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Sample records for affect cardiac function

  1. The expression of CG9940 affects the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila.

    PubMed

    Wen, Deng-Tai; Zheng, Lan; Ni, Liu; Wang, Hui; Feng, Yue; Zhang, Min

    2016-10-01

    The CG9940 gene, which encodes the NAD(+) synthase protein in Drosophila, is conserved in human, zebra fish, and mosquito. NAD(+) synthase is a homodimer, which catalyzes the final step in de novo nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, an amide transfer from either ammonia or glutamine to nicotinic acid adenine dinucleotide (NaAD). Both the CG9940 and exercise are closely relative to NAD(+) level, and NAD(+) plays important roles not only in energy metabolism and mitochondrial functions but also in aging. In our study, the expression of CG9940 was changed by UAS/GAL4 system in Drosophila. Flies were trained by a training device. Cardiac function was analyzed by M-mode traces, climbing index was measured through negative geotaxis assay, and lifespan was measured via lifespan assays. The important new findings from our present study included the following: (1) the expression of the CG9940 could affect cardiac function, mobility, and lifespan in Drosophila. Over-expression of the CG9940 gene had positive effects on Drosophila, such as enhanced aging cardiac output, reduced heart failure, delayed age-related mobility decline, and prolonged lifespan, but lower-expression of the CG9940 had negative effects on them. (2) Different expressions of the CG9940 resulted in different influences on the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila. Both normal-expression and over-expression of the CG9940 resulted in positive influences on the adaptation of cardiac functions, mobility, and lifespan to exercise in aging Drosophila such as exercise slowed age-related decline of cardiac function, mobility and extent of lifespan in these flies, while lower-expression of the CG9940 led to negative impacts on the adaptation of mobility and lifespan to exercise in Drosophila. PMID:27448710

  2. The expression of CG9940 affects the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila.

    PubMed

    Wen, Deng-Tai; Zheng, Lan; Ni, Liu; Wang, Hui; Feng, Yue; Zhang, Min

    2016-10-01

    The CG9940 gene, which encodes the NAD(+) synthase protein in Drosophila, is conserved in human, zebra fish, and mosquito. NAD(+) synthase is a homodimer, which catalyzes the final step in de novo nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, an amide transfer from either ammonia or glutamine to nicotinic acid adenine dinucleotide (NaAD). Both the CG9940 and exercise are closely relative to NAD(+) level, and NAD(+) plays important roles not only in energy metabolism and mitochondrial functions but also in aging. In our study, the expression of CG9940 was changed by UAS/GAL4 system in Drosophila. Flies were trained by a training device. Cardiac function was analyzed by M-mode traces, climbing index was measured through negative geotaxis assay, and lifespan was measured via lifespan assays. The important new findings from our present study included the following: (1) the expression of the CG9940 could affect cardiac function, mobility, and lifespan in Drosophila. Over-expression of the CG9940 gene had positive effects on Drosophila, such as enhanced aging cardiac output, reduced heart failure, delayed age-related mobility decline, and prolonged lifespan, but lower-expression of the CG9940 had negative effects on them. (2) Different expressions of the CG9940 resulted in different influences on the adaptation of cardiac function, mobility, and lifespan to exercise in aging Drosophila. Both normal-expression and over-expression of the CG9940 resulted in positive influences on the adaptation of cardiac functions, mobility, and lifespan to exercise in aging Drosophila such as exercise slowed age-related decline of cardiac function, mobility and extent of lifespan in these flies, while lower-expression of the CG9940 led to negative impacts on the adaptation of mobility and lifespan to exercise in Drosophila.

  3. AMP-activated protein kinase alpha2 deficiency affects cardiac cardiolipin homeostasis and mitochondrial function

    PubMed Central

    Athéa, Yoni; Viollet, Benoît; Mateo, Philippe; Rousseau, Delphine; Novotova, Marta; Garnier, Anne; Vaulont, Sophie; Wilding, James R.; Grynberg, Alain; Veksler, Vladimir; Hoerter, Jacqueline; Ventura-Clapier, Renée

    2007-01-01

    AMP-activated protein kinase (AMPK) plays an important role in controlling energy homeostasis and is envisioned as a promising target to treat metabolic disorders. In the heart, AMPK is involved in short-term regulation and in transcriptional control of proteins involved in energy metabolism. Here, we investigated whether deletion of AMPKα2, the main cardiac catalytic isoform, alters mitochondrial function and biogenesis. Body weight, heart weight and AMPKα1 expression were similar in control littermate and AMPKa2−/− mice. Despite normal oxygen consumption in perfused hearts, maximal oxidative capacity, measured using saponin permeabilized cardiac fibers, was ≈30 % lower in AMPKa2−/− mice with octanoate, pyruvate or glutamate+malate but not with succinate as substrates, showing an impairment at complex-I of the respiratory chain. This effect was associated with a 25% decrease in mitochondrial cardiolipin content, the main mitochondrial membrane phospholipid that is crucial for complex-I activity, and by a 13% decrease in mitochondrial content of linoleic acid, the main fatty acid of cardiolipins. The decrease in cardiolipin content could be explained by mRNA down-regulation of rate limiting enzymes of both cardiolipin synthesis (CDS2) and remodeling (ALCAT1). These data reveal a new role for AMPKα2 subunit in the regulation of cardiac muscle oxidative capacity via cardiolipin homeostasis. PMID:17327449

  4. Strategies for tissue engineering cardiac constructs to affect functional repair following myocardial infarction.

    PubMed

    Ye, Kathy Yuan; Black, Lauren Deems

    2011-10-01

    Tissue-engineered cardiac constructs are a high potential therapy for treating myocardial infarction. These therapies have the ability to regenerate or recreate functional myocardium following the infarction, restoring some of the lost function of the heart and thereby preventing congestive heart failure. Three key factors to consider when developing engineered myocardial tissue include the cell source, the choice of scaffold, and the use of biomimetic culture conditions. This review details the various biomaterials and scaffold types that have been used to generate engineered myocardial tissues as well as a number of different methods used for the fabrication and culture of these constructs. Specific bioreactor design considerations for creating myocardial tissue equivalents in vitro, such as oxygen and nutrient delivery as well as physical stimulation, are also discussed. Lastly, a brief overview of some of the in vivo studies that have been conducted to date and their assessment of the functional benefit in repairing the injured heart with engineered myocardial tissue is provided.

  5. Functional cardiac tissue engineering

    PubMed Central

    Liau, Brian; Zhang, Donghui; Bursac, Nenad

    2013-01-01

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

  6. Biomechanics of Cardiac Function

    PubMed Central

    Voorhees, Andrew P.; Han, Hai-Chao

    2015-01-01

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

  7. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  8. Timing of obstetrical assistance affects peripartal cardiac autonomic function and early maternal behavior of dairy cows.

    PubMed

    Kovács, Levente; Kézér, Fruzsina Luca; Ruff, Ferenc; Szenci, Ottó

    2016-10-15

    Peripartal autonomic nervous system function and early maternal behavior were investigated in 79 multiparous Holstein-Friesian cows. Animals were allocated into four groups based on the technology of calving management: 1) unassisted calving in a group pen (UCG; N=19), 2) unassisted calving in an individual pen (UCI; N=21), 3) assisted calving with appropriately timed obstetrical assistance (ACA; N=20), and 4) assisted calving with premature obstetrical assistance (ACP; N=19). Heart rate, the high frequency (HF) component of heart rate variability (HRV) as a measure of vagal activity and the ratio between the low frequency (LF) and HF components (LF/HF ratio) as a parameter of sympathetic nervous system activity were calculated. Heart rate and HRV parameters were presented as areas under the curves (AUC) for the following periods: 1) prepartum period (between 96h before the onset of calving restlessness and the onset of restlessness), 2) parturition (between the onset calving restlessness and delivery), and 3) postpartum period (during a 48-h period after delivery). Pain-related behaviors were recorded during parturition (i.e., the occurrence of vocalization and stretching the neck towards the abdomen) and during a 2-h observation period after calving (i.e., the occurrence of vocalization, stretching the neck towards the abdomen and the duration of standing with an arched back). Early maternal behavior was observed during the first 2h following calving as follows: 1) latency and duration of sniffing calf's head/body, and 2) latency and duration of licking calf's head/body. No difference was found across groups in autonomic function before the onset of calving restlessness. Area under the heart rate curve was higher in ACP cows during parturition (39.6±2.5beats/min×h) compared to UCG, UCI and ACA animals (AUC=13.1±0.9beats/min×h, AUC=22.3±1.4beats/min×h and AUC=25.0±2.1beats/min×h, respectively). Area under the heart rate curve did not differ across the UCG

  9. 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.

  10. 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

  11. 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

  12. Obesity-metabolic derangement exacerbates cardiomyocyte loss distal to moderate coronary artery stenosis in pigs without affecting global cardiac function.

    PubMed

    Li, Zi-Lun; Ebrahimi, Behzad; Zhang, Xin; Eirin, Alfonso; Woollard, John R; Tang, Hui; Lerman, Amir; Wang, Shen-Ming; Lerman, Lilach O

    2014-04-01

    Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups (n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50-70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.

