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Sample records for cardiac pumping function

  1. 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

  2. Two functionally different Na/K pumps in cardiac ventricular myocytes

    PubMed Central

    1995-01-01

    The whole-cell patch-clamp technique was used to voltage clamp acutely isolated myocytes at -60 mV and study effects of ionic environment on Na/K pump activity. In quiescent guinea pig myocytes, normal intracellular Na+ is approximately 6 mM, which gives a total pump current of 0.25 +/- 0.09 pA/pF, and an inward background sodium current of 0.75 +/- 0.26 pA/pF. The average capacitance of a cell is 189 +/- 61 pF. Our main conclusion is the total Na/K pump current comprises currents from two different types of pumps, whose functional responses to the extracellular environment are different. Pump current was reversibly blocked with two affinities by extracellular dihydro-ouabain (DHO). We determined dissociation constants of 72 microM for low affinity (type-1) pumps and 0.75 microM for high affinity (type-h) pumps. These dissociation constants did not detectably change with two intracellular Na+ concentrations, one saturating and one near half- saturating, and with two extracellular K+ concentrations of 4.6 and 1.0 mM. Ion effects on type-h pumps were therefore measured using 5 microM DHO and on total pump current using 1 mM DHO. Extracellular K+ half- maximally activated the type-h pumps at 0.4 mM and the type-1 at 3.7 mM. Extracellular H+ blocked the type-1 pumps with half-maximal blockade at a pH of 7.71 whereas the type-h pumps were insensitive to extracellular pH. Both types of pumps responded similarly to changes in intracellular-Na+, with 9.6 mM causing half-maximal activation. Neither changes in intracellular pH between 6.0 and 7.2, nor concentrations of intracellular K+ of 140 mM or below, had any effect on either type of pump. The lack of any effect of intracellular K+ suggests the dissociation constants are in the molar range so this step in the pump cycle is not rate limiting under normal physiological conditions. Changes in intracellular-Na+ did not affect the half-maximal activation by extracellular K+, and vice versa. We found DHO-blockade of Na/K pump

  3. Biomechanics of Cardiac Function.

    PubMed

    Voorhees, Andrew P; Han, Hai-Chao

    2015-10-01

    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

  4. Cardiac Na Channels: Structure to Function.

    PubMed

    DeMarco, K R; Clancy, C E

    2016-01-01

    Heart rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. Opening of the primary cardiac voltage-gated sodium (NaV1.5) channel initiates cellular depolarization and the propagation of an electrical action potential that promotes coordinated contraction of the heart. The regularity of these contractile waves is critically important since it drives the primary function of the heart: to act as a pump that delivers blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. Perturbations to NaV1.5 may alter the structure, and hence the function, of the ion channel and are associated downstream with a wide variety of cardiac conduction pathologies, such as arrhythmias. PMID:27586288

  5. Symmetry of cardiac function assessment.

    PubMed

    Bai, Xu-Fang; Ma, Amy X

    2016-09-01

    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

  6. 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

  7. 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.

  8. Characterization of the electrogenic sodium pump in cardiac Purkinje fibres

    PubMed Central

    Eisner, D. A.; Lederer, W. J.

    1980-01-01

    1. The Na pump is examined in sheep cardiac Purkinje fibres using a two micro-electrode voltage clamp technique. 2. After reducing the external K concentration, [K]o, to zero for 2 min or more, subsequent addition of an `activator cation' (known to activate the Na pump in other preparations) produces a transient increase of outward current. This outward current transient is abolished by 10-5 M-strophanthidin (cf. Gadsby & Cranefield, 1979a). 3. It is concluded that this transient increase of outward current is a result of a transient stimulation of the sodium pump by the raised [Na]i following exposure to 0-Ko. Although this current transient may reflect the activity of an electrogenic Na pump, it is difficult to use K as the activator cation to establish this point. This is due to the extracellular K depletion that occurs during Na pump reactivation and the subsequent change that this K depletion produces in the current—voltage relationship of the Purkinje fibre. 4. Rbo or Cso have been used instead of Ko to reactivate the Na pump when examining the transient increase of outward current. On adding either of these cations after exposing a preparation to a solution without such `activator cations', the outward current transient is relatively voltage independent over a wide range of potentials (-90 to +10 mV). It is concluded that, following the addition of Rbo or Cso, the transient increase of outward current is a direct measure of the transient increase of the electrogenic Na pump current. 5. Increasing [Rb]o or [Cs]o over the range of 0-40 mM increases the rate of decay of the electrogenic Na pump current transient. Using a simple model (cf. Rang & Ritchie, 1968), it is shown that the decay rate constant of the electrogenic Na pump current transient is a good measure of the degree of activation of the external site of the Na pump. At a given concentration of activator cation, Rbo produces a greater activation of the Na pump than does Cso. The K0.5 for Rbo is 6

  9. Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure.

    PubMed

    Townsend, DeWayne; Blankinship, Michael J; Allen, James M; Gregorevic, Paul; Chamberlain, Jeffrey S; Metzger, Joseph M

    2007-06-01

    Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration resulting from the loss of the cytoskeletal protein dystrophin. Most patients develop significant cardiomyopathy, with heart failure being the second leading cause of death in DMD. Compared with the extensive studies on skeletal muscle defects and potential therapy in DMD, very little attention has been directed at the increasing incidence of heart failure in DMD. Here we show that a single systemic injection of recombinant adeno-associated virus (rAAV2/6) harboring micro-dystrophin leads to extensive cardiac transduction, with micro-dystrophin correctly localized at the periphery of the cardiac myocytes and functionally associated with the sarcolemmal membrane. Significantly, micro-dystrophin gene transfer corrected the baseline end-diastolic volume defect in the mdx mouse heart and prevented cardiac pump failure induced by dobutamine stress testing in vivo, although several parameters of systolic function were not corrected. These results demonstrate that systemic gene delivery of micro-dystrophin can restore ventricular distensibility and protect the mdx myocardium from pump dysfunction during adrenergic stimulation in vivo. PMID:17440445

  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. Cardiac displacement during off-pump coronary artery bypass grafting surgery: effect on sublingual microcirculation and cerebral oxygenation.

    PubMed

    Atasever, Bektas; Boer, Christa; Speekenbrink, Ron; Seyffert, Jan; Goedhart, Peter; de Mol, Bas; Ince, Can

    2011-12-01

    Cardiac displacement during off-pump coronary artery bypass (OPCAB) surgery causes a fall in cardiac output. Here, we investigate how this drop in systemic perfusion is transferred to the oxygenation of sublingual and cerebral tissue. Sublingual microcirculatory perfusion or microcirculatory hemoglobin oxygen saturation (μHbSO(2)) measurements were performed using sidestream dark-field imaging and reflectance spectrophotometry, respectively (both n = 12). The cerebral tissue oxygenation index was measured by near-infrared spectrophotometry (n = 12). Cardiac output was calculated by pulse contour analysis of arterial pressure. Cardiac displacement reduced the cardiac output from 4.3 ± 0.8 to 1.2 ± 0.3 l/min (P < 0.05), paralleled by a decrease in μHbSO(2) from 64.2 ± 9.1 to 48.6 ± 8.7% (P < 0.01). Cardiac displacement did not change functional capillary density, while red blood cell velocity decreased from 895 ± 209 to 396 ± 178 μm/s (P<0.01). Cerebral tissue oxygenation index decreased from 69.5 ± 4.0 to 57.4 ± 8.5% (P<0.01) during cardiac displacement. After repositioning of the heart, all the values returned to baseline. Our data suggest that systemic hemodynamic alterations during cardiac displacement in OPCAB surgery reduce sublingual and cerebral tissue oxygenation. These findings are particularly important for patients at risk for the consequences of cerebral ischemia. PMID:21979985

  12. Cardiac Rehabilitation: Improving Function and Reducing Risk.

    PubMed

    Servey, Jessica T; Stephens, Mark

    2016-07-01

    Cardiac rehabilitation is a comprehensive multidisciplinary program individually tailored to the needs of patients with cardiovascular disease. The overall goals focus on improving daily function and reducing cardiovascular risk factors. Cardiac rehabilitation includes interventions aimed at lowering blood pressure and improving lipid and diabetes mellitus control, with tobacco cessation, behavioral counseling, and graded physical activity. The physical activity component typically involves 36 sessions over 12 weeks, during which patients participate in supervised exercise under cardiac monitoring. There are also intensive programs that include up to 72 sessions lasting up to 18 weeks, although these programs are not widely available. Additional components of cardiac rehabilitation include counseling on nutrition, screening for and managing depression, and assuring up-to-date immunizations. Cardiac rehabilitation is covered by Medicare and recommended for patients following myocardial infarction, bypass surgery, and stent placement, and for patients with heart failure, stable angina, and several other conditions. Despite proven benefits in mortality rates, depression, functional capacity, and medication adherence, rates of referral for cardiac rehabilitation are suboptimal. Groups less likely to be referred are older adults, women, patients who do not speak English, and persons living in areas where cardiac rehabilitation is not locally available. Additionally, primary care physicians refer patients less often than cardiologists and cardiothoracic surgeons. PMID:27386722

  13. 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

  14. Cognitive and Functional Consequence of Cardiac Arrest.

    PubMed

    Perez, Claudia A; Samudra, Niyatee; Aiyagari, Venkatesh

    2016-08-01

    Cardiac arrest is associated with high morbidity and mortality. Better-quality bystander cardiopulmonary resuscitation training, cardiocerebral resuscitation principles, and intensive post-resuscitation hospital care have improved survival. However, cognitive and functional impairment after cardiac arrest remain areas of concern. Research focus has shifted beyond prognostication in the immediate post-arrest period to identification of mechanisms for long-term brain injury and implementation of promising protocols to reduce neuronal injury. These include therapeutic temperature management (TTM), as well as pharmacologic and psychological interventions which also improve overall neurological function. Comprehensive assessment of cognitive function post-arrest is hampered by heterogeneous measures among studies. However, the domains of attention, long-term memory, spatial memory, and executive function appear to be affected. As more patients survive cardiac arrest for longer periods of time, there needs to be a greater focus on interventions that can enhance cognitive and psychosocial function post-arrest. PMID:27311306

  15. 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

  16. Functional cardiac imaging: positron emission tomography

    SciTech Connect

    Mullani, N.A.; Gould, K.L.

    1984-02-01

    Dynamic cardiovascular imaging plays a vital role in the diagnosis and treatment of cardiac disease by providing information about the function of the heart. During the past 30 years, cardiovascular imaging has evolved from the simple chest x-ray and fluoroscopy to such sophisticated techniques as invasive cardiac angiography and cinearteriography and, more recently, to noninvasive cardiac CT scanning, nuclear magnetic resonance, and positron emission tomography, which reflect more complex physiologic functions. As research tools, CT, NMR, and PET provide quantitative information on global as well as regional ventricular function, coronary artery stenosis, myocardial perfusion, glucose and fatty acid metabolism, or oxygen utilization, with little discomfort or risk to the patient. As imaging modalities become more sophisticated and more oriented toward clinical application, the prospect of routinely obtaining such functional information about the heart is becoming realistic. However, these advances are double-edged in that the interpretation of functional data is more complex than that of the anatomic imaging familiar to most physicians. They will require an enhanced understanding of the physiologic and biochemical processes, as well as of the instrumentation and techniques for analyzing the data. Of the new imaging modalities that provide functional information about the heart, PET is the most useful because it quantitates the regional distribution of radionuclides in vivo. Clinical applications, interpretation of data, and the impact of PET on our understanding of cardiac pathophysiology are discussed. 5 figures.

  17. 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…

  18. On-pump beating resection of cardiac pheochromocytoma.

    PubMed

    Kaku, Yuji; Saito, Satoshi; Saito, Hiroyuki; Yamazaki, Kenji

    2014-01-01

    We describe the case of 34-year-old woman with a cardiac pheochromocytoma that was diagnosed by scintigraphy using iodine-131 metaiodobenzylguanidine. For preoperative evaluation, we chose multidetector computed tomography instead of coronary angiography, for fear that catheter manipulation might trigger catecholamine release from the tumor; it showed that no major coronary artery branches run through the tumor. The tumor resection was carried out safely with the use of cardiopulmonary bypass and without cardiac arrest. PMID:24585652

  19. A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

    PubMed Central

    Brown, Lisa; Tadros, Hany B.; Munfakh, Nabil A.

    2015-01-01

    The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide. We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery. PMID:26504450

  20. 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. PMID:22882439

  1. Interplay between cardiac function and heart development.

    PubMed

    Andrés-Delgado, Laura; Mercader, Nadia

    2016-07-01

    Mechanotransduction refers to the conversion of mechanical forces into biochemical or electrical signals that initiate structural and functional remodeling in cells and tissues. The heart is a kinetic organ whose form changes considerably during development and disease. This requires cardiomyocytes to be mechanically durable and able to mount coordinated responses to a variety of environmental signals on different time scales, including cardiac pressure loading and electrical and hemodynamic forces. During physiological growth, myocytes, endocardial and epicardial cells have to adaptively remodel to these mechanical forces. Here we review some of the recent advances in the understanding of how mechanical forces influence cardiac development, with a focus on fluid flow forces. 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. PMID:26952935

  2. Functional cardiac imaging by random access microscopy

    PubMed Central

    Crocini, Claudia; Coppini, Raffaele; Ferrantini, Cecilia; Pavone, Francesco S.; Sacconi, Leonardo

    2014-01-01

    Advances in the development of voltage sensitive dyes and Ca2+ sensors in combination with innovative microscopy techniques allowed researchers to perform functional measurements with an unprecedented spatial and temporal resolution. At the moment, one of the shortcomings of available technologies is their incapability of imaging multiple fast phenomena while controlling the biological determinants involved. In the near future, ultrafast deflectors can be used to rapidly scan laser beams across the sample, performing optical measurements of action potential and Ca2+ release from multiple sites within cardiac cells and tissues. The same scanning modality could also be used to control local Ca2+ release and membrane electrical activity by activation of caged compounds and light-gated ion channels. With this approach, local Ca2+ or voltage perturbations could be induced, simulating arrhythmogenic events, and their impact on physiological cell activity could be explored. The development of this optical methodology will provide fundamental insights in cardiac disease, boosting new therapeutic strategies, and, more generally, it will represent a new approach for the investigation of the physiology of excitable cells. PMID:25368580

  3. Influence of vascular function and pulsatile hemodynamics on cardiac function.

    PubMed

    Bell, Vanessa; Mitchell, Gary F

    2015-09-01

    Interactions between cardiac and vascular structure and function normally are optimized to ensure delivery of cardiac output with modest pulsatile hemodynamic overhead. Aortic stiffening with age or disease impairs optimal ventricular-vascular coupling, increases pulsatile load, and contributes to left ventricular (LV) hypertrophy, reduced systolic function, and impaired diastolic relaxation. Aortic pulse pressure and timing of peak systolic pressure are well-known measures of hemodynamic ventricular-vascular interaction. Recent work has elucidated the importance of direct, mechanical coupling between the aorta and the heart. LV systolic contraction results in displacement of aortic and mitral annuli, thereby producing longitudinal stretch in the ascending aorta and left atrium, respectively. Force associated with longitudinal stretch increases systolic load on the LV. However, the resulting energy stored in the elastic elements of the proximal aorta during systole facilitates early diastolic LV recoil and rapid filling. This review discusses current views on hemodynamics and mechanics of ventricular-vascular coupling. PMID:26164466

  4. Proton Pump Inhibitor Use Is not Associated with Cardiac Arrhythmia in Critically Ill Patients

    PubMed Central

    Chen, Kenneth P.; Lee, Joon; Mark, Roger G.; Feng, Mornin; Celi, Leo A.; Danziger, John

    2016-01-01

    Hypomagnesemia can lead to cardiac arrhythmias. Recently, observational data has linked chronic proton pump inhibitor (PPI) exposure to hypomagnesemia. Whether PPI exposure increases the risk for arrhythmias has not been well studied. Using a large, single center inception cohort of critically ill patients, we examined whether PPI exposure was associated with admission electrocardiogram (ECG) readings of a cardiac arrhythmia in over 8000 patients. There were 24.5% PPI users while 6% were taking a histamine 2 antagonist. 14.3% had a cardiac arrhythmia. PPI use was associated with a 1.18 (95% CI=1.02–1.36, p=0.02) unadjusted and 0.96 (95% CI=0.83–1.12, p=0.62) adjusted risk of arrhythmia. Amongst diuretic users (n=2468), PPI use was similarly not associated with an increased risk of cardiac arrhythmia. In summary, in a large cohort of critically ill patients, PPI exposure is not associated with an increased risk of cardiac arrhythmia. PMID:25655574

  5. Measuring mitochondrial function in intact cardiac myocytes

    PubMed Central

    Dedkova, Elena N.; Blatter, Lothar A.

    2011-01-01

    Mitochondria are involved in cellular functions that go beyond the traditional role of these organelles as the power plants of the cell. Mitochondria have been implicated in several human diseases, including cardiac dysfunction, and play a role in the aging process. Many aspects of our knowledge of mitochondria stem from studies performed on the isolated organelle. Their relative inaccessibility imposes experimental difficulties to study mitochondria in their natural environment – the cytosol of intact cells – and has hampered a comprehensive understanding of the plethora of mitochondrial functions. Here we review currently available methods to study mitochondrial function in intact cardiomyocytes. These methods primarily use different flavors of fluorescent dyes and genetically encoded fluorescent proteins in conjunction with high-resolution imaging techniques. We review methods to study mitochondrial morphology, mitochondrial membrane potential, Ca2+ and Na+ signaling, mitochondrial pH regulation, redox state and ROS production, NO signaling, oxygen consumption, ATP generation and the activity of the mitochondrial permeability transition pore. Where appropriate we complement this review on intact myocytes with seminal studies that were performed on isolated mitochondria, permeabilized cells, and in whole hearts. PMID:21964191

  6. 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

  7. [Physiological functions of endoplasmic and sarcoplasmic reticulum Ca pump and pharmacology of inhibitors of the pump].

    PubMed

    Watanabe, M; Shigekawa, M

    1993-09-01

    This review is derived from the symposium held at the 66th Annual Meeting of the Japanese Pharmacological Society (March, 1993). The symposium consisted of six invited papers whose general theme was the application of recently found ATPase inhibitors selective to SR- and ER-Ca(2+)-ATPase to the analyses of the physiological and pharmacological roles of endoplasmic and sarcoplasmic reticulum Ca stores. Inhibitors used were: thapsigargin, cyclopiazonic acid, 2,5-di-(t-butyl)-1,4-benzohydroquinone and 3',3",5',5"-tetraiodosulfophthalein. Gingerol was found to facilitate the action of the ATPase. In either smooth, cardiac or skeletal muscle, sympathetic neurons or several cell lines these inhibitors affected a variety of cell functions and conditions such as contraction, ionic conductance and excitability of the plasma membrane, regulation of intracellular free Ca2+ concentration, transport of viral glycoprotein to the cell surface. Many of these studies utilized either single or cultured cell preparations or skinned muscle. These inhibitors were shown to be useful tools for investigating the SR and ER functioning as Ca sources or Ca sequestrating pumps, and further for estimating the contribution of ER or SR to regulating the flux of Ca2+ and other ions through the plasma membrane. Results of analyses using these inhibitors are discussed. PMID:8406230

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

    PubMed Central

    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 (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, 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 internal

  9. 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. PMID:22804106

  10. Bioengineered FSTL1 Patches Restore Cardiac Function Following Myocardial Infarction.

    PubMed

    Alteköester, Ann-Kristin; Harvey, Richard P

    2015-12-01

    Improving the limited ability of the heart to regenerate after infarction is crucial. Researchers now demonstrate that delivery of follistatin-like 1 (FSTL1) into injured hearts via collagen patches stimulates cardiomyocyte proliferation and cardiac functional recovery. These findings highlight the epicardium as a source of novel regenerative factors and biomimetic nanomaterials in cardiac translational medicine. PMID:26596868

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

    PubMed

    Inoue, Keiichi; Nomura, Yurika; Kandori, Hideki

    2016-05-01

    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

  12. 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.

  13. 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. PMID:25713362

  14. 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

  15. Extracellular Superoxide Dismutase Regulates Cardiac Function and Fibrosis

    PubMed Central

    Kliment, Corrine R; Suliman, Hagir B; Tobolewski, Jacob M; Reynolds, Crystal M; Day, Brian J; Zhu, Xiaodong; McTiernan, Charles F; McGaffin, Kenneth R; Piantadosi, Claude A; Oury, Tim D

    2009-01-01

    Aims Extracellular superoxide dismutase (EC-SOD) is an antioxidant that protects the heart from ischemia and the lung from inflammation and fibrosis. The role of cardiac EC-SOD under normal conditions and injury remains unclear. Cardiac toxicity, a common side effect of doxorubicin, involves oxidative stress. We hypothesize that EC-SOD is critical for normal cardiac function and protects the heart from oxidant-induced fibrosis and loss of function. Methods C57BL/6 and EC-SOD-null mice were treated with doxorubicin, 15 mg/kg (i.p.). After 15 days, echocardiography was used to assess cardiac function. Left ventricle (LV) tissue was used to assess fibrosis and inflammation by staining, western blot, and hydroxyproline analysis. Results At baseline EC-SOD-null mice have LV wall thinning and increases in LV end diastolic dimensions compared to wild type mice, but have normal cardiac function. After doxorubicin, EC-SOD-null mice have decreases in fractional shortening not apparent in WT mice. Lack of EC-SOD also leads to increases in myocardial apoptosis and significantly more LV fibrosis and inflammatory cell infiltration. Administration of the metalloporphyrin AEOL 10150 abrogates the loss of cardiac function, and potentially fibrosis, associated with doxorubicin treatment in both wild type and EC-SOD KO mice. Conclusions EC-SOD is critical for normal cardiac morphology and protects the heart from oxidant-induced fibrosis, apoptosis and loss of function. The antioxidant metalloporphyrin, AEOL 10150 effectively protects cardiac function from doxorubicin-induced oxidative stress, in vivo. These findings identify targets for the use of antioxidant agents in oxidant-induced cardiac fibrosis. PMID:19695260

  16. Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology.

    PubMed

    Periasamy, Muthu; Bhupathy, Poornima; Babu, Gopal J

    2008-01-15

    Cardiac sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) plays a central role in myocardial contractility. SERCA2a actively transports Ca(2+) into the SR and regulates cytosolic Ca(2+) concentration, SR Ca(2+) load, and the rate of contraction and relaxation of the heart. In the heart, SERCA pump activity is regulated by two small molecular weight proteins: phospholamban (PLB) and sarcolipin (SLN). Decreases in the expression levels of SERCA2a have been observed in a variety of pathological conditions. In addition, altered expression of PLB and SLN has been reported in many cardiac diseases. Thus, SERCA2a is a major regulator of intracellular Ca(2+) homeostasis, and changes in the expression and activity of the SERCA pump contribute to the decreased SR Ca(2+) content and cardiac dysfunction during pathogenesis. In this review, we discuss the mechanisms controlling SERCA pump expression and activity both during normal physiology and under pathological states. PMID:18006443

  17. Structure and function of the calcium pump.

    PubMed

    Stokes, David L; Green, N Michael

    2003-01-01

    Active transport of cations is achieved by a large family of ATP-dependent ion pumps, known as P-type ATPases. Various members of this family have been targets of structural and functional investigations for over four decades. Recently, atomic structures have been determined for Ca2+-ATPase by X-ray crystallography, which not only reveal the architecture of these molecules but also offer the opportunity to understand the structural mechanisms by which the energy of ATP is coupled to calcium transport across the membrane. This energy coupling is accomplished by large-scale conformational changes. The transmembrane domain undergoes plastic deformations under the influence of calcium binding at the transport site. Cytoplasmic domains undergo dramatic rigid-body movements that deliver substrates to the catalytic site and that establish new domain interfaces. By comparing various structures and correlating functional data, we can now begin to associate the chemical changes constituting the reaction cycle with structural changes in these domains. PMID:12598367

  18. Galectin-3, Cardiac Function, and Fibrosis.

    PubMed

    Meijers, Wouter C; López-Andrés, Natalia; de Boer, Rudolf A

    2016-08-01

    This Correspondence relates to the article by Frunza et al (Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis. Am J Pathol 2016, 186:1114-1127). PMID:27461364

  19. 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.

