreased as assist rate increased, but there were no significant changes. Stroke work decreased significantly in 50% and 75% assist. LV dP/dt min decreased significantly in 50% and 75% assist. Tau prolonged as assist rate increased, but there were no significant changes. DFT shortened significantly in 75% assist. PFR increased significantly in 75% assist. tPFR shortened significantly in 50% and 75% assist. In this study, LV relaxation delayed as an increasing of pump assist rate, but it suggested a result of reduction of cardiac work. Also, it was suggested that LVAD increases the pressure difference between the left atrium and the left ventricle

  8. Influence of angiotensin converting enzyme inhibition on pump function and cardiac contractility in patients with chronic congestive heart failure.

    PubMed Central

    Baur, L H; Schipperheyn, J J; Baan, J; van der Laarse, A; Buis, B; van der Wall, E E; Manger Cats, V; van Dijk, A D; Blokland, J A; Frölich, M

    1991-01-01

    Eleven patients with coronary artery disease and chronic heart failure were studied before and three months after the angiotensin converting enzyme inhibitor enalapril was added to their frusemide medication. The following were measured: left ventricular pressure and volume with transient occlusion of the inferior vena cava, radionuclide angiography, and hormone concentrations in plasma. As in other reported studies, the clinical condition of the patients improved and their exercise tolerance increased moderately. Addition of enalapril reduced end diastolic and systolic pressure, reduced ventricular volume, and concomitantly increased the ejection fraction. The end systolic pressure-volume relation shifted to the left as it did in a similar animal study. In the animal study unloading by a vasodilator did not induce a leftward shift, so it can be inferred that in the present study unloading combined with a decrease in the angiotensin concentration was instrumental in remodelling the heart. Though unloading was expected to have a beneficial effect on the oxygen supply/demand ratio of the heart, the patients still showed the same drop in the ejection fraction during exercise as they did before treatment with enalapril, and early diastolic filling did not improve. Normally, regression of cardiac dilatation is only found if pump function improves; the present study showed that unloading in combination with angiotensin converting enzyme inhibition reshapes the ventricle without improving intrinsic pump function. PMID:2015121

  9. Sarcomere mechanics in uniform and nonuniform cardiac muscle: a link between pump function and arrhythmias.

    PubMed

    Ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

    2008-03-01

    Starling's law and the end-systolic pressure-volume relationship (ESPVR) reflect the effect of sarcomere length (SL) on the development of stress (sigma) and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to that of skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL -[Ca2+](free) relationships (sigma-SL-Ca relationships) at submaximal [Ca2+] in intact and skinned trabeculae were similar, although the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-Ca relationship by using a kinetic model assuming that the rates of Tn-C Ca2+ binding and/or cross-bridge (XB) cycling are determined by either the SL, [Ca2+], or sigma. We analyzed the correlation between the model results and steady-state sigma measurements at varied SL at [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that the dominant feedback mechanism is SL-, sigma-, or [Ca2+]-dependent, and that the feedback mechanism regulates Tn-C Ca2+ affinity, XB kinetics, or the unitary XB force. The analysis strongly suggests that the feedback of the number of strong XBs to cardiac Tn-C Ca2+ affinity is the dominant mechanism regulating XB recruitment. Using this concept in a model of twitch-sigma accurately reproduced the sigma-SL-Ca relationship and the time courses of twitch sigma and the intracellular [Ca2+]i. The foregoing concept has equally important repercussions for the nonuniformly contracting heart, in which arrhythmogenic Ca2+ waves arise from weakened areas in the cardiac muscle. These Ca2+ waves can reversibly be induced with nonuniform excitation-contraction coupling (ECC) by the cycle of stretch and release in the border zone between the damaged and intact regions. Stimulus trains induced propagating

  10. Biomechanics of Cardiac Function

    PubMed Central

    Voorhees, Andrew P.; Han, Hai-Chao

    2015-01-01

    The heart pumps blood to maintain circulation and ensure the delivery of oxygenated blood to all the organs of the body. Mechanics play a critical role in governing and regulating heart function under both normal and pathological conditions. Biological processes and mechanical stress are coupled together in regulating myocyte function and extracellular matrix structure thus controlling heart function. Here we offer a brief introduction to the biomechanics of left ventricular function and then summarize recent progress in the study of the effects of mechanical stress on ventricular wall remodeling and cardiac function as well as the effects of wall mechanical properties on cardiac function in normal and dysfunctional hearts. Various mechanical models to determine wall stress and cardiac function in normal and diseased hearts with both systolic and diastolic dysfunction are discussed. The results of these studies have enhanced our understanding of the biomechanical mechanism in the development and remodeling of normal and dysfunctional hearts. Biomechanics provide a tool to understand the mechanism of left ventricular remodeling in diastolic and systolic dysfunction and guidance in designing and developing new treatments. PMID:26426462

  11. Motor current waveforms as an index for evaluation of native cardiac function during left ventricular support with a centrifugal blood pump.

    PubMed

    Kikugawa, D

    2001-09-01

    Control of ventricular assist devices (VADs) for native heart preservation should be attempted, and it could be one strategy for dealing with the shortage of donors in the future. In the application of a nonpulsatile blood pump for ventricular assistance from its apex to the aorta, the bypass flow and hence motor current of the pumps change in response to the ventricular pressure change. Utilizing these intrinsic characteristics of the continuous flow pumps, this study investigated whether or not motor current could be used as an index for continuous monitoring of native cardiac function. In Study 1, a centrifugal blood pump (CFP) VAD was installed between the apex and descending aorta of a mock circulatory loop. In this model, a baseline with a preload of 10 mm Hg, afterload of 40 mm Hg, and left ventricular (LV) systolic pressure of 40 mm Hg was used. The pump rpm were fixed at 1,300, 1,500, and 1,700, and LV systolic pressure was increased up to 140 mm Hg by a step of 20 mm Hg while observing the changes in LV pressure, motor current, pump flow, and aortic pressure. In Study 2, in vivo experiments were performed using 5 sheep. A left heart bypass model was created using a centrifugal pump from the ventricular apex to the descending aorta. The LV pressure was varied through administration of dopamine while observing the changes in LV pressure, pump flow, motor current, and aortic pressure at 1,500 and 1,700 rpm. An excellent correlation was observed both in vitro and in vivo studies in the relationship between motor current and LV pressure. In Study 1, the correlation coefficients were 0.77, 0.92, and 0.99 for 1,300, 1,500, and 1,700 rpm, respectively. In Study 2, they were 0.90 (Animal 1), 0.82 (Animal 2), 0.89 (Animal 3), 0.93 (Animal 4), and 0.70 (Animal 5) respectively for 1,500 rpm, and 0.94 (Animal 2), 0.85 (Animal 3), 0.94 (Animal 4), and 0.89 (Animal 5) respectively, for 1,700 rpm. The relationship between motor current and pump flow and LV pressure

  12. [Hemodynamic control by optimization of the cardiac pump].

    PubMed

    Metry, S; Fromageot, C; Brocas, J; Cherruault, Y; Guillez, A; Lelong, F

    1981-11-01

    Transport of energy appears as the ultimate finality of the force convection cardiovascular system. Blood pressure cardiac output and vascular resistances are the three major components of the circulatory system. Among them, blood pressure is regarded as the regulated parameter whose control value is the best adapted parameter, to each kind of activity, neurogenic mechanisms. The authors, considering the physiological variations of blood pressure during increasing energetic loads imposed on the organism, propose a new control function: optimization of cardiac mechanical power necessary to assure convection of the energy needed by the organism. Blood pressure is no more regarded as a constant. Simultaneous changes in cardiac output and blood pressure are both significant, adjusted to realize energetic minimisation of the cardiac pump. This cardiovascular regulation is described by a system of equations whose resolution leads to results in good accordance with physiological data.

  13. [Non-invasive determination of cardiac pump function by respiratory gas exchange measurement during submaximal exercise -- comparison with hemodynamic (heart catheterisation) data (author's transl)].

    PubMed

    Rox, J; Trieb, G; Bonzel, T; Frey, N; Sigwart, U; Gleichmann, U

    1977-11-01

    The continuous measurement of respiratory gas exchange under linearly increasing work load allows a relatively exact and reproducible localization of the point of rise of the ventilatory equivalent for oxygen (ASV). On the basis of the values of oxygen consumption (V(O2)(ASV)), oxygen pulse (O2-pulse(asv)) and relative ventilatory equivalent (Vetn. Equivalent(asv)/V(O2(ASV)), measured at the point ASV, it is possible to divide patients with different severity of heart disease into 4 groups of cardiac response to exercise: group I = normal, group II = diminished, group III = definitely limited and group IV = severely limited cardiocirculatory capacity. Simultaneous cardiac output measurements (thermodilution method) as well as the comparison with hemodynamic and angiographic data acquired during separate heart catheterization reveal good correlations between V(O2(ASV) and O2-pulse(asv) on the one hand and exercise values of cardiac output and stroke volume on the other (r = 0.82). Consequently, definite relations exist between the absolute ASV values as well as the group classification (I--IV) based on these and further heart catheterization data such as left bentricular (LV) enddiastolic pressure, LV ejection fraction, contraction pattern of the left ventricle and coronary angiogram respectively. The described method of measuring respiratory gas exchange under submaximal unsteady state bicycle exercise represents a reliable and rapid non-invasive stress test of cardiac pump function without putting too much strain on the heart patient as is frequently the case with the more familiar steady state (maximal) tests.

  14. Development of a control algorithm for a rotary blood pump: prediction of recovery from cardiac failure.

    PubMed

    Konishi, H; Misawa, Y; Fuse, K

    1998-01-01

    Under extracorporeal membrane oxygenator (ECMO) support, it is difficult to predict recovery of cardiac function. The authors examined the rotary blood pump function curve and developed a new index of dynamic vascular impedance (DVI) for controlling the ECMO system. The cases of nine patients assisted by ECMO after cardiac surgery were analyzed. The index of DVI was calculated from the pump flow and the pressure difference (delta pressure) between the inlet and outlet of the pump. Seven patients were weaned from support. In the patients with recovery of cardiac function, the index of DVI was high and the delta pressure converged on the specific value. Analysis of the rotary blood pump function curve during ECMO support reflects the pump characteristics and provides data for the management of pump speed. The index of DVI can be used to predict the timing for weaning patients from ECMO support. The authors are developing an automatic control system that uses the index of DVI.

  15. Functional cardiac tissue engineering

    PubMed Central

    Liau, Brian; Zhang, Donghui; Bursac, Nenad

    2013-01-01

    Heart attack remains the leading cause of death in both men and women worldwide. Stem cell-based therapies, including the use of engineered cardiac tissues, have the potential to treat the massive cell loss and pathological remodeling resulting from heart attack. Specifically, embryonic and induced pluripotent stem cells are a promising source for generation of therapeutically relevant numbers of functional cardiomyocytes and engineering of cardiac tissues in vitro. This review will describe methodologies for successful differentiation of pluripotent stem cells towards the cardiovascular cell lineages as they pertain to the field of cardiac tissue engineering. The emphasis will be placed on comparing the functional maturation in engineered cardiac tissues and developing heart and on methods to quantify cardiac electrical and mechanical function at different spatial scales. PMID:22397609

  16. Sarcomere mechanics in uniform and non-uniform cardiac muscle: a link between pump function and arrhythmias.

    PubMed

    ter Keurs, Henk E D J; Shinozaki, Tsuyoshi; Zhang, Ying Ming; Zhang, Mei Luo; Wakayama, Yuji; Sugai, Yoshinao; Kagaya, Yutaka; Miura, Masahito; Boyden, Penelope A; Stuyvers, Bruno D M; Landesberg, Amir

    2008-01-01

    Starling's Law and the well-known end-systolic pressure-volume relationship (ESPVR) of the left ventricle reflect the effect of sarcomere length (SL) on stress (sigma) development and shortening by myocytes in the uniform ventricle. We show here that tetanic contractions of rat cardiac trabeculae exhibit a sigma-SL relationship at saturating [Ca2+] that depends on sarcomere geometry in a manner similar to skeletal sarcomeres and the existence of opposing forces in cardiac muscle shortened below slack length. The sigma-SL-[Ca2+]free relationships (sigma-SL-CaR) at submaximal [Ca2+] in intact and skinned trabeculae were similar, albeit that the sensitivity for Ca2+ of intact muscle was higher. We analyzed the mechanisms underlying the sigma-SL-CaR using a kinetic model where we assumed that the rates of Ca2+ binding by Troponin-C (Tn-C) and/or cross-bridge (XB) cycling are determined by SL, [Ca2+] or stress. We analyzed the correlation between the model results and steady state stress measurements at varied SL and [Ca2+] from skinned rat cardiac trabeculae to test the hypotheses that: (i) the dominant feedback mechanism is SL, stress or [Ca2+]-dependent; and (ii) the feedback mechanism regulates: Tn-C-Ca2+ affinity, XB kinetics or, unitary XB-force. The analysis strongly suggests that feedback of the number of strong XBs to cardiac Tn-C-Ca2+ affinity is the dominant mechanism that regulates XB recruitment. Application of this concept in a mathematical model of twitch-stress accurately reproduced the sigma-SL-CaR and the time course of twitch-stress as well as the time course of intracellular [Ca2+]i. Modeling of the response of the cardiac twitch to rapid stress changes using the above feedback model uniquely predicted the occurrence of [Ca2+]i transients as a result of accelerated Ca2+ dissociation from Tn-C. The above concept has important repercussions for the non-uniformly contracting heart in which arrhythmogenic Ca2+ waves arise from weakened areas in cardiac

  17. Mechano-electrical feedback explains T-wave morphology and optimizes cardiac pump function: insight from a multi-scale model.

    PubMed

    Hermeling, Evelien; Delhaas, Tammo; Prinzen, Frits W; Kuijpers, Nico H L

    2012-01-01

    In the ECG, T- and R-wave are concordant during normal sinus rhythm (SR), but discordant after a period of ventricular pacing (VP). Experiments showed that the latter phenomenon, called T-wave memory, is mediated by a mechanical stimulus. By means of a mathematical model, we investigated the hypothesis that slow acting mechano-electrical feedback (MEF) explains T-wave memory. In our model, electromechanical behavior of the left ventricle (LV) was simulated using a series of mechanically and electrically coupled segments. Each segment comprised ionic membrane currents, calcium handling, and excitation-contraction coupling. MEF was incorporated by locally adjusting conductivity of L-type calcium current (g(CaL)) to local external work. In our set-up, g(CaL) could vary up to 25%, 50%, 100% or unlimited amount around its default value. Four consecutive simulations were performed: normal SR (with MEF), acute VP, sustained VP (with MEF), and acutely restored SR. MEF led to T-wave concordance in normal SR and to discordant T-waves acutely after restoring SR. Simulated ECGs with a maximum of 25-50% adaptation closely resembled those during T-wave memory experiments in vivo and also provided the best compromise between optimal systolic and diastolic function. In conclusion, these simulation results indicate that slow acting MEF in the LV can explain a) the relatively small differences in systolic shortening and mechanical work during SR, b) the small dispersion in repolarization time, c) the concordant T-wave during SR, and d) T-wave memory. The physiological distribution in electrophysiological properties, reflected by the concordant T-wave, may serve to optimize cardiac pump function. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Symmetry of cardiac function assessment

    PubMed Central

    Bai, Xu-Fang; Ma, Amy X

    2016-01-01

    Both right and left ventricles are developed from two adjacent segments of the primary heart tube. Though they are different with regard to shape and power, they mirror each other in terms of behavior. This is the first level of symmetry in cardiac function assessment. Both cardiac muscle contraction and relaxation are active. This constructs the second level of symmetry in cardiac function assessment. Combination of the two levels will help to find some hidden indexes or approaches to evaluate cardiac function. In this article, four major indexes from echocardiography were analyzed under this principal, another seventeen indexes or measurement approaches came out of the shadow, which is very helpful in the assessment of cardiac function, especially for the right cardiac function and diastolic cardiac function. PMID:27582768

  19. Outcome of Cardiac Rehabilitation Following Off-Pump Versus On-Pump Coronary Bypass Surgery.

    PubMed

    Arefizadeh, Reza; Hariri, Seyed Yaser; Moghadam, Adel Johari

    2017-06-15

    A few studies have compared the cardiac rehabilitation (CR) outcome between those who undergo conventional on-pump bypass surgery and off-pump surgery. We compared this outcome among the patients differentiated by the On-pump and off-pump surgical procedures about cardiovascular variables and psychological status. This longitudinal study recruited 318 and 102 consecutive patients who had undergone CABG (on-pump surgery, n = 318 and off-pump surgery, n = 102) and been referred to the CR clinic. The off-pump surgery patients had more improvement in their metabolic equivalents (METs) value. The physical and mental components of health-related quality of life (QOL) (based on SF-36 questionnaire) as well as depression-anxiety (based on Costello-Comrey Depression and Anxiety Scale) were notably improved in the two study groups after the CR program, while changes in the QOL components scores and also depression-anxiety score were not different between the off-pump and on-pump techniques. Regarding QOL and psychological status, there were no differences in the CR outcome between those who underwent off-pump bypass surgery and those who underwent on-pump surgery; nevertheless, the off-pump technique was superior to the on-pump method on METs improvement following CR.

  20. Mathematical Models of Cardiac Pacemaking Function

    NASA Astrophysics Data System (ADS)

    Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

    2013-10-01

    Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

  1. Optimized temporary bi-ventricular pacing improves haemodynamic function after on-pump cardiac surgery in patients with severe left ventricular systolic dysfunction: a two-centre randomized control trial

    PubMed Central

    Russell, Stuart J.; Tan, Christine; O'Keefe, Peter; Ashraf, Saeed; Zaidi, Afzal; Fraser, Alan G.; Yousef, Zaheer R.

    2012-01-01

    OBJECTIVES Optimized temporary bi-ventricular (BiV) pacing may benefit heart failure patients after on-pump cardiac surgery compared with conventional dual-chamber right ventricular (RV) pacing. An improvement in haemodynamic function with BiV pacing may reduce the duration of ‘Level 3’ intensive care. METHODS Thirty-eight patients in sinus rhythm, ejection fraction ≤35%, undergoing on-pump surgical revascularization, valve surgery or both were enrolled in this study. Before closing the sternum, temporary epicardial pacing wires were attached to the right atrium, RV outflow tract and basal posterolateral wall of the left ventricle. Patients were randomly assigned to postoperative BiV pacing with the optimization of the atrio- (AV) and inter-ventricular (VV) pacing intervals (Group 1) or conventional dual-chamber right AV pacing (Group 2). The primary end-point was the duration of ‘Level 3’ intensive care. Secondary end-points included cardiac output which was measured by thermodiluation at admission to the intensive care unit and at 6 and 18 h later, in five different pacing modes. RESULTS The duration of ‘Level 3’ care was similar between groups (40 ± 35 vs 54 ± 63 h; Group 1 vs 2; P = 0.43). Cardiac output was similar in all pacing modes at baseline. At 18 h, cardiac output with BiV pacing (5.8 l/min) was 7% higher than atrial inhibited (5.4 l/min) and 9% higher than dual-chamber RV pacing (5.3 l/min; P = 0.02 and 0.001, respectively). Optimization of the VV interval produced a further 4% increase in cardiac output compared with baseline settings (P = 0.005). CONCLUSIONS Postoperative haemodynamic function may be enhanced by temporary BiV pacing of high-risk patients after on-pump cardiac surgery. PMID:23138590

  2. Comparison and relation of indirect and direct dynamic indexes of cardiac pumping capacity in chronic heart failure.

    PubMed

    Williams, Simon G; Tzeng, Bing-H; Barker, Diane; Tan, Lip-Bun

    2005-10-15

    Cardiac power output (CPO), the product of cardiac output (CO) and mean arterial pressure (MAP), is a direct measure of cardiac pumping capability and is strongly indicative of prognosis and exercise ability in patients with chronic heart failure (CHF). However, it is not as easily measured as indirect indicators of cardiac function, such as peak oxygen consumption (VO(2)) or peak "circulatory power" (CircP), the product of VO(2) and MAP. The relation between direct and indirect indexes of cardiac pumping capacity was evaluated in 219 ambulatory patients with CHF. CircP was found to have a direct and consistent relation with CPO, overall (R = 0.93, p <0.0001) and at peak exercise (R = 0.84, p < 0.0001). The results suggest CircP to be an adequate measure of cardiac pumping capacity when the more directly measured CPO is not available.

  3. Intra-Aortic Balloon Pump Counterpulsation in the Post-Resuscitation Period is Associated with Improved Functional Outcomes in Patients Surviving an Out-of-Hospital Cardiac Arrest: Insights from a Dedicated Heart Attack Centre.

    PubMed

    Iqbal, M Bilal; Al-Hussaini, Abtehale; Rosser, Gareth; Rajakulasingam, Ramyah; Patel, Jayna; Elliott, Katharine; Mohan, Poornima; Phylactou, Maria; Green, Rebecca; Whitbread, Mark; Mason, Mark; Grocott-Mason, Richard; Smith, Robert; Ilsley, Charles

    2016-12-01

    Despite advances in cardiopulmonary resuscitation, functional survival remains low after out-of-hospital cardiac arrest (OOHCA). Intra-aortic balloon pump (IABP) therapy has recently been shown to augment cerebral blood flow. Whether IABP therapy in the post-resuscitation period improves functional outcomes is unknown. We analysed 174 consecutive patients who were successfully resuscitated from an OOHCA between 2011-2013 at Harefield Hospital, London. We analysed functional status at discharge and mortality up to one year. A total of 55 patients (32.1%) received IABP therapy. Comparing those receiving IABP with those not receiving IABP, there was no difference in favourable functional status at discharge (49.1% vs. 57.1%, p=0.321); and mortality at one year (45.5% vs. 35.5%, p=0.164). Multivariable analyses identified IABP therapy as a strong independent predictor for favourable functional status at discharge (OR=7.51, 95% CI: 2.15-26.14, p=0.002) and this association was maintained in propensity-score adjusted analyses (OR=9.90, 95% CI: 2.11-46.33, p=0.004) and inverse probability treatment weighted analyses (OR=10.84, 95% CI: 2.75-42.69, p<0.001). However, IABP therapy was not an independent predictor for mortality at one year (HR=0.93, 95% CI: 0.52-1.65, p=0.810) and this was confirmed in both propensity-score adjusted and inverse probability treatment weighted analyses. In this observational analysis of patients surviving an OOHCA, the use of IABP therapy in the post-resuscitation period was associated with improved functional outcomes. This warrants further evaluation in larger prospective studies. Copyright © 2016 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  4. GPCR signaling and cardiac function.

    PubMed

    Capote, Leany A; Mendez Perez, Roberto; Lymperopoulos, Anastasios

    2015-09-15

    G protein-coupled receptors (GPCRs), such as β-adrenergic and angiotensin II receptors, located in the membranes of all three major cardiac cell types, i.e. myocytes, fibroblasts and endothelial cells, play crucial roles in regulating cardiac function and morphology. Their importance in cardiac physiology and disease is reflected by the fact that, collectively, they represent the direct targets of over a third of the currently approved cardiovascular drugs used in clinical practice. Over the past few decades, advances in elucidation of their structure, function and the signaling pathways they elicit, specifically in the heart, have led to identification of an increasing number of new molecular targets for heart disease therapy. Here, we review these signaling modalities employed by GPCRs known to be expressed in the cardiac myocyte membranes and to directly modulate cardiac contractility. We also highlight drugs and drug classes that directly target these GPCRs to modulate cardiac function, as well as molecules involved in cardiac GPCR signaling that have the potential of becoming novel drug targets for modulation of cardiac function in the future.

  5. Relationship between peak cardiac pumping capability and indices of cardio-respiratory fitness in healthy individuals.

    PubMed

    Jakovljevic, Djordje G; Popadic-Gacesa, Jelena Z; Barak, Otto F; Nunan, David; Donovan, Gay; Trenell, Michael I; Grujic, Nikola G; Brodie, David A

    2012-09-01

    Cardiac power output (CPO) is a unique and direct measure of overall cardiac function (i.e. cardiac pumping capability) that integrates both flow- and pressure-generating capacities of the heart. The present study assessed the relationship between peak exercise CPO and selected indices of cardio-respiratory fitness. Thirty-seven healthy adults (23 men and 14 women) performed an incremental exercise test to volitional fatigue using the Bruce protocol with gas exchange and ventilatory measurements. Following a 40-min recovery, the subjects performed a constant maximum workload exercise test at or above 95% of maximal oxygen consumption. Cardiac output was measured using the exponential CO(2) rebreathing method. The CPO, expressed in W, was calculated as the product of the mean arterial blood pressure and cardiac output. At peak exercise, CPO was well correlated with cardiac output (r = 0·92, P<0·01), stroke volume (r = 0·90, P<0·01) and peak oxygen consumption (r = 0·77, P<0·01). The coefficient of correlation was moderate between CPO and anaerobic threshold (r = 0·47, P<0·01), oxygen pulse (r = 0·57, P<0·01), minute ventilation (r = 0·53, P<0·01) and carbon dioxide production (r = 0·56, P<0·01). Small but significant relationship was found between peak CPO and peak heart rate (r = 0·23, P<0·05). These findings suggest that only peak cardiac output and stroke volume truly reflect CPO. Other indices of cardio-respiratory fitness such as oxygen consumption, anaerobic threshold, oxygen pulse, minute ventilation, carbon dioxide production and heart rate should not be used as surrogates for overall cardiac function and pumping capability of the heart.

  6. The effect of electrical conductivity of myocardium on cardiac pumping efficacy: a computational study.

    PubMed

    Yuniarti, Ana Rahma; Lim, Ki Moo

    2017-01-10

    The existence of non-excitable cells in the myocardium leads to the increasing conduction non-uniformity and decreasing myocardial electrical conductivity. Slowed myocardial conduction velocity (MCV) believed to enhance the probability of cardiac arryhthmia and alter the cardiac mechanical pumping efficacy, even in sinus rhythm. Though several studies on the correlation between MCV and cardiac electrical instabilities exist, there has been no study concerning correlation or causality between MCV and cardiac mechanical pumping efficacy, due to the limitation in clinical methods to document and evaluate cardiac mechanical responses directly. The goal of this study was to examine quantitatively the cardiac pumping efficacy under various MCV conditions using three-dimensional (3D) electromechanical model of canine's failing ventricle. The electromechanical model used in this study composed of the electrical model coupled with the mechanical contraction model along with a lumped model of the circulatory system. The electrical model consisted of 241,725 nodes and 1,298,751 elements of tetrahedral mesh, whereas the mechanical model consisted of 356 nodes and 172 elements of hexahedral mesh with Hermite basis. First, we performed the electrical simulation for five different MCV conditions, from 30 to 70 cm/s with 10 cm/s interval during sinus pacing. Then, we compared the cardiac electrical and mechanical responses of each MCV condition, such as the electrical activation time (EAT), pressure, volume, and energy consumption of the myocardium. The energy consumption of the myocardium was calculated by integrating ATP consumption rate of each node in myofilament model. The result showed that under higher MCV conditions, the EAT, energy consumption, end diastolic and systolic volume are gradually decreased. Meanwhile, the systolic pressure, stroke volume, stroke work, and stroke work to ATP are increased as the MCV values increased. The cardiac functions and performances are

  7. Return of Viable Cardiac Function After Sonographic Cardiac Standstill in Pediatric Cardiac Arrest.

    PubMed

    Steffen, Katherine; Thompson, W Reid; Pustavoitau, Aliaksei; Su, Erik

    2017-01-01

    Sonographic cardiac standstill during adult cardiac arrest is associated with failure to get return to spontaneous circulation. This report documents 3 children whose cardiac function returned after standstill with extracorporeal membranous oxygenation. Sonographic cardiac standstill may not predict cardiac death in children.

  8. Preoperative intra-aortic balloon pumping in high-risk cardiac surgery patients.

    PubMed

    Moon, Chooza

    2012-01-01

    Intra-aortic balloon pumping increases myocardial oxygen supply and decreases myocardial oxygen demand by inflation and deflation of the balloon. This leads to increased perfusion of the coronary arteries during diastole. This technology has been used for critically ill cardiac patients for more than 30 years. The literature suggests that preoperative use of an intra-aortic balloon pump can be effective in high-risk coronary artery bypass grafting patients. Preoperative benefits of this technology may yield positive outcomes in terms of hemodynamic effect, decreased length of stay in both the intensive care unit and the hospital, and the reduction of complications. However, the intra-aortic balloon pump must be used with a profound understanding of proper mechanism and function, monitoring, and observation for potential complications. This requires excellent critical care nursing management.

  9. Anisotropic reinforcement of acute anteroapical infarcts improves pump function.

    PubMed

    Fomovsky, Gregory M; Clark, Samantha A; Parker, Katherine M; Ailawadi, Gorav; Holmes, Jeffrey W

    2012-07-01

    We hypothesize that a therapy that improves left ventricular (LV) pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of LV function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, whereas isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at baseline, 45 minutes after coronary ligation (ischemia), and 30 minutes later, after surgical reinforcement in the longitudinal direction (anisotropic). Ischemia shifted the end-systolic pressure-volume relationship and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. We conclude that anisotropic reinforcement is a promising new approach to improving LV function after a large myocardial infarction.

  10. From syncitium to regulated pump: a cardiac muscle cellular update

    PubMed Central

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information on Ca2+ microdomains and local control theory, with particular emphasis on the role of Ca2+ sparks as a key regulatory component of ventricular myocyte contraction dynamics. Recent information pertaining to local Ca2+ cycling in sinoatrial nodal cells (SANCs) as a mechanism underlying cardiac automaticity is also presented as part of the recently described coupled-clock pacemaker system. The details of this regulation are emerging; however, the notion that the sequestration and release of Ca2+ from internal stores in SANCs (similar to that observed in ventricular myocytes) regulates the rhythmic excitation of the heart (i.e., membrane ion channels) is an important advancement in this area. The regulatory role of cardiac adrenergic receptors on cardiac rate and function is also included, and fundamental concepts related to intracellular signaling are discussed. An important point of emphasis is that whole organ cardiac dynamics can be traced back to cellular events regulating intracellular Ca2+ homeostasis and, as such, provides an important conceptual framework from which students can begin to think about whole organ physiology in health and disease. Greater synchrony of Ca2+-regulatory mechanisms between ventricular and pacemaker cells should enhance student comprehension of complex regulatory phenomenon in cardiac muscle. PMID:21385997

  11. Measuring Dynamic Transfer Functions of Cavitating Pumps

    NASA Technical Reports Server (NTRS)

    Baun, Daniel

    2007-01-01

    A water-flow test facility has been built to enable measurement of dynamic transfer functions (DTFs) of cavitating pumps and of inducers in such pumps. Originally, the facility was intended for use in an investigation of the effects of cavitation in a rocket-engine low-pressure oxygen turbopump. The facility can also be used to measure DTFs of cavitating pumps in general

  12. On the mechanics of cardiac function of Drosophila embryo.

    PubMed

    Wu, Mingming; Sato, Thomas N

    2008-01-01

    The heart is a vital organ that provides essential circulation throughout the body. Malfunction of cardiac pumping, thus, leads to serious and most of the times, to fatal diseases. Mechanics of cardiac pumping is a complex process, and many experimental and theoretical approaches have been undertaken to understand this process. We have taken advantage of the simplicity of the embryonic heart of an invertebrate, Drosophila melanogaster, to understand the fundamental mechanics of the beating heart. We applied a live imaging technique to the beating embryonic heart combined with analytical imaging tools to study the dynamic mechanics of the pumping. Furthermore, we have identified one mutant line that exhibits aberrant pumping mechanics. The Drosophila embryonic heart consists of only 104 cardiac cells forming a simple straight tube that can be easily accessed for real-time imaging. Therefore, combined with the wealth of available genetic tools, the embryonic Drosophila heart may serve as a powerful model system for studies of human heart diseases, such as arrhythmia and congenital heart diseases. We, furthermore, believe our mechanistic data provides important information that is useful for our further understanding of the design of biological structure and function and for engineering the pumps for medical uses.

  13. The role of prophylactic intra-aortic balloon pump counterpulsation (IABP) in emergency non-cardiac surgery.

    PubMed

    Samad, Khalid; Khan, Fauzia Anis

    2006-01-01

    Patients with recent myocardial infarction (MI), congestive heart failure, severe angina, or uncorrected multivessel coronary artery disease are at increased risk of cardiac complications after urgent major non-cardiac surgery. Although invasive haemodynamic monitoring and preoperative optimization of cardiac status may lead to some reduction in the rate of perioperative cardiac events, the mortality from such events still remains high. The use of an intra-aortic balloon pump (IABP) may play a role in such patients by improving the function of the injured heart. We report our experience with the use of perioperative IABP in a patient with unstable angina and recent MI who underwent urgent cholecystectomy. There were no perioperative cardiac events while the IABP was in place. The anaesthetic concerns, intraoperative and postoperative monitoring and care and usefulness of IABP will be discussed.

  14. Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

    PubMed Central

    Groeneveld, AB Johan; Jansen, Evert K; Verheij, Joanne

    2007-01-01

    Background Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs. Methods To test this hypothesis, we studied the postoperative pulmonary leak index (PLI) for 67Ga-transferrin and (transpulmonary) extravascular lung water (EVLW) in consecutive patients undergoing on-pump (n = 31) and off-pump (n = 8) cardiac surgery. We also studied transfusion history, radiographs, ventilatory and gas exchange variables. Results The postoperative PLI and EVLW were elevated above normal in 42 and 29% after on-pump surgery and 63 and 37% after off-pump surgery, respectively (ns). Transfusion of red blood cell (RBC) concentrates, PLI, EVLW, occurrence of atelectasis, ventilatory variables and duration of mechanical ventilation did not differ between groups, whereas patients with atelectasis had higher venous admixture and airway pressures than patients without atelectasis (P = 0.037 and 0.049). The PLI related to number of RBC concentrates infused (P = 0.025). Conclusion The lung vascular injury in about half of patients after cardiac surgery is not caused by CPB perfusion but by trauma necessitating RBC transfusion, so that off-pump surgery may not afford a benefit in this respect. However, atelectasis rather than lung vascular injury is a major determinant of postoperative pulmonary dysfunction, irrespective of CPB perfusion. PMID:17300720

  15. Normal cardiac function in mice with supraphysiological cardiac creatine levels

    PubMed Central

    Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A.; Jacobs, Danny O.

    2013-01-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies. PMID:24271489

  16. Normal cardiac function in mice with supraphysiological cardiac creatine levels.

    PubMed

    Santacruz, Lucia; Hernandez, Alejandro; Nienaber, Jeffrey; Mishra, Rajashree; Pinilla, Miguel; Burchette, James; Mao, Lan; Rockman, Howard A; Jacobs, Danny O

    2014-02-01

    Creatine and phosphocreatine levels are decreased in heart failure, and reductions in myocellular phosphocreatine levels predict the severity of the disease and portend adverse outcomes. Previous studies of transgenic mouse models with increased creatine content higher than two times baseline showed the development of heart failure and shortened lifespan. Given phosphocreatine's role in buffering ATP content, we tested the hypothesis whether elevated cardiac creatine content would alter cardiac function under normal physiological conditions. Here, we report the creation of transgenic mice that overexpress the human creatine transporter (CrT) in cardiac muscle under the control of the α-myosin heavy chain promoter. Cardiac transgene expression was quantified by qRT-PCR, and human CrT protein expression was documented on Western blots and immunohistochemistry using a specific anti-CrT antibody. High-energy phosphate metabolites and cardiac function were measured in transgenic animals and compared with age-matched, wild-type controls. Adult transgenic animals showed increases of 5.7- and 4.7-fold in the content of creatine and free ADP, respectively. Phosphocreatine and ATP levels were two times as high in young transgenic animals but declined to control levels by the time the animals reached 8 wk of age. Transgenic mice appeared to be healthy and had normal life spans. Cardiac morphometry, conscious echocardiography, and pressure-volume loop studies demonstrated mild hypertrophy but normal function. Based on our characterization of the human CrT protein expression, creatine and phosphocreatine content, and cardiac morphometry and function, these transgenic mice provide an in vivo model for examining the therapeutic value of elevated creatine content for cardiac pathologies.

  17. Developmental regulation of cation pumps in skeletal and cardiac muscle.

    PubMed

    Dauncey, M J; Harrison, A P

    1996-03-01

    The prenatal and early postnatal periods are critical stages during which long-term development can be affected. For example, retardation of growth during these periods is closely linked to the occurrence of adult degenerative diseases. Appropriate development of muscle is essential for numerous functions, including movement, posture, thermogenesis, breathing and maintenance of the circulation. Defects in normal muscle development could thus impair any of these functions in the neonate and may also have long-term consequences for the health of the individual. Central to normal muscle structure and function is the appropriate development not only of the sarcomeric proteins but also of the sarcolemma, transverse-tubules, sarcoplasmic reticulum and associated membrane-bound ATPases. Long-term regulation of these ATPases is by changes in their concentration, whereas short-term regulation is mediated by alterations in enzyme activity. This review focuses on changes in total concentrations of Na+, K+, and Ca(2+)-ATPases during prenatal and postnatal life, in functionally diverse muscles of mammalian species born at different stages of maturity. Both these cation pumps belong to multigene families and changes in relative abundance of their specific isoforms are also considered because they may have important consequences for contractile performance during distinct stages of development. Finally, potential regulatory mechanisms which alter markedly during normal ontogeny are discussed. These include intrinsic factors such as hormones and contractile activity, extrinsic factors such as nutrition and environmental temperature, and interactions between these variables which are known to be especially important during postnatal development.

  18. Clinical effectiveness of centrifugal pump to produce pulsatile flow during cardiopulmonary bypass in patients undergoing cardiac surgery.

    PubMed

    Gu, Y John; van Oeveren, Willem; Mungroop, Hubert E; Epema, Anne H; den Hamer, Inez J; Keizer, Jorrit J; Leuvenink, Ron P; Mariani, Massimo A; Rakhorst, Gerhard

    2011-02-01

    Although the centrifugal pump has been widely used as a nonpulsatile pump for cardiopulmonary bypass (CPB), little is known about its performance as a pulsatile pump for CPB, especially on its efficacy in producing hemodynamic energy and its clinical effectiveness. We performed a study to evaluate whether the Rotaflow centrifugal pump produces effective pulsatile flow during CPB and whether the pulsatile flow in this setting is clinically effective in adult patients undergoing cardiac surgery. Thirty-two patients undergoing CPB for elective coronary artery bypass grafting were randomly allocated to a pulsatile perfusion group (n = 16) or a nonpulsatile perfusion group (n = 16). All patients were perfused with the Rotaflow centrifugal pump. In the pulsatile group, the centrifugal pump was adjusted to the pulsatile mode (60 cycles/min) during aortic cross-clamping, whereas in the nonpulsatile group, the pump was kept in its nonpulsatile mode during the same period of time. Compared with the nonpulsatile group, the pulsatile group had a higher pulse pressure (P < 0.01) and a fraction higher energy equivalent pressure (EEP, P = 0.058). The net gain of pulsatile flow, represented by the surplus hemodynamic energy (SHE), was found much higher in the CPB circuit than in patients (P < 0.01). Clinically, there was no difference between the pulsatile and nonpulsatile groups with regard to postoperative acute kidney injury, endothelial activation, or inflammatory response. Postoperative organ function and the duration of hospital stay were similar in the two patient groups. In conclusion, pulsatile CPB with the Rotaflow centrifugal pump is associated with a small gain of EEP and SHE, which does not seem to be clinically effective in adult cardiac surgical patients.

  19. NOTE: Increasing cardiac output and decreasing oxygenation sequence in pump twins of acardiac twin pregnancies

    NASA Astrophysics Data System (ADS)

    van Gemert, Martin J. C.; Umur, Asli; van den Wijngaard, Jeroen P. H. M.; Van Bavel, Ed; Vandenbussche, Frank P. H. A.; Nikkels, Peter G. J.

    2005-02-01

    An acardiac twin pregnancy is a rare but serious complication of monochorionic twinning and consists of an acardiac twin and a pump twin. The acardiac twin is a severely malformed fetus that lacks most organs, particularly a heart, but grows during pregnancy because it is perfused by the developmentally normal pump twin via a set of arterioarterial and venovenous placental anastomoses. Pump twins die intrauterine or neonatally in about 50% of the cases. Because the effects of an acardiac mass on the pump twin's development are incompletely known, methods for outcome prognosis are currently not available. We sought to derive simple relations for the pump twin's excess cardiac output and decreased oxygenation and to use available clinical cases for a preliminary test of the model. As a method, we used a theoretical flow model to represent the fetoplacental circulation of an acardiac twin pregnancy and estimated blood deoxygenation and reoxygenation following perfusion of the two bodies and placentas, respectively. The results show the pump twin's excess cardiac output and decrease of venous oxygen saturation to depend on the ratio of pump twin to acardiac twin umbilical blood flow, whose ratio can be measured by ultrasonography. The clinical cases show a decreasing umbilical flow ratio with gestation. In conclusion, prospective serial study is necessary to test whether measurement of umbilical flow ratios allows monitoring the pump twin's pathophysiologic development, possibly resulting in a guideline for prognosis of pump twin survival.

  20. Functional check of telescoping transfer pumps

    SciTech Connect

    Sharpe, C.L.

    1994-04-29

    Activities are defined which constitute a functional check of a telescoping transfer pump (TTP). This report is written to the Procedures group of HLW and particularly applies to those TTP`s which are the sole means of emergency transfer from a HLW waste tank.

  1. Development of a pump flow estimator for rotary blood pumps to enhance monitoring of ventricular function.

    PubMed

    Granegger, Marcus; Moscato, Francesco; Casas, Fernando; Wieselthaler, Georg; Schima, Heinrich

    2012-08-01

    Estimation of instantaneous flow in rotary blood pumps (RBPs) is important for monitoring the interaction between heart and pump and eventually the ventricular function. Our group has reported an algorithm to derive ventricular contractility based on the maximum time derivative (dQ/dt(max) as a substitute for ventricular dP/dt(max) ) and pulsatility of measured flow signals. However, in RBPs used clinically, flow is estimated with a bandwidth too low to determine dQ/dt(max) in the case of improving heart function. The aim of this study was to develop a flow estimator for a centrifugal pump with bandwidth sufficient to provide noninvasive cardiac diagnostics. The new estimator is based on both static and dynamic properties of the brushless DC motor. An in vitro setup was employed to identify the performance of pump and motor up to 20 Hz. The algorithm was validated using physiological ventricular and arterial pressure waveforms in a mock loop which simulated different contractilities (dP/dt(max) 600 to 2300 mm Hg/s), pump speeds (2 to 4 krpm), and fluid viscosities (2 to 4 mPa·s). The mathematically estimated pump flow data were then compared to the datasets measured in the mock loop for different variable combinations (flow ranging from 2.5 to 7 L/min, pulsatility from 3.5 to 6 L/min, dQ/dt(max) from 15 to 60 L/min/s). Transfer function analysis showed that the developed algorithm could estimate the flow waveform with a bandwidth up to 15 Hz (±2 dB). The mean difference between the estimated and measured average flows was +0.06 ± 0.31 L/min and for the flow pulsatilities -0.27 ± 0.2 L/min. Detection of dQ/dt(max) was possible up to a dP/dt(max) level of 2300 mm Hg/s. In conclusion, a flow estimator with sufficient frequency bandwidth and accuracy to allow determination of changes in ventricular contractility even in the case of improving heart function was developed.

  2. From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update

    ERIC Educational Resources Information Center

    Korzick, Donna H.

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

  3. From Syncitium to Regulated Pump: A Cardiac Muscle Cellular Update

    ERIC Educational Resources Information Center

    Korzick, Donna H.

    2011-01-01

    The primary purpose of this article is to present a basic overview of some key teaching concepts that should be considered for inclusion in an six- to eight-lecture introductory block on the regulation of cardiac performance for graduate students. Within the context of cardiac excitation-contraction coupling, this review incorporates information…

  4. Simultaneous quantification of myocardial perfusion, oxidative metabolism, cardiac efficiency and pump function at rest and during supine bicycle exercise using 1-11C-acetate PET--a pilot study.

    PubMed

    Sörensen, Jens; Valind, Sven; Andersson, Lars G

    2010-07-01

    PET using 1-(11)C-acetate (ACE-PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k(mono)). We evaluated the feasibility of quantitative ACE-PET during exercise. Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate-pressure product (RPP) was recorded repeatedly. MBF, k(mono) in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. MBF increased from 0.71 +/- 0.17 to 2.48 +/- 0.25 ml min(-1) per ml, LV-k(mono) from 0.050 +/- 0.005 to 0.146 +/- 0.021 min(-1), RV-k(mono) from 0.023 + 0.006 to 0.087 + 0.014 min(-1), RPP from 4.7 +/- 0.8 to 13.2 +/- 1.4 mmHg x min(-1) x 10(3) and Cardiac Output from 5.2 +/- 1.1 to 12.3 +/- 1.2 l min (-1) (all P < 0.001). Cardiac efficiency was unchanged (P = 0.99). Lung uptake decreased from 1.1 +/- 0.2 to 0.6 +/- 0.1 ml g(-1) (P < 0.001). A number of important parameters related to cardiac function can be quantified non-invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.

  5. Vortex pumping for routine cardiac surgery: a comparative study.

    PubMed

    Wheeldon, D R; Bethune, D W; Gill, R D

    1990-01-01

    Vortex pumping has become popular for mechanical assist applications, but has only recently received serious consideration for use as the arterial pump of choice for routine open-heart surgery. We report on a prospective randomized study designed to evaluate this pump in routine use. Sixteen patients undergoing routine coronary artery surgery were randomized into two groups in which the only difference in equipment and technique was the use of a Stockert roller pump in group S and a Biomedicus vortex pump in group B. The groups were compared with respect to haematology, perioperative fluid balance, transfusion requirements, complement activation, haemolysis and microbubble transmission. The groups were reasonably well matched, with slightly longer mean bypass and ischaemic times in group S (94.8 vs 105.5 minutes and 75.7 and 83.8 minutes respectively). Group B patients showed significant improvements over group S patients with respect to preservation of platelet numbers, decreased complement activation and reduced microbubble transmission. The afterload sensitivity of the vortex pump did not present the perfusionist with any practical problems although a different technique is required for initiating and terminating bypass. We conclude that vortex pumping would seem to offer better blood handling for routine use. More extensive testing is required to establish whether or not this would be reflected in clinically measurable improved patient outcome.

  6. Evaluation of a compressive-type skeletal muscle pump for cardiac assistance.

    PubMed

    Mizuhara, H; Koshiji, T; Nishimura, K; Nomoto, S; Matsuda, K; Ban, T

    1999-01-01

    Recent investigations have focused on using the latissimus dorsi muscle for cardiac assistance. Although cardiomyoplasty has been applied clinically, other procedures remain experimental, but promising, modes of cardiac assistance. We assessed the latissimus dorsi muscle as an in situ energy source for circulatory assist devices. We developed a pneumatic chamber as a compressive-type muscle actuator. The chamber was implanted under the latissimus dorsi muscle and converted contractile power into pneumatic pressure. The effect of chamber position and size and the influence on muscle blood flow were examined. After muscle conditioning, the pump performance of a circulatory assist device driven by the chamber was evaluated. The chamber functioned better when placed in the proximal position of the latissimus dorsi muscle. The size affected the generated pneumatic pressure, and the higher resting pressure of the chamber reduced the muscle blood flow. The maximum stroke work of the circulatory assist device was greater than that of the right ventricle but less than that of the left ventricle. The chamber could drive the circulatory assist device against the systemic range of afterload in which a high preload was available. Long-term adhesion surrounding the chamber reduced the pressure generation capability. The compressive-type muscle actuator using the latissimus dorsi muscle generated acceptable hemodynamic work for right ventricular bypass or aortic counterpulsation.

  7. [Coronary revascularization: off-pump versus on-pump--a comparison of behavior of biochemical cardiac ischemia markers].

    PubMed

    Peivandi, A A; Hake, U; Dahm, M; Opfermann, U T; Peetz, D; Hafner, G; Loos, A H; Tzanova, I; Oelert, H

    2002-03-01

    Recently, coronary artery bypass grafting (CABG) on the beating heart with avoidance of extracorporeal circulation (off-pump CABG technique) has been gaining increasing importance in modern cardiac surgery. The object of this prospective study was to compare postoperative kinetic and patterns of cardiac troponin I (cTnI), T (cTnT), and creatine kinase MB (CKMB) activities after off-pump CABG versus conventional on-pump CABG. We studied 106 patients who underwent first-time elective on-pump (group I, n = 69, 56 male, 13 female, mean age: 64.3 +/- 9.9 years, mean ejection fraction: 56 +/- 15%) or off-pump (group II, n = 37, 24 male, 13 female, mean age: 68.4 +/- 9.1 years, mean ejection fraction: 57 +/- 13%) CABG surgery via median sternotomy. CTn I and cTnT levels, total creatine kinase (CK) and CK-MB activities in the serum were measured before operation, up on arrival at the ICU and 6, 12, 24, 48 and 120 hours later. Serial 12-lead ECGs were recorded preoperatively and on days 1, 2 and 5. Serum concentrations of cardiac troponins in all patients were preoperatively either not detectable or in the normal range and significantly increased after surgery. In group I, one patient developed a Q wave myocardial infarction, one patient a non-Q wave infarction and two patients a new left bundle branch block on the ECG. One patient of group II developed a new Q-wave myocardial infarction and another patient permanent atrial fibrillation associated with a continuous arrhythmia. All patients with a myocardial infarction in the ECG showed significant elevation of concentrations or activities of these biochemical markers. The median postoperative peak values for cTnI were measured at 24 h in both groups (2.7 micrograms/l, 95%-CI: [2.2, 3.2] in group I and 1.1 micrograms/l, 95%-CI: [0.5, 1.3] in group II). CTnT postoperatively presented an earlier median peak of 0.128 microgram/l at 12 h in group II (95%-CI: [0.041, 0.146]) than in group I at 48 h (0.298 microgram/l, 95%-CI: [0

  8. Levosimendan vs. intra-aortic balloon pump in high-risk cardiac surgery.

    PubMed

    Lomivorotov, Vladimir V; Cherniavskiy, Alexander M; Boboshko, Vladimir A; Kornilov, Igor A; Lomivorotov, Vladimir N; Karaskov, Alexander M

    2011-04-01

    The purpose of our study was to compare the efficiency of levosimendan and preventive intra-aortic balloon pump in high-risk cardiac patients (left ventricular ejection fraction <35%) operated under cardiopulmonary bypass. In 20 patients, intra-aortic balloon pump was started 16-18 h before surgery; another 20 had a levosimendan infusion starting after induction of anesthesia with an initial bolus of 12 μg·kg(-1) for 10 min, followed by 0.1 μg·kg(-1)·min(-1) for 24 h. Postoperative complications, hemodynamics, and markers of cardiac damage were analyzed. In the levosimendan group, cardiac index was significantly higher 5 min after cardiopulmonary bypass, at the end of the operation, 2 and 4 h after perfusion, compared to the intra-aortic balloon pump group. The level of troponin I in the levosimendan group was significantly lower at 6 h after the operation. Intensive care unit stay was significantly shorter in the levosimendan group. It was concluded that the use of levosimendan in high-risk cardiac patients is as effective as intra-aortic balloon pump, in terms of maintaining stable hemodynamic during and after operations under cardiopulmonary bypass. The lower level of troponin I at 6 h postoperatively suggests cardioprotective properties of levosimendan, but requires further investigation.

  9. Intracellular sodium affects ouabain interaction with the Na/K pump in cultured chick cardiac myocytes

    PubMed Central

    1990-01-01

    Whether a given dose of ouabain will produce inotropic or toxic effects depends on factors that affect the apparent affinity (K0.5) of the Na/K pump for ouabain. To accurately resolve these factors, especially the effect of intracellular Na concentration (Nai), we have applied three complementary techniques for measuring the K0.5 for ouabain in cultured embryonic chick cardiac myocytes. Under control conditions with 5.4 mM Ko, the value of the K0.5 for ouabain was 20.6 +/- 1.2, 12.3 +/- 1.7, and 6.6 +/- 0.4 microM, measured by voltage-clamp, Na-selective microelectrode, and equilibrium [3H]ouabain-binding techniques, respectively. A significant difference in the three techniques was the time of exposure to ouabain (30 s-30 min). Since increased duration of exposure to ouabain would increase Nai, monensin was used to raise Nai to investigate what effect Nai might have on the apparent affinity of block by ouabain. Monensin enhanced the rise in Na content induced by 1 microM ouabain. In the presence of 1 microM [3H]ouabain, total binding was found to be a saturating function of Na content. Using the voltage- clamp method, we found that the value of the K0.5 for ouabain was lowered by nearly an order of magnitude in the presence of 3 microM monensin to 2.4 +/- 0.2 microM and the magnitude of the Na/K pump current was increased about threefold. Modeling the Na/K pump as a cyclic sequence of states with a single state having high affinity for ouabain shows that changes in Nai alone are sufficient to cause a 10- fold change in K0.5. These results suggest that Nai reduces the value of the apparent affinity of the Na/K pump for ouabain in 5.4 mM Ko by increasing its turnover rate, thus increasing the availability of the conformation of the Na/K pump that binds ouabain with high affinity. PMID:2299333

  10. Proteasome functional insufficiency in cardiac pathogenesis

    PubMed Central

    Li, Jie; Zheng, Hanqiao; Su, Huabo; Powell, Saul R.

    2011-01-01

    The ubiquitin-proteasome system (UPS) is responsible for the degradation of most cellular proteins. Alterations in cardiac UPS, including changes in the degradation of regulatory proteins and proteasome functional insufficiency, are observed in many forms of heart disease and have been shown to play an important role in cardiac pathogenesis. In the past several years, remarkable progress in understanding the mechanisms that regulate UPS-mediated protein degradation has been achieved. A transgenic mouse model of benign enhancement of cardiac proteasome proteolytic function has been created. This has led to the first demonstration of the necessity of proteasome functional insufficiency in the genesis of important pathological processes. Cardiomyocyte-restricted enhancement of proteasome proteolytic function by overexpression of proteasome activator 28α protects against cardiac proteinopathy and myocardial ischemia-reperfusion injury. Additionally, exciting advances have recently been achieved in the search for a pharmacological agent to activate the proteasome. These breakthroughs are expected to serve as an impetus to further investigation into the involvement of UPS dysfunction in molecular pathogenesis and to the development of new therapeutic strategies for combating heart disease. An interplay between the UPS and macroautophagy is increasingly suggested in noncardiac systems but is not well understood in the cardiac system. Further investigations into the interplay are expected to provide a more comprehensive picture of cardiac protein quality control and degradation. PMID:21949118

  11. Ultrasound assessment of fetal cardiac function

    PubMed Central

    Crispi, Fàtima; Valenzuela‐Alcaraz, Brenda; Cruz‐Lemini, Monica

    2015-01-01

    Abstract Introduction: Fetal heart evaluation with US is feasible and reproducible, although challenging due to the smallness of the heart, the high heart rate and limited access to the fetus. However, some cardiac parameters have already shown a strong correlation with outcomes and may soon be incorporated into clinical practice. Materials and Methods: Cardiac function assessment has proven utility in the differential diagnosis of cardiomyopathies or prediction of perinatal mortality in congenital heart disease. In addition, some cardiac parameters with high sensitivity such as MPI or annular peak velocities have shown promising results in monitoring and predicting outcome in intrauterine growth restriction or congenital diaphragmatic hernia. Conclusion: Cardiac function can be adequately evaluated in most fetuses when appropriate expertise, equipment and time are available. Fetal cardiac function assessment is a promising tool that may soon be incorporated into clinical practice to diagnose, monitor or predict outcome in some fetal conditions. Thus, more research is warranted to further define specific protocols for each fetal condition that may affect cardiac function. PMID:28191192

  12. Cardiac Myosin Binding Protein-C Phosphorylation and Cardiac Function

    PubMed Central

    Sadayappan, Sakthivel; Gulick, James; Osinska, Hanna; Martin, Lisa A.; Hahn, Harvey S.; Dorn, Gerald W.; Klevitsky, Raisa; Seidman, Christine E.; Seidman, Jonathan G.; Robbins., Jeffrey

    2005-01-01

    The role of cardiac myosin binding protein-C (cMyBP-C) phosphorylation in cardiac physiology or pathophysiology is unclear. To investigate the status of cMyBP-C phosphorylation in vivo, we determined its phosphorylation state in stressed and unstressed mouse hearts. cMyBP-C phosphorylation is significantly decreased during the development of heart failure or pathologic hypertrophy. We then generated transgenic (TG) mice in which cMyBP-C’s phosphorylation sites were changed to nonphosphorylatable alanines (MyBP-CAllP−). A TG line showing ~40% replacement with MyBP-CAllP− showed no changes in morbidity or mortality but displayed depressed cardiac contractility, altered sarcomeric structure and upregulation of transcripts associated with a hypertrophic response. To explore the effect of complete replacement of endogenous cMyBP-C with MyBP-CAllP−, the mice were bred into the MyBP-C(t/t) background, in which less than 10% of normal levels of a truncated MyBP-C are present. Although MyBP-CAllP− was incorporated into the sarcomere and expressed at normal levels, the mutant protein could not rescue the MyBP-C(t/t) phenotype. The mice developed significant cardiac hypertrophy with myofibrillar disarray and fibrosis, similar to what was observed in the MyBP-C(t/t) animals. In contrast, when the MyBP-C(t/t) mice were bred to a TG line expressing normal MyBP-C (MyBP-CWT), the MyBP-C(t/t) phenotype was rescued. These data suggest that cMyBP-C phosphorylation is essential for normal cardiac function. PMID:16224063

  13. Classification of physiologically significant pumping states in an implantable rotary blood pump: effects of cardiac rhythm disturbances.

    PubMed

    Karantonis, Dean M; Lovell, Nigel H; Ayre, Peter J; Mason, David G; Cloherty, Shaun L

    2007-06-01

    Methods of speed control for implantable rotary blood pumps (iRBPs) are vital for providing implant recipients with sufficient blood flow to cater for their physiological requirements. The detection of pumping states that reflect the physiological state of the native heart forms a major component of such a control method. Employing data from a number of acute animal experiments, five such pumping states have been previously identified: regurgitant pump flow, ventricular ejection (VE), nonopening of the aortic valve (ANO), and partial collapse (intermittent [PVC-I] and continuous [PVC-C]) of the ventricle wall. An automated approach that noninvasively detects such pumping states, employing a classification and regression tree (CART), has also been developed. An extension to this technique, involving an investigation into the effects of cardiac rhythm disturbances on the state detection process, is discussed. When incorporating animal data containing arrhythmic events into the CART model, the strategy showed a marked improvement in detecting pumping states as compared to the model devoid of arrhythmic data: state VE--57.4/91.7% (sensitivity/specificity) improved to 97.1/100.0%; state PVC-I--66.7/83.1% improved to 100.0/88.3%, and state PVC-C--11.1/66.2% changed to 0.0/100%. With a simplified binary scheme differentiating suction (PVC-I, PVC-C) and nonsuction (VE, ANO) states, suction was initially detected with 100/98.5% sensitivity/specificity, whereas with the subsequent improved model, both these states were detected with 100% sensitivity. The accuracy achieved demonstrates the robustness of the technique presented, and substantiates its inclusion into any iRBP control methodology.

  14. Functions of Autophagy in Pathological Cardiac Hypertrophy

    PubMed Central

    Li, Zhenhua; Wang, Jian; Yang, Xiao

    2015-01-01

    Pathological cardiac hypertrophy is the response of heart to various biomechanical and physiopathological stimuli, such as aging, myocardial ischemia and hypertension. However, a long-term exposure to the stress makes heart progress to heart failure. Autophagy is a dynamic self-degradative process necessary for the maintenance of cellular homeostasis. Accumulating evidence has revealed a tight link between cardiomyocyte autophagy and cardiac hypertrophy. Sophisticatedly regulated autophagy protects heart from various physiological and pathological stimuli by degradating and recycling of protein aggregates, lipid drops, or organelles. Here we review the recent progresses concerning the functions of autophagy in cardiac hypertrophy induced by various hypertrophic stimuli. Moreover, the therapeutic strategies targeting autophagy for cardiac hypertrophy will also be discussed. PMID:25999790

  15. The Impact of Roller Pump vs. Centrifugal Pump on Homologous Blood Transfusion in Pediatric Cardiac Surgery.

    PubMed

    Datt, Bharat; Nguyen, Moui B; Plancher, Gary; Ruzmetov, Mark; O'Brien, Michael; Kube, Alicia; Munro, Hamish M; Pourmoghadam, Kamal K; DeCampli, William M

    2017-03-01

    Centrifugal pumps are considered to be less destructive to blood elements (1) when compared to roller pumps. However, their large prime volumes render them unsuitable as arterial pumps in heart lung machine (HLM) circuitry for children. In November of 2014, the circuit at Arnold Palmer Hospital, a Biomedicus BP-50 with kinetic assist venous drainage (KAVD) and 1/4″ tubing was converted to a roller pump in the arterial position with gravity drainage. Vacuum-assisted venous drainage (VAVD) was mounted on the HLM as a backup, but not used. Tubing was changed to 3/16″ in the arterial line in patients <13 kg. A retrospective study with a total of 140 patients compared patients placed on cardiopulmonary bypass (CPB) with Biomedicus centrifugal pumps and KAVD (Centrifugal Group, n = 40) to those placed on CPB with roller pumps and gravity drainage (Roller Group, n = 100). Patients requiring extra-corporeal membrane oxygenation (ECMO)/cardio-pulmonary support (CPS) or undergoing a hybrid procedure were excluded. Re-operation or circulatory arrest patients were not excluded. Prime volumes decreased by 57% from 456 ± 34 mL in the Centrifugal Group to 197 ± 34 mL in the Roller Group (p < .001). There was a corresponding increase in hematocrit (HCT) of blood primes and also on CPB. Intraoperative homologous blood transfusions also decreased 55% from 422 mL in the Centrifugal Group to 231 mL in the Roller Group (p < .001). The Society of Thoracic Surgeons--European Association for Cardio-Thoracic Surgery (STAT) categorized intubation times and hospital length of stay (LOS) for all infants showed a trend toward reduction, but was not statistically significant. Overall mortality was 5% utilizing the centrifugal configuration and 0% in the roller pump cohort. We demonstrated that the transition to roller pumps in the arterial position of the HLM considerably reduced our priming volume and formed a basis for a comprehensive blood conservation program. By maintaining higher

  16. The Impact of Roller Pump vs. Centrifugal Pump on Homologous Blood Transfusion in Pediatric Cardiac Surgery

    PubMed Central

    Datt, Bharat; Nguyen, Moui B.; Plancher, Gary; Ruzmetov, Mark; O'Brien, Michael; Kube, Alicia; Munro, Hamish M.; Pourmoghadam, Kamal K.; DeCampli, William M.

    2017-01-01

    Abstract: Centrifugal pumps are considered to be less destructive to blood elements (1) when compared to roller pumps. However, their large prime volumes render them unsuitable as arterial pumps in heart lung machine (HLM) circuitry for children. In November of 2014, the circuit at Arnold Palmer Hospital, a Biomedicus BP-50 with kinetic assist venous drainage (KAVD) and 1/4″ tubing was converted to a roller pump in the arterial position with gravity drainage. Vacuum-assisted venous drainage (VAVD) was mounted on the HLM as a backup, but not used. Tubing was changed to 3/16″ in the arterial line in patients <13 kg. A retrospective study with a total of 140 patients compared patients placed on cardiopulmonary bypass (CPB) with Biomedicus centrifugal pumps and KAVD (Centrifugal Group, n = 40) to those placed on CPB with roller pumps and gravity drainage (Roller Group, n = 100). Patients requiring extra-corporeal membrane oxygenation (ECMO)/cardio-pulmonary support (CPS) or undergoing a hybrid procedure were excluded. Re-operation or circulatory arrest patients were not excluded. Prime volumes decreased by 57% from 456 ± 34 mL in the Centrifugal Group to 197 ± 34 mL in the Roller Group (p < .001). There was a corresponding increase in hematocrit (HCT) of blood primes and also on CPB. Intraoperative homologous blood transfusions also decreased 55% from 422 mL in the Centrifugal Group to 231 mL in the Roller Group (p < .001). The Society of Thoracic Surgeons--European Association for Cardio-Thoracic Surgery (STAT) categorized intubation times and hospital length of stay (LOS) for all infants showed a trend toward reduction, but was not statistically significant. Overall mortality was 5% utilizing the centrifugal configuration and 0% in the roller pump cohort. We demonstrated that the transition to roller pumps in the arterial position of the HLM considerably reduced our priming volume and formed a basis for a comprehensive blood conservation program. By maintaining

  17. Novel endoscope system with plasma flushing for off-pump cardiac surgery.

    PubMed

    Masamune, Ken; Horiuchi, Tetsuya; Mizutani, Masahiro; Yamashita, Hiromasa; Tsukihara, Hiroyuki; Motomura, Noboru; Takamoto, Shinichi; Liao, Hongen; Dohi, Takeyoshi

    2009-01-01

    The purpose of this study is to develop a new endoscope for performing simple surgical tasks inside a cardiac atrium/chamber filled with blood, i.e., for performing "off-pump" cardiac surgeries. In general, it is very difficult to observe the inner wall of the vessels containing circulating blood because the light from the endoscope is scattered by the red blood cells. "Plasma flushing" performed using the separator system is developed to observe the inner side of the heart filled with blood and to remove blood cells from the front of the endoscope tip. The system was used in in vitro quantitative measurement of the device performance and in vivo experiments on a swine. In these experiments, we successfully obtained high-resolution images of the interior of the heart during off-pump surgery.