  13. Cardiac Function and Dysfunction in Sepsis.

    PubMed

    Fenton, Kimberly E; Parker, Margaret M

    2016-06-01

    Cardiac function and dysfunction are important in the clinical outcomes of sepsis and septic shock. Cardiac dysfunction is not a single entity, but is a broad spectrum of syndromes that result in biventricular cardiac dysfunction manifested by both systolic and diastolic dysfunction and is influenced by cardiac loading conditions (ie, preload and afterload). Elucidating the underlying pathophysiology has proved to be complex. This article emphasizes the underlying pathophysiology of cardiac dysfunction and explores recent evidence related to diagnosis, including the utility of biomarkers, the role of echocardiography, and management goals and treatment. PMID:27229645

  14. Treatment of affective disorders in cardiac disease.

    PubMed

    Mavrides, Nicole; Nemeroff, Charles B

    2015-06-01

    Patients with cardiovascular disease (CVD) commonly have syndromal major depression, and depression has been associated with an increased risk of morbidity and mortality. Prevalence of depression is between 17% and 47% in CVD patients. Pharmacologic and psychotherapeutic interventions have long been studied, and in general are safe and somewhat efficacious in decreasing depressive symptoms in patients with CVD. The impact on cardiac outcomes remains unclear. The evidence from randomized controlled clinical trials indicates that antidepressants, especially selective serotonin uptake inhibitors, are overwhelmingly safe, and likely to be effective in the treatment of depression in patients with CVD. This review describes the prevalence of depression in patients with CVD, the physiological links between depression and CVD, the treatment options for affective disorders, and the clinical trials that demonstrate efficacy and safety of antidepressant medications and psychotherapy in this patient population. Great progress has been made in understanding potential mediators between major depressive disorder and CVD--both health behaviors and shared biological risks such as inflammation.

  15. Cardiac-Specific YAP Activation Improves Cardiac Function and Survival in an Experimental Murine MI Model

    PubMed Central

    Lin, Zhiqiang; von Gise, Alexander; Zhou, Pingzhu; Gu, Fei; Ma, Qing; Jiang, Jiangming; Yau, Allan L.; Buck, Jessica N.; Gouin, Katryna A.; van Gorp, Pim R. R.; Zhou, Bin; Chen, Jinghai; Seidman, Jonathan G.; Wang, Da-zhi; Pu, William T.

    2014-01-01

    Rationale Yes-Associated Protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte (CM) proliferation. Objective We hypothesized that YAP activation after myocardial infarction would preserve cardiac function and improve survival. Methods and Results We used a cardiac-specific, inducible expression system to activate YAP in adult mouse heart. Activation of YAP in adult heart promoted CM proliferation and did not deleteriously affect heart function. Furthermore, YAP activation after myocardial infarction (MI) preserved heart function and reduced infarct size. Using adeno-associated virus subtype 9 (AAV9) as a delivery vector, we expressed human YAP in the adult murine myocardium immediately after MI. We found that AAV9:hYAP significantly improved cardiac function and mouse survival. AAV9:hYAP did not exert its salutary effects by reducing CM apoptosis. Rather, AAV9:hYAP stimulated adult CM proliferation. Gene expression profiling indicated that AAV9:hYAP stimulated expression of cell cycle genes and promoted a less mature cardiac gene expression signature. Conclusions Cardiac specific YAP activation after MI mitigated myocardial injury, improved cardiac function, and enhanced survival. These findings suggest that therapeutic activation of YAP or its downstream targets, potentially through AAV-mediated gene therapy, may be a strategy to improve outcome after MI. PMID:24833660

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Role of NRSF/REST in the regulation of cardiac gene expression and function.

    PubMed

    Kuwahara, Koichiro

    2013-01-01

    Alterations in the cardiac gene program affect both cardiac structure and function, and play a key role in the progression of pathological cardiac remodeling and heart failure. For instance, reactivation of fetal cardiac genes in adults is a consistent feature of cardiac hypertrophy and heart failure. Investigation of the transcriptional regulation of cardiac genes revealed a transcriptional repressor, neuron-restrictive silencer factor (NRSF), also called repressor element-1 silencing factor (REST), to be an important regulator of multiple fetal cardiac genes. Inhibition of NRSF in the heart leads to cardiac dysfunction and sudden arrhythmic death accompanied by re-expression of various fetal genes, including those encoding fetal ion channels, such as the HCN channels and T-type Ca(2+) channels. These findings shed light on the crucial regulatory function of NRSF in the heart and its importance for maintaining normal cardiac integrity. PMID:24126098

  1. Assessment of cardiac function: magnetic resonance and computed tomography.

    PubMed

    Greenberg, S B

    2000-10-01

    A complete cardiac study requires both anatomic and physiologic evaluation. Cardiac function can be evaluated noninvasively by magnetic resonance imaging (MRI)or ultrafast computed tomography (CT). MRI allows for evaluation of cardiac function by cine gradient echo imaging of the ventricles and flow analysis across cardiac valves and the great vessels. Cine gradient echo imaging is useful for evaluation of cardiac wall motion, ventricular volumes and ventricular mass. Flow analysis allows for measurement of velocity and flow during the cardiac cycle that reflects cardiac function. Ultrafast CT allows for measurement of cardiac indices similar to that provided by gradient echo imaging of the ventricles.

  2. 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).

  3. The endothelial function in cardiac surgery.

    PubMed

    Ranucci, M

    2006-06-01

    Cardiac operations with cardiopulmonary bypass exerts many different actions which modify the natural function of endothelial cells. The main determinant is the activation of the coagulation system both through the intrinsic and extrinsic pathways, leading to an overwhelming thrombin formation. To counteract the coagulant effects of thrombin, heparin is used in large doses. As a result, the endothelium is asked to promote all its anticoagulant properties, basically through the AT release from the surface, the tissue factor pathway inhibitor release, and the activation of the protein C protein S system. At the end of cardiac operations, all these systems are depleted, and low levels of antithrombin, tissue factor pathway inhibitor, protein C are available for further anticoagulant effects. There is the evidence that levels of antithrombin activity below 50% at the end of cardiac operations with cardiopulmonary bypass are associated to bad outcomes in terms of surgical revision rate, thromboembolic events, and neurological events. Exogenous antithrombin administration has a well defined action in limiting thrombin formation during cardiac operations; however, we are still lacking an evidence-based information about the clinical impact of this and others possible preventive strategies based on exogenous administration of antithrombin before or during cardiac operations. PMID:16682923

  4. [Assessment and evaluation of cardiac function].

    PubMed

    Yazaki, Y

    1993-05-01

    Assessment and evaluation of cardiac function have become commonplace in the care of cardiac patients with acute or chronic disorders, since therapy of most cardiac diseases is designed specifically to improve ventricular function. Now, various techniques are available for quantitative measurements of the size, shape and motion of the ventricle. Ventricular dysfunction is defined with two components, systolic and diastolic dysfunction, and can be described hemodynamically in terms of the ventricular pressure-volume diagram. Pure systolic dysfunction is associated with a depression in the end-systolic pressure-volume relation, using the Frank-Starling relation to restore cardiac output toward normal. In contrast, pure diastolic dysfunction is associated with preservation of the end-systolic pressure-volume relation but distortion of the diastolic relation, showing higher diastolic pressure at any given volume. However, in patients presenting clinically with heart failure, both systolic and diastolic dysfunction are usually observed. In this context, factors and disorders that influence ventricular dysfunction are described, considering extrinsic or intrinsic to the ventricular chambers.

  5. Effect of growth hormone on cardiac function.

    PubMed

    Lombardi, G; Colao, A; Ferone, D; Marzullo, P; Orio, F; Longobardi, S; Merola, B

    1997-01-01

    At present, there is a growing body of evidence implicating growth hormone (GH) and/or insulin-like growth factor-I (IGF-I) in the intricate cascade of events connected with the regulation of heart development and hypertrophy. In addition, advanced clinical manifestations of abnormal GH levels almost always include impaired cardiac function, which may reduce life expectancy. This finding is related both to a primary impairment of heart structure and function and to metabolic changes such as hyperlipidaemia, increased body fat and premature atherosclerosis. Acromegalic cardiomyopathy is better correlated with disease duration than with GH or IGF-I levels. Myocardial hypertrophy with interstitial fibrosis, lymphomononuclear infiltration and areas of monocyte necrosis often result in increased right and left ventricular mass concentric hypertrophy. Conversely, patients with childhood or adult-onset GH deficiency (GHD) have a reduced left ventricular mass (LVM) and ejection fraction (EF) and the indices of left ventricular systolic function remained markedly depressed during exercise. Cardiac function is reported to improve during octreotide and GH replacement treatment in acromegaly and GHD, respectively. The evidence that GH can increase cardiac mass suggests its use in the treatment of idiopathic dilated cardiomyopathy. In a recent study on such patients, the administration of recombinant GH (rGH) was demonstrated to increase myocardial mass and reduce the size of the left ventricular chamber, resulting in improved haemodynamics, myocardial energy metabolism and clinical status. PMID:9350445

  6. Drosophila, Genetic Screens, and Cardiac Function

    PubMed Central

    Wolf, Matthew J.; Rockman, Howard A.