  20. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  1. An innovative approach to evaluate a cardiac function based on surface measurement.

    PubMed

    Uematsu, M; Shiraishi, Y; Sekine, K; Yambe, T; Saijo, Y; Park, Y; Ando, H; Matsumoto, T; Takeda, S; Iwasaki, K; Umezu, M

    2005-01-01

    Major function of the heart is to pump blood flow up to all tissues or organs in the body, and it is generally recognized that cardiac function under various diseased conditions are mainly represented by a relationship between blood flow and pressure inside of the heart. In this report, an original proposal of evaluation method on cardiac function is introduced through a simultaneous measurement of various points of cardiac muscular surface. An optical three-dimensional location sensor was employed to measure a displacement change of anatomically specific points on heart surface. Then, changes in strain in each regional surface area were quantitatively obtained. This result indicated similar tendency obtained from echocardiogram. It was also indicated that there was a difference in displacements and phrases between control and arrhythmia. Moreover, strain change in regional area was coincident with a contraction of natural heart. It was found that an attempt to superimpose the data of strain change onto the video images of natural heart was extremely helpful to understand a cardiac function visually. PMID:17282050

  2. Using exercise to measure and modify cardiac function.

    PubMed

    Platt, Colin; Houstis, Nicholas; Rosenzweig, Anthony

    2015-02-01

    Exercise is the archetype of physiologic demands placed on the cardiovascular system. Acute responses provide an informative assessment of cardiovascular function and fitness, while repeated exercise promotes cardiovascular health and evokes important molecular, structural, and functional changes contributing to its effects in primary and secondary prevention. Here we examine the use of exercise in murine models, both as a phenotypic assay and as a provocative intervention. We first review the advantages and limitations of exercise testing for assessing cardiac function, then highlight the cardiac structural and cellular changes elicited by chronic exercise and key molecular pathways that mediate these effects. PMID:25651177

  3. Analysis of cardiac function by MRI and stereology.

    PubMed

    Roberts, N; Cruz-Orive, L M; Bourne, M; Herfkens, R J; Karwoski, R A; Whitehouse, G H

    1997-07-01

    Design-based stereology and phase contrast magnetic resonance imaging (MRI) were combined to monitor changes in the volume of the four chambers of the human heart during the cardiac cycle. The data set consisted of 18 adjacent slices (or 'scanning levels') of 0.5 cm thickness, perpendicular to the long axis of the body, and encompassing the whole heart of a healthy volunteer. At each scanning level, a cardiac gated MR image was obtained at each of 16 equally spaced time frames within the cardiac cycle. Given stationarity with respect to time, absence of image artefacts and appropriate definition of chamber boundaries, for each time frame unbiased estimates of total blood volume in the relevant heart chambers were efficiently obtained using the Cavalieri method and point counting. Combined with a proper MRI acquisition, modern stereological methods constitute an efficient and reliable tool to quantify cardiac function noninvasively. PMID:9263438

  4. Natriuretic peptides stimulate the cardiac sodium pump via NPR-C-coupled NOS activation.

    PubMed

    William, M; Hamilton, E J; Garcia, A; Bundgaard, H; Chia, K K M; Figtree, G A; Rasmussen, H H

    2008-04-01

    Natriuretic peptides (NPs) and their receptors (NPRs) are expressed in the heart, but their effects on myocyte function are poorly understood. Because NPRs are coupled to synthesis of cGMP, an activator of the sarcolemmal Na(+)-K(+) pump, we examined whether atrial natriuretic peptide (ANP) regulates the pump. We voltage clamped rabbit ventricular myocytes and identified electrogenic Na(+)-K(+) pump current (arising from the 3:2 Na(+):K(+) exchange and normalized for membrane capacitance) as the shift in membrane current induced by 100 micromol/l ouabain. Ten nanomoles per liter ANP stimulated the Na(+)-K(+) pump when the intracellular compartment was perfused with pipette solutions containing 10 mmol/l Na(+) but had no effect when the pump was at near maximal activation with 80 mmol/l Na(+) in the pipette solution. Stimulation was abolished by inhibition of cGMP-activated protein kinase with KT-5823, nitric oxide (NO)-activated guanylyl cyclase with 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ), or NO synthase with N(G)-nitro-L-arginine methyl ester (L-NAME). Since synthesis of cGMP by NPR-A and NPR-B is not NO dependent or ODQ sensitive, we exposed myocytes to AP-811, a highly selective ligand for the NPR-C "clearance" receptor. It abolished ANP-induced pump stimulation. Conversely, the selective NPR-C agonist ANP(4-23) reproduced stimulation. The stimulation was blocked by l-NAME. To examine NO production in response to ANP(4-23), we loaded myocytes with the NO-sensitive fluorescent dye diacetylated diaminofluorescein-2 and examined them by confocal microscopy. ANP(4-23) induced a significant increase in fluorescence, which was abolished by L-NAME. We conclude that NPs stimulate the Na(+)-K(+) pump via an NPR-C and NO-dependent pathway. PMID:18272821

  5. Multi-Function Gas Fired Heat Pump

    SciTech Connect

    Abu-Heiba, Ahmad; Vineyard, Edward Allan

    2015-11-30

    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.

  6. Losartan decreases cardiac muscle fibrosis and improves cardiac function in dystrophin-deficient mdx mice.

    PubMed

    Spurney, Christopher F; Sali, Arpana; Guerron, Alfredo D; Iantorno, Micaela; Yu, Qing; Gordish-Dressman, Heather; Rayavarapu, Sree; van der Meulen, Jack; Hoffman, Eric P; Nagaraju, Kanneboyina

    2011-03-01

    Recent studies showed that chronic administration of losartan, an angiotensin II type I receptor antagonist, improved skeletal muscle function in dystrophin-deficient mdx mice. In this study, C57BL/10ScSn-Dmd(mdx)/J female mice were either untreated or treated with losartan (n = 15) in the drinking water at a dose of 600 mg/L over a 6-month period. Cardiac function was assessed via in vivo high frequency echocardiography and skeletal muscle function was assessed using grip strength testing, Digiscan monitoring, Rotarod timing, and in vitro force testing. Fibrosis was assessed using picrosirius red staining and Image J analysis. Gene expression was evaluated using real-time polymerized chain reaction (RT-PCR). Percentage shortening fraction was significantly decreased in untreated (26.9% ± 3.5%) mice compared to losartan-treated (32.2% ± 4.2%; P < .01) mice. Systolic blood pressure was significantly reduced in losartan-treated mice (56 ± 6 vs 69 ± 7 mm Hg; P < .0005). Percentage cardiac fibrosis was significantly reduced in losartan-treated hearts (P < .05) along with diaphragm (P < .01), extensor digitorum longus (P < .05), and gastrocnemius (P < .05) muscles compared to untreated mdx mice. There were no significant differences in skeletal muscle function between treated and untreated groups. Chronic treatment with losartan decreases cardiac and skeletal muscle fibrosis and improves cardiac systolic function in dystrophin-deficient mdx mice. PMID:21304057

  7. Species-dependent adaptation of the cardiac Na+/K+ pump kinetics to the intracellular Na+ concentration

    PubMed Central

    Lewalle, Alexandre; Niederer, Steven A; Smith, Nicolas P

    2014-01-01

    The Na+/K+ ATPase (NKA) plays a critical role in maintaining ionic homeostasis and dynamic function in cardiac myocytes, within both the in vivo cell and in silico models. Physiological conditions differ significantly between mammalian species. However, most existing formulations of NKA used to simulate cardiac function in computational models are derived from a broad range of experimental sources spanning many animal species. The resultant inability of these models to discern species-specific features is a significant obstacle to achieving a detailed quantitative and comparative understanding of physiological behaviour in different biological contexts. Here we present a framework for characterising the steady-state NKA current using a biophysical mechanistic model specifically designed to provide a mechanistic explanation of the NKA flux supported by self-consistent species-specific data. We thus compared NKA kinetics specific to guinea- pig and rat ventricular myocytes. We observe that the apparent binding affinity for sodium in the rat is significantly lower, whereas the overall pump cycle rate is doubled, in comparison to the guinea pig. This sensitivity of NKA to its regulatory substrates compensates for the differences in Na+ concentrations between the cell types. NKA is thereby maintained within its dynamic range over a wide range of pacing frequencies in these two species, despite significant disparities in sodium concentration. Hence, by replacing a conventional generic NKA model with our rat-specific NKA formula into a whole-cell simulation, we have, for the first time, been able to accurately reproduce the action potential duration and the steady-state sodium concentration as functions of pacing frequency. PMID:25362154

  8. Cardiac Function in Young and Old Little Mice

    PubMed Central

    Reddy, Anilkumar K.; Amador-Noguez, Daniel; Darlington, Gretchen J.; Scholz, Beth A.; Michael, Lloyd H.; Hartley, Craig J.; Entman, Mark L.; Taffet, George E.

    2009-01-01

    We studied cardiac function in young and old, wild-type (WT), and longer-living Little mice using cardiac flow velocities, echocardiographic measurements, and left ventricular (LV) pressure (P) to determine if enhanced reserves were in part responsible for longevity in these mice. Resting/baseline cardiac function, as measured by velocities, LV dimensions, +dP/dtmax, and −dP/dtmax, was significantly lower in young Little mice versus young WT mice. Fractional shortening (FS) increased significantly, and neither +dP/dtmax nor −dP/dtmax declined with age in Little mice. In contrast, old WT mice had no change in FS but had significantly lower +dP/dtmax and −dP/dtmax versus young WT mice. Significant decreases were observed in the velocity indices of old Little mice versus old WT mice, but other parameters were unchanged. The magnitude of dobutamine stress response remained unchanged with age in Little mice, while that in WT mice decreased. These data suggest that while resting cardiac function in Little mice versus WT mice is lower at young age, it is relatively unaltered with aging. Additionally, cardiac function in response to stress was maintained with age in Little mice but not in their WT counterparts. Thus, some mouse models of increased longevity may not be associated with enhanced reserves. PMID:18166681

  9. Assessment of cardiac function during mechanical circulatory support: the quest for a suitable clinical index.

    PubMed

    Ferreira, Antonio L; Wang, Yajuan; Gorcsan, John; Antaki, James F

    2011-01-01

    A new index to assess left ventricular (LV) function in patients implanted with continuous flow left-ventricular assist devices (LVADs) is proposed. Derived from the pump flow signal, this index is defined as the coefficient (k) of the semilogarithmic relationship between "pseudo-ejection" fraction (pEF) and the volume discharged by the pump in diastole, (V d). pEF is defined as the ratio of the "pseudo-stroke volume" (pSV) to V d. The pseudo-stroke volume is the difference between V d and the volume discharged by the pump in systole (V s), both obtained by integrating pump flow with respect to time in a cardiac cycle. k was compared in-vivo with others two indices: the LV pressure-based index, M(TP), and the pump flow-based index, I(Q). M(TP) is the slope of the linear regression between the "triple-product" and end-diastolic pressure, EDP. The triple-product, TP = LV SP.dP/dt(max). HR, is the product of LV systolic pressure, maximum time-derivative of LV pressure, and heart rate. I(Q) is the slope of the linear regression between maximum time-derivative of pump flow, dQ/dt(max), and pump flow peak-to-peak amplitude variation, Q(P2P). To test the response of k to contractile state changes, contractility was altered through pharmacological interventions. The absolute value of k decreased from 1.354 ± 0.25 (baseline) to 0.685 ± 0.21 after esmolol infusion. The proposed index is sensitive to changes in inotropic state, and has the potential to be used clinically to assess contractile function of patients implanted with VAD. PMID:22254290

  10. Skeletal muscle Na,K-pump concentration in children and its relationship to cardiac glycoside distribution.

    PubMed

    Kjeldsen, K; Grøn, P

    1989-08-01

    Skeletal muscle Na,K-pump (cardiac glycoside receptor) concentration was quantified in 18 0- to 8-year-old human subjects by vanadate facilitated [3H]ouabain binding to intact vastus lateralis samples obtained at autopsy. No age-dependent change in [3H]ouabain binding site concentration was observed. Mean value +/- S.E.M. was 268 +/- 17 pmol/g wet wt. (n = 18), range 182 to 433 pmol/g wet wt. At the age of 1 day, 3.5 month and 8 years and 8 months, unspecific uptake and retention of [3H]ouabain was 1.6, 1.4 and 1.5% of the total uptake and retention; release of specifically bound [3H]ouabain during the washout procedure took place with T 1/2 of 97, 90 and 73 hr; and apparent affinity constants for [3H]ouabain binding (KD) was 1.3 x 10(-8), 0.9 x 10(-8) and 1.2 x 10(-8) mol/l. [3H]Ouabain binding site concentrations and kinetics were in agreement with values from adults except that in children apparent affinity constant (KD) was 1.7 times the value in adults. The observation of no age-dependent changes in human skeletal muscle Na,K-adenosine triphosphatase concentration was at variance with the observations of such changes in animals. The total number of Na,K-pumps in the pool of skeletal muscles increased from 10 to 50 times that in the heart from birth to old age. The skeletal muscle pool of Na,K-pumps seems to constitute a distribution volume of importance during digitalization in children as well as adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2547946

  11. 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. PMID:27111147

  12. Off-pump versus on-pump coronary artery revascularization: effects on pulmonary function.

    PubMed

    e Silva, Ana M R P; Saad, Roberto; Stirbulov, Roberto; Rivetti, Luiz A

    2010-07-01

    Many studies have shown important changes in lung function tests after coronary artery surgeries. It is controversial if off-pump surgery can give a better and shorter recovery than the on-pump. A prospective study was conducted on 42 patients submitted to coronary artery surgery and divided into two groups: 21 off-pump using intraluminal shunt (G (I)) and 21 on-pump (G (II)), matched by the anatomical location of the coronary arteries lesions. All patients had spirometric evaluation, blood gas measurements and alveolo-arterial oxygen gradient (A-aDO(2)), at the fourth and 10th postoperative days (PO(4) and PO(10)). Preoperatively, G(I) and G(II) had similar results (P>0.372). Spirometry showed decreases at PO(4) and remained decreased until PO(10) for both groups, with significant differences between the groups. The blood gas measurements showed reduction in arterial oxygen pressure (PaO(2)) and carbon dioxide pressure (PaCO(2)), while there was an increase in A-aDO(2) at PO(4) and PO(10) in both groups. The results suggest that different changes occur in pulmonary function when the surgery is performed with or without cardiopulmonary bypass. The off-pump patients showed significantly greater improvement than the on-pump group. PMID:20403972

  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. PMID:24970234

  14. Influence of chronic kidney disease on cardiac structure and function.

    PubMed

    Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef

    2015-09-01

    Chronic kidney disease (CKD), the presence of kidney dysfunction and/or damage, is a worldwide public health issue. Although CKD is independently associated with various subtypes of cardiovascular diseases, a recent international collaborative meta-analysis demonstrates that CKD is particularly strongly associated with heart failure, suggesting its critical impact on cardiac structure and function. Although numerous studies have investigated the association of CKD and cardiac structure and function, these studies substantially vary regarding source populations and methodology (e.g., measures of CKD and/or parameters of cardiac structure and function), making it difficult to reach universal conclusions. Nevertheless, in this review, we comprehensively examine relevant studies, discuss potential mechanisms linking CKD to alteration of cardiac structure and function, and demonstrate clinical implications as well as potential future research directions. We exclusively focus on studies investigating both CKD measures, kidney function (i.e., glomerular filtration rate [GFR], creatinine clearance, or levels of filtration markers), and kidney damage represented by albuminuria, since current international clinical guidelines of CKD recommend staging CKD and assessing its clinical risk based on both GFR and albuminuria. PMID:26194332

  15. 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

  16. Acupuncture effects on cardiac functions measured by cardiac magnetic resonance imaging in a feline model.

    PubMed

    Lin, Jen-Hsou; Shih, Chen-Haw; Kaphle, Krishna; Wu, Leang-Shin; Tseng, Weng-Yih; Chiu, Jen-Hwey; Lee, Tzu-Chi; Wu, Ying-Ling

    2010-06-01

    The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology. PMID:18955311

  17. ROS Regulate Cardiac Function via a Distinct Paracrine Mechanism

    PubMed Central

    Lim, Hui-Ying; Wang, Weidong; Chen, Jianming; Ocorr, Karen; Bodmer, Rolf

    2014-01-01

    SUMMARY Reactive oxygen species (ROS) can act cell autonomously and in a paracrine manner by diffusing into nearby cells. Here, we reveal a ROS-mediated paracrine signaling mechanism that does not require entry of ROS into target cells. We found that under physiological conditions, nonmyocytic pericardial cells (PCs) of the Drosophila heart contain elevated levels of ROS compared to the neighboring cardiomyocytes (CMs). We show that ROS in PCs act in a paracrine manner to regulate normal cardiac function, not by diffusing into the CMs to exert their function, but by eliciting a downstream D-MKK3-D-p38 MAPK signaling cascade in PCs that acts on the CMs to regulate their function. We find that ROS-D-p38 signaling in PCs during development is also important for establishing normal adult cardiac function. Our results provide evidence for a previously unrecognized role of ROS in mediating PC/CM interactions that significantly modulates heart function. PMID:24656823

  18. LINC complex proteins in cardiac structure, function, and disease

    PubMed Central

    Stroud, Matthew J; Banerjee, Indroneal; Lowe, Jennifer; Chen, Ju

    2014-01-01

    The LINC (LInker of Nucleoskeleton and Cytoskeleton) 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 are causative for 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. PMID:24481844

  19. Secondary Sphere Formation Enhances the Functionality of Cardiac Progenitor Cells

    PubMed Central

    Cho, Hyun-Jai; Lee, Ho-Jae; Youn, Seock-Won; Koh, Seok-Jin; Won, Joo-Yun; Chung, Yeon-Ju; Cho, Hyun-Ju; Yoon, Chang-Hwan; Lee, Sae-Won; Lee, Eun Ju; Kwon, Yoo-Wook; Lee, Hae-Young; Lee, Sang Hun; Ho, Won-Kyung; Park, Young-Bae; Kim, Hyo-Soo

    2012-01-01

    Loss of cardiomyocytes impairs cardiac function after myocardial infarction (MI). Recent studies suggest that cardiac stem/progenitor cells could repair the damaged heart. However, cardiac progenitor cells are difficult to maintain in terms of purity and multipotency when propagated in two-dimensional culture systems. Here, we investigated a new strategy that enhances potency and enriches progenitor cells. We applied the repeated sphere formation strategy (cardiac explant → primary cardiosphere (CS) formation → sphere-derived cells (SDCs) in adherent culture condition → secondary CS formation by three-dimensional culture). Cells in secondary CS showed higher differentiation potentials than SDCs. When transplanted into the infarcted myocardium, secondary CSs engrafted robustly, improved left ventricular (LV) dysfunction, and reduced infarct sizes more than SDCs did. In addition to the cardiovascular differentiation of transplanted secondary CSs, robust vascular endothelial growth factor (VEGF) synthesis and secretion enhanced neovascularization in the infarcted myocardium. Microarray pathway analysis and blocking experiments using E-selectin knock-out hearts, specific chemicals, and small interfering RNAs (siRNAs) for each pathway revealed that E-selectin was indispensable to sphere initiation and ERK/Sp1/VEGF autoparacrine loop was responsible for sphere maturation. These results provide a simple strategy for enhancing cellular potency for cardiac repair. Furthermore, this strategy may be implemented to other types of stem/progenitor cell-based therapy. PMID:22713697

  20. Controlling the Structural and Functional Anisotropy of Engineered Cardiac Tissues

    PubMed Central

    Bursac, N

    2014-01-01

    The ability to control the degree of structural and functional anisotropy in 3D engineered cardiac tissues would have high utility for both in vitro studies of cardiac muscle physiology and pathology as well as potential tissue engineering therapies for myocardial infarction. Here, we applied a high aspect ratio soft lithography technique to generate network-like tissue patches seeded with neonatal rat cardiomyocytes. Fabricating longer elliptical pores within the patch networks increased the overall cardiomyocyte and extracellular matrix (ECM) alignment within the patch. Improved uniformity of cell and matrix alignment yielded an increase in anisotropy of action potential propagation and faster longitudinal conduction velocity (LCV). Cardiac tissue patches with a higher degree of cardiomyocyte alignment and electrical anisotropy also demonstrated greater isometric twitch forces. After two weeks of culture, specific measures of electrical and contractile function (LCV = 26.8 ± 0.8 cm/s, specific twitch force = 8.9 ± 1.1 mN/mm2 for the longest pores studied) were comparable to those of neonatal rat myocardium. We have thus described methodology for engineering of highly functional 3D engineered cardiac tissues with controllable degree of anisotropy. PMID:24717534

  1. Evaluation of ventricular function with gated cardiac magnetic resonance imaging.

    PubMed

    Osbakken, M; Yuschok, T

    1986-01-01

    To determine the feasibility of using planar images obtained with gated cardiac magnetic resonance imaging (MRI) techniques to evaluate ventricular contractile function, cardiac chamber volume (V), and ejection fraction (EF) were calculated using MR images obtained in five previously catheterized patients. Patients were imaged with a .15-Tesla 55-cm bore magnet using the ECG to gate the images. Spin echo pulse sequences (30/500, TE/TR) were used to produce images in the transverse (T), coronal (C), and sagittal (S) planes at end diastole (ED) and end systole (ES). Slice thickness was 1.5 cm, with 2-mm resolution. A calibration grid was imaged in each plane to determine correction factors. Cardiac chamber areas were determined via planimetry. An area-length-volume algorithm was used to obtain EDV and ESV. Three combinations of biplane images in ES and ED were used (T/C, T/S, C/S). Volume data were used to calculate EF. Contrast ventriculogram volumes tended to be greater than MRI volumes, but EFs were similar with both techniques. In conclusion, gated cardiac MR images can be used to evaluate the ventricular function parameters of volume and ejection fraction. PMID:3731263

  2. Assessment of pulmonary function tests in cardiac patients.

    PubMed

    El-Sobkey, Salwa B; Gomaa, Magdi

    2011-04-01

    This study was aimed to assess the pulmonary function tests (PFTs) in cardiac patients; with ischemic or rheumatic heart diseases as well as in patients who underwent coronary artery bypass graft (CABG) or valvular procedures. For the forty eligible participants, the pulmonary function was measured using the spirometry test before and after the cardiac surgery. Data collection sheet was used for the patient's demographic and intra-operative information. Cardiac diseases and surgeries had restrictive negative impact on PFTs. Before surgery, vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), ratio between FEV1 and FVC, and maximum voluntary ventilation (MVV) recorded lower values for rheumatic patients than ischemic patients (P values were 0.01, 0.005, 0.0001, 0.031, and 0.035, respectively). Moreover, patients who underwent valvular surgery had lower PFTs than patients who underwent CABG with significant differences for VC, FVC, FEV1, and MVV tests (P values were 0.043, 0.011, 0.040, and 0.020, respectively). No definite causative factor appeared to be responsible for those results although mechanical deficiency and incisional chest pain caused by cardiac surgery are doubtful. More comprehensive investigation is required to resolve the case. PMID:23960642

  3. 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.

  4. Accelerated MRI for the assessment of cardiac function.

    PubMed

    Axel, Leon; Otazo, Ricardo

    2016-07-01

    Heart disease is a worldwide public health problem; assessment of cardiac function is an important part of the diagnosis and management of heart disease. MRI of the heart can provide clinically useful information on cardiac function, although it is still not routinely used in clinical practice, in part because of limited imaging speed. New accelerated methods for performing cardiovascular MRI (CMR) have the potential to provide both increased imaging speed and robustness to CMR, as well as access to increased functional information. In this review, we will briefly discuss the main methods currently employed to accelerate CMR methods, such as parallel imaging, k-t undersampling and compressed sensing, as well as new approaches that extend the idea of compressed sensing and exploit sparsity to provide richer information of potential use in clinical practice. PMID:27033471

  5. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  6. Dependence of Na-K pump current on internal Na+ in mammalian cardiac myocytes.