  18. A Separate Pool of Cardiac Phospholemman That Does Not Regulate or Associate with the Sodium Pump

    PubMed Central

    Wypijewski, Krzysztof J.; Howie, Jacqueline; Reilly, Louise; Tulloch, Lindsay B.; Aughton, Karen L.; McLatchie, Linda M.; Shattock, Michael J.; Calaghan, Sarah C.; Fuller, William

    2013-01-01

    Phospholemman (PLM), the principal quantitative sarcolemmal substrate for protein kinases A and C in the heart, regulates the cardiac sodium pump. Much like phospholamban, which regulates the related ATPase SERCA, PLM is reported to oligomerize. We investigated subpopulations of PLM in adult rat ventricular myocytes based on phosphorylation status. Co-immunoprecipitation identified two pools of PLM: one not associated with the sodium pump phosphorylated at Ser63 and one associated with the pump, both phosphorylated at Ser68 and unphosphorylated. Phosphorylation of PLM at Ser63 following activation of PKC did not abrogate association of PLM with the pump, so its failure to associate with the pump was not due to phosphorylation at this site. All pools of PLM co-localized to cell surface caveolin-enriched microdomains with sodium pump α subunits, despite the lack of caveolin-binding motif in PLM. Mass spectrometry analysis of phosphospecific immunoprecipitation reactions revealed no unique protein interactions for Ser63-phosphorylated PLM, and cross-linking reagents also failed to identify any partner proteins for this pool. In lysates from hearts of heterozygous transgenic animals expressing wild type and unphosphorylatable PLM, Ser63-phosphorylated PLM co-immunoprecipitated unphosphorylatable PLM, confirming the existence of PLM multimers. Dephosphorylation of the PLM multimer does not change sodium pump activity. Hence like phospholamban, PLM exists as a pump-inhibiting monomer and an unassociated oligomer. The distribution of different PLM phosphorylation states to different pools may be explained by their differential proximity to protein phosphatases rather than a direct effect of phosphorylation on PLM association with the pump. PMID:23532852

  19. Cardiac mitochondria exhibit dynamic functional clustering

    PubMed Central

    Kurz, Felix T.; Aon, Miguel A.; O'Rourke, Brian; Armoundas, Antonis A.

    2014-01-01

    Multi-oscillatory behavior of mitochondrial inner membrane potential ΔΨm in self-organized cardiac mitochondrial networks can be triggered by metabolic or oxidative stress. Spatio-temporal analyses of cardiac mitochondrial networks have shown that mitochondria are heterogeneously organized in synchronously oscillating clusters in which the mean cluster frequency and size are inversely correlated, thus suggesting a modulation of cluster frequency through local inter-mitochondrial coupling. In this study, we propose a method to examine the mitochondrial network's topology through quantification of its dynamic local clustering coefficients. Individual mitochondrial ΔΨm oscillation signals were identified for each cardiac myocyte and cross-correlated with all network mitochondria using previously described methods (Kurz et al., 2010a). Time-varying inter-mitochondrial connectivity, defined for mitochondria in the whole network whose signals are at least 90% correlated at any given time point, allowed considering functional local clustering coefficients. It is shown that mitochondrial clustering in isolated cardiac myocytes changes dynamically and is significantly higher than for random mitochondrial networks that are constructed using the Erdös–Rényi model based on the same sets of vertices. The network's time-averaged clustering coefficient for cardiac myocytes was found to be 0.500 ± 0.051 (N = 9) vs. 0.061 ± 0.020 for random networks, respectively. Our results demonstrate that cardiac mitochondria constitute a network with dynamically connected constituents whose topological organization is prone to clustering. Cluster partitioning in networks of coupled oscillators has been observed in scale-free and chaotic systems and is therefore in good agreement with previous models of cardiac mitochondrial networks. PMID:25228884

  20. Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps.

    PubMed

    Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

    2016-05-06

    In addition to the well-known light-driven outward proton pumps, novel ion-pumping rhodopsins functioning as outward Na(+) and inward Cl(-) pumps have been recently found in eubacteria. They convert light energy into transmembrane electrochemical potential difference, similar to the prototypical archaeal H(+) pump bacteriorhodopsin (BR) and Cl(-) pump halorhodopsin (HR). The H(+), Na(+), and Cl(-) pumps possess the conserved respective DTE, NDQ, and NTQ motifs in the helix C, which likely serve as their functional determinants. To verify this hypothesis, we attempted functional interconversion between selected pumps from each category by mutagenesis. Introduction of the proton-pumping motif resulted in successful Na(+) → H(+) functional conversion. Introduction of the respective characteristic motifs with several additional mutations leads to successful Na(+) → Cl(-) and Cl(-) → H(+) functional conversions, whereas remaining conversions (H(+) → Na(+), H(+) → Cl(-), Cl(-) → Na(+)) were unsuccessful when mutagenesis of 4-6 residues was used. Phylogenetic analysis suggests that a H(+) pump is the common ancestor of all of these rhodopsins, from which Cl(-) pumps emerged followed by Na(+) pumps. We propose that successful functional conversions of these ion pumps are achieved exclusively when mutagenesis reverses the evolutionary amino acid sequence changes. Dependence of the observed functional conversions on the direction of evolution strongly suggests that the essential structural mechanism of an ancestral function is retained even after the gain of a new function during natural evolution, which can be evoked by a few mutations. By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro.

  1. Asymmetric Functional Conversion of Eubacterial Light-driven Ion Pumps*

    PubMed Central

    Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

    2016-01-01

    In addition to the well-known light-driven outward proton pumps, novel ion-pumping rhodopsins functioning as outward Na+ and inward Cl− pumps have been recently found in eubacteria. They convert light energy into transmembrane electrochemical potential difference, similar to the prototypical archaeal H+ pump bacteriorhodopsin (BR) and Cl− pump halorhodopsin (HR). The H+, Na+, and Cl− pumps possess the conserved respective DTE, NDQ, and NTQ motifs in the helix C, which likely serve as their functional determinants. To verify this hypothesis, we attempted functional interconversion between selected pumps from each category by mutagenesis. Introduction of the proton-pumping motif resulted in successful Na+ → H+ functional conversion. Introduction of the respective characteristic motifs with several additional mutations leads to successful Na+ → Cl− and Cl− → H+ functional conversions, whereas remaining conversions (H+ → Na+, H+ → Cl−, Cl− → Na+) were unsuccessful when mutagenesis of 4–6 residues was used. Phylogenetic analysis suggests that a H+ pump is the common ancestor of all of these rhodopsins, from which Cl− pumps emerged followed by Na+ pumps. We propose that successful functional conversions of these ion pumps are achieved exclusively when mutagenesis reverses the evolutionary amino acid sequence changes. Dependence of the observed functional conversions on the direction of evolution strongly suggests that the essential structural mechanism of an ancestral function is retained even after the gain of a new function during natural evolution, which can be evoked by a few mutations. By contrast, the gain of a new function needs accumulation of multiple mutations, which may not be easily reproduced by limited mutagenesis in vitro. PMID:26929409

  2. Acetyl-l-carnitine and oxfenicine on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats.

    PubMed

    Wang, Chih-Hsien; Wang, Shoei-Shen; Ko, Wen-Je; Chen, Yih-Sharng; Chang, Chun-Yi; Chang, Ru-Wen; Chang, Kuo-Chu

    2013-01-01

    In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship. Diabetes was induced by a single tail vein injection of 55 mg kg(-1) streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L(-1) in drinking water) or oxfenicine (150 mg kg(-1) by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine. Acetyl-l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility

  3. Renal function after off-pump versus on-pump coronary artery bypass grafting.

    PubMed

    Singh, Rana Sandip; Thingnam, Shyam Kumar Singh; Mishra, Anand Kumar; Verma, Indu; Kumar, Vikas

    2017-01-01

    Background Renal dysfunction is a well-recognized major complication after coronary artery bypass grafting. Off-pump coronary artery bypass theoretically appears to have less impact on renal function. We estimated preoperative and postoperative creatinine clearance as a marker of renal dysfunction in patients undergoing off-pump and on-pump coronary artery bypass. Methods Thirty patients undergoing coronary artery bypass were randomly allocated to undergo either on-pump ( n = 15) or off-pump surgery ( n = 15). The two groups had similar preoperative demographic characteristics. Serum creatinine and creatinine clearance were measured for 4 days postoperatively and the results were compared with preoperative levels. Results The rise in serum creatinine on postoperative day 1 was 0.28 mgċdL(-1) in the on-pump group and 0.22 mgċdL(-1) in the off-pump group ( p = 0.27); on postoperative day 4 it was 0.15 mgċdL(-1) and 0.10 mgċdL(-1), respectively, ( p = 0.28). Similarly, the fall in creatinine clearance was 17.34 mLċmin(-1) in the on-pump group and 19.62 mLċmin(-1) in the off-pump group on postoperative day 1 ( p = 0.42), and 10.9 and 10.94 mLċmin(-1), respectively, on postoperative day 4 ( p = 0.64). Conclusion Renal function is not affected by the technique of coronary artery bypass surgery, whether with or without cardiopulmonary bypass, in spite of the theoretical advantage of off-pump surgery. Our study suggests that off-pump coronary artery bypass surgery does not confer significant protection from postoperative renal dysfunction in low-risk patients, when compared with on-pump surgery.

  4. Centrifugal pump and roller pump in adult cardiac surgery: a meta-analysis of randomized controlled trials.

    PubMed

    Saczkowski, Richard; Maklin, Michelle; Mesana, Thierry; Boodhwani, Munir; Ruel, Marc

    2012-08-01

    Centrifugal pump (CP) and roller pump (RP) designs are the dominant main arterial pumps used in cardiopulmonary bypass (CPB). Trials reporting clinical outcome measures comparing CP and RP are controversial. Therefore, a meta-analysis was undertaken to evaluate clinical variables from randomized controlled trials (RCTs). Keyword searches were performed on Medline (1966-2011), EmBase (1980-2011), and CINAHL (1981-2011) for studies comparing RP and CP as the main arterial pump in adult CPB. Pooled fixed-effects estimates for dichotomous and continuous data were calculated as an odds ratio and weighted-mean difference, respectively. The P value was utilized to assess statistical significance (P < 0.05) between CP and RP groups. Eighteen RCTs met inclusion criteria, which represented 1868 patients (CP = 961, RP = 907). The prevailing operation was isolated coronary artery bypass graft surgery (CP = 88%, RP = 87%). Fixed-effects pooled estimates were performed for end-of-CPB (ECP) and postoperative day one (PDO) for platelet count (ECP: P = 0.51, PDO: P = 0.16), plasma free hemoglobin (ECP: P = 0.36, PDO: P = 0.24), white blood cell count (ECP: P = 0.21, PDO: P = 0.66), and hematocrit (ECP: P = 0.06, PDO: P = 0.51). No difference was demonstrated for postoperative blood loss (P = 0.65) or red blood cell transfusion (P = 0.71). Intensive care unit length of stay (P = 0.30), hospital length of stay (P = 0.33), and mortality (P = 0.91) were similar between the CP and RP groups. Neurologic outcomes were not amenable to pooled analysis; nevertheless, the results were inconclusive. There was no reported pump-related malfunction or mishap. The meta-analysis of RCTs comparing CP and RP in adult cardiac surgery suggests no significant difference for hematological variables, postoperative blood loss, transfusions, neurological outcomes, or mortality. © 2012, Copyright the Authors. Artificial Organs © 2012

  5. Na+/K+ pump inhibition induces cell shrinkage in cultured chick cardiac myocytes.

    PubMed

    Smith, T W; Rasmusson, R L; Lobaugh, L A; Lieberman, M

    1993-01-01

    Myocardial cell swelling occurs in ischemia and in reperfusion injury before the onset of irreversible injury. Swelling has been attributed to failure of the Na+/K+ pump and the accumulation of intracellular Na+. To evaluate the role of the pump-leak model of cell volume maintenance, short term changes in cell volume in response to Na+/K+ pump inhibition were studied in aggregates of cultured embryonic chick cardiac myocytes using optical and biochemical methods. Exposure to 100 microM ouabain over 20 min induced cell shrinkage of approximately 10%. Cell water was also decreased by Na+/K+ pump inhibition; incubation for 1 hr either in the presence of 100 microM ouabain or in K(+)-free solution reduced cell water by 18.4% and 28.4% respectively. When exposed to ouabain in the absence of extracellular Ca2+, the aggregates swelled by approximately 15%, indicating that extracellular Ca2+ was required for the ouabain-induced shrinkage to occur. Ouabain still caused shrinkage, however, in the presence of the Ca2+ channel blockers verapamil (10 microM) and nifedipine (10 microM), suggesting that Na+/Ca2+ exchange, rather than Ca2+ channels, is the route for Ca2+ influx during Na+/K+ pump inhibition. Efflux of amino acids (taurine, aspartate, glutamate, glycine and alanine) from confluent monolayers of chick heart cells exposed to ouabain for 20 min was nearly double that observed in control solution. These results suggest that, during Na+/K+ pump inhibition, chick heart cells can limit accumulation of intracellular sodium by means of Na+/Ca2+ exchange, and that a rise in intracellular [Ca2+], also mediated by Na+/Ca2+ exchange, promotes the loss of amino acids and ions to cause cell shrinkage. Therefore, swelling during ischemic injury may not result from Na+/K+ pump failure alone, but may reflect the exhaustion of alternative volume regulatory transport mechanisms.

  6. Mechanisms contributing to the cardiac inotropic effect of Na pump inhibition and reduction of extracellular Na

    PubMed Central

    1987-01-01

    Reduction of the transsarcolemmal [Na] gradient in rabbit cardiac muscle leads to an increase in the force of contraction. This has frequently been attributed to alteration of Ca movements via the sarcolemmal Na/Ca exchange system. However, the specific mechanisms that mediate the increased force at individual contractions have not been clearly established. In the present study, the [Na] gradient was decreased by reduction of extracellular [Na] or inhibition of the Na pump by either the cardioactive steroid acetylstrophanthidin or by reduction of extracellular [K]. Contractile performance and changes in extracellular Ca (sensed by double-barreled Ca-selective microelectrodes) were studied in order to elucidate the underlying basis for the increase in force. In the presence of agents that inhibit sarcoplasmic reticulum (SR) function (10 mM caffeine, 100-500 nM ryanodine), reduction of the [Na] gradient produced increases in contractile force similar to that observed in the absence of caffeine or ryanodine. It is concluded that an intact, functioning SR is not required for the inotropic effect of [Na] gradient reduction (at least in rabbit ventricle). However, this does not exclude a possible contribution of enhanced SR Ca release in the inotropic response to [Na] gradient reduction in the absence of caffeine or ryanodine. Acetylstrophanthidin (3-5 microM) usually leads to an increase in the magnitude of extracellular Ca depletions associated with individual contractions. However, acetylstrophanthidin can also increase extracellular Ca accumulation during the contraction, especially at potentiated contractions. This extracellular Ca accumulation can be suppressed by ryanodine and it is suggested that this apparent enhancement of Ca efflux is secondary to an enhanced release of Ca from the SR. Under conditions where Ca efflux during contractions is minimized (after a rest interval in the presence of ryanodine), acetylstrophanthidin increased both the rate and the

  7. Improved Outcome of Cardiac Extracorporeal Membrane Oxygenation in Infants and Children Using Magnetic Levitation Centrifugal Pumps.

    PubMed

    Luciani, Giovanni Battista; Hoxha, Stiljan; Torre, Salvatore; Rungatscher, Alessio; Menon, Tiziano; Barozzi, Luca; Faggian, Giuseppe

    2016-01-01

    Extracorporeal membrane oxygenation (ECMO) has traditionally been and, for the most part, still is being performed using roller pumps. Use of first-generation centrifugal pumps has yielded controversial outcomes, perhaps due to mechanical properties of the same and the ensuing risk of hemolysis and renal morbidity. Latest-generation centrifugal pumps, using magnetic levitation (ML), exhibit mechanical properties which may have overcome limitations of first-generation devices. This retrospective study aimed to assess the safety and efficacy of veno-arterial (V-A) ECMO for cardiac indications in neonates, infants, and children, using standard (SP) and latest-generation ML centrifugal pumps. Between 2002 and 2014, 33 consecutive neonates, infants, and young children were supported using V-A ECMO for cardiac indications. There were 21 males and 12 females, with median age of 29 days (4 days-5 years) and a median body weight of 3.2 kg (1.9-18 kg). Indication for V-A ECMO were acute circulatory collapse in ICU or ward after cardiac repair in 16 (49%) patients, failure to wean after repair of complex congenital heart disease in 9 (27%), fulminant myocarditis in 4 (12%), preoperative sepsis in 2 (6%), and refractory tachy-arrhythmias in 2 (6%). Central cannulation was used in 27 (81%) patients and peripheral in 6. Seven (21%) patients were supported with SP and 26 (79%) with ML centrifugal pumps. Median duration of support was 82 h (range 24-672 h), with 26 (79%) patients weaned from support. Three patients required a second ECMO run but died on support. Seventeen (51%) patients required peritoneal dialysis for acute renal failure. Overall survival to discharge was 39% (13/33 patients). All patients with fulminant myocarditis and with refractory arrhythmias were weaned, and five (83%) survived, whereas no patient supported for sepsis survived. Risk factors for hospital mortality included lower (<2.5 kg) body weight (P = 0.02) and rescue ECMO after cardiac

  8. The effects of cardiopulmonary bypass on pulmonary function during robotic cardiac surgery.

    PubMed

    Wang, G; Xiao, S; Gao, C

    2015-04-01

    We aimed to investigate the effects of cardiopulmonary bypass (CPB) on pulmonary function under the conditions of one-lung ventilation (OLV) and carbon dioxide pneumothorax in robotic cardiac surgery. Ninety-eight patients underwent robotic cardiac surgery using the da Vinci Surgical System, including 58 on-pump surgeries and 40 off-pump surgeries. Respiratory parameters and arterial blood gases were assessed at the following time points: 25 min after the induction of anesthesia under two-lung ventilation (T1), 25 min after OLV (T2), 25 min after the termination of CPB under OLV in the on-pump group or 25 min after the main surgery intervention in the off-pump group (T3) and 20 min before the end of surgery (T4). Dynamic lung compliance (Cdyn), alveolar-arterial PO2 difference (PA-aDO2), oxygenation index (OI) and artery-alveolar O2 pressure ratio (a/A) were calculated. No significant differences in pulmonary function parameters between T2 and T3 were observed in the off-pump group. However, in the on-pump group, compared with those at T2, PETCO2, Ppeak, PaCO2 and PA-aDO2 at T3 were higher, whereas SpO2, Cdyn, PaO2, OI and a/A were lower (p<0.05). Comparisons between the two groups at T3 indicated that SpO2, Cdyn, PaO2, OI and a/A were higher, while Ppeak, PaCO2 and PA-aDO2 were lower in the off-pump group (p<0.01). In robotic cardiac surgery under the conditions of OLV and carbon dioxide pneumothorax, CPB worsened pulmonary function and tolerance to OLV and carbon dioxide pneumothorax. © The Author(s) 2014.

  9. Membrane potential hyperpolarization in Mammalian cardiac cells by synchronization modulation of Na/K pumps.

    PubMed

    Chen, Wei; Dando, Robin

    2008-02-01

    In previously reported work, we developed a new technique, synchronization modulation, to electrically activate Na/K pump molecules. The fundamental mechanism involved in this technique is a dynamic entrainment procedure of the pump molecules, carried out in a stepwise pattern. The entrainment procedure consists of two steps: synchronization and modulation. We theoretically predicted that the pump functions can be activated exponentially as a function of the membrane potential. We have experimentally demonstrated synchronization of the Na/K pump molecules and acceleration of their pumping rates by many fold through use of voltage-clamp techniques, directly monitoring the pump currents. We further applied this technique to intact skeletal muscle fibers from amphibians and found significant effects on the membrane resting potential. Here, we extend our study to intact mammalian cardiomyocytes. We employed a noninvasive confocal microscopic fluorescent imaging technique to monitor electric field-induced changes in ionic concentration gradient and membrane resting potential. Our results further confirm that the well-designed synchronization modulation electric field can effectively accelerate the Na/K pumping rate, increasing the ionic concentration gradient across the cell membrane and hyperpolarizing the membrane resting potential.

  10. Proton pump inhibitors for functional dyspepsia.

    PubMed

    Pinto-Sanchez, Maria Ines; Yuan, Yuhong; Bercik, Premysl; Moayyedi, Paul

    2017-03-08

    Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD. To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia. We searched in the following electronic databases: the Cochrane Library (to January 2016), MEDLINE (OvidSP; to February 2016), Embase (OvidSP; to February 2016), and SIGLE grey literature (up to February 2016) and clinical trial registries; we handsearched abstracts from conferences up to February 2016. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information. All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group). Two review authors independently assessed eligibility, trial quality and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review. We identified 23 RCTs from 22 papers (with 8759

  11. Cardiac function in trisomy 21 fetuses.

    PubMed

    Clur, S A B; Oude Rengerink, K; Ottenkamp, J; Bilardo, C M

    2011-02-01

    Trisomy 21 is associated with an increased nuchal translucency thickness (NT), abnormal ductus venosus (DV) flow at 11-14 weeks' gestation and congenital heart defects (CHD), and cardiac dysfunction has been hypothesized as the link between them. We therefore aimed to investigate whether cardiac function is altered in trisomy 21 fetuses. Between December 2003 and June 2009, we performed echocardiography on 46 trisomy 21 fetuses (28 with structurally normal heart and 18 with CHD) and on 191 chromosomally/phenotypically normal fetuses with a confirmed normal heart (87 with normal NT and 104 with NT ≥ 95(th) percentile), between 11 and 35 weeks' gestation. Measurements included: E- and A-wave peak velocity, E/A velocity ratio and E/time velocity integral (TVI) ratio over atrioventricular valves; myocardial performance index (MPI); semilunar valve peak velocity and acceleration time; stroke volume (SV); cardiac output; and DV pulsatility index for veins (PIV) at 11-14 weeks' gestation. Data were categorized into three different age groups for analysis (11 to 13 + 6, 14 to 21 + 6 and 22 to 35 weeks' gestation). The tricuspid valve (TV) A-wave velocity and aortic valve peak velocity were significantly reduced in trisomy 21 compared with normal fetuses. Other highly significant differences found in trisomy 21 fetuses at 11-14 weeks' were increased TV-E/A ratio and DV-PIV, and decreased pulmonary valve peak velocity. We also observed evidence of left ventricular (LV) systolic dysfunction, reduced SV and increased MPI. After 14 weeks' gestation, the mitral valve A-wave peak velocity and E/TVI ratio were significantly reduced in the trisomy 21 fetuses with normal hearts compared with the controls with increased NT. In comparison with controls with normal or increased NT, cardiac function in trisomy 21 fetuses is abnormal irrespective of the presence of CHD. Evidence for cardiac loading (increased preload and afterload) and LV systolic (in the first trimester) and later

  12. Multi-Function Gas Fired Heat Pump

    SciTech Connect

    Abu-Heiba, Ahmad; Vineyard, Edward Allan

    2015-11-01

    The aim of this project was to design a residential fuel fired heat pump and further improve efficiency in collaboration with an industry partner – Southwest Gas, the developer of the Nextaire commercial rooftop fuel-fired heat pump. Work started in late 2010. After extensive search for suitable engines, one manufactured by Marathon was selected. Several prototypes were designed and built over the following four years. Design changes were focused on lowering the cost of components and the cost of manufacturing. The design evolved to a final one that yielded the lowest cost. The final design also incorporates noise and vibration reduction measures that were verified to be effective through a customer survey. ETL certification is currently (as of November 2015) underway. Southwest Gas is currently in talks with GTI to reach an agreement through which GTI will assess the commercial viability and potential of the heat pump. Southwest Gas is searching for investors to manufacture the heat pump and introduce it to the market.

  13. Efflux Pump Control Alters Synthetic Gene Circuit Function.

    PubMed

    Diao, Junchen; Charlebois, Daniel A; Nevozhay, Dmitry; Bódi, Zoltán; Pál, Csaba; Balázsi, Gábor

    2016-07-15

    Synthetic biology aims to design new biological systems for predefined purposes, such as the controlled secretion of biofuels, pharmaceuticals, or other chemicals. Synthetic gene circuits regulating an efflux pump from the ATP-binding cassette (ABC) protein family could achieve this. However, ABC efflux pumps can also drive out intracellular inducer molecules that control the gene circuits. This will introduce an implicit feedback that could alter gene circuit function in ways that are poorly understood. Here, we used two synthetic gene circuits inducible by tetracycline family molecules to regulate the expression of a yeast ABC pump (Pdr5p) that pumps out the inducer. Pdr5p altered the dose-responses of the original gene circuits substantially in Saccharomyces cerevisiae. While one aspect of the change could be attributed to the efflux pumping function of Pdr5p, another aspect remained unexplained. Quantitative modeling indicated that reduced regulator gene expression in addition to efflux pump function could fully explain the altered dose-responses. These predictions were validated experimentally. Overall, we highlight how efflux pumps can alter gene circuit dynamics and demonstrate the utility of mathematical modeling in understanding synthetic gene circuit function in new circumstances.

  14. Profound regulation of Na/K pump activity by transient elevations of cytoplasmic calcium in murine cardiac myocytes

    PubMed Central

    Lu, Fang-Min; Deisl, Christine; Hilgemann, Donald W

    2016-01-01

    Small changes of Na/K pump activity regulate internal Ca release in cardiac myocytes via Na/Ca exchange. We now show conversely that transient elevations of cytoplasmic Ca strongly regulate cardiac Na/K pumps. When cytoplasmic Na is submaximal, Na/K pump currents decay rapidly during extracellular K application and multiple results suggest that an inactivation mechanism is involved. Brief activation of Ca influx by reverse Na/Ca exchange enhances pump currents and attenuates current decay, while repeated Ca elevations suppress pump currents. Pump current enhancement reverses over 3 min, and results are similar in myocytes lacking the regulatory protein, phospholemman. Classical signaling mechanisms, including Ca-activated protein kinases and reactive oxygen, are evidently not involved. Electrogenic signals mediated by intramembrane movement of hydrophobic ions, such as hexyltriphenylphosphonium (C6TPP), increase and decrease in parallel with pump currents. Thus, transient Ca elevation and Na/K pump inactivation cause opposing sarcolemma changes that may affect diverse membrane processes. DOI: http://dx.doi.org/10.7554/eLife.19267.001 PMID:27627745

  15. Mechanosensing and Regulation of Cardiac Function

    PubMed Central

    Dostal, David E; Feng, Hao; Nizamutdinov, Damir; Golden, Honey B; Afroze, Syeda H; Dostal, Joseph D; Jacob, John C; Foster, Donald M; Tong, Carl; Glaser, Shannon; Gerilechaogetu, FNU

    2014-01-01

    The role of mechanical force as an important regulator of structure and function of mammalian cells, tissues, and organs has recently been recognized. However, mechanical overload is a pathogenesis or comorbidity existing in a variety of heart diseases, such as hypertension, aortic regurgitation and myocardial infarction. Physical stimuli sensed by cells are transmitted through intracellular signal transduction pathways resulting in altered physiological responses or pathological conditions. Emerging evidence from experimental studies indicate that β1-integrin and the angiotensin II type I (AT1) receptor play critical roles as mechanosensors in the regulation of heart contraction, growth and leading to heart failure. Integrin link the extracellular matrix and the intracellular cytoskeleton to initiate the mechanical signalling, whereas, the AT1 receptor could be activated by mechanical stress through an angiotensin-II-independent mechanism. Recent studies show that both Integrin and AT1 receptor and their downstream signalling factors including MAPKs, AKT, FAK, ILK and GTPase regulate heart function in cardiac myocytes. In this review we describe the role of mechanical sensors residing within the plasma membrane, mechanical sensor induced downstream signalling factors and its potential roles in cardiac contraction and growth. PMID:25485172

  16. Alterations in cardiac sarcolemmal Ca/sup 2 +/ pump activity during diabetes mellitus

    SciTech Connect

    Heyliger, C.E.; Prakash, A.; McNeill, J.

    1987-03-01

    Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca/sup 2 +/ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca/sup 2 +/ transport, little appears to be known about its Ca/sup 2 +/ transporting capability in the diabetic myocardium. In this regard, the authors have examined the status of the cardiac sarcolemmal Ca/sup 2 +/ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection. Ca/sup 2 +/ pump activity assessed by measuring its Ca/sup 2 +/-stimulated adenosine triphosphatase and Ca/sup 2 +/-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca/sup 2 +/ pump is defective in the diabetic myocardium and may be involved in the altered Ca/sup 2 +/ transport of the heart during diabetes mellitus.

  17. Cardiac Function Remains Impaired Despite Reversible Cardiac Remodeling after Acute Experimental Viral Myocarditis

    PubMed Central

    Gotzhein, Frauke; Escher, Felicitas; Blankenberg, Stefan; Westermann, Dirk

    2017-01-01

    Background. Infection with Coxsackievirus B3 induces myocarditis. We aimed to compare the acute and chronic phases of viral myocarditis to identify the immediate effects of cardiac inflammation as well as the long-term effects after resolved inflammation on cardiac fibrosis and consequently on cardiac function. Material and Methods. We infected C57BL/6J mice with Coxsackievirus B3 and determined the hemodynamic function 7 as well as 28 days after infection. Subsequently, we analyzed viral burden and viral replication in the cardiac tissue as well as the expression of cytokines and matrix proteins. Furthermore, cardiac fibroblasts were infected with virus to investigate if viral infection alone induces profibrotic signaling. Results. Severe cardiac inflammation was determined and cardiac fibrosis was consistently colocalized with inflammation during the acute phase of myocarditis. Declined cardiac inflammation but no significantly improved hemodynamic function was observed 28 days after infection. Interestingly, cardiac fibrosis declined to basal levels as well. Both cardiac inflammation and fibrosis were reversible, whereas the hemodynamic function remains impaired after healed viral myocarditis in C57BL/6J mice. PMID:28352641

  18. Liver Function Tests Following Open Cardiac Surgery

    PubMed Central

    Sabzi, Feridoun; Faraji, Reza

    2015-01-01

    Introduction: The cardiopulmonary bypass may have multiple systemic effects on the body organs as liver. This prospective study was planned to explore further the incidence and significance of this change. Methods: Two hundred patients with coronary artery bypass grafting (CABG), were randomly selected for the study. Total and indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase were measured preoperatively and at 24, 48 and 72 hours, following coronary artery bypass grafting. Postoperative value of the liver function tests with respect to hypothermia or hypotension were compared by one way analysis of variance for repeated measure and compared with t test. Patient’s characteristics with bilirubin value (≤1.5 mg or >1.5 mg) were compared with t test. Results: A significant increase of total bilirubin, aspartate aminotransferase, and alkaline phosphatase were noted in the third postoperative day. Significant relation was seen between hypotension and alkaline phosphatase, and aspartate aminotransferase change but hypothermia had not affected alanine aminotransferase, total bilirubin and indirect bilirubin change. Pump time, alanine aminotransferase in third postoperative day and direct bilirubin in first and second day of postoperative period had significant relation with pre and post-operative bilirubin change. Conclusion: Transient but not permanent alterations of hepatic enzymes after coronary artery bypass grafting presumably attributed to the decreased hepatic flow, hypoxia, or pump-induced inflammation. PMID:26191391

  19. Endoscope system with plasma flushing and coaxial round jet nozzle for off-pump cardiac surgery.

    PubMed

    Horiuchi, Tetsuya; Masamune, Ken; Iwase, Yuki; Ymashita, Hiromasa; Tsukihara, Hiroyuki; Motomura, Noboru; Ohta, Yuji; Dohi, Takeyoshi

    2011-07-01

    To develop a new endoscope for performing simple surgical tasks inside the blood-filled cardiac atrium/chamber, that is, "off-pump" cardiac surgeries. We developed the endoscope system with plasma flushing and coaxial round jet nozzle. The "plasma flushing" system was invented to observe the interior of the blood-filled heart by displacing blood cells in front of the endoscope tip. However, some areas could not be observed with simple flushing of the liquid because the flushed liquid mixed with blood. Further, a large amount of liquid had to be flushed, which posed a risk of cardiac damage caused by excess volume. Therefore, to safely capture high-resolution images of the interior of the heart, an endoscope with a coaxial round jet nozzle through which plasma is flushed has been developed. And to reduce the volume of flushed liquid, the synchronization system of heartbeat and the endoscope system with plasma flushing has been developed. We conducted an in vivo experiment to determine whether we could observe intracardiac tissues in swine without the use of a heart-lung machine. As a result, we successfully observed intracardiac tissues without using a heart-lung machine. By using a coaxial nozzle, we could even observe the tricuspid valve. Moreover, we were able to save up to 30% of the flushed liquid by replacing the original system with a synchronization system. And we evaluated the performance of the endoscope with the coaxial round jet nozzle by conducting fluid analysis and an in vitro experiment. We successfully observed intracardiac tissues without using a heart-lung machine. By using a coaxial nozzle, we could even observe the tricuspid valve. And by replacing an original system to a synchronization system, we were able to save up to 30% of the flushed liquid. As a follow-up study, we plan to create a surgical flexible device for valve disease that can grasp, staple, and repair cardiac valves by endoscopic visualization.

  20. Acute methamphetamine exposure inhibits cardiac contractile function.

    PubMed

    Turdi, Subat; Schamber, Robbie M; Roe, Nathan D; Chew, Herbert G; Culver, Bruce; Ren, Jun

    2009-09-10

    Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (+/-dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (+/-dLdt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), resting and electrically stimulated increase of intracellular Ca(2+) as well as intracellular Ca(2+) decay. Our results revealed that acute methamphetamine exposure depressed +/-dP/dt, PS and rise of intracellular Ca(2+) without affecting +/-dLdt, TPS, TR(90), resting intracellular Ca(2+) and intracellular Ca(2+) decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, +/-dLdt and shortened TR(90) without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban, associated with upregulated Na(+)-Ca(2+) exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response.

  1. Acute Methamphetamine Exposure Inhibits Cardiac Contractile Function

    PubMed Central

    Turdi, Subat; Schamber, Robbie M.; Roe, Nathan D.; Chew, Herbert G.; Culver, Bruce; Ren, Jun

    2009-01-01

    Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30 min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam® system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (± dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (± dLdt), time-to-PS (TPS), time-to-90% relengthening (TR90), resting and electrically-stimulated increase of intracellular Ca2+ as well as intracellular Ca2+ decay. Our results revealed that acute methamphetamine exposure depressed ± dP/dt, PS and rise of intracellular Ca2+ without affecting ± dLdt, TPS, TR90, resting intracellular Ca2+ and intracellular Ca2+ decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, ± dLdt and shortened TR90 without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and phospholamban, associated with upregulated Na+-Ca2+ exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response. PMID:19481142

  2. Methylprednisolone Protects Cardiac Pumping Mechanics from Deteriorating in Lipopolysaccharide-Treated Rats.

    PubMed

    Ko, Ya-Hui; Tsai, Ming-Shian; Chang, Ru-Wen; Chang, Chun-Yi; Wang, Chih-Hsien; Wu, Ming-Shiou; Liang, Jin-Tung; Chang, Kuo-Chu

    2015-01-01

    It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg(-1) d(-1)) for 2 weeks. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg(-1) d(-1)) for 2 weeks. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (E max) and the theoretical maximum flow (Q max), using the elastance-resistance model. Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in E max associated with the increased Q max in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased E max, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Q max, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV

  3. Preoperative regional cerebral oxygen saturation is a predictor of postoperative delirium in on-pump cardiac surgery patients: a prospective observational trial

    PubMed Central

    2011-01-01

    Introduction Postoperative delirium is an important problem in patients undergoing major surgery. Cerebral oximetry is a non-invasive method to detect imbalances in the cerebral oxygen supply/demand-ratio. Low preoperative cerebral oxygen saturation (ScO2) levels have been associated with postoperative delirium in non-cardiac surgery patients. The present prospective observational study determines the relationship between pre- and intra-operative ScO2 levels and postoperative delirium in patients undergoing on-pump cardiac surgery. Methods After approval of the local ethical committee and written informed consent, N = 231 patients scheduled for elective/urgent cardiac surgery were enrolled. Delirium was assessed by the confusion-assessment-method for the intensive care unit (CAM-ICU) on the first three days after surgery. ScO2 was obtained on the day before surgery, immediately before surgery and throughout the surgical procedure. Preoperative cognitive function, demographic, surgery related, and intra- and post-operative physiological data were registered. Results Patients with delirium had lower pre- and intra-operative ScO2 readings, were older, had lower mini-mental-status-examination(MMSE) scores, higher additive EuroScore and lower preoperative haemoglobin-levels. The binary logistic regression identified older age, lower MMSE, neurological or psychiatric disease and lower preoperative ScO2 as independent predictors of postoperative delirium. Conclusions The presented study shows that a low preoperative ScO2 is associated with postoperative delirium after on-pump cardiac surgery. PMID:21929765

  4. Determinants of respiratory pump function in patients with cystic fibrosis.

    PubMed

    Dassios, Theodore

    2015-01-01

    Respiratory failure constitutes the major cause of morbidity and mortality in patients with Cystic Fibrosis (CF). Respiratory failure could either be due to lung parenchyma damage or to insufficiency of the respiratory pump which consists of the respiratory muscles, the rib cage and the neuromuscular transmission pathways. Airway obstruction, hyperinflation and malnutrition have been historically recognised as the major determinants of respiratory pump dysfunction in CF. Recent research has identified chronic infection, genetic predisposition, dietary and pharmaceutical interventions as possible additional determinants of this impairment. Furthermore, new methodological approaches in assessing respiratory pump function have led to a better understanding of the pathogenesis of respiratory pump failure in CF. Finally, respiratory muscle function could be partially preserved in CF patients with structured interventions such as aerobic exercise, inspiratory muscle training and non-invasive ventilation and CF patients could consequently be relatively protected from respiratory fatigue and respiratory failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Foetal cardiac function: assessing new technologies.

    PubMed

    Gardiner, Helena M

    2014-10-01

    Assessment of foetal cardiac function is more challenging than in the adult, in whom emerging technologies are tested. The postnatal cardio-respiratory interaction is replaced by the cardio-placental circulation and impedance of the brain, and distal vascular beds play an important role in modulating flow to enable its redistribution in the foetal body. Prenatal specialists, comprising obstetricians and cardiologists, have tested a variety of traditional methodologies, as well as non-Doppler offline ultrasound methods in the foetus. This article reviews the development of techniques, outlines their use, and draws attention to pitfalls in adapting technologies validated in the adult heart to the small, fast beating, remote, and largely ungated foetal heart.

  6. Hemolysis during cardiac extracorporeal membrane oxygenation: a case-control comparison of roller pumps and centrifugal pumps in a pediatric population.

    PubMed

    Byrnes, Jonathan; McKamie, Wes; Swearingen, Christopher; Prodhan, Parthak; Bhutta, Adnan; Jaquiss, Robert; Imamura, Michiaki; Fiser, Richard

    2011-01-01

    Extracorporeal membrane oxygenation (ECMO) is a lifesaving therapy, which has been used for the support of children with a broad range of diseases. Two pumps of differing mechanisms have been used to generate the extracorporeal flow: roller-head pumps and centrifugal pumps. Seven patients supported during ECMO with Levitronix Centrimag (Centrimag group [CG]) were matched to 14 patients supported with Stockert-Shiley SIII (Stockert-Shiley group [SSG]) at a single institution from July 2007 to July 2009. We hypothesized that hemolysis as measured by plasma-free hemoglobin (PFH) is elevated in the SSG versus the CG during cardiac ECMO. Categorical data were analyzed using Fisher's exact test. Plasma-free hemoglobin differences between groups were analyzed using both Wilcoxon rank sum and beta regression. Overall, SSG patients had two times the odds of having a higher PFH than CG patients adjusting for repeated measures (odds ratio [OR] = 1.96, 95% confidence interval [CI]: [1.15-3.34], p < 0.014). Differences between circuit failure in the first 168 hours did not reach statistical significance (1/7 CG vs. 7/14 SSG; p = 0.174). In this population of cardiac patients requiring ECMO support, more hemolysis occurred in the SSG, a roller-head pump supported group, when compared with the CG, a centrifugal pump supported group. Differences in circuit life did not reach statistical significance. This pilot study contrasts with past studies, which have demonstrated more hemolysis occurring with centrifugal pumps when compared with roller-head pumps.

  7. An analysis of the energetic cost of the branchial and cardiac pumps during sustained swimming in trout.

    PubMed

    Farrell, A P; Steffensen, J F

    1987-09-01

    Experimental data are available for the oxygen cost of the branchial and cardiac pumps in fish. These data were used to theoretically analyze the relative oxygen cost of these pumps during rest and swimming in rainbow troutSalmo gairdneri. Efficiency of the heart increases with activity and so the relative oxygen cost of the cardiac pumps decreased from 4.6% at rest to 1.9% at the critical swimming speed. The relative oxygen cost of the branchial pump is significant in the resting and slowly swimming fish, being 10 to 15% of total oxygen uptake. However, when swimming trout switch to a ram mode of ventilation, a considerable saving in oxygen cost is accrued by switching the cost of ventilation from the branchial to the tail musculature. Thus, the relative oxygen cost of the branchial and cardiac pumps actually decreases at critical swimming speed compared to rest and therefore is unlikely to be a major limiting factor in maximum oxygen delivery to the tissues.

  8. Altered cardiac autonomic nervous function in depression

    PubMed Central

    2013-01-01

    Background Depression is an independent risk factor for coronary artery disease. Autonomic instability may play a mediating or moderating role in this relationship; however this is not well understood. The objective of this study was to explore cardiac autonomic function and cardiac arrhythmia in depression, the correlation between depression severity and Heart Rate Variability (HRV) related indices, and the prevalence of arrhythmia. Methods Individuals (n = 53) with major depression as assessed by the Diagnostic and Statistical Manual of Mental Disorders, who had a Hamilton Rating Scale for Depression (HAMD) score ≥20 and a Zung Self-Rating Depression Scale score > 53 were compared to 53 healthy individuals, matched for age and gender. Multichannel Electrocardiograph ECG-92C data were collected over 24 hours. Long-term changes in HRV were used to assess the following vagally mediated changes in autonomic tone, expressed as time domain indices: Standard deviation of the NN intervals (SDNN), standard deviation of 5 min averaged NN intervals (SDANN), Root Mean Square of the Successive Differences (RMSSD) and percentage of NN intervals > 50 ms different from preceding interval (pNN50). Pearson’s correlations were conducted to explore the strength of the association between depression severity (using the SDS and HRV related indices, specifically SDNN and low frequency domain / high frequency domain (LF/HF)). Results The values of SDNN, SDANN, RMSSD, PNN50 and HF were lower in the depression group compared to the control group (P<.05). The mean value of the LF in the depression group was higher than the in control group (P<.05). Furthermore the ratio of LF/HF was higher among the depression group than the control group (P<.05). A linear relationship was shown to exist between the severity of the depression and HRV indices. In the depression group, the prevalence of arrhythmia was significantly higher than in the control group (P<.05), particularly

  9. Angiogenesis and cardiac hypertrophy: maintenance of cardiac function and causative roles in heart failure.

    PubMed

    Oka, Toru; Akazawa, Hiroshi; Naito, Atsuhiko T; Komuro, Issei

    2014-01-31

    Cardiac hypertrophy is an adaptive response to physiological and pathological overload. In response to the overload, individual cardiac myocytes become mechanically stretched and activate intracellular hypertrophic signaling pathways to re-use embryonic transcription factors and to increase the synthesis of various proteins, such as structural and contractile proteins. These hypertrophic responses increase oxygen demand and promote myocardial angiogenesis to dissolve the hypoxic situation and to maintain cardiac contractile function; thus, these responses suggest crosstalk between cardiac myocytes and microvasculature. However, sustained pathological overload induces maladaptation and cardiac remodeling, resulting in heart failure. In recent years, specific understanding has increased with regard to the molecular processes and cell-cell interactions that coordinate myocardial growth and angiogenesis. In this review, we summarize recent advances in understanding the regulatory mechanisms of coordinated myocardial growth and angiogenesis in the pathophysiology of cardiac hypertrophy and heart failure.

  10. Change of Na+ pump current reversal potential in sheep cardiac Purkinje cells with varying free energy of ATP hydrolysis.

    PubMed Central

    Glitsch, H G; Tappe, A

    1995-01-01

    1. The Na(+)-K+ pump current, Ip, of cardioballs from isolated sheep cardiac Purkinje cells was measured at 30-34 degrees C by means of whole-cell recording. 2. Under physiological conditions Ip is an outward current. Experimental conditions which cause a less negative free energy of intracellular ATP hydrolysis (delta GATP) and steeper sarcolemmal gradients for the pumped Na+ and Cs+ ions evoked an Ip in the inward direction over a wide range of membrane potentials. The reversal of the Ip direction was reversible. 3. The inwardly directed Ip increased with increasingly negative membrane potentials and amounted to -0.13 +/- 0.03 microA cm-2 (mean +/- S.E.M.; n = 6) at -95 mV. 4. The reversal potential (Erev) of Ip was studied as a function of delta GATP at constant sarcolemmal gradients of the pumped cations. 5. In order to vary delta GATP the cell interior was dialysed with patch pipette solutions containing 10 mM ATP and different concentrations of ADP and inorganic phosphate. The media were composed to produce delta GATP levels of about -58, -49 and -39 kJ mol-1. 6. A less negative delta GATP shifted Erev to more positive membrane potentials. From measurements of Ip as a function of membrane potential Erev was estimated to be -195, -115 and -60 mV at delta GATP levels of approximately -58, -49 and -39 kJ mol-1, respectively. The calculated Erev amounted to -224 mV at delta GATP approximately -58 kJ mol-1, -126 mV at delta GATP approximately 49 kJ mol-1 and -24 mV at delta GATP approximately -39 kJ mol-1. 7. Possible reasons for the discrepancy between estimated and calculated Erev values are discussed. 8. Shifting delta GATP to less negative values not only altered Erev but also diminished Ip at each membrane potential tested. The maximal Ip (Ip,max), which can be activated by external Cs+ (Cs+o), decreased under these conditions, whereas [Cs+]o causing half-maximal Ip activation remained unchanged. Similarly, the voltage dependence of Ip activation by Cs+o was

  11. Patients and complication with off-pump vs. on-pump cardiac surgery - a single surgeon experience.

    PubMed

    Rukosujew, Andreas; Klotz, Stefan; Reitz, Christiane; Gogarten, Wiebke; Welp, Henryk; Scheld, Hans H

    2007-12-01

    Off-pump operations (OPCAB) are growingly used for patients with coronary artery disease (CAD) and may be associated with improved outcomes when compared with coronary artery bypass grafting (CABG) using extracorporeal circulation (ECC), especially in patients with comorbidities. The aim of this study is to compare the intra- and postoperative results of OPCAB complete arterial myocardial revascularization with standard on-pump CABG under respect of comorbidities. We report about the implementing of the off-pump technique in our institution from November 2004 to May 2006. Sixty-two patients with CABG in off-pump technique were compared to a control group of 129 patients with CABG using ECC. The off-pump technique was mostly used in patients with vascular and pulmonary diseases. All operations were performed by the same surgeon. All off-pumps were performed using both internal thoracic arteries (ITA) or left ITA and radial artery (RA) in T-graft technique, while in the on-pump group only the LITA and saphenous vein were used. The conversion rate from OPCAB to conventional CABG was 3.2% (two patients). Peripheral vascular disease (PVD) and chronic obstructive pulmonary disease (COPD) were significant more often in the off-pump group. Other preoperative risk factors were comparable between the groups. Operation time was significantly longer in the off-pump group. Postoperative symptomatic transient psychotic syndromes were more often in the on-pump group. Outcome was similar, despite significant longer operation time in off-pump group. Off-pump coronary artery surgery can be performed in patients with comorbidities with similar outcome compared to on-pump surgery.

  12. Pump

    SciTech Connect

    Johnson, J.W.; Abdul.Hye, A.B.M.

    1983-10-25

    A pump for injecting chemicals into a well employs a pivot arm for synchronous movement with a well pump. The pivot arm causes reciprocation of a plunger within the body of the chemical pump. The plunger, during its upward stroke causes the entry of chemicals from an outside source into the pump body and, during its downward stroke, causes the exiting of the chemicals into the well. (2 claims.

  13. Regulation of pumping function of the heart in developing body under changing regimens of motor activity.

    PubMed

    Vafina, E Z; Abzalov, R A; Abzalov, N I; Nikitin, A S; Gulyakov, A A

    2014-06-01

    We analyzed parameters of the pumping function of the heart in rats subjected to enhanced motor activity after a preliminary 70-day hypokinesia under conditions of α- and β-adrenergic receptor stimulation with norepinephrine followed by blockade of β-adrenergic receptor with propranolol (obsidian) and α1-adrenergic receptors with doxazosin. After norepinephrine administration, the HR and cardiac output were higher in rats with enhanced physical activity after preliminary hypokinesia than in rats with low physical activity. After propranolol administration, stroke volume and cardiac output in 100-day-old rats with limited activity were lower, and HR higher was than in rats with enhanced physical activity after preliminary 70-day hypokinesia. After administration of doxazosin, rats with limited motor activity demonstrated more pronounced changes in HR than rats with enhanced physical activity after preliminary 70-day hypokinesia.

  14. Transient receptor potential vanilloid 2 function regulates cardiac hypertrophy via stretch-induced activation.

    PubMed

    Koch, Sheryl E; Mann, Adrien; Jones, Shannon; Robbins, Nathan; Alkhattabi, Abdullah; Worley, Mariah C; Gao, Xu; Lasko-Roiniotis, Valerie M; Karani, Rajiv; Fulford, Logan; Jiang, Min; Nieman, Michelle; Lorenz, John N; Rubinstein, Jack

    2017-03-01

    Hypertension (increased afterload) results in cardiomyocyte hypertrophy leading to left ventricular hypertrophy and subsequently, heart failure with preserved ejection fraction. This study was performed to test the hypothesis that transient receptor potential vanilloid 2 subtype (TRPV2) function regulates hypertrophy under increased afterload conditions. We used functional (pore specific) TRPV2 knockout mice to evaluate the effects of increased afterload-induced stretch on cardiac size and function via transverse aortic constriction (TAC) as well as hypertrophic stimuli including adrenergic and angiotensin stimulation via subcutaneous pumps. Wild-type animals served as control for all experiments. Expression and localization of TRPV2 was investigated in wild-type cardiac samples. Changes in cardiac function were measured in vivo via echocardiography and invasive catheterization. Molecular changes, including protein and real-time PCR markers of hypertrophy, were measured in addition to myocyte size. TRPV2 is significantly upregulated in wild-type mice after TAC, though not in response to beta-adrenergic or angiotensin stimulation. TAC-induced stretch stimulus caused an upregulation of TRPV2 in the sarcolemmal membrane. The absence of functional TRPV2 resulted in significantly reduced left ventricular hypertrophy after TAC, though not in response to beta-adrenergic or angiotensin stimulation. The decreased development of hypertrophy was not associated with significant deterioration of cardiac function. We conclude that TRPV2 function, as a stretch-activated channel, regulates the development of cardiomyocyte hypertrophy in response to increased afterload.

  15. Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition.

    PubMed

    Chia, Karin K M; Liu, Chia-Chi; Hamilton, Elisha J; Garcia, Alvaro; Fry, Natasha A; Hannam, William; Figtree, Gemma A; Rasmussen, Helge H

    2015-08-15

    Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na(+)-K(+) pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na(+)-K(+) pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na(+)-K(+) pump current (Ip). Coexposure to 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na(+)-K(+) pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47(phox) NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22(phox) subunit, and it decreased O2 (·-)-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47(phox) indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22(phox) and p47(phox) NADPH oxidase subunits and decrease β1-Na(+)-K(+) pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. Copyright © 2015 the American Physiological Society.

  16. Stimulation of the cardiac myocyte Na+-K+ pump due to reversal of its constitutive oxidative inhibition

    PubMed Central

    Chia, Karin K. M.; Liu, Chia-Chi; Hamilton, Elisha J.; Garcia, Alvaro; Fry, Natasha A.; Hannam, William; Figtree, Gemma A.

    2015-01-01

    Protein kinase C can activate NADPH oxidase and induce glutathionylation of the β1-Na+-K+ pump subunit, inhibiting activity of the catalytic α-subunit. To examine if signaling of nitric oxide-induced soluble guanylyl cyclase (sGC)/cGMP/protein kinase G can cause Na+-K+ pump stimulation by counteracting PKC/NADPH oxidase-dependent inhibition, cardiac myocytes were exposed to ANG II to activate NADPH oxidase and inhibit Na+-K+ pump current (Ip). Coexposure to 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1) to stimulate sGC prevented the decrease of Ip. Prevention of the decrease was abolished by inhibition of protein phosphatases (PP) 2A but not by inhibition of PP1, and it was reproduced by an activator of PP2A. Consistent with a reciprocal relationship between β1-Na+-K+ pump subunit glutathionylation and pump activity, YC-1 decreased ANG II-induced β1-subunit glutathionylation. The decrease induced by YC-1 was abolished by a PP2A inhibitor. YC-1 decreased phosphorylation of the cytosolic p47phox NADPH oxidase subunit and its coimmunoprecipitation with the membranous p22phox subunit, and it decreased O2·−-sensitive dihydroethidium fluorescence of myocytes. Addition of recombinant PP2A to myocyte lysate decreased phosphorylation of p47phox indicating the subunit could be a substrate for PP2A. The effects of YC-1 to decrease coimmunoprecipitation of p22phox and p47phox NADPH oxidase subunits and decrease β1-Na+-K+ pump subunit glutathionylation were reproduced by activation of nitric oxide-dependent receptor signaling. We conclude that sGC activation in cardiac myocytes causes a PP2A-dependent decrease in NADPH oxidase activity and a decrease in β1 pump subunit glutathionylation. This could account for pump stimulation with neurohormonal oxidative stress expected in vivo. PMID:26084308

  17. Cardiac dilatation and pump dysfunction without intrinsic myocardial systolic failure following chronic beta-adrenoreceptor activation.

    PubMed

    Osadchii, Oleg E; Norton, Gavin R; McKechnie, Richard; Deftereos, Dawn; Woodiwiss, Angela J

    2007-04-01

    There is no direct evidence to indicate that pump dysfunction in a dilated chamber reflects the impact of chamber dilatation rather than the degree of intrinsic systolic failure resulting from myocardial damage. In the present study, we explored the relative roles of intrinsic myocardial systolic dysfunction and chamber dilatation as mediators of left ventricular (LV) pump dysfunction. Administration of isoproterenol, a beta-adrenoreceptor agonist, for 3 mo to rats (0.1 mg.kg(-1).day(-1)) resulted in LV pump dysfunction as evidenced by a reduced LV endocardial fractional shortening (echocardiography) and a decrease in the slope of the LV systolic pressure-volume relation (isolated heart preparations). Although chronic beta-adrenoreceptor activation induced cardiomyocyte damage (deoxynucleotidyl transferase-mediated dUTP nick-end labeling) as well as beta(1)- and beta(2)-adrenoreceptor inotropic downregulation (attenuated contractile responses to dobutamine and salbutamol), these changes failed to translate into alterations in intrinsic myocardial contractility. Indeed, LV midwall fractional shortening (echocardiography) and the slope of the LV systolic stress-strain relation (isolated heart preparations) were unchanged. A normal intrinsic myocardial systolic function, despite the presence of cardiomyocyte damage and beta-adrenoreceptor inotropic downregulation, was ascribed to marked increases in myocardial norepinephrine release, to upregulation of alpha-adrenoreceptor-mediated contractile effects as determined by phenylephrine responsiveness, and to compensatory LV hypertrophy. LV pump failure was attributed to LV dilatation, as evidenced by increased LV internal dimensions (echocardiography), and a right shift and increased volume intercept of the LV diastolic pressure-volume relation. In conclusion, chronic sympathetic stimulation, despite reducing beta-adrenoreceptor-mediated inotropic responses and promoting myocyte apoptosis, may nevertheless induce pump

  18. Platelet function and hemolysis in centrifugal pumps: in vitro investigations.

    PubMed

    Steines, D; Westphal, D; Göbel, C; Reul, H; Rau, G

    1999-08-01

    The effects of centrifugal pumps on blood components other than erythrocytes, namely platelets and their interaction with the coagulation system, are not very well known. In a comparative study with three centrifugal pumps (BioMedicus BP-80, St. Jude Isoflow, and Sarns Delphin) and the Stockert roller pump hemolysis, platelet counts, thromboplastin and partial thromboplastin times, as well as resonance thrombography (RTG) parameters for the assessment of platelet and coagulation function were evaluated in vitro. Normalized indices of hemolysis (NIH) with ACD anticoagulation after 360 minutes were 0.008+/-0.004 (Isoflow), 0.018+/-0.017 (BP-80), 0.085+/-0.051 (Delphin), and 0.049+/-0.010 g/1001 (roller pump). Plasmatic coagulation was activated in all circuits. Platelet function was severely inhibited by the BP-80, indicated by increase in RTG platelet time to 358%+/-150% of initial values compared to 42%+/-29% (Isoflow), 40%+/-20% (Delphin), and 12%+/-10% (roller pump). Fibrin polymerization was affected similarly. The large surface area of the BP-80 leads to an extensive activation of platelets and plasminogen.

  19. A novel, low cost, disposable, pediatric pulsatile rotary ventricular pump for cardiac surgery that provides a physiological flow pattern.

    PubMed

    Mazur, Daniel E; Osterholzer, Kathryn R; Toomasian, John M; Merz, Scott I

    2008-01-01

    Research is underway to develop a novel, low cost, disposable pediatric pulsatile rotary ventricular pump (PRVP) for cardiac surgery that provides a physiological flow pattern. This is believed to offer reduced morbidity and risk exposure within this population. The PRVP will have a durable design suitable for use in short- to mid-length prolonged support after surgery without changing pumps. The design is based on proprietary MC3 technology which provides variable pumping volume per stroke, thereby allowing the pump to respond to hemodynamic status changes of the patient. The novel pump design also possesses safety advantages that prevent retrograde flow, and maintain safe circuit pressures upon occlusion of the inlet and outlet tubing. The design is ideal for simple, safe and natural flow support. Computational methods have been developed that predict output for pump chambers of varying geometry. A scaled chamber and pump head (diameter = 4 in) were prototyped to demonstrate target performance for pediatrics (2 L/min at 100 rpm). A novel means of creating a pulsatile flow and pressure output at constant RPM was developed and demonstrated to create significant surplus hydraulic energy (>10%) in a simplified mock patient circuit.

  20. Effect of prolonged space flight on cardiac function and dimensions

    NASA Technical Reports Server (NTRS)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1977-01-01

    By taking advantage of the capabilities of echocardiography to measure noninvasively left ventricular volume, stroke volume, and ejection fraction, and of the fact that the astronauts were routinely subjected to lower body negative pressure (whereby cardiac filling is progressively decreased), it was possible to construct classic ventricular function curves noninvasively, thereby obviating the difficulties encountered in comparing cardiac function at different end-diastolic volumes preflight and postflight. In this manner, the effect of an 84-day period of weightlessness on cardiac structure and function was evaluated in the Skylab 4 astronauts.

  1. Pump function curve shape for a model lymphatic vessel.

    PubMed

    Bertram, C D; Macaskill, C; Moore, J E

    2016-07-01

    The transport capacity of a contractile segment of lymphatic vessel is defined by its pump function curve relating mean flow-rate and adverse pressure difference. Numerous system characteristics affect curve shape and the magnitude of the generated flow-rates and pressures. Some cannot be varied experimentally, but their separate and interacting effects can be systematically revealed numerically. This paper explores variations in the rate of change of active tension and the form of the relation between active tension and muscle length, factors not known from experiment to functional precision. Whether the pump function curve bends toward or away from the origin depends partly on the curvature of the passive pressure-diameter relation near zero transmural pressure, but rather more on the form of the relation between active tension and muscle length. A pump function curve bending away from the origin defines a well-performing pump by maximum steady output power. This behaviour is favoured by a length/active-tension relationship which sustains tension at smaller lengths. Such a relationship also favours high peak mechanical efficiency, defined as output power divided by the input power obtained from the lymphangion diameter changes and active-tension time-course. The results highlight the need to pin down experimentally the form of the length/active-tension relationship.

  2. Removal of the Cardiac Troponin I N-terminal Extension Improves Cardiac Function in Aged Mice*

    PubMed Central

    Biesiadecki, Brandon J.; Tachampa, Kittipong; Yuan, Chao; Jin, Jian-Ping; de Tombe, Pieter P.; Solaro, R. John

    2010-01-01

    The cardiac troponin I (cTnI) isoform contains a unique N-terminal extension that functions to modulate activation of cardiac myofilaments. During cardiac remodeling restricted proteolysis of cTnI removes this cardiac specific N-terminal modulatory extension to alter myofilament regulation. We have demonstrated expression of the N-terminal-deleted cTnI (cTnI-ND) in the heart decreased the development of the cardiomyopathy like phenotype in a β-adrenergic-deficient transgenic mouse model. To investigate the potential beneficial effects of cTnI-ND on the development of naturally occurring cardiac dysfunction, we measured the hemodynamic and biochemical effects of cTnI-ND transgenic expression in the aged heart. Echocardiographic measurements demonstrate cTnI-ND transgenic mice exhibit increased systolic and diastolic functions at 16 months of age compared with age-matched controls. This improvement likely results from decreased Ca2+ sensitivity and increased cross-bridge kinetics as observed in skinned papillary bundles from young transgenic mice prior to the effects of aging. Hearts of cTnI-ND transgenic mice further exhibited decreased β myosin heavy chain expression compared to age matched non-transgenic mice as well as altered cTnI phosphorylation. Finally, we demonstrated cTnI-ND expressed in the heart is not phosphorylated indicating the cTnI N-terminal is necessary for the higher level phosphorylation of cTnI. Taken together, our data suggest the regulated proteolysis of cTnI during cardiac stress to remove the unique cardiac N-terminal extension functions to improve cardiac contractility at the myofilament level and improve overall cardiac function. PMID:20410305

  3. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A.; Miller, Jack J. J.; Christian, Helen C.; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A.

    2015-01-01

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. PMID:25713362

  4. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.

    PubMed

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A; Miller, Jack J J; Christian, Helen C; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Larner, Fiona; Tyler, Damian J; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

    2015-03-10

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation.

  5. A dynamic double helical band as a model for cardiac pumping.

    PubMed

    Grosberg, Anna; Gharib, Morteza

    2009-06-01

    We address here, by means of finite-element computational modeling, two features of heart mechanics and, most importantly, their timing relationship: one of them is the ejected volume and the other is the twist of the heart. The corner stone of our approach is to take the double helical muscle fiber band as the dominant active macrostructure behind the pumping function. We show that this double helical model easily reproduces a physiological maximal ejection fraction of up to 60% without exceeding the limit on local muscle fiber contraction of 15%. Moreover, a physiological ejection fraction can be achieved independently of the excitation pattern. The left ventricular twist is also largely independent of the type of excitation. However, the physiological relationship between the ejection fraction and twist can only be reproduced with Purkinje-type excitation schemes. Our results indicate that the proper timing coordination between twist and ejection dynamics can be reproduced only if the excitation front originates in the septum region near the apex. This shows that the timing of the excitation is directly related to the productive pumping operation of the heart and illustrates the direction for possible bioinspired pump design.

  6. Effect of sensor location on regional cerebral oxygen saturation measured by INVOS 5100 in on-pump cardiac surgery.

    PubMed

    Cho, Ah-Reum; Kwon, Jae-Young; Kim, Choongrak; Hong, Jung-Min; Kang, Christine

    2017-04-01

    Near-infrared spectroscopy sensors often cannot be attached at the commercially recommended locations because combined use of neurological monitoring systems is common during on-pump cardiac surgery. The primary purpose of this study was to compare the incidence of regional cerebral oxygen desaturation and regional cerebral oxygen saturation values detected using near-infrared spectroscopy between the upper and lower forehead during on-pump cardiac surgery. A prospective observational study was conducted with 25 adult patients scheduled for elective on-pump cardiac surgery. Regional cerebral oxygen saturations at the left upper and lower forehead and other clinical measurements were monitored intraoperatively. McNemar's test was used to analyze differences in the incidence of cerebral regional oxygen desaturation between the left upper and lower forehead. Two-way repeated measures ANOVA with post hoc Bonferroni correction was used to compare the regional cerebral oxygen saturation at each time point. There was a significantly higher incidence of regional cerebral oxygen desaturation at the upper than lower forehead only at 1 h after initiation of aortic cross-clamping. There were significant differences between the left upper and lower regional cerebral oxygen saturation values throughout the observation period. Regional cerebral oxygen saturation was significantly lower at the upper than lower forehead during on-pump cardiac surgery. However, disagreements in detection of cerebral regional oxygen desaturation were only significant at 1 h after initiation of aortic cross-clamping. WHO-ICTRP, Clinical Research Information Service (CRiS). ID: KCT0000971. URL: https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=3678&type=my .

  7. Off-Pump versus On-Pump Coronary Artery Bypass Grafting Outcomes Stratified by Preoperative Renal Function

    PubMed Central

    Zhao, Yue; Lough, Fredrick C.; Schroeder, Elizabeth; Seneff, Michael G.; Brennan, J. Matthew

    2012-01-01

    Clinical trials of off-pump coronary artery bypass grafting (CABG) have largely excluded patients with CKD. Here, we sought to determine whether pump status affects outcomes in patients with CKD. Using a nonrandomized cohort of 742,909 non-emergent, isolated CABG cases, which included 158,561 off-pump cases, in the Society of Thoracic Surgery Database from 2004 through 2009, we evaluated the association between pump status (off-pump versus on-pump) and in-hospital death or incident renal replacement therapy (RRT) across strata of preoperative renal function. We used propensity methods to adjust patient- and center-level analyses for imbalances in baseline patient risk. Patients who received on-pump and off-pump CABG had similar mean age and distribution of preoperative estimated GFR (eGFR). In a propensity-weighted analysis, off-pump CABG was associated with a reduction in the composite in-hospital death or RRT, with patients having lower preoperative renal function exhibiting greater benefit, on average. The risk difference (on-pump minus off-pump) ranged from 0.05 (95% confidence interval, −0.06 to 0.16) per 100 patients for eGFR ≥90 ml/min per 1.73 m2 to 3.66 (95% confidence interval, 2.14–5.18) per 100 patients for eGFR 15–29 ml/min per 1.73 m2. Both component endpoints suggested the same trend. In summary, these data suggest that patients with CKD experience less death or incident RRT when treated with off-pump compared with on-pump CABG. The reduction in incident RRT, not death, drove this effect on the composite among patients with low eGFR. Prospective trials comparing these procedures in patients with impaired preoperative renal function are warranted. PMID:22595302

  8. Operation Everest II: Preservation of Cardiac Function at Extreme Altitude,

    DTIC Science & Technology

    1986-10-01

    environmental control. The exercise intensity was measured in terms of both physical work and oxygen uptake. Oxygen uptakes at submaximal work loads were...observation was reported in one subject exercising at 5800 m (18). Both in this subject and in our subjects, a role for hypoxia was suggested in that the...at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme

  9. Control of a rotary pulsatile cardiac assist pump driven by an electric motor without a pressure sensor to avoid collapse of the pump inlet.