    2011-01-01

    The fruit fly, Drosophila melanogaster, has been used to study genetics, development, and signaling for nearly a century but only over the past few decades has this tremendous resource been the focus of cardiovascular research. Fly genetics offers sophisticated transgenic systems, molecularly-defined genomic deficiencies, genome-wide transgenic RNAi lines, and numerous curated mutants to perform genetic screens. As a genetically-tractable model, the fly facilitates gene discovery and can complement mammalian models of disease. The circulatory system in the fly is comprised of well-defined sets of cardiomyocytes and methodological advances have permitted accurate characterization of cardiac morphology and function. Thus, fly genetics and genomics offers new approaches for gene discovery of adult cardiac phenotypes to identify evolutionarily conserved molecular signals that drive cardiovascular disease. PMID:21921272

  7. 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.

  8. Thymosin-β4 prevents cardiac rupture and improves cardiac function in mice with myocardial infarction.

    PubMed

    Peng, Hongmei; Xu, Jiang; Yang, Xiao-Ping; Dai, Xiangguo; Peterson, Edward L; Carretero, Oscar A; Rhaleb, Nour-Eddine

    2014-09-01

    Thymosin-β4 (Tβ4) promotes cell survival, angiogenesis, and tissue regeneration and reduces inflammation. Cardiac rupture after myocardial infarction (MI) is mainly the consequence of excessive regional inflammation, whereas cardiac dysfunction after MI results from a massive cardiomyocyte loss and cardiac fibrosis. It is possible that Tβ4 reduces the incidence of cardiac rupture post-MI via anti-inflammatory actions and that it decreases adverse cardiac remodeling and improves cardiac function by promoting cardiac cell survival and cardiac repair. C57BL/6 mice were subjected to MI and treated with either vehicle or Tβ4 (1.6 mg·kg(-1)·day(-1) ip via osmotic minipump) for 7 days or 5 wk. Mice were assessed for 1) cardiac remodeling and function by echocardiography; 2) inflammatory cell infiltration, capillary density, myocyte apoptosis, and interstitial collagen fraction histopathologically; 3) gelatinolytic activity by in situ zymography; and 4) expression of ICAM-1 and p53 by immunoblot analysis. Tβ4 reduced cardiac rupture that was associated with a decrease in the numbers of infiltrating inflammatory cells and apoptotic myocytes, a decrease in gelatinolytic activity and ICAM-1 and p53 expression, and an increase in the numbers of CD31-positive cells. Five-week treatment with Tβ4 ameliorated left ventricular dilation, improved cardiac function, markedly reduced interstitial collagen fraction, and increased capillary density. In a murine model of acute MI, Tβ4 not only decreased mortality rate as a result of cardiac rupture but also significantly improved cardiac function after MI. Thus, the use of Tβ4 could be explored as an alternative therapy in preventing cardiac rupture and restoring cardiac function in patients with MI.

  9. 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

  10. Functional consequences of caspase activation in cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Communal, Catherine; Sumandea, Marius; de Tombe, Pieter; Narula, Jagat; Solaro, R. John; Hajjar, Roger J.

    2002-04-01

    Cardiomyocyte apoptosis is present in many cardiac disease states, including heart failure and ischemic heart disease. Apoptosis is associated with the activation of caspases that mediate the cleavage of vital and structural proteins. However, the functional contribution of apoptosis to these conditions is not known. Furthermore, in cardiac myocytes, apoptosis may not be complete, allowing the cells to persist for a prolonged period within the myocardium. Therefore, we examined whether caspase-3 cleaved cardiac myofibrillar proteins and, if so, whether it affects contractile function. The effects of caspase-3 were studied in vitro on individual components of the cardiac myofilament including -actin, -actinin, myosin heavy chain, myosin light chain 1/2, tropomyosin, cardiac troponins (T, I, C), and the trimeric troponin complex. Exposure of the myofibrillar protein (listed above) to caspase-3 for 4 h resulted in the cleavage of -actin and -actinin, but not myosin heavy chain, myosin light chain 1/2, and tropomyosin, into three fragments (30, 20, and 15 kDa) and one major fragment (45 kDa), respectively. When cTnT, cTnI, and cTnC were incubated individually with caspase-3, there was no detectable cleavage. However, when the recombinant troponin complex was exposed to caspase-3, cTnT was cleaved, resulting in fragments of 25 kDa. Furthermore, rat cardiac myofilaments exposed to caspase-3 exhibited similar patterns of myofibrillar protein cleavage. Treatment with the caspase inhibitor DEVD-CHO or z-VAD-fmk abolished the cleavage. Myofilaments, isolated from adult rat ventricular myocytes after induction of apoptotic pathway by using -adrenergic stimulation, displayed a similar pattern of actin and TnT cleavage. Exposure of skinned fiber to caspase-3 decreased maximal Ca2+-activated force and myofibrillar ATPase activity. Our results indicate that caspase-3 cleaved myofibrillar proteins, resulting in an impaired force/Ca2+ relationship and myofibrillar ATPase activity

  11. 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

  12. Factors Affecting on Serum Lactate After Cardiac Surgery

    PubMed Central

    Joudi, Marjan; Fathi, Mehdi; Soltani, Ghasem; Izanloo, Azra

    2014-01-01

    Background: The relation between elevated blood lactate level and mortality and morbidity rates after coronary bypass surgery is a proven subject. One of the factors that seems to affect directly the blood lactate level is the storage duration of packed red blood cells. Objectives: This study aimed to evaluate the effect of storage duration of transfused blood on serum lactate during cardiac surgery and up to 24 hours after that in the ICU. Patients and Methods: In a cross-sectional study, 228 patients referred to three hospitals of Mashhad University of Medical Sciences for open cardiac surgery, was enrolled using systematic random sampling method. Immediately after accessing arterial line, the first sample of arterial blood gas (ABG) was obtained. For evaluation of lactate levels, the next samples were obtained at the end of surgery and after 24 hours of staying ICU. Results: Among 5 factors which affected lactate level during surgery, diabetes and higher ejection fraction (EF) reduced changes of the lactate level. On the other hand, the number of infused blood units, duration of on-pump time, and the mean storage duration of blood units were associated with elevated serum lactate during surgery. A significant relationship was found between blood storage duration and serum lactate levels 24 hours after surgery. Conclusions: Comparing the serum lactate level before operation and 24 hours after the operation showed that the number of received blood units had a significant effect on serum lactate. We found no significant effect for blood storage duration; however, the number of given blood units was more significant. PMID:25632379

  13. Cardiac autonomic function in healthy young smokers.

    PubMed

    Erdem, Alim; Ayhan, Suzi Selim; Öztürk, Serkan; Özlü, Mehmet Fatih; Alcelik, Aytekin; Sahin, Safak; Tosun, Mehmet; Erdem, Fatma Hizal; Gumustekin, Kenan; Yazici, Mehmet

    2015-01-01

    The present study examined the heart rate turbulence (HRT) and heart rate variability (HRV) parameters in healthy young smokers (<40 years) to assess the effects of smoking on cardiac autonomic function. The study included 75 smokers with a history of habitual smoking for at least 1 year (41 males and 34 females; mean age, 29.3 ± 7.3 years) and 30 nonsmokers (hospital staff; 16 males and 14 females; mean age, 29.0 ± 6.1 years). Addiction to smoking was evaluated using the modified Fagerström test for nicotine-dependence index (NDI). HRT, HRV, basic clinical and echocardiographic, and Holter test parameters were compared between groups. No significant differences between the two groups were found in the basic clinical and echocardiographic variables. Turbulence onset (TO) was significantly higher in the smoking group than in the controls, and turbulence slope was significantly lower in the smokers, than in the controls (p < 0.05). Standard deviation of all normal-to-normal (NN) interval index (SDNNI) was the only HRV parameter that was significantly different between the smoking and control groups (p < 0.05). The NDI was positively correlated with the TO (p < 0.05). Smoking impairs the baroregulatory function in healthy young smokers, particularly the HRT parameters and SDNNI. Our findings highlight the importance of complete smoking cessation.

  14. Sperm function in affective illness.

    PubMed

    Amsterdam, J; Winokur, A; Levin, R

    1981-04-01

    There is evidence for functional changes in the hypothalamic-pituitary-gonadal axis of patients with affective disorders. Little is known concerning spermatogenesis or sperm function in depressed men. We systematically evaluated the sperm indices in a group of depressed males complaining of diminished libido, and a healthy control group. No differences were noted in sperm parameters between the groups.

  15. Function and Therapeutic Potential of Noncoding RNAs in Cardiac Fibrosis.

    PubMed

    Creemers, Esther E; van Rooij, Eva

    2016-01-01

    Cardiac fibrosis as a result of excessive extracellular matrix deposition leads to stiffening of the heart, which can eventually lead to heart failure. An important event in cardiac fibrosis is the transformation of fibroblasts into myofibroblasts, which secrete large amounts of extracellular matrix proteins. Although the function of protein-coding genes in myofibroblast activation and fibrosis have been a topic of investigation for a long time, it has become clear that noncoding RNAs also play key roles in cardiac fibrosis. This review discusses the involvement of microRNAs and long noncoding RNAs in cardiac fibrosis and summarizes the issues related to translating these findings into real-life therapies.

  16. 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.