    PubMed

    Mogul, D J; Singer, D H; Ten Eick, R E

    1990-08-01

    Na-K pump current (Ipump) is a function of the intracellular Na+ concentration [( Na+]i). We examined the quantitative relationship between Ipump and [Na+]i in isolated guinea pig ventricular myocytes under steady-state conditions. [Na+]i was controlled and "clamped" at several selected concentrations using wide-tipped pipette microelectrodes, and membrane current was measured using the whole cell patch voltage-clamp technique. Ipump generated at a holding potential of -40 mV was determined by measuring the change in steady-state holding current before and during exposure to dihydroouabain (1 mM); Ipump was measured at 11 levels of [Na+]i ranging from 0 to 80 mM (n = 63) with only one measurement per cell and normalized to cell capacitance to account for differences between myocytes in sarcolemmal surface area. Ipump exhibited a nonlinear dependence on [Na+]i; a Hill analysis of the relationship yielded a half-maximal [Na+]i for pump stimulation of 43.2 mM and a Hill coefficient of 1.53. An alternative analysis of the experimental data was performed assuming that occupation of three internal binding sites by Na+ is required for enzyme turnover. Regression analysis gave the best fit when only two different binding affinities (KD) are postulated. The values are KD1 = 1 mM, KD2 = KD3 = 29 mM. From the analysis using the latter model, the level of [Na+]i at which Ipump saturated closely approximated the theoretical saturation level calculated from published estimates of pump turnover rate and density. The maximal sensitivity of the Na-K pump to changes in [Na+]i occurs when internal [Na+] is within the range for the normal resting physiological level. PMID:2167023

  7. 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

  8. 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. PMID:18043164

  9. Functional design criteria for pumping and instrumentation control (PIC) skids

    SciTech Connect

    BOETTGER, J.S.

    1999-08-25

    Radioactive liquid and semisolid waste from operation of Hanford's nuclear fuel processing plants is stored in 177 underground storage tanks located in the 200 Areas of the Hanford site. 28 of these tanks are of double-shell construction. The remaining 149 tanks are of single-shell construction. Only the newer, double-shell tanks (DST) can meet current requirements for containment of dangerous waste. Therefore, the single-shell tanks (SST) are being ''interim stabilized,'' which is the process of removing liquid from the waste through the use of a jet pump installed in a saltwell which penetrates the waste. Lockheed Martin Hanford Company has decided to purchase additional Pumping and Instrumentation Control (PIC) skids to monitor and control the operation of saltwell jet pumps in SSTs. Similar PIC skids are already in use at several locations. The PIC skids will shut off all power to equipment/instruments if preset limits are exceeded for such conditions as flammable gas, leak detection, pressure and flow, as well as provide air and water necessary for saltwell pumping activities. This document outlines the functional design criteria for pumping and instrumentation control (PIC) skids to support the interim stabilization effort for saltwell pumping.

  10. Implantation of cardiac progenitor cells using self-assembling peptide improves cardiac function after myocardial infarction.

    PubMed

    Tokunaga, Masakuni; Liu, Mei-Lan; Nagai, Toshio; Iwanaga, Koji; Matsuura, Katsuhisa; Takahashi, Toshinao; Kanda, Masato; Kondo, Naomichi; Wang, Pin; Naito, Atsuhiko T; Komuro, Issei

    2010-12-01

    Implantation of various types of cells into the heart has been reported to be effective for heart failure, however, it is unknown what kinds of cells are most suitable for myocardial repair. To examine which types of cells are most effective, we injected cell-Puramatrix™ (PM) complex into the border area and overlaid the cell-PM patch on the myocardial infarction (MI) area. We compared cardiac morphology and function at 2 weeks after transplantation. Among clonal stem cell antigen-1 positive cardiac progenitors with PM (cSca-1/PM), bone marrow mononuclear cells with PM (BM/PM), skeletal myoblasts with PM (SM/PM), adipose tissue-derived mesenchymal cells with PM (AMC/PM), PM alone (PM), and non-treated MI group (MI), the infarct area of cSca-1/PM was smaller than that of BM/PM, SM/PM, PM and MI. cSca-1/PM and AMC/PM attenuated ventricular enlargement and restored cardiac function in comparison with MI. Capillary density in the infarct area of cSca-1/PM was higher than that of other five groups. The percentage of TUNEL positive cardiomyocytes in the infarct area of cSca-1/PM was lower than that of MI and PM. cSca-1 secreted VEGF and some of them differentiated into cardiomyocytes and vascular smooth muscle cells. These results suggest that transplantation of cSca-1/PM most effectively prevents cardiac remodeling and dysfunction through angiogenesis, inhibition of apoptosis and myocardial regeneration. PMID:20869968

  11. Regulation of cardiac metabolism and function by lipogenic factors.

    PubMed

    Bednarski, Tomasz; Pyrkowska, Aleksandra; Opasińska, Agnieszka; Dobrzyń, Paweł

    2016-01-01

    The heart has a limited capacity for lipogenesis and de novo lipid synthesis. However, expression of lipogenic genes in cardiomyocytes is unexpectedly high. Recent studies showed that lipogenic genes are important factors regulating cardiac metabolism and function. Long chain fatty acids are a major source of ATP required for proper heart function, and under aerobic conditions, the heart derives 60-90% of the energy necessary for contractile function from fatty acid oxidation. On the other hand, cardiac lipid over-accumulation (e.g. ceramides, diacylglycerols) leads to heart dysfunction. Downregulation of the lipogenic genes' expression (e.g. sterol regulatory element binding protein 1, stearoyl-CoA desaturase, acetyl-CoA kwacarboxylase) decreased heart steatosis and cardiomyocyte apoptosis, improving systolic and diastolic function of the left ventricle. Lipogenic factors also regulate fatty acids and glucose utilization in the heart, underlining their important role in maintaining energetic homeostasis in pathological states. Fatty acid synthase, the enzyme catalyzing fatty acids de novo synthesis, affects cardiac calcium signaling through regulation of L-type calcium channel activity. Thus, a growing body of evidence suggests that the role of lipogenic genes in cardiomyocytes may be distinct from other tissues. Here, we review recent advances made in understanding the role of lipogenic genes in the control of heart metabolism and its involvement in the pathogenesis of lipotoxic cardiomyopathy. PMID:27333934

  12. Pulling on my heartstrings: mechanotransduction in cardiac development and function

    PubMed Central

    McCormick, Margaret E.; Tzima, Ellie

    2016-01-01

    Purpose of review Endothelial cells line the surface of the cardiovascular system and display a large degree of heterogeneity due to developmental origin and location. Despite this heterogeneity, all endothelial cells are exposed to wall shear stress (WSS) imparted by the frictional force of flowing blood, which plays an important role in determining the endothelial cell phenotype. Although the effects of WSS have been greatly studied in vascular endothelial cells, less is known about the role of WSS in regulating cardiac function and cardiac endothelial cells. Recent findings Recent advances in genetic and imaging technologies have enabled a more thorough investigation of cardiac hemodynamics. Using developmental models, shear stress sensing by endocardial endothelial cells has been shown to play an integral role in proper cardiac development including morphogenesis and formation of the conduction system. In the adult, less is known about hemodynamics and endocardial endothelial cells, but a clear role for WSS in the development of coronary and valvular disease is increasingly appreciated. Summary Future research will further elucidate a role for WSS in the developing and adult heart, and understanding this dynamic relationship may represent a potential therapeutic target for the treatment of cardiomyopathies. PMID:26906028

  13. 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. PMID:23084034

  14. Subclinical hypothyroidism effects on cardiac function.

    PubMed

    Niafar, M; Toufan, M; Ghafoori, S; Aghamohammadzadeh, N

    2009-08-01

    To evaluate heart function in subclinical hypothyroid women in comparison with healthy subjects, a prospective study was performed on newly detected subclinical hypothyroid women presenting to endocrinology clinic of Tabriz Sina Hospital from October 2007 to February 2008. Thirty five women with Subclinical Hypothyroidism (SH) in case group were matched with 35 healthy euthyroid women in control group. All patients in both groups were studied by two dimensional echocardiography and Tissue Doppler Imaging (TDI) in Tabriz Shahid Madani Hospital. The FT4 and TSH levels were measured. Comparison of TDI results in Right Ventricle (RV) showed the significantly lower mean T(v) excursion in case group with no significant difference in other parameters. In Left Ventricle (LV), the mean A(m), A(v) and E(v)/E(m) were significantly higher and E/A was lower in the case group, but there was no significant difference in other parameters. No RV diastolic dysfunction was documented in both groups. There was no case with LV systolic dysfunction in both groups. There were 21 (60%) patients with LV diastolic dysfunction in the case group comparing with 11 (31.4%) cases in the control group (p = 0.016, OR = 0.306). Frequency of LV diastolic dysfunction was significantly higher in the case group in patients aged > or = 40 years (94.1% vs. 53.3%; p = 0.013). There was no case of pericardial effusion in the studied population. According to our results, SH may cause LV diastolic dysfunction. Likewise, minor RV systolic dysfunction might be seen in these patients. PMID:19943461

  15. [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). PMID:25588185

  16. 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. PMID:27185045

  17. 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

  18. 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

  19. 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. PMID:27056419

  20. The Insular Cortex and the Regulation of Cardiac Function.

    PubMed

    Oppenheimer, Stephen; Cechetto, David

    2016-04-01

    Cortical representation of the heart challenges the orthodox view that cardiac regulation is confined to stereotyped, preprogrammed and rigid responses to exteroceptive or interoceptive environmental stimuli. The insula has been the region most studied in this regard; the results of clinical, experimental, and functional radiological studies show a complex interweave of activity with patterns dynamically varying regarding lateralization and antero-posterior distribution of responsive insular regions. Either acting alone or together with other cortical areas including the anterior cingulate, medial prefrontal, and orbito-frontal cortices as part of a concerted network, the insula can imbue perceptions with autonomic color providing emotional salience, and aiding in learning and behavioral decision choice. In these functions, cardiovascular input and the right anterior insula appear to play an important, if not pivotal role. At a more basic level, the insula gauges cardiovascular responses to exteroceptive and interoceptive stimuli, taking into account memory, cognitive, and reflexive constructs thereby ensuring appropriate survival responses and maintaining emotional and physiological homeostasis. When acquired derangements to the insula occur after stroke, during a seizure or from abnormal central processing of interoceptive or exteroceptive environmental cues as in psychiatric disorders, serious consequences can arise including cardiac electrophysiological, structural and contractile dysfunction and sudden cardiac death. PMID:27065176

  1. Electrophysiological Modeling of Cardiac Ventricular Function: From Cell to Organ

    PubMed Central

    Winslow, R. L.; Scollan, D. F.; Holmes, A.; Yung, C. K.; Zhang, J.; Jafri, M. S.

    2005-01-01

    Three topics of importance to modeling the integrative function of the heart are reviewed. The first is modeling of the ventricular myocyte. Emphasis is placed on excitation-contraction coupling and intracellular Ca2+ handling, and the interpretation of experimental data regarding interval-force relationships. Second, data on use of diffusion tensor magnetic resonance (DTMR) imaging for measuring the anatomical structure of the cardiac ventricles are presented. A method for the semi-automated reconstruction of the ventricles using a combination of gradient recalled acquisition in the steady state (GRASS) and DTMR images is described. Third, we describe how these anatomically and biophysically based models of the cardiac ventricles can be implemented on parallel computers. PMID:11701509

  2. Proangiogenic scaffolds as functional templates for cardiac tissue engineering

    PubMed Central

    Madden, Lauran R.; Mortisen, Derek J.; Sussman, Eric M.; Dupras, Sarah K.; Fugate, James A.; Cuy, Janet L.; Hauch, Kip D.; Laflamme, Michael A.; Murry, Charles E.; Ratner, Buddy D.

    2010-01-01

    We demonstrate here a cardiac tissue-engineering strategy addressing multicellular organization, integration into host myocardium, and directional cues to reconstruct the functional architecture of heart muscle. Microtemplating is used to shape poly(2-hydroxyethyl methacrylate-co-methacrylic acid) hydrogel into a tissue-engineering scaffold with architectures driving heart tissue integration. The construct contains parallel channels to organize cardiomyocyte bundles, supported by micrometer-sized, spherical, interconnected pores that enhance angiogenesis while reducing scarring. Surface-modified scaffolds were seeded with human ES cell-derived cardiomyocytes and cultured in vitro. Cardiomyocytes survived and proliferated for 2 wk in scaffolds, reaching adult heart densities. Cardiac implantation of acellular scaffolds with pore diameters of 30–40 μm showed angiogenesis and reduced fibrotic response, coinciding with a shift in macrophage phenotype toward the M2 state. This work establishes a foundation for spatially controlled cardiac tissue engineering by providing discrete compartments for cardiomyocytes and stroma in a scaffold that enhances vascularization and integration while controlling the inflammatory response. PMID:20696917

  3. 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.

  4. 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.

  5. 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. PMID:17284482

  6. 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.

  7. Highly Elastic Micropatterned Hydrogel for Engineering Functional Cardiac Tissue

    PubMed Central

    Annabi, Nasim; Tsang, Kelly; Mithieux, Suzanne M.; Nikkhah, Mehdi; Ameri, Afshin

    2013-01-01

    Heart failure is a major international health issue. Myocardial mass loss and lack of contractility are precursors to heart failure. Surgical demand for effective myocardial repair is tempered by a paucity of appropriate biological materials. These materials should conveniently replicate natural human tissue components, convey persistent elasticity, promote cell attachment, growth and conformability to direct cell orientation and functional performance. Here, microfabrication techniques are applied to recombinant human tropoelastin, the resilience-imparting protein found in all elastic human tissues, to generate photocrosslinked biological materials containing well-defined micropatterns. These highly elastic substrates are then used to engineer biomimetic cardiac tissue constructs. The micropatterned hydrogels, produced through photocrosslinking of methacrylated tropoelastin (MeTro), promote the attachment, spreading, alignment, function, and intercellular communication of cardiomyocytes by providing an elastic mechanical support that mimics their dynamic mechanical properties in vivo. The fabricated MeTro hydrogels also support the synchronous beating of cardiomyocytes in response to electrical field stimulation. These novel engineered micropatterned elastic gels are designed to be amenable to 3D modular assembly and establish a versatile, adaptable foundation for the modeling and regeneration of functional cardiac tissue with potential for application to other elastic tissues. PMID:24319406

  8. 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

  9. 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. PMID:26063704

  10. 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

  11. Sleep Disordered Breathing: Hypertension and Cardiac Structure and Function.

    PubMed

    Querejeta Roca, Gabriela; Shah, Amil M

    2015-12-01

    Obstructive sleep apnea (OSA) is a common form of sleep disordered breathing and has a relatively high prevalence in the general population. The frequency and severity of OSA is associated with age, male sex, and obesity, and OSA has been linked to cardiovascular complications and death. Importantly, OSA has a strong association with both prevalent and incidental hypertension and has a particularly high prevalence in patients with resistant hypertension. In these patients, CPAP and other OSA-directed treatments have been proposed as therapy to help control blood pressure (BP), especially in patients who have not attained optimal BP control despite maximum pharmacological therapy. OSA has also been associated with alterations in cardiac structure and function, although most studies are small and highly limited in study design. Existing data suggest an association between OSA greater left ventricle (LV) mass and hypertrophy that appears independent of confounders including hypertension and obesity. Although less clear and more controversial, OSA severity has been linked to LV systolic and diastolic function, pulmonary hypertension, and right ventricular hypertrophy. Further studies are needed to confirm the potential causal role of OSA in these observed associations with cardiac abnormalities. PMID:26493391

  12. Effects of experimental cardiac volume loading on left atrial phasic function in healthy dogs.

    PubMed

    Osuga, Tatsuyuki; Nakamura, Kensuke; Morita, Tomoya; Nisa, Khoirun; Yokoyama, Nozomu; Sasaki, Noboru; Morishita, Keitaro; Ohta, Hiroshi; Takiguchi, Mitsuyoshi

    2016-09-01

    OBJECTIVE To elucidate the relationship between acute volume overload and left atrial phasic function in healthy dogs. ANIMALS 6 healthy Beagles. PROCEDURES Dogs were anesthetized. A Swan-Ganz catheter was placed to measure mean pulmonary capillary wedge pressure (PCWP). Cardiac preload was increased by IV infusion with lactated Ringer solution at 150 mL/kg/h for 90 minutes. Transthoracic echocardiography was performed before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after volume loading began. At each echocardiographic assessment point, apical 4-chamber images were recorded and analyzed to derive time-left atrial area curves. Left atrial total (for reservoir function), passive (for conduit function), and active (for booster-pump function) fractional area changes were calculated from the curves. RESULTS Volume overload resulted in a significant increase from baseline in PCWP from 15 to 90 minutes after volume loading began. All fractional area changes at 15 to 90 minutes were significantly increased from baseline. In multiple regression analysis, quadratic regression models were better fitted to the relationships between PCWP and each of the total and active fractional area changes than were linear regression models. A linear regression model was better fitted to the relationship between PCWP and passive fractional area change. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that left atrial phasic function assessed on the basis of left atrial phasic areas was enhanced during experimental cardiac volume loading in healthy dogs. The effect of volume load should be considered when evaluating left atrial phasic function by indices derived from left atrial phasic sizes. PMID:27580106

  13. Use of intra-aortic balloon pump support for oozing-type cardiac rupture after acute myocardial infarction.

    PubMed

    Zhang, Zhi-Ping; Su, Xi; Liu, Cheng-Wei; Song, Dan; Peng, Jian; Wu, Ming-Xiang; Yang, Yu-Chun; Liu, Bo; Xu, Cheng-Yi; Wang, Fang

    2016-01-01

    Left ventricular free wall rupture usually leads to acute hemopericardium and sudden cardiac death resulting in cardiac tamponade. Rarely, only a few patients with subacute free wall rupture such as oozing-type ventricular rupture or left ventricular false aneurysm may permit time for pericardiocentesis and surgery. We report a 63-year-old man with ST-elevation myocardial infarction who underwent primary percutaneous coronary intervention about 12 hours from the onset, and cardiac tamponade occurred on the second day. An intra-aortic balloon pump (IABP) was immediately inserted for hemodynamic support. After 100 mL of pericardial fresh blood was drained from the percardial cavity, his hemodynamic collapse was promptly improved with IABP support. In the following 24 hours, about 600 mL of hemorrhagic pericardial fluid was drained. The most likely diagnosis was concerning for oozing-type ventricular rupture, and a conservative approach was decided. The patient survived to the acute phase under IABP support and was discharged with complete recovery. PMID:26145582

  14. Associations between Kidney Function and Subclinical Cardiac Abnormalities in CKD

    PubMed Central

    Hsu, Chi-yuan; Li, Yongmei; Mishra, Rakesh K.; Keane, Martin; Rosas, Sylvia E.; Dries, Daniel; Xie, Dawei; Chen, Jing; He, Jiang; Anderson, Amanda; Go, Alan S.; Shlipak, Michael G.

    2012-01-01

    Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories ≥60, 45–59, 30–44, and <30 ml/min per 1.73 m2, respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m2 had twofold higher odds of LVH (OR=2.20, 95% CI=1.40–3.40; P<0.001) relative to subjects with eGFR≥60 ml/min per 1.73 m2. This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30–44 ml/min per 1.73 m2 also significantly associated with LVH and abnormal LV geometry compared with eGFR≥60 ml/min per 1.73 m2. In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables. PMID:22935481

  15. 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. PMID:19940994

  16. Dietary interaction of high fat and marginal copper deficiency on cardiac contractile function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High fat and copper deficient diets impair heart function leading to cardio hypertrophy, increased lipid droplet volume and compromised contractile function, resembling liptoxic cardiac dysfunction. However, the combined effect of the two on cardiac function is unknown. The purpose or objective of t...

  17. 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

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

    PubMed

    H, Schotola; Aj, Wetz; Af, Popov; I, Bergmann; Bc, Danner; Fa, Schöndube; M, Bauer; A, Bräuer

    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. PMID:27608341

  19. Homeobox Protein Hop Functions in the Adult Cardiac Conduction System

    PubMed Central

    Ismat, Fraz A.; Zhang, Maozhen; Kook, Hyun; Huang, Bin; Zhou, Rong; Ferrari, Victor A.; Epstein, Jonathan A.; Patel, Vickas V.

    2006-01-01

    Hop is an unusual homeobox gene expressed in the embryonic and adult heart. Hop acts downstream of Nkx2–5 during development, and Nkx2–5 mutations are associated with cardiac conduction system (CCS) defects. Inactivation of Hop in the mouse is lethal in half of the expected null embryos. Here, we show that Hop is expressed strongly in the adult CCS. Hop−/− adult mice display conduction defects below the atrioventricular node (AVN) as determined by invasive electrophysiological testing. These defects are associated with decreased expression of connexin40. Our results suggest that Hop functions in the adult CCS and demonstrate conservation of molecular hierarchies between embryonic myocardium and the specialized conduction tissue of the mature heart. PMID:15790958

  20. 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.

  1. The effect of gravitational acceleration on cardiac diastolic function: a biofluid mechanical perspective with initial results.

    PubMed

    Pantalos, George M; Bennett, Thomas E; Sharp, M Keith; Woodruff, Stewart J; O'Leary, Sean D; Gillars, Kevin J; Schurfranz, Thomas; Everett, Scott D; Lemon, Mark; Schwartz, John

    2005-08-01

    Echocardiographic measurements of astronaut cardiac function have documented an initial increase, followed by a progressive reduction in both left ventricular end-diastolic volume index and stroke volume with entry into microgravity (micro-G). The investigators hypothesize that the observed reduction in cardiac filling may, in part, be due to the absence of a gravitational acceleration dependent, intraventricular hydrostatic pressure difference in micro-G that exists in the ventricle in normal gravity (1-G) due to its size and anatomic orientation. This acceleration-dependent pressure difference, DeltaP(LV), between the base and the apex of the heart for the upright posture can be estimated to be 6660 dynes/cm(2) ( approximately 5 mm Hg) on Earth. DeltaP(LV) promotes cardiac diastolic filling on Earth, but is absent in micro-G. If the proposed hypothesis is correct, cardiac pumping performance would be diminished in micro-G. To test this hypothesis, ventricular function experiments were conducted in the 1-G environment using an artificial ventricle pumping on a mock circulation system with the longitudinal axis anatomically oriented for the upright posture at 45 degrees to the horizon. Additional measurements were made with the ventricle horizontally oriented to null DeltaP(LV)along the apex-base axis of the heart as would be the case for the supine posture, but resulting in a lesser hydrostatic pressure difference along the minor (anterior-posterior) axis. Comparative experiments were also conducted in the micro-G environment of orbital space flight on board the Space Shuttle. This paper reviews the use of an automated cardiovascular simulator flown on STS-85 and STS-95 as a Get Away Special payload to test this hypothesis. The simulator consisted of a pneumatically actuated, artificial ventricle connected to a closed-loop, fluid circuit with adjustable compliance and resistance elements to create physiologic pressure and flow conditions. Ventricular

  2. Impact of an environmental relevant concentration of 17α-ethinylestradiol on the cardiac function of bullfrog tadpoles.

    PubMed

    Salla, Raquel F; Gamero, Fernando U; Rissoli, Rafael Z; Dal-Medico, Samuel E; Castanho, Luciano Mendes; Carvalho, Cleoni dos Santos; Silva-Zacarin, Elaine C M; Kalinin, Ana L; Abdalla, Fabio C; Costa, Monica J

    2016-02-01

    This study evaluated if a concentration of 17α-ethinylestradiol (EE2 - 10 ng L(-1) for 96 h) normally found in Brazilian surface waters exerts any impact on cardiac function of bullfrog tadpoles (25 Gosner stage), Lithobates catesbeianus. During exposure, the animals' activity level (AL -% of active individuals) was monitored twice a day. Then, the in loco heart rate (f(H) - bpm) was determined, as well as the relative ventricular mass (RVM - % of body mass). Afterwards, cardiac ventricles were mounted for isometric force recordings (CS - mN mm(-2)), and determination of the cardiac pumping capacity (CPC - mN mm(-2) min(-1)). EE2 did not affect tadpoles' AL, although it resulted in a tachycardia in animals exposed to EE2 (f(H) = 66 bpm) when compared to controls (f(H) = 52 bpm), suggesting that EE2 acts directly on the cardiac muscle of tadpoles, rather than being a result of an increased cardiac demand due to a higher activity level (i.e., avoidance response). Additionally, EE2 exerted a positive inotropic response, which resulted in a higher CPC, which occurred independently of an increase in the number of myofibrils of EE2-exposed animals, since RVM remained similar between experimental groups. Thus, the increase on cardiac demand induced by the exposure to EE2 elevates considerably the animal energy expenditure, diverting a large amount of energy that tadpoles could use for their growth and development. These alterations can make amphibians more susceptible to predators and reduce the likelihood to reach reproductive stage. PMID:26539711

  3. 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.