    PubMed

    Trinkl, J; Havlik, P; Mesana, T; Mitsui, N; Morita, S; Demunck, J L; Tourres, J L; Monties, J R

    1993-01-01

    Our ventricular assist device uses a valveless volumetric pump operating on the Maillard-Wankel rotary principle. It is driven by an electric motor and provides a semi pulsatile flow. At each cycle, blood is actively aspirated into the device, and overpumping results in collapse at the pump inlet. To prevent overpumping, it is necessary to ensure that pump intake does not exceed venous return. Poor long-term reliability rules out the use of current implantable pressure sensors for this purpose. To resolve this problem, we have developed a method of control based on monitoring of the intensity of electric current consumed by the motor. The method consists of real time monitoring of current intensity at the beginning of each pump cycle. A sudden change in intensity indicates underfilling, and motor speed is reduced to prevent collapse. The current consumed by the motor also depends on the afterload, but the form of the signal remains the same when afterload changes. After demonstrating the feasibility of this technique in a simulator, we are now testing it in animals. We were able to detect and prevent collapse due to overpumping by the cardiac assist device. This system also enables us to know the maximum possible assistance and to thus adapt assistance to the user.

  10. Pulmonary functions in petrol pump workers: a preliminary study.

    PubMed

    Singhal, Mayank; Khaliq, Farah; Singhal, Siddarth; Tandon, O P

    2007-01-01

    Occupational exposures to petrol/diesel vapors have been shown to affect functioning of different systems of the body. The present study was planned to assess the pulmonary functions in petrol pump workers (filling attendants) who are continuously exposed to petrol/diesel vapors during duty hours. Thirty healthy non-smoker males working in petrol pump for more than one year formed the study group, while thirty healthy non-smoker males from hospital staff served as control group. The pulmonary functions were assessed using computerized spirometer. The FVC and FEV1 were decreased in the study group while their ratio did not differ much. Both the inspiratory and expiratory flow rates were also decreased in the study group. These findings point towards adverse effects of petrol/diesel fumes mainly on lower airways with restrictive pattern of disease.

  11. Echocardiographic assessment of cardiac morphology and function in Xenopus.

    PubMed

    Bartlett, Heather L; Escalera, Robert B; Patel, Sonali S; Wedemeyer, Elesa W; Volk, Kenneth A; Lohr, Jamie L; Reinking, Benjamin E

    2010-04-01

    Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses.

  12. Echocardiographic Assessment of Cardiac Morphology and Function in Xenopus

    PubMed Central

    Bartlett, Heather L; Escalera, Robert B; Patel, Sonali S; Wedemeyer, Elesa W; Volk, Kenneth A; Lohr, Jamie L; Reinking, Benjamin E

    2010-01-01

    Advances using Xenopus as a model permit valuable inquiries into cardiac development from embryo to adult. Noninvasive methods are needed to study cardiac function longitudinally. The objective of this study was to evaluate the feasibility of echocardiographic studies in Xenopus and establish normative data of adult cardiac structure and function. Doppler and 2D echocardiograms and electrocardiograms were acquired from adult Xenopus laevis and X. tropicalis. Frogs were exposed to either isoflurane or tricaine to discern the effect of sedating agents on cardiac function. Cardiac dimensions, morphology, flow velocities, and electrophysiologic intervals were measured and evaluated by using bivariate and regression analyses. Normal cardiac dimensions relative to body weight and species were established by echocardiography. Normal conduction intervals were determined by electrocardiography and did not vary by body weight or species. Anesthetic agent did not affect ejection fraction or flow velocity but did alter the QRS duration and QT interval. Echocardiographic and electrocardiographic studies in Xenopus provide information about cardiac anatomy and physiology and can readily be used for longitudinal analyses of developmental inquiries. Body weight, species, and anesthetic agent are factors that should be considered in experimental design and analyses. PMID:20412684

  13. Cardiac telomere length in heart development, function, and disease.

    PubMed

    Booth, S A; Charchar, F J

    2017-07-01

    Telomeres are repetitive nucleoprotein structures at chromosome ends, and a decrease in the number of these repeats, known as a reduction in telomere length (TL), triggers cellular senescence and apoptosis. Heart disease, the worldwide leading cause of death, often results from the loss of cardiac cells, which could be explained by decreases in TL. Due to the cell-specific regulation of TL, this review focuses on studies that have measured telomeres in heart cells and critically assesses the relationship between cardiac TL and heart function. There are several lines of evidence that have identified rapid changes in cardiac TL during the onset and progression of heart disease as well as at critical stages of development. There are also many factors, such as the loss of telomeric proteins, oxidative stress, and hypoxia, that decrease cardiac TL and heart function. In contrast, antioxidants, calorie restriction, and exercise can prevent both cardiac telomere attrition and the progression of heart disease. TL in the heart is also indicative of proliferative potential and could facilitate the identification of cells suitable for cardiac rejuvenation. Although these findings highlight the involvement of TL in heart function, there are important questions regarding the validity of animal models, as well as several confounding factors, that need to be considered when interpreting results and planning future research. With these in mind, elucidating the telomeric mechanisms involved in heart development and the transition to disease holds promise to prevent cardiac dysfunction and potentiate regeneration after injury. Copyright © 2017 the American Physiological Society.

  14. Efficacy of prophylactic intra-aortic balloon pump therapy in chronic heart failure patients undergoing cardiac surgery.

    PubMed

    Yildirim, Yalin; Pecha, Simon; Kubik, Mathias; Alassar, Yousuf; Deuse, Tobias; Hakmi, Samer; Reichenspurner, Hermann

    2014-11-01

    This study investigated the efficacy of prophylactic intraoperative intra-aortic balloon pump (IABP) usage in chronic heart failure patients with severely reduced left ventricular function undergoing elective cardiac surgery. Between January 2008 and December 2012, 107 patients with severely reduced left ventricular ejection fraction (LVEF <35%) received prophylactic intraoperative IABP implantation during open-heart surgery. Surgical procedures performed were isolated coronary artery bypass grafting (CABG) in 35 patients (32.7%), aortic valve replacement in 12 (11.2%), mitral valve repair or replacement in 15 (14.0%), combined valve and CABG procedures in 27 (25.2%), and other surgical procedures in 18 (16.8%). Results and outcomes were compared with those in a propensity score-matched cohort of 107 patients who underwent cardiac surgery without intraoperative IABP implantation. Matching criteria were age, gender, LVEF, and surgical procedure. Duration of intensive care unit (ICU) stay, duration of hospital stay, and 30-day mortality were markers of outcome. In the IABP group, mean patient age was 69.1 ± 13.7 years; 66.4% (70) were male. All IABPs were placed intraoperatively. Mean duration of IABP application time was 42.4 ± 8.7 h. IABP-related complications occurred in five patients (4.7%), including one case of inguinal bleeding, one case of mesenteric ischemia, and ischemia of the lower limb in three patients. No stroke or major bleeding occurred during IABP support. Mean durations of ICU and hospital stay were 3.38 ± 2.15 days and 7.69 ± 2.02 days, respectively, in the IABP group, and 4.20 ± 3.14 days and 8.57 ± 3.26 days in the control group, showing statistically significant reductions in duration of ICU and hospital stay in the IABP group (ICU stay, P = 0.036; hospital stay, P = 0.015). Thirty-day survival rates were 92.5 and 94.4% in the IABP and control group, respectively, showing no statistically significant difference (P = 0.75). IABP usage in

  15. Assessment of Hydraulic Performance and Biocompatibility of a MagLev Centrifugal Pump System Designed for Pediatric Cardiac or Cardiopulmonary Support

    PubMed Central

    Dasse, Kurt A.; Gellman, Barry; Kameneva, Marina V.; Woolley, Joshua R.; Johnson, Carl A.; Gempp, Thomas; Marks, John D.; Kent, Stella; Koert, Andrew; Richardson, J. Scott; Franklin, Steve; Snyder, Trevor A.; Wearden, Peter; Wagner, William R.; Gilbert, Richard J.; Borovetz, Harvey S.

    2011-01-01

    The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the Pedi-VAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to ¼ in. For the expected range of pediatric flow (0.3–3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future. PMID:18043164

  16. Assessment of hydraulic performance and biocompatibility of a MagLev centrifugal pump system designed for pediatric cardiac or cardiopulmonary support.

    PubMed

    Dasse, Kurt A; Gellman, Barry; Kameneva, Marina V; Woolley, Joshua R; Johnson, Carl A; Gempp, Thomas; Marks, John D; Kent, Stella; Koert, Andrew; Richardson, J Scott; Franklin, Steve; Snyder, Trevor A; Wearden, Peter; Wagner, William R; Gilbert, Richard J; Borovetz, Harvey S

    2007-01-01

    The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the PediVAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to (1/4) in. For the expected range of pediatric flow (0.3-3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future.

  17. PUMPS

    DOEpatents

    Thornton, J.D.

    1959-03-24

    A pump is described for conveving liquids, particure it is not advisable he apparatus. The to be submerged in the liquid to be pumped, a conduit extending from the high-velocity nozzle of the injector,and means for applying a pulsating prcesure to the surface of the liquid in the conduit, whereby the surface oscillates between positions in the conduit. During the positive half- cycle of an applied pulse liquid is forced through the high velocity nozzle or jet of the injector and operates in the manner of the well known water injector and pumps liquid from the main intake to the outlet of the injector. During the negative half-cycle of the pulse liquid flows in reverse through the jet but no reverse pumping action takes place.

  18. Assessment of cardiac parameters in evaluation of cardiac functions in patients with thalassemia major.

    PubMed

    Oztarhan, Kazim; Delibas, Yavuz; Salcioglu, Zafer; Kaya, Guldemet; Bakari, Suleyman; Bornaun, Helen; Aydogan, Gonul

    2012-04-01

    The aim of the study was to evaluate cardiac function and early cardiac dysfunction of patients followed as thalassemia major. In this study, the authors compared 100 patients, diagnosed as thalassemia major with mean age 11.84 ± 4.35, with 60 healthy control subjects at the same age between 2008 and 2011. Early diagnosis of iron overload that may occur after repeated transfusions is important in this patient group. To detect early iron accumulation, the authors compared ferritin with the echo findings, the 24-hour Holter, and cardiac magnetic resonance imaging (MRI) T2* values in the patients of same age and sex, treated with chelators, without heart failure, nonsplenectomized, and do not differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic functions (ejection fraction [EF], shortening fraction [SF]), left ventricular measurements, left ventricular diastolic functions, T2* image on cardiac magnetic resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to show the early failure of cardiac functions. In this study the authors confirmed that iron-related cardiac toxicity damages electrical activity earlier than myocardial contractility. Left ventricular diastolic diameter (LVDd), left ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly higher in the patient group with ectopia. Patients with ectopia are the ones in whom LVM and LVDd are increased. In thalassemia major patients with ectopia, LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in patients with ectopia rather than nonectopic patients. The standard deviation all normal RR interval series (SDNN) was found clearly lower in thalassemia major group with ectopia than control group because it is assumed that increase in cardiac sympathetic neuronal activity is related to exposure to chronic diastolic and systolic failure.

  19. [S3-Guideline: Recommendations for intra-aortic balloon pumping in cardiac surgery].

    PubMed

    Pilarczyk, Kevin; Bauer, Adrian; Boening, Andreas; von der Brelie, Michael; Eichler, Ingolf; Gohrbandt, Bernard; Groesdonk, Heinrich Volker; Haake, Nils; Heringlake, Matthias; Langebartels, Georg; Markewitz, Andreas; Thiele, Holger; Trummer, Georg; Marggraf, Günter

    2015-01-01

    Although intra-aortic balloon pumping (IABP) is the most frequently used mechanical cardiac assist device in cardiothoracic surgery, there are only guidelines for substantive sections of aortic counterpulsation including prophylactic and postoperative use. In contrast, evidence-based recommendations are still lacking concerning intraoperative use, management, contraindication and other relevant issues. According to international surveys, important aspects of IABP usage show a wide variation in clinical practice. The results of a national questionnaire performed before initiation of this guideline confirmed these findings and demonstrated a clear need for the development of a consensus-based guideline. Therefore, the presented multidisciplinary S-3-guideline was developed under the direction of the German Society for Thoracic and Cardiovascular Surgery (Deutsche Gesellschaft für Thorax-, Herz- und Gefäßchirurgie, DGTHG) to make evidence-based recommendations for the usage of aortic counterpulsation after cardiothoracic surgery according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF) and the Medical Centre for Quality (Ärztliches Zentrum für Qualität - (ÄZQ)). Main topics discussed in this guideline involve IABP support in the prophylactic, preoperative, intraoperative and postoperative setting as well as the treatment of right heart failure, contraindications, anticoagulation, monitoring, weaning, and limitations of IABP therapy. The presented 15 key messages of the guideline were approved after two consensus meetings under moderation of the AWMF with participation of the German Society of Cardiology (DGK), German Society of Anaesthesiology and Intensive Care Medicine (DGAI), German Interdisciplinary Association for Intensive Care (DIVI) and the German Society for Cardiovascular Engineering (DGfK).

  20. Cardiac I-1c overexpression with reengineered AAV improves cardiac function in swine ischemic heart failure.

    PubMed

    Ishikawa, Kiyotake; Fish, Kenneth M; Tilemann, Lisa; Rapti, Kleopatra; Aguero, Jaume; Santos-Gallego, Carlos G; Lee, Ahyoung; Karakikes, Ioannis; Xie, Chaoqin; Akar, Fadi G; Shimada, Yuichi J; Gwathmey, Judith K; Asokan, Aravind; McPhee, Scott; Samulski, Jade; Samulski, Richard Jude; Sigg, Daniel C; Weber, Thomas; Kranias, Evangelia G; Hajjar, Roger J

    2014-12-01

    Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF.

  1. Determinants of biventricular cardiac function: a mathematical model study on geometry and myofiber orientation.

    PubMed

    Pluijmert, Marieke; Delhaas, Tammo; de la Parra, Adrián Flores; Kroon, Wilco; Prinzen, Frits W; Bovendeerd, Peter H M

    2017-04-01

    In patient-specific mathematical models of cardiac electromechanics, usually a patient-specific geometry and a generic myofiber orientation field are used as input, upon which myocardial tissue properties are tuned to clinical data. It remains unclear to what extent deviations in myofiber orientation and geometry between model and patient influence model predictions on cardiac function. Therefore, we evaluated the sensitivity of cardiac function for geometry and myofiber orientation in a biventricular (BiV) finite element model of cardiac mechanics. Starting out from a reference geometry in which myofiber orientation had no transmural component, two new geometries were defined with either a 27 % decrease in LV short- to long-axis ratio, or a 16 % decrease of RV length, but identical LV and RV cavity and wall volumes. These variations in geometry caused differences in both local myofiber and global pump work below 6 %. Variation of fiber orientation was induced through adaptive myofiber reorientation that caused an average change in fiber orientation of [Formula: see text] predominantly through the formation of a component in transmural direction. Reorientation caused a considerable increase in local myofiber work [Formula: see text] and in global pump work [Formula: see text] in all three geometries, while differences between geometries were below 5 %. The findings suggest that implementing a realistic myofiber orientation is at least as important as defining a patient-specific geometry. The model for remodeling of myofiber orientation seems a useful approach to estimate myofiber orientation in the absence of accurate patient-specific information.

  2. EANM/ESC guidelines for radionuclide imaging of cardiac function.

    PubMed

    Hesse, B; Lindhardt, T B; Acampa, W; Anagnostopoulos, C; Ballinger, J; Bax, J J; Edenbrandt, L; Flotats, A; Germano, G; Stopar, T Gmeiner; Franken, P; Kelion, A; Kjaer, A; Le Guludec, D; Ljungberg, M; Maenhout, A F; Marcassa, C; Marving, J; McKiddie, F; Schaefer, W M; Stegger, L; Underwood, R

    2008-04-01

    Radionuclide imaging of cardiac function represents a number of well-validated techniques for accurate determination of right (RV) and left ventricular (LV) ejection fraction (EF) and LV volumes. These first European guidelines give recommendations for how and when to use first-pass and equilibrium radionuclide ventriculography, gated myocardial perfusion scintigraphy, gated PET, and studies with non-imaging devices for the evaluation of cardiac function. The items covered are presented in 11 sections: clinical indications, radiopharmaceuticals and dosimetry, study acquisition, RV EF, LV EF, LV volumes, LV regional function, LV diastolic function, reports and image display and reference values from the literature of RVEF, LVEF and LV volumes. If specific recommendations given cannot be based on evidence from original, scientific studies, referral is given to "prevailing or general consensus". The guidelines are designed to assist in the practice of referral to, performance, interpretation and reporting of nuclear cardiology studies for the evaluation of cardiac performance.

  3. A separate pool of cardiac phospholemman that does not regulate or associate with the sodium pump: multimers of phospholemman in ventricular muscle.

    PubMed

    Wypijewski, Krzysztof J; Howie, Jacqueline; Reilly, Louise; Tulloch, Lindsay B; Aughton, Karen L; McLatchie, Linda M; Shattock, Michael J; Calaghan, Sarah C; Fuller, William

    2013-05-10

    Phospholemman regulates the plasmalemmal sodium pump in excitable tissues. In cardiac muscle, a subpopulation of phospholemman with a unique phosphorylation signature associates with other phospholemman molecules but not with the pump. Phospholemman oligomers exist in cardiac muscle. Much like phospholamban regulation of SERCA, phospholemman exists as both a sodium pump inhibiting monomer and an unassociated oligomer. Phospholemman (PLM), the principal quantitative sarcolemmal substrate for protein kinases A and C in the heart, regulates the cardiac sodium pump. Much like phospholamban, which regulates the related ATPase SERCA, PLM is reported to oligomerize. We investigated subpopulations of PLM in adult rat ventricular myocytes based on phosphorylation status. Co-immunoprecipitation identified two pools of PLM: one not associated with the sodium pump phosphorylated at Ser(63) and one associated with the pump, both phosphorylated at Ser(68) and unphosphorylated. Phosphorylation of PLM at Ser(63) following activation of PKC did not abrogate association of PLM with the pump, so its failure to associate with the pump was not due to phosphorylation at this site. All pools of PLM co-localized to cell surface caveolin-enriched microdomains with sodium pump α subunits, despite the lack of caveolin-binding motif in PLM. Mass spectrometry analysis of phosphospecific immunoprecipitation reactions revealed no unique protein interactions for Ser(63)-phosphorylated PLM, and cross-linking reagents also failed to identify any partner proteins for this pool. In lysates from hearts of heterozygous transgenic animals expressing wild type and unphosphorylatable PLM, Ser(63)-phosphorylated PLM co-immunoprecipitated unphosphorylatable PLM, confirming the existence of PLM multimers. Dephosphorylation of the PLM multimer does not change sodium pump activity. Hence like phospholamban, PLM exists as a pump-inhibiting monomer and an unassociated oligomer. The distribution of different PLM

  4. The effects of malnutrition on cardiac function in African children.

    PubMed

    Silverman, Jonathan A; Chimalizeni, Yamikani; Hawes, Stephen E; Wolf, Elizabeth R; Batra, Maneesh; Khofi, Harriet; Molyneux, Elizabeth M

    2016-02-01

    Cardiac dysfunction may contribute to high mortality in severely malnourished children. Our objective was to assess the effect of malnutrition on cardiac function in hospitalised African children. Prospective cross-sectional study. Public referral hospital in Blantyre, Malawi. We enrolled 272 stable, hospitalised children ages 6-59 months, with and without WHO-defined severe acute malnutrition. Cardiac index, heart rate, mean arterial pressure, stroke volume index and systemic vascular resistance index were measured by the ultrasound cardiac output monitor (USCOM, New South Wales, Australia). We used linear regression with generalised estimating equations controlling for age, sex and anaemia. Our primary outcome, cardiac index, was similar between those with and without severe malnutrition: difference=0.22 L/min/m(2) (95% CI -0.08 to 0.51). No difference was found in heart rate or stroke volume index. However, mean arterial pressure and systemic vascular resistance index were lower in children with severe malnutrition: difference=-8.6 mm Hg (95% CI -12.7 to -4.6) and difference=-200 dyne s/cm(5)/m(2) (95% CI -320 to -80), respectively. In this largest study to date, we found no significant difference in cardiac function between hospitalised children with and without severe acute malnutrition. Further study is needed to determine if cardiac function is diminished in unstable malnourished children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  5. Mammalian enabled (Mena) is a critical regulator of cardiac function.

    PubMed

    Aguilar, Frédérick; Belmonte, Stephen L; Ram, Rashmi; Noujaim, Sami F; Dunaevsky, Olga; Protack, Tricia L; Jalife, Jose; Todd Massey, H; Gertler, Frank B; Blaxall, Burns C

    2011-05-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena(-/-)) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena(-/-) mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena(-/-) hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena(-/-) mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.

  6. Control of cardiac function and venous return in thyrotoxic calves.

    PubMed

    Gay, R; Lee, R W; Appleton, C; Olajos, M; Martin, G V; Morkin, E; Goldman, S

    1987-03-01

    The mechanisms responsible for maintenance of the high-output state associated with thyrotoxicosis have been investigated by measurement of cardiac-function curves and venous compliance during ganglionic blockade with trimethaphan. Thirteen calves were injected daily with L-thyroxine (200 micrograms/kg) for 12-14 days. Thyroxine treatment increased heart rate (70%), left ventricular systolic pressure (22%), cardiac output (120%), left ventricular maximum rate of pressure development (dP/dt) (56%), and total blood volume (18%) and decreased systemic vascular resistance (39%). These hemodynamic changes persisted during ganglionic blockade or autonomic blockade with atropine and propranolol. Cardiac-function curves in conscious thyrotoxic calves were displaced upward and to the left. Mean circulatory filling pressure (MCFP), measured during anesthesia, was increased from 8 +/- 1 to 12 +/- 1 mmHg. During autonomic and ganglionic blockade MCFP remained elevated after treatment with thyroxine. Venous compliance decreased from 2.1 +/- 0.2 to 1.3 +/- 0.1 ml X mmHg-1 X kg-1 after thyroxine. Unstressed vascular volume was increased from 52.3 +/- 1.1 to 67.1 +/- 0.9 ml/kg. Thus the elevated cardiac output and new cardiac-function curve in thyrotoxicosis are associated with a combination of increased inotropic state, increased blood volume, and decreased venous compliance. These effects are not the result of autonomic influences and may represent direct actions of thyroid hormone on the heart and peripheral venous circulation.

  7. Valveless pumping mechanics of the embryonic heart during cardiac looping: Pressure and flow through micro-PIV.

    PubMed

    Bark, D L; Johnson, B; Garrity, D; Dasi, L P

    2017-01-04

    Cardiovascular development is influenced by the flow-induced stress environment originating from cardiac biomechanics. To characterize the stress environment, it is necessary to quantify flow and pressure. Here, we quantify the flow field in a developing zebrafish heart during the looping stage through micro-particle imaging velocimetry and by analyzing spatiotemporal plots. We further build upon previous methods to noninvasively quantify the pressure field at a low Reynolds number using flow field data for the first time, while also comparing the impact of viscosity models. Through this method, we show that the atrium builds up pressure to ~0.25mmHg relative to the ventricle during atrial systole and that atrial expansion creates a pressure difference of ~0.15mmHg across the atrium, resulting in efficient cardiac pumping. With these techniques, it is possible to noninvasively fully characterize hemodynamics during heart development.

  8. Mixing and pumping functions of the intestine of zebrafish larvae.

    PubMed

    Yang, Jinyou; Shimogonya, Yuji; Ishikawa, Takuji

    2017-02-07

    Due to its transparency, the intestine of zebrafish larvae has been widely used in studies of gastrointestinal diseases and the microbial flora of the gut. However, transport phenomena in the intestine of zebrafish larvae have not been fully clarified. In this study, therefore, transport caused by peristaltic motion in the intestine of zebrafish larvae was investigated by numerical simulation. An anatomically realistic three-dimensional geometric model of the intestine at various times after feeding was constructed based on the experimental data of Field et al. (2009). The flow of digested chyme was analyzed using the governing equations of fluid mechanics, together with peristaltic motion and long-term contraction of the intestinal wall. The results showed that retrograde peristaltic motion was the main contributor to the mixing function. The dispersion caused by peristalsis over 30min was in the order of 10(-12)m(2)/s, which is greater than the Brownian diffusion of a sphere of 0.4µm diameter. In contrast, anterograde peristaltic motion contributed mainly to the pumping function. The pressure decrease due to peristalsis was in the order of millipascals, which may reduce the activation and maintenance heat of intestinal muscle. These findings enhance our understanding of the mixing and pumping functions of the intestine of zebrafish larvae.

  9. Cardiac function in long-term survivors of childhood lymphoma.

    PubMed

    Friedberg, Mark K; Solt, Ido; Weyl-Ben-Arush, Myriam; Braver, Yulia; Lorber, Avraham

    2011-01-20

    Objectives. We studied long-term effects of therapy for childhood lymphoma on cardiac function. Design and patients. We prospectively evaluated 45 survivors of childhood lymphoma, using clinical parameters, electrocardiography and echocardiography. Further comparisons were made between lymphoma subgroups and between males and females. Results. Mean age at diagnosis was 9.1 years. Mean followup duration was 10.9 years. The NYHA functional class was I in 43 patients and II in 2 patients. A prolonged QTc interval (>0.44 msec) was found in 8 patients. Left ventricular (LV) systolic function and compliance were normal (LV shortening fraction 40 ± 5.6%; cardiac index 2.84 ± 1.13 L/min/m(2); E/A wave ratio 2.5 ± 1.3; mean ± S.D.), LV mass was normal (97 ± 40 grams/m(2), mean ± S.D.). Mitral regurgitation was observed in 7/45 patients (16%). Asymptomatic pericardial effusions were found in 3/45 (7%) patients. Conclusions. Long-term follow-up shows that most parameters of cardiac function are normal in survivors of childhood lymphoma. This is likely due to relatively low doses of anthracyclines in modern protocol modalities. Abnormalities in mitral valve flow, QTc prolongation and in a small proportion of survivors, and functional capacity necessitate long-term cardiac follow-up of these patients.

  10. Impairment of cardiac function and energetics in experimental renal failure.

    PubMed Central

    Raine, A E; Seymour, A M; Roberts, A F; Radda, G K; Ledingham, J G

    1993-01-01

    Cardiac function and energetics in experimental renal failure in the rat (5/6 nephrectomy) have been investigated by means of an isolated perfused working heart preparation and an isometric Langendorff preparation using 31P nuclear magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001) at all levels of preload and afterload in the renal failure groups than in the pair-fed sham operated control group. In control hearts, cardiac output increased with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic hearts failed in high calcium perfusate. Collection of 31P NMR spectra from hearts of renal failure and control animals during 30 min normoxic Langendorff perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01) in uremic hearts. During low flow ischemia, there was a substantial decrease in phosphocreatine in the uremic hearts and an accompanying marked increase in release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We conclude that cardiac function is impaired in experimental renal failure, in association with abnormal cardiac energetics and increased susceptibility to ischemic damage. Disordered myocardial calcium utilization may contribute to these derangements. PMID:8254048

  11. Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat.

    PubMed

    Nakamura, T; Hayashi, K; Seki, J; Fukuda, S; Noda, H; Nakatani, T; Takano, H; Akutsu, T

    1992-01-01

    Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.

  12. EPAC expression and function in cardiac fibroblasts and myofibroblasts

    SciTech Connect

    Olmedo, Ivonne; Muñoz, Claudia; Guzmán, Nancy; Catalán, Mabel; Vivar, Raúl; Ayala, Pedro; Humeres, Claudio; Aránguiz, Pablo; García, Lorena; Velarde, Victoria; Díaz-Araya, Guillermo

    2013-10-15

    In the heart, cardiac fibroblasts (CF) and cardiac myofibroblasts (CMF) are the main cells responsible for wound healing after cardiac insult. Exchange protein activated by cAMP (EPAC) is a downstream effector of cAMP, and it has been not completely studied on CF. Moreover, in CMF, which are the main cells responsible for cardiac healing, EPAC expression and function are unknown. We evaluated in both CF and CMF the effect of transforming growth factor β1 (TGF-β1) on EPAC-1 expression. We also studied the EPAC involvement on collagen synthesis, adhesion, migration and collagen gel contraction. Method: Rat neonatal CF and CMF were treated with TGF-β1 at different times and concentrations. EPAC-1 protein levels and Rap1 activation were measured by western blot and pull down assay respectively. EPAC cellular functions were determined by adhesion, migration and collagen gel contraction assay; and collagen expression was determined by western blot. Results: TGF-β1 through Smad and JNK significantly reduced EPAC-1 expression in CF, while in CMF this cytokine increased EPAC-1 expression through ERK1/2, JNK, p38, AKT and Smad3. EPAC activation was able to induce higher Rap1-GTP levels in CMF than in CF. EPAC and PKA, both cAMP effectors, promoted CF and CMF adhesion on fibronectin, as well as CF migration; however, this effect was not observed in CMF. EPAC but not PKA activation mediated collagen gel contraction in CF, while in CMF both PKA and EPAC mediated collagen gel contraction. Finally, the EPAC and PKA activation reduced collagen synthesis in CF and CMF. Conclusion: TGF-β1 differentially regulates the expression of EPAC in CF and CMF; and EPAC regulates differentially CF and CMF functions associated with cardiac remodeling. - Highlights: • TGF-β1 regulates EPAC-1 expression in cardiac fibroblast and myofibroblast. • Rap-1GTP levels are higher in cardiac myofibroblast than fibroblast. • EPAC-1 controls adhesion, migration and collagen synthesis in cardiac

  13. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade.

    PubMed

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A; Hamilton, Elisha J; Figtree, Gemma A; Rasmussen, Helge H

    2015-09-01

    Dysregulated nitric oxide (NO)- and superoxide (O2 (·-))-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na(+)-K(+) pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na(+)-K(+) pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47(phox) and membranous p22(phox) NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47(phox) to p22(phox) with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na(+)-K(+) pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22(phox) with p47(phox), abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na(+)-K(+) pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na(+)-K(+) pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes.

  14. β3-Adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade

    PubMed Central

    Karimi Galougahi, Keyvan; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A.; Hamilton, Elisha J.; Figtree, Gemma A.

    2015-01-01

    Dysregulated nitric oxide (NO)- and superoxide (O2·−)-dependent signaling contributes to the pathobiology of diabetes-induced cardiovascular complications. We examined if stimulation of β3-adrenergic receptors (β3-ARs), coupled to endothelial NO synthase (eNOS) activation, relieves oxidative inhibition of eNOS and the Na+-K+ pump induced by hyperglycemia. Hyperglycemia was established in male New Zealand White rabbits by infusion of the insulin receptor antagonist S961 for 7 days. Hyperglycemia increased tissue and blood indexes of oxidative stress. It induced glutathionylation of the Na+-K+ pump β1-subunit in cardiac myocytes, an oxidative modification causing pump inhibition, and reduced the electrogenic pump current in voltage-clamped myocytes. Hyperglycemia also increased glutathionylation of eNOS, which causes its uncoupling, and increased coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits, consistent with NADPH oxidase activation. Blocking translocation of p47phox to p22phox with the gp91ds-tat peptide in cardiac myocytes ex vivo abolished the hyperglycemia-induced increase in glutathionylation of the Na+-K+ pump β1-subunit and decrease in pump current. In vivo treatment with the β3-AR agonist CL316243 for 3 days eliminated the increase in indexes of oxidative stress, decreased coimmunoprecipitation of p22phox with p47phox, abolished the hyperglycemia-induced increase in glutathionylation of eNOS and the Na+-K+ pump β1-subunit, and abolished the decrease in pump current. CL316243 also increased coimmunoprecipitation of glutaredoxin-1 with the Na+-K+ pump β1-subunit, which may reflect facilitation of deglutathionylation. In vivo β3-AR activation relieves oxidative inhibition of key cardiac myocyte proteins in hyperglycemia and may be effective in targeting the deleterious cardiac effects of diabetes. PMID:26063704

  15. Exercise capacity in patients supported with rotary blood pumps is improved by a spontaneous increase of pump flow at constant pump speed and by a rise in native cardiac output.

    PubMed

    Jacquet, Luc; Vancaenegem, Olivier; Pasquet, Agnès; Matte, Pascal; Poncelet, Alain; Price, Joel; Gurné, Olivier; Noirhomme, Philippe

    2011-07-01

    Exercise capacity is improved in patients supported with continuous flow rotary blood pumps (RP). The aim of this study was to investigate the mechanisms underlying this improvement. Ten patients implanted with a RP underwent cardiopulmonary exercise testing (CPET) at 6 months after surgery with hemodynamic and metabolic measurements (RP group). A group of 10 matched heart failure patients were extracted from our heart transplant database, and the results of their last CPET before transplantation were used for comparison (heart failure [HF] group). Peak VO(2) was significantly higher in RP than in HF patients (15.8 ± 6.2 vs. 10.9 ± 3 mL O(2)/kg.min) reaching 52 ± 16% of their predicted peak VO(2). The total output measured by a Swan-Ganz catheter increased from 5.6 ± 1.6 to 9.2 ± 1.8 L/min in the RP group and was significantly higher at rest and at peak exercise than in the HF group, whose output increased from 3.5 ± 0.4 to 5.6 ± 1.6 L/min. In the RP group, the estimated pump flow increased from 5.3 ± 0.4 to 6.2 ± 0.8, whereas the native cardiac output increased from 0.0 ± 0.5 to 3 ± 1.7 L/min. Cardiac output at peak exercise was inversely correlated with age (r = -0.86, P = 0.001) and mean pulmonary artery pressure (r = -0.75, P = 0.012). Maximal exercise capacity is improved in patients supported by RP as compared to matched HF patients and reaches about 50% of the expected values. Both a spontaneous increase of pump flow at constant pump speed and an increase of the native cardiac output contribute to total flow elevation. These findings may suggest that an automatic pump speed adaptation during exercise would further improve the exercise capacity. This hypothesis should be examined.

  16. Cardiac nuclear receptors: architects of mitochondrial structure and function.

    PubMed

    Vega, Rick B; Kelly, Daniel P

    2017-04-03

    The adult heart is uniquely designed and equipped to provide a continuous supply of energy in the form of ATP to support persistent contractile function. This high-capacity energy transduction system is the result of a remarkable surge in mitochondrial biogenesis and maturation during the fetal-to-adult transition in cardiac development. Substantial evidence indicates that nuclear receptor signaling is integral to dynamic changes in the cardiac mitochondrial phenotype in response to developmental cues, in response to diverse postnatal physiologic conditions, and in disease states such as heart failure. A subset of cardiac-enriched nuclear receptors serve to match mitochondrial fuel preferences and capacity for ATP production with changing energy demands of the heart. In this Review, we describe the role of specific nuclear receptors and their coregulators in the dynamic control of mitochondrial biogenesis and energy metabolism in the normal and diseased heart.

  17. Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function

    PubMed Central

    Dongaonkar, Ranjeet M.; Stewart, Randolph H.; Geissler, Hans J.; Laine, Glen A.

    2010-01-01

    The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease. PMID:20472566

  18. Biohybrid cardiac ECM-based hydrogels improve long term cardiac function post myocardial infarction.

    PubMed

    Efraim, Yael; Sarig, Hadar; Cohen Anavy, Noa; Sarig, Udi; de Berardinis, Elio; Chaw, Su-Yin; Krishnamoorthi, Muthukumar; Kalifa, Jérôme; Bogireddi, Hanumakumar; Duc, Thang Vu; Kofidis, Theodoros; Baruch, Limor; Boey, Freddy Y C; Venkatraman, Subbu S; Machluf, Marcelle

    2017-03-01

    Injectable scaffolds for cardiac tissue regeneration are a promising therapeutic approach for progressive heart failure following myocardial infarction (MI). Their major advantage lies in their delivery modality that is considered minimally invasive due to their direct injection into the myocardium. Biomaterials comprising such scaffolds should mimic the cardiac tissue in terms of composition, structure, mechanical support, and most importantly, bioactivity. Nonetheless, natural biomaterial-based gels may suffer from limited mechanical strength, which often fail to provide the long-term support required by the heart for contraction and relaxation. Here we present newly-developed injectable scaffolds, which are based on solubilized decellularized porcine cardiac extracellular matrix (pcECM) cross-linked with genipin alone or engineered with different amounts of chitosan to better control the gel's mechanical properties while still leveraging the ECM biological activity. We demonstrate that these new biohybrid materials are naturally remodeled by mesenchymal stem cells, while supporting high viabilities and affecting cell morphology and organization. They exhibit neither in vitro nor in vivo immunogenicity. Most importantly, their application in treating acute and long term chronic MI in rat models clearly demonstrates the significant therapeutic potential of these gels in the long-term (12weeks post MI). The pcECM-based gels enable not only preservation, but also improvement in cardiac function eight weeks post treatment, as measured using echocardiography as well as hemodynamics. Infiltration of progenitor cells into the gels highlights the possible biological remodeling properties of the ECM-based platform.

  19. Short-term and long-term cognitive function and cerebral perfusion in off-pump and on-pump coronary artery bypass patients.

    PubMed

    Chernov, Vladimir I; Efimova, Nataliya Yu; Efimova, Irina Yu; Akhmedov, Shamil D; Lishmanov, Yuri B

    2006-01-01

    The aim of this study was to evaluate cognitive function, as measured by serial neuropsychological testing, and cerebral perfusion, as measured by brain SPECT scanning in patients with coronary artery diseases (CAD) following off-pump and on-pump coronary artery bypass graft surgery. Besides, the relationship between cerebral blood flow, cognitive functions, surgery parameters, and cardiac function in these patients were estimated. Also, brain-protective effects of instenon were studied. Brain SPECT and comprehensive neuropsychological testing were performed 1 day before, 10-14 days and 6 months after coronary artery bypass graft surgery (CABG). The study involved 65 patients (62 males and 3 females, mean age 55+/-2) who underwent CABG with cardiopulmonary bypass (CPB) (43 pts) and off-pump coronary revascularization (OPCAB) using the Octopus stabilization system (22 pts). In 21 cases employing CPB, for prevention of the impairments of cerebral perfusion and cognitive deficit instenon was administered. CABG with the use of extracorporeal circulation is complicated by short-term and long-term neurocognitive dysfunction (in 96 and 55% cases, correspondingly). Also, in the early period after CABG, in 68% patients, decrease in regional cerebral blood flow (rCBF) was found, and after 6 months brain perfusion was lower than the baseline in 55% cases. Relationship between postoperative rCBF changes and the dynamics of cognitive function was found in early period and after 6 months following CABG. The coronary revascularization on beating heart or preventive administration of instenon in CPB patients helps significantly to diminish the risk of cerebrovascular complication.

  20. The effects of residual pump blood on patient plasma free haemoglobin levels post cardiac surgery.

    PubMed

    Schotola, H; Wetz, A J; Popov, A F; Bergmann, I; Danner, B C; Schöndube, F A; Bauer, M; Bräuer, A

    2016-09-01

    At the end of cardiopulmonary bypass, there are invariably several hundred millilitres of residual pump blood in the reservoir, which can either be re-transfused or discarded. The objective of this prospective observational study was to investigate the quality of the residual pump blood, focusing on plasma free haemoglobin (pfHb) and blood cell counts. Fifty-one consecutive patients were included in the study. Forty-nine units of residual pump blood and 58 units of transfused red blood cell (RBC) concentrates were analysed. The mean preoperative pfHb of the patients was 0.057 ± 0.062 g/l, which increased gradually to 0.55 ± 0.36 g/l on arrival in the intensive care unit postoperatively. On the first postoperative day, the mean pfHb had returned to within the normal range. Our data showed that haemoglobin, haematocrit, and erythrocyte counts of residual pump blood were approximately 40% of the values in standardised RBC concentrates. Plasma free haemoglobin was significantly higher in residual pump blood compared to RBC concentrates, and nearly twice as high as the pfHb in patient blood samples taken contemporaneously. Our findings indicate that residual pump blood pfHb levels are markedly higher compared to patients' blood and RBC concentrates, but that its administration does not significantly increase patients' pfHb levels.

  1. Propofol Induction's Effect on Cardiac Function

    ClinicalTrials.gov

    2015-03-31

    This Study Was Focused to Evaluate Feasibility of Doppler Tissue Monitoring During the Induction Anesthesia,; and Evaluate Routine Propofol Induction's Effect on Myocardial Tissue Motion, Using Non-invasive Doppler Tissue and 2D Speckle Tracking Imaging.; This is the First Study, to Our Knowledge, Which Has Evaluated the Possible Impact of Propofol Induction on LV Function.

  2. Skeletal and cardiac muscle pericytes: Functions and therapeutic potential.

    PubMed

    Murray, Iain R; Baily, James E; Chen, William C W; Dar, Ayelet; Gonzalez, Zaniah N; Jensen, Andrew R; Petrigliano, Frank A; Deb, Arjun; Henderson, Neil C

    2017-03-01

    Pericytes are periendothelial mesenchymal cells residing within the microvasculature. Skeletal muscle and cardiac pericytes are now recognized to fulfill an increasing number of functions in normal tissue homeostasis, including contributing to microvascular function by maintaining vessel stability and regulating capillary flow. In the setting of muscle injury, pericytes contribute to a regenerative microenvironment through release of trophic factors and by modulating local immune responses. In skeletal muscle, pericytes also directly enhance tissue healing by differentiating into myofibers. Conversely, pericytes have also been implicated in the development of disease states, including fibrosis, heterotopic ossication and calcification, atherosclerosis, and tumor angiogenesis. Despite increased recognition of pericyte heterogeneity, it is not yet clear whether specific subsets of pericytes are responsible for individual functions in skeletal and cardiac muscle homeostasis and disease.

  3. Flow Rate In Microfluidic Pumps As A Function Of Tension and Pump Motor Head Speed

    NASA Astrophysics Data System (ADS)

    Irwin, Anthony; McBride, Krista

    2015-03-01

    As the use of microfluidic devices has become more common in recent years the need for standardization within the pump systems has grown. The pumps are ball bearing rotor microfluidic pumps and work off the idea of peristalsis. The rapid contraction and relaxation propagating down a tube or a microfluidic channel. The ball bearings compress the tube (occlusion) and move along part of the tube length forcing fluid to move inside of the tube in the same direction of the ball bearings. When the ball bearing rolls off the area occupied by the microfluidic channel, its walls and ceiling undergo restitution and a pocket of low pressure is briefly formed pulling more of the liquid into the pump system. Before looking to standardize the pump systems it must be known how the tension placed by the pumps bearing heads onto the PDMS inserts channels affect the pumps performance (mainly the flow rate produced). The relationship of the speed at which the bearings on the motor head spin and the flow rate must also be established. This research produced calibration curves for flow rate vs. tension and rpm. These calibration curves allow the devices to be set to optimal user settings by simply varying either the motor head tension or the motor head speed. I would like to acknowledge the help and support of Vanderbilt University SyBBURE program, Christina Marasco, Stacy Sherod, Franck Block and Krista McBride.

  4. Small molecule cardiogenol C upregulates cardiac markers and induces cardiac functional properties in lineage-committed progenitor cells.

    PubMed

    Mike, Agnes K; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D; Weitzer, Georg; Hilber, Karlheinz

    2014-01-01

    Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited transdifferentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy.

  5. [Ventricular pump function under ectopic excitation of the frog heart].

    PubMed

    Kibler, N A; Belogolova, A S; Vaĭkshnoraĭte, M A; Azarov, Ia E; Shmakov, D N

    2008-02-01

    The ventricular pump function under ectopic excitation of the heart was studied in decapitated and pithed adult frogs Rana temporaria (n = 21) at 18-19 degrees C. The intraventricular pressure was recorded with a catheter via ventricular wall. During pacing of the ventricular base and apex, the systolic pressure decreased (6.1 +/- 4.5 mm Hg and 8.9 +/- 5.0 mm Hg, respectively) as compared to the supraventricular rhythm (8.9 +/- 5.0 mm Hg, p < 0.05). The end-diastolic pressure decreased insignificantly both under basal and apical pacing. The systolic rate of pressure rise during dP/dtmax decreased under ventricular pacing, especially during pacing of the ventricular apex, as compared to the supraventricular rhythm (14.4 +/- 6/9 mm Hg/s and 22.1 +/- 11.2 mm Hg/s, respectively, p < 0.003). The isovolumetric relaxation (dP/dtmin) slowed during apical pacing as compared to the supraventricular rhythm (-25.1 +/- 13.6 and -35.6 +/- 18.3 mm Hg/s, respectively, p < 0.03). Ectopic excitation of the ventricular base and apex resulted in increase of the QRS duration (93 +/- 33 ms and 81 +/- 30 ms, respectively) as compared to the supraventricular rhythm (63 +/- 13 ms, p < 0.05). Thus, pacing of different ventricular areas ventricular myocardium with the ventricular pump function being reduced more obviously during the apical pacing compared to the pacing of ventricular base.

  6. [What is the utility of proton pump inhibitor testing in non-cardiac chest pain?].

    PubMed

    Huamán, José Wálter; Aliaga, Verónica; Domenech, Gemma; Videla, Sebastián; Saperas, Esteban

    2014-10-01

    Noncardiac chest pain (NCCP) often represents a diagnostic and therapeutic challenge. Given that gastroesophageal reflux disease (GERD) is the most common cause of NCCP, initial treatment with proton-pump inhibitors (PPI) has been proposed for all patients (PPI testing), reserving esophageal function testing solely for non-responders. The aim of the present study was to provide evidence on the clinical utility of PPI testing with high-dose pantoprazole in patients with NCCP. We carried out a study of diagnostic performance with a cohort design in patients with NCCP, who had been assessed by the Cardiology Service. All patients underwent upper endoscopy, esophageal manometry, and 24h esophageal pH monitoring before PPI testing with pantoprazole 40 mg every 12h for 1 month. Before and after treatment, we assessed the severity (intensity and frequency) of chest pain, quality of life, and anxiety and depression by means of specific questionnaires. The diagnosis of GERD was based on a pathological finding of esophageal pH monitoring. A positive response to PPI testing was defined as an improvement in chest pain >50% compared with the baseline score after 1 month of PPI therapy. We included 30 consecutive patients (17 men/13 women) with a mean age of 49 years. Of these 30 patients, 20 with NCCP had GERD (67%, 95%CI: 47%-83%). A positive response to PPI therapy was observed in 13 of the 30 (43%) patients with NCCP: 11 of the 20 (55%) patients in the GERD-positive group and 2 of the 10 (20%) in the GERD-negative group. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PPI testing was 55%, 80%, 85%, 47% and 63%, respectively. A significant reduction in chest pain after pantoprazole therapy (P=.003) and a slight non significant improvement in anxiety and depression was achieved in the GERD-positive group as compared to the GERD-negative group. In NCCP, PPI testing with pantoprazole has a low sensitivity for the diagnosis of

  7. Motor function improvement following intrathecal baclofen pump placement in a patient with locked-in syndrome.

    PubMed

    Cairns, Kevin; Stein, Joel

    2002-04-01

    We describe a patient with locked-in syndrome who had minimal volitional motor function and severe spasticity in all four extremities. The patient showed a significant improvement in volitional motor function following intrathecal baclofen pump therapy to control spasticity. This case study suggests that intrathecal baclofen pump therapy might improve motor function in select patients with locked-in syndrome.

  8. Cardiac function and cardiac events 1-year postpartum in women with congenital heart disease.

    PubMed

    Kampman, Marlies A M; Balci, Ali; Groen, Henk; van Dijk, Arie P J; Roos-Hesselink, Jolien W; van Melle, Joost P; Sollie-Szarynska, Krystyna M; Wajon, Elly M C J; Mulder, Barbara J M; van Veldhuisen, Dirk J; Pieper, Petronella G

    2015-02-01

    Pregnancy is increasingly common in women with congenital heart disease (CHD), but little is known about long-term cardiovascular outcome after pregnancy in these patients. We studied the incidence of cardiovascular events 1-year postpartum and compared cardiac function prepregnancy and 1-year postpartum in women with CHD. From our national, prospective multicenter cohort study, 172 women were studied. Follow-up with clinical evaluation and echocardiography and NT-proBNP measurement were performed during pregnancy and 12 months postpartum. Cardiovascular events were defined as need for an urgent invasive cardiovascular procedure, heart failure, arrhythmia, thromboembolic events, myocardial infarction, cardiac arrest, cardiac death, endocarditis, and aortic dissection. Cardiovascular events were observed after 11 pregnancies (6.4%). Women with cardiovascular events postpartum had significant higher NT-proBNP values at 20-week gestation (191 [137-288] vs 102.5 [57-167]; P = .049) and 1-year postpartum compared with women without cardiovascular events postpartum (306 [129-592] vs 105 [54-187] pg/mL; P = .014). Women with cardiovascular events during pregnancy were at higher risk for late cardiovascular events (HR 7.1; 95% CI 2.0-25.3; P = .003). In women with cardiovascular events during pregnancy, subpulmonary end-diastolic diameter had significantly increased 1-year postpartum (39.0 [36.0-48.0] to 44.0 [40.0-50.0]; P = .028). No other significant differences were found in cardiac function or size 1-year postpartum compared with preconception values. Cardiovascular events are relatively rare 1 year after pregnancy in women with CHD. Women with cardiovascular events during pregnancy are prone to develop cardiovascular events 1-year postpartum and have increased subpulmonary ventricular diameter compared with preconception values. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Impaired regulation of cardiac function in sepsis, SIRS, and MODS.

    PubMed

    Werdan, Karl; Schmidt, Hendrik; Ebelt, Henning; Zorn-Pauly, Klaus; Koidl, Bernd; Hoke, Robert Sebastian; Heinroth, Konstantin; Müller-Werdan, Ursula

    2009-04-01

    In sepsis, systemic inflammatory response syndrome (SIRS), and multiorgan dysfunction syndrome (MODS), a severe prognostically relevant cardiac autonomic dysfunction exists, as manifested by a strong attenuation of sympathetically and vagally mediated heart rate variability (HRV). The mechanisms underlying this attenuation are not limited to the nervous system. They also include alterations of the cardiac pacemaker cells on a cellular level. As shown in human atrial cardiomyocytes, endotoxin interacts with cardiac hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which mediate the pacemaker current If and play an important role in transmitting sympathetic and vagal signals on heart rate and HRV. Moreover, endotoxin sensitizes cardiac HCN channels to sympathetic signals. These findings identify endotoxin as a pertinent modulator of the autonomic nervous regulation of heart function. In MODS, the vagal pathway of the autonomic nervous system is particularly compromised, leading to an attenuation of the cholinergic antiinflammatory reflex. An amelioration of the blunted vagal activity appears to be a promising novel therapeutic target to achieve a suppression of the inflammatory state and thereby an improvement of prognosis in MODS patients. Preliminary data revealed therapeutic benefits (increased survival rates and improvements of the depressed vagal activity) of the administration of statins, beta-blockers, and angiotensin-converting enzyme inhibitors in patients with MODS.

  10. Exercise improves cardiac autonomic function in obesity and diabetes.

    PubMed

    Voulgari, Christina; Pagoni, Stamatina; Vinik, Aaron; Poirier, Paul

    2013-05-01

    Physical activity is a key element in the prevention and management of obesity and diabetes. Regular physical activity efficiently supports diet-induced weight loss, improves glycemic control, and can prevent or delay type 2 diabetes diagnosis. Furthermore, physical activity positively affects lipid profile, blood pressure, reduces the rate of cardiovascular events and associated mortality, and restores the quality of life in type 2 diabetes. However, recent studies have documented that a high percentage of the cardiovascular benefits of exercise cannot be attributed solely to enhanced cardiovascular risk factor modulation. Obesity in concert with diabetes is characterized by sympathetic overactivity and the progressive loss of cardiac parasympathetic influx. These are manifested via different pathogenetic mechanisms, including hyperinsulinemia, visceral obesity, subclinical inflammation and increased thrombosis. Cardiac autonomic neuropathy is an underestimated risk factor for the increased cardiovascular morbidity and mortality associated with obesity and diabetes. The same is true for the role of physical exercise in the restoration of the heart cardioprotective autonomic modulation in these individuals. This review addresses the interplay of cardiac autonomic function in obesity and diabetes, and focuses on the importance of exercise in improving cardiac autonomic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Cardiac Structure and Function in Cushing's Syndrome: A Cardiac Magnetic Resonance Imaging Study

    PubMed Central

    Roux, Charles; Salenave, Sylvie; Kachenoura, Nadjia; Raissouni, Zainab; Macron, Laurent; Guignat, Laurence; Jublanc, Christel; Azarine, Arshid; Brailly, Sylvie; Young, Jacques; Mousseaux, Elie; Chanson, Philippe

    2014-01-01

    Background: Patients with Cushing's syndrome have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but echo-based measurements may have limited accuracy in obese patients. No data are available on right ventricular (RV) and left atrial (LA) size and function in these patients. Objectives: The objective of the study was to evaluate LV, RV, and LA structure and function in patients with Cushing's syndrome by means of cardiac magnetic resonance, currently the reference modality in assessment of cardiac geometry and function. Methods: Eighteen patients with active Cushing's syndrome and 18 volunteers matched for age, sex, and body mass index were studied by cardiac magnetic resonance. The imaging was repeated in the patients 6 months (range 2–12 mo) after the treatment of hypercortisolism. Results: Compared with controls, patients with Cushing's syndrome had lower LV, RV, and LA ejection fractions (P < .001 for all) and increased end-diastolic LV segmental thickness (P < .001). Treatment of hypercortisolism was associated with an improvement in ventricular and atrial systolic performance, as reflected by a 15% increase in the LV ejection fraction (P = .029), a 45% increase in the LA ejection fraction (P < .001), and an 11% increase in the RV ejection fraction (P = NS). After treatment, the LV mass index and end-diastolic LV mass to volume ratio decreased by 17% (P < .001) and 10% (P = .002), respectively. None of the patients had late gadolinium myocardial enhancement. Conclusion: Cushing's syndrome is associated with subclinical biventricular and LA systolic dysfunctions that are reversible after treatment. Despite skeletal muscle atrophy, Cushing's syndrome patients have an increased LV mass, reversible upon correction of hypercortisolism. PMID:25093618

  12. Cardiac autonomic function and oesophageal acid sensitivity in patients with non-cardiac chest pain

    PubMed Central

    Tougas, G; Spaziani, R; Hollerbach, S; Djuric, V; Pang, C; Upton, A; Fallen, E; Kamath, M

    2001-01-01

    BACKGROUND—Acid reflux can elicit non-cardiac chest pain (NCCP), possibly through altered visceral sensory or autonomic function. The interactions between symptoms, autonomic function, and acid exposure are poorly understood.
AIM—To examine autonomic function in NCCP patients during exposure to oesophageal acid infusion.
SUBJECTS AND METHODS—Autonomic activity was assessed using power spectral analysis of heart rate variability (PSHRV), before and during oesophageal acidification (0.1 N HCl), in 28 NCCP patients (40.5 (10) years; 13 females) and in 10 matched healthy controls. Measured PSHRV indices included high frequency (HF) (0.15-0.5 Hz) and low frequency (LF) (0.06-0.15 Hz) power to assess vagal and sympathetic activity, respectively.
RESULTS—A total of 19/28 patients had angina-like symptoms elicited by acid. There were no significant manometric changes observed in either acid sensitive or insensitive patients. Acid sensitive patients had a higher baseline heart rate (82.9 (3.1) v 66.7 (3.5) beats/min; p<0.005) and lower baseline vagal activity (HF normalised area: 31.1 (1.9)% v 38.9 (2.3)%; p< 0.03) than acid insensitive patients. During acid infusion, vagal cardiac outflow increased (p<0.03) in acid sensitive but not in acid insensitive patients.
CONCLUSIONS—Patients with angina-like pain during acid infusion have decreased resting vagal activity. The symptoms elicited by perception of acid are further associated with a simultaneous increase in vagal activity in keeping with a vagally mediated pseudoaffective response.


Keywords: reflux disease; non-cardiac chest pain; acid reflux; autonomic nervous system; vagal response; sympathetic activity; heart rate variability; power spectrum analysis PMID:11600476

  13. Na/K pump inactivation, subsarcolemmal Na measurements, and cytoplasmic ion turnover kinetics contradict restricted Na spaces in murine cardiac myocytes.

    PubMed

    Lu, Fang-Min; Hilgemann, Donald W

    2017-07-03

    Decades ago, it was proposed that Na transport in cardiac myocytes is modulated by large changes in cytoplasmic Na concentration within restricted subsarcolemmal spaces. Here, we probe this hypothesis for Na/K pumps by generating constitutive transsarcolemmal Na flux with the Na channel opener veratridine in whole-cell patch-clamp recordings. Using 25 mM Na in the patch pipette, pump currents decay strongly during continuous activation by extracellular K (τ, ∼2 s). In contradiction to depletion hypotheses, the decay becomes stronger when pump currents are decreased by hyperpolarization. Na channel currents are nearly unchanged by pump activity in these conditions, and conversely, continuous Na currents up to 0.5 nA in magnitude have negligible effects on pump currents. These outcomes are even more pronounced using 50 mM Li as a cytoplasmic Na congener. Thus, the Na/K pump current decay reflects mostly an inactivation mechanism that immobilizes Na/K pump charge movements, not cytoplasmic Na depletion. When channel currents are increased beyond 1 nA, models with unrestricted subsarcolemmal diffusion accurately predict current decay (τ ∼15 s) and reversal potential shifts observed for Na, Li, and K currents through Na channels opened by veratridine, as well as for Na, K, Cs, Li, and Cl currents recorded in nystatin-permeabilized myocytes. Ion concentrations in the pipette tip (i.e., access conductance) track without appreciable delay the current changes caused by sarcolemmal ion flux. Importantly, cytoplasmic mixing volumes, calculated from current decay kinetics, increase and decrease as expected with osmolarity changes (τ >30 s). Na/K pump current run-down over 20 min reflects a failure of pumps to recover from inactivation. Simulations reveal that pump inactivation coupled with Na-activated recovery enhances the rapidity and effectivity of Na homeostasis in cardiac myocytes. In conclusion, an autoregulatory mechanism enhances cardiac Na/K pump activity when

  14. Goal-directed Therapy Improves the Outcome of High-risk Cardiac Patients Undergoing Off-pump Coronary Artery Bypass

    PubMed Central

    Kapoor, Poonam Malhotra; Magoon, Rohan; Rawat, Rajinder Singh; Mehta, Yatin; Taneja, Sameer; Ravi, R; Hote, Milind P

    2017-01-01

    Background: There has been a constant emphasis on developing management strategies to improve the outcome of high-risk cardiac patients undergoing surgical revascularization. The performance of coronary artery bypass surgery on an off-pump coronary artery bypass (OPCAB) avoids the risks associated with extra-corporeal circulation. The preliminary results of goal-directed therapy (GDT) for hemodynamic management of high-risk cardiac surgical patients are encouraging. The present study was conducted to study the outcome benefits with the combined use of GDT with OPCAB as compared to the conventional hemodynamic management. Material and Method: Patients with the European System for Cardiac Operative Risk Evaluation ≥3 scheduled for OPCAB were randomly divided into two groups; the control and GDT groups. The GDT group included the monitoring and optimization of advanced parameters, including cardiac index (CI), systemic vascular resistance index, oxygen delivery index, stroke volume variation; continuous central venous oxygen saturation (ScVO2), global end-diastolic volume, and extravascular lung water (EVLW), using FloTrac™, PreSep™, and EV-1000® monitoring panels, in addition to the conventional hemodynamic management in the control group. The hemodynamic parameters were continuously monitored for 48 h in Intensive Care Unit (ICU) and corrected according to GDT protocol. A total of 163 patients consented for the study. Result: Seventy-five patients were assigned to the GDT group and 88 patients were in the control group. In view of 9 exclusions from the GDT group and 12 exclusions from control group, 66 patients in the GDT group and 76 patients in control group completed the study. Conclusion: The length of stay in hospital (LOS-H) (7.42 ± 1.48 vs. 5.61 ± 1.11 days, P < 0.001) and ICU stay (4.2 ± 0.82 vs. 2.53 ± 0.56 days, P < 0.001) were significantly lower in the GDT group as compared to control group. The duration of inotropes (3.24 ± 0.73 vs. 2.89

  15. Goal-directed therapy improves the outcome of high-risk cardiac patients undergoing off-pump coronary artery bypass.

    PubMed

    Kapoor, Poonam Malhotra; Magoon, Rohan; Rawat, Rajinder Singh; Mehta, Yatin; Taneja, Sameer; Ravi, R; Hote, Milind P

    2017-01-01

    There has been a constant emphasis on developing management strategies to improve the outcome of high-risk cardiac patients undergoing surgical revascularization. The performance of coronary artery bypass surgery on an off-pump coronary artery bypass (OPCAB) avoids the risks associated with extra-corporeal circulation. The preliminary results of goal-directed therapy (GDT) for hemodynamic management of high-risk cardiac surgical patients are encouraging. The present study was conducted to study the outcome benefits with the combined use of GDT with OPCAB as compared to the conventional hemodynamic management. Patients with the European System for Cardiac Operative Risk Evaluation ≥3 scheduled for OPCAB were randomly divided into two groups; the control and GDT groups. The GDT group included the monitoring and optimization of advanced parameters, including cardiac index (CI), systemic vascular resistance index, oxygen delivery index, stroke volume variation; continuous central venous oxygen saturation (ScVO 2 ), global end-diastolic volume, and extravascular lung water (EVLW), using FloTrac™ , PreSep™ , and EV-1000 ® monitoring panels, in addition to the conventional hemodynamic management in the control group. The hemodynamic parameters were continuously monitored for 48 h in Intensive Care Unit (ICU) and corrected according to GDT protocol. A total of 163 patients consented for the study. Seventy-five patients were assigned to the GDT group and 88 patients were in the control group. In view of 9 exclusions from the GDT group and 12 exclusions from control group, 66 patients in the GDT group and 76 patients in control group completed the study. The length of stay in hospital (LOS-H) (7.42 ± 1.48 vs. 5.61 ± 1.11 days, P < 0.001) and ICU stay (4.2 ± 0.82 vs. 2.53 ± 0.56 days, P < 0.001) were significantly lower in the GDT group as compared to control group. The duration of inotropes (3.24 ± 0.73 vs. 2.89 ± 0.68 h, P = 0.005) was also significantly lower

  16. A comparison of survival between on-pump and off-pump left internal mammary artery bypass graft surgery for isolated left anterior descending coronary artery disease: an analysis of the UK National Adult Cardiac Surgery Audit Registry.

    PubMed

    Hickey, Graeme L; Pullan, Mark; Oo, Aung; Mediratta, Neeraj; Chalmers, John; Bridgewater, Ben; Poullis, Michael

    2016-05-01

    To determine if the use of cardiopulmonary bypass is associated with all-cause in-hospital and mid-term survival for patients undergoing left internal mammary artery (LIMA) to left anterior descending (LAD) coronary artery bypass grafting (CABG) for single coronary vessel disease. Data from the National Adult Cardiac Surgery Audit registry for all elective and urgent isolated CABG procedures performed between April 2003 and March 2013 in first-time cardiac surgery patients were extracted. Experienced surgeons (those with ≥300 records) were classified by their technique preference (as 'off-pump preference', 'mixed practice', 'on-pump preference') based on their entire isolated CABG data. In-hospital mortality and time to death were analysed using logistic and Cox proportional hazards regression models, respectively. From a total of 3402 records, 65.5% were performed off-pump. There were 16 (0.47%) in-hospital deaths: 6 (0.51%) in the on-pump group and 10 (0.45%) in the off-pump group. The risk-adjusted odds ratio of in-hospital mortality in the direction of on-pump was 1.09 [95% confidence interval (CI): 0.39-3.04; P = 0.86]. The overall 5-year survival in the on- and off-pump groups was 93.1 and 93.4%, respectively. The adjusted hazard ratio (HR) for mortality in the direction of on-pump CABG was 1.15 (95% CI: 0.89-1.49; P = 0.28). Comparing off-pump cases performed by experienced CABG surgeons with a preference for the off-pump technique with on-pump cases performed by surgeons with a preference for the on-pump technique indicated a significant difference (HR for on-pump = 1.72; 95% CI: 1.19-2.47; P = 0.004). Elective and urgent first-time CABG for isolated LAD disease is associated with excellent mid-term survival in the England and Wales population, conferring a 5-year survival rate of 93.1 and 93.4% in the on-pump and off-pump groups, respectively. There was no difference in risk-adjusted survival between the on-pump and off-pump techniques when analysing all

  17. Cardiac-specific miRNA in cardiogenesis, heart function, and cardiac pathology (with focus on myocardial infarction).