  17. 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

  18. Neuropeptide F peptides act through unique signaling pathways to affect cardiac activity.

    PubMed

    Setzu, M; Biolchini, M; Lilliu, A; Manca, M; Muroni, P; Poddighe, S; Bass, C; Angioy, A M; Nichols, R

    2012-02-01

    Elucidating how neuropeptides affect physiology may result in delineating peptidergic mechanisms and identifying antagonists for application in basic and translational science. Human neuropeptide Y (NPY) regulates cardiac activity; frequently invertebrates contain orthologs of vertebrate peptides. We report invertebrate NPY-like neuropeptide F (NPF) arrested the signal frequency of the slow phase of the cardiac cycle (EC50 = 1 pM); however, signal frequency of the fast phase was affected only minimally. Neuropeptide F decreased the duration of the slow phase by ~70% (EC50 = 0.6 pM), but increased the duration of the fast phase by ~57% (EC50 = 10nM). Short NPF-1 (sNPF-1) decreased the signal frequency of the slow phase by ~70% (EC50 = 9 nM); yet, signal frequency of the fast phase was unaffected. Short NPF-1 decreased the duration of the slow phase ~55% (EC50 ~50 nM), but increased the duration of the fast phase ~20% without dose dependency. Neuropeptide F and sNPF-1 increased isoelectric period duration. This novel report demonstrated NPY-like peptides are cardioactive but functionally unique. These data contribute to understanding how invertebrate orthologs affect cardiovascular activity. Dipteran fast and slow phases may be generated from separate pacemakers in the abdominal heart and in the anterior thoracocephalic aorta, respectively. Thus, our research suggests NPF and sNPF-1 act through different mechanisms to regulate cardiac activity. Invertebrate NPY-like peptides act in olfaction and feeding yet mechanisms which are associated with their cardioactive effects remain unknown; our work may provide evidence linking their roles in sensory response and cardiac activity.

  19. Neuropeptide F peptides act through unique signaling pathways to affect cardiac activity

    PubMed Central

    Setzu, M.; Biolchini, M.; Lilliu, A.; Manca, M.; Muroni, P.; Poddighe, S.; Bass, C.; Angioy, A.M.; Nichols, R.

    2012-01-01

    Elucidating how neuropeptides affect physiology may result in delineating peptidergic mechanisms and identifying antagonists for application in basic and translational science. Human neuropeptide Y (NPY) regulates cardiac activity; frequently invertebrates contain orthologs of vertebrate peptides. We report invertebrate NPY-like neuropeptide F (NPF) arrested the signal frequency of the slow phase of the cardiac cycle (EC50 = 1 pM); however, signal frequency of the fast phase was affected only minimally. Neuropeptide F decreased the duration of the slow phase by ~70% (EC50 = 0.6 pM), but increased the duration of the fast phase by ~57% (EC50 = 10 nM). Short NPF-1 (sNPF-1) decreased the signal frequency of the slow phase by ~70% (EC50 = 9 nM); yet, signal frequency of the fast phase was unaffected. Short NPF-1 decreased the duration of the slow phase ~55% (EC50 ~ 50 nM), but increased the duration of the fast phase ~20% without dose dependency. Neuropeptide F and sNPF-1 increased isoelectric period duration. This novel report demonstrated NPY-like peptides are cardioactive but functionally unique. These data contribute to understanding how invertebrate orthologs affect cardiovascular activity. Dipteran fast and slow phases may be generated from separate pacemakers in the abdominal heart and in the anterior thoracocephalic aorta, respectively. Thus, our research suggests NPF and sNPF-1 act through different mechanisms to regulate cardiac activity. Invertebrate NPY-like peptides act in olfaction and feeding yet mechanisms which are associated with their cardioactive effects remain unknown; our work may provide evidence linking their roles in sensory response and cardiac activity. PMID:22289500

  20. 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

  1. 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.

  2. Assessment of Cardiac Function--Basic Principles and Approaches.

    PubMed

    Spinale, Francis G

    2015-09-20

    Increased access and ability to visualize the heart has provided a means to measure a myriad of cardiovascular parameters in real or near real time. However, without fundamental knowledge regarding the basis for cardiac contraction and how to evaluate cardiac function in terms of loading conditions and inotropic state, appropriate interpretation of these cardiovascular parameters can be difficult and can lead to misleading conclusions regarding the functional state of the cardiac muscle. Thus, in this series of Comprehensive Physiology, the basic properties of cardiac muscle function, the cardiac cycle, and determinants of pump function will be reviewed. These basic concepts will then be integrated by presenting approaches in which the effects of preload, afterload, and myocardial contractility can be examined. Moreover, the utility of the pressure-volume relation in terms of assessing both myocardial contractility as well as critical aspects of diastolic performance will be presented. Finally, a generalized approach for the assessment and interpretation of cardiac function within the intact cardiovascular system will be presented.

  3. 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

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

    PubMed

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

    2012-04-01

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

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

    PubMed

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

    2014-12-01

    Cardiac gene therapy has emerged as a promising option to treat advanced heart failure (HF). Advances in molecular biology and gene targeting approaches are offering further novel options for genetic manipulation of the cardiovascular system. The aim of this study was to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) using a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116). One month after a large anterior myocardial infarction, 20 Yorkshire pigs randomly received intracoronary injection of either high-dose BNP116.I-1c (1.0 × 10(13) vector genomes (vg), n = 7), low-dose BNP116.I-1c (3.0 × 10(12) vg, n = 7), or saline (n = 6). Compared to baseline, mean left ventricular ejection fraction increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group, whereas it decreased by 7% in the saline group. Additionally, preload-recruitable stroke work obtained from pressure-volume analysis demonstrated significantly higher cardiac performance in the high-dose group. Likewise, other hemodynamic parameters, including stroke volume and contractility index indicated improved cardiac function after the I-1c gene transfer. Furthermore, BNP116 showed a favorable gene expression pattern for targeting the heart. In summary, I-1c overexpression using BNP116 improves cardiac function in a clinically relevant model of ischemic HF. PMID:25023328

  6. Factors affecting postoperative blood loss in children undergoing cardiac surgery.

    PubMed

    Faraoni, David; Van der Linden, Philippe

    2014-01-01

    We hypothesized that the influence of cyanotic disease on postoperative blood loss is closely related to age in children undergoing cardiac surgery. Here, we demonstrate that the presence of a cyanotic disease is associated with increased postoperative blood loss in children aged 1 to 6 months. Children with cyanotic disease and aged<1 month who received fresh frozen plasma during cardiopulmonary bypass had less postoperative blood loss and higher maximal clot firmness on FIBTEM than cyanotic children from all other groups. Additional studies are needed to define optimal pathophysiology-based management in children undergoing cardiac surgery. PMID:24512988

  7. 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.

  8. Albumin fiber scaffolds for engineering functional cardiac tissues.

    PubMed

    Fleischer, Sharon; Shapira, Assaf; Regev, Omri; Nseir, Nora; Zussman, Eyal; Dvir, Tal

    2014-06-01

    In recent years attempts to engineer contracting cardiac patches were focused on recapitulation of the myocardium extracellular microenvironment. We report here on our work, where for the first time, a three-dimensional cardiac patch was fabricated from albumin fibers. We hypothesized that since albumin fibers' mechanical properties resemble those of cardiac tissue extracellular matrix (ECM) and their biochemical character enables their use as protein carriers, they can support the assembly of cardiac tissues capable of generating strong contraction forces. Here, we have fabricated aligned and randomly oriented electrospun albumin fibers and investigated their structure, mechanical properties, and chemical nature. Our measurements showed that the scaffolds have improved elasticity as compared to synthetic electrospun PCL fibers, and that they are capable of adsorbing serum proteins, such as laminin leading to strong cell-matrix interactions. Moreover, due to the functional groups on their backbone, the fibers can be chemically modified with essential biomolecules. When seeded with rat neonatal cardiac cells the engineered scaffolds induced the assembly of aligned cardiac tissues with high aspect ratio cardiomyocytes and massive actinin striation. Compared to synthetic fibrous scaffolds, cardiac cells cultured within aligned or randomly oriented scaffolds formed functional tissues, exhibiting significantly improved function already on Day 3, including higher beating rate (P = 0.0002 and P < 0.0001, respectively), and higher contraction amplitude (P = 0.009 and P = 0.003, respectively). Collectively, our results suggest that albumin electrospun scaffolds can play a key role in contributing to the ex vivo formation of a contracting cardiac muscle tissue.

  9. Image based physiological monitoring of cardiac function

    NASA Astrophysics Data System (ADS)

    Maier, Corinna S.; Bock, Michael; Semmler, Wolfhard; Lorenz, Christine H.

    2008-03-01

    A new framework for image based physiological cardiac monitoring is proposed based on repeated imaging of critical slice locations in an interventional MRI environment. The aim of this work is to provide a method of detecting pathological changes in the left ventricular (LV) myocardial wall motion where the standard ECG methods are not possible due to distortions by the magnetic field. First MRI LV short axis images are acquired for different phases of the cardiac cycle over RR intervals. Then LV contours are detected based on an established segmentation algorithm. The contour's Fourier Descriptors are calculated to classify myocardial wall into two classes: contracted or not contracted. The classifier is trained during an initial observation period before a pathological change might occur during an intervention. A contour rejected by the classifier using the unconditional, predictive probability of the contour's observation vector as confidence measure is interpreted as a probably pathologic change in the LV myocardial wall motion. To evaluate the performance of the classifier a simple model is introduced for simulating the contours of a pathological, ischemic, LV myocardial wall. The overall performance of the classifier on 516 samples based on healthy volunteer images and 3096 simulated ischemic samples yielded a mean classification error for supervised training of 5.7% and for unsupervised training of 8.7%.