  4. 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.

  5. 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

  6. Primary Cardiac Lymphoma: Diagnosis and the Impact of Chemotherapy on Cardiac Structure and Function.

    PubMed

    Pagé, Maude; Grasso, Agata E; Carpenter, John-Paul; Sheppard, Mary N; Karwatowski, Stefan P; Mohiaddin, Raad H

    2016-07-01

    We report a case of primary cardiac lymphoma presenting as myopericarditis and rapidly deteriorating into biventricular heart failure and ventricular arrhythmias. Computed tomography and cardiac magnetic resonance (CMR) imaging showed extensive myocardial infiltration with typical patterns on tissue characterization CMR images, raising clinical suspicion. Diagnosis was confirmed by myocardial histologic examination. Marked regression of tumor burden was apparent after 6 cycles of anthracycline-based chemotherapy. This case illustrates that a high degree of suspicion for this rare entity is mandated to institute timely treatment. Rapid tumor lysis may induce life-threatening acute cardiac decompensation that requires intensive monitoring and support therapy. PMID:26755242

  7. Molecular mechanism regulating myosin and cardiac functions by ELC.

    PubMed

    Lossie, Janine; Köhncke, Clemens; Mahmoodzadeh, Shokoufeh; Steffen, Walter; Canepari, Monica; Maffei, Manuela; Taube, Martin; Larchevêque, Oriane; Baumert, Philipp; Haase, Hannelore; Bottinelli, Roberto; Regitz-Zagrosek, Vera; Morano, Ingo

    2014-07-18

    The essential myosin light chain (ELC) is involved in modulation of force generation of myosin motors and cardiac contraction, while its mechanism of action remains elusive. We hypothesized that ELC could modulate myosin stiffness which subsequently determines its force production and cardiac contraction. Therefore, we generated heterologous transgenic mouse (TgM) strains with cardiomyocyte-specific expression of ELC with human ventricular ELC (hVLC-1; TgM(hVLC-1)) or E56G-mutated hVLC-1 (hVLC-1(E56G); TgM(E56G)). hVLC-1 or hVLC-1(E56G) expression in TgM was around 39% and 41%, respectively of total VLC-1. Laser trap and in vitro motility assays showed that stiffness and actin sliding velocity of myosin with hVLC-1 prepared from TgM(hVLC-1) (1.67 pN/nm and 2.3 μm/s, respectively) were significantly higher than myosin with hVLC-1(E56G) prepared from TgM(E56G) (1.25 pN/nm and 1.7 μm/s, respectively) or myosin with mouse VLC-1 (mVLC-1) prepared from C57/BL6 (1.41 pN/nm and 1.5 μm/s, respectively). Maximal left ventricular pressure development of isolated perfused hearts in vitro prepared from TgM(hVLC-1) (80.0 mmHg) were significantly higher than hearts from TgM(E56G) (66.2 mmHg) or C57/BL6 (59.3±3.9 mmHg). These findings show that ELCs decreased myosin stiffness, in vitro motility, and thereby cardiac functions in the order hVLC-1>hVLC-1(E56G)≈mVLC-1. They also suggest a molecular pathomechanism of hypertrophic cardiomyopathy caused by hVLC-1 mutations. PMID:24911555

  8. 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

  9. Normalization of Naxos plakoglobin levels restores cardiac function in mice.

    PubMed

    Zhang, Zhiwei; Stroud, Matthew J; Zhang, Jianlin; Fang, Xi; Ouyang, Kunfu; Kimura, Kensuke; Mu, Yongxin; Dalton, Nancy D; Gu, Yusu; Bradford, William H; Peterson, Kirk L; Cheng, Hongqiang; Zhou, Xinmin; Chen, Ju

    2015-04-01

    Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease. PMID:25705887

  10. Changes of Cardiac Function During Ultradistance Trail Running.

    PubMed

    Jouffroy, Romain; Caille, Vincent; Perrot, Stéphane; Vieillard-Baron, Antoine; Dubourg, Olivier; Mansencal, Nicolas

    2015-10-15

    Previous studies have noted reversible cardiac dysfunction during marathon races, but few data are available concerning ultradistance trail running. The aim of this study was to assess echocardiographic parameters during ultradistance trail running. We performed an observational study in 66 participants to the 80-km Ecotrail of Paris Ile de France. All subjects had echocardiographic examinations before the race and on arrival, and 28 of them underwent serial echocardiographic examinations during the race (21 and 53 km). A single experienced physician performed all echocardiographic examinations, and the same protocol was always used (conventional 2-dimensional and Doppler left ventricular parameters and longitudinal strain). All echocardiographic parameters of left ventricular (LV) systolic function were significantly decreased on arrival (p ≤0.002). A significant reduction of LV systolic function was observed in 48% of study subjects on arrival. No significant modification was observed at 21 or at 53 km, and only global longitudinal strain was significantly decreased (p = 0.0008). At arrival, mitral E/A ratio and average mitral tissue Doppler imaging e' wave were significantly decreased (p = 0.0001 and p = 0.0004, respectively), but these changes were observed from 21 km. In conclusion, ultradistance trail running can lead to abnormalities of LV systolic and diastolic functions in amateur runners. Diastolic dysfunction arises earlier than systolic dysfunction. Left ventricular systolic dysfunction occurred in 48% of the study subjects and was detected early by assessment of longitudinal strain. PMID:26294134

  11. 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

  12. 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

  13. Sinus node function in first three weeks after cardiac transplantation.

    PubMed Central

    Mackintosh, A F; Carmichael, D J; Wren, C; Cory-Pearce, R; English, T A

    1982-01-01

    Donor sinus node function was studied in 10 patients from day 4 to day 24 after cardiac transplantation. Cycle length, atrial arrhythmias, corrected sinus node recovery time, and estimated sinoatrial conduction time were recorded daily. Five patients had at least two sets of results suggesting sinus node dysfunction (group A) while five patients had no such abnormalities (group B). The prognosis in group A was poor, with four of the five patients dying within four months of the operation; one unexpected death from arrhythmias was recorded by ambulatory electrocardiographic monitoring. All five patients in group B survived for at least eight months. In nine patients sinus node function varied from day to day, with corrected sinus node recovery time reaching a peak at 11 to 18 days after operation. The longest corrected sinus node recovery time was 11 160 ms. Neither the differences between the patients, nor the day to day variation, could be explained solely by the degree of rejection as assessed by biopsy or by the ischaemia time of the heart during procurement. Sinus node dysfunction soon after transplantation is associated with a poorer prognosis and might be the terminal event in some cases. Images PMID:6756446

  14. The effect of cardiac glycosides on the Na+ pump current-voltage relationship of isolated rat and guinea-pig heart cells.

    PubMed Central

    Hermans, A N; Glitsch, H G; Verdonck, F

    1994-01-01

    1. Whole-cell recording from isolated rat and guinea-pig ventricular myocytes revealed a change of the cardiac Na+ pump current (Ip)-voltage (V) relationship by cardiac glycosides, specific inhibitors of the Na(+)-K+ pump. 2. Dihydro-ouabain (DHO) diminished Ip in rat ventricular cells at 0 mV in a concentration-dependent manner. 3. The concentration-response curve of Ip inhibition caused by DHO was shifted to higher [DHO] at higher extracellular K+ concentrations ([K+]o) or at more negative membrane potentials. 4. In rat myocytes, DHO immediately flattened the normalized cardiac Ip-V curve and evoked or enhanced a region of negative slope. 5. Ouabain, at concentrations which caused a comparable inhibition of Ip, exerted DHO-like effects on the Ip-V relationship of rat ventricular myocytes. However, the effects developed more slowly. 6. A slowly developing alteration of the Ip-V curve was also observed upon application of DHO to guinea-pig ventricular cells. The range of [DHO] used was about 100-fold lower than that applied to rat ventricular cells, but was equally effective for Ip inhibition. 7. Increasing the K+ concentration of DHO-containing media affected the existing equilibrium of DHO binding to the cardiac Na(+)-K+ pump. A new equilibrium was reached within about 3 s in rat ventricular myocytes, but only within about 50 s in guinea-pig ventricular cells under the experimental conditions chosen. 8. It is concluded that the changes of the cardiac Ip-V curve induced by cardiac glycosides are mediated by voltage-dependent variations of the local [K+]o at the K+ binding sites of the Na(+)-K+ pump in an 'access channel'. The variations were estimated by means of the Boltzmann equation. The estimations agreed with those derived from the measured DHO binding to the Na(+)-K+ pump at various [K+]o. A new equilibrium of glycoside binding to the pump is established at the altered [K+]o. The time necessary to reach the new binding equilibrium varies with the

  15. 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

  16. 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

  17. The Role of Cardiac Troponin T Quantity and Function in Cardiac Development and Dilated Cardiomyopathy

    PubMed Central

    Ahmad, Ferhaan; Banerjee, Sanjay K.; Lage, Michele L.; Huang, Xueyin N.; Smith, Stephen H.; Saba, Samir; Rager, Jennifer; Conner, David A.; Janczewski, Andrzej M.; Tobita, Kimimasa; Tinney, Joseph P.; Moskowitz, Ivan P.; Perez-Atayde, Antonio R.; Keller, Bradley B.; Mathier, Michael A.; Shroff, Sanjeev G.; Seidman, Christine E.; Seidman, J. G.

    2008-01-01

    Background Hypertrophic (HCM) and dilated (DCM) cardiomyopathies result from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings We ablated Tnnt2 to produce heterozygous Tnnt2+/− mice, and crossbreeding produced homozygous null Tnnt2−/− embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/−/TGWT) or mutant (Tnnt2+/−/TGK210Δ) transgenes. Tnnt2+/− mice relative to wildtype had significantly reduced transcript (0.82±0.06[SD] vs. 1.00±0.12 arbitrary units; p = 0.025), but not protein (1.01±0.20 vs. 1.00±0.13 arbitrary units; p = 0.44). Tnnt2+/− mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/−/TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18±4 vs. 29±7%; p<0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/−/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/−/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34±0.08 vs. 5.58±0.03 at sarcomere length 1.9 µm, p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2−/− embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal

  18. Altered mechanical state in the embryonic heart results in time-dependent decreases in cardiac function.

    PubMed

    Johnson, Brennan; Bark, David; Van Herck, Ilse; Garrity, Deborah; Dasi, Lakshmi Prasad

    2015-11-01

    Proper blood flow patterns are critical for normal cardiac morphogenesis, a process that occurs rapidly in order to support further development of all tissue and organs. Previously, intracardiac fluid forces have been shown to play a critical role in cardiac morphogenesis. Altered blood flow in early development can result in an array of cardiac defects including ventricular septal defects, valve malformations, and impaired cardiac looping. However, given the dynamic and highly transient nature of cardiac morphogenesis, time dependency of the mechanical environment as an epigenetic factor in relation to intracardiac forces must be significant. Here, we show that abnormal cardiac loading adversely influences cardiac morphology only during certain time windows, thus confirming that mechanical factors are a time-dependent epigenetic factor. To illustrate this, groups of zebrafish embryos were spaced at 6-h increments from 24 to 48 h post-fertilization (hpf) in which embryos were centrifuged to generate a noninvasive alteration of cardiac preload in addition to an overall hypergravity environment. We found that earlier and later treatment groups responded with altered morphology and function, while the group with altered preload from 30 to 36 hpf had no effect. These results demonstrate the inherently time-dependent nature of epigenetic factors as pertaining to intracardiac forces and external mechanical factors. Further, it underscores the highly coupled nature of programmed biology and mechanical forces during cardiac morphogenesis. Future studies with respect to surgical correction during cardiac morphogenesis must consider timing to optimize therapeutic impact. PMID:25976479

  19. 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. PMID:27277901

  20. Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization.

    PubMed

    Guex, A G; Frobert, A; Valentin, J; Fortunato, G; Hegemann, D; Cook, S; Carrel, T P; Tevaearai, H T; Giraud, M N

    2014-07-01

    Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS). PMID:24531014

  1. 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

  2. Cardiac cytoarchitecture - why the "hardware" is important for heart function!

    PubMed

    Ehler, Elisabeth

    2016-07-01

    Cells that constitute fully differentiated tissues are characterised by an architecture that makes them perfectly suited for the job they have to do. This is especially obvious for cardiomyocytes, which have an extremely regular shape and display a paracrystalline arrangement of their cytoplasmic components. This article will focus on the two major cytoskeletal multiprotein complexes that are found in cardiomyocytes, the myofibrils, which are responsible for contraction and the intercalated disc, which mediates mechanical and electrochemical contact between individual cardiomyocytes. Recent studies have revealed that these two sites are also crucial in sensing excessive mechanical strain. Signalling processes will be triggered that## lead to changes in gene expression and eventually lead to an altered cardiac cytoarchitecture in the diseased heart, which results in a compromised function. Thus, understanding these changes and the signals that lead to them is crucial to design treatment strategies that can attenuate these processes. 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. PMID:26577135

  3. Anti-rat soluble IL-6 receptor antibody down-regulates cardiac IL-6 and improves cardiac function following trauma-hemorrhage.

    PubMed

    Yang, Shaolong; Hu, Shunhua; Choudhry, Mashkoor A; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

    2007-03-01

    Although anti-IL-6-mAb down-regulates cardiac IL-6 and attenuates IL-6-mediated cardiac dysfunction following trauma-hemorrhage, it is not known whether blockade of IL-6 receptor will down-regulate cardiac IL-6 and improve cardiac function under those conditions. Six groups of male adult rats (275-325 g) were used: sham/trauma-hemorrhage+vehicle, sham/trauma-hemorrhage+IgG, sham/trauma-hemorrhage+anti-rat sIL-6R. Rats underwent trauma-hemorrhage (removal of 60% of the circulating blood volume and fluid resuscitation after 90 min). Vehicle (V), normal goat IgG or anti-rat sIL-6R (16.7 microg/kg BW) was administered intra-peritoneally in the middle of resuscitation. Two hours later, cardiac function was measured by ICG dilution technique; blood samples collected, cardiomyocytes isolated, and cardiomyocyte nuclei were then extracted. Cardiac IL-6, IL-6R, gp130, IkappaB-alpha/P-IkappaB-alpha, NF-kappaB, and ICAM-1 expressions were measured by immunoblotting. Plasma IL-6 and cardiomyocyte NF-kappaB DNA-binding activity were determined by ELISA. In additional animals, heart harvested and cardiac MPO activity and CINC-1 and -3 were also measured. In another group of rats, cardiac function was measure by microspheres at 24 h following trauma-hemorrhage. Cardiac function was depressed and cardiac IL-6, P-IkappaB-alpha, NF-kappaB and its DNA-binding activity, ICAM-1, MPO activity, and CINC-1 and -3 were markedly increased after trauma-hemorrhage. Moreover, cardiac dysfunction was evident even 24 h after trauma-hemorrhage. Administration of sIL-6R following trauma-hemorrhage: (1) improved cardiac output at 2 h and 24 h (p<0.05); (2) down-regulated both cardiac IL-6 and IL-6R (p<0.05); and (3) attenuated cardiac P-IkappaB-alpha, NF-kappaB, NF-kappaB DNA-binding activity, ICAM-1, CINC-1, -3, and MPO activity (p<0.05). IgG did not significantly influence the above parameters. Thus, IL-6-mediated up-regulation of cardiac NF-kappaB, ICAM-1, CINC-1, -3, and MPO activity likely

  4. Competitive displacement of wild-type phospholamban from the Ca2+-free cardiac calcium pump by phospholamban mutants with different binding affinities.

    PubMed

    Chen, Zhenhui

    2014-11-01

    Phospholamban (PLB) regulates the cardiac Ca(2+) pump (SERCA2a). To test how different species of PLB mutants compete to interact with the Ca(2+)-free, E2 conformation of SERCA2a, using the insect cell expression system, we examined how various exogenous PLB mutants regulated SER-20G-PLB, a chimeric WT-SERCA2a-Gly-WT-PLB construct, which retains a fully catalytic active Ca(2+)-pump and its intrinsically regulatory PLB-tether. Exogenous gain-of-function PLB mutants dominantly super-inhibited the WT-PLB-tethered SERCA2a. Further, in the Ca(2+)-free condition, co-expressed normal- or super-inhibitory PLB mutant with either engineered N30C or V49C residue cross-linked to Lys328 or V89C of SER-20G-PLB at the cytoplasmic or transmembrane domain, respectively, suggesting that these freely diffusing PLB mutants completely replaced the WT-PLB-tether and fit into the binding pocket previously occupied by WT-PLB. Micromolar Ca(2+) completely inhibited cross-linking, yielding a similar Ca(2+)-dependency regardless of the presence of the WT-PLB-tether. In contrast, the PLB mutant with the loss-of-function L31A mutation has decreased binding affinity for SERCA2a, thus cross-linking weakly to the WT-PLB-tethered SERCA2a, and only marginally affected the activity of SER-20G-PLB. Thus, there is a reversible equilibrium between different PLB mutants for binding to E2, in which PLB mutants possessing higher binding affinity for SERCA2a produce a more stable E2·PLB and lower Ca(2+) affinity. PMID:25194792

  5. 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.

  6. Design and formulation of functional pluripotent stem cell-derived cardiac microtissues

    PubMed Central

    Thavandiran, Nimalan; Dubois, Nicole; Mikryukov, Alexander; Massé, Stéphane; Beca, Bogdan; Simmons, Craig A.; Deshpande, Vikram S.; McGarry, J. Patrick; Chen, Christopher S.; Nanthakumar, Kumaraswamy; Keller, Gordon M.; Radisic, Milica; Zandstra, Peter W.

    2013-01-01

    Access to robust and information-rich human cardiac tissue models would accelerate drug-based strategies for treating heart disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. We used computational modeling of tissue contraction and assembly mechanics in conjunction with microfabricated constraints to guide the design of aligned and functional 3D human pluripotent stem cell (hPSC)-derived cardiac microtissues that we term cardiac microwires (CMWs). Miniaturization of the platform circumvented the need for tissue vascularization and enabled higher-throughput image-based analysis of CMW drug responsiveness. CMW tissue properties could be tuned using electromechanical stimuli and cell composition. Specifically, controlling self-assembly of 3D tissues in aligned collagen, and pacing with point stimulation electrodes, were found to promote cardiac maturation-associated gene expression and in vivo-like electrical signal propagation. Furthermore, screening a range of hPSC-derived cardiac cell ratios identified that 75% NKX2 Homeobox 5 (NKX2-5)+ cardiomyocytes and 25% Cluster of Differentiation 90 OR (CD90)+ nonmyocytes optimized tissue remodeling dynamics and yielded enhanced structural and functional properties. Finally, we demonstrate the utility of the optimized platform in a tachycardic model of arrhythmogenesis, an aspect of cardiac electrophysiology not previously recapitulated in 3D in vitro hPSC-derived cardiac microtissue models. The design criteria identified with our CMW platform should accelerate the development of predictive in vitro assays of human heart tissue function. PMID:24255110

  7. Estrogen-related receptor α (ERRα) and ERRγ are essential coordinators of cardiac metabolism and function.

    PubMed

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

    2015-04-01

    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

  8. 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

  9. Dependence of Na+ pump current on external monovalent cations and membrane potential in rabbit cardiac Purkinje cells.

    PubMed Central

    Bielen, F V; Glitsch, H G; Verdonck, F

    1991-01-01

    the apparent affinity of the Na(+)-K+ pump towards K+ in cardiac Purkinje cells depends on both the membrane potential and the extracellular Na+ concentration. 11. The region of negative slope of the Ip-V curve observed in cells which were superfused with media containing low concentrations of K+ or its congeners strongly suggests the existence of at least two voltage-sensitive steps in the cardiac Na(+)-K+ pump cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:1665855

  10. 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

  11. 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

  12. Targeting pleiotropic signaling pathways to control adult cardiac stem cell fate and function

    PubMed Central

    Pagliari, Stefania; Jelinek, Jakub; Grassi, Gabriele; Forte, Giancarlo

    2014-01-01

    The identification of different pools of cardiac progenitor cells resident in the adult mammalian heart opened a new era in heart regeneration as a means to restore the loss of functional cardiac tissue and overcome the limited availability of donor organs. Indeed, resident stem cells are believed to participate to tissue homeostasis and renewal in healthy and damaged myocardium although their actual contribution to these processes remain unclear. The poor outcome in terms of cardiac regeneration following tissue damage point out at the need for a deeper understanding of the molecular mechanisms controlling CPC behavior and fate determination before new therapeutic strategies can be developed. The regulation of cardiac resident stem cell fate and function is likely to result from the interplay between pleiotropic signaling pathways as well as tissue- and cell-specific regulators. Such a modular interaction—which has already been described in the nucleus of a number of different cells where transcriptional complexes form to activate specific gene programs—would account for the unique responses of cardiac progenitors to general and tissue-specific stimuli. The study of the molecular determinants involved in cardiac stem/progenitor cell regulatory mechanisms may shed light on the processes of cardiac homeostasis in health and disease and thus provide clues on the actual feasibility of cardiac cell therapy through tissue-specific progenitors. PMID:25071583

  13. Limb salvage following iatrogenic arterial injury: complications of cardiac support using intra-aortic balloon pumps.

    PubMed

    Hunt, Adam; Waldin, Owen; Slim, Hani; Brar, Ranjeet

    2016-01-01

    This is a unique case report describing complex limb salvage in a patient who experienced acute limb ischaemia due to a complication of intra-aortic balloon pump (IABP) counterpulsation. This case focuses on a patient who had an IABP counterpulsation device inserted following myocardial infarction, requiring urgent coronary artery bypass grafting for acute coronary syndrome. Postoperatively, the IABP could not be removed, with consequent iliac thrombosis and acute limb ischaemia. Emergency femoral-to-femoral crossover bypass was performed using a polytetrafluoroethylene graft. A portion of the IABP balloon tip was entrapped and retained, however, and became the focus of delayed septicaemia, resulting in graft infection and wound breakdown 6 weeks later. Explantation of the residual balloon tip, ligation of the right external iliac artery and redo femoral-femoral crossover using the great saphenous vein were successfully performed. PMID:27268290

  14. Functional Outcomes: One Year after a Cardiac Arrest

    PubMed Central

    Raina, Ketki D.; Rittenberger, Jon C.; Holm, Margo B.; Callaway, Clifton W.

    2015-01-01

    Objective. The study aim was to characterize the time-course of recovery in impairments, activity limitations, participation restrictions, disability, and quality of life during the first year after cardiac arrest. Secondarily, the study described the associations between the instruments used to measure each of these domains. Methods. Measures of global disability (Cerebral Performance Category, CPC, Modified Rankin Scale, mRS), quality of life, activity limitations, participation restrictions, and affective and cognitive impairments were administered to 29 participants 1, 6, and 12 months after cardiac arrest. Results. Global measures of disability indicated recovery between one month and one year after cardiac arrest (mean CPC: 2.1 versus 1.69,  P < 0.05; mean mRS: 2.55 versus 1.83, P < 0.05). While global measures of disability were moderately associated with participation, they were poorly associated with other measures. The cohort endorsed depressive symptomatology throughout the year but did not have detectable cognitive impairment. Conclusions. Recovery from cardiac arrest is multifaceted and recovery continues for months depending upon the measures being used. Measures of global disability, reintegration into the community, and quality of life yield different information. Future clinical trials should include a combination of measures to yield the most complete representation of recovery after cardiac arrest. PMID:26421282

  15. Acute Hemodynamic Efficacy of a 32-ml Subcutaneous Counterpulsation Device in a Calf Model of Diminished Cardiac Function

    PubMed Central

    Koenig, Steven C.; Litwak, Kenneth N.; Giridharan, Guruprasad A.; Pantalos, George M.; Dowling, Robert D.; Prabhu, Sumanth D.; Slaughter, Mark S.; Sobieski, Michael A.; Spence, Paul A.