    PubMed

    Chistiakov, Dimitry A; Orekhov, Alexander N; Bobryshev, Yuri V

    2016-05-01

    Cardiac miRNAs (miR-1, miR133a, miR-208a/b, and miR-499) are abundantly expressed in the myocardium. They play a central role in cardiogenesis, heart function and pathology. While miR-1 and miR-133a predominantly control early stages of cardiogenesis supporting commitment of cardiac-specific muscle lineage from embryonic stem cells and mesodermal precursors, miR-208 and miR-499 are involved in the late cardiogenic stages mediating differentiation of cardioblasts to cardiomyocytes and fast/slow muscle fiber specification. In the heart, miR-1/133a control cardiac conductance and automaticity by regulating all phases of the cardiac action potential. miR-208/499 located in introns of the heavy chain myosin genes regulate expression of sarcomeric contractile proteins. In cardiac pathology including myocardial infarction (MI), expression of cardiac miRNAs is markedly altered that leads to deleterious effects associated with heart wounding, arrhythmia, increased apoptosis, fibrosis, hypertrophy, and tissue remodeling. In acute MI, circulating levels of cardiac miRNAs are significantly elevated making them to be a promising diagnostic marker for early diagnosis of acute MI. Great cardiospecific capacity of these miRNAs is very helpful for enhancing regenerative properties and survival of stem cell and cardiac progenitor transplants and for reprogramming of mature non-cardiac cells to cardiomyocytes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. The relationship between cardiac resynchronization therapy and diastolic function.

    PubMed

    Egnaczyk, Gregory F; Chung, Eugene S

    2014-03-01

    Cardiac resynchronization therapy (CRT) improves measures of systolic function and clinical status. However, its effect on diastolic function is not well established. Commonly used parameters of diastolic function are measured from echocardiography, using pulse wave and tissue Doppler technologies, as well as timing and deformation data. Review of the existing studies that address the relationship between diastolic function and CRT shows conflicting data, but general trends can be deduced. Baseline elevated filling pressure appears to identify patients most likely to derive improvement in that particular parameter. Intrinsic relaxation does not appear to be significantly impacted by CRT. Generally, changes in diastolic properties after CRT appear to be linked to changes in systolic function. Specific therapy aimed at diastolic asynchrony is lacking, partly due to an unclear relationship between diastolic asynchrony and diastolic dysfunction, and the inability to specifically impact diastolic timing with a systolic intervention such as CRT.

  19. Amalaki rasayana, a traditional Indian drug enhances cardiac mitochondrial and contractile functions and improves cardiac function in rats with hypertrophy.

    PubMed

    Kumar, Vikas; Aneesh, Kumar A; Kshemada, K; Ajith, Kumar G S; Binil, Raj S S; Deora, Neha; Sanjay, G; Jaleel, A; Muraleedharan, T S; Anandan, E M; Mony, R S; Valiathan, M S; Santhosh, Kumar T R; Kartha, C C

    2017-08-17

    We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated. Histology, gene and protein expression analysis were done in heart tissues. Chemical composition of AR was analyzed by HPLC, HPTLC and LC-MS. AR intake improved (P < 0.05) cardiac function in aging rats and decreased LVH (P < 0.05) in AC rats as well as increased (P < 0.05) fatigue time in treadmill exercise in both groups. In heart tissues of AR administered rats of both the groups, SERCA2, CaM, Myh11, antioxidant, autophagy, oxidative phosphorylation and TCA cycle proteins were up regulated. ADRB1/2 and pCREB expression were increased; pAMPK, NF-kB were decreased. AR has thus a beneficial effect on myocardial energetics, muscle contractile function and exercise tolerance capacity.

  20. Complete Reversion of Cardiac Functional Adaptation Induced by Exercise Training.

    PubMed

    Oláh, Attila; Kellermayer, Dalma; Mátyás, Csaba; Németh, Balázs Tamás; Lux, Árpád; Szabó, Lilla; Török, Marianna; Ruppert, Mihály; Meltzer, Anna; Sayour, Alex Ali; Benke, Kálmán; Hartyánszky, István; Merkely, Béla; Radovits, Tamás

    2017-03-01

    Long-term exercise training is associated with characteristic cardiac adaptation, termed athlete's heart. Our research group previously characterized in vivo left ventricular (LV) function of exercise-induced cardiac hypertrophy in detail in a rat model; however, the effect of detraining on LV function is still unclear. We aimed at evaluating the reversibility of functional alterations of athlete's heart after detraining. Rats (n = 16) were divided into detrained exercised (DEx) and detrained control (DCo) groups. Trained rats swam 200 min·d for 12 wk, and control rats were taken into water for 5 min·d. After the training period, both groups remained sedentary for 8 wk. We performed echocardiography at weeks 12 and 20 to investigate the development and regression of exercise-induced structural changes. LV pressure-volume analysis was performed to calculate cardiac functional parameters. LV samples were harvested for histological examination. Echocardiography showed robust LV hypertrophy after completing the training protocol (LV mass index = 2.61 ± 0.08 DEx vs 2.04 ± 0.04 g·kg DCo, P < 0.05). This adaptation regressed after detraining (LV mass index = 2.01 ± 0.03 vs 1.97 ± 0.05 g·kg, n.s.), which was confirmed by postmortem measured heart weight and histological morphometry. After the 8-wk-long detraining period, a regression of the previously described exercise-induced cardiac functional alterations was observed (DEx vs DCo): stroke volume (SV; 144.8 ± 9.0 vs 143.9 ± 9.6 μL, P = 0.949), active relaxation (τ = 11.5 ± 0.3 vs 11.3 ± 0.4 ms, P = 0.760), contractility (preload recruitable stroke work = 69.5 ± 2.7 vs 70.9 ± 2.4 mm Hg, P = 0.709), and mechanoenergetic (mechanical efficiency = 68.7 ± 1.2 vs 69.4 ± 1.8, P = 0.742) enhancement reverted completely to control values. Myocardial stiffness remained unchanged; moreover, no fibrosis was observed after the detraining period. Functional consequences of exercise-induced physiological LV hypertrophy

  1. Positron emission tomographic imaging of cardiac sympathetic innervation and function

    SciTech Connect

    Goldstein, D.S.; Chang, P.C.; Eisenhofer, G.; Miletich, R.; Finn, R.; Bacher, J.; Kirk, K.L.; Bacharach, S.; Kopin, I.J. )

    1990-05-01

    Sites of uptake, storage, and metabolism of ({sup 18}F)fluorodopamine and excretion of ({sup 18}F)fluorodopamine and its metabolites were visualized using positron emission tomographic (PET) scanning after intravenous injection of the tracer into anesthetized dogs. Radioactivity was concentrated in the renal pelvis, heart, liver, spleen, salivary glands, and gall bladder. Uptake of 18F by the heart resulted in striking delineation of the left ventricular myocardium. Pretreatment with desipramine markedly decreased cardiac positron emission, consistent with dependence of the heart on neuronal uptake (uptake-1) for removal of circulating catecholamines. In reserpinized animals, cardiac positron emission was absent within 30 minutes after injection of ({sup 18}F)-6-fluorodopamine, demonstrating that the emission in untreated animals was from radioactive labeling of the sympathetic storage vesicles. Decreased positron emission from denervated salivary glands confirmed that the tracer was concentrated in sympathetic neurons. Radioactivity in the gall bladder and urinary system depicted the hepatic and renal excretion of the tracer and its metabolites. Administration of tyramine or nitroprusside increased and ganglionic blockade with trimethaphan decreased the rate of loss of myocardial radioactivity. The results show that PET scanning after administration of ({sup 18}F)fluorodopamine can be used to visualize sites of sympathetic innervation, follow the metabolism and renal and hepatic excretion of catecholamines, and examine cardiac sympathetic function.

  2. [Intrinsic cardiac ganglia].

    PubMed

    Birand, Ahmet

    2008-12-01

    Heart has been considered as the source and the seat of emotions, passion and love. But from the dawn of XIXth century, scientists have emphasized that the heart, though life depends on its ceaseless activity, is merely a electromechanical pump, pumping oxygenated blood. Nowadays, we all know that heart pumps blood commensurate with the needs of the body and this unending toil, and its regulation depends on the intrinsic properties of the myocardium, Frank-Starling Law and neurohumoral contribution. It has been understood, though not clearly enough, that these time-tensions may cause structural or functional cardiac impairments and arrhythmias are related to the autonomic nervous system. Less well known and less taken in account in daily cardiology practice is the fact that heart has an intrinsic cardiac nervous system, or "heart brain" consisting of complex ganglia, intrinsic cardiac ganglia containing afferent (receiving), local circuit (interneurons) and efferent (transmitting) sympathetic and parasympathetic neurons. This review enlightens structural and functional aspects of intrinsic cardiac ganglia as the very first step in the regulation of cardiac function. This issue is important for targets of pharmacological treatment and techniques of cardiac surgery interventions as repair of septal defects, valvular interventions and congenital corrections.

  3. Successful resuscitation of cardiac arrest caused by CO2 embolism with intra-aortic injection of epinephrine during off-pump coronary bypass surgery -a case report-.

    PubMed

    Lee, Choon Soo; Yoon, Yeo Sam; Shim, Jae-Kwang; Lim, Hyun Kyoung

    2013-12-01

    Although compressed gas (CO2) blowers have been used safely to aid accurate grafting during off-pump coronary bypass surgery, hemodynamic collapse due to gas embolism into the right coronary artery may occur. Supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability. However, right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications, even when performing resuscitative measures such as direct cardiac massage. We herein report a case of cardiac arrest that was caused by a right coronary gas embolism and that could not be restored by cardiac resuscitation. When supportive measures fail, direct aortic injection of epinephrine to increase the coronary perfusion pressure can be attempted before initiating cardiopulmonary bypass, and this approach may be life-saving in situations that limit systemic drug delivery from the venous side despite the performance of direct cardiac massage.

  4. Isosmotic media prevent edema in amphibian larvae without cardiac function.

    PubMed

    Smith, S C

    2000-03-01

    The absence of cardiac and circulatory function causes severe edema in amphibian embryos. Analyzing the roles of embryonic and larval circulation in respiration may thus be confounded by the increased diffusion distance and decreased surface area/volume ratio caused by edema. Similarly, detailed morphological analyses of embryos/larvae with defective circulatory or renal function is difficult or impossible due to the gross morphological anomalies engendered by edematous swelling. To circumvent these problems, two media have been developed which are isosmotic with the plasma of a common experimental amphibian species (Ambystoma mexicanun). These media are remarkably effective in preventing fluid accumulation in embryos and larvae lacking heart function and, when used in slightly lower concentrations, cause no apparent harm to embryos and larvae with normal circulation for periods up to 3 weeks. These media should prove useful for a variety of studies on the developmental physiology of the circulatory system and possibly also when examining the development of renal function and ionoregulation.

  5. Comparing S-100 beta protein levels and neurocognitive functions between patients undergoing on-pump and off-pump coronary artery bypass grafting.

    PubMed

    Bayram, Huseyin; Hidiroglu, Mete; Cetin, Levent; Kucuker, Aslihan; Iriz, Erkan; Uguz, Emrah; Saglam, Fethi; Sener, Erol

    2013-06-15

    In the present study, we aimed to investigate the effects of off-pump coronary artery bypass grafting and on-pump cardiopulmonary bypass on the serum S-100 beta (S-100B) protein levels and neurocognitive functions of the patients. Sixty-four patients undergoing coronary artery bypass grafting (CABG) were enrolled in the study and were divided into two groups: off-pump (group I, n = 24) and on-pump CABG (group II, n = 40) group. Serum S-100B levels were measured before and 0, 6, and 24 h after the operation. Neurocognitive function tests were done preoperatively and were repeated in the postoperative period as well. Serum S-100B levels were similar between the two groups preoperatively. However, median S-100B levels at 0, 6, and 24 h after the surgery were found to be significantly lower in the off-pump CABG group than in the on-pump group. The preoperative neurocognitive functions of the patients were similar between the two groups, whereas neurocognitive function was found to be significantly impaired postoperatively in the on-pump group in comparison with the off-pump CABG group. We concluded that off-pump CABG is associated with decreased serum S100 protein levels and less impairment on neurocognitive functions compared with the on-pump group. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Isolated pulmonary regurgitation causes decreased right ventricular longitudinal function and compensatory increased septal pumping in a porcine model.

    PubMed

    Kopic, S; Stephensen, S S; Heiberg, E; Arheden, H; Bonhoeffer, P; Ersbøll, M; Vejlstrup, N; Søndergaard, L; Carlsson, M

    2017-06-05

    Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR. Piglets were divided into a control (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2-3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow-up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end-diastole to end-systole in the cardiac short axis and long axis. PR resulted in a lower longitudinal contribution to RV stroke volume, compared to controls (60.0 ± 2.6% vs. 73.6 ± 3.8%; P = 0.012). Furthermore, a compensatory increase in septal contribution to RVSV was observed (11.0 ± 1.6% vs. -3.1 ± 1.5%; P < 0.0001). The left ventricle (LV) showed counter-regulation with an increased longitudinal LVSV. Changes in RV longitudinal function were reversed by PPVR. These findings suggest that PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients. © 2017 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

  7. Protecting Mitochondrial Bioenergetic Function during Resuscitation from Cardiac Arrest

    PubMed Central

    Gazmuri, Raúl J.; Radhakrishnan, Jeejabai

    2012-01-01

    Synopsis Successful resuscitation from cardiac arrest requires reestablishment of aerobic metabolism by reperfusion with oxygenated blood of tissues that have been deprived of oxygen for variables periods of time. However, reperfusion concomitantly activates pathogenic mechanisms known as “reperfusion injury.” At the core of reperfusion injury are mitochondria, playing a critical role as effectors and targets of such injury. Mitochondrial injury compromises oxidative phosphorylation and also prompts release of cytochrome c to the cytosol and bloodstream where it correlates with severity of injury. Main drivers of such injury include Ca2+ overload and oxidative stress. Preclinical work shows that limiting myocardial cytosolic Na+ overload at the time of reperfusion attenuates mitochondrial Ca2+ overload and maintains oxidative phosphorylation yielding functional myocardial benefits that include preservation of left ventricular distensibility. Preservation of left ventricular distensibility enables hemodynamically more effective chest compression. Similar myocardial effect have been reported using erythropoietin hypothesized to protect mitochondrial bioenergetic function presumably through activation of pathways similar to those activated during preconditioning. Incorporation of novel and clinical relevant strategies to protect mitochondrial bioenergetic function are expected to attenuate injury at the time of reperfusion and enhance organ viability ultimately improving resuscitation and survival from cardiac arrest. PMID:22433486

  8. Effect of prolonged space flight on cardiac function and dimensions

    NASA Technical Reports Server (NTRS)

    Henry, W. L.; Epstein, S. E.; Griffith, J. M.; Goldstein, R. E.; Redwood, D. R.

    1974-01-01

    Echocardiographic studies were performed preflight 5 days before launch and on recovery day and 1, 2, 4, 11, 31 and 68 days postflight. From these echocardiograms measurements were made. From these primary measurements, left ventricular end-diastolic volume, end-systolic volume, stroke volume, and mass were derived using the accepted assumptions. Findings in the Scientist Pilot and Pilot resemble those seen in trained distance runners. Wall thickness measurements were normal in all three crewmembers preflight. Postflight basal studies were unchanged in the Commander on recovery day through 68 days postflight in both the Scientist Pilot and Pilot, however, the left ventricular end-diastolic volume, stroke volume, and mass were decreased slightly. Left ventricular function curves were constructed for the Commander and Pilot by plotting stroke volume versus end-diastolic volume. In both astronauts, preflight and postflight data fell on the same straight line demonstrating that no deterioration in cardiac function had occurred. These data indicate that the cardiovascular system adapts well to prolonged weightlessness and suggest that alterations in cardiac dimensions and function are unlikely to limit man's future in space.

  9. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    NASA Astrophysics Data System (ADS)

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-06-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, freestanding electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function.

  10. Engineered hybrid cardiac patches with multifunctional electronics for online monitoring and regulation of tissue function

    PubMed Central

    Feiner, Ron; Engel, Leeya; Fleischer, Sharon; Malki, Maayan; Gal, Idan; Shapira, Assaf; Shacham-Diamand, Yosi; Dvir, Tal

    2016-01-01

    In cardiac tissue engineering approaches to treat myocardial infarction, cardiac cells are seeded within three-dimensional porous scaffolds to create functional cardiac patches. However, current cardiac patches do not allow for online monitoring and reporting of engineered-tissue performance, and do not interfere to deliver signals for patch activation or to enable its integration with the host. Here, we report an engineered cardiac patch that integrates cardiac cells with flexible, free-standing electronics and a 3D nanocomposite scaffold. The patch exhibited robust electronic properties, enabling the recording of cellular electrical activities and the on-demand provision of electrical stimulation for synchronizing cell contraction. We also show that electroactive polymers containing biological factors can be deposited on designated electrodes to release drugs in the patch microenvironment on-demand. We expect that the integration of complex electronics within cardiac patches will eventually provide therapeutic control and regulation of cardiac function. PMID:26974408

  11. Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function.

    PubMed

    Chiellini, Grazia; Frascarelli, Sabina; Ghelardoni, Sandra; Carnicelli, Vittoria; Tobias, Sandra C; DeBarber, Andrea; Brogioni, Simona; Ronca-Testoni, Simonetta; Cerbai, Elisabetta; Grandy, David K; Scanlan, Thomas S; Zucchi, Riccardo

    2007-05-01

    3-Iodothyronamine T1AM is a novel endogenous thyroid hormone derivative that activates the G protein-coupled receptor known as trace anime-associated receptor 1 (TAAR1). In the isolated working rat heart and in rat cardiomyocytes, T1AM produced a reversible, dose-dependent negative inotropic effect (e.g., 27+/-5, 51+/-3, and 65+/-2% decrease in cardiac output at 19, 25, and 38 microM concentration, respectively). An independent negative chronotropic effect was also observed. The hemodynamic effects of T1AM were remarkably increased in the presence of the tyrosine kinase inhibitor genistein, whereas they were attenuated in the presence of the tyrosine phosphatase inhibitor vanadate. No effect was produced by inhibitors of protein kinase A, protein kinase C, calcium-calmodulin kinase II, phosphatidylinositol-3-kinase, or MAP kinases. Tissue cAMP levels were unchanged. In rat ventricular tissue, Western blot experiments with antiphosphotyrosine antibodies showed reduced phosphorylation of microsomal and cytosolic proteins after perfusion with synthetic T1AM; reverse transcriptase-polymerase chain reaction experiments revealed the presence of transcripts for at least 5 TAAR subtypes; specific and saturable binding of [125I]T1AM was observed, with a dissociation constant in the low micromolar range (5 microM); and endogenous T1AM was detectable by tandem mass spectrometry. In conclusion, our findings provide evidence for the existence of a novel aminergic system modulating cardiac function.

  12. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-2, Pump Functional Testing.

    ERIC Educational Resources Information Center

    Wasel, Ed; Espy, John

    This second in a series of eight modules for a course titled Mechanical Inspection describes typical pump functional tests which are performed after pump installation and prior to release of the plant for unrestricted power operation. The module follows a typical format that includes the following sections: (1) introduction, (2) module…

  13. Nuclear Technology. Course 30: Mechanical Inspection. Module 30-2, Pump Functional Testing.

    ERIC Educational Resources Information Center

    Wasel, Ed; Espy, John

    This second in a series of eight modules for a course titled Mechanical Inspection describes typical pump functional tests which are performed after pump installation and prior to release of the plant for unrestricted power operation. The module follows a typical format that includes the following sections: (1) introduction, (2) module…

  14. Approximating the head characteristics and characteristic surfaces of dynamic pumps by means of an exponential function

    NASA Astrophysics Data System (ADS)

    Shekun, G. D.

    2009-08-01

    Results obtained from statistical and experimental studies of the head characteristics of commercially available centrifugal and free-vortex pumps are presented. A regression equation in the form of an exponential function written in a reduced-relative system of coordinates for approximating the head characteristics of blade pumps is obtained.

  15. Cytoskeletal Basis of Ion Channel Function in Cardiac Muscle

    PubMed Central

    Vatta, Matteo; Faulkner, Georgine

    2009-01-01

    Summary The heart is a force-generating organ that responds to self-generated electrical stimuli from specialized cardiomyocytes. This function is modulated by sympathetic and parasympathetic activity. In order to contract and accommodate the repetitive morphological changes induced by the cardiac cycle, cardiomyocytes depend on their highly evolved and specialized cytoskeletal apparatus. Defects in components of the cytoskeleton, in the long term, affect the ability of the cell to compensate at both functional and structural levels. In addition to the structural remodeling, the myocardium becomes increasingly susceptible to altered electrical activity leading to arrhythmogenesis. The development of arrhythmias secondary to structural remodeling defects has been noted, although the detailed molecular mechanisms are still elusive. Here I will review the current knowledge of the molecular and functional relationships between the cytoskeleton and ion channels and, I will discuss the future impact of new data on molecular cardiology research and clinical practice. PMID:19774097

  16. Fractalkine neutralization improves cardiac function after myocardial infarction

    PubMed Central

    Gu, Xiaosong; Xu, Jiang; Yang, Xiao-Ping; Peterson, Edward; Harding, Pamela

    2015-01-01

    Concentrations of the chemokine fractalkine (FKN) are increased in patients with chronic heart failure, and our previous studies show that aged mice lacking the prostaglandin E2 EP4 receptor subtype (EP4-KO) have increased cardiac FKN, with a phenotype of dilated cardiomyopathy. However, how FKN participates in the pathogenesis of heart failure has rarely been studied. We hypothesized that FKN contributes to the pathogenesis of heart failure and that anti-FKN treatment prevents heart failure induced by myocardial infarction (MI) more effectively in EP4-KO mice. Male EP4-KO mice and wild-type littermates underwent sham or MI surgery and were treated with an anti-FKN antibody or control IgG. At 2 weeks post-MI, echocardiography was performed and hearts were excised for determination of infarct size, immunohistochemistry and Western blot of signalling molecules. Given that FKN protein levels in the left ventricle were increased to a similar extent in both strains after MI and that anti-FKN treatment improved survival and cardiac function in both strains, we subsequently used only wild-type mice to examine the mechanisms whereby anti-FKN is cardioprotective. Myocyte cross-sectional area and interstitial collagen fraction were reduced after anti-FKN treatment, as were macrophage migration and gelatinase activity. Activation of ERK1/2 and p38 MAPK were reduced after neutralization of FKN. In vitro, FKN increased fibroblast proliferation. In conclusion, increased FKN contributes to heart failure after MI. This effect is not exacerbated in EP4-KO mice, suggesting that there is no link between FKN and lack of EP4. Overall, inhibition of FKN may be important to preserve cardiac function post-MI. PMID:25943588

  17. The effect of childhood obesity on cardiac functions.

    PubMed

    Üner, Abdurrahman; Doğan, Murat; Epcacan, Zerrin; Epçaçan, Serdar

    2014-03-01

    Obesity is a metabolic disorder defined as excessive accumulation of body fat, which is made up of genetic, environmental, and hormonal factors and has various social, psychological, and medical complications. Childhood obesity is a major indicator of adult obesity. The aim of this study is to evaluate the cardiac functions via electrocardiography (ECG), echocardiography (ECHO), and treadmill test in childhood obesity. A patient group consisting of 30 obese children and a control group consisting of 30 non-obese children were included in the study. The age range was between 8 and 17 years. Anthropometric measurements, physical examination, ECG, ECHO, and treadmill test were done in all patients. P-wave dispersion (PD) was found to be statistically significantly high in obese patients. In ECHO analysis, we found that end-diastolic diameter, end-systolic diameter, left ventricle posterior wall thickness, and interventricular septum were significantly greater in obese children. In treadmill test, exercise capacity was found to be significantly lower and the hemodynamic response to exercise was found to be defective in obese children. Various cardiac structural and functional changes occur in childhood obesity and this condition includes important cardiovascular risks. PD, left ventricle end-systolic and end-diastolic diameter, left ventricle posterior wall thickness, interventricular septum thickness, exercise capacity, and hemodynamic and ECG measurements during exercise testing are useful tests to determine cardiac dysfunctions and potential arrhythmias even in early stages of childhood obesity. Early recognition and taking precautions for obesity during childhood is very important to intercept complications that will occur in adulthood.

  18. Cardiac autonomic functions in children with familial Mediterranean fever.

    PubMed

    Şahin, Murat; Kır, Mustafa; Makay, Balahan; Keskinoğlu, Pembe; Bora, Elçin; Ünsal, Erbil; Ünal, Nurettin

    2016-05-01

    Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disease in the world. The long-term effects of subclinical inflammation in FMF are not well recognized. Some studies have suggested that FMF is associated with cardiac autonomic dysfunction in adult FMF patients. The objective of this study was to investigate the cardiac autonomic functions in pediatric FMF patients by using several autonomic tests. Thirty-five patients with FMF and 35 healthy controls were enrolled in this cross-sectional study. Demographic data, disease-specific data, and orthostatic symptoms were recorded. In all participants, 12-lead electrocardiography (ECG), 24 h ambulatory electrocardiographic monitoring, transthoracic echocardiography, treadmill exercise test, and head upright tilt-table (HUTT) test were performed. The heart rate recovery (HRR) indices of the two groups were similar. Also, chronotropic response was similar in both groups. The time-domain parameters of heart rate variability (HRV) were similar in both groups, except mean RR (p = 0.024). Frequencies of ventricular and supraventricular ectopic stimuli were similar in both groups. There were no statistically significant differences between the groups in average QT and average corrected QT interval length, average QT interval dispersion, and average QT corrected dispersion. There was no significant difference between the two groups regarding the ratio of clinical dysautonomic reactions on HUTT. However, we observed a significantly higher rate of dysautonomic reactions on HUTT in patients with exertional leg pain than that in patients without (p = 0.013). When the fractal dimension of time curves were compared, FMF patients exhibited significantly lower diastolic blood pressure parameters than controls in response to HUTT. Cardiovascular autonomic dysfunction in children with FMF is not prominent. Particularly, patients with exertional leg pain are more prone to have dysautonomic features

  19. Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats.

    PubMed

    Supakul, Luerat; Pintana, Hiranya; Apaijai, Nattayaporn; Chattipakorn, Siriporn; Shinlapawittayatorn, Krekwit; Chattipakorn, Nipon

    2014-04-01

    Garlic has been shown to exhibit antioxidant effects and cardioprotective properties. However, the effects of garlic extract on the heart in insulin resistance induced by long-term high-fat-diet consumption are not well defined. Therefore, we sought to determine the effects of garlic extract in the obese insulin-resistant rats. Male Wistar rats (180-200 g) were divided into two groups: normal-diet or high-fat-diet (n = 24/group) fed for 12 weeks. Rats in each groups were divided into three subgroups (n = 8 each): vehicle or garlic extract (250 or 500 mg/kg/day, respectively) treated for 28 days. At the end of the treatment, the metabolic parameters, heart rate variability (HRV), cardiac function, and cardiac mitochondrial function were determined. Rats that received a high-fat-diet for 12 weeks had increased body weight, visceral fat, plasma insulin levels, total cholesterol, oxidative stress levels, depressed HRV, and cardiac mitochondrial dysfunction. Garlic extract at both concentrations significantly decreased the plasma insulin, total cholesterol, homeostasis model assessment index, and oxidative stress levels. Furthermore, garlic extract at both doses restored the HRV, cardiac function, and cardiac mitochondrial function. We concluded that garlic extract at both concentrations exerted cardioprotective effects against cardiac dysfunction and mitochondrial dysfunction in obese insulin-resistant rats.

  20. Off-pump coronary artery bypass grafting for a left main lesion due to cardiac allograft vasculopathy in Japan: first report of a case.

    PubMed

    Fujita, Tomoyuki; Kobayashi, Junjiro; Hata, Hiroki; Murata, Yoshihiro; Seguchi, Osamu; Yanase, Masanobu; Shimahara, Yusuke; Sato, Shunsuke; Nakatani, Takeshi

    2014-10-01

    Cardiac allograft vasculopathy (CAV) is a major cause of mortality after transplantation. We treated a 44-year-old female with off-pump coronary artery bypass grafting (OPCAB) 4 years after heart transplantation. Annual examinations, including coronary angiography and intravenous ultrasound (IVUS), revealed a severe lesion in the left main trunk. The left internal mammary artery was successfully anastomosed to the left anterior descending artery in an off-pump manner. To ensure that patients have a good long-term outcome after heart transplantation, routine examinations, including IVUS, are crucial, because of the nature of CAV. OPCAB is a good option for a left main trunk lesion due to CAV.

  1. Longstanding Hyperthyroidism Is Associated with Normal or Enhanced Intrinsic Cardiomyocyte Function despite Decline in Global Cardiac Function

    PubMed Central

    Redetzke, Rebecca A.; Gerdes, A. Martin

    2012-01-01

    Thyroid hormones (THs) play a pivotal role in cardiac homeostasis. TH imbalances alter cardiac performance and ultimately cause cardiac dysfunction. Although short-term hyperthyroidism typically leads to heightened left ventricular (LV) contractility and improved hemodynamic parameters, chronic hyperthyroidism is associated with deleterious cardiac consequences including increased risk of arrhythmia, impaired cardiac reserve and exercise capacity, myocardial remodeling, and occasionally heart failure. To evaluate the long-term consequences of chronic hyperthyroidism on LV remodeling and function, we examined LV isolated myocyte function, chamber function, and whole tissue remodeling in a hamster model. Three-month-old F1b hamsters were randomized to control or 10 months TH treatment (0.1% grade I desiccated TH). LV chamber remodeling and function was assessed by echocardiography at 1, 2, 4, 6, 8, and 10 months of treatment. After 10 months, terminal cardiac function was assessed by echocardiography and LV hemodynamics. Hyperthyroid hamsters exhibited significant cardiac hypertrophy and deleterious cardiac remodeling characterized by myocyte lengthening, chamber dilatation, decreased relative wall thickness, increased wall stress, and increased LV interstitial fibrotic deposition. Importantly, hyperthyroid hamsters demonstrated significant LV systolic and diastolic dysfunction. Despite the aforementioned remodeling and global cardiac decline, individual isolated cardiac myocytes from chronically hyperthyroid hamsters had enhanced function when compared with myocytes from untreated age-matched controls. Thus, it appears that long-term hyperthyroidism may impair global LV function, at least in part by increasing interstitial ventricular fibrosis, in spite of normal or enhanced intrinsic cardiomyocyte function. PMID:23056390

  2. Cardiac Cyclic Nucleotide Phosphodiesterases: Function, Regulation, and Therapeutic Prospects

    PubMed Central

    Knight, W. E.; Yan, C.

    2014-01-01

    The second messengers cAMP and cGMP exist in multiple discrete compartments and regulate a variety of biological processes in the heart. The cyclic nucleotide phosphodiesterases, by catalyzing the hydrolysis of cAMP and cGMP, play crucial roles in controlling the amplitude, duration, and compartmentalization of cyclic nucleotide signaling. Over 60 phosphodiesterase isoforms, grouped into 11 families, have been discovered to date. In the heart, both cAMP- and cGMP-hydrolyzing phosphodiesterases play important roles in physiology and pathology. At least 7 of the 11 phosphodiesterase family members appear to be expressed in the myocardium, and evidence supports phosphodiesterase involvement in regulation of many processes important for normal cardiac function including pacemaking and contractility, as well as many pathological processes including remodeling and myocyte apoptosis. Pharmacological inhibitors for a number of phosphodiesterase families have also been used clinically or preclinically to treat several types of cardiovascular disease. In addition, phosphodiesterase inhibitors are also being considered for treatment of many forms of disease outside the cardiovascular system, raising the possibility of cardiovascular side effects of such agents. This review will discuss the roles of phosphodiesterases in the heart, in terms of expression patterns, regulation, and involvement in physiological and pathological functions. Additionally, the cardiac effects of various phosphodiesterase inhibitors, both potentially beneficial and detrimental, will be discussed. PMID:22951903

  3. Selective Stimulation of Cardiac Lymphangiogenesis Reduces Myocardial Edema and Fibrosis Leading to Improved Cardiac Function Following Myocardial Infarction.

    PubMed

    Henri, Orianne; Pouehe, Chris; Houssari, Mahmoud; Galas, Ludovic; Nicol, Lionel; Edwards-Lévy, Florence; Henry, Jean-Paul; Dumesnil, Anais; Boukhalfa, Inès; Banquet, Sébastien; Schapman, Damien; Thuillez, Christian; Richard, Vincent; Mulder, Paul; Brakenhielm, Ebba

    2016-04-12

    The lymphatic system regulates interstitial tissue fluid balance, and lymphatic malfunction causes edema. The heart has an extensive lymphatic network displaying a dynamic range of lymph flow in physiology. Myocardial edema occurs in many cardiovascular diseases, eg, myocardial infarction (MI) and chronic heart failure, suggesting that cardiac lymphatic transport may be insufficient in pathology. Here, we investigate in rats the impact of MI and subsequent chronic heart failure on the cardiac lymphatic network. Further, we evaluate for the first time the functional effects of selective therapeutic stimulation of cardiac lymphangiogenesis post-MI. We investigated cardiac lymphatic structure and function in rats with MI induced by either temporary occlusion (n=160) or permanent ligation (n=100) of the left coronary artery. Although MI induced robust, intramyocardial capillary lymphangiogenesis, adverse remodeling of epicardial precollector and collector lymphatics occurred, leading to reduced cardiac lymphatic transport capacity. Consequently, myocardial edema persisted for several months post-MI, extending from the infarct to noninfarcted myocardium. Intramyocardial-targeted delivery of the vascular endothelial growth factor receptor 3-selective designer protein VEGF-CC152S, using albumin-alginate microparticles, accelerated cardiac lymphangiogenesis in a dose-dependent manner and limited precollector remodeling post-MI. As a result, myocardial fluid balance was improved, and cardiac inflammation, fibrosis, and dysfunction were attenuated. We show that, despite the endogenous cardiac lymphangiogenic response post-MI, the remodeling and dysfunction of collecting ducts contribute to the development of chronic myocardial edema and inflammation-aggravating cardiac fibrosis and dysfunction. Moreover, our data reveal that therapeutic lymphangiogenesis may be a promising new approach for the treatment of cardiovascular diseases. © 2016 American Heart Association, Inc.

  4. Evaluation of platelet function in dogs with cardiac disease using the PFA-100 platelet function analyzer.

    PubMed

    Clancey, Noel; Burton, Shelley; Horney, Barbara; Mackenzie, Allan; Nicastro, Andrea; Côté, Etienne

    2009-09-01

    Cardiac disease has the potential to alter platelet function in dogs. Evaluation of platelet function using the PFA-100 analyzer in dogs of multiple breeds and with a broad range of cardiac conditions would help clarify the effect of cardiac disease on platelets. The objective of this study was to assess differences in closure time (CT) in dogs with cardiac disease associated with murmurs, when compared with that of healthy dogs. Thirty-nine dogs with cardiac murmurs and turbulent blood flow as determined echocardiographically were included in the study. The dogs represented 23 different breeds. Dogs with murmurs were further divided into those with atrioventricular valvular insufficiency (n=23) and subaortic stenosis (n=9). Fifty-eight clinically healthy dogs were used as controls. CTs were determined in duplicate on a PFA-100 analyzer using collagen/ADP cartridges. Compared with CTs in the control group (mean+/-SD, 57.6+/-5.9 seconds; median, 56.5 seconds; reference interval, 48.0-77.0 seconds), dogs with valvular insufficiency (mean+/-SD, 81.9+/-26.3 seconds; median, 78.0 seconds; range, 52.5-187 seconds), subaortic stenosis (71.4+/-16.5 seconds; median, 66.0 seconds; range, 51.5-95.0 seconds), and all dogs with murmurs combined (79.6+/-24.1 seconds; median, 74.0 seconds; range, 48.0-187 seconds) had significantly prolonged CTs (P<.01). The PFA-100 analyzer is useful in detecting platelet function defects in dogs with cardiac murmurs, most notably those caused by mitral and/or tricuspid valvular insufficiency or subaortic stenosis. The form of turbulent blood flow does not appear to be an important factor in platelet hypofunction in these forms of cardiac disease.

  5. Cardiac myosin-binding protein C decorates F-actin: Implications for cardiac function

    PubMed Central

    Whitten, Andrew E.; Jeffries, Cy M.; Harris, Samantha P.; Trewhella, Jill

    2008-01-01

    Cardiac myosin-binding protein C (cMyBP-C) is an accessory protein of striated muscle sarcomeres that is vital for maintaining regular heart function. Its 4 N-terminal regulatory domains, C0-C1-m-C2 (C0C2), influence actin and myosin interactions, the basic contractile proteins of muscle. Using neutron contrast variation data, we have determined that C0C2 forms a repeating assembly with filamentous actin, where the C0 and C1 domains of C0C2 attach near the DNase I-binding loop and subdomain 1 of adjacent actin monomers. Direct interactions between the N terminus of cMyBP-C and actin thereby provide a mechanism to modulate the contractile cycle by affecting the regulatory state of the thin filament and its ability to interact with myosin. PMID:19011110

  6. Protein kinase-dependent oxidative regulation of the cardiac Na+–K+ pump: evidence from in vivo and in vitro modulation of cell signalling

    PubMed Central

    Galougahi, Keyvan Karimi; Liu, Chia-Chi; Garcia, Alvaro; Fry, Natasha A S; Hamilton, Elisha J; Rasmussen, Helge H; Figtree, Gemma A

    2013-01-01

    The widely reported stimulation of the cardiac Na+–K+ pump by protein kinase A (PKA) should oppose other effects of PKA to increase contractility of the normal heart. It should also reduce harmful raised myocyte Na+ levels in heart failure, yet blockade of the β1 adrenergic receptor (AR), coupled to PKA signalling, is beneficial. We treated rabbits with the β1 AR antagonist metoprolol to modulate PKA activity and studied cardiac myocytes ex vivo. Metoprolol increased electrogenic pump current (Ip) in voltage clamped myocytes and reduced glutathionylation of the β1 pump subunit, an oxidative modification causally related to pump inhibition. Activation of adenylyl cyclase with forskolin to enhance cAMP synthesis or inclusion of the catalytic subunit of PKA in patch pipette solutions abolished the increase in Ip in voltage clamped myocytes induced by treatment with metoprolol, supporting cAMP/PKA-mediated pump inhibition. Metoprolol reduced myocardial PKA and protein kinase C (PKC) activities, reduced coimmunoprecipitation of cytosolic p47phox and membranous p22phox NADPH oxidase subunits and reduced myocardial O2•−-sensitive dihydroethidium fluorescence. Treatment also enhanced coimmunoprecipitation of the β1 pump subunit with glutaredoxin 1 that catalyses de-glutathionylation. Since angiotensin II induces PKC-dependent activation of NADPH oxidase, we examined the effects of angiotensin-converting enzyme inhibition with captopril. This treatment had no effect on PKA activity but reduced the activity of PKC, reduced β1 subunit glutathionylation and increased Ip. The PKA-induced Na+–K+ pump inhibition we report should act with other mechanisms that enhance contractility of the normal heart but accentuate the harmful effects of raised cytosolic Na+ in the failing heart. This scheme is consistent with the efficacy of β1 AR blockade in the treatment of heart failure. PMID:23587884

  7. Digoxin Induces Cardiac Hypertrophy Without Negative Effects on Cardiac Function and Physical Performance in Trained Normotensive Rats.

    PubMed

    Neves, Claodete Hasselstrom; Tibana, Ramires Alsamir; Prestes, Jonato; Voltarelli, Fabricio Azevedo; Aguiar, Andreo Fernando; Ferreira Mota, Gustavo Augusto; de Sousa, Sergio Luiz Borges; Leopoldo, Andre Soares; Leopoldo, Ana Paula Lima; Mueller, Andre; Aguiar, Danilo Henrique; Navalta, James Wilfred; Sugizaki, Mario Mateus

    2017-04-01

    Cardiotonic drugs and exercise training promote cardiac inotropic effects, which may affect training-induced cardiac adaptations. This study investigated the effects of long-term administration of digoxin on heart structure and function, and physical performance of rats submitted to high-intensity interval training (HIIT). Male Wistar rats, 60 days old, were divided into control (C), digoxin (DIGO), trained (T), and trained with digoxin (TDIGO). Digoxin was administered by gavage (30 µg/kg/day) for 75 days. The HIIT program consisted of treadmill running 60 min/day (8 min at 80% of the maximum speed (MS) and 2 min at 20% of the MS), 5 days per week during 60 days. The main cardiac parameters were evaluated by echocardiograph and cardiomyocyte area was determined by histology. There were no group x time effects of digoxin, HIIT or interactions (digoxin and HIIT) on functional echocardiographic parameters (heart rate; ejection fraction) or in the maximum exercise test. There was a group x time interaction, as evidenced by observed cardiac hypertrophy in the TDIGO group evaluated by ratio of left ventricle weight to body weight (p<0.002) and cardiomyocyte area (p<0.000002). Long-term administration of digoxin promoted cardiac hypertrophy without affecting cardiac function and physical performance in rats submitted to HIIT.

  8. Effect of hypokinesia on contractile function of cardiac muscle

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Trikhpoyeva, A. M.; Gorina, M. S.

    1980-01-01

    Rats were subjected to hypokinesia for two months and the contractile function of isolated papillary muscle was studied. Hypokinesia reduced significantly the isotonic contraction rate which depended on the ATPase activity of the myofibrils; it also reduced the rate and index of relaxation which depended on the functional capacity of the Ca(++) pump of the sarcoplasmic reticulum. The maximum force of isometric contraction determined by the quantity of actomyosin bridges in the myofibrils did not change after hypokinesia. This complex of changes is contrary to that observed in adaptation to exercise when the rate of isotonic contraction and relaxation increases while the force of isometric contraction does not change. The possible mechanism of this stability of the contractile force during adaptation and readaptation of the heart is discussed.

  9. Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking Na+/K+ Pump As Revealed by Experiments and Simulation

    PubMed Central

    Takeuchi, Ayako; Tatsumi, Shuji; Sarai, Nobuaki; Terashima, Keisuke; Matsuoka, Satoshi; Noma, Akinori

    2006-01-01

    Although the Na+/K+ pump is one of the key mechanisms responsible for maintaining cell volume, we have observed experimentally that cell volume remained almost constant during 90 min exposure of guinea pig ventricular myocytes to ouabain. Simulation of this finding using a comprehensive cardiac cell model (Kyoto model incorporating Cl− and water fluxes) predicted roles for the plasma membrane Ca2+-ATPase (PMCA) and Na+/Ca2+ exchanger, in addition to low membrane permeabilities for Na+ and Cl−, in maintaining cell volume. PMCA might help maintain the [Ca2+] gradient across the membrane though compromised, and thereby promote reverse Na+/Ca2+ exchange stimulated by the increased [Na+]i as well as the membrane depolarization. Na+ extrusion via Na+/Ca2+ exchange delayed cell swelling during Na+/K+ pump block. Supporting these model predictions, we observed ventricular cell swelling after blocking Na+/Ca2+ exchange with KB-R7943 or SEA0400 in the presence of ouabain. When Cl− conductance via the cystic fibrosis transmembrane conductance regulator (CFTR) was activated with isoproterenol during the ouabain treatment, cells showed an initial shrinkage to 94.2 ± 0.5%, followed by a marked swelling 52.0 ± 4.9 min after drug application. Concomitantly with the onset of swelling, a rapid jump of membrane potential was observed. These experimental observations could be reproduced well by the model simulations. Namely, the Cl− efflux via CFTR accompanied by a concomitant cation efflux caused the initial volume decrease. Then, the gradual membrane depolarization induced by the Na+/K+ pump block activated the window current of the L-type Ca2+ current, which increased [Ca2+]i. Finally, the activation of Ca2+-dependent cation conductance induced the jump of membrane potential, and the rapid accumulation of intracellular Na+ accompanied by the Cl− influx via CFTR, resulting in the cell swelling. The pivotal role of L-type Ca2+ channels predicted in the simulation was

  10. Electrophysiologic abnormalities of cardiac function in progressive systemic sclerosis.

    PubMed

    Rokas, S; Mavrikakis, M; Agrios, N; Mylonas, D; Antoniadou, L; Moulopoulos, S

    1996-01-01

    The heart has been generally recognized as a target organ in progressive systemic sclerosis. Noninvasive studies have assessed the incidence and prognostic importance of cardiac arrhythmias in these patients. However, detailed exploration of the function of impulse formation and the conduction system of the heart in these patients has never been reported. Therefore, invasive electrophysiologic studies were performed in 30 patients with systemic sclerosis, all of whom had neither obvious cardiac involvement nor cardiac arrhythmias, and in 32 subjects with no evidence of heart disease, who served as a control group. Corrected sinus node recovery time in patients with systemic sclerosis was significantly longer (P < .001) than in the control group, as was the HV interval (P < .05). Of the 30 patients with systemic sclerosis, 10 had an HV interval of 60 ms or longer. In four patients with systemic sclerosis, the recorded AH interval exceeded 125 ms. The intra-atrial conduction time tended to increase to a significant degree (P < .05) in patients with systemic sclerosis. The interatrial conduction time was much longer (P < .001), and the maximal conduction delay to the atrioventricular junction and to the distal coronary sinus was much greater in the patients with systemic sclerosis than in the control group (P < .001 for both). Supraventricular tachyarrhythmias were induced in 15 patients with systemic sclerosis versus 3 control group subjects (P < .001). With respect to corrected sinus node recovery time, AH and HV intervals, atrial vulnerability, and ventricular tachycardia, 3 of the 30 patients with systemic sclerosis had abnormal findings in one of these parameters and 14 had abnormalities in more than one. These results suggest that a broad spectrum of electrophysiologic abnormalities is present in patients with systemic sclerosis, which can be revealed only by invasive studies. Furthermore, this study provides additional support for the hypothesis that diffuse

  11. Evaluation of cardiac function in patients with thalassemia intermedia.

    PubMed

    Nouri, Nm; Naderi, M; Rajaie, S; Dorgalaleh, A; Tabibian, Sh

    2013-01-01

    Thalassemia intermedia is a variety of beta thalassemia which shows clinical symptoms somewhere between asymptomatic carriers and thalassemia major. Cardiac dysfunctions due to chronic anemia and hemosiderosis are the major causes of death in these patients. The purpose of this study is to evaluate cardiac function in these patients by echocardiography. This case-control study was conducted on 22 thalassemic patients (mean: 16.5±5.8 years) and 66 healthy individuals (mean:16.07± 2.9years) as a control group from January 2007 to July 2008. There was no sign of cardiac involvement by physical examination, chest x-ray and ECG in patients. Echocardiographic parameters were measured in groups, and finally data was analyzed by SPSS software. The mean of left ventricular myocardial performance index (MPI) (P-value=0.0001) and left ventricular mass index (LVMI) (P-value=0.0001) have statistically significant difference. Mean of interventricular septal dimension in diastole (IVSD), left ventricular posterior wall thickness in diastole (LVPWD), interventricular septal dimension in systole (IVSS) and left ventricular posterior wall dimension in systole (LVPWS) were also statistically significant with a P-value of, 0.002, 0.001, 0.01, 0.003, respectively. Aortic Pre-ejection period/Ejection time (PEP/ET) (P-value=0.009), ejection fraction (EF) (P-value=0.019), fractional shortening (SF) (P-value=0.041), left ventricular isovolumetric contraction time (ICT) (P-value=0.0001) and left ventricular isovolumetric relaxation time (IRT) (P-value=0.0001) were statistically significant. Mean of right ventricular MPI (P-value=0.0001) and IRT (P-value=0.0001) were also significantly different between two groups. Others echocardiographic parameters were not statistically significant (P-value>0.05). Heart failures are earlier affected thalassemia intermedia patients compared with control group.

  12. Histamine H3 activation depresses cardiac function in experimental sepsis.

    PubMed

    Li, X; Eschun, G; Bose, D; Jacobs, H; Yang, J J; Light, R B; Mink, S N

    1998-11-01

    In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

  13. Cardiac function adaptations in hibernating grizzly bears (Ursus arctos horribilis).

    PubMed

    Nelson, O Lynne; Robbins, Charles T

    2010-03-01

    Research on the cardiovascular physiology of hibernating mammals may provide insight into evolutionary adaptations; however, anesthesia used to handle wild animals may affect the cardiovascular parameters of interest. To overcome these potential biases, we investigated the functional cardiac phenotype of the hibernating grizzly bear (Ursus arctos horribilis) during the active, transitional and hibernating phases over a 4 year period in conscious rather than anesthetized bears. The bears were captive born and serially studied from the age of 5 months to 4 years. Heart rate was significantly different from active (82.6 +/- 7.7 beats/min) to hibernating states (17.8 +/- 2.8 beats/min). There was no difference from the active to the hibernating state in diastolic and stroke volume parameters or in left atrial area. Left ventricular volume:mass was significantly increased during hibernation indicating decreased ventricular mass. Ejection fraction of the left ventricle was not different between active and hibernating states. In contrast, total left atrial emptying fraction was significantly reduced during hibernation (17.8 +/- 2.8%) as compared to the active state (40.8 +/- 1.9%). Reduced atrial chamber function was also supported by reduced atrial contraction blood flow velocities and atrial contraction ejection fraction during hibernation; 7.1 +/- 2.8% as compared to 20.7 +/- 3% during the active state. Changes in the diastolic cardiac filling cycle, especially atrial chamber contribution to ventricular filling, appear to be the most prominent macroscopic functional change during hibernation. Thus, we propose that these changes in atrial chamber function constitute a major adaptation during hibernation which allows the myocardium to conserve energy, avoid chamber dilation and remain healthy during a period of extremely low heart rates. These findings will aid in rational approaches to identifying underlying molecular mechanisms.

  14. [Cardiac MRI for determining functional left ventricular parameters].

    PubMed

    Miller, S; Hahn, U; Bail, D M; Helber, U; Nägele, T; Scheule, A M; Schick, F; Duda, S H; Claussen, C D

    1999-01-01

    To prove the accuracy of MR methods in the determination of left ventricular (LV) functional parameters and anatomy. At 1.5 T, 20 healthy volunteers and 22 patients with aortic valvular disease (stenosis n = 15, regurgitation n = 7) were examined. Functional parameters like cardiac output, ejection fraction, end-diastolic volume, aortic flow maximum, and time interval from the R-wave to maximum flow were obtained using a velocity encoding 2D FLASH sequence (TR 24 ms, TE 5 ms, venc 250 cm/sec) and segmented breath-hold cine FLASH 2D technique (TR 100 ms, TE 4.8 ms, flip angle 25 degrees, temporal resolution 50 ms). Invasive measurements (Fick principle) served as gold standard, intra- and interobserver variability were determined. Differences of functional parameters between normal volunteers and patients were detectable at a high level of significance (p < 0.0001). For cardiac output a superior correlation with the gold standard was found using flow measurements (r = 0.66, p < 0.0007) compared to volumetric calculations from cine studies (r = 0.47, p < 0.02). Interobserver variability was 2.5 +/- 2.7%/4.5 +/- 6.9% (flow quantification/calculations from cine studies), intraobserver variability was 1.7 +/- 1.6%/3.3 +/- 2.2%. MRI is an appropriate tool for determining LV functional parameters and anatomy. Differences between normal volunteers and patients with aortic valvular disease can be detected reliably. Flow measurements turned out to be more accurate than calculations from cine images. Therefore, flow quantification techniques should be preferred for clinical use.

  15. Beneficial triple-site cardiac resynchronization in a patient supported with an intra-aortic balloon pump for end-stage heart failure

    PubMed Central

    Ciszewski, Jan; Maciąg, Aleksander; Gepner, Katarzyna; Smolis-Bąk, Edyta

    2014-01-01

    The authors present the case of a 62-year-old male patient with an implantable cardioverter-defibrillator and end-stage heart failure supported with an intra-aortic balloon pump. Implantation of a triple-site cardiac resynchronization system and complex heart failure treatment brought a significant improvement, return to home activity and 17-month survival. The patient died due to heart failure aggravation. Within this time he was rehospitalized and successfully treated twice for an electrical storm. PMID:24799927

  16. Beneficial triple-site cardiac resynchronization in a patient supported with an intra-aortic balloon pump for end-stage heart failure.

    PubMed

    Ciszewski, Jan; Maciąg, Aleksander; Gepner, Katarzyna; Smolis-Bąk, Edyta; Sterliński, Maciej

    2014-01-01

    The authors present the case of a 62-year-old male patient with an implantable cardioverter-defibrillator and end-stage heart failure supported with an intra-aortic balloon pump. Implantation of a triple-site cardiac resynchronization system and complex heart failure treatment brought a significant improvement, return to home activity and 17-month survival. The patient died due to heart failure aggravation. Within this time he was rehospitalized and successfully treated twice for an electrical storm.

  17. Cardiac optogenetics.

    PubMed

    Entcheva, Emilia

    2013-05-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart.

  18. Cardiac optogenetics

    PubMed Central

    2013-01-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart. PMID:23457014

  19. The Transfer Functions of Cardiac Tissue during Stochastic Pacing

    PubMed Central

    de Lange, Enno; Kucera, Jan P.

    2009-01-01

    Abstract The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K+]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction. PMID:19134481

  20. Functional requirements for portable exhauster system to be used during saltwell pumping

    SciTech Connect

    Nelson, O.D.

    1998-07-25

    This document defines functional requirements for portable exhausters used to ventilate primary tanks during saltwell pumping, and provide back-up to primary and annulus ventilation systems at C-106 and AY-102.

  1. Low-dose dasatinib rescues cardiac function in Noonan syndrome

    PubMed Central

    Yi, Jae-Sung; Huang, Yan; Kwaczala, Andrea T.; Kuo, Ivana Y.; Ehrlich, Barbara E.; Campbell, Stuart G.; Giordano, Frank J.; Bennett, Anton M.

    2016-01-01

    Noonan syndrome (NS) is a common autosomal dominant disorder that presents with short stature, craniofacial dysmorphism, and cardiac abnormalities. Activating mutations in the PTPN11 gene encoding for the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase-2 (SHP2) causes approximately 50% of NS cases. In contrast, NS with multiple lentigines (NSML) is caused by mutations that inactivate SHP2, but it exhibits some overlapping abnormalities with NS. Protein zero-related (PZR) is a SHP2-binding protein that is hyper-tyrosyl phosphorylated in the hearts of mice from NS and NSML, suggesting that PZR and the tyrosine kinase that catalyzes its phosphorylation represent common targets for these diseases. We show that the tyrosine kinase inhibitor, dasatinib, at doses orders of magnitude lower than that used for its anticancer activities inhibited PZR tyrosyl phosphorylation in the hearts of NS mice. Low-dose dasatinib treatment of NS mice markedly improved cardiomyocyte contractility and functionality. Remarkably, a low dose of dasatinib reversed the expression levels of molecular markers of cardiomyopathy and reduced cardiac fibrosis in NS and NSML mice. These results suggest that PZR/SHP2 signaling is a common target of both NS and NSML and that low-dose dasatinib may represent a unifying therapy for the treatment of PTPN11-related cardiomyopathies. PMID:27942593

  2. Pulsatile extracorporeal circulation during on-pump cardiac surgery enhances aortic wall shear stress.

    PubMed

    Assmann, Alexander; Benim, Ali Cemal; Gül, Fethi; Lux, Philipp; Akhyari, Payam; Boeken, Udo; Joos, Franz; Feindt, Peter; Lichtenberg, Artur

    2012-01-03

    Controversy on superiority of pulsatile versus non-pulsatile extracorporeal circulation in cardiac surgery still continues. Stroke as one of the major adverse events during cardiopulmonary bypass is, in the majority of cases, caused by mobilization of aortic arteriosclerotic plaques that is inducible by pathologically elevated wall shear stress values. The present study employs computational fluid dynamics to evaluate the aortic blood flow and wall shear stress profiles under the influence of antegrade or retrograde perfusion with pulsatile versus non-pulsatile extracorporeal circulation. While, compared to physiological flow, a non-pulsatile perfusion resulted in generally decreased blood velocities and only moderately increased shear forces (48 Pa versus 20 Pa antegradely and 127 Pa versus 30 Pa retrogradely), a pulsatile perfusion extensively enhanced the occurrence of turbulences, maximum blood flow speed and maximum wall shear stress (1020 Pa versus 20 Pa antegradely and 1178 Pa versus 30 Pa retrogradely). Under these circumstances arteriosclerotic embolism has to be considered. Further simulations and experimental work are necessary to elucidate the impact of our findings on the scientific discourse of pulsatile versus non-pulsatile extracorporeal circulation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Network interactions within the canine intrinsic cardiac nervous system: implications for reflex control of regional cardiac function

    PubMed Central

    Beaumont, Eric; Salavatian, Siamak; Southerland, E Marie; Vinet, Alain; Jacquemet, Vincent; Armour, J Andrew; Ardell, Jeffrey L

    2013-01-01

    The aims of the study were to determine how aggregates of intrinsic cardiac (IC) neurons transduce the cardiovascular milieu versus responding to changes in central neuronal drive and to determine IC network interactions subsequent to induced neural imbalances in the genesis of atrial fibrillation (AF). Activity from multiple IC neurons in the right atrial ganglionated plexus was recorded in eight anaesthetized canines using a 16-channel linear microelectrode array. Induced changes in IC neuronal activity were evaluated in response to: (1) focal cardiac mechanical distortion; (2) electrical activation of cervical vagi or stellate ganglia; (3) occlusion of the inferior vena cava or thoracic aorta; (4) transient ventricular ischaemia, and (5) neurally induced AF. Low level activity (ranging from 0 to 2.7 Hz) generated by 92 neurons was identified in basal states, activities that displayed functional interconnectivity. The majority (56%) of IC neurons so identified received indirect central inputs (vagus alone: 25%; stellate ganglion alone: 27%; both: 48%). Fifty per cent transduced the cardiac milieu responding to multimodal stressors applied to the great vessels or heart. Fifty per cent of IC neurons exhibited cardiac cycle periodicity, with activity occurring primarily in late diastole into isovolumetric contraction. Cardiac-related activity in IC neurons was primarily related to direct cardiac mechano-sensory inputs and indirect autonomic efferent inputs. In response to mediastinal nerve stimulation, most IC neurons became excessively activated; such network behaviour preceded and persisted throughout AF. It was concluded that stochastic interactions occur among IC local circuit neuronal populations in the control of regional cardiac function. Modulation of IC local circuit neuronal recruitment may represent a novel approach for the treatment of cardiac disease, including atrial arrhythmias. PMID:23818689

  4. The Effects of Bariatric Surgery on Cardiac Structure and Function: a Systematic Review of Cardiac Imaging Outcomes.

    PubMed

    Aggarwal, Ravi; Harling, Leanne; Efthimiou, Evangelos; Darzi, Ara; Athanasiou, Thanos; Ashrafian, Hutan

    2016-05-01

    Obesity is associated with cardiac dysfunction, atherosclerosis, and increased cardiovascular risk. It can be lead to obesity cardiomyopathy and severe heart failure, which in turn raise morbidity and mortality while carrying a negative impact on quality of life. There is increasing clinical and mechanistic evidence on the metabolic and weight loss effects of bariatric surgery on improving cardiac structure and function in obese patients. The objective of this study was to quantify the effects of bariatric surgery on cardiac structure and function by appraising cardiac imaging changes before and after metabolic operations. This is a comprehensive systematic review of studies reporting pre-operative and post-operative echocardiographic or magnetic resonance cardiac indices in obese patients undergoing bariatric surgery. Studies were quality scored, and data were meta-analyzed using random effects modeling. Bariatric surgery is associated with significant improvements in the weighted incidence of a number of cardiac indices including a decrease in left ventricular mass index (11.2%, 95% confidence intervals (CI) 8.2-14.1%), left ventricular end-diastolic volume (13.28 ml, 95% CI 5.22-21.34 ml), and left atrium diameter (1.967 mm, 95% CI 0.980-2.954). There were beneficial increases in left ventricular ejection fraction (1.198%, 95%CI -0.050-2.347) and E/A ratio (0.189%, 95%CI -0.113-0.265). Bariatric surgery offers beneficial cardiac effects on diastolic function, systolic function, and myocardial structure in obese patients. These may derive from surgical modulation of an enterocardiac axis. Future studies must focus on higher evidence levels to better identify the most successful bariatric approaches in preventing and treating the broad spectrum of obesity-associated heart disease while also enhancing treatment strategies in the management of obesity cardiomyopathy.

  5. Small Molecule Cardiogenol C Upregulates Cardiac Markers and Induces Cardiac Functional Properties in Lineage-Committed Progenitor Cells

    PubMed Central

    Mike, Agnes K.; Koenig, Xaver; Koley, Moumita; Heher, Philipp; Wahl, Gerald; Rubi, Lena; Schnürch, Michael; Mihovilovic, Marko D.; Weitzer, Georg; Hilber, Karlheinz

    2015-01-01

    Background/Aims Cell transplantation into the heart is a new therapy after myocardial infarction. Its success, however, is impeded by poor donor cell survival and by limited trans-differentiation of the transplanted cells into functional cardiomyocytes. A promising strategy to overcome these problems is the induction of cardiomyogenic properties in donor cells by small molecules. Methods Here we studied cardiomyogenic effects of the small molecule compound cardiogenol C (CgC), and structural derivatives thereof, on lineage-committed progenitor cells by various molecular biological, biochemical, and functional assays. Results Treatment with CgC up-regulated cardiac marker expression in skeletal myoblasts. Importantly, the compound also induced cardiac functional properties: first, cardiac-like sodium currents in skeletal myoblasts, and secondly, spontaneous contractions in cardiovascular progenitor cell-derived cardiac bodies. Conclusion CgC induces cardiomyogenic function in lineage-committed progenitor cells, and can thus be considered a promising tool to improve cardiac repair by cell therapy. PMID:24481283

  6. Targeted inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis and Preserves Heart Function in Adverse Cardiac Remodeling

    PubMed Central

    Zhang, Jie; Fan, Guangpu; Zhao, Hui; Wang, Zhiwei; Li, Fei; Zhang, Peide; Zhang, Jing; Wang, Xu; Wang, Wei

    2017-01-01

    Cardiac fibrosis in post-myocardial infarction (MI), seen in both infarcted and non-infarcted myocardium, is beneficial to the recovery of heart function. But progressively pathological fibrosis impairs ventricular function and leads to poor prognosis. FAK has recently received attention as a potential mediator of fibrosis, our previous study reported that pharmacological inhibition of FAK can attenuate cardiac fibrosis in post MI models. However, the long-term effects on cardiac function and adverse cardiac remodelling were not clearly investigated. In this study, we tried to determine the preliminary mechanisms in regulating CF transformation to myofibroblasts and ECM synthesis relevant to the development of adverse cardiac remolding in vivo and in vitro. Our study provides even more evidence that FAK is directly related to the activation of CF in hypoxia condition in a dose-dependent and time-dependent manner. Pharmacological inhibition of FAK significantly reduces myofibroblast differentiation; our in vivo data demonstrated that a FAK inhibitor significantly decreases fibrotic score, and preserves partial left ventricular function. Both PI3K/AKT signalling and ERK1/2 are necessary for hypoxia-induced CF differentiation and ECM synthesis; this process also involves lysyl oxidase (LOX). These findings suggest that pharmacological inhibition of FAK may become an effective therapeutic strategy against adverse fibrosis. PMID:28225063

  7. Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function.

    PubMed

    Wang, Vicky Y; Lam, H I; Ennis, Daniel B; Cowan, Brett R; Young, Alistair A; Nash, Martyn P

    2009-10-01

    The majority of patients with clinically diagnosed heart failure have normal systolic pump function and are commonly categorized as suffering from diastolic heart failure. The left ventricle (LV) remodels its structure and function to adapt to pathophysiological changes in geometry and loading conditions, which in turn can alter the passive ventricular mechanics. In order to better understand passive ventricular mechanics, a LV finite element (FE) model was customized to geometric data segmented from in vivo tagged magnetic resonance images (MRI) data and myofibre orientation derived from ex vivo diffusion tensor MRI (DTMRI) of a canine heart using nonlinear finite element fitting techniques. MRI tissue tagging enables quantitative evaluation of cardiac mechanical function with high spatial and temporal resolution, whilst the direction of maximum water diffusion in each voxel of a DTMRI directly corresponds to the local myocardial fibre orientation. Due to differences in myocardial geometry between in vivo and ex vivo imaging, myofibre orientations were mapped into the geometric FE model using host mesh fitting (a free form deformation technique). Pressure recordings, temporally synchronized to the tagging data, were used as the loading constraints to simulate the LV deformation during diastole. Simulation of diastolic LV mechanics allowed us to estimate the stiffness of the passive LV myocardium based on kinematic data obtained from tagged MRI. Integrated physiological modelling of this kind will allow more insight into mechanics of the LV on an individualized basis, thereby improving our understanding of the underlying structural basis of mechanical dysfunction under pathological conditions.

  8. Transcriptional Control of Cardiac Fuel Metabolism and Mitochondrial Function

    PubMed Central

    Leone, T.C.; Kelly, D.P.

    2012-01-01

    As a persistent pump, the mammalian heart demands a high-capacity mitochondrial system. Significant progress has been made in delineating the gene regulatory networks that control mitochondrial biogenesis and function in striated muscle. The PPARγ coactivator-1 (PGC-1) coactivators serve as inducible boosters of downstream transcription factors that control the expression of genes involved in mitochondrial energy transduction, ATP synthesis, and biogenesis. PGC-1 gain-of-function and loss-of-function studies targeting two PGC-1 family members, PGC-1α and PGC-1β, have provided solid evidence that these factors are both necessary and sufficient for perinatal mitochondrial biogenesis and maintenance of high-capacity mitochondrial function in postnatal heart. In humans, during the development of heart failure owing to hypertension or obesity-related diabetes, the activity of the PGC-1 coactivators, and several downstream target transcription factors, is altered. Gene targeting studies in mice have demonstrated that loss of PGC-1α and PGC-1β in heart leads to heart failure. Interestingly, the pattern of dysregulation within the PGC-1 transcriptional regulatory circuit distinguishes the heart disease caused by hypertension from that caused by diabetes. This transcriptional regulatory cascade and downstream metabolic pathways should be considered as targets for novel etiology-specific therapeutics aimed at the early stages of heart failure. PMID:22096028

  9. Regulation of cardiac function during a cold pressor test in athletes and untrained subjects.

    PubMed

    Ifuku, Hirotoshi; Moriyama, Kayo; Arai, Kuniko; Shiraishi-Hichiwa, Yumiko

    2007-09-01

    By using (dP/dt)/P of carotid artery pulse, a non-invasive index of cardiac contractility, we examined the regulatory mechanism of cardiac function during a cold pressor test in athletes and untrained subjects. Twenty-four healthy subjects (9 athletes, 8 untrained subjects, and 7 hyperreactors of 4 athletes and 3 untrained subjects with a rise of 15 mmHg or greater in systolic and/or diastolic blood pressure) underwent the cold pressor test according to Hines and Brown (Am Heart J 11:1-9, 1936): immersion of the right hand in 4 degrees C water for 1 min. Although mean blood pressure increased during the cold stress in all the groups, cardiac function differed. In athletes, heart rate and cardiac contractility caused cardiac output to increase while total peripheral resistance (TPR) did not change. In untrained subjects, however, heart rate and cardiac contractility tended to decrease cardiac output and thus TPR increased. In hyperreactors, heart rate and cardiac contractility increased during cold stress, and also TPR increased. After the end of the test, heart rate and cardiac contractility decreased only in untrained group. The findings that during a cold pressor test heart rate and cardiac contractility are enhanced in athletes but depressed in untrained subjects indicate that the state of physical training influences cardiac sympathetic neural reactivity to cold stress, except for hyperreactors.