  10. Functional evolution of cardiac microRNAs in heart development and functions.

    PubMed

    Lin, Chen-Ching; Chang, Yao-Ming; Pan, Cheng-Tsung; Chen, Chien-Chang; Ling, Li; Tsao, Ku-Chi; Yang, Ruey-Bing; Li, Wen-Hsiung

    2014-10-01

    MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression either by degrading target mRNAs or by suppressing protein translation. miRNAs have been found to be involved in many biological processes, such as development, differentiation, and growth. However, the evolution of miRNA regulatory functions and networks has not been well studied. In this study, we conducted a cross-species analysis to study the evolution of cardiac miRNAs and their regulatory functions and networks. We found that conserved cardiac miRNA target genes have maintained highly conserved cardiac functions. Additionally, most of cardiac miRNA target genes in human with annotations of cardiac functions evolved from the corresponding homologous targets, which are also involved in heart development-related functions. On the basis of these results, we investigated the functional evolution of cardiac miRNAs and presented a functional evolutionary map. From this map, we identified the evolutionary time at which the cardiac miRNAs became involved in heart development or function and found that the biological processes of heart development evolved earlier than those of heart functions, for example, heart contraction/relaxation or cardiac hypertrophy. Our study of the evolution of the cardiac miRNA regulatory networks revealed the emergence of new regulatory functional branches during evolution. Furthermore, we discovered that early evolved cardiac miRNA target genes tend to participate in the early stages of heart development. This study sheds light on the evolution of developmental features of genes regulated by cardiac miRNAs.

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

    PubMed Central

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

    1993-01-01

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

  12. Does certificate of need affect cardiac outcomes and costs?

    PubMed

    Ho, Vivian

    2006-12-01

    Several U.S. states enforce Certificate of Need (CON) regulations, which limit the number of hospitals performing open heart surgery or coronary angioplasty. CON regulations were intended to restrain cost growth and improve quality of care. This study compares mortality rates and costs for cardiac care in states with and without CON. CON appears to raise hospital procedure volume and lower the average cost of care. However, CON is associated with little reduction in inpatient mortality, and it may lead hospitals to operate on more patients than they would otherwise. The claimed welfare benefits of CON regulations require careful reconsideration. PMID:17340175

  13. 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

  14. Visualization and analysis of functional cardiac MRI data

    NASA Astrophysics Data System (ADS)

    McVeigh, Elliot R.; Guttman, Michael A.; Poon, Eric; Pisupati, Chandrasekhar; Moore, Christopher C.; Zerhouni, Elias A.; Solaiyappan, Meiyappan; Heng, PhengAnn

    1994-05-01

    Rapid analysis of large multi-dimensional data sets is critical for the successful implementation of a comprehensive MR cardiac exam. We have developed a software package for the analysis and visualization of cardiac MR data. The program allows interactive visualization of time and space stacks of MRI data, automatic segmentation of myocardial borders and myocardial tagging patterns, and visualization of functional parameters such a motion, strain, and blood flow, mapped as colors in an interactive dynamic 3D volume rendering of the beating heart.

  15. Cardiac iron removal and functional cardiac improvement by different iron chelation regimens in thalassemia major patients.

    PubMed

    Cassinerio, Elena; Roghi, Alberto; Pedrotti, Patrizia; Brevi, Francesca; Zanaboni, Laura; Graziadei, Giovanna; Pattoneri, Paolo; Milazzo, Angela; Cappellini, Maria Domenica

    2012-09-01

    Heart failure due to myocardial iron overload remains the leading cause of morbidity and mortality in adult thalassemia major (TM) patients. We evaluated the removal of cardiac iron and the changes of cardiac function by different iron chelation in TM patients by T2* cardiac magnetic resonance (CMR). Sixty-seven TM patients (27 males/40 females; mean age, 35 ± 6 years) on different chelation regimens underwent T2* CMR at baseline (t (0)), after 6-14 months (t (1)) and after 32 ± 7 months (t (2)). Patients were divided in four groups according to chelation treatment: group A (deferasirox), group B (deferoxamine), group C (combined treatment, deferoxamine plus deferiprone) and group D (deferiprone alone). Myocardial T2* at t (0) was <10 ms in 8 patients, between 10 and 20 ms in 22 patients and ≥ 20 ms in 37 patients. Progressive changes in T2* were observed at t (1) and t (2). Ten patients (10/36, 27.8 %) in group A, three patients (3/15, 20 %) in group B and three patients (3/12, 25 %) in group C moved from an abnormal T2* to normal values. We observed an improvement of left ventricular ejection fraction and a reduction of end-systolic and end-diastolic left ventricular volumes only in patients in group A with baseline cardiac T2* between 10 and 20 ms. Rigorous compliance to any chelation therapy at proper doses significantly improve myocardial T2*. Treatment with deferasirox significantly improves left ventricular function. Combination therapy seems to ameliorate cardiac T2* in a shorter period of time in severe siderosis.

  16. 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

  17. Is Affect Aversive to Young Children with Autism: Behavioral and Cardiac Responses to Experimenter Distress.

    ERIC Educational Resources Information Center

    Corona, Rosalie; Dissanayake, Cheryl; Arbelle, Shoshana; Wellington, Peter; Sigman, Marian

    1998-01-01

    Compared attention, behavioral reaction, facial affect, and cardiac responses of 22 autistic and 22 mentally retarded preschoolers to emotional displays. Found that both groups looked more at the experimenter and displayed more interest and concern when the experimenter showed strong distress than when she showed neutral affect. Autistic…

  18. 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.

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

    PubMed Central

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

    2011-01-01

    Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/− mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/− hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/− mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction. PMID:21335464

  20. 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

  1. 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.

  2. 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

  3. 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

  4. The cardiac connexome: Non-canonical functions of connexin43 and their role in cardiac arrhythmias.

    PubMed

    Leo-Macias, Alejandra; Agullo-Pascual, Esperanza; Delmar, Mario

    2016-02-01

    Connexin43 is the major component of gap junctions, an anatomical structure present in the cardiac intercalated disc that provides a low-resistance pathway for direct cell-to-cell passage of electrical charge. Recent studies have shown that in addition to its well-established function as an integral membrane protein that oligomerizes to form gap junctions, Cx43 plays other roles that are independent of channel (or perhaps even hemi-channel) formation. This article discusses non-canonical functions of Cx43. In particular, we focus on the role of Cx43 as a part of a protein interacting network, a connexome, where molecules classically defined as belonging to the mechanical junctions, the gap junctions and the sodium channel complex, multitask and work together to bring about excitability, electrical and mechanical coupling between cardiac cells. Overall, viewing Cx43 as a multi-functional protein, beyond gap junctions, opens a window to better understand the function of the intercalated disc and the pathological consequences that may result from changes in the abundance or localization of Cx43 in the intercalated disc subdomain. PMID:26673388

  5. Placebo Sleep Affects Cognitive Functioning

    ERIC Educational Resources Information Center

    Draganich, Christina; Erdal, Kristi

    2014-01-01

    The placebo effect is any outcome that is not attributed to a specific treatment but rather to an individual's mindset (Benson & Friedman, 1996). This phenomenon can extend beyond its typical use in pharmaceutical drugs to involve aspects of everyday life, such as the effect of sleep on cognitive functioning. In 2 studies examining whether…

  6. 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

  7. 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

  8. H2O2 alters rat cardiac sarcomere function and protein phosphorylation through redox signaling.

    PubMed

    Avner, Benjamin S; Hinken, Aaron C; Yuan, Chao; Solaro, R John

    2010-09-01

    ROS, such as H(2)O(2), are a component of pathological conditions in many organ systems and have been reported to be elevated in cardiac pathophysiology. The experiments presented here test the hypothesis that H(2)O(2) induces alterations in cardiac myofilament function by the posttranslational modification of sarcomeric proteins indirectly through PKC signaling. In vitro assessment of actomyosin Mg(2+)-ATPase activity of myofibrillar fractions showed blunted relative ATP consumption in the relaxed state (pCa 8.0) in response to treatment with 0.5 mM H(2)O(2) before myofilament isolation. The effect was attributable to downstream "redox signaling," inasmuch as the direct application of H(2)O(2) to isolated myofibrils did not alter Mg(2+)-ATPase activity. Ca(2+)-ATPase activity, which was used as a measure of myofibrillar myosin function, was unaffected by H(2)O(2). Functional experiments using rat cardiac trabeculae treated with 0.5 or 5 mM H(2)O(2) followed by detergent extraction of membranes demonstrated increased Ca(2+) sensitivity of force production, a faster rate of force redevelopment, and (for 5 mM) decreased maximum tension. Biochemical analysis of myocardial samples treated with 0.5 mM H(2)O(2) demonstrated increased phosphorylation of two sarcomeric proteins: cardiac troponin I and myosin-binding protein-C. These changes were eliminated by a general PKC inhibitor. However, H(2)O(2) and the general PKC activator PMA induced different phosphorylation patterns in cardiomyocytes in which PKC-delta was elevated by viral infection. These data provide evidence that PKC-dependent redox signaling affects the function of cardiac myofilaments and indicate modification of specific proteins through this signaling mechanism.