    2010-01-01

    The acute hemodynamic efficacy of an implantable counter-pulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  16. Acute hemodynamic efficacy of a 32-ml subcutaneous counterpulsation device in a calf model of diminished cardiac function.

    PubMed

    Koenig, Steven C; Litwak, Kenneth N; Giridharan, Guruprasad A; Pantalos, George M; Dowling, Robert D; Prabhu, Sumanth D; Slaughter, Mark S; Sobieski, Michael A; Spence, Paul A

    2008-01-01

    The acute hemodynamic efficacy of an implantable counterpulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation. PMID:19033769

  17. 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

  18. Ionic mechanisms of cardiac cell swelling induced by blocking Na+/K+ pump as revealed by experiments and simulation.

    PubMed

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

    2006-11-01

    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 Ca(2+)-ATPase (PMCA) and Na(+)/Ca(2+) exchanger, in addition to low membrane permeabilities for Na(+) and Cl(-), in maintaining cell volume. PMCA might help maintain the [Ca(2+)] gradient across the membrane though compromised, and thereby promote reverse Na(+)/Ca(2+) exchange stimulated by the increased [Na(+)](i) as well as the membrane depolarization. Na(+) extrusion via Na(+)/Ca(2+) exchange delayed cell swelling during Na(+)/K(+) pump block. Supporting these model predictions, we observed ventricular cell swelling after blocking Na(+)/Ca(2+) 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 Ca(2+) current, which increased [Ca(2+)](i). Finally, the activation of Ca(2+)-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

  19. Aerobic exercise training reduces cardiac function in adult male offspring exposed to prenatal hypoxia.

    PubMed

    Reyes, Laura M; Kirschenman, Raven; Quon, Anita; Morton, Jude S; Shah, Amin; Davidge, Sandra T

    2015-09-01

    Intrauterine growth restriction (IUGR) has been associated with increased susceptibility to myocardial ischemia-reperfusion (I/R) injury. Exercise is an effective preventive intervention for cardiovascular diseases; however, it may be detrimental in conditions of compromised health. The aim of this study was to determine whether exercise training can improve cardiac performance after I/R injury in IUGR offspring. We used a hypoxia-induced IUGR model by exposing pregnant Sprague-Dawley rats to 21% oxygen (control) or hypoxic (11% oxygen; IUGR) conditions from gestational day 15 to 21. At 10 wk of age, offspring were randomized to a sedentary group or to a 6-wk exercise protocol. Transthoracic echocardiography assessments were performed after 6 wk. Twenty-four hours after the last bout of exercise, ex vivo cardiac function was determined using a working heart preparation. With exercise training, there was improved baseline cardiac performance in male control offspring but a reduced baseline cardiac performance in male IUGR exercised offspring (P < 0.05). In male offspring, exercise decreased superoxide generation in control offspring, while in IUGR offspring, it had the polar opposite effect (interaction P ≤ 0.05). There was no effect of IUGR or exercise on cardiac function in female offspring. In conclusion, in male IUGR offspring, exercise may be a secondary stressor on cardiac function. A reduction in cardiac performance along with an increase in superoxide production in response to exercise was observed in this susceptible group. PMID:26157059

  20. Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids.

    PubMed

    Richards, Dylan J; Tan, Yu; Coyle, Robert; Li, Yang; Xu, Ruoyu; Yeung, Nelson; Parker, Arran; Menick, Donald R; Tian, Bozhi; Mei, Ying

    2016-07-13

    The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell-cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair. PMID:27328393

  1. Interoception across Modalities: On the Relationship between Cardiac Awareness and the Sensitivity for Gastric Functions

    PubMed Central

    Herbert, Beate M.; Muth, Eric R.; Pollatos, Olga; Herbert, Cornelia

    2012-01-01

    The individual sensitivity for ones internal bodily signals (“interoceptive awareness”) has been shown to be of relevance for a broad range of cognitive and affective functions. Interoceptive awareness has been primarily assessed via measuring the sensitivity for ones cardiac signals (“cardiac awareness”) which can be non-invasively measured by heartbeat perception tasks. It is an open question whether cardiac awareness is related to the sensitivity for other bodily, visceral functions. This study investigated the relationship between cardiac awareness and the sensitivity for gastric functions in healthy female persons by using non-invasive methods. Heartbeat perception as a measure for cardiac awareness was assessed by a heartbeat tracking task and gastric sensitivity was assessed by a water load test. Gastric myoelectrical activity was measured by electrogastrography (EGG) and subjective feelings of fullness, valence, arousal and nausea were assessed. The results show that cardiac awareness was inversely correlated with ingested water volume and with normogastric activity after water load. However, persons with good and poor cardiac awareness did not differ in their subjective ratings of fullness, nausea and affective feelings after drinking. This suggests that good heartbeat perceivers ingested less water because they subjectively felt more intense signals of fullness during this lower amount of water intake compared to poor heartbeat perceivers who ingested more water until feeling the same signs of fullness. These findings demonstrate that cardiac awareness is related to greater sensitivity for gastric functions, suggesting that there is a general sensitivity for interoceptive processes across the gastric and cardiac modality. PMID:22606278

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

    PubMed

    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 Ca(2+) signal. Promisingly, our smartly formulated Ca(2+)-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. 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

  4. 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.

  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. PMID:26496001

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

    PubMed Central

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

    2009-01-01

    Summary 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 Gαq 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 Gαq 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 β-adrenergic stimulation in Gαq transgenic mice. Consistent with this observation, ROCK1 deletion prevented down-regulation of type V/VI adenylyl cyclase expression, which is associated with the impaired β-adrenergic signaling in Gαq mice. The present study establishes for the first time a role for ROCK1 in cardiac dilation and contractile dysfunction. PMID:18178218

  7. 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

  8. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    PubMed Central

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  9. Functional Analysis of the Engineered Cardiac Tissue Grown on Recombinant Spidroin Fiber Meshes

    PubMed Central

    Teplenin, Alexander; Krasheninnikova, Anna; Agladze, Nadezhda; Sidoruk, Konstantin; Agapova, Olga; Agapov, Igor; Bogush, Vladimir; Agladze, Konstantin

    2015-01-01

    In the present study, we examined the ability of the recombinant spidroin to serve as a substrate for the cardiac tissue engineering. For this purpose, isolated neonatal rat cardiomyocytes were seeded on the electrospun spidroin fiber matrices and cultured to form the confluent cardiac monolayers. Besides the adhesion assay and immunostaining analysis, we tested the ability of the cultured cardiomyocytes to form a functional cardiac syncytium by studying excitation propagation in the cultured tissue with the aid of optical mapping. It was demonstrated that recombinant spidroin fiber meshes are directly suitable for the adherence and growth of the cardiomyocytes without additional coating with the attachment factors, such as fibronectin. PMID:25799394

  10. Recovery of brain function after cardiac arrest, case report and review.

    PubMed

    Nekoui, A; Tresierra, del Carmen Escalante; Abdolmohammadi, S; Charbonneau, S; Blaise, G

    2016-01-01

    Cerebral hypoxia during cardiac arrest is the leading cause of mortality and morbidity in survival victims. To reduce cerebral damage, studies focus on finding effective treatments during the resuscitation period. Our report focuses on a 36-year-old police officer who had had two cardiac arrests (one at home and one at the hospital). After acute treatment, his cardiac and brain functions recovered impressively. Neuropsychological results were normal except for mild anomia. He also reported some retrograde memory loss. Surprisingly, he also reported an improvement in a very specific capacity, his episodic memory. We here review the possible causes and mechanisms that may have affected his memory abilities. PMID:27363214

  11. Systematic Characterization of the Murine Mitochondrial Proteome Using Functionally Validated Cardiac Mitochondria

    PubMed Central

    Zhang, Jun; Li, Xiaohai; Mueller, Michael; Wang, Yueju; Zong, Chenggong; Deng, Ning; Vondriska, Thomas M.; Liem, David A.; Yang, Jeong-In; Korge, Paavo; Honda, Henry; Weiss, James N.; Apweiler, Rolf; Ping, Peipei

    2009-01-01

    Mitochondria play essential roles in cardiac pathophysiology and the murine model has been extensively used to investigate cardiovascular diseases. In the present study, we characterized murine cardiac mitochondria using an LC/MS/MS approach. We extracted and purified cardiac mitochondria; validated their functionality to ensure the final preparation contains necessary components to sustain their normal function; and subjected these validated organelles to LC/MS/MS-based protein identification. A total of 940 distinct proteins were identified from murine cardiac mitochondria, among which, 480 proteins were not previously identified by major proteomic profiling studies. The 940 proteins consist of functional clusters known to support oxidative phosphorylation, metabolism and biogenesis. In addition, there are several other clusters--including proteolysis, protein folding, and reduction/oxidation signaling-which ostensibly represent previously under-appreciated tasks of cardiac mitochondria. Moreover, many identified proteins were found to occupy other subcellular locations, including cytoplasm, ER, and golgi, in addition to their presence in the mitochondria. These results provide a comprehensive picture of the murine cardiac mitochondrial proteome and underscore tissue- and species-specification. Moreover, the use of functionally intact mitochondria insures that the proteomic observations in this organelle are relevant to its normal biology and facilitates decoding the interplay between mitochondria and other organelles. PMID:18348319

  12. Cellular and Functional Imaging of Cardiac Transplant Rejection

    PubMed Central

    Wu, Yijen L.; Ye, Qing

    2011-01-01

    Heart transplantation is now an established treatment for patients suffering from end-stage heart diseases. With the advances in immunosuppressive treatment, the survival rate for transplant patients has improved greatly. However, allograft rejection, both acute and chronic, after heart transplantation is still a limitation leading to morbidity and mortality. The current clinical gold standard for screening rejection is endomyocardial biopsy (EMB), which is not only invasive, but also error-prone, due to the limited sample size and the site location of sampling. It would be highly desirable to have reliable and noninvasive alternatives for EMB in monitoring cardiac allograft rejection. The objective of this review is to highlight how cardiovascular imaging can contribute to noninvasively detecting and to evaluating both acute and chronic allograft rejection after heart transplantation, in particular, cardiovascular MRI (CMRI); and how CMRI can assess both immune cell infiltration at the rejecting organ, and the cardiac dysfunctions resulting from allograft rejection. PMID:21359095

  13. Nitrite reductase function of deoxymyoglobin: oxygen sensor and regulator of cardiac energetics and function.

    PubMed

    Rassaf, Tienush; Flögel, Ulrich; Drexhage, Christine; Hendgen-Cotta, Ulrike; Kelm, Malte; Schrader, Jürgen

    2007-06-22

    Although the primary function of myoglobin (Mb) has been considered to be cellular oxygen storage and supply, recent studies have suggested to classify Mb as a multifunctional allosteric enzyme. In the heart, Mb acts as a potent scavenger of nitric oxide (NO) and contributes to the attenuation of oxidative damage. Here we report that a dynamic cycle exists in which a decrease in tissue oxygen tension drives the conversion of Mb from being an NO scavenger in normoxia to an NO producer in hypoxia. The NO generated by reaction of deoxygenated Mb with nitrite is functionally relevant and leads to a downregulation of cardiac energy status, which was not observed in mice lacking Mb. As a consequence, myocardial oxygen consumption is reduced and cardiac contractility is dampened in wild-type mice. We propose that this pathway represents a novel homeostatic mechanism by which a mismatch between oxygen supply and demand in muscle is translated into the fractional increase of deoxygenated Mb exhibiting enhanced nitrite reductase activity. Thus, Mb may act as an oxygen sensor which through NO can adjust muscle energetics to limited oxygen supply. PMID:17495223

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

    PubMed

    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. PMID:26974408

  15. Proteasome inhibition slightly improves cardiac function in mice with hypertrophic cardiomyopathy

    PubMed Central

    Schlossarek, Saskia; Singh, Sonia R.; Geertz, Birgit; Schulz, Herbert; Reischmann, Silke; Hübner, Norbert; Carrier, Lucie

    2014-01-01

    A growing line of evidence indicates a dysfunctional ubiquitin-proteasome system (UPS) in cardiac diseases. Anti-hypertrophic effects and improved cardiac function have been reported after treatment with proteasome inhibitors in experimental models of cardiac hypertrophy. Here we tested whether proteasome inhibition could also reverse the disease phenotype in a genetically-modified mouse model of hypertrophic cardiomyopathy (HCM), which carries a mutation in Mybpc3, encoding the myofilament protein cardiac myosin-binding protein C. At 7 weeks of age, homozygous mutant mice (KI) have 39% higher left ventricular mass-to-body-weight ratio and 29% lower fractional area shortening (FAS) than wild-type (WT) mice. Both groups were treated with epoxomicin (0.5 mg/kg/day) or vehicle for 1 week via osmotic minipumps. Epoxomicin inhibited the chymotrypsin-like activity by ~50% in both groups. All parameters of cardiac hypertrophy (including the fetal gene program) were not affected by epoxomicin treatment in both groups. In contrast, FAS was 12% and 35% higher in epoxomicin-treated than vehicle-treated WT and KI mice, respectively. To identify which genes or pathways could be involved in this positive effect, we performed a transcriptome analysis in KI and WT neonatal cardiac myocytes, treated or not with the proteasome inhibitor MG132 (1 μM, 24 h). This revealed 103 genes (four-fold difference; 5% FDR) which are commonly regulated in both KI and WT cardiac myocytes. Thus, even in genetically-modified mice with manifest HCM, proteasome inhibition showed beneficial effects, at least with regard to cardiac function. Targeting the UPS in cardiac diseases remains therefore a therapeutic option. PMID:25566086

  16. Cardiac function and rejection following transplantation of the heart

    SciTech Connect

    Schober, O.; Schuler, S.; Gratz, K.; Warnecke, H.; Lang, W.; Hetzer, R.; Creutzig, H.

    1985-05-01

    It was the purpose of the study to evaluate the noninvasive detection of rejection following cardiac transplantation. Multigated cardiac blood pool imaging (MUGA) at rest with assessment of ejection fraction (EF) and regional wall motion was determined prospectively in 14 patients with 180 studies (follow up 5.1 +- 3.2 months) following orthotopic cardiac transplantation. The results were compared with histological examination of a percutaneous endocardial biopsy specimen (EMB) from the right ventricle. Diagnosis of rejection by EF measurement was defined by a decrease of 10% if EF < 70%, and 15% if EF > 70%. In 152 studies a normal MUGA study correlated with none rejection as defined by EMB. In 14 of 22 studies with moderate or severe rejection decrease of EF followed the rejection with a delay of 5 days. Septal wall motion abnormalities were typical. In 6 studies an abnormal temporal course of EF was not related to a similar finding in EMB. A sensitivity of 69% and a specifity of 96% can be estimated in the investigated group, in which all patients survived during the period of the study. It is concluded that rejection can be excluded by noninvasive MUGA (specifity 96%) and that MUGA is predictive of rejection (sensitivity 67%) mostly with a delay of 5 days.

  17. 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…

  18. 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

  19. Reflexly evoked coactivation of cardiac vagal and sympathetic motor outflows: observations and functional implications.

    PubMed

    Paton, Julian F R; Nalivaiko, Eugene; Boscan, Pedro; Pickering, Anthony E

    2006-12-01

    1. The purpose of the present review is to highlight the pattern of activity in the parasympathetic and sympathetic nerves innervating the heart during their reflex activation. 2. We describe the well-known reciprocal control of cardiac vagal and sympathetic activity during the baroreceptor reflex, but point out that this appears to be the exception rather than the rule and that many other reflexes reviewed herein (e.g. peripheral chemoreceptor, nociceptor, diving response and oculocardiac) involve simultaneous coactivation of both autonomic limbs. 3. The heart rate response during simultaneous activation of cardiac autonomic outflows is unpredictable because it does not simply reflect the summation of opposing influences. Indeed, it can result in bradycardia (peripheral chemoreceptor, diving and corneal), tachycardia (nociceptor) and, in some circumstances, can predispose to malignant arrhythmias. 4. We propose that this cardiac autonomic coactivation may allow greater cardiac output during bradycardia (increased ventricular filling time and stronger contraction) than activation of the sympathetic limb alone. This may be important when pumping blood into a constricted vascular tree, such as is the case during the peripheral chemoreceptor reflex and the diving response. PMID:17184509

  20. Assessment of cardiac function in mice lacking the mitochondrial calcium uniporter.

    PubMed

    Holmström, Kira M; Pan, Xin; Liu, Julia C; Menazza, Sara; Liu, Jie; Nguyen, Tiffany T; Pan, Haihui; Parks, Randi J; Anderson, Stasia; Noguchi, Audrey; Springer, Danielle; Murphy, Elizabeth; Finkel, Toren

    2015-08-01

    Mitochondrial calcium is thought to play an important role in the regulation of cardiac bioenergetics and function. The entry of calcium into the mitochondrial matrix requires that the divalent cation pass through the inner mitochondrial membrane via a specialized pore known as the mitochondrial calcium uniporter (MCU). Here, we use mice deficient of MCU expression to rigorously assess the role of mitochondrial calcium in cardiac function. Mitochondria isolated from MCU(-/-) mice have reduced matrix calcium levels, impaired calcium uptake and a defect in calcium-stimulated respiration. Nonetheless, we find that the absence of MCU expression does not affect basal cardiac function at either 12 or 20months of age. Moreover, the physiological response of MCU(-/-) mice to isoproterenol challenge or transverse aortic constriction appears similar to control mice. Thus, while mitochondria derived from MCU(-/-) mice have markedly impaired mitochondrial calcium handling, the hearts of these animals surprisingly appear to function relatively normally under basal conditions and during stress. PMID:26057074

  1. Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins.

    PubMed

    Gross, Sean M; Lehman, Steven L

    2016-06-01

    Protein phosphorylation plays an important role in regulating cardiac contractile function, but phosphorylation is not thought to play a regulatory role in skeletal muscle. To examine how myofilament phosphorylation arose in the human heart, we analyzed the amino acid sequences of 25 cardiac phosphorylation sites in animals ranging from fruit flies to humans. These analyses indicated that of the 25 human phosphorylation sites examined, 11 have been conserved across vertebrates and four have been sporadically present in vertebrates. Furthermore, all 11 of the cardiac sites found across vertebrates were present in skeletal muscle isoforms, along with three sites that were sporadically present. Based on the conservation of amino acid sequences between cardiac and skeletal contractile proteins, we tested for phosphorylation in mammalian skeletal muscle using several biochemical techniques and found evidence that multiple myofilament proteins were phosphorylated. Several of these phosphorylation sites were validated using mass spectrometry, including one site that is present in slow- and fast-twitch troponin I (TnI), but was lost in cardiac TnI. Thus, several myofilament phosphorylation sites present in the human heart likely arose in invertebrate muscle, have been evolutionarily conserved in skeletal muscle, and potentially have functional effects in both skeletal and cardiac muscle. PMID:26993364

  2. 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. PMID:26712849

  3. Acceleration of crossbridge kinetics by protein kinase A phosphorylation of cardiac myosin binding protein C modulates cardiac function.

    PubMed

    Tong, Carl W; Stelzer, Julian E; Greaser, Marion L; Powers, Patricia A; Moss, Richard L

    2008-10-24

    Normal cardiac function requires dynamic modulation of contraction. beta1-adrenergic-induced protein kinase (PK)A phosphorylation of cardiac myosin binding protein (cMyBP)-C may regulate crossbridge kinetics to modulate contraction. We tested this idea with mechanical measurements and echocardiography in a mouse model lacking 3 PKA sites on cMyBP-C, ie, cMyBP-C(t3SA). We developed the model by transgenic expression of mutant cMyBP-C with Ser-to-Ala mutations on the cMyBP-C knockout background. Western blots, immunofluorescence, and in vitro phosphorylation combined to show that non-PKA-phosphorylatable cMyBP-C expressed at 74% compared to normal wild-type (WT) and was correctly positioned in the sarcomeres. Similar expression of WT cMyBP-C at 72% served as control, ie, cMyBP-C(tWT). Skinned myocardium responded to stretch with an immediate increase in force, followed by a transient relaxation of force and finally a delayed development of force, ie, stretch activation. The rate constants of relaxation, k(rel) (s-1), and delayed force development, k(df) (s-1), in the stretch activation response are indicators of crossbridge cycling kinetics. cMyBP-C(t3SA) myocardium had baseline k(rel) and k(df) similar to WT myocardium, but, unlike WT, k(rel) and k(df) were not accelerated by PKA treatment. Reduced dobutamine augmentation of systolic function in cMyBP-C(t3SA) hearts during echocardiography corroborated the stretch activation findings. Furthermore, cMyBP-C(t3SA) hearts exhibited basal echocardiographic findings of systolic dysfunction, diastolic dysfunction, and hypertrophy. Conversely, cMyBP-C(tWT) hearts performed similar to WT. Thus, PKA phosphorylation of cMyBP-C accelerates crossbridge kinetics and loss of this regulation leads to cardiac dysfunction. PMID:18802026

  4. 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

  5. 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.

  6. 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…

  7. Effect of Obesity on Cardiac Function in Children and Adolescents: A Review

    PubMed Central

    Rowland, Thomas W.

    2007-01-01

    Increases in cardiac mass, ventricular dimensions, and stroke volume are typically observed in obese adults, accompanied by evidence of diminished ventricular systolic and diastolic function. Given sufficient severity and duration of excessive body fat, signs of overt congestive heart failure may ensue (cardiomyopathy of obesity). This review of cardiac findings in obese children and adolescents indicates similar anatomic features as well as early subclinical findings of ventricular dysfunction. However, cardiac functional reserve (cardiovascular fitness) appears to be preserved even in those with morbid levels of obesity. Key pointsExcessive body fat increases the work output of the heart.Longstanding increases in heart work result in abnormalities of heart function.Early findings of such changes can be observed in adolescents with severe obesity. PMID:24149418

  8. Development of a magnetically suspended centrifugal pump as a cardiac assist device for long-term application.

    PubMed

    Nishimura, K; Park, C H; Akamatsu, T; Yamada, T; Ban, T

    1996-01-01

    To overcome problems with the shaft seal in conventional centrifugal pumps, the authors have been developing a magnetically suspended centrifugal pump (MSCP) that operates as a valveless, sealless, and bearingless pump. The prototype of the MSCP was modified with respect to size of the volute diffuser and impeller blade profiles. A hemolysis test in vitro using a new version of the MSCP was performed in comparison with a commercially available centrifugal pump. The test circuit for the hemolysis test comprised a blood reservoir, a pump, and polyvinyl tubes, and was filled with fresh heparinized bovine blood. The pumping conditions were a flow rate of 5 L/min and a pump head afterload of 100 mmHg. The index of hemolysis in the MSCP was significantly lower than that in the Biomedicus pump (0.0035 +/- 0.0025 versus 0.0097 +/- 0.0056 g/100 L, p < 0.05). Reduction in the platelet count during pumping also was lower in the MSCP compared with the Biomedicus pump at both 6 hrs and 12 hrs of pumping (p < 0.01). This MSCP may be advantageous for extended use of assist devices, not only from the theoretical point of view, but in a practical sense after the results of the current hemolysis test. PMID:8808462

  9. Vagus Nerve Stimulation Improves Cardiac Function by Preventing Mitochondrial Dysfunction in Obese-Insulin Resistant Rats

    PubMed Central

    Samniang, Bencharunan; Shinlapawittayatorn, Krekwit; Chunchai, Titikorn; Pongkan, Wanpitak; Kumfu, Sirinart; Chattipakorn, Siriporn C.; KenKnight, Bruce H.; Chattipakorn, Nipon

    2016-01-01

    Long-term high-fat diet (HFD) consumption leads to not only obese-insulin resistance, but also impaired left ventricular (LV) function. Vagus nerve stimulation (VNS) has been shown to exert cardioprotection. However, its effects on the heart and metabolic parameters under obese-insulin resistant condition is not known. We determined the effects of VNS on metabolic parameters, heart rate variability (HRV) and LV function in obese-insulin resistant rats. Male Wistar rats were fed with HFD for 12 weeks, and were randomly divided into sham and VNS groups. VNS was applied for the next 12 weeks. Echocardiography, blood pressure and HRV were examined. Blood samples were collected for metabolic parameters. At the end, the heart was removed for determination of apoptosis, inflammation, oxidative stress, and cardiac mitochondrial function. VNS for 12 weeks significantly decreased plasma insulin, HOMA index, total cholesterol, triglyceride, LDL and visceral fat. Serum adiponectin was significantly increased in the VNS group. VNS also significantly decreased blood pressure, improved HRV and LV function, decreased cardiac MDA, TNF-α and Bax levels, and improved cardiac mitochondrial function. VNS improves metabolic and hemodynamic parameters, and the LV function via its ability against apoptosis, inflammation and oxidative stress, and preserved cardiac mitochondrial function in obese-insulin resistant rats. PMID:26830020

  10. 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.