  10. In vivo assessment of cardiac metabolism and function in the abdominal aortic banding model of compensated cardiac hypertrophy

    PubMed Central

    Seymour, Anne-Marie L.; Giles, Lucia; Ball, Vicky; Miller, Jack J.; Clarke, Kieran; Carr, Carolyn A.; Tyler, Damian J.

    2015-01-01

    Aims Left ventricular hypertrophy is an adaptive response of the heart to chronic mechanical overload and can lead to functional deterioration and heart failure. Changes in cardiac energy metabolism are considered as key to the hypertrophic remodelling process. The concurrence of obesity and hypertrophy has been associated with contractile dysfunction, and this work therefore aimed to investigate the in vivo structural, functional, and metabolic remodelling that occurs in the hypertrophied heart in the setting of a high-fat, high-sucrose, Western diet (WD). Methods and results Following induction of cardiac hypertrophy through abdominal aortic banding, male Sprague Dawley rats were exposed to either a standard diet or a WD (containing 45% fat and 16% sucrose) for up to 14 weeks. Cardiac structural and functional characteristics were determined by CINE MRI, and in vivo metabolism was investigated using hyperpolarized 13C-labelled pyruvate. Cardiac hypertrophy was observed at all time points, irrespective of dietary manipulation, with no evidence of cardiac dysfunction. Pyruvate dehydrogenase flux was unchanged in the hypertrophied animals at any time point, but increased incorporation of the 13C label into lactate was observed by 9 weeks and maintained at 14 weeks, indicative of enhanced glycolysis. Conclusion Hypertrophied hearts revealed little evidence of a switch towards increased glucose oxidation but rather an uncoupling of glycolytic metabolism from glucose oxidation. This was maintained under conditions of dietary stress provided by a WD but, at this compensated phase of hypertrophy, did not result in any contractile dysfunction. PMID:25750189

  11. Significance of new Q waves and their location in postoperative ECGs after elective on-pump cardiac surgery: An observational cohort study.

    PubMed

    Mauermann, Eckhard; Bolliger, Daniel; Fassl, Jens; Grapow, Martin; Seeberger, Esther E; Seeberger, Manfred D; Filipovic, Miodrag; Lurati Buse, Giovanna A L

    2017-05-01

    The clinical significance of new pathological Q waves after on-pump cardiac surgery is uncertain. To determine whether or not either the occurrence per se or the location of new pathological Q waves after on-pump cardiac surgery is associated with 12-month, all-cause mortality and/or major adverse cardiac events (MACEs). Observational cohort study. Single university hospital from January 2007 to October 2010. Consecutive adult patients undergoing elective on-pump cardiac surgery with MACE-free survival until at least the 7th postoperative day and available ECGs both preoperatively and on the 7th postoperative day (n = 1464). We conducted a subgroup analysis in patients undergoing isolated coronary artery bypass grafting (n = 740). Our primary endpoint was 12-month, all-cause mortality and/or MACE, defined as acute coronary syndrome, cardiac arrest, congestive heart failure or re-vascularisation at 12 months. Using logistic regression, we examined the prognostic value of new pathological Q waves according to the Minnesota ECG Code, adjusting for the EuroSCORE II, cardiopulmonary bypass time and peak postoperative troponin T concentrations. We included 1464 patients (74% men; mean ± SD age 66 ± 10 years) and observed 103 (7.0%) all-cause deaths and/or MACEs at 12 months. A total of 236 patients (16.1%) had definite or probable new pathological Q waves according to the Minnesota ECG Code. The occurrence of new pathological Q waves per se was not associated with our primary endpoint [adjusted odds ratio, 0.970 (95% confidence interval, 0.540 to 1.648)]. However, the occurrence of a new pathological Q wave in V1 to V5 (anterior) was a strong independent predictor for poor outcome [adjusted odds ratio, 3.461 (95% confidence interval, 1.501 to 7.242)]. The current analysis suggests that for patients undergoing elective on-pump cardiac surgery, only new pathological Q waves in V1 to V5 (anterior) in the 7th postoperative day ECG are associated with 12

  12. The effect of age on the relationship between cardiac and vascular function.

    PubMed

    Houghton, David; Jones, Thomas W; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A; Trenell, Michael I; Jakovljevic, Djordje G

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P<0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P<0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P<0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P<0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r=-0.73, P=0.02) and cardiac output (r=-0.69, P=0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people.

  13. Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

    NASA Technical Reports Server (NTRS)

    Levine, Benjamin D.; Bungo, Michael W.; Platts, Steven H.; Hamilton, Douglas R.; Johnston, Smith L.

    2009-01-01

    Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers.

  14. Renal function changes after elective cardiac surgery with cardiopulmonary bypass.

    PubMed

    de Moraes Lobo, E M; Burdmann, E A; Abdulkader, R C

    2000-01-01

    Cardiac surgery can either induce acute renal failure or improve GFR by improving the cardiac performance. In order to study renal function changes after elective cardiac surgery (CS) with cardiopulmonary bypass (CPBP), 21 patients undergoing valvular CS (VCS) or coronary artery bypass (CAB) were prospectively evaluated in three time periods: before, 24 hours after surgery and 48 hours after surgery. Patients were divided in 2 groups according to the GFR percent change in comparison to the baseline value found 24 hours after CS (deltaGFR24): Group 1, deltaGFR24 decrease higher than 20% (n = 11) and Group 2, deltaGFR24 decrease < or = 20% or deltaGFR24 increase (n = 10). In Group 1, 73% of the patients underwent VCS (p = 0.05 vs. Group 2) and all of them had previous VCS in sharp contrast with Group 2, where none of the patients had previous CS (p = 0.006). Patients in Group I required more volume replacement than Group 2 during the first 24 hours after CS: 2,699+/-704 mL versus 217+/-603 mL respectively, p = 0.019. Despite similar baseline GFR, Group 1 presented lower GFR 24 hours after CS when compared to Group 2 (39+/-5 versus 75+/-8 mL/(min x 1.73m2), p = 0.001) and a significantly different deltaGFR 48 hours after CS as compared to Group 2 (-21+/-11 versus +88+/-36%, p<0.01). Baseline sodium fractional excretion (FENa) in Group 1 was lower than in Group 2 (0.27+/-0.04 versus 0.70+/-0.12%, p = 0.01). No changes were observed after CS in urinary osmolality (Uosm) and urinary pH (UpH) in both groups. The deltaGFR24 showed positive correlation with baseline FENa (r = 0.44 p = 0.04) and negative correlation with volume balance during the first 24h after CS (r = -0.63, p = 0.007). More patients in Group 1 required nitroprusside than in Group 2 (66% vs. 14%, p = 0.04). Anesthesia time was shorter in Group 1 as compared to Group 2: 323+/-21 vs. 395+/-26 min, p = 0.04. No significant hemolysis occurred during CS in either group. There were no differences in age, gender

  15. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats

    PubMed Central

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; da Silva, Priscyla Oliveira; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-01-01

    Background Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. Objectives To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. Methods We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. Results In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). Conclusion We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  16. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

    PubMed

    Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

    2009-01-01

    The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores. Copyright 2008 S. Karger AG, Basel.

  17. Executive function and cardiac autonomic regulation in depressive disorders.

    PubMed

    Hoffmann, Alexandra; Ettinger, Ulrich; Reyes Del Paso, Gustavo A; Duschek, Stefan

    2017-08-18

    Executive function impairments have been frequently observed in depressive disorders. Moreover, reduced heart rate variability (HRV) has repeatedly been described, especially in the high frequency band (i.e., respiratory sinus arrhythmia, RSA), suggesting lower vagal cardiac outflow. The study tested the hypothesis of involvement of low vagal tone in executive dysfunction in depression. In addition to RSA, HRV in the low frequency (LF) band was assessed. In 36 patients with depression and 36 healthy subjects, electrocardiography recordings were accomplished at rest and during performance of five executive function tasks (number-letter task, n-back task, continuous performance test, flanker task, and antisaccade task). Patients displayed increased error rates and longer reaction times in the task-switching condition of the number-letter task, in addition to increased error rates in the n-back task and the final of two blocks of the antisaccade task. In patients, both HRV parameters were lower during all experimental phases. RSA correlated negatively with reaction time during task-switching. This finding confirms reduced performance across different executive functions in depression and suggests that, in addition to RSA, LF HRV is also diminished. However, the hypothesis of involvement of low parasympathetic tone in executive dysfunction related to depression received only limited support. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Functional Effects of Hyperthyroidism on Cardiac Papillary Muscle in Rats.

    PubMed

    Vieira, Fabricio Furtado; Olivoto, Robson Ruiz; Silva, Priscyla Oliveira da; Francisco, Julio Cesar; Fogaça, Rosalvo Tadeu Hochmuller

    2016-12-01

    Hyperthyroidism is currently recognized to affect the cardiovascular system, leading to a series of molecular and functional changes. However, little is known about the functional influence of hyperthyroidism in the regulation of cytoplasmic calcium and on the sodium/calcium exchanger (NCX) in the cardiac muscle. To evaluate the functional changes in papillary muscles isolated from animals with induced hyperthyroidism. We divided 36 Wistar rats into a group of controls and another of animals with hyperthyroidism induced by intraperitoneal T3 injection. We measured in the animals' papillary muscles the maximum contraction force, speed of contraction (+df/dt) and relaxation (-df/dt), contraction and relaxation time, contraction force at different concentrations of extracellular sodium, post-rest potentiation (PRP), and contraction force induced by caffeine. In hyperthyroid animals, we observed decreased PRP at all rest times (p < 0.05), increased +df/dt and -df/dt (p < 0.001), low positive inotropic response to decreased concentration of extracellular sodium (p < 0.001), reduction of the maximum force in caffeine-induced contraction (p < 0.003), and decreased total contraction time (p < 0.001). The maximal contraction force did not differ significantly between groups (p = 0.973). We hypothesize that the changes observed are likely due to a decrease in calcium content in the sarcoplasmic reticulum, caused by calcium leakage, decreased expression of NCX, and increased expression of a-MHC and SERCA2.

  19. Psychological functioning in parents of children undergoing elective cardiac surgery.

    PubMed

    Wray, Jo; Sensky, Tom

    2004-04-01

    To assess levels of distress, the marital relationship, and styles of coping of parents of children with congenital heart disease, to evaluate any change in these parameters following elective cardiac surgery for their child, and to compare these parents with parents of children undergoing another form of hospital treatment, and with parents of healthy children. A prospective study in which parents were assessed the day before the surgical procedure being undergone by their child, and 12 months afterwards. We assessed three groups of parents of 75 children, aged from birth to 16.9 years. The first was a group whose children were undergoing surgery because of congenital heart disease, the second was a group whose children were undergoing transplantation of bone marrow, and the third was a group whose children were healthy. Measures used for assessment included the General Health Questionnaire, the Dyadic adjustment scale, and the Utrecht coping list. Parents in both groups of children undergoing surgery had significantly higher rates of distress prior to the surgical procedures than did the parents of the healthy children, but within those whose children were undergoing cardiac surgery, there were no differences between parents of children with cyanotic and acyanotic lesions. Following treatment, there was a significant reduction in the levels of distress in both groups whose children had undergone surgery. There were few differences between any of the groups on the other parameters, and the evaluated indexes showed stability over time. Despite elevated levels of psychological distress prior to surgical procedures, which had fallen after one year, the stability of other parameters of parental functioning over time suggests that the surgical interventions are of less significance than either factors attributable to the presence of chronic illness, or the individual characteristics of the parents.

  20. Intramyocardial delivery of HMGB1 by a novel thermosensitive hydrogel attenuates cardiac remodeling and improves cardiac function after myocardial infarction.

    PubMed

    He, Yi-Yu; Wen, Ying; Zheng, Xiao-Xin; Jiang, Xue-Jun

    2013-04-01

    High-mobility group box 1 (HMGB1), a nuclear protein, has been recently reported to attenuate cardiac remodeling after myocardial infarction (MI). This study was designed to investigate whether this effect could be strengthened by local intramyocardial injection of HMGB1 along with a novel Dex-PCL-HEMA/PNIPAAm hydrogel and ascertain its possible mechanism of action. Rat models were induced by coronary artery ligation. Phosphate-buffered solution, Dex-PCL-HEMA/PNIPAAm hydrogel, HMGB1 in phosphate-buffered solution, or HMGB1 in hydrogel was injected into a peri-infarcted area of cardiac tissue immediately after MI. The injection of HMGB1 along with hydrogel improved cardiac function and reduced collagen content. Additionally, the number of c-Kit/Ki67, α-sarcomeric/MEF2C, and α-sarcomeric/Ki67 cells were increased significantly compared with the results of using either agent alone. HMGB1 injection with Dex-PCL-HEMA/PNIPAAm hydrogel attenuates cardiac remodeling and improves cardiac function after MI by inducing myocardial regeneration.

  1. [Application of brain natriuretic peptide in evaluation of cardiac function in forensic medicine].

    PubMed

    Gao, Wei-Min; Mao, Rui-Ming; Du, Zhong-Bo; Mi, Li; Zhu, Bao-Ll

    2011-10-01

    Brain natriuretic peptide (BNP) is a major marker for evaluating cardiac function and has been widely used in clinical practice. Recent researches show that BNP is also useful for identification of sudden cardiac death in forensic pathology. This article reviews the molecular structure and biological characteristics of the BNP and its application as a functional indicate in forensic medicine. It shows that the expression of BNP in cardiac muscles, together with the expression of BNP in blood and pericardium liquid can be used to evaluate the pathological physiology changes and dysfunction degrees of the heart during the cardiac sudden death.

  2. High Interleukin 17 Expression Is Correlated With Better Cardiac Function in Human Chagas Disease

    PubMed Central

    Magalhães, Luisa M. D.; Villani, Fernanda N. A.; Nunes, Maria do Carmo P.; Gollob, Kenneth J.; Rocha, Manoel O. C.; Dutra, Walderez O.

    2013-01-01

    This study was designed to investigate whether the expression of interleukin 17 (IL-17) is associated with the indeterminate or cardiac clinical forms of Chagas disease and whether IL-17 expression can be correlated with patients' cardiac function. Our results demonstrated that cardiac Chagas patients have a lower intensity of expression of IL-17 by total lymphocytes and lower frequency of circulating T helper 17 cells. Correlative analysis showed that high IL-17 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Therefore, IL-17 expression can be a protective factor to prevent myocardial damage in human Chagas disease. PMID:23204182

  3. Physiologically inspired cardiac scaffolds for tailored in vivo function and heart regeneration

    PubMed Central

    Kaiser, Nicholas J; Coulombe, Kareen L K

    2015-01-01

    Tissue engineering is well suited for the treatment of cardiac disease due to the limited regenerative capacity of native cardiac tissue and the loss of function associated with endemic cardiac pathologies, such as myocardial infarction and congenital heart defects. However, the physiological complexity of the myocardium imposes extensive requirements on tissue therapies intended for these applications. In recent years, the field of cardiac tissue engineering has been characterized by great innovation and diversity in the fabrication of engineered tissue scaffolds for cardiac repair and regeneration to address these problems. From early approaches that attempted only to deliver cardiac cells in a hydrogel vessel, significant progress has been made in understanding the role of each major component of cardiac living tissue constructs (namely cells, scaffolds, and signaling mechanisms) as they relate to mechanical, biological, and electrical in vivo performance. This improved insight, accompanied by modern material science techniques, allows for the informed development of complex scaffold materials that are optimally designed for cardiac applications. This review provides a background on cardiac physiology as it relates to critical cardiac scaffold characteristics, the degree to which common cardiac scaffold materials fulfill these criteria, and finally an overview of recent in vivo studies that have employed this type of approach. PMID:25970645

  4. The effect of milrinone on the right ventricular function in patients with reduced right ventricular function undergoing off-pump coronary artery bypass graft surgery.

    PubMed

    Lee, Jong Hwa; Oh, Young Jun; Shim, Yon Hee; Hong, Yong Woo; Yi, Gijong; Kwak, Young Lan

    2006-10-01

    This investigation evaluated the effect of continuous milrinone infusion on right ventricular (RV) function during off-pump coronary artery bypass graft (OPCAB) surgery in patients with reduced RV function. Fifty patients scheduled for OPCAB, with thermodilution RV ejection fraction (RVEF) <35% after anesthesia induction, were randomly allocated to either milrinone (0.5 microg/kg/min) or control (saline) group. Hemodynamic variables and RV volumetric data measured by thermodilution method were collected as follows: after anesthesia induction (T1); 10 min after heart displacement for obtuse marginal artery anastomosis (T2); after pericardial closure (T3). Cardiac index and heart rate increased and systemic vascular resistance significantly decreased in milrinone group at T2. Initially lower RVEF of milrinone group was eventually comparable to control group after milrinone infusion. RVEF did not significantly change at T2 and T3 in both groups. RV end-diastolic volume in milrinone group consistently decreased from the baseline at T2 and T3. Continuous infusion of milrinone without a bolus demonstrated potentially beneficial effect on cardiac output and RV afterload in patients with reduced RV function during OPCAB. However, aggressive augmentation of intravascular volume seems to be necessary to maximize the effect of the milrinone in these patients.

  5. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis

    PubMed Central

    Wei, Cheng-Yu; Kung, Woon-Man; Chou, Yi-Sheng; Wang, Yao-Chin; Tai, Hsu-Chih; Wei, James Cheng-Chung

    2016-01-01

    Abstract Ankylosing spondylitis (AS) is a chronic inflammatory disease involing spine and enthesis. The primary aim of this study is to investigate the autonomic nervous system (ANS) function and the association between ANS and the functional status or disease activity in AS. The study included 42 AS patients, all fulfilling the modified New York criteria. All the patients are totally symptom free for ANS involvement and had normal neurological findings. These AS patients and 230 healthy volunteers receive analysis of 5 minutes heart rate variability (HRV) in lying posture. In addition, disease activity and functional status of these AS patients are assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Global Score (BAS-G). Both groups were age and sex-matched. Although the HRV analysis indicates that the peaks of total power (TP, 0–0.5 Hz) and high-frequency power (HF, 0.15–0.40 Hz) are similar in both groups, the activities of low-frequency power (LF, 0.04–0.15 Hz), LF in normalized units (LF%), and the ratio of LF to HF (LF/HF) in AS patients are obviously lower than healthy controls. The erythrocyte sedimentation rate and C-reactive protein revealed negative relationship with HF. The AS patients without peripheral joint disease have higher LF, TP, variance, LF%, and HF than the patients with peripheral joint disease. The AS patients without uvetis have higher HF than the patients with uvetis. The total scores of BASDI, BASFI, and BAS-G do not show any association to HRV parameters. AS patients have significantly abnormal cardiac autonomic regulation. This is closely related with some inflammatory activities. Reduced autonomic function may be one of the factors of high cardiovascular risk in AS patients. PMID:27227940

  6. Regular Football Practice Improves Autonomic Cardiac Function in Male Children

    PubMed Central

    Fernandes, Luis; Oliveira, Jose; Soares-Miranda, Luisa; Rebelo, Antonio; Brito, Joao

    2015-01-01

    Background: The role of the autonomic nervous system (ANS) in the cardiovascular regulation is of primal importance. Since it has been associated with adverse conditions such as cardiac arrhythmias, sudden death, sleep disorders, hypertension and obesity. Objectives: The present study aimed to investigate the impact of recreational football practice on the autonomic cardiac function of male children, as measured by heart rate variability. Patients and Methods: Forty-seven male children aged 9 - 12 years were selected according to their engagement with football oriented practice outside school context. The children were divided into a football group (FG; n = 22) and a control group (CG; n = 25). The FG had regular football practices, with 2 weekly training sessions and occasional weekend matches. The CG was not engaged with any physical activity other than complementary school-based physical education classes. Data from physical activity, physical fitness, and heart rate variability measured in time and frequency domains were obtained. Results: The anthropometric and body composition characteristics were similar in both groups (P > 0.05). The groups were also similar in time spent daily on moderate-to-vigorous physical activities (FG vs. CG: 114 ± 64 vs. 87 ± 55 minutes; P > 0.05). However, the FG performed better (P < 0.05) in Yo-Yo intermittent endurance test (1394 ± 558 vs. 778 ± 408 m) and 15-m sprint test (3.06 ± 0.17 vs. 3.20 ± 0.23 s). Also, the FG presented enhanced autonomic function. Significant differences were detected (P < 0.05) between groups for low frequency normalized units (38.0 ± 15.2 vs. 47.3 ± 14.2 n.u (normalized units)), high frequency normalized units (62.1 ± 15.2 vs. 52.8 ± 14.2 n.u.), and LF:HF ratio (0.7 ± 0.4 vs. 1.1 ± 0.6 ms2). Conclusions: Children engaged with regular football practice presented enhanced physical fitness and autonomic function, by increasing vagal tone at rest. PMID:26448848

  7. Developmental stage-dependent effects of cardiac fibroblasts on function of stem cell-derived engineered cardiac tissues

    PubMed Central

    Liau, Brian; Jackman, Christopher P.; Li, Yanzhen; Bursac, Nenad

    2017-01-01

    We investigated whether the developmental stage of mouse cardiac fibroblasts (CFs) influences the formation and function of engineered cardiac tissues made of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs). Engineered cardiac tissue patches were fabricated by encapsulating pure mESC-CMs, mESC-CMs + adult CFs, or mESC-CMs + fetal CFs in fibrin-based hydrogel. Tissue patches containing fetal CFs exhibited higher velocity of action potential propagation and contractile force amplitude compared to patches containing adult CFs, while pure mESC-CM patches did not form functional syncytium. The functional improvements in mESC-CM + fetal CF patches were associated with differences in structural remodeling and increased expression of proteins involved in cardiac function. To determine role of paracrine signaling, we cultured pure mESC-CMs within miniature tissue “micro-patches” supplemented with media conditioned by adult or fetal CFs. Fetal CF-conditioned media distinctly enhanced CM spreading and contractile activity, which was shown by pathway inhibitor experiments and Western blot analysis to be mediated via MEK-ERK signaling. In mESC-CM monolayers, CF-conditioned media did not alter CM spreading or MEK-ERK activation. Collectively, our studies show that 3D co-culture of mESC-CMs with embryonic CFs is superior to co-culture with adult CFs for in vitro generation of functional myocardium. Ensuring consistent developmental stages of cardiomyocytes and supporting non-myocytes may be a critical factor for promoting functional maturation of engineered cardiac tissues. PMID:28181589

  8. Metoprolol Improves Endothelial Function in Patients with Cardiac Syndrome X

    PubMed Central

    Majidinia, Maryam; Rasmi, Yousef; Khadem Ansari, Mohammad Hassan; Seyed-Mohammadzad, MirHossein; Saboory, Ehsan; Shirpoor, Alireza

    2016-01-01

    Endothelial dysfunction which is manifested by the loss of nitric oxide bioavailability, is an increasingly recognized cause of cardiac syndrome X (CSX) and beta blockers are used for the treatment of this syndrome. Thus, the aim of this study was to investigate effects of metoprolol, as a beta blocker, on endothelial function in CSX patients. The study included 25 CSX patients (20 female/ 5 male, mean age: 55.36±10.31 years) who received metoprolol (50 mg BID) for one month. In addition, 25 healthy controls (20 female/ 5 male, mean age: 54.32 ±9.27 years) were enrolled. Levels of endothelin-1, E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) in controls and CSX patients were measured, both at the baseline and after the treatment, by the enzyme-linked immunosorbent assay. In CSX patients, at the baseline, levels of E-selectin and VCAM-1 were significantly higher than those of the controls. In addition, levels of these biomarkers in CSX patients after the treatment significantly decreased compared to the baseline. In spite of similar tendency, these differences were not significant for endothelin-1. In conclusion, metoprolol therapy improves endothelial function. Thus, it may be a suggested choice for CSX treatment. However, further studies are needed to confirm the clinical significance of metoprolol therapy for CSX patients. PMID:27980592

  9. Haemoglobin, blood volume, cardiac function, and aerobic power.

    PubMed

    Gledhill, N; Warburton, D; Jamnik, V

    1999-02-01

    Alterations in [Hb], which are mediated through changes in arterial oxygen content, and alterations in BV, which are mediated through changes in cardiac output (Q), have a significant effect on both VO2max and aerobic performance. If BV is held constant, a decrease in [Hb] (anaemia) causes a decrease in VO2max and aerobic performance, while an increase in [Hb] (blood doping) causes an increase in VO2max and aerobic performance. If [Hb] is held constant, an increase in BV can cause and increase in both VO2max and aerobic performance, while a decrease in BV can cause a decrease in VO2max and aerobic performance. In addition, an increase in BV can compensate for moderate reductions in [Hb] through increase in Q, allowing VO2max to remain unchanged or even increase. Also, a large portion of the difference in the enhanced cardiovascular function of endurance athletes is due to their high BV and the resultant enhancement of diastolic function. Hence, optimizing both [Hb] and BV is a very important consideration for endurance performance.

  10. Measurement of Cardiac Angiotensin II by Immunoassays, HPLC-Chip/Mass Spectrometry, and Functional Assays.

    PubMed

    De Mello, Walmor C; Gerena, Yamil

    2017-01-01

    The molecular mechanisms related to the effect of angiotensin II, its level on cardiac tissues, as well as its overexpression represent an important aspect of cardiovascular pharmacology and pathology. Severe alterations of cardiac functions are induced by hypertension including activation of circulating and local cardiac renin angiotensin systems. In this chapter, we are providing the methods and materials necessary for further investigation of this important topic.

  11. Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs.

    PubMed

    Matsuura, Timothy R; Bartos, Jason A; Tsangaris, Adamantios; Shekar, Kadambari Chandra; Olson, Matthew D; Riess, Matthias L; Bienengraeber, Martin; Aufderheide, Tom P; Neumar, Robert W; Rees, Jennifer N; McKnite, Scott H; Dikalova, Anna E; Dikalov, Sergey I; Douglas, Hunter F; Yannopoulos, Demetris

    2017-04-10

    Background Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10 percent. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after fifteen minutes of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR).

  12. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: functional significance.

    PubMed

    Clausen, Torben

    2013-10-01

    During excitation, muscle cells gain Na(+) and lose K(+), leading to a rise in extracellular K(+) ([K(+)]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na(+),K(+)-ATPase (also known as the Na(+),K(+) pump) is often essential for adequate clearance of extracellular K(+). As a result of their electrogenic action, Na(+),K(+) pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na(+),K(+)-pump function and the capacity of the Na(+),K(+) pumps to fill these needs require quantification of the total content of Na(+),K(+) pumps in skeletal muscle. Inhibition of Na(+),K(+)-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na(+),K(+)-pump transport rate or increasing the content of Na(+),K(+) pumps enhances muscle excitability and contractility. Measurements of [(3)H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na(+),K(+) pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na(+),K(+)-ATPase may show inconsistent results. Measurements of Na(+) and K(+) fluxes in intact isolated muscles show that, after Na(+) loading or intense excitation, all the Na(+),K(+) pumps are functional, allowing calculation of the maximum Na(+),K(+)-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na(+),K(+) pumps are regulated by exercise, inactivity, K(+) deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the α-subunit isoforms of the Na(+),K(+)-ATPase have detected a relative increase in their

  13. Quantification of Na+,K+ pumps and their transport rate in skeletal muscle: Functional significance

    PubMed Central

    2013-01-01

    During excitation, muscle cells gain Na+ and lose K+, leading to a rise in extracellular K+ ([K+]o), depolarization, and loss of excitability. Recent studies support the idea that these events are important causes of muscle fatigue and that full use of the Na+,K+-ATPase (also known as the Na+,K+ pump) is often essential for adequate clearance of extracellular K+. As a result of their electrogenic action, Na+,K+ pumps also help reverse depolarization arising during excitation, hyperkalemia, and anoxia, or from cell damage resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to evaluate Na+,K+-pump function and the capacity of the Na+,K+ pumps to fill these needs require quantification of the total content of Na+,K+ pumps in skeletal muscle. Inhibition of Na+,K+-pump activity, or a decrease in their content, reduces muscle contractility. Conversely, stimulation of the Na+,K+-pump transport rate or increasing the content of Na+,K+ pumps enhances muscle excitability and contractility. Measurements of [3H]ouabain binding to skeletal muscle in vivo or in vitro have enabled the reproducible quantification of the total content of Na+,K+ pumps in molar units in various animal species, and in both healthy people and individuals with various diseases. In contrast, measurements of 3-O-methylfluorescein phosphatase activity associated with the Na+,K+-ATPase may show inconsistent results. Measurements of Na+ and K+ fluxes in intact isolated muscles show that, after Na+ loading or intense excitation, all the Na+,K+ pumps are functional, allowing calculation of the maximum Na+,K+-pumping capacity, expressed in molar units/g muscle/min. The activity and content of Na+,K+ pumps are regulated by exercise, inactivity, K+ deficiency, fasting, age, and several hormones and pharmaceuticals. Studies on the α-subunit isoforms of the Na+,K+-ATPase have detected a relative increase in their number in response to exercise and the glucocorticoid dexamethasone but have not

  14. Authentication of Radial Versus Femoral Arterial Pressure Waveform-Derived Cardiac Output With Transesophageal Echocardiography-Derived Cardiac Output Measurements in Patients Undergoing On-Pump Coronary Bypass Surgery.

    PubMed

    Maddali, Madan Mohan; Waje, Niranjan Dilip; Sathiya, Panchatcharam Murthi

    2017-08-01

    The aim of this study was to ascertain if arterial waveform-derived cardiac output measurements from radial and femoral cannulation sites were reliable as compared with transesophageal echocardiography (TEE)-derived cardiac output (CO) values, and which of the CO measurements derived from radial and the femoral arterial pressure waveforms closely tracked simultaneously measured TEE-derived CO values. This study also aimed to ascertain if cardiopulmonary bypass (CPB) would impact the accuracy of arterial pressure-derived CO values from either of the 2 sites. A prospective observational study. Tertiary care cardiac center. Cardiac surgical patients undergoing on-pump primary coronary artery bypass surgery. Waveform-derived CO monitoring through radial and femoral artery cannulation using a FloTrac/Vigileo system. Twenty-seven consecutive cardiac surgical patients undergoing on-pump primary coronary artery bypass surgery were included in the study. Cardiac output was measured sequentially by the arterial pressure waveform analysis method from radial and femoral arterial sites and compared with simultaneously measured TEE-derived CO. Cardiac output data were obtained in triplicate at 6 predefined time intervals: before and after sternotomy, 5, 15, and 30 minutes after separation from CPB and prior to shifting the patient out of the operating room. The overall bias of the study was 0.11 and 0.27, the percentage error was 19.31 and 18.45, respectively, for radial and femoral arterial waveform-derived CO values as compared with TEE-derived CO measurements. The overall precision as compared with the TEE-derived CO values was 16.94 and 15.95 for the radial and femoral cannulation sites, respectively. The bias calculated by the Bland-Altman method suggested that CO measurements from the radial arterial site were in closer agreement with TEE-derived CO values at all time periods, and the relation was not affected by CPB. However, percentage error and precision calculations

  15. Nature's pumps

    NASA Astrophysics Data System (ADS)

    Vogel, Steven

    1994-10-01

    Although diverse in both form and function, the fluid-forcing devices in organisms have many of the capabilities and limitations of pumps of human design. Nature's pumps certainly look quite different from those of our technology, but all of them perform the same task. The author examines a few of these with an eye toward technological parallels and the two functional classes -- positive-displacement pumps and fluid-dynamic pumps.

  16. Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

    PubMed Central

    O’Connell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.

    2014-01-01

    Adrenergic receptors (AR) are G-protein-coupled receptors (GPCRs) that have a crucial role in cardiac physiology in health and disease. Alpha1-ARs signal through Gαq, and signaling through Gq, for example, by endothelin and angiotensin receptors, is thought to be detrimental to the heart. In contrast, cardiac alpha1-ARs mediate important protective and adaptive functions in the heart, although alpha1-ARs are only a minor fraction of total cardiac ARs. Cardiac alpha1-ARs activate pleiotropic downstream signaling to prevent pathologic remodeling in heart failure. Mechanisms defined in animal and cell models include activation of adaptive hypertrophy, prevention of cardiac myocyte death, augmentation of contractility, and induction of ischemic preconditioning. Surprisingly, at the molecular level, alpha1-ARs localize to and signal at the nucleus in cardiac myocytes, and, unlike most GPCRs, activate “inside-out” signaling to cause cardioprotection. Contrary to past opinion, human cardiac alpha1-AR expression is similar to that in the mouse, where alpha1-AR effects are seen most convincingly in knockout models. Human clinical studies show that alpha1-blockade worsens heart failure in hypertension and does not improve outcomes in heart failure, implying a cardioprotective role for human alpha1-ARs. In summary, these findings identify novel functional and mechanistic aspects of cardiac alpha1-AR function and suggest that activation of cardiac alpha1-AR might be a viable therapeutic strategy in heart failure. PMID:24368739

  17. Reduced Right Ventricular Function Predicts Long-Term Cardiac Re-Hospitalization after Cardiac Surgery

    PubMed Central

    Goldsmith, Yulia; Chan, Jacqueline; Iskandir, Marina; Gulkarov, Iosif; Tortolani, Anthony; Brener, Sorin J.; Sacchi, Terrence J.; Heitner, John F.

    2015-01-01

    Background The significance of right ventricular ejection fraction (RVEF), independent of left ventricular ejection fraction (LVEF), following isolated coronary artery bypass grafting (CABG) and valve procedures remains unknown. The aim of this study is to examine the significance of abnormal RVEF by cardiac magnetic resonance (CMR), independent of LVEF in predicting outcomes of patients undergoing isolated CABG and valve surgery. Methods From 2007 to 2009, 109 consecutive patients (mean age, 66 years; 38% female) were referred for pre-operative CMR. Abnormal RVEF and LVEF were considered <35% and <45%, respectively. Elective primary procedures include CABG (56%) and valve (44%). Thirty-day outcomes were perioperative complications, length of stay, cardiac re-hospitalizations and early mortaility; long-term (> 30 days) outcomes included, cardiac re-hospitalization, worsening congestive heart failure and mortality. Mean clinical follow up was 14 months. Findings Forty-eight patients had reduced RVEF (mean 25%) and 61 patients had normal RVEF (mean 50%) (p<0.001). Fifty-four patients had reduced LVEF (mean 30%) and 55 patients had normal LVEF (mean 59%) (p<0.001). Patients with reduced RVEF had a higher incidence of long-term cardiac re-hospitalization vs. patients with normal RVEF (31% vs.13%, p<0.05). Abnormal RVEF was a predictor for long-term cardiac re-hospitalization (HR 3.01 [CI 1.5-7.9], p<0.03). Reduced LVEF did not influence long-term cardiac re-hospitalization. Conclusion Abnormal RVEF is a stronger predictor for long-term cardiac re-hospitalization than abnormal LVEF in patients undergoing isolated CABG and valve procedures. PMID:26197273

  18. 3-week hiking holidays at moderate altitude do not impair cardiac function in individuals with metabolic syndrome.

    PubMed

    Mair, Johannes; Hammerer-Lercher, Angelika; Mittermayr, Markus; Klingler, Anton; Humpeler, Egon; Pachinger, Otmar; Schobersberger, Wolfgang

    2008-01-11

    We studied the influence of a 3-week hiking vacation at moderate altitude on cardiac pump and endocrine function. 18 males (mean age: 55 years, range 36-60) with metabolic syndrome participated in a 3-week structured guided hiking vacation program (4 times per week at 55-65% of maximal heart rate, total exercise time 29 h). Echocardiography, B-type natriuretic peptide (BNP), NT-proBNP, and endothelin-1 measurements were performed at baseline in Innsbruck (576 m a.s.l., Austria), on the first day at moderate altitude (Obertauern, 1700 m a.s.l., Austria), after 3 weeks in Obertauern, and at follow-up in Innsbruck. We found no adverse cardiovascular effects and no significant changes in echocardiographic measures of systolic or diastolic function, estimated systolic pulmonary artery pressure, exercise capacities, BNP and NT-proBNP, or endothelin-1 concentrations. The blood pressure at rest significantly decreased from baseline to follow-up.

  19. Exchangers man the pumps: Functional interplay between proton pumps and proton-coupled Ca(2+) exchangers

    USDA-ARS?s Scientific Manuscript database

    Tonoplast-localised proton-coupled Ca(2+) transporters encoded by cation/H(+) exchanger (CAX) genes play a critical role in sequestering Ca(2+) into the vacuole. These transporters may function in coordination with Ca(2+) release channels, to shape stimulus-induced cytosolic Ca(2+) elevations. Recen...

  20. ANGPTL2 activity in cardiac pathologies accelerates heart failure by perturbing cardiac function and energy metabolism

    PubMed Central

    Tian, Zhe; Miyata, Keishi; Kadomatsu, Tsuyoshi; Horiguchi, Haruki; Fukushima, Hiroyuki; Tohyama, Shugo; Ujihara, Yoshihiro; Okumura, Takahiro; Yamaguchi, Satoshi; Zhao, Jiabin; Endo, Motoyoshi; Morinaga, Jun; Sato, Michio; Sugizaki, Taichi; Zhu, Shunshun; Terada, Kazutoyo; Sakaguchi, Hisashi; Komohara, Yoshihiro; Takeya, Motohiro; Takeda, Naoki; Araki, Kimi; Manabe, Ichiro; Fukuda, Keiichi; Otsu, Kinya; Wada, Jun; Murohara, Toyoaki; Mohri, Satoshi; Yamashita, Jun K.; Sano, Motoaki; Oike, Yuichi

    2016-01-01

    A cardioprotective response that alters ventricular contractility or promotes cardiomyocyte enlargement occurs with increased workload in conditions such as hypertension. When that response is excessive, pathological cardiac remodelling occurs, which can progress to heart failure, a leading cause of death worldwide. Mechanisms underlying this response are not fully understood. Here, we report that expression of angiopoietin-like protein 2 (ANGPTL2) increases in pathologically-remodeled hearts of mice and humans, while decreased cardiac ANGPTL2 expression occurs in physiological cardiac remodelling induced by endurance training in mice. Mice overexpressing ANGPTL2 in heart show cardiac dysfunction caused by both inactivation of AKT and sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2a signalling and decreased myocardial energy metabolism. Conversely, Angptl2 knockout mice exhibit increased left ventricular contractility and upregulated AKT-SERCA2a signalling and energy metabolism. Finally, ANGPTL2-knockdown in mice subjected to pressure overload ameliorates cardiac dysfunction. Overall, these studies suggest that therapeutic ANGPTL2 suppression could antagonize development of heart failure. PMID:27677409

  1. New developments in paediatric cardiac functional ultrasound imaging.

    PubMed

    de Korte, Chris L; Nillesen, Maartje M; Saris, Anne E C M; Lopata, Richard G P; Thijssen, Johan M; Kapusta, Livia

    2014-07-01

    Ultrasound imaging can be used to estimate the morphology as well as the motion and deformation of tissues. If the interrogated tissue is actively deforming, this deformation is directly related to its function and quantification of this deformation is normally referred as 'strain imaging'. Tissue can also be deformed by applying an internal or external force and the resulting, induced deformation is a function of the mechanical tissue characteristics. In combination with the load applied, these strain maps can be used to estimate or reconstruct the mechanical properties of tissue. This technique was named 'elastography' by Ophir et al. in 1991. Elastography can be used for atherosclerotic plaque characterisation, while the contractility of the heart or skeletal muscles can be assessed with strain imaging. Rather than using the conventional video format (DICOM) image information, radio frequency (RF)-based ultrasound methods enable estimation of the deformation at higher resolution and with higher precision than commercial methods using Doppler (tissue Doppler imaging) or video image data (2D speckle tracking methods). However, the improvement in accuracy is mainly achieved when measuring strain along the ultrasound beam direction, so it has to be considered a 1D technique. Recently, this method has been extended to multiple directions and precision further improved by using spatial compounding of data acquired at multiple beam steered angles. Using similar techniques, the blood velocity and flow can be determined. RF-based techniques are also beneficial for automated segmentation of the ventricular cavities. In this paper, new developments in different techniques of quantifying cardiac function by strain imaging, automated segmentation, and methods of performing blood flow imaging are reviewed and their application in paediatric cardiology is discussed.

  2. A flatness-based control approach to drug infusion for cardiac function regulation

    NASA Astrophysics Data System (ADS)

    Rigatos, Gerasimos; Zervos, Nikolaos; Melkikh, Alexey

    2016-12-01

    A new control method based on differential flatness theory is developed in this article, aiming at solving the problem of regulation of haemodynamic parameters, Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs, such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account. Using the principle of dynamic extension, which means that by considering certain control inputs and their derivatives as additional state variables, a state-space description for the heart's function is obtained. It is proven that the dynamic model of the heart is a differentially flat one. This enables its transformation into a linear canonical and decoupled form, for which the design of a stabilizing feedback controller becomes possible. The proposed feedback controller is of proven stability and assures fast and accurate tracking of the reference setpoints by the outputs of the heart's dynamic model. Moreover, by using a Kalman Filter-based disturbances' estimator, it becomes possible to estimate in real-time and compensate for the model uncertainty and external perturbation inputs that affect the heart's model.

  3. Flatness-based control approach to drug infusion for cardiac function regulation.

    PubMed

    Rigatos, Gerasimos; Zervos, Nikolaos; Melkikh, Alexey

    2017-02-01

    A new control method based on differential flatness theory is developed in this study, aiming at solving the problem of regulation of haemodynamic parameters. Actually control of the cardiac output (volume of blood pumped out by heart per unit of time) and of the arterial blood pressure is achieved through the administered infusion of cardiovascular drugs such as dopamine and sodium nitroprusside. Time delays between the control inputs and the system's outputs are taken into account. Using the principle of dynamic extension, which means that by considering certain control inputs and their derivatives as additional state variables, a state-space description for the heart's function is obtained. It is proven that the dynamic model of the heart is a differentially flat one. This enables its transformation into a linear canonical and decoupled form, for which the design of a stabilising feedback controller becomes possible. The proposed feedback controller is of proven stability and assures fast and accurate tracking of the reference setpoints by the outputs of the heart's dynamic model. Moreover, by using a Kalman filter-based disturbances' estimator, it becomes possible to estimate in real-time and compensate for the model uncertainty and external perturbation inputs that affect the heart's model.

  4. Qishen Yiqi Drop Pill improves cardiac function after myocardial ischemia

    PubMed Central

    JianXin, Chen; Xue, Xu; ZhongFeng, Li; Kuo, Gao; FeiLong, Zhang; ZhiHong, Li; Xian, Wang; HongCai, Shang

    2016-01-01

    Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. 1H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine. PMID:27075394

  5. Polybromo protein BAF180 functions in mammalian cardiac chamber maturation

    PubMed Central

    Wang, Zhong; Zhai, Weiguo; Richardson, James A.; Olson, Eric N.; Meneses, Juanito J.; Firpo, Meri T.; Kang, Chulho; Skarnes, William C.; Tjian, Robert

    2004-01-01

    BAF and PBAF are two related mammalian chromatin remodeling complexes essential for gene expression and development. PBAF, but not BAF, is able to potentiate transcriptional activation in vitro mediated by nuclear receptors, such as RXRα, VDR, and PPARγ. Here we show that the ablation of PBAF-specific subunit BAF180 in mouse embryos results in severe hypoplastic ventricle development and trophoblast placental defects, similar to those found in mice lacking RXRα and PPARγ. Embryonic aggregation analyses reveal that in contrast to PPARγ-deficient mice, the heart defects are likely a direct result of BAF180 ablation, rather than an indirect consequence of trophoblast placental defects. We identified potential target genes for BAF180 in heart development, such as S100A13 as well as retinoic acid (RA)-induced targets RARβ2 and CRABPII. Importantly, BAF180 is recruited to the promoter of these target genes and BAF180 deficiency affects the RA response for CRABPII and RARβ2. These studies reveal unique functions of PBAF in cardiac chamber maturation. PMID:15601824

  6. The functional morphology and role of cardiac telocytes in myocardium regeneration.

    PubMed

    Varga, Ivan; Danisovic, Lubos; Kyselovic, Jan; Gazova, Andrea; Musil, Peter; Miko, Michal; Polak, Stefan

    2016-05-19

    Key morphological discoveries in recent years have included the discovery of new cell populations inside the heart called cardiac telocytes. These newly described cells of the connective tissue have extremely long cytoplasmic processes through which they form functionally connected three-dimensional networks that connect cells of the immune system, nerve fibers, cardiac stem cells, and cardiac muscle cells. Based on their functions, telocytes are also referred to as "connecting cells" or "nurse cells" for cardiac progenitor stem cells. In this critical review, we provide a summary of the latest research on cardiac telocytes localized in all layers of the heart - from the historical background of their discovery, through ultrastructural, immunohistochemical, and functional characterizations, to the application of this knowledge to the fields of cardiology, stem cell research, and regenerative medicine.

  7. Cardiac Function in 7-8-Year-Old Offspring of Women with Type 1 Diabetes

    PubMed Central

    Rijpert, Maarten; Breur, Johannes M. P. J.; Evers, Inge M.; de Valk, Harold W.; Heijnen, Cobi J.; Meijboom, Folkert J.; Visser, Gerard H. A.

    2011-01-01

    Offspring of type 1 diabetic mothers (ODMs) are at risk of short-term and long-term complications, such as neonatal macrosomia (birth weight >90th percentile), hypertrophic cardiomyopathy, and cardiovascular morbidity in later life. However, no studies have been performed regarding cardiac outcome. In this study, we investigated cardiac dimensions and function in 30 ODMs at 7-8 years of age in relation to neonatal macrosomia and maternal glycemic control during pregnancy and compared these with those in a control group of 30 children of nondiabetic women. We found that cardiac dimensions and systolic and diastolic function parameters in ODMs were comparable with those in controls. Neonatal macrosomia and poorer maternal glycemic control during pregnancy were not related to worse cardiac outcome in ODM. We conclude that cardiac function at 7-8 years of age in offspring of women with type 1 diabetes is reassuring and comparable with that in controls. PMID:22144987

  8. Respiratory and cardiac function in congenital muscular dystrophies with alpha dystroglycan deficiency.

    PubMed

    Pane, M; Messina, S; Vasco, G; Foley, A R; Morandi, L; Pegoraro, E; Mongini, T; D'Amico, A; Bianco, F; Lombardo, M E; Scalise, R; Bruno, C; Berardinelli, A; Pini, A; Moroni, I; Mora, M; Toscano, A; Moggio, M; Comi, G; Santorelli, F M; Bertini, E; Muntoni, F; Mercuri, E

    2012-08-01

    The aim of this retrospective study was to assess respiratory and cardiac function in a large cohort of patients with congenital muscular dystrophies (CMD) with reduced glycosylation of alphadystroglycan (α-DG). Thirteen of the 115 patients included in the study died between the age of 1 month and 20 years. The age at last follow up of the surviving 102 ranged between 1 year and 68 years (median: 9.3 years). Cardiac involvement was found in 7 of the 115 (6%), 5 with dilated cardiomyopathy, 1 cardiac conductions defects and 1 mitral regurgitation. Respiratory function was impaired in 14 (12%). Ten of the 14 required non invasive nocturnal respiratory support, while the other four required invasive ventilation. Cardiac or respiratory involvement was found in patients with mutations in FKRP, POMT1, POMT2. All of the patients in whom mutation in POMGnT1 were identified had normal cardiac and respiratory function.

  9. Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function.

    PubMed

    Alpert, Martin A; Omran, Jad; Bostick, Brian P

    2016-12-01

    Obesity produces a variety of hemodynamic alterations that may cause changes in cardiac morphology which predispose to left and right ventricular dysfunction. Various neurohormonal and metabolic alterations commonly associated with obesity may contribute to these abnormalities of cardiac structure and function. These changes in cardiovascular hemodynamics, cardiac morphology, and ventricular function may, in severely obese patients, predispose to heart failure, even in the absence of other forms of heart disease (obesity cardiomyopathy). In normotensive obese patients, cardiac involvement is commonly characterized by elevated cardiac output, low peripheral vascular resistance, and increased left ventricular (LV) end-diastolic pressure. Sleep-disordered breathing may lead to pulmonary arterial hypertension and, in association with left heart failure, may contribute to elevation of right heart pressures. These alterations, in association with various neurohormonal and metabolic abnormalities, may produce LV hypertrophy; impaired LV diastolic function; and less commonly, LV systolic dysfunction. Many of these alterations are reversible with substantial voluntary weight loss.

  10. Olmesartan attenuates cardiac hypertrophy and improves cardiac diastolic function in spontaneously hypertensive rats through inhibition of calcineurin pathway.

    PubMed

    Fu, Mingqiang; Zhou, Jingmin; Xu, Jianfeng; Zhu, Hongmin; Liao, Jianquan; Cui, Xiaotong; Sun, Aijun; Fu, Michael; Zou, Yunzeng; Hu, Kai; Ge, Junbo

    2014-03-01

    To test whether olmesartan ameliorates cardiac diastolic dysfunction in spontaneously hypertensive rats (SHRs) through calcineurin pathway. Twenty-four male SHRs of 6 months were divided into saline- (n = 12) and olmesartan-treated (n = 12) groups. Age-matched WKY (n = 12) rats served as controls. Saline (10 mL·kg·d) or the same volume of olmesartan liquor (2.5 mg·kg·d) was administered by gavage for 3 months. Heart rate, systolic blood pressure, cardiac structure, and function and histological studies were determined. Expression of calcineurin and downstream NFAT3 were also detected. Compared with age-matched Wistar Kyoto rats, SHRs of 6 months exhibited evident cardiac hypertrophy and diastolic dysfunction as demonstrated by elevated systolic blood pressure and E/E', decreased E/A and E'/A', while F, left ventricular ejection fraction and fractional shortening remained unimpaired. Treatment with olmesartan significantly decreased systolic blood pressure and ventricular hypertrophy, attenuated fibrosis, and improved diastolic function (all P < 0.05). Meanwhile, both calcineurin and NFAT3 expressions were downregulated in olmesartan group compared with the other 2 groups (both P < 0.05). These data suggest the beneficial effect of olmesartan on cardiac structure and diastolic dysfunction, and it may be mediated through calcineurin pathway. This indicates a new therapeutic target for diastolic dysfunction.

  11. Risk of Out-of-Hospital Sudden Cardiac Death in Users of Domperidone, Proton Pump Inhibitors, or Metoclopramide: A Population-Based Nested Case-Control Study.

    PubMed

    Arana, Alejandro; Johannes, Catherine B; McQuay, Lisa J; Varas-Lorenzo, Cristina; Fife, Daniel; Rothman, Kenneth J

    2015-12-01

    Epidemiological studies have linked domperidone use with serious cardiac arrhythmias, including sudden cardiac death, but data on age, dose, and duration of use are limited. The aim of this study was to assess the risk of out-of-hospital sudden cardiac death associated with domperidone use versus proton pump inhibitors (PPIs), metoclopramide, or non-use of all three medications, and to evaluate the risk of sudden cardiac death in relation to age and domperidone dose. This was a population-based case-control study nested in a cohort of subjects aged ≥2 years in the Clinical Practice Research Datalink with one or more prescriptions for domperidone, any PPI, or metoclopramide from 2005 to 2011. Out-of-hospital sudden cardiac death was assessed by linkage with Hospital Episode Statistics and death certificates. Controls were matched on age, sex, and medical practice. The risk of sudden cardiac death in domperidone users versus risk in users of PPIs or metoclopramide was evaluated with multivariable conditional logistic regression; case-crossover analysis addressed possible residual confounding. From the study cohort (n = 681,104), 3239 sudden cardiac death cases were matched to 12,572 controls. The adjusted odds ratio (95 % confidence interval) for sudden cardiac death with current use of domperidone alone was 1.71 (0.92-3.18) versus non-use of study medications, 1.26 (0.68-2.34) versus current PPI use, and 0.40 (0.17-0.94) current metoclopramide use. The adjusted odds ratio (95 % confidence interval) relative to exposure to no study drug for domperidone >30 mg/day (eight cases, five controls) was 3.20 (0.59-17.3) and 1.65 (0.89-3.07) for age ≥61 years (27 cases, 49 controls). The odds ratio (95 % confidence interval) was 3.17 (1.72-5.83) for within-person periods of domperidone use versus non-use in the case-crossover analysis. Compared with non-use of any study drug, current domperidone use was associated with sudden cardiac death in nested case-control and case

  12. Research on the function orientation of pumped-storage plant in China

    NASA Astrophysics Data System (ADS)

    Feng, Jun-shu; Bo, Yuan; Wu, Sheng-yu; Zhang, Fu-qiang; Hao, Wei-hua

    2017-01-01

    With the growth of electrical load and development of clean energy, peak regulation of power system has been paid more attention to, in which case pumped-storage plant becomes the most efficient and economical way against peak load and the ensurance of safe and stable system operation. However, the dispatch and operation mode of pumped-storage plant is a little unreasonable at present in our country, due to the insufficient acknowledge of plants’ function orientation in different regions. This paper studied the standard of classifying pumped-storage plants, by dividing the plant function into three types security oriented, peak shaving oriented and renewable energy accommodation oriented, based on the local load characteristic, structure of power supply, accommodating capability of renewable energy, nuclear energy, etc. Finally, according to the current and future development situation of five Chinese regions, the function orientation partition of pumped-storage plant is given, which has profound guiding and practical significance for pumped-storage plant dispatch and operation.

  13. Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast.

    PubMed

    Schuetzer-Muehlbauer, Manuela; Willinger, Birgit; Egner, Ralf; Ecker, Gerhard; Kuchler, Karl

    2003-09-01

    The enhanced efflux of antifungal drugs through ATP-binding cassette (ABC) transporters constitutes a major cause of clinical multidrug resistance (MDR). The inhibition of drug efflux pumps by specific compounds is considered to be a feasible strategy to overcome clinical antifungal resistance. Therefore, several blockers of mammalian and yeast ABC drug pumps, including FK506, propafenones, as well as the antifungal drug terbinafine were tested for their capacity to reverse CDR-mediated azole resistance in bakers yeast and in clinical isolates of Candida albicans. We have functionally expressed the C. albicans Cdr1p and Cdr2p transporters in hypersensitive Saccharomyces cerevisiae recipient strains lacking several endogenous ABC pumps. Cdr1p and Cdr2p were functional in yeast, as they conferred pronounced drug resistance to known antifungal drugs, including azoles and terbinafine. We employ two functional assays to demonstrate that ABC pump inhibitors reverse CDR-mediated antifungal resistance, thereby restoring drug susceptibility of yeast cells and resistant clinical isolates. Our results suggest that reversal of antifungal resistance can be achieved through ABC pump-dependent and independent mechanisms.

  14. Pulmonary function and adverse cardiovascular outcomes: Can cardiac function explain the link?

    PubMed

    Burroughs Peña, Melissa S; Dunning, Allison; Schulte, Phillip J; Durheim, Michael T; Kussin, Peter; Checkley, William; Velazquez, Eric J

    2016-12-01

    The complex interaction between pulmonary function, cardiac function and adverse cardiovascular events has only been partially described. We sought to describe the association between pulmonary function with left heart structure and function, all-cause mortality and incident cardiovascular hospitalization. This study is a retrospective analysis of patients evaluated in a single tertiary care medical center. We used multivariable linear regression analyses to examine the relationship between FVC and FEV1 with left ventricular ejection fraction (LVEF), left ventricular internal dimension in systole and diastole (LVIDS, LVIDD) and left atrial diameter, adjusting for baseline characteristics, right ventricular function and lung hyperinflation. We also used Cox proportional hazards models to examine the relationship between FVC and FEV1 with all-cause mortality and cardiac hospitalization. A total of 1807 patients were included in this analysis with a median age of 61 years and 50% were female. Decreased FVC and FEV1 were both associated with decreased LVEF. In individuals with FVC less than 2.75 L, decreased FVC was associated with increased all-cause mortality after adjusting for left and right heart echocardiographic variables (hazard ratio [HR] 0.49, 95% CI 0.29, 0.82, respectively). Decreased FVC was associated with increased cardiac hospitalization after adjusting for left heart size (HR 0.80, 95% CI 0.67, 0.96), even in patients with normal LVEF (HR 0.75, 95% CI 0.57, 0.97). In a tertiary care center reduced pulmonary function was associated with adverse cardiovascular events, a relationship that is not fully explained by left heart remodeling or right heart dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Platelet endothelial cell adhesion molecule-1 mediates endothelial-cardiomyocyte communication and regulates cardiac function.

    PubMed

    McCormick, Margaret E; Collins, Caitlin; Makarewich, Catherine A; Chen, Zhongming; Rojas, Mauricio; Willis, Monte S; Houser, Steven R; Tzima, Ellie

    2015-01-19

    Dilated cardiomyopathy is characterized by impaired contractility of cardiomyocytes, ventricular chamber dilatation, and systolic dysfunction. Although mutations in genes expressed in the cardiomyocyte are the best described causes of reduced contractility, the importance of endothelial-cardiomyocyte communication for proper cardiac function is increasingly appreciated. In the present study, we investigate the role of the endothelial adhesion molecule platelet endothelial cell adhesion molecule (PECAM-1) in the regulation of cardiac function. Using cell culture and animal models, we show that PECAM-1 expressed in endothelial cells (ECs) regulates cardiomyocyte contractility and cardiac function via the neuregulin-ErbB signaling pathway. Conscious echocardiography revealed left ventricular (LV) chamber dilation and systolic dysfunction in PECAM-1(-/-) mice in the absence of histological abnormalities or defects in cardiac capillary density. Despite deficits in global cardiac function, cardiomyocytes isolated from PECAM-1(-/-) hearts displayed normal baseline and isoproterenol-stimulated contractility. Mechanistically, absence of PECAM-1 resulted in elevated NO/ROS signaling and NRG-1 release from ECs, which resulted in augmented phosphorylation of its receptor ErbB2. Treatment of cardiomyocytes with conditioned media from PECAM-1(-/-) ECs resulted in enhanced ErbB2 activation, which was normalized by pre-treatment with an NRG-1 blocking antibody. To determine whether normalization of increased NRG-1 levels could correct cardiac function, PECAM-1(-/-) mice were treated with the NRG-1 blocking antibody. Echocardiography showed that treatment significantly improved cardiac function of PECAM-1(-/-) mice, as revealed by increased ejection fraction and fractional shortening. We identify a novel role for PECAM-1 in regulating cardiac function via a paracrine NRG1-ErbB pathway. These data highlight the importance of tightly regulated cellular communication for proper

  16. Comparison of cardiac output measures by transpulmonary thermodilution, pulse contour analysis, and pulmonary artery thermodilution during off-pump coronary artery bypass surgery: a subgroup analysis of the cardiovascular anaesthesia registry at a single tertiary centre.

    PubMed

    Cho, Youn Joung; Koo, Chang-Hoon; Kim, Tae Kyong; Hong, Deok Man; Jeon, Yunseok

    2016-12-01

    tracking the changes thereof when compared with pulmonary artery bolus thermodilution in patients with preserved cardiac function during off-pump coronary artery bypass surgery. Trial registration NCT01713192 (ClinicalTrials.gov).

  17. Cardiac function during resuscitation from hemorrhagic shock with polymerized bovine hemoglobin-based oxygen therapeutic.

    PubMed

    Ao-Ieong, Eilleen S Y; Williams, Alexander; Jani, Vivek; Cabrales, Pedro

    2017-06-01

    Hemorrhage impairs myocardial contractile function and decreases oxygen delivery. This study investigates how polymerized bovine hemoglobin (PolyHb) solutions affect cardiac function after resuscitation from hemorrhagic shock (HS). Hamsters were hemorrhaged and resuscitated with PolyHb at 8.5 g/dL and 11.5 g/dL. Left ventricle (LV) function was assessed during shock and resuscitation using a miniaturize conductance catheter. PolyHb resuscitation had no beneficial effects in cardiac function; it increased cardiac afterload and systemic vascular resistance (SVR) of 46 and 116% for 8.5 and 11.5 g/dL, respectively. Study findings indicate that preclinical evaluation of cardiac function is essential to develop safe and efficacious alternatives to blood transfusion.

  18. Estrogen-Related Receptor α (ERRα) and ERRγ Are Essential Coordinators of Cardiac Metabolism and Function

    PubMed Central

    Wang, Ting; McDonald, Caitlin; Petrenko, Nataliya B.; Leblanc, Mathias; Wang, Tao; Giguere, Vincent; Evans, Ronald M.; Patel, Vickas V.

    2015-01-01

    Almost all cellular functions are powered by a continuous energy supply derived from cellular metabolism. However, it is little understood how cellular energy production is coordinated with diverse energy-consuming cellular functions. Here, using the cardiac muscle system, we demonstrate that nuclear receptors estrogen-related receptor α (ERRα) and ERRγ are essential transcriptional coordinators of cardiac energy production and consumption. On the one hand, ERRα and ERRγ together are vital for intact cardiomyocyte metabolism by directly controlling expression of genes important for mitochondrial functions and dynamics. On the other hand, ERRα and ERRγ influence major cardiomyocyte energy consumption functions through direct transcriptional regulation of key contraction, calcium homeostasis, and conduction genes. Mice lacking both ERRα and cardiac ERRγ develop severe bradycardia, lethal cardiomyopathy, and heart failure featuring metabolic, contractile, and conduction dysfunctions. These results illustrate that the ERR transcriptional pathway is essential to couple cellular energy metabolism with energy consumption processes in order to maintain normal cardiac function. PMID:25624346

  19. Characterization of the RND family of multidrug efflux pumps: in silico to in vivo confirmation of four functionally distinct subgroups.

    PubMed

    Godoy, Patricia; Molina-Henares, Antonio J; de la Torre, Jesús; Duque, Estrella; Ramos, Juan L

    2010-11-01

    We have developed a generalized profile that identifies members of the root-nodulation-cell-division (RND) family of efflux pumps and classifies them into four functional subfamilies. According to Z-score values, efflux pumps can be grouped by their metabolic function, thus making it possible to distinguish pumps involved in antibiotic resistance (group 1) from those involved in metal resistance (group 3). In silico data regarding efflux pumps in group 1 were validated after identification of RND efflux pumps in a number of environmental microbes that were isolated as resistant to ethidium bromide. Analysis of the Pseudomonas putida KT2440 genome identified efflux pumps in all groups. A collection of mutants in efflux pumps and a screening platform consisting of 50 drugs were created to assign a function to the efflux pumps. We validated in silico data regarding efflux pumps in groups 1 and 3 using 9 different mutants. Four mutants belonging to group 2 were found to be more sensitive than the wild-type to oxidative stress-inducing agents such as bipyridyl and methyl viologen. The two remaining mutants belonging to group 4 were found to be more sensitive than the parental to tetracycline and one of them was particularly sensitive to rubidium and chromate. By effectively combining in vivo data with generalized profiles and gene annotation data, this approach allowed the assignment, according to metabolic function, of both known and uncharacterized RND efflux pumps into subgroups, thereby providing important new insight into the functions of proteins within this family.

  20. The origin and function of calmodulin regulated Ca2+ pumps in plants.

    PubMed

    Boursiac, Yann; Harper, Jeffrey F

    2007-12-01

    While Ca2+ signaling plays an important role in both plants and animals, the machinery that codes and decodes these signals have evolved to show interesting differences and similarities. For example, typical plant and animal cells both utilize calmodulin (CaM)-regulated Ca2+ pumps at the plasma membrane to help control cytoplasmic Ca2+ levels. However, in flowering plants this family of pumps has evolved with a unique structural arrangement in which the regulatory domain is located at the N-terminal instead of C-terminal end. In addition, some of the plant isoforms have evolved to function at endomembrane locations. For the 14 Ca2+ pumps present in the model plant Arabidopsis, molecular genetic analyses are providing exciting insights into their function in diverse aspects of plant growth and development.