  9. 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

  10. MicroRNA-34a regulates cardiac ageing and function.

    PubMed

    Boon, Reinier A; Iekushi, Kazuma; Lechner, Stefanie; Seeger, Timon; Fischer, Ariane; Heydt, Susanne; Kaluza, David; Tréguer, Karine; Carmona, Guillaume; Bonauer, Angelika; Horrevoets, Anton J G; Didier, Nathalie; Girmatsion, Zenawit; Biliczki, Peter; Ehrlich, Joachim R; Katus, Hugo A; Müller, Oliver J; Potente, Michael; Zeiher, Andreas M; Hermeking, Heiko; Dimmeler, Stefanie

    2013-03-01

    Ageing is the predominant risk factor for cardiovascular diseases and contributes to a significantly worse outcome in patients with acute myocardial infarction. MicroRNAs (miRNAs) have emerged as crucial regulators of cardiovascular function and some miRNAs have key roles in ageing. We propose that altered expression of miRNAs in the heart during ageing contributes to the age-dependent decline in cardiac function. Here we show that miR-34a is induced in the ageing heart and that in vivo silencing or genetic deletion of miR-34a reduces age-associated cardiomyocyte cell death. Moreover, miR-34a inhibition reduces cell death and fibrosis following acute myocardial infarction and improves recovery of myocardial function. Mechanistically, we identified PNUTS (also known as PPP1R10) as a novel direct miR-34a target, which reduces telomere shortening, DNA damage responses and cardiomyocyte apoptosis, and improves functional recovery after acute myocardial infarction. Together, these results identify age-induced expression of miR-34a and inhibition of its target PNUTS as a key mechanism that regulates cardiac contractile function during ageing and after acute myocardial infarction, by inducing DNA damage responses and telomere attrition.

  11. Playing with cardiac "redox switches": the "HNO way" to modulate cardiac function.

    PubMed

    Tocchetti, Carlo G; Stanley, Brian A; Murray, Christopher I; Sivakumaran, Vidhya; Donzelli, Sonia; Mancardi, Daniele; Pagliaro, Pasquale; Gao, Wei Dong; van Eyk, Jennifer; Kass, David A; Wink, David A; Paolocci, Nazareno

    2011-05-01

    The nitric oxide (NO(•)) sibling, nitroxyl or nitrosyl hydride (HNO), is emerging as a molecule whose pharmacological properties include providing functional support to failing hearts. HNO also preconditions myocardial tissue, protecting it against ischemia-reperfusion injury while exerting vascular antiproliferative actions. In this review, HNO's peculiar cardiovascular assets are discussed in light of its unique chemistry that distinguish HNO from NO(•) as well as from reactive oxygen and nitrogen species such as the hydroxyl radical and peroxynitrite. Included here is a discussion of the possible routes of HNO formation in the myocardium and its chemical targets in the heart. HNO has been shown to have positive inotropic/lusitropic effects under normal and congestive heart failure conditions in animal models. The mechanistic intricacies of the beneficial cardiac effects of HNO are examined in cellular models. In contrast to β-receptor/cyclic adenosine monophosphate/protein kinase A-dependent enhancers of myocardial performance, HNO uses its "thiophylic" nature as a vehicle to interact with redox switches such as cysteines, which are located in key components of the cardiac electromechanical machinery ruling myocardial function. Here, we will briefly review new features of HNO's cardiovascular effects that when combined with its positive inotropic/lusitropic action may render HNO donors an attractive addition to the current therapeutic armamentarium for treating patients with acutely decompensated congestive heart failure.

  12. 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.

  13. Environmentally persistent free radicals decrease cardiac function before and after ischemia/reperfusion injury in vivo

    PubMed Central

    Lord, Kevin; Moll, David; Lindsey, John K.; Mahne, Sarah; Raman, Girija; Dugas, Tammy; Cormier, Stephania; Troxlair, Dana; Lomnicki, Slawo; Dellinger, Barry; Varner, Kurt

    2011-01-01

    Exposure to airborne particles is associated with increased cardiovascular morbidity and mortality. During the combustion of chlorine-containing hazardous materials and fuels, chlorinated hydrocarbons chemisorb to the surface of transition metal-oxide-containing particles, reduce the metal, and form an organic free radical. These radical-particle systems can survive in the environment for days and are called environmentally persistent free radicals (EPFRs). This study determined whether EPFRs could decrease left ventricular function before and after ischemia and reperfusion (I/R) in vivo. Male Brown Norway rats were dosed (8 mg/kg, i.t.) 24 hr prior to testing with particles containing the EPFR of 1, 2-dichlorobenzene (DCB230). DCB230 treatment decreased systolic and diastolic function. DCB230 also produced pulmonary and cardiac inflammation. After ischemia, systolic, but not diastolic function was significantly decreased in DCB230-treated rats. Ventricular function was not affected by I/R in control rats. There was greater oxidative stress in the heart and increased 8-isoprostane (biomarker of oxidative stress) in the plasma of treated vs control rats after I/R. These data demonstrate for the first time that DCB230 can produce inflammation and significantly decrease cardiac function at baseline and after I/R in vivo. Furthermore, these data suggest that EPFRs may be a risk factor for cardiac toxicity in healthy individuals and individuals with ischemic heart disease. Potential mechanisms involving cytokines/chemokines and/or oxidative stress are discussed. PMID:21385100

  14. Systolic and diastolic cardiac function in acromegaly. An echocardiographic study.

    PubMed

    Galanti, G; Cappelli, B; Diricatti, G; Mininni, S; Vono, M C; Gensini, G F

    1996-01-01

    The aim of this study was to establish the existence of primary acromegalic cardiomyopathy different from the cardiovascular complications often associated with acromegaly. Thirty-four acromegalic patients, referred to our non-invasive laboratory and divided into two groups on the basis of the presence of hypertension, underwent echocardiographic studies. A control group of 34 subjects individually matched with the patients for age, sex, and blood pressure values was also studied. To evaluate cardiac function during exercise, the normotensive acromegalics, the control group, and a group of 9 athletes with left ventricular mass comparable to that of the acromegalic subjects underwent a handgrip test. Cardiac mass was increased in all patients; hypertensive patients had a greater increase than normotensive patients (144.9 +/- 38 vs 120.9 +/- 20.8 g/m, p < 0.02). Systolic wall stress and percent fractional shortening, although similar to the values confirmed in controls, were modified in the hypertensive patients (wall stress 77.5 +/- 9.3 vs 60.8 +/- 9.4 dyne/cm2, p < 0.01). In all patients, diastolic function at rest was similar to that in controls, although the hypertensive patients had deteriorated diastolic function (E peak 56.9 +/- 12.4 vs 71 +/- 15 cm/s, p < 0.01; A peak 70.4 +/- 21.1 vs 52.3 +/- 16.4 cm/s, p < 0.03; E/A ratio 0.89 +/- 0.37 vs 1.38 +/- 0.35, p < 0.02). During handgrip testing, wall stress in both the normotensive acromegalics and the control subjects increased but remained unchanged in the athlete group; percent fractional shortening decreased in all patients and controls but increased slightly in the athlete group. In conclusion, cardiac hypertrophy caused by GH hyperincretion does not improve acromegalic heart activity: diastolic function, although normal at rest, appears deficient during isometric exercise.

  15. Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post-infarcted cardiac function in rats.

    PubMed

    Zhao, Baoyin; Liao, Zhaofu; Chen, Shang; Yuan, Ziqiang; Yilin, Chen; Lee, Kenneth K H; Qi, Xufeng; Shen, Xiaotao; Zheng, Xin; Quinn, Thomas; Cai, Dongqing

    2014-05-01

    The midterm effects of cardiac telocytes (CTs) transplantation on myocardial infarction (MI) and the cellular mechanisms involved in the beneficial effects of CTs transplantation are not understood. In the present study, we have revealed that transplantation of CTs was able to significantly decrease the infarct size and improved cardiac function 14 weeks after MI. It has established that CT transplantation exerted a protective effect on the myocardium and this was maintained for at least 14 weeks. The cellular mechanism behind this beneficial effect on MI was partially attributed to increased cardiac angiogenesis, improved reconstruction of the CT network and decreased myocardial fibrosis. These combined effects decreased the infarct size, improved the reconstruction of the LV and enhanced myocardial function in MI. Our findings suggest that CTs could be considered as a potential cell source for therapeutic use to improve cardiac repair and function following MI, used either alone or in tandem with stem cells.

  16. 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.

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

    PubMed Central

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

    2016-01-01

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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. The effect of childhood obesity on cardiac functions.