  11. Cardiac myocyte follistatin-like 1 functions to attenuate hypertrophy following pressure overload.

    PubMed

    Shimano, Masayuki; Ouchi, Noriyuki; Nakamura, Kazuto; van Wijk, Bram; Ohashi, Koji; Asaumi, Yasuhide; Higuchi, Akiko; Pimentel, David R; Sam, Flora; Murohara, Toyoaki; van den Hoff, Maurice J B; Walsh, Kenneth

    2011-10-25

    Factors secreted by the heart, referred to as "cardiokines," have diverse actions in the maintenance of cardiac homeostasis and remodeling. Follistatin-like 1 (Fstl1) is a secreted glycoprotein expressed in the adult heart and is induced in response to injurious conditions that promote myocardial hypertrophy and heart failure. The aim of this study was to investigate the role of cardiac Fstl1 in the remodeling response to pressure overload. Cardiac myocyte-specific Fstl1-KO mice were constructed and subjected to pressure overload induced by transverse aortic constriction (TAC). Although Fstl1-KO mice displayed no detectable baseline phenotype, TAC led to enhanced cardiac hypertrophic growth and a pronounced loss in ventricular performance by 4 wk compared with control mice. Conversely, mice that acutely or chronically overexpressed Fstl1 were resistant to pressure overload-induced hypertrophy and cardiac failure. Fstl1-deficient mice displayed a reduction in TAC-induced AMP-activated protein kinase (AMPK) activation in heart, whereas Fstl1 overexpression led to increased myocardial AMPK activation under these conditions. In cultured neonatal cardiomyocytes, administration of Fstl1 promoted AMPK activation and antagonized phenylephrine-induced hypertrophy. Inhibition of AMPK attenuated the antihypertrophic effect of Fstl1 treatment. These results document that cardiac Fstl1 functions as an autocrine/paracrine regulatory factor that antagonizes myocyte hypertrophic growth and the loss of ventricular performance in response to pressure overload, possibly through a mechanism involving the activation of the AMPK signaling axis. PMID:21987816

  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. Galnt1 Is Required for Normal Heart Valve Development and Cardiac Function

    PubMed Central

    Tian, E; Stevens, Sharon R.; Guan, Yu; Springer, Danielle A.; Anderson, Stasia A.; Starost, Matthew F.; Patel, Vyomesh; Ten Hagen, Kelly G.; Tabak, Lawrence A.

    2015-01-01

    Congenital heart valve defects in humans occur in approximately 2% of live births and are a major source of compromised cardiac function. In this study we demonstrate that normal heart valve development and cardiac function are dependent upon Galnt1, the gene that encodes a member of the family of glycosyltransferases (GalNAc-Ts) responsible for the initiation of mucin-type O-glycosylation. In the adult mouse, compromised cardiac function that mimics human congenital heart disease, including aortic and pulmonary valve stenosis and regurgitation; altered ejection fraction; and cardiac dilation, was observed in Galnt1 null animals. The underlying phenotype is aberrant valve formation caused by increased cell proliferation within the outflow tract cushion of developing hearts, which is first detected at developmental stage E11.5. Developing valves from Galnt1 deficient animals displayed reduced levels of the proteases ADAMTS1 and ADAMTS5, decreased cleavage of the proteoglycan versican and increased levels of other extracellular matrix proteins. We also observed increased BMP and MAPK signaling. Taken together, the ablation of Galnt1 appears to disrupt the formation/remodeling of the extracellular matrix and alters conserved signaling pathways that regulate cell proliferation. Our study provides insight into the role of this conserved protein modification in cardiac valve development and may represent a new model for idiopathic valve disease. PMID:25615642

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. Adipose stem cell sheets improved cardiac function in the rat myocardial infarction, but did not alter cardiac contractile responses to β-adrenergic stimulation.

    PubMed

    Otsuki, Yuki; Nakamura, Yoshinobu; Harada, Shingo; Yamamoto, Yasutaka; Ogino, Kazuhide; Morikawa, Kumi; Ninomiya, Haruaki; Miyagawa, Shigeru; Sawa, Yoshiki; Hisatome, Ichiro; Nishimura, Motonobu

    2015-01-01

    Adipose stem cells (ASCs) are a source of regenerative cells available for autologous transplantation to hearts. We compared protective actions of ASC sheets on rat myocardial infarction (MI) in comparison with those of skeletal myoblast cell sheets. Their effects on infarcted hearts were evaluated by biological, histochemical as well as physiological analyses. ASC sheets secreted higher concentrations of angiogenic factors (HGF, VEGF, and bFGF; P < 0.05) under normoxic and hypoxic conditions than those of myoblast cell sheets, associated with reduction of cell apoptosis (P < 0.05). Like myoblast cell sheets, ASC sheets improved cardiac function (P < 0.05) and decreased the plasma level of ANP (P < 0.05) in MI hearts. ASC sheets restored cardiac remodeling characterized by fibrosis, cardiac hypertrophy and impaired angiogenesis (P < 0.05), which was associated with increases in angiogenic factors (P < 0.05). In isolated perfused rat hearts, ASC sheets improved both systolic and diastolic functions, which was comparable to cardiac functions of myoblast cell sheets, while both cell sheets failed to restore cardiac contractile response to either isoproterenol, pimobendan or dibutyryl cAMP. These results indicated that ASC sheets improved cardiac function and remodeling of MI hearts mediated by their paracrine action and this improvement was comparable to those by myoblast cell sheets. PMID:25749147

  19. Molecule specific effects of PKA-mediated phosphorylation on rat isolated heart and cardiac myofibrillar function.

    PubMed

    Hanft, Laurin M; Cornell, Timothy D; McDonald, Colin A; Rovetto, Michael J; Emter, Craig A; McDonald, Kerry S

    2016-07-01

    Increased cardiac myocyte contractility by the β-adrenergic system is an important mechanism to elevate cardiac output to meet hemodynamic demands and this process is depressed in failing hearts. While increased contractility involves augmented myoplasmic calcium transients, the myofilaments also adapt to boost the transduction of the calcium signal. Accordingly, ventricular contractility was found to be tightly correlated with PKA-mediated phosphorylation of two myofibrillar proteins, cardiac myosin binding protein-C (cMyBP-C) and cardiac troponin I (cTnI), implicating these two proteins as important transducers of hemodynamics to the cardiac sarcomere. Consistent with this, we have previously found that phosphorylation of myofilament proteins by PKA (a downstream signaling molecule of the beta-adrenergic system) increased force, slowed force development rates, sped loaded shortening, and increased power output in rat skinned cardiac myocyte preparations. Here, we sought to define molecule-specific mechanisms by which PKA-mediated phosphorylation regulates these contractile properties. Regarding cTnI, the incorporation of thin filaments with unphosphorylated cTnI decreased isometric force production and these changes were reversed by PKA-mediated phosphorylation in skinned cardiac myocytes. Further, incorporation of unphosphorylated cTnI sped rates of force development, which suggests less cooperative thin filament activation and reduced recruitment of non-cycling cross-bridges into the pool of cycling cross-bridges, a process that would tend to depress both myocyte force and power. Regarding MyBP-C, PKA treatment of slow-twitch skeletal muscle fibers caused phosphorylation of MyBP-C (but not slow skeletal TnI (ssTnI)) and yielded faster loaded shortening velocity and ∼30% increase in power output. These results add novel insight into the molecular specificity by which the β-adrenergic system regulates myofibrillar contractility and how attenuation of PKA

  20. Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?

    PubMed Central

    Gu, Shi; Doughman, Yong Qiu; Peterson, Lindsy M.; Mai, Katherine; McHale, Quinn; Jenkins, Michael W.; Linask, Kersti K.; Rollins, Andrew M.; Watanabe, Michiko

    2013-01-01

    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. PMID:24271490

  1. 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. PMID:24271490

  2. A review of heart chamber segmentation for structural and functional analysis using cardiac magnetic resonance imaging.

    PubMed

    Peng, Peng; Lekadir, Karim; Gooya, Ali; Shao, Ling; Petersen, Steffen E; Frangi, Alejandro F

    2016-04-01

    Cardiovascular magnetic resonance (CMR) has become a key imaging modality in clinical cardiology practice due to its unique capabilities for non-invasive imaging of the cardiac chambers and great vessels. A wide range of CMR sequences have been developed to assess various aspects of cardiac structure and function, and significant advances have also been made in terms of imaging quality and acquisition times. A lot of research has been dedicated to the development of global and regional quantitative CMR indices that help the distinction between health and pathology. The goal of this review paper is to discuss the structural and functional CMR indices that have been proposed thus far for clinical assessment of the cardiac chambers. We include indices definitions, the requirements for the calculations, exemplar applications in cardiovascular diseases, and the corresponding normal ranges. Furthermore, we review the most recent state-of-the art techniques for the automatic segmentation of the cardiac boundaries, which are necessary for the calculation of the CMR indices. Finally, we provide a detailed discussion of the existing literature and of the future challenges that need to be addressed to enable a more robust and comprehensive assessment of the cardiac chambers in clinical practice. PMID:26811173

  3. 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. PMID:26700795

  4. Clinical investigation: thyroid function test abnormalities in cardiac arrest associated with acute coronary syndrome

    PubMed Central

    Iltumur, Kenan; Olmez, Gonul; Arıturk, Zuhal; Taskesen, Tuncay; Toprak, Nizamettin

    2005-01-01

    Introduction It is known that thyroid homeostasis is altered during the acute phase of cardiac arrest. However, it is not clear under what conditions, how and for how long these alterations occur. In the present study we examined thyroid function tests (TFTs) in the acute phase of cardiac arrest caused by acute coronary syndrome (ACS) and at the end of the first 2 months after the event. Method Fifty patients with cardiac arrest induced by ACS and 31 patients with acute myocardial infarction (AMI) who did not require cardioversion or cardiopulmonary resuscitation were enrolled in the study, as were 40 healthy volunteers. The patients were divided into three groups based on duration of cardiac arrest (<5 min, 5–10 min and >10 min). Blood samples were collected for thyroid-stimulating hormone (TSH), tri-iodothyronine (T3), free T3, thyroxine (T4), free T4, troponin-I and creatine kinase-MB measurements. The blood samples for TFTs were taken at 72 hours and at 2 months after the acute event in the cardiac arrest and AMI groups, but only once in the control group. Results The T3 and free T3 levels at 72 hours in the cardiac arrest group were significantly lower than in both the AMI and control groups (P < 0.0001). On the other hand, there were no significant differences between T4, free T4 and TSH levels between the three groups (P > 0.05). At the 2-month evaluation, a dramatic improvement was observed in T3 and free T3 levels in the cardiac arrest group (P < 0.0001). In those patients whose cardiac arrest duration was in excess of 10 min, levels of T3, free T3, T4 and TSH were significantly lower than those in patients whose cardiac arrest duration was under 5 min (P < 0.001, P < 0.001, P < 0.005 and P < 0.05, respectively). Conclusion TFTs are significantly altered in cardiac arrest induced by ACS. Changes in TFTs are even more pronounced in patients with longer periods of resuscitation. The changes in the surviving patients were characterized by euthyroid sick

  5. 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

  6. Engineering a growth factor embedded nanofiber matrix niche to promote vascularization for functional cardiac regeneration.

    PubMed

    Lakshmanan, Rajesh; Kumaraswamy, Priyadharshini; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2016-08-01

    The major loss of tissue extracellular matrix (ECM) after myocardial ischemia is a serious burden that gradually leads to heart failure. Due to lack of available treatment methods to restore the cardiac function, various research strategies have come up to treat the ischemic myocardium. However these have met with limited success due to the complexity of the cardiac tissue, which exhibits a nanofibrous collagenous matrix with spatio-temporal localization of a combination of growth factors. To mimic the topographical and chemical cues of the natural cardiac tissue, we have fabricated a growth factor embedded nanofibrous scaffold through electrospinning. In our previous work, we have reported a nanofibrous matrix made of PLCL and PEOz with an average diameter of 500 nm. The scaffold properties were specifically characterized in vitro for cardio-compatibility. In the present study, we have loaded dual growth factors VEGF and bFGF in the nanofiber matrix and investigated its suitability for cardiac tissue engineering. The encapsulation and release of dual growth factors from the matrix were studied using XPS and ELISA. Bioactivity of the loaded growth factors towards proliferation and migration of endothelial cells (HUVECs) was evaluated through MTS and Boyden chamber assays respectively. The efficiency of growth factors on the nanofibrous matrix to activate signaling molecules was studied in HUVECs through gene expression analysis. Preclinical evaluation of the growth factor embedded nanofibrous patch in a rabbit acute myocardial infarction (AMI) model was studied and cardiac function assessment was made through ECG and echocardiography. The evidence for angiogenesis in the patch secured regions was analyzed through histopathology and immunohistochemistry. Our results confirm the effectiveness of growth factor embedded nanofiber matrix in restoration of cardiac function after ischemia when compared to conventional patch material thereby exhibiting promise as a

  7. EFFECTS OF PRENATAL NITROFEN EXPOSURE ON CARDIAC STRUCTURE AND FUNCTION IN THE RAT

    EPA Science Inventory

    The herbicide nitrofen was administered to pregnant Fischer-344 and Sprague-Dawley rats on days 10-13 of gestation (po., 20 or 40 mg/kg daily) and its effects on cardiac structure and function were investigated in the offspring. In the 21-day fetuses, nitrofen did not influence i...

  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. In utero dimethadione exposure causes postnatal disruption in cardiac structure and function in the rat.

    PubMed

    Aasa, Kristiina L; Purssell, Elizabeth; Adams, Michael A; Ozolinš, Terence R S

    2014-12-01

    In utero exposure of rat embryos to dimethadione (DMO), the N-demethylated teratogenic metabolite of the anticonvulsant trimethadione, induces a high incidence of cardiac heart defects including ventricular septal defects (VSDs). The same exposure regimen also leads to in utero cardiac functional deficits, including bradycardia, dysrhythmia, and a reduction in cardiac output (CO) and ejection fraction that persist until parturition (10 days after the final dose). Despite a high rate of spontaneous postnatal VSD closure, we hypothesize that functional sequelae will persist into adulthood. Pregnant Sprague Dawley rats were administered six 300 mg/kg doses of DMO, one every 12 h in mid-pregnancy beginning on the evening of gestation day 8. Postnatal cardiac function was assessed in control (CTL) and DMO-exposed offspring using radiotelemetry and ultrasound at 3 and 11 months of age, respectively. Adult rats exposed to DMO in utero had an increased incidence of arrhythmia, elevated blood pressure and CO, greater left ventricular volume and elevated locomotor activity versus CTL. The mean arterial pressure of DMO-exposed rats was more sensitive to changes in dietary salt load compared with CTL. Importantly, most treated rats had functional deficits in the absence of a persistent structural defect. It was concluded that in utero DMO exposure causes cardiovascular deficits that persist into postnatal life in the rat, despite absence of visible structural anomalies. We speculate this is not unique to DMO, suggesting possible health implications for infants with unrecognized gestational chemical exposures. PMID:25239635

  11. Parametric shape representation by a deformable NURBS model for cardiac functional measurements.

    PubMed

    Chen, Sheng Yong; Guan, Qiu

    2011-03-01

    This paper proposes a method of parametric representation and functional measurement of 3-D cardiac shapes in a deformable nonuniform rational B-splines (NURBS) model. This representation makes it very easy to automatically evaluate the functional parameters and myocardial kinetics of the heart, since quantitative analysis can be followed in a simple way. In the model, local deformation and motion on the cardiac shape are expressed in adjustable parameters. Especially, an effective integral algorithm is used for volumetric measurement of a NURBS shape since the volume is the most basic parameter in cardiac functional analysis. This method promises the numerical computation to be very convenient, efficient, and accurate, in comparison with traditional methods. Practical experiments are carried out, and results show that the algorithm can get satisfactory measurement accuracy and efficiency. The parametric NURBS model in cylindrical coordinates is not only very suitable to fit the anatomical surfaces of a cardiac shape, but also easy for geometric transformation and nonrigid registration, and able to represent local dynamics and kinetics, and thus, can easily be applied for quantitative and functional analysis of the heart. PMID:20952325

  12. Functionally conservative substitutions at cardiac troponin I S43/45.

    PubMed

    Lang, Sarah E; Stevenson, Tamara K; Xu, Dongyang; O'Connell, Ryan; Westfall, Margaret V

    2016-07-01

    A phospho-null Ala substitution at protein kinase C (PKC)-targeted cardiac troponin I (cTnI) S43/45 reduces myocyte and cardiac contractile function. The goal of the current study was to test whether cTnIS43/45N is an alternative, functionally conservative substitution in cardiac myocytes. Partial and more extensive endogenous cTnI replacement was similar at 2 and 4 days after gene transfer, respectively, for epitope-tagged cTnI and cTnIS43/45N. This replacement did not significantly change thin filament stoichiometry. In functional studies, there were no significant changes in the amplitude and/or rates of contractile shortening and re-lengthening after this partial (2 days) and extensive (4 days) replacement with cTnIS43/45N. The cTnIS43/45N substitution also was not associated with adaptive changes in the myocyte Ca(2+) transient or in phosphorylation of the protein kinase A and C-targeted cTnIS23/24 site. These results provide evidence that cTnIS43/45N is a functionally conservative substitution, and may be appropriate for use as a phospho-null in rodent models designed for studies on PKC modulation of cardiac performance. PMID:26869200

  13. Analysis of 2-d ultrasound cardiac strain imaging using joint probability density functions.

    PubMed

    Ma, Chi; Varghese, Tomy

    2014-06-01

    Ultrasound frame rates play a key role for accurate cardiac deformation tracking. Insufficient frame rates lead to an increase in signal de-correlation 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 bi-modal distributions in the joint probability density indicate inaccurate strain estimation over a cardiac cycle. In this study, we utilize similar analysis to evaluate a 2-D multi-level displacement tracking and strain estimation algorithm for cardiac strain imaging. The effect of different frame rates, final kernel dimensions and a comparison of radio frequency and envelope based processing are evaluated using echo signals derived from a 3-D finite element cardiac model and five healthy volunteers. Cardiac simulation model analysis demonstrates 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 radio frequency signals. On the other hand, even a frame rate of 250 Hz 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 radio frequency analysis. We also show that an increase in the final kernel dimensions significantly affect the strain probability distribution and joint probability density function generated, with a smaller effect on the variation in the accumulated mean strain estimated over a cardiac cycle. Our results demonstrate that radio frequency frame rates currently achievable on clinical cardiac ultrasound systems are sufficient for accurate analysis of the strain probability distribution, when a multi-level 2-D

  14. Molecular Modulation of Actomyosin Function by Cardiac Myosin-Binding Protein C

    PubMed Central

    Previs, Michael J.; Michalek, Arthur J.; Warshaw, David M.

    2014-01-01

    Cardiac myosin-binding protein C is a key regulator of cardiac contractility and is capable of both activating the thin filament to initiate actomyosin motion generation and governing maximal sliding velocities. While MyBP-C’s C-terminus localizes the molecule within the sarcomere the N-terminus appears to confer regulatory function by binding to the myosin motor domain and/or actin. Literature pertaining to how MyBP-C binding to the myosin motor domain and or actin leads to MyBP-C’s dual modulatory roles that can impact actomyosin interactions are discussed. PMID:24407948

  15. 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.

  16. Age-related changes in tissue macrophages precede cardiac functional impairment.

    PubMed

    Pinto, Alexander R; Godwin, James W; Chandran, Anjana; Hersey, Lucy; Ilinykh, Alexei; Debuque, Ryan; Wang, Lina; Rosenthal, Nadia A

    2014-05-01

    Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. PMID:24861132

  17. 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. PMID:26578113

  18. [Anesthetic management for laparoscopic sigmoidectomy in a patient with impaired ventricular function caused by cardiac sarcoidosis].

    PubMed

    Nagata, Hirofumi; Sato, Yoshiharu; Oouchi, Sueko; Wakimoto, Masahiro; Ishikawa, Ko; Suzuki, Kenji

    2012-08-01

    It has been demonstrated that laparoscopic surgery can reduce surgical trauma and postoperative pain, allowing earlier recovery and hospital discharge. However, because patients with severe cardiac depression may not tolerate the adverse respiratory and cardiovascular effects of pneumoperitoneum with a head-up or head-down tilt position, laparoscopic surgery has been avoided in these patients. The present case with low ventricular function (ejection fraction=23-27%) due to cardiac sarcoidosis could successfully undergo laparoscopic sigmoidectomy by using pulmonary artery catheterization. Therefore, laparoscopic surgery can be performed in patients with cardiac dysfunction if the cardiopulmonary responses caused by pneumoperitoneum with a head-up or head-down tilt are sufficiently considered and adverse hemodynamic responses appropriately detected and treated through invasive monitoring techniques such as pulmonary artery catheterization and/or transesophageal echocardiography. PMID:22991812

  19. Pump combiner loss as a function of input numerical aperture power distribution

    NASA Astrophysics Data System (ADS)

    Sévigny, Benoit; Poirier, Pierre; Faucher, Mathieu

    2009-02-01

    High-power combiner designs (such as kilowatt-class combiners and beyond) are increasingly aggressive on brightness conservation in order to reduce the brightness loss of the pumps as much as possible in both direct diode combining and pump and signal coupling, especially with the advent of next-generation high-power pumps. Since most of the pump loss is due to brightness loss across the combiner, tighter designs (close to the brightness limit) are considerably more sensitive to variations in the input power distribution as a function of numerical aperture; for instance, next-generation, high-power multi-emitter pumps are likely to have larger numerical apertures than conventional single-emitter diodes. As a consequence, pump insertion loss for a given combiner design sitting close to the brightness limit should be dependant on the input power distribution. Aside from presenting a manufacturing challenge, high brightness combiners also imply more sophisticated testing to allow a deeper understanding of the loss with respect to the far-field distribution of the pump inputs and thus enable the extrapolation of loss for an arbitrary, cylindrically symmetric radiant intensity distribution. In this paper, we present a novel test method to measure loss as a function of numerical aperture (NA) fill factor using a variable NA source with square-shaped far field distributions. Results are presented for a range of combiners, such as 7x1 and 19x1 pump combiners, with different brightness ratio and fiber inputs. Combiners violating the brightness conservation equation are also characterized in order to estimate the loss as a function of input power vs. NA distribution and fill factor.

  20. 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. PMID:26908713

  1. 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

  2. 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

  3. 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

  4. Heart-specific Rpd3 downregulation enhances cardiac function and longevity.

    PubMed

    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

    2015-09-01

    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

  5. [Research of Left Ventricle Function Analysis Using Real-time Cardiac Magnetic Resonance Imaging].