  1. Myocardin-related transcription factors are required for cardiac development and function.

    PubMed

    Mokalled, Mayssa H; Carroll, Kelli J; Cenik, Bercin K; Chen, Beibei; Liu, Ning; Olson, Eric N; Bassel-Duby, Rhonda

    2015-10-15

    Myocardin-Related Transcription Factors A and B (MRTF-A and MRTF-B) are highly homologous proteins that function as powerful coactivators of serum response factor (SRF), a ubiquitously expressed transcription factor essential for cardiac development. The SRF/MRTF complex binds to CArG boxes found in the control regions of genes that regulate cytoskeletal dynamics and muscle contraction, among other processes. While SRF is required for heart development and function, the role of MRTFs in the developing or adult heart has not been explored. Through cardiac-specific deletion of MRTF alleles in mice, we show that either MRTF-A or MRTF-B is dispensable for cardiac development and function, whereas deletion of both MRTF-A and MRTF-B causes a spectrum of structural and functional cardiac abnormalities. Defects observed in MRTF-A/B null mice ranged from reduced cardiac contractility and adult onset heart failure to neonatal lethality accompanied by sarcomere disarray. RNA-seq analysis on neonatal hearts identified the most altered pathways in MRTF double knockout hearts as being involved in cytoskeletal organization. Together, these findings demonstrate redundant but essential roles of the MRTFs in maintenance of cardiac structure and function and as indispensible links in cardiac cytoskeletal gene regulatory networks. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Functional Relevance of Coronary Artery Disease by Cardiac Magnetic Resonance and Cardiac Computed Tomography: Myocardial Perfusion and Fractional Flow Reserve

    PubMed Central

    Andreini, Daniele; Bertella, Erika; Mushtaq, Saima; Guaricci, Andrea Igoren; Pepi, Mauro

    2015-01-01

    Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality and it is responsible for an increasing resource burden. The identification of patients at high risk for adverse events is crucial to select those who will receive the greatest benefit from revascularization. To this aim, several non-invasive functional imaging modalities are usually used as gatekeeper to invasive coronary angiography, but the diagnostic yield of elective invasive coronary angiography remains unfortunately low. Stress myocardial perfusion imaging by cardiac magnetic resonance (stress-CMR) has emerged as an accurate technique for diagnosis and prognostic stratification of the patients with known or suspected CAD thanks to high spatial and temporal resolution, absence of ionizing radiation, and the multiparametric value including the assessment of cardiac anatomy, function, and viability. On the other side, cardiac computed tomography (CCT) has emerged as unique technique providing coronary arteries anatomy and more recently, due to the introduction of stress-CCT and noninvasive fractional flow reserve (FFR-CT), functional relevance of CAD in a single shot scan. The current review evaluates the technical aspects and clinical experience of stress-CMR and CCT in the evaluation of functional relevance of CAD discussing the strength and weakness of each approach. PMID:25692133

  3. Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation.

    PubMed

    Moak, Jeffrey P; Goldstein, David S; Eldadah, Basil A; Saleem, Ahmed; Holmes, Courtney; Pechnik, Sandra; Sharabi, Yehonatan

    2007-12-01

    Power spectral analysis of heart rate variability (HRV) has been used to indicate cardiac autonomic function. High-frequency power relates to respiratory sinus arrhythmia and therefore to parasympathetic cardiovagal tone; however, the relationship of low-frequency (LF) power to cardiac sympathetic innervation and function has been controversial. Alternatively, LF power might reflect baroreflexive modulation of autonomic outflows. We studied normal volunteers and chronic autonomic failure syndrome patients with and without loss of cardiac noradrenergic nerves to examine the relationships of LF power with cardiac sympathetic innervation and baroreflex function. We compared LF power of HRV in patients with cardiac sympathetic denervation, as indicated by low myocardial concentrations of 6-[(18)F] fluorodopamine-derived radioactivity or low rates of norepinephrine entry into coronary sinus plasma (cardiac norepinephrine spillover) to values in patients with intact innervation, at baseline, during infusion of yohimbine, which increases exocytotic norepinephrine release from sympathetic nerves, or during infusion of tyramine, which increases non-exocytotic release. Baroreflex-cardiovagal slope (BRS) was calculated from the cardiac interbeat interval and systolic pressure during the Valsalva maneuver. LF power was unrelated to myocardial 6-[(18)F] fluorodopamine-derived radioactivity or cardiac norepinephrine spillover. In contrast, the log of LF power correlated positively with the log of BRS (r=0.72, P <0.0001). Patients with a low BRS (cardiac innervation. Tyramine and yohimbine increased LF power in subjects with normal BRS but not in those with low BRS. BRS at baseline predicted LF responses to tyramine and yohimbine. LF power reflects baroreflex function, not cardiac sympathetic innervation.

  4. Regulatory effects of phospholamban on cardiac function in intact mice.

    PubMed

    Lorenz, J N; Kranias, E G

    1997-12-01

    Phospholamban (PLB) regulates Ca(2+)-adenosinetriphosphatase activity in cardiac sarcoplasmic reticulum and participates in the regulation of myocardial performance. Animal models with altered levels of PLB permit in vivo evaluation of the physiological role of PLB. This study examined left ventricular (LV) performance in intact PLB heterozygous and homozygous mice under basal and stimulated conditions. A Millar Mikro-Tip transducer was inserted into the right carotid artery and advanced into the LV for direct measurement of ventricular pressure and the first derivative of intraventricular pressure (dP/dt). Baseline blood pressures were increased in PLB heterozygotes and even more so in PLB homozygotes compared with wild types (WT), and there were no differences in heart rate or LV end-diastolic pressure. The increase in pressure was primarily caused by an increase in systolic pressure. Baseline values for positive and negative dP/dt were linearly correlated with PLB levels. In PLB heterozygotes, contractile response to isoproterenol (Iso) was blunted compared with WT, but maximum rates of contraction were similar between the two groups. Contractile performance in PLB homozygous mice, which under baseline conditions was similar to maximum levels seen in WT, showed a blunted response to Iso, and maximum rates of contraction were significantly greater than in either of the other groups, indicating an essential but perhaps not exclusive role for PLB in mediating the inotropic effects of beta-adrenergic agonists. The effects of Iso on negative dP/dt were also blunted in both PLB heterozygous and PLB homozygous animals. Our results demonstrate that myocardial function in highly dependent on PLB level and suggest that the cardiovascular effects of PLB perturbations are largely uncompensated for in the intact mouse.

  5. Genetic Variants Associated With Cardiac Structure and Function

    PubMed Central

    Vasan, Ramachandran S.; Glazer, Nicole L.; Felix, Janine F.; Lieb, Wolfgang; Wild, Philipp S.; Felix, Stephan B.; Watzinger, Norbert; Larson, Martin G.; Smith, Nicholas L.; Dehghan, Abbas; Großhennig, Anika; Schillert, Arne; Teumer, Alexander; Schmidt, Reinhold; Kathiresan, Sekar; Lumley, Thomas; Aulchenko, Yurii S.; König, Inke R.; Zeller, Tanja; Homuth, Georg; Struchalin, Maksim; Aragam, Jayashri; Bis, Joshua C.; Rivadeneira, Fernando; Erdmann, Jeanette; Schnabel, Renate B.; Dörr, Marcus; Zweiker, Robert; Lind, Lars; Rodeheffer, Richard J.; Greiser, Karin Halina; Levy, Daniel; Haritunians, Talin; Deckers, Jaap W.; Stritzke, Jan; Lackner, Karl J.; Völker, Uwe; Ingelsson, Erik; Kullo, Iftikhar; Haerting, Johannes; O’Donnell, Christopher J.; Heckbert, Susan R.; Stricker, Bruno H.; Ziegler, Andreas; Reffelmann, Thorsten; Redfield, Margaret M.; Werdan, Karl; Mitchell, Gary F.; Rice, Kenneth; Arnett, Donna K.; Hofman, Albert; Gottdiener, John S.; Uitterlinden, Andre G.; Meitinger, Thomas; Blettner, Maria; Friedrich, Nele; Wang, Thomas J.; Psaty, Bruce M.; van Duijn, Cornelia M.; Wichmann, H.-Erich; Munzel, Thomas F.; Kroemer, Heyo K.; Benjamin, Emelia J.; Rotter, Jerome I.; Witteman, Jacqueline C.; Schunkert, Heribert; Schmidt, Helena; Völzke, Henry; Blankenberg, Stefan

    2010-01-01

    Context Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n=12 612 individuals of European ancestry; 55% women, aged 26–95 years; examinations between 1978–2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n=4094 people of European ancestry). Using a prespecified P value threshold of 5×10−7 to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. Main Outcome Measures Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. Results In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). Conclusions We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate

  6. The effect of age on the relationship between cardiac and vascular function

    PubMed Central

    Houghton, David; Jones, Thomas W.; Cassidy, Sophie; Siervo, Mario; MacGowan, Guy A.; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age-related changes in cardiac and vascular function are associated with increased risk of cardiovascular mortality and morbidity. The aim of the present study was to define the effect of age on the relationship between cardiac and vascular function. Haemodynamic and gas exchange measurements were performed at rest and peak exercise in healthy individuals. Augmentation index was measured at rest. Cardiac power output, a measure of overall cardiac function, was calculated as the product of cardiac output and mean arterial blood pressure. Augmentation index was significantly higher in older than younger participants (27.7 ± 10.1 vs. 2.5 ± 10.1%, P < 0.01). Older people demonstrated significantly higher stroke volume and mean arterial blood pressure (P < 0.05), but lower heart rate (145 ± 13 vs. 172 ± 10 beats/min, P < 0.01) and peak oxygen consumption (22.5 ± 5.2 vs. 41.2 ± 8.4 ml/kg/min, P < 0.01). There was a significant negative relationship between augmentation index and peak exercise cardiac power output (r = −0.73, P = 0.02) and cardiac output (r = −0.69, P = 0.03) in older participants. Older people maintain maximal cardiac function due to increased stroke volume. Vascular function is a strong predictor of overall cardiac function in older but in not younger people. PMID:26590322

  7. Effects of interleukin-37 on cardiac function after myocardial infarction in mice

    PubMed Central

    Xu, Daoying; Wang, Aiqin; Jiang, Fengqin; Hu, Junhong; Zhang, Xiuzhou

    2015-01-01

    Background: Interleukin-37 (IL-37) is a new discovered member of the interleukin family and plays anti-inflammatory effect in some inflammatory disease. A recent study found that IL-37 elevated significantly in peripheral blood of patients with acute myocardial infarction. We aimed to explore the effect IL-37 on cardiac function after mice myocardial infarction (MI) and its mechanism. Methods: Acute MI mouse model was established and divided into three groups: sham group, MI group and IL-37 treatment group. MPO expression was detected by immunohistochemistry; NF-κB signaling pathway was tested by Western blot; and cardiac function was measured by echocardiography. Results: Compared with MI mice, IL-37 treatment showed an obvious decrease of MPO expression, suppression of p-p65 expression, and improved cardiac function by decreasing left ventricular shortening fraction (LVFS). Conclusion: IL-37 may improve MI mice cardiac function via inhibition of inflammatory NF-κB signaling pathway. PMID:26191225

  8. Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels

    PubMed Central

    Maltsev, Alexander V.; Maltsev, Victor A.; Stern, Michael D.

    2017-01-01

    Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates. PMID:28792496

  9. Stabilization of diastolic calcium signal via calcium pump regulation of complex local calcium releases and transient decay in a computational model of cardiac pacemaker cell with individual release channels.

    PubMed

    Maltsev, Alexander V; Maltsev, Victor A; Stern, Michael D

    2017-08-01

    Intracellular Local Ca releases (LCRs) from sarcoplasmic reticulum (SR) regulate cardiac pacemaker cell function by activation of electrogenic Na/Ca exchanger (NCX) during diastole. Prior studies demonstrated the existence of powerful compensatory mechanisms of LCR regulation via a complex local cross-talk of Ca pump, release and NCX. One major obstacle to study these mechanisms is that LCR exhibit complex Ca release propagation patterns (including merges and separations) that have not been characterized. Here we developed new terminology, classification, and computer algorithms for automatic detection of numerically simulated LCRs and examined LCR regulation by SR Ca pumping rate (Pup) that provides a major contribution to fight-or-flight response. In our simulations the faster SR Ca pumping accelerates action potential-induced Ca transient decay and quickly clears Ca under the cell membrane in diastole, preventing premature releases. Then the SR generates an earlier, more synchronized, and stronger diastolic LCR signal activating an earlier and larger inward NCX current. LCRs at higher Pup exhibit larger amplitudes and faster propagation with more collisions to each other. The LCRs overlap with Ca transient decay, causing an elevation of the average diastolic [Ca] nadir to ~200 nM (at Pup = 24 mM/s). Background Ca (in locations lacking LCRs) quickly decays to resting Ca levels (<100 nM) at high Pup, but remained elevated during slower decay at low Pup. Release propagation is facilitated at higher Pup by a larger LCR amplitude, whereas at low Pup by higher background Ca. While at low Pup LCRs show smaller amplitudes, their larger durations and sizes combined with longer transient decay stabilize integrals of diastolic Ca and NCX current signals. Thus, the local interplay of SR Ca pump and release channels regulates LCRs and Ca transient decay to insure fail-safe pacemaker cell operation within a wide range of rates.

  10. Evaluation of the human fetal cardiac size and function.

    PubMed

    Veille, J C; Sivakoff, M; Nemeth, M

    1990-01-01

    Two-dimensional-directed M-mode echocardiography was done on 80 normal fetuses between the 17th to 42nd weeks of gestation. The M-mode beam transected the ventricles at the level of the chordae tendineae at the tip of atrioventricular valves. Right and left ventricular dimensions and free wall thicknesses correlated well with gestational age. Calculated measurements showed a good correlation of the stroke volume and cardiac output with gestational age. The right ventricular dimension, however, was significantly greater than the left ventricular one. Fractional shortening of the right and left ventricle did not change significantly with advancing gestational age. This study indicates that the human fetal right ventricle dimension, stroke volume, and cardiac output are slightly larger than that of the left ventricle. This study also suggests that the human fetus increases its cardiac output to match its growth and it does so by increasing ventricular size rather than fractional shortening or heart rate.

  11. Cardiac resynchronization therapy improves the uptake of MIBI-99mTc and cardiac function.

    PubMed

    Brandão, Simone Cristina Soares; Giorgi, Maria Clementina; Nishioka, Silvana D'Orio; Martinelli Filho, Martino; Soares, José; Meneghetti, José Cláudio

    2008-09-01

    This case shows the improvement promoted by cardiac resynchronization therapy (CRT) on myocardial perfusion and left ventricular (LV) performance assessed by gated myocardial perfusion scintigraphy. The patient had idiopathic dilated cardiomyopathy, left bundle branch block and severe heart failure despite optimized medical treatment. After CRT, clinical improvement, QRS reduction and improvement of previously hypoperfused anterior and septal walls were observed. There was also decrease in LV end-diastolic and systolic volumes and increase in LV ejection fraction.

  12. Clinical evaluation of the Spiral Pump® after improvements to the original project in patients submitted to cardiac surgeries with cardiopulmonary bypass

    PubMed Central

    Dinkhuysen, MD, PhD, Jarbas Jakson; de Andrade, Aron Jose Pazin; Leme, MsC, Juliana; Silva, Cibele; Medina, Claudia Sanches; Pereira, Cristiane Célia; Biscegli, PhD, José Francisco

    2014-01-01

    Objective The objective of this paper is to present the results from Spiral Pump clinical trial after design modifications performed at its previous project. This pump applies axial end centrifugal hydraulic effects for blood pumping during cardiopulmonary bypass for patients under cardiac surgery. Methods This study was performed in 52 patients (51% males), between 20 to 80 (67±14.4) years old weighing 53 to 102 (71.7±12.6) kg, mostly under myocardial revascularization surgery (34.6%) and valvular surgery (32.8%). Besides the routine evaluation of the data observed in these cases, we monitored pump rotational speed, blood flow, cardiopulmonary bypass duration, urine free hemoglobin for blood cell trauma analysis (+ to 4+), lactate desidrogenase (UI/L), fibrinogen level (mg/dL) and platelet count (nº/mm3). Results Besides maintaining appropriate blood pressure and metabolic parameters it was also observed that the Free Hemoglobin levels remained normal, with a slight increase after 90 minutes of cardiopulmonary bypass. The Lactate Dehydrogenase showed an increase, with medians varying between 550-770 IU/L, whereas the decrease in Fibrinogen showed medians of 130-100 mg/dl. The number of platelets showed a slight decrease with the medians ranging from 240,000 to 200,000/mm3. No difficulty was observed during perfusion terminations, nor were there any immediate deaths, and all patients except one, were discharged in good condition. CONCLUSION The Spiral Pump, as blood propeller during cardiopulmonary bypass, demonstrated to be reliable and safe, comprising in a good option as original and national product for this kind of application. PMID:25372905

  13. Disruption of ROCK1 gene attenuates cardiac dilation and improves contractile function in pathological cardiac hypertrophy.

    PubMed

    Shi, Jianjian; Zhang, Yi-Wei; Summers, Lelia J; Dorn, Gerald W; Wei, Lei

    2008-03-01

    The development of left ventricular cardiomyocyte hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response. However, persistent stress eventually leads to dilated heart failure, which is a common cause of heart failure in human hypertensive and valvular heart disease. We have recently reported that Rho-associated coiled-coil containing protein kinase 1 (ROCK1) homozygous knockout mice exhibited reduced cardiac fibrosis and cardiomyocyte apoptosis, while displaying a preserved compensatory hypertrophic response to pressure overload. In this study, we have tested the effects of ROCK1 deficiency on cardiac hypertrophy, dilation, and dysfunction. We have shown that ROCK1 deletion attenuated left ventricular dilation and contractile dysfunction, but not hypertrophy, in a transgenic model of Galphaq overexpression-induced hypertrophy which represents a well-characterized and highly relevant genetic mouse model of pathological hypertrophy. Although the development of cardiomyocyte hypertrophy was not affected, ROCK1 deletion in Galphaq mice resulted in a concentric hypertrophic phenotype associated with reduced induction of hypertrophic markers indicating that ROCK1 deletion could favorably modify hypertrophy without inhibiting it. Furthermore, ROCK1 deletion also improved contractile response to beta-adrenergic stimulation in Galphaq transgenic mice. Consistent with this observation, ROCK1 deletion prevented down-regulation of type V/VI adenylyl cyclase expression, which is associated with the impaired beta-adrenergic signaling in Galphaq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction.

  14. Functional possibilities for forming different inverse population distributions in diode-side-pumped laser heads

    SciTech Connect

    Grechin, S G; Nikolaev, P P; Sharandin, E A

    2014-10-31

    The functional possibilities of diode-side-pumped laser heads of solid-state lasers for forming inverse population distributions of different types are analysed. The invariants determining the relationship between the laser head parameters upon scaling are found. The results of comparative experimental studies are presented. (lasers)

  15. Functional Dissection of the Proton Pumping Modules of Mitochondrial Complex I

    PubMed Central

    Sokolova, Lucie; Zwicker, Klaus; Barth, Hans-Dieter; Morgner, Nina; Heide, Heinrich; Steger, Mirco; Nübel, Esther; Zickermann, Volker; Kerscher, Stefan; Brutschy, Bernhard; Radermacher, Michael; Brandt, Ulrich

    2011-01-01

    Mitochondrial complex I, the largest and most complicated proton pump of the respiratory chain, links the electron transfer from NADH to ubiquinone to the pumping of four protons from the matrix into the intermembrane space. In humans, defects in complex I are involved in a wide range of degenerative disorders. Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic complex I confirmed that the redox reactions are confined entirely to the hydrophilic peripheral arm of the L-shaped molecule and take place at a remarkable distance from the membrane domain. While this clearly implies that the proton pumping within the membrane arm of complex I is driven indirectly via long-range conformational coupling, the molecular mechanism and the number, identity, and localization of the pump-sites remains unclear. Here, we report that upon deletion of the gene for a small accessory subunit of the Yarrowia complex I, a stable subcomplex (nb8mΔ) is formed that lacks the distal part of the membrane domain as revealed by single particle analysis. The analysis of the subunit composition of holo and subcomplex by three complementary proteomic approaches revealed that two (ND4 and ND5) of the three subunits with homology to bacterial Mrp-type Na+/H+ antiporters that have been discussed as prime candidates for harbouring the proton pumps were missing in nb8mΔ. Nevertheless, nb8mΔ still pumps protons at half the stoichiometry of the complete enzyme. Our results provide evidence that the membrane arm of complex I harbours two functionally distinct pump modules that are connected in series by the long helical transmission element recently identified by X-ray structural analysis. PMID:21886480

  16. Nano-imaging of the beating mouse heart in vivo: Importance of sarcomere dynamics, as opposed to sarcomere length per se, in the regulation of cardiac function.

    PubMed

    Kobirumaki-Shimozawa, Fuyu; Oyama, Kotaro; Shimozawa, Togo; Mizuno, Akari; Ohki, Takashi; Terui, Takako; Minamisawa, Susumu; Ishiwata, Shin'ichi; Fukuda, Norio

    2016-01-01

    Sarcomeric contraction in cardiomyocytes serves as the basis for the heart's pump functions in mammals. Although it plays a critical role in the circulatory system, myocardial sarcomere length (SL) change has not been directly measured in vivo under physiological conditions because of technical difficulties. In this study, we developed a high speed (100-frames per second), high resolution (20-nm) imaging system for myocardial sarcomeres in living mice. Using this system, we conducted three-dimensional analysis of sarcomere dynamics in left ventricular myocytes during the cardiac cycle, simultaneously with electrocardiogram and left ventricular pressure measurements. We found that (a) the working range of SL was on the shorter end of the resting distribution, and (b) the left ventricular-developed pressure was positively correlated with the SL change between diastole and systole. The present findings provide the first direct evidence for the tight coupling of sarcomere dynamics and ventricular pump functions in the physiology of the heart.

  17. The impact of off-pump surgery in end-organ function: practical end-points.

    PubMed

    Parissis, Haralabos; Mbarushimana, Simon; Ramesh, Bandigowdanapalya C; Parissis, Mondrian; Lampridis, Savvas; Mhandu, Peter; Al-Alao, Bassel

    2015-11-10

    Most surgeons perform coronary bypass surgery with the aid of cardiopulmonary bypass, which inflicts a massive systemic inflammatory response to the body leading to adverse clinical outcome. In an attempt to make CABG less invasive, interest have been diverted to the off pump technique.The current review attempts to bring an insight onto the last ten years knowledge on the off-pump impact in end organ function, with an aim to draw some clear conclusions in order to allow practitioners to reflect on the subject.

  18. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction

    PubMed Central

    Martin, Kenneth; Turner, Elizebeth C.; Kumar, Arun H.; Browne, Tara; Caplice, Noel M.

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function. PMID:26407006

  19. Systemic and Cardiac Depletion of M2 Macrophage through CSF-1R Signaling Inhibition Alters Cardiac Function Post Myocardial Infarction.

    PubMed

    Leblond, Anne-Laure; Klinkert, Kerstin; Martin, Kenneth; Turner, Elizebeth C; Kumar, Arun H; Browne, Tara; Caplice, Noel M

    2015-01-01

    The heart hosts tissue resident macrophages which are capable of modulating cardiac inflammation and function by multiple mechanisms. At present, the consequences of phenotypic diversity in macrophages in the heart are incompletely understood. The contribution of cardiac M2-polarized macrophages to the resolution of inflammation and repair response following myocardial infarction remains to be fully defined. In this study, the role of M2 macrophages was investigated utilising a specific CSF-1 receptor signalling inhibition strategy to achieve their depletion. In mice, oral administration of GW2580, a CSF-1R kinase inhibitor, induced significant decreases in Gr1lo and F4/80hi monocyte populations in the circulation and the spleen. GW2580 administration also induced a significant depletion of M2 macrophages in the heart after 1 week treatment as well as a reduction of cardiac arginase1 and CD206 gene expression indicative of M2 macrophage activity. In a murine myocardial infarction model, reduced M2 macrophage content was associated with increased M1-related gene expression (IL-6 and IL-1β), and decreased M2-related gene expression (Arginase1 and CD206) in the heart of GW2580-treated animals versus vehicle-treated controls. M2 depletion was also associated with a loss in left ventricular contractile function, infarct enlargement, decreased collagen staining and increased inflammatory cell infiltration into the infarct zone, specifically neutrophils and M1 macrophages. Taken together, these data indicate that CSF-1R signalling is critical for maintaining cardiac tissue resident M2-polarized macrophage population, which is required for the resolution of inflammation post myocardial infarction and, in turn, for preservation of ventricular function.

  20. Cardiac tamponade (image)

    MedlinePlus

    Cardiac tamponade is a condition involving compression of the heart caused by blood or fluid accumulation in the space ... they cannot adequately fill or pump blood. Cardiac tamponade is an emergency condition that requires hospitalization.

  1. A portable cadmium telluride multidetector probe for cardiac function monitoring

    NASA Astrophysics Data System (ADS)

    Arntz, Y.; Chambron, J.; Dumitresco, B.; Eclancher, B.; Prat, V.

    1999-06-01

    A new nuclear stethoscope based on a matrix of small CdTe semiconductor detectors has been developed for studying the cardiac performance by gamma ventriculography at the equilibrium, in rest and stress conditions, in the early and recovery phases of the coronary disease and to follow the long-term therapy. The light-weight probe consists of an array of 64 detectors 5×5×2 mm grouped in 16 independent units in a lead shielded aluminum box including 16 preamplifiers. The probe is connected to an electronic box containing DC power supply, 16 channel amplifiers, discriminators and counters, two analog-triggering ECG channels, and interface to a PC. The left ventricle activity is, preferentially, detected by using a low-resolution matching convergent collimator. A physical evaluation of the probe has been performed, both with static tests and dynamically with a hydraulic home-built model of beating heart ventricle paced by a rhythm simulator. The sum of the 16 detectors activity provided a radiocardiogram (RCG) which well depicted the filling and ejection of the cardiac beats, allowing to compare the clinically relevant parameters of the cardiac performance, proportional variables of the stroke volume (SV), ejection fraction (EF) and ventricular flow-rate with the known absolute values programmed on the model. The portable system is now in operation for clinical assessment of cardiac patients.

  2. Rationally engineered Troponin C modulates in vivo cardiac function and performance in health and disease

    PubMed Central

    Shettigar, Vikram; Zhang, Bo; Little, Sean C.; Salhi, Hussam E.; Hansen, Brian J.; Li, Ning; Zhang, Jianchao; Roof, Steve R.; Ho, Hsiang-Ting; Brunello, Lucia; Lerch, Jessica K.; Weisleder, Noah; Fedorov, Vadim V.; Accornero, Federica; Rafael-Fortney, Jill A.; Gyorke, Sandor; Janssen, Paul M. L.; Biesiadecki, Brandon J.; Ziolo, Mark T.; Davis, Jonathan P.

    2016-01-01

    Treatment for heart disease, the leading cause of death in the world, has progressed little for several decades. Here we develop a protein engineering approach to directly tune in vivo cardiac contractility by tailoring the ability of the heart to respond to the Ca2+ signal. Promisingly, our smartly formulated Ca2+-sensitizing TnC (L48Q) enhances heart function without any adverse effects that are commonly observed with positive inotropes. In a myocardial infarction (MI) model of heart failure, expression of TnC L48Q before the MI preserves cardiac function and performance. Moreover, expression of TnC L48Q after the MI therapeutically enhances cardiac function and performance, without compromising survival. We demonstrate engineering TnC can specifically and precisely modulate cardiac contractility that when combined with gene therapy can be employed as a therapeutic strategy for heart disease. PMID:26908229

  3. Anesthetics alter the physical and functional properties of the Ca-ATPase in cardiac sarcoplasmic reticulum.

    PubMed Central

    Karon, B S; Geddis, L M; Kutchai, H; Thomas, D D

    1995-01-01

    We have studied the effects of the local anesthetic lidocaine, and the general anesthetic halothane, on the function and oligomeric state of the CA-ATPase in cardiac sarcoplasmic reticulum (SR). Oligomeric changes were detected by time-resolved phosphorescence anisotropy (TPA). Lidocaine inhibited and aggregated the Ca-ATPase in cardiac SR. Micromolar calcium or 0.5 M lithium chloride protected against lidocaine-induced inhibition, indicating that electrostatic interactions are essential to lidocaine inhibition of the Ca-ATPase. The phospholamban (PLB) antibody 2D12, which mimics PLB phosphorylation, had no effect on lidocaine inhibition of the Ca-ATPase in cardiac SR. Inhibition and aggregation of the Ca-ATPase in cardiac SR occurred at lower concentrations of lidocaine than necessary to inhibit and aggregate the Ca-ATPase in skeletal SR, suggesting that the cardiac isoform of the enzyme has a higher affinity for lidocaine. Halothane inhibited and aggregated the Ca-ATPase in cardiac SR. Both inhibition and aggregation of the Ca-ATPase by halothane were much greater in the presence of PLB antibody or when PLB was phosphorylated, indicating a protective effect of PLB on halothane-induced inhibition and aggregation. The effects of halothane on cardiac SR are opposite from the effects of halothane observed in skeletal SR, where halothane activates and dissociates the Ca-ATPase. These results underscore the crucial role of protein-protein interactions on Ca-ATPase regulation and anesthetic perturbation of cardiac SR. PMID:7756557

  4. Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

    PubMed

    Onofriescu, Mihai; Siriopol, Dimitrie; Voroneanu, Luminita; Hogas, Simona; Nistor, Ionut; Apetrii, Mugurel; Florea, Laura; Veisa, Gabriel; Mititiuc, Irina; Kanbay, Mehmet; Sascau, Radu; Covic, Adrian

    2015-01-01

    .29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

  5. Tetralogy of Fallot Cardiac Function Evaluation and Intelligent Diagnosis Based on Dual-Source Computed Tomography Cardiac Images.

    PubMed

    Cai, Ken; Rongqian, Yang; Li, Lihua; Xie, Zi; Ou, Shanxing; Chen, Yuke; Dou, Jianhong

    2016-05-01

    Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) of the cyanotic type. Studies on ventricular functions have received an increasing amount of attention as the development of diagnosis and treatment technology for CHD continues to advance. Reasonable options for imaging examination and accurate assessment of preoperative and postoperative left ventricular functions of TOF patients are important in improving the cure rate of TOF radical operation, therapeutic evaluation, and judgment prognosis. Therefore, with the aid of dual-source computed tomography (DSCT), cardiac images with high temporal resolution and high definition, we measured the left ventricular time-volume curve using image data and calculating the left ventricular function parameters to conduct the preliminary evaluation on TOF patients. To comprehensively evaluate the cardiac function, the segmental ventricular wall function parameters were measured, and the measurement results were mapped to a bull's eye diagram to realize the standardization of segmental ventricular wall function evaluation. Finally, we introduced a new clustering method based on auto-regression model parameters and combined this method with Euclidean distance measurements to establish an intelligent diagnosis of TOF. The results of this experiment show that the TOF evaluation and the intelligent diagnostic methods proposed in this article are feasible. Copyright © 2015 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

    PubMed Central

    Liu, Zuheng; Liu, Hai-Yue; Zhou, Haobin; Zhan, Qiong; Lai, Wenyan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2017-01-01

    Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD. PMID:28919891

  7. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice.

    PubMed

    Liu, Zuheng; Liu, Hai-Yue; Zhou, Haobin; Zhan, Qiong; Lai, Wenyan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2017-01-01

    Physical exercise is commonly regarded as protective against cardiovascular disease (CVD). Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI). Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma) that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  8. Artificial gravity with ergometric exercise preserves the cardiac, but not cerebrovascular, functions during 4 days of head-down bed rest.

    PubMed

    Yang, Chang-Bin; Wang, Yong-Chun; Gao, Yuan; Geng, Jie; Wu, Yan-Hong; Zhang, Yu; Shi, Fei; Sun, Xi-Qing

    2011-12-01

    Cardiovascular and musculoskeletal deconditioning occurring in long-term spaceflight requires new strategies to counteract these adverse effects. We previously reported that a short-arm centrifuge produced artificial gravity (AG), together with ergometer, has an approving effect on promoting cardiovascular function. The current study sought to investigate whether the cardiac and cerebrovascular functions were maintained and improved using a strategy of AG combined with exercise training on cardiovascular function during 4-day head-down bed rest (HDBR). Twelve healthy male subjects were assigned to a control group (CONT, n=6) and an AG combined with ergometric exercise training group (CM, n=6). Simultaneously, cardiac pumping and systolic functions, cerebral blood flow were measured before, during, and after HDBR. The results showed that AG combined with ergometric exercise caused an increase trend of number of tolerance, however, there was no significant difference between the two groups. After 4-day HDBR in the CONT group, heart rate increased significantly (59±6 vs 66±7 beats/min), while stroke volume (98±12 vs 68±13 mL) and cardiac output (6±1 vs 4±1 L/min) decreased significantly (p<0.05). All subjects had similar drops on cerebral vascular function. Volume regulating hormone aldosterone increased in both groups (by 119.9% in CONT group and 112.8% in the CM group), but only in the CONT group there were a significant changes (p<0.05). Angiotensin II was significantly increased by 140.5% after 4-day HDBR in the CONT group (p<0.05), while no significant changes were observed in the CM group. These results indicated that artificial gravity with ergometric exercise successfully eliminated changes induced by simulated weightlessness in heart rate, volume regulating hormones, and cardiac pumping function and partially maintained cardiac systolic function. Hence, a daily 1h alternating +1.0 and +2.0 Gz with 40 W exercise training appear to be an effective

  9. Cardiac proteasome functional insufficiency plays a pathogenic role in diabetic cardiomyopathy.

    PubMed

    Li, Jie; Ma, Wenxia; Yue, Guihua; Tang, Yaoliang; Kim, Il-Man; Weintraub, Neal L; Wang, Xuejun; Su, Huabo

    2017-01-01

    Diabetic cardiomyopathy is a major risk factor in diabetic patients but its pathogenesis remains poorly understood. The ubiquitin-proteasome system (UPS) facilitates protein quality control by degrading unnecessary and damaged proteins in eukaryotic cells, and dysfunction of UPS is implicated in various cardiac diseases. However, the overall functional status of the UPS and its pathophysiological role in diabetic cardiomyopathy have not been determined. Type I diabetes was induced in wild-type and transgenic mice expressing a UPS functional reporter (GFPdgn) by injections of streptozotocin (STZ). STZ-induced diabetes progressively impaired cardiac UPS function as evidenced by the accumulation of GFPdgn proteins beginning two weeks after diabetes induction, and by a buildup of total and lysine (K) 48-linked polyubiquitinated proteins in the heart. To examine the functional role of the UPS in diabetic cardiomyopathy, cardiac overexpression of PA28α (PA28αOE) was used to enhance proteasome function in diabetic mouse hearts. PA28αOE diabetic mice displayed exhibited restoration of cardiac UPS function, as demonstrated by the diminished accumulation of GFPdgn and polyubiquitinated proteins. Moreover, PA28αOE diabetic mice exhibited reduced myocardial collagen deposition, decreased cardiomyocyte apoptosis, and improved cardiac systolic and diastolic function. Impairment of cardiac UPS function is an early event in STZ-induced diabetes. Overexpression of PA28α attenuates diabetes-induced proteotoxic stress and cardiomyopathy, suggesting a potential therapeutic role for enhancement of cardiac proteasome function in this disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Performance of Automated Software in the Assessment of Segmental Left Ventricular Function in Cardiac CT: Comparison with Cardiac Magnetic Resonance.

    PubMed

    Wang, Rui; Meinel, Felix G; Schoepf, U Joseph; Canstein, Christian; Spearman, James V; De Cecco, Carlo N

    2015-12-01

    To evaluate the accuracy, reliability and time saving potential of a novel cardiac CT (CCT)-based, automated software for the assessment of segmental left ventricular function compared to visual and manual quantitative assessment of CCT and cardiac magnetic resonance (CMR). Forty-seven patients with suspected or known coronary artery disease (CAD) were enrolled in the study. Wall thickening was calculated. Segmental LV wall motion was automatically calculated and shown as a colour-coded polar map. Processing time for each method was recorded. Mean wall thickness in both systolic and diastolic phases on polar map, CCT, and CMR was 9.2 ± 0.1 mm and 14.9 ± 0.2 mm, 8.9 ± 0.1 mm and 14.5 ± 0.1 mm, 8.3 ± 0.1 mm and 13.6 ± 0.1 mm, respectively. Mean wall thickening was 68.4 ± 1.5 %, 64.8 ± 1.4 % and 67.1 ± 1.4 %, respectively. Agreement for the assessment of LV wall motion between CCT, CMR and polar maps was good. Bland-Altman plots and ICC indicated good agreement between CCT, CMR and automated polar maps of the diastolic and systolic segmental wall thickness and thickening. The processing time using polar map was significantly decreased compared with CCT and CMR. Automated evaluation of segmental LV function with polar maps provides similar measurements to manual CCT and CMR evaluation, albeit with substantially reduced analysis time. • Cardiac computed tomography (CCT) can accurately assess segmental left ventricular wall function. • A novel automated software permits accurate and fast evaluation of wall function. • The software may improve the clinical implementation of segmental functional analysis.

  11. Scaffold Proteins Regulating Extracellular Regulated Kinase Function in Cardiac Hypertrophy and Disease

    PubMed Central

    Liang, Yan; Sheikh, Farah

    2016-01-01

    The mitogen activated protein kinase (MAPK)-extracellular regulated kinase 1/2 (ERK1/2) pathway is a central downstream signaling pathway that is activated in cardiac muscle cells during mechanical and agonist-mediated hypertrophy. Studies in genetic mouse models deficient in ERK-associated MAPK components pathway have further reinforced a direct role for this pathway in stress-induced cardiac hypertrophy and disease. However, more recent studies have highlighted that these signaling pathways may exert their regulatory functions in a more compartmentalized manner in cardiac muscle. Emerging data has uncovered specific MAPK scaffolding proteins that tether MAPK/ERK signaling specifically at the sarcomere and plasma membrane in cardiac muscle and show that deficiencies in these scaffolding proteins alter ERK activity and phosphorylation, which are then critical in altering the cardiac myocyte response to stress-induced hypertrophy and disease progression. In this review, we provide insights on ERK-associated scaffolding proteins regulating cardiac myofilament function and their impact on cardiac hypertrophy and disease. PMID:26973524

  12. Cardiac tamponade in a neonate: a dreadful condition—need for functional echo

    PubMed Central

    Iyer, Venkatesh Harohalli Aswathanarayana; Sharma, Deepa Mohan; Charki, Siddhu; Mohanty, Pankaj Kumar

    2014-01-01

    Cardiac tamponade is a clinical emergency. Detection of a swinging heart rate is one of the earliest markers of large pericardial effusion, in which the four cardiac chambers are free to float in a phasic manner. We present a case of a preterm baby, one of the twins, who developed sudden onset of deterioration in the form of swinging heart rate, fluctuation in blood pressure and desaturation, requiring emergency intubation and inotropic support. Bedside functional echo was performed, which demonstrated cardiac tamponade; an immediate echocardiography-guided tap was initiated and fluid was aspirated from the pericardial space. PMID:25535228

  13. Evaluation of ventricular wall stress and cardiac function in patients with dilated cardiomyopathy.

    PubMed

    Scardulla, Francesco; Rinaudo, Antonino; Pasta, Salvatore; Scardulla, Cesare

    2016-01-01

    Dilated cardiomyopathy is a heart disease characterized by both left ventricular dilatation and left ventricular systolic dysfunction, leading to cardiac remodeling and ultimately heart failure. We aimed to investigate the effect of dilated cardiomyopathy on the pump performance and myocardial wall mechanics using patient-specific finite element analysis. Results evinced pronounced end-systolic wall stress on left ventricular wall of patients with dilated cardiomyopathy as compared to that of normal hearts. In dilated cardiomyopathy, both end-diastolic and end-systolic pressure-volume relationships of left ventricle and right ventricle were shifted to the right compared to controls, suggesting reduced myocardial contractility. We hereby propose that finite element analysis represents a useful tool to assess the myocardial wall stress and cardiac work, which are responsible for progressive left ventricular deterioration and poor clinical course.

  14. Resveratrol, an activator of SIRT1, upregulates AMPK and improves cardiac function in heart failure.

    PubMed

    Gu, X S; Wang, Z B; Ye, Z; Lei, J P; Li, L; Su, D F; Zheng, X

    2014-01-21

    Reduced AMP-activated protein kinase (AMPK) expression has been shown to play a significant role in the cardiac dysfunction in heart failure. This study was designed to examine the effect of resveratrol, a potent activator of silent information regulator (SIRT1), on cardiac function and AMPK expression in heart failure. Adult male rat left anterior descending arteries were ligated, and they were fed with either a regular diet or a diet enriched with resveratrol. Heart failure was produced by myocardial infarction, and was associated with markedly increased AMPK and SIRT1 protein levels. Resveratrol treatment had a tremendous beneficial effect, both in terms of improving AMPK expression and on cardiac function. Decreased cardiac function and AMPK expression were also found in SIRT1 knockout (+/-) mice. In cultured cardiomyocytes, resveratrol increased AMPK and SIRT1 expressions, and overexpression of SIRT1 was found to be sufficient to activate AMPK in H9c2 cells. In contrast, pretreatment of cardiomyocytes with an SIRT1 antagonist, nicotinamide, blocked these beneficial effects of resveratrol. Therefore, the protective effects of resveratrol were found to be dependent on its ability to activate SIRT1 and improve AMPK expression. These results demonstrated that in heart failure, the enzymatic activity of cardiac SIRT1 is increased, which contributes to increased expression of AMPK, and resveratrol enhances the expression of AMPK and improves cardiac function through the activation of SIRT1.

  15. Analysis of Cardiac Myocyte Maturation Using CASAAV, A Platform for Rapid Dissection of Cardiac Myocyte Gene Function In Vivo.

    PubMed

    Guo, Yuxuan; VanDusen, Nathan J; Zhang, Lina; Gu, Weiliang; Sethi, Isha; Guatimosim, Silvia; Ma, Qing; Jardin, Blake D; Ai, Yulan; Zhang, Donghui; Chen, Biyi; Guo, Ang; Yuan, Guo-Cheng; Song, Long-Sheng; Pu, William T

    2017-03-29

    Rationale: Loss-of-function studies in cardiac myocytes (CMs) are currently limited by the need for appropriate conditional knockout alleles. The factors that regulate CM maturation are poorly understood. Prior studies on CM maturation have been confounded by heart dysfunction caused by whole organ gene inactivation. Objective: To develop a new technical platform to rapidly characterize cell-autonomous gene function in postnatal murine CMs and apply it to identify genes that regulate T-tubules, a hallmark of mature cardiac myocytes. Methods and Results: We developed CASAAV (CRISPR/Cas9-AAV9-based somatic mutagenesis), a platform in which AAV9 delivers tandem guide RNAs targeting a gene of interest and cardiac troponin T promoter (cTNT)-driven Cre to Rosa(Cas9GFP/Cas9GFP) neonatal mice. When directed against junctophilin-2 (Jph2), a gene previously implicated in T-tubule maturation, we achieved efficient, rapid, and CM-specific JPH2 depletion. High-dose AAV9 ablated JPH2 in 64% CMs and caused lethal heart failure, whereas low-dose AAV9 ablated JPH2 in 22% CMs and preserved normal heart function. In the context of preserved heart function, CMs lacking JPH2 developed T-tubules that were nearly morphologically normal, indicating that JPH2 does not have a major, cell-autonomous role in T-tubule maturation. However, in hearts with severe dysfunction, both AAV-transduced and non-transduced CMs exhibited T-tubule disruption, which was more severe in the transduced subset. These data indicate that cardiac dysfunction disrupts T-tubule structure, and that JPH2 protects T-tubules in this context. We then used CASAAV to screen 8 additional genes for required, cell-autonomous roles in T-tubule formation. We identified ryanodine receptor 2 (RYR2) as a novel, cell-autonomously required T-tubule maturation factor. Conclusions: CASAAV is a powerful tool to study cell-autonomous gene functions. Genetic mosaics are invaluable to accurately define cell-autonomous gene function. JPH2

  16. Cardiac size and function in pregnancy-induced hypertension.

    PubMed

    Veille, J C; Hosenpud, J D; Morton, M J

    1984-11-01

    The physiologic cardiac enlargement characteristic of normal pregnancy could result in important left ventricular dysfunction in the presence of elevated blood pressure. Using M-mode echocardiography, we measured left ventricular dimensions, fractional shortening, and radius-to-wall thickness ratio in 23 patients who had a diagnosis of pregnancy-induced hypertension at rest and during isometric exercise. Seventeen subjects with normal pregnancies were similarly studied and served as controls. The average gestation of patients with pregnancy-induced hypertension was 38 +/- 2 weeks, and that of control subjects was 37 +/- 1 weeks. The average age was 25 +/- 5 years for patients with pregnancy-induced hypertension, and that for control subjects was 29 +/- 4 years. The patients with pregnancy-induced hypertension did not show the normal eccentric cardiac enlargement observed during pregnancy; the average radius-to-wall thickness ratio was reduced in patients with pregnancy-induced hypertension. Fractional shortening, a reflection of ventricular performance, was maintained both at rest and during exercise in the hypertensive group. One patient, who did not show a reduced radius-to-wall thickness ratio, had marked reduction of left ventricular performance in the presence of severe pregnancy-induced hypertension. Left ventricular performance in most subjects with pregnancy-induced hypertension is normal. Preservation of left ventricular performance despite increased arterial pressure may be related to the absence of eccentric gestational cardiac enlargement.

  17. Temporal averaging of two-dimensional correlation functions for velocity vector imaging of cardiac blood flow.

    PubMed

    Takahashi, Hiroki; Hasegawa, Hideyuki; Kanai, Hiroshi

    2015-07-01

    Ultrasonic imaging of blood flow in the cardiac lumen is a very useful tool to evaluate the pumping function of the human heart. The speckle tracking technique makes it possible to estimate the blood velocity vector. However, a stable estimation of the velocity vector of blood flow is difficult because signal-to-noise ratios of echoes from tiny blood particles are low. In this study, the speckle tracking technique with averaging of multiple two-dimensional correlation functions was employed for stable estimation of the blood velocity vector. Multiple two-dimensional correlation functions can be averaged during a very short period by using the echo data acquired by high-frame-rate echocardiography with diverging beam transmission. A steady flow experiment using blood-mimicking fluid (mean fluid velocity 0.2 m/s, flow angle 56° from the transducer surface) was implemented to investigate the effect of the averaging of two-dimensional correlation functions at a frame rate of 6024 Hz. First, to examine the averaging duration required for stable estimation of the flow velocity vector, the accuracies of vector estimates were evaluated at different durations for averaging of two-dimensional correlation functions in the steady flow measurement. It was found that the proposed averaging process with an averaging duration of over 8 frames could reduce the directional error in vector estimation to almost half that of the conventional speckle tracking technique. In subsequent experiments, the averaging duration was set at 12 frames corresponding to 2 ms. Measurements of steady flow at higher velocities were further implemented. The steady flow measurements with higher flow velocities of 0.4 and 0.6 m/s were simulated by changing the frame interval of the echo data at a flow velocity of 0.2 m/s. Although the averaging duration was a mere 2 ms, directional errors at mean flow velocities of 0.2, 0.4, and 0.6 m/s were reduced significantly. In an in vivo experiment of the healthy

  18. The meaning of the turning point of the index of motor current amplitude curve in controlling a continuous flow pump or evaluation of left ventricular function.

    PubMed

    Endo, G J; Kojima, K; Nakamura, K; Matsuzaki, Y; Onitsuka, T

    2003-03-01

    In this series, we investigated the meaning of the t-point of index of motor current amplitude (ICA) curve from a point of view of flow rate on in vitro and in vivo studies. On mock circulation loop and left ventricular assist device (LVAD)-equipped pigs, we detected the t-point and compared the pump flow at the t-point with the simultaneous cardiac output. The pump flow at the t-point showed high correlation against the simultaneous cardiac output for in vitro or in vivo study. By detection of the t-point of the ICA curve and measuring or estimating the pump flow at t-point, the cardiac output may be assessed without any sensor in various cardiac conditions.

  19. c-Cbl Inhibition Improves Cardiac function and Survival in Response to Myocardial Ischemia

    PubMed Central

    Rafiq, Khadija; Kolpakov, Mikhail A; Seqqat, Rachid; Guo, Jianfen; Guo, Xinji; Qi, Zhao; Yu, Daohai; Mohapatra, Bhopal; Zutshi, Neha; An, Wei; Band, Hamid; Sanjay, Archana; Houser, Steven R; Sabri, Abdelkarim

    2014-01-01

    Background The proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiquitin ligase activity that targets receptor and non-receptor tyrosine kinases, resulting in their ubiquitination and down-regulation. However, the function of c-Cbl in the control of cardiac function is currently unknown. In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocardial ischemia. Methods and Results We show increased c-Cbl expression in human ischemic and dilated cardiomyopathy hearts and in response to pathological stress stimuli in mice. c-Cbl deficient mice demonstrated a more robust functional recovery after myocardial ischemia reperfusion injury, as well as significantly reduced myocyte apoptosis and improved cardiac function. Ubiquitination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and focal adhesion kinase, were significantly reduced in c-Cbl knockout mice. Inhibition of c-Cbl expression or its ubiquitin ligase activity in cardiac myocytes offered protection against H2O2 stress. Interestingly, c-Cbl deletion reduced the risk of death and increased cardiac functional recovery after chronic myocardial ischemia. This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogenesis and increased expression of vascular endothelial growth factor (VEGF)-a and VEGF receptor type 2 in the infarcted region. Conclusions c-Cbl activation promotes myocyte apoptosis, inhibits angiogenesis and causes adverse cardiac remodeling after myocardial infarction. These findings point to c-Cbl as a potential therapeutic target for the maintenance of cardiac function and remodeling after myocardial ischemia. PMID:24583314

  20. Cardiac function and tolerance to ischemia–reperfusion injury in chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Lennon-Edwards, Shannon L.; Edwards, David G.

    2014-01-01

    Background Cardiac dysfunction is an independent risk factor of ischemic heart disease and mortality in chronic kidney disease (CKD) patients, yet the relationship between impaired cardiac function and tolerance to ischemia–reperfusion (IR) injury in experimental CKD remains unclear. Methods Cardiac function was assessed in 5/6 ablation–infarction (AI) and sham male Sprague–Dawley rats at 20 weeks of age, 8 weeks post-surgery using an isolated working heart system. This included measures taken during manipulation of preload and afterload to produce left ventricular (LV) function curves as well as during reperfusion following a 15-min ischemic bout. In addition, LV tissue was used for biochemical tissue analysis. Results Cardiac function was impaired in AI animals during preload and afterload manipulations. Cardiac functional impairments persisted post-ischemia in the AI animals, and 36% of AI animals did not recover sufficiently to achieve aortic overflow following ischemia (versus 0% of sham animals). However, for those animals able to withstand the ischemic perturbation, no difference was observed in percent recovery of post-ischemic cardiac function between groups. Urinary NOx (nitrite + nitrate) excretion was lower in AI animals and accompanied by reduced LV endothelial nitric oxide synthase and NOx. LV antioxidants superoxide dismutase-1 and -2 were reduced in AI animals, whereas glutathione peroxidase-1/2 as well as NADPH-oxidase-4 and H2O2 were increased in these animals. Conclusions Impaired cardiac function appears to predispose AI rats to poor outcomes following short-duration ischemic insult. These findings could be, in part, mediated by increased oxidative stress via nitric oxide-dependent and -independent mechanisms. PMID:24151020

  1. Early postnatal rat ventricle resection leads to long‐term preserved cardiac function despite tissue hypoperfusion

    PubMed Central

    Zogbi, Camila; Saturi de Carvalho, Ana E. T.; Nakamuta, Juliana S.; Caceres, Viviane de M.; Prando, Silvana; Giorgi, Maria C. P.; Rochitte, Carlos E.; Meneghetti, Jose C.; Krieger, Jose E.

    2014-01-01

    Abstract One‐day‐old mice display a brief capacity for heart regeneration after apex resection. We sought to examine this response in a different model and to determine the impact of this early process on long‐term tissue perfusion and overall cardiac function in response to stress. Apical resection of postnatal rats at day 1 (P1) and 7 (P7) rendered 18 ± 1.0% and 16 ± 1.3% loss of cardiac area estimated by magnetic resonance imaging (MRI), respectively (P > 0.05). P1 was associated with evidence of cardiac neoformation as indicated by Troponin I and Connexin 43 expression at 21 days postresection, while in the P7 group mainly scar tissue replacement ensued. Interestingly, there was an apparent lack of uniform alignment of newly formed cells in P1, and we detected cardiac tissue hypoperfusion for both groups at 21 and 60 days postresection using SPECT scanning. Direct basal cardiac function at 60 days, when the early lesion is undetectable, was preserved in all groups, whereas under hemodynamic stress the degree of change on LVDEP, Stroke Volume and Stroke Work indicated diminished overall cardiac function in P7 (P < 0.05). Furthermore, the End‐Diastolic Pressure–Volume relationship and increased interstitial collagen deposition in P7 is consistent with increased chamber stiffness. Taken together, we provide evidence that early cardiac repair response to apex resection in rats also leads to cardiomyocyte neoformation and is associated to long‐term preservation of cardiac function despite tissue hypoperfusion. PMID:25168870

  2. Overhydration, Cardiac Function and Survival in Hemodialysis Patients

    PubMed Central

    Voroneanu, Luminita; Hogas, Simona; Nistor, Ionut; Apetrii, Mugurel; Florea, Laura; Veisa, Gabriel; Mititiuc, Irina; Kanbay, Mehmet; Sascau, Radu; Covic, Adrian

    2015-01-01

    patients in both univariate (HR = 2.46, 95%CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48–7.02 for RFO >17.4%) Cox regression analysis. Conclusions The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations. PMID:26274811

  3. Platelet function during cardiopulmonary bypass using multiple electrode aggregometry: comparison of centrifugal and roller pumps.

    PubMed

    Kehara, Hiromu; Takano, Tamaki; Ohashi, Noburo; Terasaki, Takamitsu; Amano, Jun

    2014-11-01

    Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β-thromboglobin (β-TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β-TG concentrations were similar 60 min after pump cessation and before sternotomy

  4. Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression.

    PubMed

    Byrne, Nikole J; Levasseur, Jody; Sung, Miranda M; Masson, Grant; Boisvenue, Jamie; Young, Martin E; Dyck, Jason R B

    2016-05-15

    Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result in the recovery of cardiac function, substrate metabolism, and transcriptional reprogramming as well as determined the temporal relationship of these changes. Male C57Bl/6 mice were subjected to either Sham or transverse aortic constriction (TAC) surgery to induce HF. After HF development, mice with severe HF (% ejection fraction < 30) underwent a second surgery to remove the aortic constriction (debanding, DB). Three weeks following DB, there was a near complete recovery of systolic and diastolic function, and gene expression of several markers for hypertrophy/HF were returned to values observed in healthy controls. Interestingly, pressure-overload-induced left ventricular hypertrophy (LVH) and cardiac substrate metabolism were restored at 1-week post-DB, which preceded functional recovery. The regression of severe HF is associated with early and dramatic improvements in cardiac energy metabolism and LVH normalization that precede restored cardiac function, suggesting that metabolic and structural improvements may be critical determinants for functional recovery. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

  5. Elevated expression of the metabolic regulator receptor-interacting protein 140 results in cardiac hypertrophy and impaired cardiac function.

    PubMed

    Fritah, Asmaà; Steel, Jennifer H; Nichol, Donna; Parker, Nadeene; Williams, Sharron; Price, Anthony; Strauss, Leena; Ryder, Timothy A; Mobberley, Margaret A; Poutanen, Matti; Parker, Malcolm; White, Roger

    2010-06-01

    Receptor-interacting protein 140 (RIP140) is a ligand-dependent cofactor for nuclear receptors that regulate networks of genes involved in cellular processes, including metabolism. An important role for RIP140 in metabolic control has been identified in RIP140 null mice, whose phenotypes include derepression of genes involved in energy mobilization or catabolism in adipocytes and a switch to more oxidative fibres in skeletal muscle. We hypothesized that ubiquitous expression of RIP140 would suppress metabolic processes, leading to defects in development or cellular function. The primary effect of exogenous expression of RIP140 mRNA (real-time PCR) and protein (western blotting) in transgenic mice is impaired postnatal heart function. There was rapid onset of cardiac hypertrophy and ventricular fibrosis, detected microscopically, in male RIP140 transgenic mice from 4 weeks of age, resulting in 25% mortality by 5 months. RIP140 exogenous expression in the heart leads to decreased mitochondria state III and state IV membrane potential and oxygen consumption. Quantitative PCR showed more than 50% reduced expression of genes involved in mitochondrial activity and fatty acid metabolism, including mitochondrial transcription factor A, cytochrome oxidase VIIa, cytochrome XII, CD36, medium-chain acyl dehydrogenase, and fatty acid transport protein, many of which are known targets for nuclear receptors, including peroxisome proliferator-activated receptors PPARalpha and PPARdelta and oestrogen-related receptors ERRalpha and ERRgamma. This study demonstrates that RIP140 is an important cofactor in postnatal cardiac function and that inhibition of the action of RIP140 may provide a model system to investigate specific interventions designed to prevent or delay the onset of cardiac disease.

  6. Posterior papillary muscle anchoring affects remote myofiber stress and pump function: finite element analysis.

    PubMed

    Pantoja, Joe Luis; Ge, Liang; Zhang, Zhihong; Morrel, William G; Guccione, Julius M; Grossi, Eugene A; Ratcliffe, Mark B

    2014-10-01

    The role of posterior papillary muscle anchoring (PPMA) in the management of chronic ischemic mitral regurgitation (CIMR) is controversial. We studied the effect of anchoring point direction and relocation displacement on left ventricular (LV) regional myofiber stress and pump function. Previously described finite element models of sheep 16 weeks after posterolateral myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring insertion plus different PPM anchoring techniques were simulated. Anchoring points tested included both commissures and the central anterior mitral annulus; relocation displacement varied from 10% to 40% of baseline diastolic distance from the PPM to the anchor points on the annulus. For each reconstruction scenario, myofiber stress in the MI, border zone, and remote myocardium as well as pump function were calculated. PPMA caused reductions in myofiber stress at end-diastole and end-systole in all regions of the left ventricle that were proportional to the relocation displacement. Although stress reduction was greatest in the MI region, it also occurred in the remote region. The maximum 40% displacement caused a slight reduction in LV pump function. However, with the correction of regurgitation by MA plus PPMA, there was an overall increase in forward stroke volume. Finally, anchoring point direction had no effect on myofiber stress or pump function. PPMA reduces remote myofiber stress, which is proportional to the absolute distance of relocation and independent of anchoring point. Aggressive use of PPMA techniques to reduce remote myofiber stress may accelerate reverse LV remodeling without impairing LV function. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Mechanical cardiac assistance.

    PubMed

    Sezai, Y

    1998-08-01

    In our institute, we have intensively introduced both pulsatile and non-pulsatile mechanical cardiac assist devices, such as the pneumatic ventricular assist device (VAD) and percutaneous cardiopulmonary support (PCPS), using a centrifugal pump. From various kinds of clinical views, these cases were estimated and evaluated retrospectively according to the weaning results, long-term survival rate and cause of death. Based upon our experiences and clinical results, an alternate strategy of mechanical cardiac assistance for severe heart failure is suggested as follows. In the case of post-cardiotomy cardiogenic shock or low output syndrome, PCPS system should be applied firstly under intra-aortic balloon pumping (IABP) assist for a maximum of 2-3 days. If the native cardiac function does not recover and more long-term support is needed, several types of VAD, which are more powerful and durable devices should be introduced, according to end organ function and expected support duration. In order to obtain better clinical results, we have to select an appropriate device depending on the limited availability of supporting duration. Generally speaking, centrifugal pumps can support in short-term duration, while pulsatile devices cover the broad spectrum of the supporting period. Pneumatic VADs can cover short-term to long-term support up to a year, and electric VADs can cover over 1 year, and can be used as a bridge to heart transplantation.

  8. Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery.

    PubMed

    Mauermann, Eckhard; Bolliger, Daniel; Fassl, Jens; Grapow, Martin; Seeberger, Esther E; Seeberger, Manfred D; Filipovic, Miodrag; Lurati Buse, Giovanna A L

    2017-10-01

    Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality. We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality. We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014-1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007-1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754-0.878] versus area under curve: 0.870 [95% confidence interval, 0.822-0.917], respectively; P

  9. Cardiac autonomic function in patients with diabetes improves with practice of comprehensive yogic breathing program

    PubMed Central

    Jyotsna, Viveka P.; Ambekar, Smita; Singla, Rajiv; Joshi, Ansumali; Dhawan, Anju; Kumar, Neeta; Deepak, K. K.; Sreenivas, V.

    2013-01-01

    Background: The aim of this study was to observe the effect comprehensive yogic breathing (Sudarshan Kriya Yoga [SKY] and Pranayam) had on cardiac autonomic functions in patients with diabetes. Materials and Methods: This is a prospective randomized controlled intervention trial. Cardiac autonomic functions were assessed in 64 diabetics. Patients were randomized into two groups, one group receiving standard therapy for diabetes and the other group receiving standard therapy for diabetes and comprehensive yogic breathing program. Standard therapy included dietary advice, brisk walking for 45 min daily, and administration of oral antidiabetic drugs. Comprehensive yogic breathing program was introduced to the participants through a course of 12 h spread over 3 days. It was an interactive session in which SKY, a rhythmic cyclical breathing, preceded by Pranayam is taught under the guidance of a certified teacher. Cardiac autonomic function tests were done before and after 6 months of intervention. Results: In the intervention group, after practicing the breathing techniques for 6 months, the improvement in sympathetic functions was statistically significant (P 0.04). The change in sympathetic functions in the standard therapy group was not significant (P 0.75). Parasympathetic functions did not show any significant change in either group. When both parasympathetic and sympathetic cardiac autonomic functions were considered, there was a trend toward improvement in patients following comprehensive yogic breathing program (P 0.06). In the standard therapy group, no change in cardiac autonomic functions was noted (P 0.99). Conclusion: Cardiac autonomic functions improved in patients with diabetes on standard treatment who followed the comprehensive yogic breathing program compared to patients who were on standard therapy alone. PMID:23869306

  10. Evaluation of cardiac function using transthoracic echocardiography in patients with myocardial injury secondary to methomyl poisoning.

    PubMed

    Lee, Dong Keon; Cho, Nam Hyub; Kim, Oh Hyun; Go, Jin; Kim, Tae Hoon; Cha, Kyoung Chul; Kim, Hyun; Lee, Kang Hyun; Hwang, Sung Oh; Cha, Yong Sung

    2015-07-01

    Generally, the mortality rate for cases of carbamate poisoning is low, but fatalities secondary to methomyl poisoning have been reported including a case report of cardiac toxicity following short-term exposure to methomyl. There have been no reports, however, regarding patterns of cardiac toxicity after exposure to methomyl. Therefore, we investigated the prevalence and patterns of myocardial injury using a biochemical marker, troponin I (TnI), and evaluated cardiac function using transthoracic echocardiography (TTE). We conducted a retrospective review of 14 consecutive methomyl poisoning cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between January 2009 and December 2013. On ECG analysis, ST depression and T-wave inversion were seen in five patients (35.7%) and one patient (7.1%), respectively. On cardiac biochemical marker analysis, initial TnI was elevated in 11 patients (78.6%). TTE was performed in nine patients among the 11 patients in whom TnI was found to be elevated. Of the nine patients that underwent TTE, three patients (33.3%) showed a reduced ejection fraction (EF), and RWMA was noted in two patients. There were two patients (22.2%) that had both reduced systolic function and RWMA. One patient did not regain normal systolic function on admission. None of the three patients with reduced EF received any specific treatment to support cardiac function. One patient expired due to pneumonia, and one patient was transferred as moribund. We followed up on 12 patients who survived to discharge for 6-44 months. One patient (8.3%) was died to follow-up, and 11 patients survived without any further complications. Methomyl exposure can cause direct myocardial injury and reversible cardiac dysfunction. Monitoring of TnI levels and TTE for evaluation of cardiac function may be useful in the workup of patients suffering from methomyl poisoning.

  11. Distribution functions in plasmas generated by a volume source of fission fragments. [in nuclear pumped lasers

    NASA Technical Reports Server (NTRS)

    Deese, J. E.; Hassan, H. A.

    1979-01-01

    The role played by fission fragments and electron distribution functions in nuclear pumped lasers is considered and procedures for their calculations are outlined. The calculations are illustrated for a He-3/Xe mixture where fission is provided by the He-3(n,p)H-3 reaction. Because the dominant ion in the system depends on the Xe fraction, the distribution functions cannot be determined without the simultaneous consideration of a detailed kinetic model. As is the case for wall sources of fission fragments, the resulting plasmas are essentially thermal but the electron distribution functions are non-Maxwellian.

  12. Cardiac function as related to adrenergic activity in hypertensive left ventricular hypertrophy.

    PubMed

    Agabiti-Rosei, E; Muiesan, M L; Romanelli, G; Castellano, M; Beschi, M; Alicandri, C; Muiesan, G

    1987-06-01

    Studies in experimental animals and in hypertensive patients have shown that changes in cardiac anatomy and function are not just a simple consequence of the increased pressure load. The activity of the sympathetic nervous system is one of the factors that may influence cardiac performance and also, possibly, the cardiac anatomy of hypertensive patients. Animal studies have strongly suggested a possible role of adrenergic factors in the development of left ventricular hypertrophy. In man, plasma catecholamines are usually higher in hypertensive patients with left ventricular hypertrophy, and a correlation between left ventricular mass and plasma noradrenaline has also been observed. The decrease of cardiac performance after acute beta blockade has been found to be directly related to basal plasma noradrenaline concentration. An impaired response to beta-adrenergic stimulation has been reported in hypertensive animals and has been confirmed in hypertensive patients with left ventricular hypertrophy.

  13. False dyssynchrony: problem with image-based cardiac functional analysis using x-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Kidoh, Masafumi; Shen, Zeyang; Suzuki, Yuki; Ciuffo, Luisa; Ashikaga, Hiroshi; Fung, George S. K.; Otake, Yoshito; Zimmerman, Stefan L.; Lima, Joao A. C.; Higuchi, Takahiro; Lee, Okkyun; Sato, Yoshinobu; Becker, Lewis C.; Fishman, Elliot K.; Taguchi, Katsuyuki

    2017-03-01

    We have developed a digitally synthesized patient which we call "Zach" (Zero millisecond Adjustable Clinical Heart) phantom, which allows for an access to the ground truth and assessment of image-based cardiac functional analysis (CFA) using CT images with clinically realistic settings. The study using Zach phantom revealed a major problem with image-based CFA: "False dyssynchrony." Even though the true motion of wall segments is in synchrony, it may appear to be dyssynchrony with the reconstructed cardiac CT images. It is attributed to how cardiac images are reconstructed and how wall locations are updated over cardiac phases. The presence and the degree of false dyssynchrony may vary from scan-to-scan, which could degrade the accuracy and the repeatability (or precision) of image-based CT-CFA exams.

  14. Dmpk gene deletion or antisense knockdown does not compromise cardiac or skeletal muscle function in mice

    PubMed Central

    Carrell, Samuel T.; Carrell, Ellie M.; Auerbach, David; Pandey, Sanjay K.; Bennett, C. Frank; Dirksen, Robert T.; Thornton, Charles A.