    PubMed

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

    2014-03-01

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

  3. Pulmonary functions before and after pediatric cardiac surgery.

    PubMed

    Agha, Hala; El Heinady, Fatma; El Falaky, Mona; Sobih, Alae

    2014-03-01

    This study aimed to assess pulmonary functions before and after cardiac surgery in infants with congenital heart diseases and pulmonary overflow and to clarify which echocardiographic parameter correlates best with lung mechanics. Between 2008 and 2009, 30 infants with left-to-right shunt congenital acyanotic heart diseases who had indications for reparative surgery of these lesions were assessed by echocardiography and infant pulmonary function tests before the operation and 6 months afterward. Tests using baby body plethysmography were performed to assess the following infant pulmonary functions: tidal volume, respiratory rate, respiratory system compliance (C(rs)) and respiratory system resistance, functional residual capacity (FRC), and airway resistance. The mean age of the patients was 10.47 ± 3.38 months, and their mean weight was 6.81 ± 1.67 kg. Ventricular septal defect and combined lesions were the predominant cardiac diseases (26.7%). Comparison of the infant pulmonary function tests showed a highly significant improvement in all the parameters between the preoperative and 6-month postoperative visits (p < 0.0001). Systolic pulmonary artery pressure had a statistically significant negative correlation with C(rs) (r = -0.493, p = 0.006) and a positive correlation with FRC (r = 0.450, p = 0.013). The findings showed that C(rs) had a statistically significant negative correlation with the pulmonary artery size (r = -0.398, p = 0.029) and the left atrium size (r = -0.395, p = 0.031), whereas the pulmonary artery size had a statistically positive correlation with effective resistance (r = 0.416, p = 0.022) and specific effective resistance (r = 0.604, p = 0.0001). Surgical correction of left-to-right shunt congenital heart diseases had a positive impact on lung compliance, airway resistance, and FRC. Noninvasive echocardiographic parameters assessing pulmonary vascular engorgement and pulmonary artery pressure were closely related to these infant pulmonary

  4. Assessment of Cardiac Autonomic Functions in Medical Students With Type D Personality

    PubMed Central

    Panwar, R. Abhilasha Singh

    2016-01-01

    Introduction Type D personality experiences joint occurrence of Negative Affectivity and Social Inhibition. It is an emerging risk factor for cardiovascular disease, with prevalence being 18-53% among cardiac patients. Type D personality people have exaggerated cardiovascular activity mediated by increased sympathetic drive and decreased vagal control of the heart which leads to enhanced risk of hypertension and is an independent risk factor for coronary heart disease. Aim To compare the cardiac autonomic function of Type D and non-Type D students. To compare cardiac autonomic functions among male and female students and students with and without family history of hypertension and coronary artery disease among Type D. To find the most affected test among Type D students. Materials and Methods Thirty Type D and 30 non- Type D medical students were identified by DS14. The Parasympathetic cardiac autonomic tests done assessed Heart Rate response to valsalva manoeuvre, immediate heart rate response to standing and heart rate variation during deep breathing. Sympathetic tests assessed BP response to standing and Sustained Hand Grip. The heart rate and R-R interval measurement were got from lead II of ECG recordings on Polyrite D. Statistical analysis was done using SPSS software. Unpaired student’s t-test was used and p-value <0.05 was considered to be statistically significant. Results Type D students showed slightly decreased parasympathetic activity and increased sympathetic activity when compared to non-Type D students even though there was no statistically significant difference between them. There is a statistically significant decrease in valsalva ratio among females (p<0.01) when compared to males. There is a statistically significant decrease in 30:15 ratio and BP response to handgrip (p<0.05) among students with family history of hypertension and coronary artery disease when compared with students with no family history of coronary artery disease. Valsalva

  5. Functional cardiac lipolysis in mice critically depends on comparative gene identification-58.

    PubMed

    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

    2013-04-01

    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.

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

    PubMed Central

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

    2013-01-01

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

  7. 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

  8. Functions of Myosin Light Chain-2 (MYL2) In Cardiac Muscle and Disease

    PubMed Central

    Sheikh, Farah; Lyon, Robert C.; Chen, Ju

    2015-01-01

    Myosin light chain-2 (MYL2, also called MLC-2) is an ∼19 kDa sarcomeric protein that belongs to the EF-hand calcium binding protein superfamily and exists as three major isoforms encoded by three distinct genes in mammalian striated muscle. Each of the three different MLC-2 genes (MLC-2f; fast twitch skeletal isoform, MLC-2v; cardiac ventricular and slow twitch skeletal isoform, MLC-2a; cardiac atrial isoform) has a distinct developmental expression pattern in mammals. Genetic loss-of-function studies in mice demonstrated an essential role for cardiac isoforms of MLC-2, MLC-2v and MLC-2a, in cardiac contractile function during early embryogenesis. In the adult heart, MLC-2v function is regulated by phosphorylation, which displays a specific expression pattern (high in epicardium and low in endocardium) across the heart. These data along with new data from computational models, genetic mouse models, and human studies have revealed a direct role for MLC-2v phosphorylation in cross-bridge cycling kinetics, calcium-dependent cardiac muscle contraction, cardiac torsion, cardiac function and various cardiac diseases. This review focuses on the regulatory functions of MLC-2 in the embryonic and adult heart, with an emphasis on phosphorylation-driven actions of MLC-2v in adult cardiac muscle, which provide new insights into mechanisms regulating myosin cycling kinetics and human cardiac diseases. PMID:26074085

  9. Transpulmonary thermodilution-derived cardiac function index identifies cardiac dysfunction in acute heart failure and septic patients: an observational study

    PubMed Central

    2009-01-01

    Introduction There is limited clinical experience with the single-indicator transpulmonary thermodilution (pulse contour cardiac output, or PiCCO) technique in critically ill medical patients, particularly in those with acute heart failure (AHF). Therefore, we compared the cardiac function of patients with AHF or sepsis using the pulmonary artery catheter (PAC) and the PiCCO technology. Methods This retrospective observational study was conducted in the medical intensive care unit of a university hospital. Twelve patients with AHF and nine patients with severe sepsis or septic shock had four simultaneous hemodynamic measurements by PAC and PiCCO during a 24-hour observation period. Comparisons between groups were made with the use of the Mann-Whitney U test. Including all measurements, correlations between data pairs were established using linear regression analysis and are expressed as the square of Pearson's correlation coefficients (r2). Results Compared to septic patients, AHF patients had a significantly lower cardiac index, cardiac function index (CFI), global ejection fraction, mixed venous oxygen saturation (SmvO2) and pulmonary vascular permeability index, but higher pulmonary artery occlusion pressure. All patients with a CFI less than 4.5 per minute had an SmvO2 not greater than 70%. In both groups, the CFI correlated with the left ventricular stroke work index (sepsis: r2 = 0.30, P < 0.05; AHF: r2 = 0.23, P < 0.05) and cardiac power (sepsis: r2 = 0.39, P < 0.05; AHF: r2 = 0.45, P < 0.05). Conclusions In critically ill medical patients, assessment of cardiac function using transpulmonary thermodilution technique is an alternative to the PAC. A low CFI identifies cardiac dysfunction in both AHF and septic patients. PMID:19671146

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

    PubMed

    Smith, S C

    2000-03-01

    The absence of cardiac and circulatory function causes severe edema in amphibian embryos. Analyzing the roles of embryonic and larval circulation in respiration may thus be confounded by the increased diffusion distance and decreased surface area/volume ratio caused by edema. Similarly, detailed morphological analyses of embryos/larvae with defective circulatory or renal function is difficult or impossible due to the gross morphological anomalies engendered by edematous swelling. To circumvent these problems, two media have been developed which are isosmotic with the plasma of a common experimental amphibian species (Ambystoma mexicanun). These media are remarkably effective in preventing fluid accumulation in embryos and larvae lacking heart function and, when used in slightly lower concentrations, cause no apparent harm to embryos and larvae with normal circulation for periods up to 3 weeks. These media should prove useful for a variety of studies on the developmental physiology of the circulatory system and possibly also when examining the development of renal function and ionoregulation. PMID:10764226

  11. 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.

  12. 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

  13. Disruption of Sarcoendoplasmic Reticulum Calcium ATPase Function in Drosophila Leads to Cardiac Dysfunction

    PubMed Central

    Abraham, Dennis M.; Wolf, Matthew J.

    2013-01-01

    Abnormal sarcoendoplasmic reticulum Calcium ATPase (SERCA) function has been associated with poor cardiac function in humans. While modifiers of SERCA function have been identified and studied using animal models, further investigation has been limited by the absence of a model system that is amenable to large-scale genetic screens. Drosophila melanogaster is an ideal model system for the investigation of SERCA function due to the significant homology to human SERCA and the availability of versatile genetic screening tools. To further the use of Drosophila as a model for examining the role of SERCA in cardiac function, we examined cardiac function in adult flies. Using optical coherence tomography (OCT) imaging in awake, adult Drosophila, we have been able to characterize cardiac chamber dimensions in flies with disrupted in Drosophila SERCA (CaP60A). We found that the best studied CaP60A mutant, the conditional paralytic mutant CaP60Akum170, develops marked bradycardia and chamber enlargement that is closely linked to the onset of paralysis and dependent on extra cardiac CaP60A. In contrast to prior work, we show that disruption of CaP60A in a cardiac specific manner results in cardiac dilation and dysfunction rather than alteration in heart rate. In addition, the co-expression of a calcium release channel mutation with CaP60A kum170 is sufficient to rescue the cardiac phenotype but not paralysis. Finally, we show that CaP60A overexpression is able to rescue cardiac function in a model of Drosophila cardiac dysfunction similar to what is observed in mammals. Thus, we present a cardiac phenotype associated with Drosophila SERCA dysfunction that would serve as additional phenotyping for further large-scale genetic screens for novel modifiers of SERCA function. PMID:24098595