    PubMed

    Yang, Fan; He, Yan; Zhang, Jie; Wu, Yin

    2015-12-01

    Real-time free breathing cardiac cine imaging is a reproducible method with shorter acquisition time and without breath-hold for cardiac magnetic resonance imaging. However, the detection of end-diastole and end-systole frames of real-time free breathing cardiac cine imaging for left ventricle function analysis is commonly completed by visual identification, which is time-consuming and laborious. In order to save processing time, we propose a method for semi-automatic identification of end-diastole and end-systole frames. The method fits respiratory motion signal and acquires the expiration phase, end-diastole and end-systole frames by cross correlation coefficient. The procedure successfully worked on ten healthy volunteers and validated by the analysis of left ventricle function compared to the standard breath-hold steady-state free precession cardiac cine imaging without any significant statistical differences. The results demonstrated that the present method could correctly detect end-diastole and end-systole frames. In the future, this technique may be used for rapid left ventricle function analysis in clinic. PMID:27079101

  6. Diosmin pretreatment improves cardiac function and suppresses oxidative stress in rat heart after ischemia/reperfusion.

    PubMed

    Senthamizhselvan, Oomaidurai; Manivannan, Jeganathan; Silambarasan, Thangarasu; Raja, Boobalan

    2014-08-01

    Reperfusion of ischemic tissue leads to the generation of oxygen derived free radicals which plays an important role in cellular damage. Objective of the current study is to evaluate the cardio-protective and antioxidant effect of diosmin on ischemia-reperfusion related cardiac dysfunction, oxidative stress and apoptosis. Diosmin (50 and 100 mg/kg body weight (bw)) was given every day to the rats orally throughout the experimental period. Ischemia/reperfusion protocol was carried out ex vivo using langendorff perfusion method and the cardiac functional recovery was assessed in terms of percentage rate pressure product. Coronary effluents of LDH and CK-MB activities, antioxidant enzyme activities, lipid peroxidation products, activity of TCA cycle enzymes were evaluated. Moreover, in vitro superoxide anion and hydroxyl radical scavenging potential of diosmin was also quantified. Finally, quantitative real-time PCR was used for assessing Bcl-2 mRNA expression in heart. Cardiac functional recovery was impaired after reperfusion compared with continuously perfused heart. It was significantly prevented by diosmin treatment. Impaired antioxidant enzyme activities and elevated lipid peroxidation products level were also significantly suppressed. The activity of TCA cycle enzymes was protected against reperfusion stress. Down regulated Bcl-2 was also significantly increased. This study concluded that diosmin pretreatment prevents all the impaired patterns including cardiac function, oxidative stress and apoptosis associated with reperfusion in control heart by its antioxidant role. PMID:24769512

  7. 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

  8. 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. PMID:24936220

  9. 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. PMID:26116573

  10. RNA splicing regulated by RBFOX1 is essential for cardiac function in zebrafish

    PubMed Central

    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

    2015-01-01

    ABSTRACT 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. PMID:26116573

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. Simplified thermodynamic functions for vapor-liquid phase separation and fountain effect pumps

    NASA Technical Reports Server (NTRS)

    Yuan, S. W. K.; Hepler, W. A.; Frederking, T. H. K.

    1984-01-01

    He-4 fluid handling devices near 2 K require novel components for non-Newtonian fluid transport in He II. Related sizing of devices has to be based on appropriate thermophysical property functions. The present paper presents simplified equilibrium state functions for porous media components which serve as vapor-liquid phase separators and fountain effect pumps.

  13. Rapid D-Affine Biventricular Cardiac Function with Polar Prediction

    PubMed Central

    Gilbert, Kathleen; Cowan, Brett; Suinesiaputra, Avan; Occleshaw, Christopher; Young, Alistair

    2014-01-01

    Although many solutions have been proposed for left ventricular functional analysis of the heart, right and left (bi-) ventricular function has been problematic due to the complex geometry and large motions. Biventricular function is particularly important in congenital heart disease, the most common type of birth defects. We describe a rapid interactive analysis tool for biventricular function which incorporates 1) a 3D+ time finite element model of biventricular geometry, 2) a fast prediction step which estimates an initial geometry in a polar coordinate system, and 3) a Cartesian update which penalizes deviations from affine transformations (D-Affine) from a prior. Solution times were very rapid, enabling interaction in real time using guide point modeling. The method was applied to 13 patients with congenital heart disease and compared with the clinical gold standard of manual tracing. Results between the methods showed good correlation (R2 > 0.9) and good precision (volume<17ml; mass<11g) for both chambers. PMID:25485422

  14. Comparative connective tissue structure-function relationships in biologic pumps.

    PubMed

    Factor, S M; Robinson, T F

    1988-02-01

    A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid. PMID:2448546

  15. Cardiac Ultrasonography in the critical care setting: a practical approach to asses cardiac function and preload for the "non-cardiologist".

    PubMed

    Vermeiren, Guy L J; Malbrain, Manu L N G; Walpot, Jeroen M J B

    2015-01-01

    Cardiac ultrasonography has become an indispensible tool in the management of hemodynamically unstable critically ill patients. Some consider it as the modern stethoscope. Echocardiography is non-invasive and safe while the modern portable devices allow to be used at the bedside in order to provide fast, specific and vital information regarding the hemodynamic status, as well as the function, structure and anatomy of the heart. In this review, we will give an overview of cardiac function in general followed by an assessment of left ventricular function using echocardiography with calculation of cardiac output, left ventricular ejection fraction (EF), fractional shortening, fractional area contraction, M mode EF, 2D planimetry and 3D volumetry. We will briefly discuss mitral annulus post systolic excursion (MAPSE), calculation of dP/dt, speckle tracking or eyeballing to estimate EF for the experienced user. In a following section, we will discuss how to assess cardiac preload and diastolic function in 4 simple steps. The first step is the assessment of systolic function. The next step assesses the left atrium. The third step evaluates the diastolic flow patterns and E/e' ratio. The final step integrates the information of the previous steps. Echocardiography is also the perfect tool to evaluate right ventricular function with tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging, together with inferior vena cava dimensions and systolic pulmonary artery pressure and right ventricular systolic pressure measurement. Finally, methods to assess fluid responsiveness with echocardiography are discussed with the inferior vena cava collapsibility index and the variation on left ventricle outflow tract peak velocity and velocity time integral. Cardiac ultrasonography is an indispensible tool for the critical care physician to assess cardiac preload, afterload and contractile function in hemodynamically unstable patients in order to fine-tune treatment

  16. Resveratrol attenuated estrogen-deficient-induced cardiac dysfunction: role of AMPK, SIRT1, and mitochondrial function

    PubMed Central

    Meng, Zijun; Jing, Hongjiang; Gan, Lu; Li, Hua; Luo, Bingde

    2016-01-01

    Large epidemiological studies suggest that there are important differences in the incidence and severity of a wide variety of cardiac diseases, between premenopausal and menopausal women. Recently, it has been demonstrated that resveratrol may has similar function as estrogen. However, whether resveratrol replacement could mimic estrogen to protect heart in ovariectomized mice remains completely unknown. Firstly, the present study has used OVX/CAL model to investigate the effect of RSV on ischemic heart. Echocardiography analysis revealed that RSV administration significantly improved cardiac contractile function in estrogen-deficient mice. RSV also significantly reduced CK and LDH release, and heart infarct size in OVX/CAL group. Secondly, mitochondrial functions, including MRC activities, MDA level, and mitochondrial swelling, were evaluated in OVX mice. It was found that supplementation with RSV could restore mitochondrial function dampened by OVX. Thirdly, these protective functions mediated by RSV were mainly attributed to the enhancement of SIRT1/AMPK activity. In summary, the results support a potential role of resveratrol in the protection of cardiac functions under estrogen depletion status. PMID:27398147

  17. Interparental Relationship Dynamics and Cardiac Vagal Functioning in Infancy

    PubMed Central

    Graham, Alice M.; Ablow, Jennifer C.; Measelle, Jeffrey R.

    2010-01-01

    This study examined associations between interparental relationship dynamics and vagus system functioning in infancy. The functioning of the vagus system, part of the parasympathetic nervous system, indexes emotional reactivity and regulation. Interparental avoidance and dyadic adjustment constitute the focus of this study in order to bring attention to relationship dynamics not subsumed under overt conflict. Infants’ baseline vagal tone and change in vagal tone in response to a novel toy were assessed at five months in a sample of high-risk mother-infant dyads (n = 77). Maternal report of interparental avoidance demonstrated an association with infants’ baseline vagal tone, while interparental dyadic adjustment was associated with change in infants’ vagal tone from baseline to the novel toy. Infant gender moderated these associations. Maternal sensitivity did not mediate interparental relationship dynamics and infants’ vagal functioning. Results are discussed in the context of emotional security theory. PMID:20727595

  18. Hand2 ensures an appropriate environment for cardiac fusion by limiting Fibronectin function.

    PubMed

    Garavito-Aguilar, Zayra V; Riley, Heather E; Yelon, Deborah

    2010-10-01

    Heart formation requires the fusion of bilateral cardiomyocyte populations as they move towards the embryonic midline. The bHLH transcription factor Hand2 is essential for cardiac fusion; however, the effector genes that execute this function of Hand2 are unknown. Here, we provide in zebrafish the first evidence for a downstream component of the Hand2 pathway that mediates cardiac morphogenesis. Although hand2 is expressed in cardiomyocytes, mosaic analysis demonstrates that it plays a non-autonomous role in regulating cardiomyocyte movement. Gene expression profiles reveal heightened expression of fibronectin 1 (fn1) in hand2 mutant embryos. Reciprocally, overexpression of hand2 leads to decreased Fibronectin levels. Furthermore, reduction of fn1 function enables rescue of cardiac fusion in hand2 mutants: bilateral cardiomyocyte populations merge and exhibit improved tissue architecture, albeit without major changes in apicobasal polarity. Together, our data provide a novel example of a tissue creating a favorable environment for its morphogenesis: the Hand2 pathway establishes an appropriate environment for cardiac fusion through negative modulation of Fn1 levels. PMID:20724450

  19. Mesodermal iPSC–derived progenitor cells functionally regenerate cardiac and skeletal muscle

    PubMed Central

    Quattrocelli, Mattia; Swinnen, Melissa; Giacomazzi, Giorgia; Camps, Jordi; Barthélemy, Ines; Ceccarelli, Gabriele; Caluwé, Ellen; Grosemans, Hanne; Thorrez, Lieven; Pelizzo, Gloria; Muijtjens, Manja; Verfaillie, Catherine M.; Blot, Stephane; Janssens, Stefan; Sampaolesi, Maurilio

    2015-01-01

    Conditions such as muscular dystrophies (MDs) that affect both cardiac and skeletal muscles would benefit from therapeutic strategies that enable regeneration of both of these striated muscle types. Protocols have been developed to promote induced pluripotent stem cells (iPSCs) to differentiate toward cardiac or skeletal muscle; however, there are currently no strategies to simultaneously target both muscle types. Tissues exhibit specific epigenetic alterations; therefore, source-related lineage biases have the potential to improve iPSC-driven multilineage differentiation. Here, we determined that differential myogenic propensity influences the commitment of isogenic iPSCs and a specifically isolated pool of mesodermal iPSC-derived progenitors (MiPs) toward the striated muscle lineages. Differential myogenic propensity did not influence pluripotency, but did selectively enhance chimerism of MiP-derived tissue in both fetal and adult skeletal muscle. When injected into dystrophic mice, MiPs engrafted and repaired both skeletal and cardiac muscle, reducing functional defects. Similarly, engraftment into dystrophic mice of canine MiPs from dystrophic dogs that had undergone TALEN-mediated correction of the MD-associated mutation also resulted in functional striatal muscle regeneration. Moreover, human MiPs exhibited the same capacity for the dual differentiation observed in murine and canine MiPs. The findings of this study suggest that MiPs should be further explored for combined therapy of cardiac and skeletal muscles. PMID:26571398

  20. LRRC10 is required to maintain cardiac function in response to pressure overload.

    PubMed

    Brody, Matthew J; Feng, Li; Grimes, Adrian C; Hacker, Timothy A; Olson, Timothy M; Kamp, Timothy J; Balijepalli, Ravi C; Lee, Youngsook

    2016-01-15

    We previously reported that the cardiomyocyte-specific leucine-rich repeat containing protein (LRRC)10 has critical functions in the mammalian heart. In the present study, we tested the role of LRRC10 in the response of the heart to biomechanical stress by performing transverse aortic constriction on Lrrc10-null (Lrrc10(-/-)) mice. Mild pressure overload induced severe cardiac dysfunction and ventricular dilation in Lrrc10(-/-) mice compared with control mice. In addition to dilation and cardiomyopathy, Lrrc10(-/-) mice showed a pronounced increase in heart weight with pressure overload stimulation and a more dramatic loss of cardiac ventricular performance, collectively suggesting that the absence of LRRC10 renders the heart more disease prone with greater hypertrophy and structural remodeling, although rates of cardiac fibrosis and myocyte dropout were not different from control mice. Lrrc10(-/-) cardiomyocytes also exhibited reduced contractility in response to β-adrenergic stimulation, consistent with loss of cardiac ventricular performance after pressure overload. We have previously shown that LRRC10 interacts with actin in the heart. Here, we show that His(150) of LRRC10 was required for an interaction with actin, and this interaction was reduced after pressure overload, suggesting an integral role for LRRC10 in the response of the heart to mechanical stress. Importantly, these experiments demonstrated that LRRC10 is required to maintain cardiac performance in response to pressure overload and suggest that dysregulated expression or mutation of LRRC10 may greatly sensitize human patients to more severe cardiac disease in conditions such as chronic hypertension or aortic stenosis. PMID:26608339

  1. Renal Perfusion Index Reflects Cardiac Systolic Function in Chronic Cardio-Renal Syndrome

    PubMed Central

    Lubas, Arkadiusz; Ryczek, Robert; Kade, Grzegorz; Niemczyk, Stanisław

    2015-01-01

    Background Cardiac dysfunction can modify renal perfusion, which is crucial to maintain sufficient kidney tissue oxygenation. Renal cortex perfusion assessed by dynamic ultrasound method is related both to renal function and cardiac hemodynamics. The aim of the study was to test the hypothesis that Renal Perfusion Index (RPI) can more closely reflect cardiac hemodynamics and differentiate etiology of chronic cardio-renal syndrome. Material/Methods Twenty-four patients with hypertension and chronic kidney disease (CKD) at 2–4 stage (12 with hypertensive nephropathy and 12 with CKD prior to hypertension) were enrolled in the study. Blood tests, 24-h ABPM, echocardiography, and ultrasonography with estimation of Total renal Cortical Perfusion intensity and Renal Perfusion Index (RPI) were performed. Results In the group of all patients, RPI correlated with left ventricular stoke volume (LVSV), and cardiac index, but not with markers of renal function. In multiple stepwise regression analysis CKD-EPI(Cys-Cr) (b=−0.360), LVSV (b=0.924) and MAP (b=0.376) together independently influenced RPI (R2=0.74; p<0.0001). RPI<0.567 allowed for the identification of patients with chronic cardio-renal syndrome with sensitivity of 41.7% and specificity of 83.3%. Conclusions Renal perfusion index relates more strongly to cardiac output than to renal function, and could be helpful in recognizing chronic cardio-renal syndrome. Applicability of RPI in diagnosing early abnormalities in the cardio-renal axis requires further investigation. PMID:25881555

  2. Sudden Cardiac Arrest in Patients with Preserved Left Ventricular Systolic Function: A Clinical Dilemma

    PubMed Central

    Sawhney, Navinder; Narayan, Sanjiv M.

    2009-01-01

    Stratifying the risk for sudden cardiac arrest (SCA) in individuals with preserved systolic function remains a pressing public health problem. Current guidelines for the implantation of cardiac defibrillators largely ignore patients with preserved systolic function, even though they account for the majority of cases. However, risk stratification for such individuals is increasingly feasible. Notably, most individuals who experience SCA have structural heart disease, even if undiagnosed. Thus, clinical risk scores have been developed to identify high risk. Moreover, there are now promising data that T-Wave Alternans (TWA), alone and in combination with other indices, effectively predicts SCA in this population. This article presents our current understanding of SCA due to ventricular arrhythmias in patients with preserved LV systolic function, and attempts to build a framework to predict risk in this population. PMID:19251226

  3. Functional 3-D cardiac co-culture model using bioactive chitosan nanofiber scaffolds.

    PubMed

    Hussain, Ali; Collins, George; Yip, Derek; Cho, Cheul H

    2013-02-01

    The in vitro generation of a three-dimensional (3-D) myocardial tissue-like construct employing cells, biomaterials, and biomolecules is a promising strategy in cardiac tissue regeneration, drug testing, and tissue engineering applications. Despite significant progress in this field, current cardiac tissue models are not yet able to stably maintain functional characteristics of cardiomyocytes for long-term culture and therapeutic purposes. The objective of this study was to fabricate bioactive 3-D chitosan nanofiber scaffolds using an electrospinning technique and exploring its potential for long-term cardiac function in the 3-D co-culture model. Chitosan is a natural polysaccharide biomaterial that is biocompatible, biodegradable, non-toxic, and cost effective. Electrospun chitosan was utilized to provide structural scaffolding characterized by scale and architectural resemblance to the extracellular matrix (ECM) in vivo. The chitosan fibers were coated with fibronectin via adsorption in order to enhance cellular adhesion to the fibers and migration into the interfibrous milieu. Ventricular cardiomyocytes were harvested from neonatal rats and studied in various culture conditions (i.e., mono- and co-cultures) for their viability and function. Cellular morphology and functionality were examined using immunofluorescent staining for alpha-sarcomeric actin (SM-actin) and gap junction protein, Connexin-43 (Cx43). Scanning electron microscopy (SEM) and light microscopy were used to investigate cellular morphology, spatial organization, and contractions. Calcium indicator was used to monitor calcium ion flux of beating cardiomyocytes. The results demonstrate that the chitosan nanofibers retained their cylindrical morphology in long-term cell cultures and exhibited good cellular attachment and spreading in the presence of adhesion molecule, fibronectin. Cardiomyocyte mono-cultures resulted in loss of cardiomyocyte polarity and islands of non-coherent contractions. However

  4. Comparison of 4D-microSPECT and microCT for murine cardiac function

    PubMed Central

    Befera, Nicholas T.; Badea, Cristian T.; Johnson, G. Allan

    2014-01-01

    Purpose The objective of this study was to compare a new generation of four-dimensional (4D) microSPECT with microCT for quantitative in vivo assessment of murine cardiac function. Procedures 4D isotropic cardiac images were acquired from normal C57BL/6 mice with either microSPECT at 350-micron resolution (n=6) or microCT at 88-micron resolution (n=6). One additional mouse with myocardial infarction (MI) was scanned with both modalities. Prior to imaging, mice were injected with either 99mTc -tetrofosmin for microSPECT, or a liposomal blood pool contrast agent for microCT. Segmentation of the left ventricle (LV) was performed using Vitrea (Vital Images) software, to derive global and regional function. Results Measures of global LV function between microSPECT and microCT groups were comparable (e.g. ejection fraction=71±6%-microSPECT and 68±4%-microCT). Regional functional indices (wall motion, wall thickening, regional ejection fraction) were also similar for the two modalities. In the mouse with MI, microSPECT identified a large perfusion defect that was not evident with microCT. Conclusions Despite lower spatial resolution, microSPECT was comparable to microCT in the quantitative evaluation of cardiac function. MicroSPECT offers an advantage over microCT in the ability to evaluate myocardial perfusion radiotracer distribution and function simultaneously. MicroSPECT should be considered as an alternative to microCT and MR for preclinical cardiac imaging in the mouse. PMID:24037175

  5. Feasibility of temporary biventricular pacing after off-pump coronary artery bypass grafting in patients with reduced left ventricular function.

    PubMed

    Wang, Daniel Y; Kelly, Lauren A; Richmond, Marc E; Quinn, T Alexander; Cheng, Bin; Spotnitz, Michelle D; Cabreriza, Santos E; Naka, Yoshifumi; Stewart, Allan S; Smith, Craig R; Spotnitz, Henry M

    2013-01-01

    In selected patients undergoing cardiac surgery, our research group previously showed that optimized temporary biventricular pacing can increase cardiac output one hour after weaning from cardiopulmonary bypass. Whether pacing is effective after beating-heart surgery is unknown. Accordingly, in this study we examined the feasibility of temporary biventricular pacing after off-pump coronary artery bypass grafting. The effects of optimized pacing on cardiac output were measured with an electromagnetic aortic flow probe at the conclusion of surgery in 5 patients with a preoperative mean left ventricular ejection fraction of 0.26 (range, 0.15-0.35). Atrioventricular (7) and interventricular (9) delay settings were optimized in randomized order. Cardiac output with optimized biventricular pacing was 4.2 ± 0.7 L/min; in sinus rhythm, it was 3.8 ± 0.5 L/min. Atrial pacing at a matched heart rate resulted in cardiac output intermediate to that of sinus rhythm and biventricular pacing (4 ± 0.6 L/min). Optimization of atrioventricular and interventricular delay, in comparison with nominal settings, trended toward increased flow. This study shows that temporary biventricular pacing is feasible in patients with preoperative left ventricular dysfunction who are undergoing off-pump coronary artery bypass grafting. Further study of the possible clinical benefits of this intervention is warranted. PMID:24082369

  6. Effect on the cardiac function of repeated LBNP during a 1-month head down tilt

    NASA Astrophysics Data System (ADS)

    Arbeille, Ph.; Lebouard, D.; Massabuau, M.; Pottier, J. M.; Patat, F.; Pourcelot, L.; Guell, A.

    Cardiovascular assessment by ultrasound methods was performed during two long duration (1 month) Head Down Tilt (HDT) on 6 healthy volunteers. On a first 1 month HDT session, 3 of the 6 subjects (A, B, C) had daily several lower body negative pressure tests (LBNP), whereas the 3 subjects remaining (D, E, F) rested without LBNP. On a second 1 month HDT session subjects D, E, and F had daily LBNP tests and the A, B and C subjects did not. The cardiac function was assessed by Echocardiography (B mode, TM mode). On all the "6 non LBNP" subjects the left ventricule diastolic volume (LVDV), the stroke volume (SV) and the cardiac output (CO) increase (+10%, -15%) after HDT then decrease and remain inferior (-5%, -5%) or equal to the basal value during the HDT. Immediately after the end of the HDT the heart rate (HR) increase (+10%, +30%) whereas the cardiac parameters decrease weakly (-5%, -10%) and normalize after 3 days of recovery. On the "6 LBNP" subjects the LVDV, SV and CO increase (+10%, +15%) after 1 h HDT as in the previous group then decrease but remain superior (+5%, +15%) or equal to the basal value. After the HDT session, the HR is markedly increased (+20%, +40%) the LVDV and SV decrease (-15%, -20%) whereas the CO increases or decreases depending on the amplitude of the HR variations. These parameters do not completely normalize after 3 days recovery. Repeated LBNP sessions have a significant effect on the cardiovascular function as it maintains all cardiac parameters above the basal value. The LBNP manoeuvre can be considered as an efficient countermeasure to prevent cardiac disadaptation induced by HDT position and probably microgravity.