    2016-01-01

    Myotonic dystrophy type 1 (DM1) is a genetic disorder in which dominant-active DM protein kinase (DMPK) transcripts accumulate in nuclear foci, leading to abnormal regulation of RNA processing. A leading approach to treat DM1 uses DMPK-targeting antisense oligonucleotides (ASOs) to reduce levels of toxic RNA. However, basal levels of DMPK protein are reduced by half in DM1 patients. This raises concern that intolerance for further DMPK loss may limit ASO therapy, especially since mice with Dmpk gene deletion reportedly show cardiac defects and skeletal myopathy. We re-examined cardiac and muscle function in mice with Dmpk gene deletion, and studied post-maturity knockdown using Dmpk-targeting ASOs in mice with heterozygous deletion. Contrary to previous reports, we found no effect of Dmpk gene deletion on cardiac or muscle function, when studied on two genetic backgrounds. In heterozygous knockouts, the administration of ASOs reduced Dmpk expression in cardiac and skeletal muscle by > 90%, yet survival, electrocardiogram intervals, cardiac ejection fraction and muscle strength remained normal. The imposition of cardiac stress by pressure overload, or muscle stress by myotonia, did not unmask a requirement for DMPK. Our results support the feasibility and safety of using ASOs for post-transcriptional silencing of DMPK in muscle and heart. PMID:27522499

  15. Nicotine depresses the functions of multiple cardiac potassium channels.

    PubMed

    Wang, H; Shi, H; Wang, Z

    1999-01-01

    Nicotine is the main constituent of tobacco smoke responsible for the elevated risk of the cardiovascular disease and sudden coronary death associated with smoking, presumably by provoking cardiac arrhythmias. The cellular mechanisms may be related to the ability of nicotine to prolong action potentials and to depolarize membrane potential. However, the underlying ionic mechanisms remained unknown. We showed here that nicotine blocked multiple types of K+ currents, including the native currents in canine ventricular myocytes and the cloned channels expressed in Xenopus oocytes: A-type K+ currents (I(to)/Kv4.3), delayed rectifier K+ currents (I(Kr)/HERG) and inward rectifier K+ currents (I(K1)/Kir2.1). Most noticeably, nicotine at a concentration as low as of 10 nM significantly suppressed I(to) and Kv4.3 by approximately 20%. The effects of nicotine were independent of nicotinic receptor simulation or catecholamine release. Our results indicate that nicotine is a non-specific blocker of K+ channels and the inhibitory effects are the consequence of direct interactions between nicotine molecules and the channel proteins. Our study provided for the first time the evidence for the direct inhibition of cardiac K+ channels by nicotine and established a novel aspect of nicotine pharmacology.

  16. Functional interaction between charged nanoparticles and cardiac tissue: a new paradigm for cardiac arrhythmia?

    PubMed Central

    Ruenraroengsak, Pakatip; Shevchuk, Andrew I; Korchev, Yuri E; Lab, Max J; Tetley, Teresa D; Gorelik, Julia

    2016-01-01

    Aim To investigate the effect of surface charge of therapeutic nanoparticles on sarcolemmal ionic homeostasis and the initiation of arrhythmias. Materials & methods Cultured neonatal rat myocytes were exposed to 50 nm-charged polystyrene latex nanoparticles and examined using a combination of hopping probe scanning ion conductance microscopy, optical recording of action potential characteristics and patch clamp. Results Positively charged, amine-modified polystyrene latex nanoparticles showed cytotoxic effects and induced large-scale damage to cardiomyocyte membranes leading to calcium alternans and cell death. By contrast, negatively charged, carboxyl-modified polystyrene latex nanoparticles (NegNPs) were not overtly cytotoxic but triggered formation of 50–250-nm nanopores in the membrane. Cells exposed to NegNPs revealed pro-arrhythmic events, such as delayed afterdepolarizations, reduction in conduction velocity and pathological increment of action potential duration together with an increase in ionic current throughout the membrane, carried by the nanopores. Conclusion The utilization of charged nanoparticles is a novel concept for targeting cardiac excitability. However, this unique nanoscopic investigation reveals an altered electrophysiological substrate, which sensitized the heart cells towards arrhythmias. PMID:23140503

  17. Embryonic stem cells improve cardiac function in Doxorubicin-induced cardiomyopathy mediated through multiple mechanisms.

    PubMed

    Singla, Dinender K; Ahmed, Aisha; Singla, Reetu; Yan, Binbin

    2012-01-01

    Doxorubicin (DOX) is an effective antineoplastic agent used for the treatment of a variety of cancers. Unfortunately, its use is limited as this drug induces cardiotoxicity and heart failure as a side effect. There is no report that describes whether transplanted embryonic stem (ES) cells or their conditioned medium (CM) in DOX-induced cardiomyopathy (DIC) can repair and regenerate myocardium. Therefore, we transplanted ES cells or CM in DIC to examine apoptosis, fibrosis, cytoplasmic vacuolization, and myofibrillar loss and their associated Akt and ERK pathway. Moreover, we also determined activation of endogenous c-kit(+ve) cardiac stem cells (CSCs), levels of HGF and IGF-1, growth factors required for c-kit cell activation, and their differentiation into cardiac myocytes, which also contributes in cardiac regeneration and improved heart function. We generated DIC in C57Bl/6 mice (cumulative dose of DOX 12 mg/kg body weight, IP), and animals were treated with ES cells, CM, or cell culture medium in controls. Two weeks post-DIC, ES cells or CM transplanted hearts showed a significant (p < 0.05) decrease in cardiac apoptotic nuclei and their regulation with Akt and ERK pathway. Cardiac fibrosis observed in the ES cell or CM groups was significantly less compared with DOX and cell culture medium groups (p < 0.05). Next, cytoplasmic vacuolization and myofibrillar loss was reduced (p < 0.05) following treatment with ES cells or CM. Moreover, our data also demonstrated increased levels of c-kit(+ve) CSCs in ES cells or CM hearts and differentiated cardiac myocytes from these CSCs, suggesting endogenous cardiac regeneration. Importantly, the levels of HFG and IGF-1 were significantly increased in ES cells or CM transplanted hearts. In conclusion, we reported that transplanted ES cells or CM in DIC hearts significantly decreases various adverse pathological mechanisms as well as enhances cardiac regeneration that effectively contributes to improved heart function.

  18. Electromechanical Conditioning of Adult Progenitor Cells Improves Recovery of Cardiac Function After Myocardial Infarction.

    PubMed

    Llucià-Valldeperas, Aida; Soler-Botija, Carolina; Gálvez-Montón, Carolina; Roura, Santiago; Prat-Vidal, Cristina; Perea-Gil, Isaac; Sanchez, Benjamin; Bragos, Ramon; Vunjak-Novakovic, Gordana; Bayes-Genis, Antoni

    2017-03-01

    Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue-engineered construct with cardiac adipose tissue-derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time. Cardiac ATDPCs were electromechanically stimulated at 2-millisecond pulses of 50 mV/cm at 1 Hz and 10% stretching during 7 days. The cells were harvested, labeled, embedded in a fibrin hydrogel, and implanted over the infarcted area of the murine heart. A total of 39 animals were randomly distributed and sacrificed at 21 days: groups of grafts without cells and with stimulated or nonstimulated cells. Echocardiography and gene and protein analyses were also carried out. Physiologically stimulated ATDPCs showed increased expression of cardiac transcription factors, structural genes, and calcium handling genes. At 21 days after implantation, cardiac function (measured as left ventricle ejection fraction between presacrifice and post-MI) increased up to 12% in stimulated grafts relative to nontreated animals. Vascularization and integration with the host blood supply of grafts with stimulated cells resulted in increased vessel density in the infarct border region. Trained cells within the implanted fibrin patch expressed main cardiac markers and migrated into the underlying ischemic myocardium. To conclude, synchronous electromechanical cell conditioning before delivery may be a preferred alternative when considering strategies for heart repair after myocardial infarction. Stem Cells Translational Medicine 2017;6:970-981.

  19. Electromechanical Conditioning of Adult Progenitor Cells Improves Recovery of Cardiac Function After Myocardial Infarction

    PubMed Central

    Llucià‐Valldeperas, Aida; Soler‐Botija, Carolina; Gálvez‐Montón, Carolina; Roura, Santiago; Prat‐Vidal, Cristina; Perea‐Gil, Isaac; Sanchez, Benjamin; Bragos, Ramon; Vunjak‐Novakovic, Gordana

    2016-01-01

    Abstract Cardiac cells are subjected to mechanical and electrical forces, which regulate gene expression and cellular function. Therefore, in vitro electromechanical stimuli could benefit further integration of therapeutic cells into the myocardium. Our goals were (a) to study the viability of a tissue‐engineered construct with cardiac adipose tissue‐derived progenitor cells (cardiac ATDPCs) and (b) to examine the effect of electromechanically stimulated cardiac ATDPCs within a myocardial infarction (MI) model in mice for the first time. Cardiac ATDPCs were electromechanically stimulated at 2‐millisecond pulses of 50 mV/cm at 1 Hz and 10% stretching during 7 days. The cells were harvested, labeled, embedded in a fibrin hydrogel, and implanted over the infarcted area of the murine heart. A total of 39 animals were randomly distributed and sacrificed at 21 days: groups of grafts without cells and with stimulated or nonstimulated cells. Echocardiography and gene and protein analyses were also carried out. Physiologically stimulated ATDPCs showed increased expression of cardiac transcription factors, structural genes, and calcium handling genes. At 21 days after implantation, cardiac function (measured as left ventricle ejection fraction between presacrifice and post‐MI) increased up to 12% in stimulated grafts relative to nontreated animals. Vascularization and integration with the host blood supply of grafts with stimulated cells resulted in increased vessel density in the infarct border region. Trained cells within the implanted fibrin patch expressed main cardiac markers and migrated into the underlying ischemic myocardium. To conclude, synchronous electromechanical cell conditioning before delivery may be a preferred alternative when considering strategies for heart repair after myocardial infarction. Stem Cells Translational Medicine 2017;6:970–981 PMID:28297585

  20. Physical and functional links between anion exchanger-1 and sodium pump.

    PubMed

    Su, Ya; Al-Lamki, Rafia S; Blake-Palmer, Katherine G; Best, Alison; Golder, Zoe J; Zhou, Aiwu; Karet Frankl, Fiona E

    2015-02-01

    Anion exchanger-1 (AE1) mediates chloride-bicarbonate exchange across the plasma membranes of erythrocytes and, via a slightly shorter transcript, kidney epithelial cells. On an omnivorous human diet, kidney AE1 is mainly active basolaterally in α-intercalated cells of the collecting duct, where it is functionally coupled with apical proton pumps to maintain normal acid-base homeostasis. The C-terminal tail of AE1 has an important role in its polarized membrane residency. We have identified the β1 subunit of Na(+),K(+)-ATPase (sodium pump) as a binding partner for AE1 in the human kidney. Kidney AE1 and β1 colocalized in renal α-intercalated cells and coimmunoprecipitated (together with the catalytic α1 subunit of the sodium pump) from human kidney membrane fractions. ELISA and fluorescence titration assays confirmed that AE1 and β1 interact directly, with a Kd value of 0.81 μM. GST-AE1 pull-down assays using human kidney membrane proteins showed that the last 11 residues of AE1 are important for β1 binding. siRNA-induced knockdown of β1 in cell culture resulted in a significant reduction in kidney AE1 levels at the cell membrane, whereas overexpression of kidney AE1 increased cell surface sodium pump levels. Notably, membrane staining of β1 was reduced throughout collecting ducts of AE1-null mouse kidney, where increased fractional excretion of sodium has been reported. These data suggest a requirement of β1 for proper kidney AE1 membrane residency, and that activities of AE1 and the sodium pump are coregulated in kidney.

  1. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct

    PubMed Central

    Valarmathi, Mani T.; Fuseler, John W.; Davis, Jeffrey M.; Price, Robert L.

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty. PMID:28194397

  2. A Novel Human Tissue-Engineered 3-D Functional Vascularized Cardiac Muscle Construct.

    PubMed

    Valarmathi, Mani T; Fuseler, John W; Davis, Jeffrey M; Price, Robert L

    2017-01-01

    Organ tissue engineering, including cardiovascular tissues, has been an area of intense investigation. The major challenge to these approaches has been the inability to vascularize and perfuse the in vitro engineered tissue constructs. Attempts to provide oxygen and nutrients to the cells contained in the biomaterial constructs have had varying degrees of success. The aim of this current study is to develop a three-dimensional (3-D) model of vascularized cardiac tissue to examine the concurrent temporal and spatial regulation of cardiomyogenesis in the context of postnatal de novo vasculogenesis during stem cell cardiac regeneration. In order to achieve the above aim, we have developed an in vitro 3-D functional vascularized cardiac muscle construct using human induced pluripotent stem cell-derived embryonic cardiac myocytes (hiPSC-ECMs) and human mesenchymal stem cells (hMSCs). First, to generate the prevascularized scaffold, human cardiac microvascular endothelial cells (hCMVECs) and hMSCs were co-cultured onto a 3-D collagen cell carrier (CCC) for 7 days under vasculogenic culture conditions. In this milieu, hCMVECs/hMSCs underwent maturation, differentiation, and morphogenesis characteristic of microvessels, and formed extensive plexuses of vascular networks. Next, the hiPSC-ECMs and hMSCs were co-cultured onto this generated prevascularized CCCs for further 7 or 14 days in myogenic culture conditions. Finally, the vascular and cardiac phenotypic inductions were analyzed at the morphological, immunological, biochemical, molecular, and functional levels. Expression and functional analyses of the differentiated cells revealed neo-angiogenesis and neo-cardiomyogenesis. Thus, our unique 3-D co-culture system provided us the apt in vitro functional vascularized 3-D cardiac patch that can be utilized for cellular cardiomyoplasty.

  3. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  4. Cardiac Structure and Function in Weight Trainers Runners, and Runner/Weight Trainers.

    ERIC Educational Resources Information Center

    Elias, Barbara A.; And Others

    1991-01-01

    Study compared cardiac structure and function in adult male weight trainers, runners, and those who did both. Results indicate men who run or weight train and run have similar heart structural and functional characteristics and greater relative internal diameter and left ventricular wall thickness than men who only weight train. (SM)

  5. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  6. L-propionylcarnitine effects on cardiac carnitine content and function in secondary carnitine deficiency.

    PubMed

    Broderick, T L; DiDomenico, D; Shug, A L; Paulson, D J

    1995-04-01

    Long-term treatment with sodium pivalate, a compound conjugated to carnitine and excreted in the urine, results in carnitine deficiency and cardiac dysfunction. Since L-propionylcarnitine (LPC) is generally of benefit to cardiac function, it was of interest to determine whether it is effective in preventing the reductions in both heart carnitine content and function from occurring in carnitine deficiency. Secondary carnitine deficiency was induced in male Sprague-Dawley rats by supplementing the drinking water with 20 mM sodium pivalate for 26 weeks. Control animals received an equimolar concentration of sodium bicarbonate. At 13 weeks into treatment, a subgroup of control and sodium pivalate animals were given 80 mg/kg of LPC in their drinking water. Following treatment, isolated working hearts were perfused with buffer containing 11 mM glucose and 0.4 mM palmitate. Hearts from sodium pivalate treated animals demonstrated a severe reduction in tissue carnitine. When mechanical function was measured in these hearts, heart rate, rate-pressure product, and aortic flow were significantly depressed. Treatment with LPC, however, prevented the depletion in cardiac carnitine content and improved these cardiac parameters. Our results demonstrate that LPC treatment is beneficial in preventing the depression in cardiac function from occurring in this model of secondary carnitine deficiency.

  7. Cardiac function after acute support with direct mechanical ventricular actuation in chronic heart failure.

    PubMed

    McConnell, Patrick I; Anstadt, Mark P; Del Rio, Carlos L; Preston, Thomas J; Ueyama, Yukie; Youngblood, Brad L

    2014-01-01

    Direct mechanical ventricular actuation (DMVA) exerts direct cardiac compression/decompression and does not require blood contact. The safety and effects of DMVA support in chronically dysfunctional beating hearts in vivo have not been established. This study evaluated hemodynamics and load-independent systolic/diastolic cardiac function before/after acute support (2 hours) using DMVA in small hearts with induced chronic failure. Chronic heart failure was created in seven small dogs (15 ± 2 kg) via either serial coronary microembolizations or right-ventricular overdrive pacing. Dogs were instrumented to measure cardiac output, hemodynamic pressures, left ventricular volumes for pressure-volume analysis via preload reduction. Temporary cardiac support using a DMVA device was instituted for 2 hours. Hemodynamic and mechanical assessments, including dobutamine dose-responses, were compared both before and after support. Hemodynamic indices were preserved with support. Both left-ventricular systolic and diastolic function were improved postsupport, as the slopes of the preload-recruitable stroke work (+29 ± 7%, p < 0.05) and the end-diastolic pressure-volume relationship (EDPVR: -28 ± 9%, p < 0.05) improved post-DMVA support. Diastolic/systolic myocardial reserve, as assessed by responsiveness to dobutamine challenges, was preserved after DMVA support. Short-term DMVA support can safely and effectively sustain hemodynamics, whereas triggering favorable effects on cardiac function in the setting of chronic heart failure. In particular, DMVA support preserved load-independent diastolic function and reserve.

  8. Is low compression pressure able to improve venous pumping function in patients with venous insufficiency?

    PubMed

    Mosti, G; Partsch, H

    2010-06-01

    A too high resting pressure of compression devices is poorly tolerated and may cause skin defects, especially in patients with concomitant arterial occlusive disease. To investigate whether low compression pressure will improve venous pumping function in patients with venous incompetence. Venous pumping function was assessed in 20 patients with severe reflux in the great saphenous vein by measuring ejection fraction (EF) using strain-gauge plethysmography. Measurements were repeated after application of knee-high medical compression stockings and of inelastic bandages applied with a pressure of 20, 40 and 60 mmHg in the supine position. EF was significantly reduced compared with healthy controls. Compression stockings exerting a median pressure of 27 mmHg (interquartile range [IQR] 25-29) in the supine and 30.5 mmHg (IQR 28.25-34.25) in the standing position produced a moderate, non-significant improvement of EF of 17%. Inelastic bandages with a resting pressure of 20.5 mmHg (IQR 20-22) in the supine position resulting in a standing pressure of 36 mmHg (IQR 33-40.75) led to a significant increase of EF of 61.5% (P < 0.01). A further increase of the resting pressure to 40 and 60 mmHg achieved an increase of the EF of 91% and 98%, respectively (P < 0.001). In patients with venous pumping failure, inelastic bandages produce a significant pressure-dependent increase of EF. A significant improvement in venous pumping function was achieved with inelastic bandages even at a resting pressure of 20 mmHg.

  9. Effects of Blood Purification on Serum Levels of Inflammatory Cytokines and Cardiac Function in a Rat Model of Sepsis.

    PubMed

    Lin, Cong-Meng; Chen, Cun-Rong; Wu, Xue-Qiong; Ren, Jin-Hua; Chen, Shao-Zhen; Luo, Xiao-Feng; Mei, Xu-Qiao; Shen, Lv-Ying; Guo, Meng-Xian; Ma, Xu-Dong; Yang, Ting

    2017-01-01

    The study aimed to explore the effects of blood purification (BP) on serum levels of inflammatory cytokines and cardiac function in a rat model of sepsis. A rat model of sepsis was established by cecal ligation and puncture. All rats were divided into the normal control, sham operation, model, sham treatment, and BP treatment groups. Cardiac functions, inflammatory cytokines, myocardial enzymes, pathological score of cardiac muscle tissue, and myocardial apoptosis of rats in each group were compared. Sepsis rats had higher serum levels of inflammatory cytokines and lower cardiac function than those in the normal control and sham operation groups. Compared with the model and sham treatment groups, improved cardiac functions, decreased inflammatory cytokines, myocardial enzymes, pathological score, and myocardial apoptosis and mortality were observed in the BP treatment group. BP may reduce serum levels of inflammatory cytokines and improve cardiac function of sepsis rats. © 2017 S. Karger AG, Basel.

  10. The genetic basis of cardiac function: dissection by zebrafish (Danio rerio) screens.

    PubMed Central

    Warren, K S; Wu, J C; Pinet, F; Fishman, M C

    2000-01-01

    The vertebrate heart differs from chordate ancestors both structurally and functionally. Genetic units of form, termed 'modules', are identifiable by mutation, both in zebrafish and mouse, and correspond to features recently acquired in evolution, such as the ventricular chamber or endothelial lining of the vessels and heart. Zebrafish (Danio rerio) genetic screens have provided a reasonably inclusive set of such genes. Normal cardiac function may also be disrupted by single-gene mutations in zebrafish. Individual mutations may perturb contractility or rhythm generation. The zebrafish mutations which principally disturb cardiac contractility fall into two broad phenotypic categories, 'dilated' and 'hypertrophic'. Interestingly, these correspond to the two primary types of heart failure in humans. These disorders of early cardiac function provide candidate genes to be examined in complex human heart diseases, including arrhythmias and heart failure. PMID:11128987

  11. Gravity Reception and Cardiac Function in the Spider

    NASA Technical Reports Server (NTRS)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  12. Gravity Reception and Cardiac Function in the Spider

    NASA Technical Reports Server (NTRS)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  13. Cardiac response to hypobaric hypoxia: persistent changes in cardiac mass, function, and energy metabolism after a trek to Mt. Everest Base Camp.

    PubMed

    Holloway, Cameron J; Montgomery, Hugh E; Murray, Andrew J; Cochlin, Lowri E; Codreanu, Ion; Hopwood, Naomi; Johnson, Andrew W; Rider, Oliver J; Levett, Denny Z H; Tyler, Damian J; Francis, Jane M; Neubauer, Stefan; Grocott, Michael P W; Clarke, Kieran

    2011-02-01

    We postulated that changes in cardiac high-energy phosphate metabolism may underlie the myocardial dysfunction caused by hypobaric hypoxia. Healthy volunteers (n=14) were studied immediately before, and within 4 d of return from, a 17-d trek to Mt. Everest Base Camp (5300 m). (31)P magnetic resonance (MR) spectroscopy was used to measure cardiac phosphocreatine (PCr)/ATP, and MR imaging and echocardiography were used to assess cardiac volumes, mass, and function. Immediately after returning from Mt. Everest, total body weight had fallen by 3% (P<0.05), but left ventricular mass, adjusted for changes in body surface area, had disproportionately decreased by 11% (P<0.05). Alterations in diastolic function were also observed, with a reduction in peak left ventricular filling rates and mitral inflow E/A, by 17% (P<0.05) and 24% (P<0.01), respectively, with no change in hydration status. Compared with pretrek, cardiac PCr/ATP ratio had decreased by 18% (P<0.01). Whether the abnormalities were even greater at altitude is unknown, but all had returned to pretrek levels after 6 mo. The alterations in cardiac morphology, function, and energetics are similar to findings in patients with chronic hypoxia. Thus, a decrease in cardiac PCr/ATP may be a universal response to periods of sustained low oxygen availability, underlying hypoxia-induced cardiac dysfunction in healthy human heart and in patients with cardiopulmonary diseases.

  14. Cardiac contractile function and mitochondrial respiration in diabetes-related mouse models.

    PubMed

    Marciniak, Camille; Marechal, Xavier; Montaigne, David; Neviere, Remi; Lancel, Steve

    2014-08-21

    Pathophysiological processes underlying diabetic-related cardiomyopathies are complex. Mitochondria dysfunction is often described as a cause of cardiac impairment but its extent may depend on the type of experimental diabetes. Here we proposed to compare drug- or diet-induced models of diabetes in terms of metabolic features, cardiac and mitochondrial functions. Mice were fed with regular chow or fat-enriched diet. After three weeks, they received either citrate or streptozotocin injections for five consecutive days. Metabolic parameters, myocardial contractile function and mitochondrial respiration were measured after three more weeks. Fat mass volumes were assessed by magnetic resonance imaging. Oral glucose tolerance test, insulin tolerance test, triglyceride and adipocytokine quantification were evaluated to establish metabolic profiles. Cardiac function was assessed ex vivo onto a Langendorff column. Isolated cardiac mitochondria respiration was obtained using high-resolution oxygraphy. Mice fed with the fat-enriched regimen presented abdominal obesity, increased blood glucose, elevated leptin level, glucose intolerance, and insulin resistance. Mice treated with streptozotocin, independently of the regimen, lost their capacity to release insulin in response to glucose ingestion. Mice fed with regular chow diet and injected with streptozotocin developed cardiac dysfunction without mitochondrial respiration defect. However, both groups of high-fat diet fed mice developed cardiac alterations associated with reduction in mitochondrial oxygen consumption, despite an increase in mitochondrial biogenesis signalling. We explored three animal models mimicking type 1 and 2 diabetes. While cardiac dysfunction was present in the three groups of mice, mitochondrial respiration impairment was only obvious in models reproducing features of type 2 diabetes.

  15. Short-Term Effects of Transjugular Intrahepatic Shunt on Cardiac Function Assessed by Cardiac MRI: Preliminary Results

    SciTech Connect

    Kovacs, A.; Schepke, M.; Heller, J.; Schild, H. H.; Flacke, S.

    2010-04-15

    The purpose of this study was to assess short-term effects of transjugular intrahepatic shunt (TIPS) on cardiac function with cardiac magnetic resonance imaging (MRI) in patients with liver cirrhosis. Eleven patients (six males and five females) with intractable esophageal varices or refractory ascites were imaged with MRI at 1.5 T prior to, within 24 h after, and 4-6 months after TIPS creation (n = 5). Invasive pressures were registered during TIPS creation. MRI consisted of a stack of contiguous slices as well as phase contrast images at all four valve planes and perpendicular to the portal vein. Imaging data were analyzed through time-volume curves and first derivatives. The portoatrial pressure gradient decreased from 19.8 {+-} 2.3 to 6.6 {+-} 2.3, accompanied by a nearly two fold increase in central pressures and pulmonary capillary wedge pressure immediately after TIPS creation. Left and right end diastolic volumes and stroke volumes increased by 11, 13, and 24%, respectively (p < 0.001), but dropped back to baseline at follow-up. End systolic volumes remained unchanged. E/A ratios remained within normal range. During follow-up the left ventricular mass was larger than baseline values in all patients, with an average increase of 7.9 g (p < 0.001). In conclusion, the increased volume load shunted to the heart after TIPS creation transiently exceeded the preload reserve of the right and left ventricle, leading to significantly increased pulmonary wedge pressures and persistent enlargement of the left and right atria. Normalization of cardiac dimensions was observed after months together with mild left ventricular hypertrophy.

  16. Characterization of functional ion channels in human cardiac c-kit+ progenitor cells.

    PubMed

    Zhang, Ying-Ying; Li, Gang; Che, Hui; Sun, Hai-Ying; Li, Xin; Au, Wing-Kuk; Xiao, Guo-Sheng; Wang, Yan; Li, Gui-Rong

    2014-05-01

    Cardiac progenitor cells play an important role in cardiac repair and regeneration; however, their cellular biology and electrophysiology are not understood. The present study characterizes the functional ion channels in human cardiac c-kit(+) progenitor cells using whole-cell patch voltage-clamp, RT-PCR, and Western blots. We found that several ionic currents were present in human cardiac c-kit(+) progenitor cells, including a large-conductance Ca(2+)-activated K(+) current (BKCa) in 86 % of cells, an inwardly rectifying K(+) current (I Kir) in 84 % of cells, a transient outward K(+) current (I to) in 47 % of cells, a voltage-gated tetrodotoxin-sensitive Na(+) current (I Na,TTX) in 61 % of cells. Molecular identities of these ionic currents were determined with RT-PCR and Western-blot analysis. KCa.1.1 (for BKCa), Kir2.1 (for I Kir), Kv4.2 and Kv4.3 (for I to), Nav1.3 and Nav1.6 (for I Na.TTX) were abundantly expressed in human cardiac c-kit(+) progenitor cells, which do not resemble cardiomyocytes at all. These results demonstrate for the first time that four types of ionic currents including BKCa, I to, I Kir, and I Na.TTX, are heterogeneously present in human cardiac c-kit(+) cells, which may be involved in regulating cellular physiology.

  17. Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions.

    PubMed

    Grossman, Paul; Taylor, Edwin W

    2007-02-01

    Respiratory sinus arrhythmia (RSA, or high-frequency heart-rate variability) is frequently employed as an index of cardiac vagal tone or even believed to be a direct measure of vagal tone. However, there are many significant caveats regarding vagal tone interpretation: 1. Respiratory parameters can confound relations between RSA and cardiac vagal tone.2. Although intraindividual relations between RSA and cardiac vagal control are often strong, interindividual associations may be modest.3. RSA measurement is profoundly influenced by concurrent levels of momentary physical activity, which can bias estimation of individual differences in vagal tone.4. RSA magnitude is affected by beta-adrenergic tone.5. RSA and cardiac vagal tone can dissociate under certain circumstances.6. The polyvagal theory contains evolution-based speculations that relate RSA, vagal tone and behavioral phenomena. We present evidence that the polyvagal theory does not accurately depict evolution of vagal control of heart-rate variability, and that it ignores the phenomenon of cardiac aliasing and disregards the evolution of a functional role for vagal control of the heart, from cardiorespiratory synchrony in fish to RSA in mammals. Unawareness of these issues can lead to misinterpretation of cardiovascular autonomic mechanisms. On the other hand, RSA has been shown to often provide a reasonable reflection of cardiac vagal tone when the above-mentioned complexities are considered. Finally, a recent hypothesis is expanded upon, in which RSA plays a primary role in regulation of energy exchange by means of synchronizing respiratory and cardiovascular processes during metabolic and behavioral change.

  18. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice.

    PubMed

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy.

  19. Transplantation of multipotent Isl1+ cardiac progenitor cells preserves infarcted heart function in mice

    PubMed Central

    Li, Yunpeng; Tian, Shuo; Lei, Ienglam; Liu, Liu; Ma, Peter; Wang, Zhong

    2017-01-01

    Cell-based cardiac therapy is a promising therapeutic strategy to restore heart function after myocardial infarction (MI). However, the cell type selection and ensuing effects remain controversial. Here, we intramyocardially injected Isl1+ cardiac progenitor cells (CPCs) derived from EGFP/luciferase double-tagged mouse embryonic stem (dt-mES) cells with vehicle (fibrin gel) or phosphate-buffered saline (PBS) into the infarcted area in nude mice to assess the contribution of CPCs to the recovery of cardiac function post-MI. Our results showed that Isl1+ CPCs differentiated normally into three cardiac lineages (cardiomyocytes (CMs), endothelial cells and smooth muscle cells) both on cell culture plates and in fibrin gel. Cell retention was significantly increased when the transplanted cells were injected with vehicle. Importantly, 28 days after injection, CPCs were observed to differentiate into CMs within the infarcted area. Moreover, numerous CD31+ endothelial cells derived from endogenous revascularization and differentiation of the injected CPCs were detected. SMMHC-, Ki67- and CX-43-positive cells were identified in the injected CPC population, further demonstrating the proliferation, differentiation and integration of the transplanted CPCs in host cells. Furthermore, animal hearts injected with CPCs showed increased angiogenesis, decreased infarct size, and improved heart function. In conclusion, our studies showed that Isl1+ CPCs, when combined with a suitable vehicle, can produce notable therapeutic effects in the infarcted heart, suggesting that CPCs might be an ideal cell source for cardiac therapy. PMID:28386378

  20. Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

    PubMed

    Abad, Cesar Cavinato Cal; do Nascimento, Ademir Manuel; Dos Santos, Leandro Eziquiel; Figueroa, Diego; Ramona, Pamella; Sartori, Michele; Scapini, Katia B; Albuquerque, Oscar; Moraes-Silva, Ivana Cinthya; Coelho-Júnior, Hélio José; Rodrigues, Bruno; Mostarda, Cristiano Teixeira; De Angelis, Kátia; Irigoyen, Maria Cláudia

    2017-06-01

    The present study aimed to compare the effects of moderate-intensity continuous and high-intensity interval exercise training (ET) on exercise tolerance, cardiac morphometry and function, hemodynamic, and cardiac autonomic modulation in myocardial infarcted mice. Wild-type mice (WT) were divided into four groups: sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium infarction underwent to moderate-intensity continuous ET (MICT), and WT myocardium infarction underwent to high-intensity interval ET (MIIT). After 60 days of descending coronary artery ligation, moderate-intensity continuous ET consisted of running at 60% of maximum, while the high-intensity interval training consisted of eight sprints of 4 min at 80% of maximum and a 4-min recovery at 40% of maximum. Both exercises were performed 1 hr a day, 5 days a week, during 8 weeks. Results demonstrated that IS showed elevated exercise tolerance, as well as decreased hemodynamic and heart function, and autonomic control. On the other hand, both programs of ET were equally effective to increase all parameters, without further differences between the groups. In conclusion, the results of the present study showed that myocardial infarction leads to damage in both investigated strains and the two types of physical exercise attenuated the major impairments provoked by myocardial infarction in exercise tolerance, cardiac structure, cardiac function, hemodynamic and cardiac autonomic modulation.

  1. CHIP enhances angiogenesis and restores cardiac function after infarction in transgenic mice.

    PubMed

    Xu, Cheng-Wei; Zhang, Tian-Peng; Wang, Hong-Xia; Yang, Hui; Li, Hui-Hua

    2013-01-01

    Carboxyl terminus of Hsp70-interacting protein (CHIP) is a chaperone/ubiquitin ligase that plays an important role in stress-induced apoptosis. However, the effect of CHIP on angiogenesis, cardiac function and survival 4 weeks after myocardial infarction (MI) remain to be explored. Wild-type (WT) and transgenic mice (TG) with cardiac-specific overexpression of CHIP were used for coronary artery ligation. The cardiac function, cardiomyocyte apoptosis, inflammation and angiogenesis were examined by echocardiography, histological analysis, real-time PCR and Western blot analysis. At 4 weeks of after coronary artery ligation, echocardiography demonstrated that cardiac remodeling and dysfunction were prevented in TG mice compared with WT mice. The infarct size, cardiomyocyte apoptosis and inflammation were significantly reduced in TG mice than in WT mice. The survival rate after MI in TG mice was higher than that of WT mice. Furthermore, the levels of p53 protein was markedly decreased, but the expression of HIF-1α and VEGF, and the formation of capillary and arteriole after MI were significantly enhanced in TG mice compared with WT mice. We report the first in vivo evidence that CHIP enhances angiogenesis, inhibits inflammation, restores cardiac function, and improves survival at 4 weeks after MI. The present study expands on previous results and defines a novel mechanism. Thus, increased CHIP level may provide a novel therapeutic approach for left ventricular dysfunction after MI. Copyright © 2013 S. Karger AG, Basel.

  2. The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1activation

    PubMed Central

    Boopathy, Archana V.; Che, Pao Lin; Somasuntharam, Inthirai; Fiore, Vincent F.; Cabigas, E. Bernadette; Ban, Kiwon; Brown, Milton E.; Narui, Yoshie; Barker, Thomas H.; Yoon, Young-sup; Salaita, Khalid; García, Andrés J.; Davis, Michael E.

    2014-01-01

    Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair. PMID:24974008

  3. The modulation of cardiac progenitor cell function by hydrogel-dependent Notch1 activation.

    PubMed

    Boopathy, Archana V; Che, Pao Lin; Somasuntharam, Inthirai; Fiore, Vincent F; Cabigas, E Bernadette; Ban, Kiwon; Brown, Milton E; Narui, Yoshie; Barker, Thomas H; Yoon, Young-Sup; Salaita, Khalid; García, Andrés J; Davis, Michael E

    2014-09-01

    Myocardial infarction is the leading cause of death worldwide and phase I clinical trials utilizing cardiac progenitor cells (CPCs) have shown promising outcomes. Notch1 signaling plays a critical role in cardiac development and in the survival, cardiogenic lineage commitment, and differentiation of cardiac stem/progenitor cells. In this study, we functionalized self-assembling peptide (SAP) hydrogels with a peptide mimic of the Notch1 ligand Jagged1 (RJ) to evaluate the therapeutic benefit of CPC delivery in the hydrogels in a rat model of myocardial infarction. The behavior of CPCs cultured in the 3D hydrogels in vitro including gene expression, proliferation, and growth factor production was evaluated. Interestingly, we observed Notch1 activation to be dependent on hydrogel polymer density/stiffness with synergistic increase in presence of RJ. Our results show that RJ mediated Notch1 activation depending on hydrogel concentration differentially regulated cardiogenic gene expression, proliferation, and growth factor production in CPCs in vitro. In rats subjected to experimental myocardial infarction, improvement in acute retention and cardiac function was observed following cell therapy in RJ hydrogels compared to unmodified or scrambled peptide containing hydrogels. This study demonstrates the potential therapeutic benefit of functionalizing SAP hydrogels with RJ for CPC based cardiac repair. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Biophysical stimulation for in vitro engineering of functional cardiac tissues.

    PubMed

    Korolj, Anastasia; Wang, Erika Yan; Civitarese, Robert A; Radisic, Milica

    2017-07-01

    Engineering functional cardiac tissues remains an ongoing significant challenge due to the complexity of the native environment. However, our growing understanding of key parameters of the in vivo cardiac microenvironment and our ability to replicate those parameters in vitro are resulting in the development of increasingly sophisticated models of engineered cardiac tissues (ECT). This review examines some of the most relevant parameters that may be applied in culture leading to higher fidelity cardiac tissue models. These include the biochemical composition of culture media and cardiac lineage specification, co-culture conditions, electrical and mechanical stimulation, and the application of hydrogels, various biomaterials, and scaffolds. The review will also summarize some of the recent functional human tissue models that have been developed for in vivo and in vitro applications. Ultimately, the creation of sophisticated ECT that replicate native structure and function will be instrumental in advancing cell-based therapeutics and in providing advanced models for drug discovery and testing. © 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  5. Transition from fetal to neonatal life: changes in cardiac function assessed by speckle-tracking echocardiography.

    PubMed

    Schubert, Ulf; Müller, Matthias; Norman, Mikael; Abdul-Khaliq, Hashim

    2013-10-01

    Assessment of cardiac function by speckle-tracking (2D-S) echocardiography in the transitional period from fetal to neonatal life in a healthy population. Ultrasound assessment of cardiac function of 30 healthy fetuses at the gestational age of 28 weeks, and follow-up after birth using 2-D strain derived novel parameters such as longitudinal strain (S), strain rate (SR), tissue velocities, MPI- and E/E'-index, E/A- and E'/A'-rate of both right (RV) and left ventricles (LV) and interventricular septum (IVS) and comparison to conventionally measured cardiac stroke volume (SV), cardiac output (CO) and ejection fraction (EF). Ultrasound 2D-S performance and analysis were technically feasible and reproducible in all 30 fetuses and in the neonatal period. In fetuses, tissue velocities and SR measurements were homogenous for all regions of interest in both ventricles, and strain increased from apex to base and was significantly higher in the RV compared to LV. All calculated indices were almost identical for RV and LV. After birth, strain and strain rate exhibited significantly lower values, and systolic tissue velocities were higher in comparison to fetal values in both chambers and in all regions of interest. Speckle-tracking echocardiography is a feasible and reproducible technique in analyzing both fetal and newborn cardiac functions. Therefore, it might be useful in clinical routine examinations and give new insights in transitional physiology. © 2013. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

    PubMed

    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2016-01-01

    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  7. Cardiac autonomic denervation and functional response to neurotoxins during acute experimental Chagas' disease in rats.

    PubMed

    Teixeira, A L; Fontoura, B F; Freire-Maia, L; Chiari, E; Machado, C R; Teixeira, M M; Camargos, E R

    2001-06-20

    Severe cardiac autonomic denervation occurs in the acute Chagas' disease in rats. The present study aims at verifying whether this denervation was accompanied by impairment of heart function. Scorpionic (Tityus serrulatus) crude venom was used for neurotransmitter release in isolated hearts (Langendorff's preparation). In control hearts, the venom induced significant bradycardia followed by tachycardia. In infected animals, despite the severe (sympathetic) or moderate (parasympathetic) cardiac denervation, the venom provoked similar bradycardia but the tachycardia was higher. The hearts of infected animals beat at significantly lower rate. Atropine prevented this lower rate. Our results demonstrated sympathetic dysfunction during the acute phase of Trypanosoma cruzi infection in rats, the parasympathetic function being spared.

  8. Influence of transposed stomach on cardiac function in patients with resected esophageal cancer.

    PubMed

    Coral, R P; Constant-Neto, M; Silva, I S; Barros, S; Jawetz, J

    2004-01-01

    Although the use of the posterior mediastinum and the stomach as a reconstruction option after esophagectomy has wide acceptance, there are concerns about the potential cardiac impairment it could cause. We prospectively studied 27 patients regarding the function and the systolic diameter, diastolic diameter, shortening fraction, ejection fraction and the presence of extrinsic compression. The patients were studied preoperatively and between the 45th and 60th postoperative days. The parameters were still within normal clinical ranges. We concluded that this type of reconstruction does not harm the patients in terms of their cardiac function.

  9. Restoring the impaired cardiac calcium homeostasis and cardiac function in iron overload rats by the combined deferiprone and N-acetyl cysteine

    PubMed Central

    Wongjaikam, Suwakon; Kumfu, Sirinart; Khamseekaew, Juthamas; Chattipakorn, Siriporn C.; Chattipakorn, Nipon

    2017-01-01

    Intracellular calcium [Ca2+]i dysregulation plays an important role in the pathophysiology of iron overload cardiomyopathy. Although either iron chelators or antioxidants provide cardioprotection, a comparison of the efficacy of deferoxamine (DFO), deferiprone (DFP), deferasirox (DFX), N-acetyl cysteine (NAC) or a combination of DFP plus NAC on cardiac [Ca2+]i homeostasis in chronic iron overload has never been investigated. Male Wistar rats were fed with either a normal diet or a high iron (HFe) diet for 4 months. At 2 months, HFe rats were divided into 6 groups and treated with either a vehicle, DFO (25 mg/kg/day), DFP (75 mg/kg/day), DFX (20 mg/kg/day), NAC (100 mg/kg/day), or combined DFP plus NAC. At 4 months, the number of cardiac T-type calcium channels was increased, whereas cardiac sarcoplasmic-endoplasmic reticulum Ca2+ ATPase (SERCA) was decreased, leading to cardiac iron overload and impaired cardiac [Ca2+]i homeostasis. All pharmacological interventions restored SERCA levels. Although DFO, DFP, DFX or NAC alone shared similar efficacy in improving cardiac [Ca2+]i homeostasis, only DFP + NAC restored cardiac [Ca2+]i homeostasis, leading to restoring left ventricular function in the HFe-fed rats. Thus, the combined DFP + NAC was more effective than any monotherapy in restoring cardiac [Ca2+]i homeostasis, leading to restored myocardial contractility in iron-overloaded rats. PMID:28287621

  10. Tracking of structural and functional cardiac measures from infancy into school-age.

    PubMed

    Toemen, Liza; Gaillard, Romy; van Osch-Gevers, Lennie; Helbing, Willem A; Hofman, Albert; Jaddoe, Vincent Wv

    2017-09-01

    Objective Cardiac structure and function are important predictors for cardiovascular disease in adults. Not much is known about tracking of cardiac measures, other than left ventricular mass, from early life onwards. We examined whether and to what extent cardiac measures track from infancy into school-age. Methods We performed a population-based prospective cohort study among 1072 children. Aortic root diameter, left atrial diameter, left ventricular mass, relative wall thickness and fractional shortening were measured repeatedly by echocardiography. We explored tracking between infancy (1.5, six and 24 months) and school-age (six and 10 years). Results Of all cardiac measures, aortic root diameter, left atrial diameter and left ventricular mass were significantly correlated between infancy and school-age ( r = 0.10-0.42, all p-values < 0.01), with the strongest correlations between 24 months and 10 years. Of the different structures, aortic root diameter showed the strongest correlations. Approximately 30% of children who were in the lowest or highest quartile of a measure at the age of 1.5 months remained in that quartile at the age of 10 years. When analysing the effects of the infant cardiac measures on the same outcomes at 10 years in conditional regression models, we observed effect estimates of the same size for the different age windows. Conclusion Our results suggest moderate tracking of structural cardiac measures from early infancy until school-age, which become stronger at older ages, but not of relative wall thickness or fractional shortening. Moderate tracking of cardiac structures suggests that cardiac structures are at least partly determined in early life.

  11. Cation-Specific Conformations in a Dual-Function Ion-Pumping Microbial Rhodopsin.

    PubMed

    da Silva, Giordano F Z; Goblirsch, Brandon R; Tsai, Ah-Lim; Spudich, John L

    2015-06-30

    A recently discovered rhodopsin ion pump (DeNaR, also known as KR2) in the marine bacterium Dokdonia eikasta uses light to pump protons or sodium ions from the cell depending on the ionic composition of the medium. In cells suspended in a KCl solution, DeNaR functions as a light-driven proton pump, whereas in a NaCl solution, DeNaR conducts light-driven sodium ion pumping, a novel activity within the rhodopsin family. These two distinct functions raise the questions of whether the conformations of the protein differ in the presence of K(+) or Na(+) and whether the helical movements that result in the canonical E → C conformational change in other microbial rhodopsins are conserved in DeNaR. Visible absorption maxima of DeNaR in its unphotolyzed (dark) state show an 8 nm difference between Na(+) and K(+) in decyl maltopyranoside micelles, indicating an influence of the cations on the retinylidene photoactive site. In addition, electronic paramagnetic resonance (EPR) spectra of the dark states reveal repositioning of helices F and G when K(+) is replaced with Na(+). Furthermore, the conformational changes assessed by EPR spin-spin dipolar coupling show that the light-induced transmembrane helix movements are very similar to those found in bacteriorhodopsin but are altered by the presence of Na(+), resulting in a new feature, the clockwise rotation of helix F. The results establish the first observation of a cation switch controlling the conformations of a microbial rhodopsin and indicate specific interactions of Na(+) with the half-channels of DeNaR to open an appropriate path for ion translocation.

  12. Prophylactic furosemide infusion decreasing early major postoperative renal dysfunction in on-pump adult cardiac surgery: a randomized clinical trial

    PubMed Central

    Fakhari, Solmaz; Bavil, Fariba Mirzaei; Bilehjani, Eissa; Abolhasani, Sona; Mirinazhad, Moussa; Naghipour, Bahman

    2017-01-01

    Introduction Acute renal dysfunction is a common complication of cardiac surgery. Furosemide is used in prevention, or treatment, of acute renal dysfunction. This study was conducted to evaluate the protective effects of intra- and early postoperative furosemide infusion on preventing acute renal dysfunction in elective adult cardiac surgery. Methods Eighty-one patients, candidates of elective cardiac surgery, were enrolled in this study in either the furosemide (n=41) or placebo (n=40) group. Furosemide (2 mg/h) or 0.9% saline was administered and continued up to 12 hours postoperatively. We measured serum creatinine (Scr) at preoperative and on the second and fifth postoperative days. Then calculated estimated glomerular filtration rate (eGFR) at these times. An increase in Scr of >0.5 mg/dL and/or >25%–50%, compared to preoperative values, was considered as acute kidney injury (AKI). In contrast, an increase in Scr by >50% and/or the need for hemodialysis was regarded as acute renal failure (ARF). At the end we compared the AKI or ARF incidence between the two groups. Results On the second and fifth postoperative days, Scr was lower, and the eGFR was higher in the furosemide group. AKI incidence was similar in the two groups (11 vs 12 cases; P-value 0.622); however, ARF rate was lower in furosemide group (1 vs 6 cases; P-value 0.044). During the study period, Scr was more stable in the furosemide group, however in the placebo group, Scr initially increased and then decreased to its preoperative value after a few days. Conclusion This study showed that intra- and early postoperative furosemide infusion has a renal protective effect in adult cardiac surgery with cardiopulmonary bypass. Although this protective effect cannot be discovered in mild renal dysfunctions, it apparently reduces the rate of the more severe renal dysfunctions. A more multidisciplinary strategy may be needed in reducing the milder renal damage. PMID:28176949

  13. Independent and interactive effects of preload and afterload on the pump function of the isolated lymphangion

    PubMed Central

    Scallan, Joshua P.; Wolpers, John H.; Muthuchamy, Mariappan; Zawieja, David C.; Gashev, Anatoliy A.

    2012-01-01

    We tested the responses of single, isolated lymphangions to selective changes in preload and the effects of changing preload on the response to an imposed afterload. The methods used were similar to those described in our companion paper. Step-wise increases in input pressure (Pin; preload) over a pressure range between 0.5 and 3 cmH2O, at constant output pressure (Pout), led to increases in end-diastolic diameter, decreases in end-systolic diameter, and increases in stroke volume. From a baseline of 1 cmH2O, Pin elevation by 2–7 cmH2O consistently produced an immediate fall in stroke volume that subsequently recovered over a time course of 2–3 min. Surprisingly, this adaptation was associated with an increase in the slope of the end-systolic pressure-volume relationship, indicative of an increase in contractility. Lymphangions subjected to Pout levels exceeding their initial ejection limit would often accommodate by increasing diastolic filling to strengthen contraction sufficiently to match Pout. The lymphangion adaptation to various pressure combinations (Pin ramps with low or high levels of Pout, Pout ramps at low or intermediate levels of Pin, and combined Pin + Pout ramps) were analyzed using pressure-volume data to calculate stroke work. Under relatively low imposed loads, stroke work was maximal at low preloads (Pin ∼2 cmH2O), whereas at more elevated afterloads, the optimal preload for maximal work displayed a broad plateau over a Pin range of 5–11 cmH2O. These results provide new insights into the normal operation of the lymphatic pump, its comparison with the cardiac pump, and its potential capacity to adapt to increased loads during edemagenic and/or gravitational stress. PMID:22865389

  14. The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice.

    PubMed

    Kohsaka, Akira; Das, Partha; Hashimoto, Izumi; Nakao, Tomomi; Deguchi, Yoko; Gouraud, Sabine S; Waki, Hidefumi; Muragaki, Yasuteru; Maeda, Masanobu

    2014-01-01

    Cardiac function is highly dependent on oxidative energy, which is produced by mitochondrial respiration. Defects in mitochondrial function are associated with both structural and functional abnormalities in the heart. Here, we show that heart-specific ablation of the circadian clock gene Bmal1 results in cardiac mitochondrial defects that include morphological changes and functional abnormalities, such as reduced enzymatic activities within the respiratory complex. Mice without cardiac Bmal1 function show a significant decrease in the expression of genes associated with the fatty acid oxidative pathway, the tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart and develop severe progressive heart failure with age. Importantly, similar changes in gene expression related to mitochondrial oxidative metabolism are also observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle; thus, they show disrupted circadian rhythmicity. These findings indicate that the circadian clock system plays an important role in regulating mitochondrial metabolism and thereby maintains cardiac function.

  15. Pluripotent stem cell-derived cardiac tissue patch with advanced structure and function.

    PubMed

    Liau, Brian; Christoforou, Nicolas; Leong, Kam W; Bursac, Nenad

    2011-12-01

    Recent advances in pluripotent stem cell research have provided investigators with potent sources of cardiogenic cells. However, tissue engineering methodologies to assemble cardiac progenitors into aligned, 3-dimensional (3D) myocardial tissues capable of physiologically relevant electrical conduction and force generation are lacking. In this study, we introduced 3D cell alignment cues in a fibrin-based hydrogel matrix to engineer highly functional cardiac tissues from genetically purified mouse embryonic stem cell-derived cardiomyocytes (CMs) and cardiovascular progenitors (CVPs). Procedures for CM and CVP derivation, purification, and functional differentiation in monolayer cultures were first optimized to yield robust intercellular coupling and maximize velocity of action potential propagation. A versatile soft-lithography technique was then applied to reproducibly fabricate engineered cardiac tissues with controllable size and 3D architecture. While purified CMs assembled into a functional 3D syncytium only when supplemented with supporting non-myocytes, purified CVPs differentiated into cardiomyocytes, smooth muscle, and endothelial cells, and autonomously supported the formation of functional cardiac tissues. After a total culture time similar to period of mouse embryonic development (21 days), the engineered cardiac tissues exhibited unprecedented levels of 3D organization and functional differentiation characteristic of native neonatal myocardium, including: 1) dense, uniformly aligned, highly differentiated and electromechanically coupled cardiomyocytes, 2) rapid action potential conduction with velocities between 22 and 25 cm/s, and 3) significant contractile forces of up to 2 mN. These results represent an important advancement in stem cell-based cardiac tissue engineering and provide the foundation for exploiting the exciting progress in pluripotent stem cell research in the future tissue engineering therapies for heart disease. Copyright © 2011

  16. Nanosecond pulsed platelet-rich plasma (nsPRP) improves mechanical and electrical cardiac function following myocardial reperfusion injury.

    PubMed

    Hargrave, Barbara; Varghese, Frency; Barabutis, Nektarios; Catravas, John; Zemlin, Christian

    2016-02-01

    Ischemia and reperfusion (I/R) of the heart is associated with biochemical and ionic changes that result in cardiac contractile and electrical dysfunction. In rabbits, platelet-rich plasma activated using nanosecond pulsed electric fields (nsPRP) has been shown to improve left ventricular pumping. Here, we demonstrate that nsPRP causes a similar improvement in mouse left ventricular function. We also show that nsPRP injection recovers electrical activity even before reperfusion begins. To uncover the mechanism of nsPRP action, we studied whether the enhanced left ventricular function in nsPRP rabbit and mouse hearts was associated with increased expression of heat-shock proteins and altered mitochondrial function under conditions of oxidative stress. Mouse hearts underwent 30 min of global ischemia and 1 h of reperfusion in situ. Rabbit hearts underwent 30 min of ischemia in vivo and were reperfused for 14 days. Hearts treated with nsPRP expressed significantly higher levels of Hsp27 and Hsp70 compared to hearts treated with vehicle. Also, pretreatment of cultured H9c2 cells with nsPRP significantly enhanced the "spare respiratory capacity (SRC)" also referred to as "respiratory reserve capacity" and ATP production in response to the uncoupler FCCP. These results suggest a cardioprotective effect of nsPRP on the ischemic heart during reperfusion.

  17. [Progress of studies on mechanisms of acupuncture underlying regulation of cardiac function via autonomic nervous system].

    PubMed

    Wang, Ya-Li; Yu, Zhi; Xu, Bin

    2014-02-01

    Acupuncture therapy has been confirmed to be effective in treating cardiovascular diseases in clinical practice. Acupuncture-induced balance of the autonomic nervous system activities is one of its key mechanisms. In the present paper, the authors review progress of studies on acupuncture treatment of cardiovascular diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing cardiac sympathetic and vagal nerve activities. Due to limited experimental conditions, in-depth studies about the mechanisms of acupuncture intervention underlying improvement of cardiovascular functions are relatively fewer up to now. Along with the further development of modern biology, the mechanism of acupuncture intervention underlying regulation of cardiac function via autonomic nerve system will be revealed in detail.

  18. Chitosan hydrogel improves mesenchymal stem cell transplant survival and cardiac function following myocardial infarction in rats

    PubMed Central

    Xu, Bin; Li, Yang; Deng, Bo; Liu, Xiaojing; Wang, Lin; Zhu, Qing-Lei

    2017-01-01

    Myocardial infarction (MI) remains the leading cause of cardiovascular-associated mortality and morbidity. Improving the retention rate, survival and cardiomyocyte differentiation of mesenchymal stem cells (MSCs) is important in improving the treatment of patients with MI. In the present study, temperature-responsive chitosan hydrogel, an injectable scaffold, was used to deliver MSCs directly into the infarcted myocardium of rats following MI. Histopathology and immunohistochemical staining were used to evaluate cardiac cell survival and regeneration, and cardiac function was assessed using an echocardiograph. It was demonstrated that chitosan hydrogel increased graft size and cell retention in the ischemic heart, promoted MSCs to differentiate into cardiomyocytes and increased the effects of MSCs on neovasculature formation. Furthermore, chitosan hydrogel enhanced the effect of MSCs on the improvement of cardiac function and hemodynamics in the infarcted area of rats following MI. These findings suggest that chitosan hydrogel is an appropriate material to deliver MSCs into infarcted myocardium. PMID:28352335

  19. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    NASA Astrophysics Data System (ADS)

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  20. Engineering the heart: Evaluation of conductive nanomaterials for improving implant integration and cardiac function

    PubMed Central

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; (Mengqiu) Xing, Malcolm; Wang, Changyong

    2014-01-01

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction. PMID:24429673

  1. Engineering the heart: evaluation of conductive nanomaterials for improving implant integration and cardiac function.

    PubMed

    Zhou, Jin; Chen, Jun; Sun, Hongyu; Qiu, Xiaozhong; Mou, Yongchao; Liu, Zhiqiang; Zhao, Yuwei; Li, Xia; Han, Yao; Duan, Cuimi; Tang, Rongyu; Wang, Chunlan; Zhong, Wen; Liu, Jie; Luo, Ying; Mengqiu Xing, Malcolm; Wang, Changyong

    2014-01-16

    Recently, carbon nanotubes together with other types of conductive materials have been used to enhance the viability and function of cardiomyocytes in vitro. Here we demonstrated a paradigm to construct ECTs for cardiac repair using conductive nanomaterials. Single walled carbon nanotubes (SWNTs) were incorporated into gelatin hydrogel scaffolds to construct three-dimensional ECTs. We found that SWNTs could provide cellular microenvironment in vitro favorable for cardiac contraction and the expression of electrochemical associated proteins. Upon implantation into the infarct hearts in rats, ECTs structurally integrated with the host myocardium, with different types of cells observed to mutually invade into implants and host tissues. The functional measurements showed that SWNTs were essential to improve the performance of ECTs in inhibiting pathological deterioration of myocardium. This work suggested that conductive nanomaterials hold therapeutic potential in engineering cardiac tissues to repair myocardial infarction.

  2. Time Course of Atrophic Remodeling: Effects of Exercise on Cardiac Morpology and Function

    NASA Technical Reports Server (NTRS)

    Scott, J. M.; Martin, D.; Caine, T.; Matz, T.; Ploutz-Snyder, L. L.

    2014-01-01

    Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. Exercise training is one intervention that has been shown to confer favorable improvements in LV mass and function during unloading. However, the format and intensity of exercise required to induce optimal cardiac improvements has not been investigated. PURPOSE: This randomized, controlled trial was designed to 1) comprehensively characterize the time course of unloading-induced morpho-functional remodeling, and 2) examine the effects of high intensity exercise training on cardiac structural and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (HDBR): 17 were randomized to exercise training (ExBR) and 9 remained sedentary. Exercise consisted of integrated high intensity, continuous, and resistance exercise. We assessed cardiac morphology (left ventricular mass; LVM) and function (speckle-tracking assessment of longitudinal, radial, and circumferential strain and twist) before (BR-2), during (BR7,21,31,70), and following (BR+0, +3) HDBR. Cardiorespiratory fitness (VO2max) was evaluated before (BR- 3), during (BR4,25,46,68) and following (BR+0) HDBR. RESULTS: Sedentary HDBR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain, and an increase in twist. ExBR mitigated decreases in LVM and function. Change in twist was significantly related to change in VO2max (R=0.68, p<0.01). CONCLUSIONS: Alterations in cardiac morphology and function begin early during unloading. High-intensity exercise attenuates atrophic morphological and functional remodeling.

  3. Low frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation.

    PubMed

    Rahman, Faisal; Pechnik, Sandra; Gross, Daniel; Sewell, LaToya; Goldstein, David S

    2011-06-01

    Power spectral analysis of heart rate variability is used to assess cardiac autonomic function. The relationship of low frequency (LF) power to cardiac sympathetic tone has been unclear. We reported previously that LF power may reflect baroreflex modulation. In this study we attempted to replicate our findings in additional subject cohorts, taking into account possible influences of respiration and using different methods to measure baroreflex-cardiovagal gain (BCG). We assessed relationships of LF power, including respiration-adjusted LF power (LFa), with cardiac sympathetic innervation and baroreflex function in subjects with or without neuroimaging evidence of cardiac sympathetic denervation. Values for LF power at baseline supine, seated, and during the Valsalva maneuver were compared between subject groups with low or normal myocardial concentrations of 6-[(18)F]fluorodopamine-derived radioactivity. BCG was calculated from the slope of cardiac interbeat interval vs. systolic pressure during Phase II of the Valsalva maneuver or after i.v. nitroglycerine injection (the Oxford technique). LF and LFa were unrelated to myocardial 6-[(18)F]fluorodopamine-derived radioactivity. During sitting rest and the Valsalva maneuver logs of LF and LFa correlated positively with the log of Phase II BCG (r = 0.61, p = 0.0005; r = 0.47, p = 0.009; r = 0.69, p < 0.0001; r = 0.60, p = 0.0006). Groups with Low BCG (≤ 3 ms/mmHg) had low LF and LFa regardless of cardiac innervation. The log of LF power during supine rest correlated with the log of Oxford BCG (r = 0.74, p < 0.0001). LF power, with or without respiratory adjustment, reflects baroreflex modulation and not cardiac sympathetic tone.

  4. Reversible alterations in cardiac morphology and functions in a patient with Cushing's syndrome

    PubMed Central

    2014-01-01

    Summary A 45-year-old female was referred for endocrine evaluation of an incidental mass (31×24 mm in diameter) on the right adrenal gland. The patient was normotensive and nondiabetic, and had no history of generalised obesity (body weight, 46 kg at 20 years of age and 51.2 kg on admission); however, her waist-to-hip ratio was 0.97. Elevated urinary free cortisol levels (112–118 μg/day) and other findings indicated adrenocorticotrophic hormone-independent Cushing's syndrome due to right adrenocortical adenoma. Echocardiography before adrenalectomy revealed concentric left ventricular (LV) hypertrophy with a particular increase in interventricular septum thickness leading to impaired systolic and diastolic functions. Upon surgical remission of hypercortisolism, the asymmetric hypertrophy disappeared and the cardiac dysfunctions were considerably ameliorated. Although the mechanism(s) by which excessive cortisol contributes to LV wall thickness remain(s) unclear, serial echocardiography and cardiac multidetector-row computed tomography may support the notion that abnormal fat deposition in the myocardium owing to hypercortisolism appears to be an important factor for the reversible change in the cardiac morphology. Learning points Patients with Cushing's syndrome occasionally exhibit severe LV hypertrophy related to systolic and diastolic dysfunctions although they have neither hypertension nor diabetes mellitus.Biological remission of hypercortisolism can normalise structural and functional cardiac parameters and help in differentiating the cardiac alterations induced by excessive cortisol from those induced by other diseases.Excessive lipid accumulation within the heart before myocardial fibrosis may be implicated in reversible alterations in the cardiac morphology by Cushing's syndrome.Early diagnosis and treatment of Cushing's syndrome appear to be pivotal in preventing irreversible cardiac dysfunctions subsequent to cardiovascular events and heart

  5. Cardiac tamponade as an independent condition affecting the relationship between the plasma B-type natriuretic peptide levels and cardiac function.

    PubMed

    Minai, Kosuke; Komukai, Kimiaki; Arase, Satoshi; Nagoshi, Tomohisa; Matsuo, Seiichiro; Ogawa, Kazuo; Kayama, Yosuke; Inada, Keiichi; Tanigawa, Shin-Ichi; Takemoto, Tomoyuki; Sekiyama, Hiroshi; Date, Taro; Ogawa, Takayuki; Taniguchi, Ikuo; Yoshimura, Michihiro

    2013-07-01

    Plasma B-type natriuretic peptide (BNP) is finely regulated by the cardiac function and several extracardiac factors. Therefore, the relationship between the plasma BNP levels and the severity of heart failure sometimes seems inconsistent. The purpose of the present study was to investigate the plasma BNP levels in patients with cardiac tamponade and their changes after pericardial drainage. This study included 14 patients with cardiac tamponade who underwent pericardiocentesis. The cardiac tamponade was due to malignant diseases in 13 patients and uremia in 1 patient. The plasma BNP levels were measured before and 24-48 h after drainage. Although the patients reported severe symptoms of heart failure, their plasma BNP levels were only 71.2 ± 11.1 pg/ml before drainage. After appropriate drainage, the plasma BNP levels increased to 186.0 ± 22.5 pg/ml, which was significantly higher than that before drainage (P = 0.0002). In patients with cardiac tamponade, the plasma BNP levels were low, probably because of impaired ventricular stretching, and the levels significantly increased in response to the primary condition after drainage. This study demonstrates an additional condition that affects the relationship between the plasma BNP levels and cardiac function. If inconsistency is seen in the relationship between the plasma BNP levels and clinical signs of heart failure, the presence of cardiac tamponade should therefore be considered.

  6. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    PubMed

    Karunamuni, Ganga; Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M; Mai, Katherine; McHale, Quinn; Jenkins, Michael W; Linask, Kersti K; Rollins, Andrew M; Watanabe, Michiko

    2014-02-01

    Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.

  7. STARS is essential to maintain cardiac development and function in vivo via a SRF pathway.

    PubMed

    Chong, Nelson W; Koekemoer, Andrea L; Ounzain, Samir; Samani, Nilesh J; Shin, Jordan T; Shaw, Stanley Y

    2012-01-01

    STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function.

  8. Exercise and type 2 diabetes mellitus: changes in tissue-specific fat distribution and cardiac function.

    PubMed

    Jonker, Jacqueline T; de Mol, Pieter; de Vries, Suzanna T; Widya, Ralph L; Hammer, Sebastiaan; van Schinkel, Linda D; van der Meer, Rutger W; Gans, Rijk O B; Webb, Andrew G; Kan, Hermien E; de Koning, Eelco J P; Bilo, Henk J G; Lamb, Hildo J

    2013-11-01

    To prospectively assess the effects of an exercise intervention on organ-specific fat accumulation and cardiac function in type 2 diabetes mellitus. Written informed consent was obtained from all participants, and the study protocol was approved by the medical ethics committee. The study followed 12 patients with type 2 diabetes mellitus (seven men; mean age, 46 years ± 2 [standard error]) before and after 6 months of moderate-intensity exercise, followed by a high-altitude trekking expedition with exercise of long duration. Abdominal, epicardial, and paracardial fat volume were measured by using magnetic resonance (MR) imaging. Cardiac function was quantified with cardiac MR, and images were analyzed by a researcher who was supervised by a senior researcher (4 and 21 years of respective experience in cardiac MR). Hepatic, myocardial, and intramyocellular triglyceride (TG) content relative to water were measured with proton MR spectroscopy at 1.5 and 7 T. Two-tailed paired t tests were used for statistical analysis. Exercise reduced visceral abdominal fat volume from 348 mL ± 57 to 219 mL ± 33 (P < .01), and subcutaneous abdominal fat volume remained unchanged (P = .9). Exercise decreased hepatic TG content from 6.8% ± 2.3 to 4.6% ± 1.6 (P < .01) and paracardial fat volume from 4.6 mL ± 0.9 to 3.7 mL ± 0.8 (P = .02). Exercise did not change epicardial fat volume (P = .9), myocardial TG content (P = .9), intramyocellular lipid content (P = .3), or cardiac function (P = .5). A 6-month exercise intervention in type 2 diabetes mellitus decreased hepatic TG content and visceral abdominal and paracardial fat volume, which are associated with increased cardiovascular risk, but cardiac function was unaffected. Tissue-specific exercise-induced changes in body fat distribution in type 2 diabetes mellitus were demonstrated in this study. RSNA, 2013

  9. Cardiac Mass and Function Decrease in Bronchiolitis Obliterans Syndrome after Lung Transplantation: Relationship to Physical Activity?

    PubMed Central

    Hinrichs, Jan B.; Renne, Julius; Schoenfeld, Christian; Gutberlet, Marcel; Haverich, Axel; Warnecke, Gregor; Welte, Tobias; Wacker, Frank

    2014-01-01

    Rationale There is a need to expand knowledge on cardio-pulmonary pathophysiology of bronchiolitis obliterans syndrome (BOS) following lung transplantation (LTx). Objectives The purpose of this study was to assess MRI-derived biventricular cardiac mass and function parameters as well as flow hemodynamics in patients with and without BOS after LTx. Methods Using 1.5T cardiac MRI, measurements of myocardial structure and function as well as measurements of flow in the main pulmonary artery and ascending aorta were performed in 56 lung transplant patients. The patients were dichotomized into two gender matched groups of comparable age range: one with BOS (BOS stages 1–3) and one without BOS (BOS 0/0p). Measurements and Main Results Significantly lower biventricular cardiac mass, right and left ventricular end-diastolic volume, biventricular stroke volume, flow hemodynamics and significant higher heart rate but preserved cardiac output were observed in patients with BOS 1–3 compared to the BOS 0/0p group (p<0.05). In a stepwise logistic regression analysis global cardiac mass (p = 0.046) and days after LTx (p = 0.0001) remained independent parameters to predict BOS. In a second model an indicator for the physical fitness level - walking number of stairs - was added to the logistic regression model. In this second model, time after LTx (p = 0.005) and physical fitness (p = 0.01) remained independent predictors for BOS. Conclusion The observed changes in biventricular cardiac mass and function as well as changes in hemodynamic flow parameters in the pulmonary trunk and ascending aorta are likely attributed to the physical fitness level of patients after lung transplantation, which in turn is strongly related to lung function. PMID:25479016

  10. STARS Is Essential to Maintain Cardiac Development and Function In Vivo via a SRF Pathway

    PubMed Central

    Chong, Nelson W.; Koekemoer, Andrea L.; Ounzain, Samir; Samani, Nilesh J.; Shin, Jordan T.; Shaw, Stanley Y.

    2012-01-01

    Background STARS (STriated muscle Activator of Rho Signaling) is a sarcomeric protein expressed early in cardiac development that acts as an acute stress sensor for pathological remodeling. However the role of STARS in cardiac development and function is incompletely understood. Here, we investigated the role of STARS in heart development and function in the zebrafish model and in vitro. Methodology and Principal Findings Expression of zebrafish STARS (zSTARS) first occurs in the somites by the 16 somite stage [17 hours post fertilization (hpf)]. zSTARS is expressed in both chambers of the heart by 48 hpf, and also in the developing brain, jaw structures and pectoral fins. Morpholino-induced knockdown of zSTARS alters atrial and ventricular dimensions and decreases ventricular fractional shortening (measured by high-speed video microscopy), with pericardial edema and decreased or absent circulation [abnormal cardiac phenotypes in 126/164 (77%) of morpholino-injected embryos vs. 0/152 (0%) of control morpholino embryos]. Co-injection of zsrf (serum response factor) mRNA rescues the cardiac phenotype of zSTARS knockdown, resulting in improved fractional shortening and ventricular end-diastolic dimensions. Ectopic over-expression of STARS in vitro activates the STARS proximal promoter, which contains a conserved SRF site. Chromatin immunoprecipitation demonstrates that SRF binds to this site in vivo and the SRF inhibitor CCG-1423 completely blocks STARS proximal reporter activity in H9c2 cells. Conclusions/Significance This study demonstrates for the first time that STARS deficiency severely disrupts cardiac development and function in vivo and revealed a novel STARS-SRF feed-forward autoregulatory loop that could play an essential role in STARS regulation and cardiac function. PMID:22815879

  11. Differential Regulation of Cardiac Function and Intracardiac Cytokines by Rapamycin in Healthy and Diabetic Rats

    PubMed Central

    Luck, Christian; DeMarco, Vincent G.; Mahmood, Abuzar; Gavini, Madhavi P.

    2017-01-01

    Diabetes is comorbid with cardiovascular disease and impaired immunity. Rapamycin improves cardiac functions and extends lifespan by inhibiting the mechanistic target of rapamycin complex 1 (mTORC1). However, in diabetic murine models, Rapamycin elevates hyperglycemia and reduces longevity. Since Rapamycin is an immunosuppressant, we examined whether Rapamycin (750 μg/kg/day) modulates intracardiac cytokines, which affect the cardiac immune response, and cardiac function in male lean (ZL) and diabetic obese Zucker (ZO) rats. Rapamycin suppressed levels of fasting triglycerides, insulin, and uric acid in ZO but increased glucose. Although Rapamycin improved multiple diastolic parameters (E/E′, E′/A′, E/Vp) initially, these improvements were reversed or absent in ZO at the end of treatment, despite suppression of cardiac fibrosis and phosphoSer473Akt. Intracardiac cytokine protein profiling and Ingenuity® Pathway Analysis indicated suppression of intracardiac immune defense in ZO, in response to Rapamycin treatment in both ZO and ZL. Rapamycin increased fibrosis in ZL without increasing phosphoSer473Akt and differentially modulated anti-fibrotic IL-10, IFNγ, and GM-CSF in ZL and ZO. Therefore, fundamental difference in intracardiac host defense between diabetic ZO and healthy ZL, combined with differential regulation of intracardiac cytokines by Rapamycin in ZO and ZL hearts, underlies differential cardiac outcomes of Rapamycin treatment in health and diabetes. PMID:28408970

  12. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension

    PubMed Central

    Sala-Mercado, Javier A.; Spranger, Marty D.; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A.

    2013-01-01

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance. PMID:24014673

  13. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension.

    PubMed

    Sala-Mercado, Javier A; Spranger, Marty D; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A; O'Leary, Donal S

    2013-11-15

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance.

  14. In vivo imaging of cardiac development and function in zebrafish using light sheet microscopy.

    PubMed

    Weber, Michael; Huisken, Jan

    2015-01-01

    Detailed studies of heart development and function are crucial for our understanding of cardiac failures and pave the way for better diagnostics and treatment. However, the constant motion and close incorporation into the cardiovascular system prevent in vivo studies of the living, unperturbed heart. The complementary strengths of the zebrafish model and light sheet microscopy provide a useful platform to fill this gap. High-resolution images of the embryonic vertebrate heart are now recorded from within the living animal: deep inside the unperturbed heart we can follow cardiac contractions and measure action potentials and calcium transients. Three-dimensional reconstructions of the entire beating heart with cellular resolution give new insights into its ever-changing morphology and facilitate studies into how individual cells form the complex cardiac network. In addition, cardiac dynamics and robustness are now examined with targeted optical manipulation. Overall, the combination of zebrafish and light sheet microscopy represents a promising addition for cardiac research and opens the door to a better understanding of heart function and development.

  15. The alpha1-adrenergic receptors in cardiac hypertrophy: signaling mechanisms and functional implications.

    PubMed

    Cotecchia, Susanna; Del Vescovo, Cosmo Damiano; Colella, Matilde; Caso, Stefania; Diviani, Dario

    2015-10-01

    Cardiac hypertrophy is a complex remodeling process of the heart induced by physiological or pathological stimuli resulting in increased cardiomyocyte size and myocardial mass. Whereas cardiac hypertrophy can be an adaptive mechanism to stressful conditions of the heart, prolonged hypertrophy can lead to heart failure which represents the primary cause of human morbidity and mortality. Among G protein-coupled receptors, the α1-adrenergic receptors (α1-ARs) play an important role in the development of cardiac hypertrophy as demonstrated by numerous studies in the past decades, both in primary cardiomyocyte cultures and genetically modified mice. The results of these studies have provided evidence of a large variety of α1-AR-induced signaling events contributing to the defining molecular and cellular features of cardiac hypertrophy. Recently, novel signaling mechanisms have been identified and new hypotheses have emerged concerning the functional role of the α1-adrenergic receptors in the heart. This review will summarize the main signaling pathways activated by the α1-AR in the heart and their functional implications in cardiac hypertrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  17. Overexpressing Superoxide Dismutase 2 Induces a Supernormal Cardiac Function by Enhancing Redox-dependent Mitochondrial Function and Metabolic Dilation*

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J.; Meszaros, J. Gary; Chilian, William M.; Chen, Yeong-Renn

    2015-01-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate × MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, “spilled” over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function. PMID:26374996

  18. Cardiac systolic regional function and synchrony in endurance trained and untrained females

    PubMed Central

    Hedman, Kristofer; Tamás, Éva; Bjarnegård, Niclas; Brudin, Lars; Nylander, Eva

    2015-01-01

    Background Most studies on cardiac function in athletes describe overall heart function in predominately male participants. We aimed to compare segmental, regional and overall myocardial function and synchrony in female endurance athletes (ATH) and in age-matched sedentary females (CON). Methods In 46 ATH and 48 CON, echocardiography was used to measure peak longitudinal systolic strain and myocardial velocities in 12 left ventricular (LV) and 2 right ventricular (RV) segments. Regional and overall systolic function were calculated together with four indices of dyssynchrony. Results There were no differences in regional or overall LV systolic function between groups, or in any of the four dyssynchrony indices. Peak systolic velocity (s′) was higher in the RV of ATH than in CON (9.7±1.5 vs 8.7±1.5 cm/s, p=0.004), but not after indexing by cardiac length (p=0.331). Strain was similar in ATH and CON in 8 of 12 LV myocardial segments. In septum and anteroseptum, basal and mid-ventricular s′ was 6–7% and 17–19% higher in ATH than in CON (p<0.05), respectively, while s′ was 12% higher in CON in the basal LV lateral wall (p=0.013). After indexing by cardiac length, s′ was only higher in ATH in the mid-ventricular septum (p=0.041). Conclusions We found differences between trained and untrained females in segmental systolic myocardial function, but not in global measures of systolic function, including cardiac synchrony. These findings give new insights into cardiac adaptation to endurance training and could also be of use for sports cardiologists evaluating female athletes. PMID:27900120

  19. Lvad pump speed increase is associated with increased peak exercise cardiac output and vo2, postponed anaerobic threshold and improved ventilatory efficiency.

    PubMed

    Vignati, Carlo; Apostolo, Anna; Cattadori, Gaia; Farina, Stefania; Del Torto, Alberico; Scuri, Silvia; Gerosa, Gino; Bottio, Tomaso; Tarzia, Vincenzo; Bejko, Jonida; Sisillo, Erminio; Nicoli, Flavia; Sciomer, Susanna; Alamanni, Francesco; Paolillo, Stefania; Agostoni, Piergiuseppe

    2017-03-01

    Peak exercise cardiac output (CO) increase is associated with an increase of peak oxygen uptake (VO2), provided that arteriovenous O2 difference [Δ(Ca-Cv)O2] does not decrease. At anaerobic threshold, VO2, is related to CO. We tested the hypothesis that, in heart failure (HF) patients with left ventricular assistance device (LVAD), an acute increase of CO obtained through changes in LVAD pump speed is associated with peak exercise and anaerobic threshold VO2 increase. Fifteen of 20 patients bearing LVAD (Jarvik 2000) enrolled in the study successfully performed peak exercise evaluation. All patients had severe HF as shown by clinical evaluation, laboratory tests, echocardiography, spirometry with alveolar-capillary diffusion, and maximal cardiopulmonary exercise testing (CPET). CPETs with non-invasive CO measurements at rest and peak exercise were done on 2days at LVAD pump speed set randomly at 2 and 4. Increasing LVAD pump speed from 2 to 4 increased CO from 3.4±0.9 to 3.8±1.0L/min (ΔCO 0.4±0.6L/min, p=0.04) and from 5.3±1.3 to 5.9±1.4L/min (ΔCO 0.6±0.7L/min, p<0.01) at rest and peak exercise, respectively. Similarly, VO2 increased from 788±169 to 841±152mL/min (ΔVO2 52±76mL/min, p=0.01) and from 568±116 to 619±124mL/min (ΔVO2 69±96mL/min, p=0.02) at peak exercise and at anaerobic threshold, respectively. Δ(Ca-Cv)O2 did not change significantly, while ventilatory efficiency improved (VE/VCO2 slope from 39.9±5.4 to 34.9±8.3, ΔVE/VCO2 -5.0±6.4, p<0.01). In HF, an increase in CO with a higher LVAD pump speed is associated with increased peak VO2, postponed anaerobic threshold, and improved ventilatory efficiency. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. The antagonistic effect of K+o and dihydro-ouabain on the Na+ pump current of single rat and guinea-pig cardiac cells.

    PubMed Central

    Hermans, A N; Glitsch, H G; Verdonck, F

    1995-01-01

    1. The antagonistic effect of extracellular potassium ions (K+o) and dihydro-ouabain (DHO) on the Na(+)-K+ pump current (Ip) was studied in isolated ventricular cells. 2. The myocytes were isolated from rats and guinea-pigs, two species with different sensitivity towards cardiac glycosides. Ip measurements were performed at 32-34 degrees C by means of whole-cell recording. The membrane potential was held at -20 mV throughout. 3. The DHO concentration ([DHO]) required for half-maximal Ip inhibition (apparent KD value, KD') amounted to 2.4 x 10(-3) and 1.4 x 10(-5) M for rat and guinea-pig myocytes, respectively, at 5.4 mM K+o. 4. The data suggest one-to-one binding of DHO to the Na(+)-K+ pump and a smaller association rate constant, as well as a larger dissociation rate constant, for binding of DHO in the rat cells. 5. Ip activation by K+o was nearly identical in myocytes of both species and was measured to be half-maximal at approximately 1 mM K+o. Half-maximal Ip activation by K+o remained essentially unchanged, but Ip decreased in media containing [DHO] near the respective KD' at 5.4 mM K+o. 6. The concentration-response curve of Ip inhibition by DHO was shifted to higher [DHO] at higher [K+]o. KD' increased correspondingly. The slope of the curve was unaffected. 7. Ip and KD' displayed a similar dependence on [K+]o. 8. KD' was larger in Na(+)-free than in Na(+)-containing media under conditions in which the activation of Ip by K+o was nearly the same. 9. It is concluded that the antagonism between K+o and DHO, with regard to the activation of Ip, is non-competitive. A possible mechanism of the antagonism is discussed. The mechanism implies binding of K+o and DHO to different conformational states of the Na(+)-K+ pump which are temporarily exposed to the external face of the sarcolemma in the pump cycle. The DHO-bound states do not participate in the generation of Ip. PMID:7623280

  1. Structure and function of efflux pumps that confer resistance to drugs.

    PubMed Central

    Borges-Walmsley, M Ines; McKeegan, Kenneth S; Walmsley, Adrian R

    2003-01-01

    Resistance to therapeutic drugs encompasses a diverse range of biological systems, which all have a human impact. From the relative simplicity of bacterial cells, fungi and protozoa to the complexity of human cancer cells, resistance has become problematic. Stated in its simplest terms, drug resistance decreases the chance of providing successful treatment against a plethora of diseases. Worryingly, it is a problem that is increasing, and consequently there is a pressing need to develop new and effective classes of drugs. This has provided a powerful stimulus in promoting research on drug resistance and, ultimately, it is hoped that this research will provide novel approaches that will allow the deliberate circumvention of well understood resistance mechanisms. A major mechanism of resistance in both microbes and cancer cells is the membrane protein-catalysed extrusion of drugs from the cell. Resistant cells exploit proton-driven antiporters and/or ATP-driven ABC (ATP-binding cassette) transporters to extrude cytotoxic drugs that usually enter the cell by passive diffusion. Although some of these drug efflux pumps transport specific substrates, many are transporters of multiple substrates. These multidrug pumps can often transport a variety of structurally unrelated hydrophobic compounds, ranging from dyes to lipids. If we are to nullify the effects of efflux-mediated drug resistance, we must first of all understand how these efflux pumps can accommodate a diverse range of compounds and, secondly, how conformational changes in these proteins are coupled to substrate translocation. These are key questions that must be addressed. In this review we report on the advances that have been made in understanding the structure and function of drug efflux pumps. PMID:13678421

  2. From Gene to Function: Cell-Free Electrophysiological and Optical Analysis of Ion Pumps in Nanodiscs.

    PubMed

    Henrich, Erik; Sörmann, Janina; Eberhardt, Peter; Peetz, Oliver; Mezhyrova, Julija; Morgner, Nina; Fendler, Klaus; Dötsch, Volker; Wachtveitl, Josef; Bernhard, Frank; Bamann, Christian

    2017-09-19

    Nanodiscs that hold a lipid bilayer surrounded by a boundary of scaffold proteins have emerged as a powerful tool for membrane protein solubilization and analysis. By combining nanodiscs and cell-free expression technologies, even completely detergent-free membrane protein characterization protocols can be designed. Nanodiscs are compatible with various techniques, and due to their bilayer environment and increased stability, they are often superior to detergent micelles or liposomes for membrane protein solubilization. However, transport assays in nanodiscs have not been conducted so far, due to limitations of the two-dimensional nature of nanodisc membranes that offers no compartmentalization. Here, we study Krokinobacter eikastus rhodopsin-2 (KR2), a microbial light-driven sodium or proton pump, with noncovalent mass-spectrometric, electrophysiological, and flash photolysis measurements after its cotranslational insertion into nanodiscs. We demonstrate the feasibility of adsorbing nanodiscs containing KR2 to an artificial bilayer. This allows us to record light-induced capacitive currents that reflect KR2's ion transport activity. The solid-supported membrane assay with nanodisc samples provides reliable control over the ionic condition and information of the relative ion activity of this promiscuous pump. Our strategy is complemented with flash photolysis data, where the lifetimes of different photointermediates were determined at different ionic conditions. The advantage of using identical samples to three complementary approaches allows for a comprehensive comparability. The cell-free synthesis in combination with nanodiscs provides a defined hydrophobic lipid environment minimizing the detergent dependence often seen in assays with membrane proteins. KR2 is a promising tool for optogenetics, thus directed engineering to modify ion selectivity can be highly beneficial. Our approach, using the fast generation of functional ion pumps incorporated into

  3. Duration of red blood cell storage and outcomes in pediatric cardiac surgery: an association found for pump prime blood.

    PubMed

    Ranucci, Marco; Carlucci, Concetta; Isgrò, Giuseppe; Boncilli, Alessandra; De Benedetti, Donatella; De la Torre, Teresa; Brozzi, Simonetta; Frigiola, Alessandro

    2009-01-01

    Cardiac surgery using cardiopulmonary bypass in newborns, infants and small children often requires intraoperative red blood cell transfusions to prime the circuit and oxygenator and to replace blood lost during surgery. The purpose of this study was to investigate the influence of red blood cell storage time prior to transfusion on postoperative morbidity in pediatric cardiac operations. One hundred ninety-two consecutive children aged five years or less who underwent cardiac operations using cardiopulmonary bypass and who received red blood cells for priming the cardiopulmonary bypass circuit comprised the blood-prime group. Forty-seven patients receiving red blood cell transfusions after cardiopulmonary bypass were separately analyzed. Patients in the blood-prime group were divided into two groups based on the duration of storage of the red blood cells they received. The newer blood group included patients who received only red blood cells stored for less than or equal to four days and the older blood group included patients who received red blood cells stored for more than four days. Patients in the newer blood group had a significantly lower rate of pulmonary complications (3.5% versus 14.4%; P = 0.011) as well as a lower rate of acute renal failure (0.8% versus 5.2%; P = 0.154) than patients in the older blood group. Major complications (calculated as a composite score based on pulmonary, neurological, and gastroenterological complications, sepsis and acute renal failure) were found in 6.9% of the patients receiving newer blood and 17.1% of the patients receiving older blood (P = 0.027). After adjusting for other possible confounding variables, red blood cell storage time remained an independent predictor of major morbidity. The same association was not found for patients receiving red blood cell transfusions after cardiopulmonary bypass. The storage time of the red blood cells used for priming the cardiopulmonary bypass circuit in cardiac operations on

  4. Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice

    PubMed Central

    Al-Samir, Samer; Wang, Yong; Meissner, Joachim D.; Gros, Gerolf; Endeward, Volker

    2016-01-01

    We have studied cardiac and respiratory functions of aquaporin-1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals' hearts were analyzed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min−1 and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: (1) left ventricular wall thickness was reduced by 12%, (2) left ventricular mass, normalized to tibia length, was reduced by 10–20%, (3) cardiac muscle fiber cross sectional area was decreased by 17%, and (4) capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wild-type heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output. PMID:27252655

  5. Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

    PubMed Central

    2014-01-01

    Background Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. Materials and methods Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. Results Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF- group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF- group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF- group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. Conclusions Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of

  6. Prognostic value of left atrial function in systemic light-chain amyloidosis: a cardiac magnetic resonance study.

    PubMed

    Mohty, Dania; Boulogne, Cyrille; Magne, Julien; Varroud-Vial, Nicolas; Martin, Sylvain; Ettaif, Hind; Fadel, Bahaa M; Bridoux, Frank; Aboyans, Victor; Damy, Thibaud; Jaccard, Arnaud

    2016-09-01

    Cardiac involvement in systemic light-chain amyloidosis (AL) imparts an adverse impact on outcome. The left atrium (LA), by virtue of its anatomical location and muscular wall, is commonly affected by the amyloid process. Although LA infiltration by amyloid fibrils leads to a reduction in its pump function, the infiltration of the left ventricular (LV) myocardium results in diastolic dysfunction with subsequent increase in filling pressures and LA enlargement. Even though left atrial volume (LAV) is an independent prognostic marker in many cardiomyopathies, its value in amyloid heart disease remains to be determined. In addition, few data are available as to the prognostic value of LA function in systemic AL. Using cardiac magnetic resonance (CMR), the current study aims to assess the prognostic significance of the maximal LAV and total LA emptying fraction (LAEF) in patients with AL. Fifty-four consecutive patients (age 66 ± 10 years, 59% males) with confirmed systemic AL and mean LV ejection fraction of 60 ± 12% underwent CMR. As compared with patients with no or minimal cardiac involvement (Mayo Clinic [MC] stage I), those at moderate and high risk (MC stages II and III) had significantly larger indexed maximal LAV (36 ± 15 vs. 46 ± 13 vs. 52 ± 19 mL/m(2), P = 0.03) and indexed minimal LAV (20 ± 6 vs. 34 ± 11 vs. 44 ± 17 mL/m(2), P < 0.001), lower LAEF (42 ± 9 vs. 26 ± 13 vs. 16 ± 9%, P < 0.0001) but similar LVEF. Furthermore, myocardial late gadolinium enhancement (LGE) was more frequent and significantly associated with lower LAEF. LAEF was also significantly lower in symptomatic (NHYA ≥ II, 22 ± 14%) as compared with asymptomatic patients (NYHA class I, 33 ± 13%, P = 0.006). Two-year survival rate was lower in patients with LAEF ≤ 16% as compared with those with LAEF > 16% (37 ± 11 vs. 94 ± 4%, P = 0.001). In multivariate analysis, lower LAEF remained independently associated with a higher risk of 2-year mortality (HR = 1.08 per 1% decrease

  7. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    ERIC Educational Resources Information Center

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  8. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  9. Teaching Cardiac Autonomic Function Dynamics Employing the Valsalva (Valsalva-Weber) Maneuver

    ERIC Educational Resources Information Center

    Junqueira, Luiz Fernando, Jr.

    2008-01-01

    In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is outlined, followed by an explanation on the use of this approach for the evaluation of cardiac autonomic function based on underlying heart rate changes. The most important methodological and interpretative aspects of the Valsalva-Weber maneuver are critically updated,…

  10. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  11. Effects of interleukin-1 on cardiac fibroblast function: relevance to post-myocardial infarction remodelling.

    PubMed

    Turner, Neil A

    2014-01-01

    The cardiac fibroblast (CF) is a multifunctional and heterogeneous cell type that plays an essential role in regulating cardiac development, structure and function. Following myocardial infarction (MI), the myocardium undergoes complex structural remodelling in an attempt to repair the damaged tissue and overcome the loss of function induced by ischemia/reperfusion injury. Evidence is emerging that CF play critical roles in all stages of post-MI remodelling, including the initial inflammatory phase that is triggered in response to myocardial damage. CF are particularly responsive to the proinflammatory cytokine interleukin-1 (IL-1) whose levels are rapidly induced in the myocardium after MI. Studies from our laboratory in recent years have sought to evaluate the functional effects of IL-1 on human CF function and to determine the underlying molecular mechanisms. This review summarises these data and sets it in the context of post-MI cardiac remodelling, identifying the fibroblast as a potential therapeutic target for reducing adverse cardiac remodelling and its devastating consequences. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    PubMed Central

    Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

    2016-01-01

    Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID:27556313

  13. Cardiac and pulmonary function variability in Duchenne/Becker muscular dystrophy: an initial report.

    PubMed

    Birnkrant, David J; Ashwath, Mahi Lakshmi; Noritz, Garey H; Merrill, Michelle C; Shah, Tushar A; Crowe, Carol A; Bahler, Robert C

    2010-09-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks and then progressively declines. In this report, the authors quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. The authors concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in their clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for the use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy.

  14. Cardiac and Pulmonary Function Variability in Duchenne/Becker Muscular Dystrophy: An Initial Report

    PubMed Central

    Birnkrant, David J.; Ashwath, Mahi Lakshmi; Noritz, Garey H.; Merrill, Michelle C.; Shah, Tushar A.; Crowe, Carol A.; Bahler, Robert C.

    2013-01-01

    The Duchenne and Becker forms of muscular dystrophy are associated with dilated cardiomyopathy and are diseases in which pulmonary function peaks, then progressively declines. In this report, we quantify cardiopulmonary function variability among brothers. Brothers in 3 of 7 eligible sibships had discordant pulmonary function, with significant differences between the brothers' peak forced vital capacities and their vital capacities at last comparable age. There was no relationship between pulmonary and cardiac function among the siblings. We concluded that despite identical genetic mutations, cardiac and pulmonary function variability was common among brothers in our clinic with Duchenne or Becker muscular dystrophy. If confirmed by larger studies, these results have negative implications for use of genetic testing to predict cardiopulmonary course and response to therapies in Duchenne or Becker muscular dystrophy. PMID:20501885

  15. Healthy aging does not compromise the augmentation of cardiac function during heat stress.

    PubMed

    Gagnon, Daniel; Romero, Steven A; Ngo, Hai; Sarma, Satyam; Cornwell, William K; Poh, Paula Y S; Stoller, Douglas; Levine, Benjamin D; Crandall, Craig G

    2016-10-01

    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 (1.5°C increase in core temperature) conditions. During heat stress, increases in cardiac output were attenuated in aged adults (+2.5 ± 0.3 (95% CI) vs. young: +4.5 ± 0.5 l/min, P < 0.01) because of an attenuated chronotropic response (+30 ± 4 vs. young: +42 ± 5 beats/min, P < 0.01). In contrast to our hypothesis, a leftward shift of the Frank-Starling relation maintained stroke volume during heat stress in aged adults (76 ± 8 vs. normothermic: 74 ± 8 ml, P = 0.38) despite reductions in cardiac filling pressure (6.6 ± 1.0 vs. normothermic: 8.9 ± 1.1 mmHg, P < 0.01). In a subset of participants, volume loading was used to return cardiac filling pressure during heat stress to normothermic values, which resulted in a greater stroke volume for a given cardiac filling pressure in both groups. These results demonstrate that the Frank-Starling relation shifts during heat stress in healthy young and aged adults, thereby preserving stroke volume despite reductions in cardiac filling pressures. Copyright © 2016 the American Physiological Society.

  16. Analysis of Two-Dimensional Ultrasound Cardiac Strain Imaging using Joint Probability Density Functions

    PubMed Central

    Ma, Chi; Varghese, Tomy

    2014-01-01

    Ultrasound frame rates play a key role for accurate cardiac deformation tracking. Insufficient frame rates lead to an increase in signal decorrelation artifacts; resulting in erroneous displacement and strain estimation. Joint probability density distributions generated from estimated axial strain and its associated signal-to-noise ratio provide a useful approach to assess the minimum frame rate requirements. Previous reports have demonstrated that bimodal distributions in the joint probability density indicate inaccurate strain estimation over a cardiac cycle. In this study, we utilize similar analysis to evaluate a two-dimensional multi-level displacement tracking and strain estimation algorithm for cardiac strain imaging. The impact of different frame rates, final kernel dimensions, and a comparison of radiofrequency and envelope based processing are evaluated using echo signals derived from a three-dimensional finite element cardiac model and 5 healthy volunteers. Cardiac simulation model analysis demonstrate that the minimum frame rates required to obtain accurate joint probability distributions for the signal to noise ratio and strain, for a final kernel dimension of 1 λ by 3 A-lines, was around 42 Hz for radiofrequency signals. On the other hand, even a frame rate of 250Hz with envelope signals did not replicate the ideal joint probability distribution. For the volunteer study, clinical data was acquired only at a 34 Hz frame rate which appears to be sufficient for radiofrequency analysis. We also show that an increase in the final kernel dimensions significantly impact the strain probability distribution and joint probability density function generated; with a smaller impact on the variation in the accumulated mean strain estimated over a cardiac cycle. Our results demonstrate that radiofrequency frame rates currently achievable on clinical cardiac ultrasound systems are sufficient for accurate analysis of the strain probability distribution, when a multi

  17. Adaptive servo ventilation improves Cheyne-Stokes respiration, cardiac function, and prognosis in chronic heart failure patients with cardiac resynchronization therapy.

    PubMed

    Miyata, Makiko; Yoshihisa, Akiomi; Suzuki, Satoshi; Yamada, Shinya; Kamioka, Masashi; Kamiyama, Yoshiyuki; Yamaki, Takayoshi; Sugimoto, Koichi; Kunii, Hiroyuki; Nakazato, Kazuhiko; Suzuki, Hitoshi; Saitoh, Shu-ichi; Takeishi, Yasuchika

    2012-09-01

    Cheyne-Stokes respiration (CSR-CSA) is often observed in patients with chronic heart failure (CHF). Although cardiac resynchronization therapy (CRT) is effective for CHF patients with left ventricular dyssynchrony, it is still unclear whether adaptive servo ventilation (ASV) improves cardiac function and prognosis of CHF patients with CSR-CSA after CRT. Twenty two patients with CHF and CSR-CSA after CRT defibrillator (CRTD) implantation were enrolled in the present study and randomly assigned into two groups: 11 patients treated with ASV (ASV group) and 11 patients treated without ASV (non-ASV group). Measurement of plasma B-type natriuretic peptide (BNP) levels (before 3, and 6 months later) and echocardiography (before and 6 months) were performed in each group. Patients were followed up to register cardiac events (cardiac death and re-hospitalization) after discharge. In the ASV group, indices for apnea-hypopnea, central apnea, and oxyhemoglobin saturation were improved on ASV. BNP levels, cardiac systolic and diastolic function were improved with ASV treatment for 6 months. Importantly, the event-free rate was significantly higher in the ASV group than in the non-ASV group. ASV improves CSR-CSA, cardiac function, and prognosis in CHF patients with CRTD. Patients with CSR-CSA and post CRTD implantation would get benefits by treatment with ASV. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  18. Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frog.

    PubMed

    Ivanova, Iliyana V; Schubert, Rudolf; Duridanova, Dessislava B; Bolton, Thomas B; Lubomirov, Lubomir T; Gagov, Hristo S

    2007-11-01

    The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 +/- 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, R(p)-adenosine 3',5'-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic-pituitary-inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial alpha(1)-adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption.

  19. Autonomic control of cardiac function and myocardial oxygen consumption during hypoxic hypoxia.

    NASA Technical Reports Server (NTRS)

    Erickson, H. H.; Stone, H. L.

    1972-01-01

    Investigation in 19 conscious dogs of the importance of the sympathetic nervous system in the coronary and cardiac response to altitude (hypoxic) hypoxia. Beta-adrenergic blockade was used to minimize the cardiac effect associated with sympathetic receptors. It is shown that the autonomic nervous system, and particularly the sympathetic nervous system, is responsible for the increase in ventricular function and myocardial oxygen consumption that occurs during hypoxia. Minimizing this response through appropriate conditioning and training may improve the operating efficiency of the heart and reduce the hazard of hypoxia and other environmental stresses, such as acceleration, which are encountered in advanced aircraft systems.

  20. Linker of nucleoskeleton and cytoskeleton complex proteins in cardiac structure, function, and disease.

    PubMed

    Stroud, Matthew J; Banerjee, Indroneal; Veevers, Jennifer; Chen, Ju

    2014-01-31

    The linker of nucleoskeleton and cytoskeleton (LINC) complex, composed of proteins within the inner and the outer nuclear membranes, connects the nuclear lamina to the cytoskeleton. The importance of this complex has been highlighted by the discovery of mutations in genes encoding LINC complex proteins, which cause skeletal or cardiac myopathies. Herein, this review summarizes structure, function, and interactions of major components of the LINC complex, highlights how mutations in these proteins may lead to cardiac disease, and outlines future challenges in the field.

  1. Characterization of optically pumped semiconductor lasers in pulsed mode as a function of temperature

    NASA Astrophysics Data System (ADS)

    Bai, Yanbo; Wisdom, Jeffrey; Hyland, Patrick; Scholz, Christian; Chilla, Juan

    2017-02-01

    Self-heating of Optically Pumped Semiconductor (OPS) chip has been identified as the major limiting factor of power scaling in OPS-based lasers in continuous wave (cw) mode. In this work, characterization of OPS lasers in short pulse (100 ns) and low duty cycle (1%) regime, where self-heating is negligible, as a function of the heat sink temperature is presented. This data, combined with a rigorous thermal model, allows us to predict OPS chip performance in new cooling configurations for power scaling.

  2. Maturation status of sarcomere structure and function in human iPSC-derived cardiac myocytes.

    PubMed

    Bedada, Fikru B; Wheelwright, Matthew; Metzger, Joseph M

    2016-07-01

    Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  3. Fusion of structural and functional cardiac magnetic resonance imaging data for studying ventricular fibrillation.

    PubMed

    Magtibay, K; Beheshti, M; Foomany, F H; Balasundaram, K; Masse, S; Lai, P; Asta, J; Zamiri, N; Jaffray, D A; Nanthakumar, K; Krishnan, S; Umapathy, K

    2014-01-01

    Magnetic Resonance Imaging (MRI) techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) provide a complementing set of imaging data that can describe both the functional and structural states of biological tissues. This paper presents a Joint Independent Component Analysis (jICA) based fusion approach which can be utilized to fuse CDI and DTI data to quantify the differences between two cardiac states: Ventricular Fibrillation (VF) and Asystolic/Normal (AS/NM). Such an approach could lead to a better insight on the mechanism of VF. Fusing CDI and DTI data from 8 data sets from 6 beating porcine hearts, in effect, detects the differences between two cardiac states, qualitatively and quantitatively. This initial study demonstrates the applicability of MRI-based imaging techniques and jICA-based fusion approach in studying cardiac arrhythmias.

  4. MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and function following myocardial infarction.

    PubMed

    Koenig, Gerald C; Rowe, R Grant; Day, Sharlene M; Sabeh, Farideh; Atkinson, Jeffrey J; Cooke, Kenneth R; Weiss, Stephen J

    2012-05-01

    The myocardial extracellular matrix (ECM), an interwoven meshwork of proteins, glycoproteins, proteoglycans, and glycosaminoglycans that is dominated by polymeric fibrils of type I collagen, serves as the mechanical scaffold on which myocytes are arrayed for coordinated and synergistic force transduction. Following ischemic injury, cardiac ECM remodeling is initiated via localized proteolysis, the bulk of which has been assigned to matrix metalloproteinase (MMP) family members. Nevertheless, the key effector(s) of myocardial type I collagenolysis both in vitro and in vivo have remained unidentified. In this study, using cardiac explants from mice deficient in each of the major type I collagenolytic MMPs, including MMP-13, MMP-8, MMP-2, MMP-9, or MT1-MMP, we identify the membrane-anchored MMP, MT1-MMP, as the dominant collagenase that is operative within myocardial tissues in vitro. Extending these observations to an in vivo setting, mice heterozygous for an MT1-MMP-null allele display a distinct survival advantage and retain myocardial function relative to wild-type littermates in an experimental model of myocardial infarction, effects associated with preservation of the myocardial type I collagen network as a consequence of the decreased collagenolytic potential of cardiac fibroblasts. This study identifies MT1-MMP as a key MMP responsible for effecting postinfarction cardiac ECM remodeling and cardiac dysfunction.

  5. Generation of Functional Human Cardiac Progenitor Cells by High-Efficiency Protein Transduction

    PubMed Central

    Li, Xiao-Hong; Li, Qianqian; Jiang, Lin; Deng, Chunyu; Liu, Zaiyi; Fu, Yongheng; Zhang, Mengzhen; Tan, Honghong; Feng, Yuliang; Shan, Zhixin

    2015-01-01

    The reprogramming of fibroblasts to induced pluripotent stem cells raises the possibility that somatic cells could be directly reprogrammed to cardiac progenitor cells (CPCs). The present study aimed to assess highly efficient protein-based approaches to reduce or eliminate the genetic manipulations to generate CPCs for cardiac regeneration therapy. A combination of QQ-reagent-modified Gata4, Hand2, Mef2c, and Tbx5 and three cytokines rapidly and efficiently reprogrammed human dermal fibroblasts (HDFs) into CPCs. This reprogramming process enriched trimethylated histone H3 lysine 4, monoacetylated histone H3 lysine 9, and Baf60c at the Nkx2.5 cardiac enhancer region by the chromatin immunoprecipitation quantitative polymerase chain reaction assay. Protein-induced CPCs transplanted into rat hearts after myocardial infarction improved cardiac function, and this was related to differentiation into cardiomyocyte-like cells. These findings demonstrate that the highly efficient protein-transduction method can directly reprogram HDFs into CPCs. This protein reprogramming strategy lays the foundation for future refinements both in vitro and in vivo and might provide a source of CPCs for regenerative approaches. Significance The findings from the present study have demonstrated an efficient protein-transduction method of directly reprogramming fibroblasts into cardiac progenitor cells. These results have great potential in cell-based therapy for cardiovascular diseases. PMID:26564862

  6. Absolute Postoperative B-Type Natriuretic Peptide Concentrations, but Not Their General Trend, Are Associated With 12-Month, All-Cause Mortality After On-Pump Cardiac Surgery.

    PubMed

    Mauermann, Eckhard; Bolliger, Daniel; Fassl, Jens; Grapow, Martin; Seeberger, Esther E; Seeberger, Manfred D; Filipovic, Miodrag; Lurati Buse, Giovanna A L

    2017-09-01

    B-type natriuretic peptide (BNP) is a predictor of mortality after on-pump cardiac surgery. However, previous limited and heterogeneous studies have focused on peak concentrations at 3 to 5 days after surgery and may not offer clinicians much help in early decision-making. After confirming the predictive value of first-postoperative-day BNP in a preliminary analysis, we explored the association between isolated second-postoperative-day BNP concentrations, second-day BNP concentrations in conjunction with first-day BNP concentrations, and the change in BNP (ie, ΔBNP) from the first to the second postoperative day and 12-month, all-cause mortality. We included consecutive patients undergoing on-pump cardiac surgery in this observational, secondary analysis of prospectively collected data. We analyzed biomarkers on the first and second postoperative day. ΔBNP was defined as BNP on the second postoperative day minus BNP on the first postoperative day. The primary end point was 12-month, all-cause mortality. The secondary end point was a composite of major adverse cardiac events (MACEs) at 12 months and/or all-cause mortality at 12 months. MACE was defined as nonfatal cardiac arrest, myocardial infarction, and congestive heart failure. The association between BNP and outcomes was examined by receiver operating characteristic curves, as well as univariate and multivariable logistic regression, adjusting for the EuroSCORE II, cross-clamp time, and first-postoperative-day troponin T. We included 1199 patients in the preliminary analysis focused on BNP on postoperative day 1. In the analyses examining BNP variables requiring second-postoperative-day BNP measurement (n = 708), we observed 66 (9.3%) deaths, 48 (6.8%) MACE, and 104 (14.7%) deaths and/or MACE. Both first- and second-postoperative-day BNP were significant independent predictors of all-cause, 12-month mortality per 100 ng/L increase (adjusted odds ratio [aOR], 1.040 [95% confidence interval (CI), 1

  7. The role of sirtuins in mitochondrial function and doxorubicin-induced cardiac dysfunction.

    PubMed

    Dolinsky, Vernon W

    2017-08-28

    Anthracycline chemotherapeutics such as doxorubicin continue to be important treatments for many cancers. Through improved screening and therapy, more patients are surviving and living longer after the diagnosis of their cancer. However, anthracyclines are associated with both short- and long-term cardiotoxic effects. Doxorubicin-induced mitochondrial dysfunction is a central mechanism in the cardiotoxic effects of doxorubicin that contributes to impaired cardiac energy levels, increased reactive oxygen species production, cardiomyocyte apoptosis and the decline in cardiac function. Sirtuins are protein deacetylases that are activated by low energy levels and stimulate energy production through their activation of transcription factors and enzymatic regulators of cardiac energy metabolism. In addition, sirtuins activate oxidative stress resistance pathways. SIRT1 and SIRT3 are expressed at high levels in the cardiomyocyte. This review examines the function of sirtuins in the regulation of cardiac mitochondrial function, with a focus on their role in heart failure and an emphasis on their effects on doxorubicin-induced cardiotoxicity. We discuss the potential for sirtuin activation in combination with anthracycline chemotherapy in order to mitigate its cardiotoxic side-effects without reducing the antineoplastic activity of anthracyclines.

  8. Embryonic stem cell-based cardiopatches improve cardiac function in infarcted rats.

    PubMed

    Vallée, Jean-Paul; Hauwel, Mathieu; Lepetit-Coiffé, Matthieu; Bei, Wang; Montet-Abou, Karin; Meda, Paolo; Gardier, Stephany; Zammaretti, Prisca; Kraehenbuehl, Thomas P; Herrmann, Francois; Hubbell, Jeffrey A; Jaconi, Marisa E

    2012-03-01

    Pluripotent stem cell-seeded cardiopatches hold promise for in situ regeneration of infarcted hearts. Here, we describe a novel cardiopatch based on bone morphogenetic protein 2-primed cardiac-committed mouse embryonic stem cells, embedded into biodegradable fibrin matrices and engrafted onto infarcted rat hearts. For in vivo tracking of the engrafted cardiac-committed cells, superparamagnetic iron oxide nanoparticles were magnetofected into the cells, thus enabling detection and functional evaluation by high-resolution magnetic resonance imaging. Six weeks after transplantation into infarcted rat hearts, both local (p < .04) and global (p < .015) heart function, as well as the left ventricular dilation (p < .0011), were significantly improved (p < .001) as compared with hearts receiving cardiopatches loaded with iron nanoparticles alone. Histological analysis revealed that the fibrin scaffolds had degraded over time and clusters of myocyte enhancer factor 2-positive cardiac-committed cells had colonized most of the infarcted myocardium, including the fibrotic area. De novo CD31-positive blood vessels were formed in the vicinity of the transplanted cardiopatch. Altogether, our data provide evidence that stem cell-based cardiopatches represent a promising therapeutic strategy to achieve efficient cell implantation and improved global and regional cardiac function after myocardial infarction.

  9. Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac Function and Angiogenesis Following Infarction

    PubMed Central

    Boopathy, Archana V.; Martinez, Mario D.; Smith, Amanda Walker; Brown, Milton E.; García, Andrés J.

    2015-01-01

    Myocardial infarction (MI) is the leading cause of death worldwide. Notch1 signaling plays a critical role in cardiac development, in survival, cardiogenic lineage commitment, differentiation of cardiac stem/progenitor cells, and in regenerative responses following myocardial injury. The objective of this study was the evaluation of the therapeutic effect of delivering the Notch ligand-containing hydrogels in a rat model of MI. Self-assembling peptide (SAP) hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1 (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to the infarcted heart resulted in improvement in cardiac function back to sham-operated levels. A significant decrease in fibrosis and an increase in the endothelial vessel area and Ki67 expression were also observed in rats treated with the RJ hydrogels compared to untreated rats or rats treated with unmodified or scrambled peptide hydrogels. This study demonstrates the functional benefit of Notch1-activating peptide delivered in SAP hydrogels for cardiac repair. PMID:25982380

  10. Update on the slow delayed rectifier potassium current (I(Ks)): role in modulating cardiac function.

    PubMed

    Liu, Zhenzhen; Du, Lupei; Li, Minyong

    2012-01-01

    The slow delayed rectifier current (I(Ks)) is the slow component of cardiac delayed rectifier current and is critical for the late phase repolarization of cardiac action potential. This current is also an important target for Sympathetic Nervous System (SNS) to regulate the cardiac electivity to accommodate to heart rate alterations in response to exercise or emotional stress and can be up-regulated by β- adrenergic or other signal molecules. I(Ks) channel is originated by the co-assembly of pore-forming KCNQ1 α-subunit and accessory KCNE1 β-subunit. Mutations in any subunit can bring about severe long QT syndrome (LQT-1, LQT-5) as characterized by deliquium, seizures and sudden death. This review summarizes the normal physiological functions and molecular basis of I(Ks) channels, as well as illustrates up-to-date development on its blockers and activators. Therefore, the current extensive survey should generate fundamental understanding of the role of I(Ks) channel in modulating cardiac function and donate some instructions to the progression of I(Ks) blockers and activators as potential antiarrhythmic agents or pharmacological tools to determine the physiological and pathological function of I(Ks).

  11. Heart-specific Rpd3 downregulation enhances cardiac function and longevity

    PubMed Central

    Kopp, Zachary A.; Hsieh, Jo-Lin; Li, Andrew; Wang, William; Bhatt, Dhelni T.; Lee, Angela; Kim, Sae Yeon; Fan, David; Shah, Veevek; Siddiqui, Emaad; Ragam, Radhika; Park, Kristen; Ardeshna, Dev; Park, Kunwoo; Wu, Rachel; Parikh, Hardik; Parikh, Ayush; Lin, Yuh-Ru; Park, Yongkyu

    2015-01-01

    Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment. PMID:26399365

  12. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction

    PubMed Central

    Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

    2014-01-01

    Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium. PMID:24936220

  13. Pulsed electromagnetic field improves cardiac function in response to myocardial infarction.

    PubMed

    Hao, Chang-Ning; Huang, Jing-Juan; Shi, Yi-Qin; Cheng, Xian-Wu; Li, Hao-Yun; Zhou, Lin; Guo, Xin-Gui; Li, Rui-Lin; Lu, Wei; Zhu, Yi-Zhun; Duan, Jun-Li

    2014-01-01

    Extracorporeal pulsed electromagnetic field (PEMF) has been shown the ability to improve regeneration in various ischemic episodes. Here, we examined whether PEMF therapy facilitate cardiac recovery in rat myocardial infarction (MI), and the cellular/molecular mechanisms underlying PEMF-related therapy was further investigated. The MI rats were exposed to active PEMF for 4 cycles per day (8 minutes/cycle, 30 ± 3 Hz, 5 mT) after MI induction. The data demonstrated that PEMF treatment significantly inhibited cardiac apoptosis and improved cardiac systolic function. Moreover, PEMF treatment increased capillary density, the levels of vascular endothelial growth factor (VEGF) and hypoxic inducible factor-1α in infarct border zone. Furthermore, the number and function of circulating endothelial progenitor cells were advanced in PEMF treating rats. In vitro, PEMF induced the degree of human umbilical venous endothelial cells tubulization and increased soluble pro-angiogenic factor secretion (VEGF and nitric oxide). In conclusion, PEMF therapy preserves cardiac systolic function, inhibits apoptosis and trigger postnatal neovascularization in ischemic myocardium.

  14. Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences.

    PubMed

    Zhang, P; Su, J; Mende, U

    2012-12-15

    The heart is comprised of a syncytium of cardiac myocytes (CM) and surrounding nonmyocytes, the majority of which are cardiac fibroblasts (CF). CM and CF are highly interspersed in the myocardium with one CM being surrounded by one or more CF. Bidirectional cross talk between CM and CF plays important roles in determining cardiac mechanical and electrical function in both normal and diseased hearts. Genetically engineered animal models and in vitro studies have provided evidence that CM and CF can regulate each other's function. Their cross talk contributes to structural and electrical remodeling in both atria and ventricles and appears to be involved in the pathogenesis of various heart diseases that lead to heart failure and arrhythmia disorders. Mechanisms of CM-CF cross talk, which are not yet fully understood, include release of paracrine factors, direct cell-cell interactions via gap junctions and potentially adherens junctions and nanotubes, and cell interactions with the extracellular matrix. In this article, we provide an overview of the existing multiscale experimental and computational approaches for the investigation of cross talk between CM and CF and review recent progress in our understanding of the functional consequences and underlying mechanisms. Targeting cross talk between CM and CF could potentially be used therapeutically for the modulation of the cardiac remodeling response in the diseased heart and may lead to new strategies for the treatment of heart failure or rhythm disturbances.

  15. Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac Function and Angiogenesis Following Infarction.

    PubMed

    Boopathy, Archana V; Martinez, Mario D; Smith, Amanda Walker; Brown, Milton E; García, Andrés J; Davis, Michael E

    2015-09-01

    Myocardial infarction (MI) is the leading cause of death worldwide. Notch1 signaling plays a critical role in cardiac development, in survival, cardiogenic lineage commitment, differentiation of cardiac stem/progenitor cells, and in regenerative responses following myocardial injury. The objective of this study was the evaluation of the therapeutic effect of delivering the Notch ligand-containing hydrogels in a rat model of MI. Self-assembling peptide (SAP) hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1 (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to the infarcted heart resulted in improvement in cardiac function back to sham-operated levels. A significant decrease in fibrosis and an increase in the endothelial vessel area and Ki67 expression were also observed in rats treated with the RJ hydrogels compared to untreated rats or rats treated with unmodified or scrambled peptide hydrogels. This study demonstrates the functional benefit of Notch1-activating peptide delivered in SAP hydrogels for cardiac repair.

  16. Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions.

    PubMed

    Loichot, Cécile; Jesel, Laurence; Tesse, Angela; Tabernero, Antonia; Schoonjans, Kristina; Roul, Gérard; Carpusca, Irina; Auwerx, Johan; Andriantsitohaina, Ramaroson

    2006-07-01

    The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major role in the control of cardiac energy metabolism. The role of PPARalpha on cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARalpha did not affect systolic blood pressure and heart rate. Echocardiographic measurements demonstrated reduced systolic performance as shown by the decrease of left ventricular fractional shortening in PPARalpha -/- mice. Telemetric electrocardiography revealed neither atrio- nor intraventricular conduction defects in PPARalpha -/- mice. Also, heart rate, P-wave duration and amplitude, and QT interval were not affected. However, the amplitude of T wave from PPARalpha -/- mice was lower compared with wild-type (PPARalpha +/+) mice. When the myocardial function was measured by ex vivo Langendorff's heart preparation, basal and beta-adrenergic agonist-induced developed forces were significantly reduced in PPARalpha-null mice. In addition, Western blot analysis shows that the protein expression of beta1-adrenergic receptor is reduced in hearts from PPARalpha -/- mice. Histological analysis showed that hearts from PPARalpha -/- but not PPARalpha +/+ mice displayed myocardial fibrosis. These results suggest that PPARalpha-null mice have an alteration of cardiac contractile performance under basal and under stimulation of beta1-adrenergic receptors. These effects are associated with myocardial fibrosis. The data shed light on the role of PPARalpha in maintaining cardiac functions.

  17. Remote ischemic preconditioning improves post resuscitation cerebral function via overexpressing neuroglobin after cardiac arrest in rats.

    PubMed

    Fan, Ran; Yu, Tao; Lin, Jia-Li; Ren, Guang-Dong; Li, Yi; Liao, Xiao-Xing; Huang, Zi-Tong; Jiang, Chong-Hui

    2016-10-01

    In this study, we investigated the effects of remote ischemic preconditioning on post resuscitation cerebral function in a rat model of cardiac arrest and resuscitation. The animals were randomized into six groups: 1) sham operation, 2) lateral ventricle injection and sham operation, 3) cardiac arrest induced by ventricular fibrillation, 4) lateral ventricle injection and cardiac arrest, 5) remote ischemic preconditioning initiated 90min before induction of ventricular fibrillation, and 6) lateral ventricle injection and remote ischemic preconditioning before cardiac arrest. Reagent of Lateral ventricle injection is neuroglobin antisense oligodeoxynucleotides which initiated 24h before sham operation, cardiac arrest or remote ischemic preconditioning. Remote ischemic preconditioning was induced by four cycles of 5min of limb ischemia, followed by 5min of reperfusion. Ventricular fibrillation was induced by current and lasted for 6min. Defibrillation was attempted after 6min of cardiopulmonary resuscitation. The animals were then monitored for 2h and observed for an additionally maximum 70h. Post resuscitation cerebral function was evaluated by neurologic deficit score at 72h after return of spontaneous circulation. Results showed that remote ischemic preconditioning increased neurologic deficit scores. To investigate the neuroprotective effects of remote ischemic preconditioning, we observed neuronal injury at 48 and 72h after return of spontaneous circulation and found that remote ischemic preconditioning significantly decreased the occurrence of neuronal apoptosis and necrosis. To further comprehend mechanism of neuroprotection induced by remote ischemic preconditioning, we found expression of neuroglobin at 24h after return of spontaneous circulation was enhanced. Furthermore, administration of neuroglobin antisense oligodeoxynucleotides before induction of remote ischemic preconditioning showed that the level of neuroglobin was decreased then partly abrogated

  18. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium

    PubMed Central

    Turnbull, Irene C.; Karakikes, Ioannis; Serrao, Gregory W.; Backeris, Peter; Lee, Jia-Jye; Xie, Chaoqin; Senyei, Grant; Gordon, Ronald E.; Li, Ronald A.; Akar, Fadi G.; Hajjar, Roger J.; Hulot, Jean-Sébastien; Costa, Kevin D.

    2014-01-01

    Cardiac experimental biology and translational research would benefit from an in vitro surrogate for human heart muscle. This study investigated structural and functional properties and interventional responses of human engineered cardiac tissues (hECTs) compared to human myocardium. Human embryonic stem cell-derived cardiomyocytes (hESC-CMs, >90% troponin-positive) were mixed with collagen and cultured on force-sensing elastomer devices. hECTs resembled trabecular muscle and beat spontaneously (1.18±0.48 Hz). Microstructural features and mRNA expression of cardiac-specific genes (α-MHC, SERCA2a, and ACTC1) were comparable to human myocardium. Optical mapping revealed cardiac refractoriness with loss of 1:1 capture above 3 Hz, and cycle length dependence of the action potential duration, recapitulating key features of cardiac electrophysiology. hECTs reconstituted the Frank-Starling mechanism, generating an average maximum twitch stress of 660 μN/mm2 at Lmax, approaching values in newborn human myocardium. Dose-response curves followed exponential pharmacodynamics models for calcium chloride (EC50 1.8 mM) and verapamil (IC50 0.61 μM); isoproterenol elicited a positive chronotropic but negligible inotropic response, suggesting sarcoplasmic reticulum immaturity. hECTs were amenable to gene transfer, demonstrated by successful transduction with Ad.GFP. Such 3-D hECTs recapitulate an early developmental stage of human myocardium and promise to offer an alternative preclinical model for cardiology research.—Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J.-J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J.-S., Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. PMID:24174427

  19. High-Resolution MRI of Cardiac Function With Projection Reconstruction and Steady-State Free Precession

    PubMed Central

    Peters, Dana C.; Ennis, Daniel B.; McVeigh, Elliot R.

    2007-01-01

    The purpose of this study was to investigate the trabecular structure of the endocardial wall of the living human heart, and the effect of that structure on the measurement of myocardial function using MRI. High-resolution MR images (0.8 × 0.8 × 8 mm voxels) of cardiac function were obtained in five volunteers using a combination of undersampled projection reconstruction (PR) and steady-state free precession (SSFP) contrast in ECG-gated breath-held scans. These images provide movies of cardiac function with new levels of endocardial detail. The trabecular-papillary muscle complex, consisting of a mixture of blood and endocardial structures, is measured to constitute as much as 50% of the myocardial wall in some sectors. Myocardial wall strain measurements derived from tagged MR images show correlation between regions of trabeculae and papillary muscles and regions of high strain, leading to an overestimation of function in the lateral wall. PMID:12111934

  20. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish.

    PubMed

    Frese, Karen S; Meder, Benjamin; Keller, Andreas; Just, Steffen; Haas, Jan; Vogel, Britta; Fischer, Simon; Backes, Christina; Matzas, Mark; Köhler, Doreen; Benes, Vladimir; Katus, Hugo A; Rottbauer, Wolfgang

    2015-08-15

    Alternative splicing is one of the major mechanisms through which the proteomic and functional diversity of eukaryotes is achieved. However, the complex nature of the splicing machinery, its associated splicing regulators and the functional implications of alternatively spliced transcripts are only poorly understood. Here, we investigated the functional role of the splicing regulator rbfox1 in vivo using the zebrafish as a model system. We found that loss of rbfox1 led to progressive cardiac contractile dysfunction and heart failure. By using deep-transcriptome sequencing and quantitative real-time PCR, we show that depletion of rbfox1 in zebrafish results in an altered isoform expression of several crucial target genes, such as actn3a and hug. This study underlines that tightly regulated splicing is necessary for unconstrained cardiac function and renders the splicing regulator rbfox1 an interesting target for investigation in human heart failure and cardiomyopathy.

  1. Accumulation of Mitochondrial DNA Mutations Disrupts Cardiac Progenitor Cell Function and Reduces Survival.

    PubMed

    Orogo, Amabel M; Gonzalez, Eileen R; Kubli, Dieter A; Baptista, Igor L; Ong, Sang-Bing; Prolla, Tomas A; Sussman, Mark A; Murphy, Anne N; Gustafsson, Åsa B

    2015-09-04

    Transfer of cardiac progenitor cells (CPCs) improves cardiac function in heart failure patients. However, CPC function is reduced with age, limiting their regenerative potential. Aging is associated with numerous changes in cells including accumulation of mitochondrial DNA (mtDNA) mutations, but it is unknown how this impacts CPC function. Here, we demonstrate that acquisition of mtDNA mutations disrupts mitochondrial function, enhances mitophagy, and reduces the replicative and regenerative capacities of the CPCs. We show that activation of differentiation in CPCs is associated with expansion of the mitochondrial network and increased mitochondrial oxidative phosphorylation. Interestingly, mutant CPCs are deficient in mitochondrial respiration and rely on glycolysis for energy. In response to differentiation, these cells fail to activate mitochondrial respiration. This inability to meet the increased energy demand leads to activation of cell death. These findings demonstrate the consequences of accumulating mtDNA mutations and the importance of mtDNA integrity in CPC homeostasis and regenerative potential.

  2. Use of Lactated Ringer’s solution does not eliminate the risk of strong ion difference-related metabolic acidosis following on-pump cardiac surgery.

    PubMed

    Jovaisa, T; Vicka, V; Linkaitė, G; Guseinovaitė, J; Ringaitienė, D; Norkienė, I

    2016-01-01

    There is a growing interest in the effects of plasma sodium levels on postoperative outcomes. A trend of using balanced crystalloid solutions is based on the extensive data on chloride and the strong ion difference-related acidosis. However, effects of sodium are often overlooked in this context. The aim of the study was to establish the effects of the routine use of Lactated Ringer’s Solution (RL) on postoperative changes in sodium concentrations and whether these changes result in metabolic acidosis. We performed database analysis of 358 consecutive elective on-pump cardiac surgery cases in a tertiary referral university hospital. Approval from the institutional ethics committee was obtained for this study. Intraoperative fluid balance was 2726±1073 ml and the total volume of intravenous infusions in the first 24 hours was 5865 (±1073) ml, 95% of which was RL; 58% of the patients had metabolic acidosis with a base excess below (–)2 mmol L–1 on arrival at the intensive care unit. There was a significant correlation between a strong ion difference and base excess (p less than 0.01). A significant improvement in metabolic acidosis was noted within the first 24 hours, from a base excess of (–)2.49±2.8 to 0.32±2.6 mmol L–1 (p less than 0.001). All of the improvement in the base excess is explained by a change in the strong ion difference from the mean value of 31±4.3 to 34.2±3.6 mmol L–1 (p less than 0.001). Changes in the strong ion difference were primarily driven by changes in the serum sodium concentration, which were three-fold higher compared to those of chloride [–2.36 (±2.6) mmol L–1 (p less than 0.001) and 0.84 (±3.2) mmol L–1, respectively (p = 0.01)]. In conclusion, our data confirm that there is a direct correlation between a strong ion difference and base excess following on-pump cardiac surgery. The use of RL prevented significant hyperchloraemia, but did not eliminate the risk of strong ion difference-related metabolic acidosis. The

  3. Cardiac Remodeling and Disease: Current Understanding of STIM1/Orai1-Mediated Store-Operated Ca(2+) Entry in Cardiac Function and Pathology.

    PubMed

    Bartoli, Fiona; Sabourin, Jessica

    2017-01-01

    For a long time, Ca(2+) entry into cardiomyocytes was considered the sole domain of the L-type Ca(2+) channel. Recently, STIM1/Orai1-mediated store-operated Ca(2+) entry has been also reported to participate to Ca(2+) influx in cardiac cells and has emerged as a key player to alter Ca(2+) in the cardiomyocyte. In this review, we will highlight accumulated knowledge about the presence and the potential contribution of STIM1/Orai1-dependent SOCE to cardiac function and its role in the cardiac pathogenesis. Overall, even if STIM1/Orai1 proteins are present in the heart, contradictory results have been reported regarding their contribution to cardiac physiology and pathology, pointing out the necessity of further investigations, a major challenge over the coming years.

  4. Activation of SIRT3 by resveratrol ameliorates cardiac fibrosis and improves cardiac function via the TGF-β/Smad3 pathway.

    PubMed

    Chen, Tongshuai; Li, Jingyuan; Liu, Junni; Li, Na; Wang, Shujian; Liu, Hui; Zeng, Mei; Zhang, Yun; Bu, Peili

    2015-03-01

    Sirtuins [sirtuin (SIRT)1-SIRT7] mediate the longevity-promoting effects of calorie restriction in yeast, worms, flies, and mice. Additionally, SIRT3 is the only SIRT analog whose increased expression has been shown to be associated with longevity in humans. The polyphenol resveratrol (RSV) is the first compound discovered able to mimic calorie restriction by stimulating SIRTs. In the present study, we report that RSV activated SIRT3 in cardiac fibroblasts both in vivo and in vitro. Moreover, in wild-type mice, RSV prevented cardiac hypertrophy in response to hypertrophic stimuli. However, this protective effect was not observed in SIRT3 knockout mice. Additionally, the activation of SIRT3 by RSV ameliorated collagen deposition and improved cardiac function. In isolated cardiac fibroblasts, pretreatment with RSV suppressed fibroblast-to-myoblast transformation by inhibiting the transforming growth factor-β/Smad3 pathway. Therefore, these data indicate that the activation of SIRT3 by RSV could ameliorate cardiac fibrosis and improve cardiac function via the transforming growth factor-β/Smad3 pathway. Copyright © 2015 the American Physiological Society.

  5. Cardiac myofilaments: mechanics and regulation

    NASA Technical Reports Server (NTRS)

    de Tombe, Pieter P.; Bers, D. M. (Principal Investigator)

    2003-01-01

    The mechanical properties of the cardiac myofilament are an important determinant of pump function of the heart. This report is focused on the regulation of myofilament function in cardiac muscle. Calcium ions form the trigger that induces activation of the thin filament which, in turn, allows for cross-bridge formation, ATP hydrolysis, and force development. The structure and protein-protein interactions of the cardiac sarcomere that are responsible for these processes will be reviewed. The molecular mechanism that underlies myofilament activation is incompletely understood. Recent experimental approaches have been employed to unravel the mechanism and regulation of myofilament mechanics and energetics by activator calcium and sarcomere length, as well as contractile protein phosphorylation mediated by protein kinase A. Central to these studies is the question whether such factors impact on muscle function simply by altering thin filament activation state, or whether modulation of cross-bridge cycling also plays a part in the responses of muscle to these stimuli.

  6. ICF-based approach to evaluating functionality in cardiac rehabilitation patients after heart surgery.

    PubMed

    Racca, V; Di Rienzo, M; Mazzini, P; Ripamonti, V; Gasti, G; Spezzaferri, R; Modica, M; Ferratini, M

    2015-08-01

    Heart surgery is a frequent reason for admission to in-patient cardiac rehabilitation programmes. ICF approach has never been used to evaluate cardiac patients after major heart surger