  7. Beating heart on a chip: a novel microfluidic platform to generate functional 3D cardiac microtissues.

    PubMed

    Marsano, Anna; Conficconi, Chiara; Lemme, Marta; Occhetta, Paola; Gaudiello, Emanuele; Votta, Emiliano; Cerino, Giulia; Redaelli, Alberto; Rasponi, Marco

    2016-02-01

    In the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions. For this purpose, we developed a heart-on-a-chip platform, which recapitulates the physiologic mechanical environment experienced by cells in the native myocardium. The device includes an array of hanging posts to confine cell-laden gels, and a pneumatic actuation system to induce homogeneous uniaxial cyclic strains to the 3D cell constructs during culture. The device was used to generate mature and highly functional micro-engineered cardiac tissues (μECTs), from both neonatal rat and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), strongly suggesting the robustness of our engineered cardiac micro-niche. Our results demonstrated that the cyclic strain was effectively highly uniaxial and uniformly transferred to cells in culture. As compared to control, stimulated μECTs showed superior cardiac differentiation, as well as electrical and mechanical coupling, owing to a remarkable increase in junction complexes. Mechanical stimulation also promoted early spontaneous synchronous beating and better contractile capability in response to electric pacing. Pacing analyses of hiPSC-CM constructs upon controlled administration of isoprenaline showed further promising applications of our platform in drug discovery, delivery and toxicology fields. The proposed heart-on-a-chip device represents a relevant step forward in the field, providing a standard functional three-dimensional cardiac model to possibly predict signs of hypertrophic changes in cardiac phenotype by mechanical and biochemical co

  8. Functional TRPV2 and TRPV4 channels in human cardiac c-kit(+) progenitor cells.

    PubMed

    Che, Hui; Xiao, Guo-Sheng; Sun, Hai-Ying; Wang, Yan; Li, Gui-Rong

    2016-06-01

    The cellular physiology and biology of human cardiac c-kit(+) progenitor cells has not been extensively characterized and remains an area of active research. This study investigates the functional expression of transient receptor potential vanilloid (TRPV) and possible roles for this ion channel in regulating proliferation and migration of human cardiac c-kit(+) progenitor cells. We found that genes coding for TRPV2 and TRPV4 channels and their proteins are significantly expressed in human c-kit(+) cardiac stem cells. Probenecid, an activator of TRPV2, induced an increase in intracellular Ca(2+) (Ca(2+) i ), an effect that may be attenuated or abolished by the TRPV2 blocker ruthenium red. The TRPV4 channel activator 4α-phorbol 12-13-dicaprinate induced Ca(2+) i oscillations, which can be inhibited by the TRPV4 blocker RN-1734. The alteration of Ca(2+) i by probenecid or 4α-phorbol 12-13-dicprinate was dramatically inhibited in cells infected with TRPV2 short hairpin RNA (shRNA) or TRPV4 shRNA. Silencing TRPV2, but not TRPV4, significantly reduced cell proliferation by arresting cells at the G0/G1 boundary of the cell cycle. Cell migration was reduced by silencing TRPV2 or TRPV4. Western blot revealed that silencing TRPV2 decreased expression of cyclin D1, cyclin E, pERK1/2 and pAkt, whereas silencing TRPV4 only reduced pAkt expression. Our results demonstrate for the first time that functional TRPV2 and TRPV4 channels are abundantly expressed in human cardiac c-kit(+) progenitor cells. TRPV2 channels, but not TRPV4 channels, participate in regulating cell cycle progression; moreover, both TRPV2 and TRPV4 are involved in migration of human cardiac c-kit(+) progenitor cells. PMID:26865051

  9. Motion corrected LV quantification based on 3D modelling for improved functional assessment in cardiac MRI

    NASA Astrophysics Data System (ADS)

    Liew, Y. M.; McLaughlin, R. A.; Chan, B. T.; Aziz, Y. F. Abdul; Chee, K. H.; Ung, N. M.; Tan, L. K.; Lai, K. W.; Ng, S.; Lim, E.

    2015-04-01

    Cine MRI is a clinical reference standard for the quantitative assessment of cardiac function, but reproducibility is confounded by motion artefacts. We explore the feasibility of a motion corrected 3D left ventricle (LV) quantification method, incorporating multislice image registration into the 3D model reconstruction, to improve reproducibility of 3D LV functional quantification. Multi-breath-hold short-axis and radial long-axis images were acquired from 10 patients and 10 healthy subjects. The proposed framework reduced misalignment between slices to subpixel accuracy (2.88 to 1.21 mm), and improved interstudy reproducibility for 5 important clinical functional measures, i.e. end-diastolic volume, end-systolic volume, ejection fraction, myocardial mass and 3D-sphericity index, as reflected in a reduction in the sample size required to detect statistically significant cardiac changes: a reduction of 21-66%. Our investigation on the optimum registration parameters, including both cardiac time frames and number of long-axis (LA) slices, suggested that a single time frame is adequate for motion correction whereas integrating more LA slices can improve registration and model reconstruction accuracy for improved functional quantification especially on datasets with severe motion artefacts.

  10. Systems analysis of the mechanisms of cardiac diastolic function changes after microgravity exposure

    NASA Astrophysics Data System (ADS)

    Summers, Richard; Coleman, Thomas; Steven, Platts; Martin, David

    Detailed information concerning cardiac function was collected by two-dimensional and M-mode echocardiography at 10 days before flight and 3h after landing in astronauts returning from shuttle missions. A comparative analysis of this data suggests that cardiac diastolic function is reduced after microgravity exposure with little or no change in systolic function as measured by ejection fraction However, the mechanisms responsible for these adaptations have not been determined. In this study, an integrative computer model of human physiology that forms the framework for the Digital Astronaut Project (Guyton/Coleman/Summers Model) was used in a systems analysis of the echocardiographic data in the context of general cardiovascular physiologic functioning. The physiologic mechanisms involved in the observed changes were then determined by a dissection of model interrelationships. The systems analysis of possible physiologic mechanisms involved reveals that a loss of fluid from the myocardial interstitial space may lead to a stiffening of the myocardium and could potentially result in some of the cardiac diastolic dysfunction seen postflight. The cardiovascular dynamics may be different during spaceflight.

  11. 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.

  12. Effects of active chronic cocaine use on cardiac sympathetic neuronal function assessed by carbon-11-hydroxyephedrine

    SciTech Connect

    Melon, P.G.; Boyd, C.J.; McVey, S. |

    1997-03-01

    Cardiac toxicity of cocaine has been linked to its inhibitory effect on norepinephrine reuptake by sympathetic nerve terminals of the heart. Carbon-11-hydroxyephedrine is a positron-emitting tracer that has been validated as a highly specific marker for norepinephrine transporter activity of the sympathetic nerve terminals and thus makes possible in vivo assessment of the effect of cocaine on norepinephrine reuptake and storage in the cardiac sympathetic nerve terminals. The aim of the study was to use the catecholamine analog {sup 11}C-hydroxyephedrine with PET to determine whether active chronic use of cocaine in women modifies the function of sympathetic nerve terminals of the heart. Six normal female volunteers and nine female active chronic cocaine users were studied. Cardiac regional {sup 11}C-hydroxyephedrine uptake and blood flow, as assessed with {sup 13}N-ammonia, were determined using semi-quantitative polar map analysis of myocardial tracer distribution. Carbon-11-hydroxyephedrine cardiac retention was quantified using dynamic data acquisition and kinetic analysis of blood and tissue activity. 27 refs., 4 figs., 3 tabs.

  13. Functional and Morphological Cardiac Magnetic Resonance Imaging of Mice Using a Cryogenic Quadrature Radiofrequency Coil

    PubMed Central

    Dieringer, Matthias Alexander; Els, Antje; Waiczies, Helmar; Waiczies, Sonia; Schulz-Menger, Jeanette; Niendorf, Thoralf

    2012-01-01

    Cardiac morphology and function assessment by magnetic resonance imaging is of increasing interest for a variety of mouse models in pre-clinical cardiac research, such as myocardial infarction models or myocardial injury/remodeling in genetically or pharmacologically induced hypertension. Signal-to-noise ratio (SNR) constraints, however, limit image quality and blood myocardium delineation, which crucially depend on high spatial resolution. Significant gains in SNR with a cryogenically cooled RF probe have been shown for mouse brain MRI, yet the potential of applying cryogenic RF coils for cardiac MR (CMR) in mice is, as of yet, untapped. This study examines the feasibility and potential benefits of CMR in mice employing a 400 MHz cryogenic RF surface coil, compared with a conventional mouse heart coil array operating at room temperature. The cryogenic RF coil affords SNR gains of 3.0 to 5.0 versus the conventional approach and hence enables an enhanced spatial resolution. This markedly improved image quality – by better deliniation of myocardial borders and enhanced depiction of papillary muscles and trabeculae – and facilitated a more accurate cardiac chamber quantification, due to reduced intraobserver variability. In summary the use of a cryogenically cooled RF probe represents a valuable means of enhancing the capabilities of CMR of mice. PMID:22870323

  14. Treadmill performance and cardiac function in selected patients with coronary heart disease

    SciTech Connect

    McKirnan, M.D.; Sullivan, M.; Jensen, D.; Froelicher, V.F.

    1984-02-01

    To investigate the cardiac determinants of treadmill performance in patients able to exercise to volitional fatigue, 88 patients with coronary heart disease free of angina pectoris were tested. The exercise tests included supine bicycle radionuclide ventriculography, thallium scintigraphy and treadmill testing with expired gas analysis. The number of abnormal Q wave locations, ejection fraction, end-diastolic volume, cardiac output, exercise-induced ST segment depression and thallium scar and ischemia scores were the cardiac variables considered. Rest and exercise ejection fractions were highly correlated to thallium scar score (r . -0.72 to -0.75, p less than 0.001), but not to maximal oxygen consumption (r . 0.19 to 0.25, p less than 0.05). Fifty-five percent of the variability in predicting treadmill time or estimated maximal oxygen consumption was explained by treadmill test-induced change in heart rate (39%), thallium ischemia score (12%) and cardiac output at rest (4%). The change in heart rate induced by the treadmill test explained only 27% of the variability in measured maximal oxygen consumption. Myocardial damage predicted ejection fraction at rest and the ability to increase heart rate with treadmill exercise appeared as an essential component of exercise capacity. Exercise capacity was only minimally affected by asymptomatic ischemia and was relatively independent of ventricular function.

  15. Simple RF design for human functional and morphological cardiac imaging at 7 tesla

    NASA Astrophysics Data System (ADS)

    Versluis, M. J.; Tsekos, N.; Smith, N. B.; Webb, A. G.

    2009-09-01

    Morphological and functional cardiac MRI can potentially benefit greatly from the recent advent of commercial high-field (7 tesla and above) MRI systems. However, conventional hardware configurations at lower field using a body-coil for homogeneous transmission are not available at these field strengths. Sophisticated multiple-transmit-channel systems have been shown to be able to image the human heart at 7 tesla but such systems are currently not widely available. In this paper, we empirically optimize the design of a simple quadrature coil for cardiac imaging at 7 tesla. The size, geometry, and position have been chosen to produce a B1 field with no tissue-induced signal voids within the heart. Standard navigator echoes for gating were adapted for operation at the heart/lung interface, directly along the head-foot direction. Using this setup, conventional and high-resolution cine functional imaging have been successfully performed, as has morphological imaging of the right coronary artery.

  16. The structure and function of cardiac t-tubules in health and disease.

    PubMed

    Ibrahim, Michael; Gorelik, Julia; Yacoub, Magdi H; Terracciano, Cesare M

    2011-09-22

    The transverse tubules (t-tubules) are invaginations of the cell membrane rich in several ion channels and other proteins devoted to the critical task of excitation-contraction coupling in cardiac muscle cells (cardiomyocytes). They are thought to promote the synchronous activation of the whole depth of the cell despite the fact that the signal to contract is relayed across the external membrane. However, recent work has shown that t-tubule structure and function are complex and tightly regulated in healthy cardiomyocytes. In this review, we outline the rapidly accumulating knowledge of its novel roles and discuss the emerging evidence of t-tubule dysfunction in cardiac disease, especially heart failure. Controversy surrounds the t-tubules' regulatory elements, and we draw attention to work that is defining these elements from the genetic and the physiological levels. More generally, this field illustrates the challenges in the dissection of the complex relationship between cellular structure and function. PMID:21697171

  17. Acute response and chronic stimulus for cardiac structural and functional adaptation in a professional boxer.

    PubMed

    Oxborough, David; George, Keith; Utomi, Victor; Lord, Rachel; Morton, James; Jones, Nigel; Somauroo, John

    2014-06-01

    The individual response to acute and chronic changes in cardiac structure and function to intense exercise training is not fully understood and therefore evidence in this setting may help to improve the timing and interpretation of pre-participation cardiac screening. The following case report highlights an acute increase in right ventricular (RV) size and a reduction in left ventricular (LV) basal radial function with concomitant increase at the mid-level in response to a week's increase in training volume in a professional boxer. These adaptations settle by the second week; however, chronic physiological adaptation occurs over a 12-week period. Electrocardiographic findings demonstrate an acute lateral T-wave inversion at 1 week, which revert to baseline for the duration of training. It appears that a change in training intensity and volume generates an acute response within the RV that acts as a stimulus for chronic adaptation in this professional boxer. PMID:25988031

  18. Cardiac function in muscular dystrophy associates with abdominal muscle pathology

    PubMed Central

    Gardner, Brandon B.; Swaggart, Kayleigh A.; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M.

    2015-01-01

    Background The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Methods Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. Findings The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients. PMID:26029630

  19. Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess.

    PubMed

    Wyrwoll, Caitlin S; Noble, June; Thomson, Adrian; Tesic, Dijana; Miller, Mark R; Rog-Zielinska, Eva A; Moran, Carmel M; Seckl, Jonathan R; Chapman, Karen E; Holmes, Megan C

    2016-05-31

    Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2(-/-) mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2(+/+), Hsd11b2(+/-), and Hsd11b2(-/-) littermates from heterozygous (Hsd11b(+/-)) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2(-/-) fetuses did not undergo the normal gestational increase seen in Hsd11b2(+/+) littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2(-/-) fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2(-/-) fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2(-/-) fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction. PMID:27185937

  20. Mechanography: a non-invasive technique for the evaluation of cardiac function in children

    PubMed Central

    Spitaels, Silja; Fouron, Jean-Claude; Davignon, André

    1972-01-01

    Experience in the pediatric age group with mechanography, an indirect method of cardiovascular investigation, is described with emphasis on the recording technique and on the analysis of the tracings. A few examples are presented with comments on the morphological aspects and the time characteristics of the pulse curves, showing how much information about cardiac disease and especially myocardial function in children may be obtained. PMID:4640813

  1. Effects of real and simulated weightlessness on the cardiac and peripheral vascular functions of humans: A review.

    PubMed

    Zhu, Hui; Wang, Hanqing; Liu, Zhiqiang

    2015-01-01

    Weightlessness is an extreme environment that can cause a series of adaptive changes in the human body. Findings from real and simulated weightlessness indicate altered cardiovascular functions, such as reduction in left ventricular (LV) mass, cardiac arrhythmia, reduced vascular tone and so on. These alterations induced by weightlessness are detrimental to the health, safety and working performance of the astronauts, therefore it is important to study the effects of weightlessness on the cardiovascular functions of humans. The cardiovascular functional alterations caused by weightlessness (including long-term spaceflight and simulated weightlessness) are briefly reviewed in terms of the cardiac and peripheral vascular functions. The alterations include: changes of shape and mass of the heart; cardiac function alterations; the cardiac arrhythmia; lower body vascular regulation and upper body vascular regulation. A series of conclusions are reported, some of which are analyzed, and a few potential directions are presented. PMID:26224491

  2. Residual stress impairs pump function after surgical ventricular remodeling: A finite element analysis

    PubMed Central

    Pantoja, Joe Luis; Zhang, Zhihong; Tartibi, Mehrzad; Sun, Kay; Macmillan, Warrick; Guccione, Julius M.; Ge, Liang; Ratcliffe, Mark B.

    2016-01-01

    Objectives Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. Methods Previously described finite element models of the LV based on MRI data obtained in five sheep 16 weeks after antero-apical myocardial infarction were used. Simulated Dacron patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. Results VIRTUAL-DOR was associated with significant RS that was tensile (2.89±1.31 kPa) in the remote myocardium and compressive (234.15±65.53 kPa) in the borderzone (BZ). VIRTUAL-DOR+RS (compared to VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS with the greatest change in the BZ (43.5-fold and 7.1-fold respectively, p<0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%, p=0.0606 and 10.6%, p=0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. Conclusion Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the BZ and associated with reductions in fiber stress and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function. PMID:26341601

  3. 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)

  4. Assessment of Cardiac Functions in Infants with Cow’s Milk Allergy

    PubMed Central

    Ece, İbrahim; Demirören, Kaan; Demir, Nihat; Uner, Abdurrahman; Balli, Sevket

    2014-01-01

    Background Cow’s milk allergy is the most common food allergy in children, with rates estimated at 1.9% to 4.9%. Clinical phenotypes of cow’s milk allergy are varied and involve 1 or more target organs, with the main targets being the skin, respiratory system, and gastrointestinal tract. To date, no studies have investigated detailed cardiac function in children with cow’s milk allergy. The current study aimed to investigate cardiac function in infants with cow’s milk allergy. Material/Methods We studied 42 infants with cow’s milk allergy and 30 age- and sex-matched healthy subjects. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. Results There were no significant differences in ejection fraction or mitral and tricuspid annular plane systolic excursion between the 2 groups. Pulsed-wave Doppler-derived E/A ratios in mitral and tricuspid valves were similar in both groups. Ea/Aa ratios in the left ventricle posterior wall and right ventricle free wall were lower in patients with cow’s milk allergy than in the control group. The E/Ea ratio in the left ventricle, isovolumic relaxation time, deceleration time, and right and left ventricular myocardial performance indices were higher in patients in the study group. Conclusions Our study identified reduced early diastolic tissue Doppler velocities in infants with cow’s milk allergy. PMID:25098395

  5. Endothelin-1 critically influences cardiac function via superoxide-MMP9 cascade

    PubMed Central

    Hathaway, Catherine K.; Grant, Ruriko; Hagaman, John R.; Hiller, Sylvia; Li, Feng; Xu, Longquan; Chang, Albert S.; Madden, Victoria J.; Bagnell, C. Robert; Rojas, Mauricio; Kim, Hyung-Suk; Wu, Bingruo; Zhou, Bin; Smithies, Oliver; Kakoki, Masao

    2015-01-01

    We have generated low-expressing and high-expressing endothelin-1 genes (L and H) and have bred mice with four levels of expression: L/L, ∼20%; L/+, ∼65%; +/+ (wild type), 100%; and H/+, ∼350%. The hypomorphic L allele can be spatiotemporally switched to the hypermorphic H allele by Cre-loxP recombination. Young adult L/L and L/+ mice have dilated cardiomyopathy, hypertension, and increased plasma volumes, together with increased ventricular superoxide levels, increased matrix metalloproteinase 9 (Mmp9) expression, and reduced ventricular stiffness. H/+ mice have decreased plasma volumes and significantly heavy stiff hearts. Global or cardiomyocyte-specific switching expression from L to H normalized the abnormalities already present in young adult L/L mice. An epithelial sodium channel antagonist normalized plasma volume and blood pressure, but only partially corrected the cardiomyopathy. A superoxide dismutase mimetic made superoxide levels subnormal, reduced Mmp9 overexpression, and substantially improved cardiac function. Genetic absence of Mmp9 also improved cardiac function, but increased superoxide remained. We conclude that endothelin-1 is critical for maintaining normal contractile function, for controlling superoxide and Mmp9 levels, and for ensuring that the myocardium has sufficient collagen to prevent overstretching. Even a modest (∼35%) decrease in endothelin-1 gene (Edn1) expression is sufficient to cause cardiac dysfunction. PMID:25848038

  6. A role for matrix stiffness in the regulation of cardiac side population cell function

    PubMed Central

    Qiu, Yiling; Bayomy, Ahmad F.; Gomez, Marcus V.; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin

    2015-01-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration. PMID:25724498

  7. A role for matrix stiffness in the regulation of cardiac side population cell function.

    PubMed

    Qiu, Yiling; Bayomy, Ahmad F; Gomez, Marcus V; Bauer, Michael; Du, Ping; Yang, Yanfei; Zhang, Xin; Liao, Ronglih

    2015-05-01

    The mechanical properties of the local microenvironment may have important influence on the fate and function of adult tissue progenitor cells, altering the regenerative process. This is particularly critical following a myocardial infarction, in which the normal, compliant myocardial tissue is replaced with fibrotic, stiff scar tissue. In this study, we examined the effects of matrix stiffness on adult cardiac side population (CSP) progenitor cell behavior. Ovine and murine CSP cells were isolated and cultured on polydimethylsiloxane substrates, replicating the elastic moduli of normal and fibrotic myocardium. Proliferation capacity and cell cycling were increased in CSP cells cultured on the stiff substrate with an associated reduction in cardiomyogeneic differentiation and accelerated cell ageing. In addition, culture on stiff substrate stimulated upregulation of extracellular matrix and adhesion proteins gene expression in CSP cells. Collectively, we demonstrate that microenvironment properties, including matrix stiffness, play a critical role in regulating progenitor cell functions of endogenous resident CSP cells. Understanding the effects of the tissue microenvironment on resident cardiac progenitor cells is a critical step toward achieving functional cardiac regeneration. PMID:25724498

  8. Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58*

    PubMed Central

    Zierler, Kathrin A.; Jaeger, Doris; Pollak, Nina M.; Eder, Sandra; Rechberger, Gerald N.; Radner, Franz P. W.; Woelkart, Gerald; Kolb, Dagmar; Schmidt, Albrecht; Kumari, Manju; Preiss-Landl, Karina; Pieske, Burkert; Mayer, Bernd; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2013-01-01

    Efficient catabolism of cellular triacylglycerol (TG) stores requires the TG hydrolytic activity of adipose triglyceride lipase (ATGL). The presence of comparative gene identification-58 (CGI-58) strongly increased ATGL-mediated TG catabolism in cell culture experiments. Mutations in the genes coding for ATGL or CGI-58 in humans cause neutral lipid storage disease characterized by TG accumulation in multiple tissues. ATGL gene mutations cause a severe phenotype especially in cardiac muscle leading to cardiomyopathy that can be lethal. In contrast, CGI-58 gene mutations provoke severe ichthyosis and hepatosteatosis in humans and mice, whereas the role of CGI-58 in muscle energy metabolism is less understood. Here we show that mice lacking CGI-58 exclusively in muscle (CGI-58KOM) developed severe cardiac steatosis and cardiomyopathy linked to impaired TG catabolism and mitochondrial fatty acid oxidation. The marked increase in ATGL protein levels in cardiac muscle of CGI-58KOM mice was unable to compensate the lack of CGI-58. The addition of recombinant CGI-58 to cardiac lysates of CGI-58KOM mice completely reconstituted TG hydrolytic activities. In skeletal muscle, the lack of CGI-58 similarly provoked TG accumulation. The addition of recombinant CGI-58 increased TG hydrolytic activities in control and CGI-58KOM tissue lysates, elucidating the limiting role of CGI-58 in skeletal muscle TG catabolism. Finally, muscle CGI-58 deficiency affected whole body energy homeostasis, which is caused by impaired muscle TG catabolism and increased cardiac glucose uptake. In summary, this study demonstrates that functional muscle lipolysis depends on both CGI-58 and ATGL. PMID:23413028

  9. Cardiac function during breath-hold diving in humans: an echocardiographic study.

    PubMed

    Marabotti, C; Belardinelli, A; L'Abbate, A; Scalzini, A; Chiesa, F; Cialoni, D; Passera, M; Bedini, R

    2008-01-01

    Breath-hold diving induces, in marine mammals, a reduction of cardiac output due to a decrease of both heart rate and stroke volume. Cardiovascular changes in humans during breath-hold diving are only partially known due to the technical difficulty of studying fully immersed subjects. Recently, a submersible echocardiograph has been developed, allowing a feasible assessment of cardiac anatomy and function of subjects during diving. Aim of the study was to evaluate, by Doppler-echocardiography, the cardiovascular changes inducedby breath-hold diving in humans. Ten male subjects were studied by Doppler echocardiography in dry conditions and during breath-hold diving at 3 m depth. In addition 14 male subjects were studied, using the same protocol, before and during breath-hold diving at 10 m depth. At 3 m depth significant reductions in heart rate (-17%), stroke volume (-17%), cardiac output (-29%), left atrial dimensions, and deceleration time of early diastolic transmitral flow (DTE) were observed. At 10 m depth similar but more pronounced changes occurred. In particular, increase in early transmitral flow velocity became significant (+33%), while DTE decreased by 34%. At both depths dimensions of right cardiac chambers remained unchanged. Breath-hold diving at shallow depth induced, in humans, cardiovascular changes qualitatively similar to those observed in natural divers such as seals. The reduced dimensions of left atrium associated to a left ventricular diastolic pattern resembling that of restrictive/constrictive heart disease, suggest that the hemodynamic effects of diving could be explained, at least in part, by a constriction exerted on the heart by the reduced chest volume and the increased blood content of the lungs. Finally, the absence of dimensional changes in the right chambers suggests that most of the pulmonary blood shift occurred before cardiac imaging. PMID:18500072

  10. 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

    2015-01-01

    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. PMID:26555853