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

    PubMed

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

    2009-01-01

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

  15. Radial artery vasomotor function following transradial cardiac catheterisation

    PubMed Central

    Mitchell, A J; Mills, N L; Newby, D E; Cruden, N L M

    2016-01-01

    Aims To determine the reproducibility of flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in the assessment of radial artery vasomotor function, and to examine the effect of transradial catheterisation on radial artery injury and recovery. Methods Radial artery FMD and NMD were examined in 20 volunteers and 20 patients on four occasions (two visits at least 24 hours apart, with two assessments at each visit). In a further 10 patients, radial artery FMD was assessed in the catheterised arm prior to, at 24 hours and 3 months following cardiac catheterisation. Results There were no differences in baseline radial artery diameter (2.7±0.4 mm vs 2.7±0.4 mm), FMD (13.4±6.4 vs 12.89±5.5%) or NMD (13.6±3.8% vs 10.1±4.3%) between healthy volunteers and patients (p>0.05 for all comparisons). Mean differences for within and between day FMD were 2.53% (95% CIs −15.5% to 20.5%) and −4.3% (−18.3% to 9.7%) in patients. Compared to baseline, radial artery FMD was impaired at 24 hours (8.7±4.1% vs 3.9±2.9%, p=0.015) but not 3 months (8.7±4.1% vs 6.2±4.4, p=0.34) following transradial catheterisation. Conclusions Radial FMD is impaired early after transradial catheterisation but appears to recover by 3 months. While test–retest variability was demonstrated, our findings suggest that transradial access for cardiac catheterisation may afford a potential model of vascular injury and repair in vivo in man. PMID:27752330

  16. The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment.

    PubMed

    Schloss, Maximilian J; Horckmans, Michael; Nitz, Katrin; Duchene, Johan; Drechsler, Maik; Bidzhekov, Kiril; Scheiermann, Christoph; Weber, Christian; Soehnlein, Oliver; Steffens, Sabine

    2016-01-01

    Myocardial infarction (MI) is the leading cause of death in Western countries. Epidemiological studies show acute MI to be more prevalent in the morning and to be associated with a poorer outcome in terms of mortality and recovery. The mechanisms behind this association are not fully understood. Here, we report that circadian oscillations of neutrophil recruitment to the heart determine infarct size, healing, and cardiac function after MI Preferential cardiac neutrophil recruitment during the active phase (Zeitgeber time, ZT13) was paralleled by enhanced myeloid progenitor production, increased circulating numbers of CXCR2(hi) neutrophils as well as upregulated cardiac adhesion molecule and chemokine expression. MI at ZT13 resulted in significantly higher cardiac neutrophil infiltration compared to ZT5, which was inhibited by CXCR2 antagonism or neutrophil-specific CXCR2 knockout. Limiting exaggerated neutrophilic inflammation at this time point significantly reduced the infarct size and improved cardiac function. PMID:27226028

  17. 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

  18. 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

  19. Acute myocarditis in dengue hemorrhagic fever: a case report and review of cardiac complications in dengue-affected patients.

    PubMed

    Lee, Ing-Kit; Lee, Wen-Huei; Liu, Jien-Wei; Yang, Kuender D

    2010-10-01

    We report a case of dengue hemorrhagic fever (DHF) complicated by acute myocarditis and review the literature. A 65-year-old woman experienced DHF due to dengue virus serotype 3, complicated with acute myocarditis and acute pulmonary edema. Clinically this masqueraded as acute myocardial infarction, with an electrocardiographically depressed ST segment in precordial leads and elevated serum cardiac-specific troponin I level. Under supportive management, the patient recovered 3 days later. A total of 18 pertinent articles involving 339 dengue-affected patients with cardiac complications were found by PubMed search. Clinical manifestations of cardiac complications varied considerably, from self-limiting tachy-brady arrhythmia to severe myocardial damage, leading to hypotension and pulmonary edema. Although rare, a fatal outcome was reported in some cases of dengue with cardiac complications. To avoid otherwise preventable morbidity and mortality, physicians should have a high index of suspicion for cardiac complications in patients with dengue illness and should manage this accordingly.

  20. Inhalation of Simulated Smog Affects Cardiac Function in Mice

    EPA Science Inventory

    Rationale: The health effects of individual criteria air pollutants have been well investigated. Little is known about health effects of inhaled multi-pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the card...

  1. 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

  2. Cardiac function of the naked mole-rat: ecophysiological responses to working underground.

    PubMed

    Grimes, Kelly M; Voorhees, Andrew; Chiao, Ying Ann; Han, Hai-Chao; Lindsey, Merry L; Buffenstein, Rochelle

    2014-03-01

    The naked mole-rat (NMR) is a strictly subterranean rodent with a low resting metabolic rate. Nevertheless, it can greatly increase its metabolic activity to meet the high energetic demands associated with digging through compacted soils in its xeric natural habitat where food is patchily distributed. We hypothesized that the NMR heart would naturally have low basal function and exhibit a large cardiac reserve, thereby mirroring the species' low basal metabolism and large metabolic scope. Echocardiography showed that young (2-4 yr old) healthy NMRs have low fractional shortening (28 ± 2%), ejection fraction (43 ± 2%), and cardiac output (6.5 ± 0.4 ml/min), indicating low basal cardiac function. Histology revealed large NMR cardiomyocyte cross-sectional area (216 ± 10 μm(2)) and cardiac collagen deposition of 2.2 ± 0.4%. Neither of these histomorphometric traits was considered pathological, since biaxial tensile testing showed no increase in passive ventricular stiffness. NMR cardiomyocyte fibers showed a low degree of rotation, contributing to the observed low NMR cardiac contractility. Interestingly, when the exercise mimetic dobutamine (3 μg/g ip) was administered, NMRs showed pronounced increases in fractional shortening, ejection fraction, cardiac output, and stroke volume, indicating an increased cardiac reserve. The relatively low basal cardiac function and enhanced cardiac reserve of NMRs are likely to be ecophysiological adaptations to life in an energetically taxing environment. PMID:24363308

  3. Functional imaging as an indicator of diagnostic information in cardiac magnetic-resonance images

    NASA Astrophysics Data System (ADS)

    Klingler, Joseph W.; Andrews, Lee T.; Begeman, Michael S.; Zeiss, Jacob; Leighton, Richard F.

    1990-08-01

    Magnetic Resonance (MR) images of the human heart provide three dimensional geometric information about the location of cardiac structures throughout the cardiac cycle. Analysis of this four dimensional data set allows detection of abnormal cardiac function related to the presence of coronary artery disease. To assist in this analysis, quantitative measurements of cardiac performance are made from the MR data including ejection fractions, regional wall motion and myocardial wall thickening. Analysis of cardiac performance provided by quantitative analysis of MR data can be aided by computer graphics presentation techniques. Two and three dimensional functional images are computed to indicate regions of abnormality based on the previous methods. The two dimensional images are created using color graphics overlays on the original MR image to represent performance. Polygon surface modeling techniques are used to represent data which is three dimensional, such as blood pool volumes. The surface of these images are color encoded by regional ejection fraction, wall motion or wall thickening. A functional image sequence is constructed at each phase of the cardiac cycle and displayed as a movie loop for review by the physician. Selection of a region on the functional image allows visual interpretation of the original MR images, graphical plots of cardiac function and tabular results. Color encoding is based on absolute measurements and comparison to standard normal templates of cardiac performance.

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

    PubMed Central

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

    2016-01-01

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

  5. 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

  6. 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

  7. 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

  8. Progressive Dystrophic Pathology in Diaphragm and Impairment of Cardiac Function in FKRP P448L Mutant Mice

    PubMed Central

    Blaeser, Anthony; Awano, Hiroyuki; Wu, Bo; Lu, Qi-Long

    2016-01-01

    Mutations in the gene for fukutin-related protein represent a subset of muscular dystrophies known as dystroglycanopathies characterized by loss of functionally-glycosylated-alpha-dystroglycan and a wide range of dystrophic phenotypes. Mice generated by our lab containing the P448L mutation in the fukutin-related protein gene demonstrate the dystrophic phenotype similar to that of LGMD2I. Here we examined the morphology of the heart and diaphragm, focusing on pathology of diaphragm and cardiac function of the mutant mice for up to 12 months. Both diaphragm and heart lack clear expression of functionally-glycosylated-alpha-dystroglycan throughout the observed period. The diaphragm undergoes progressive deterioration in histology with increasing amount of centranucleation and inflammation. Large areas of mononuclear cell infiltration and fibrosis of up to 60% of tissue area were detected as early as 6 months of age. Despite a less severe morphology with only patches of mononuclear cell infiltration and fibrosis of ~5% by 12 months of age in the heart, cardiac function is clearly affected. High frequency ultrasound reveals a smaller heart size up to 10 months of age. There are significant increases in myocardial thickness and decrease in cardiac output through 12 months. Dysfunction in the heart represents a key marker for evaluating experimental therapies aimed at cardiac muscle. PMID:27711214

  9. [Comparative evaluation of the cardiac functional reserve in operated and nonoperated congenital heart defect patients].

    PubMed

    Gritsenko, V V; Gavrilenkov, V I; Mochalov, O Iu

    1981-02-01

    The functional cardiac reserve was studied in 26 non-operated and 42 operated patients with congenital heart diseases. The ratio of the maximum utilization of oxygen (VO2 max) to the heart volume (HV) was shown to be an objective quantitative index of the functional cardiac reserve. The authors believe that the value of the functional cardiac reserve may be used for the determination of risk as well as for the assessment of the rehabilitation of the rehabilitation significance of operations in patients with congenital heart diseases. PMID:7233699

  10. Cardiac metabolic pathways affected in the mouse model of barth syndrome.

    PubMed

    Huang, Yan; Powers, Corey; Madala, Satish K; Greis, Kenneth D; Haffey, Wendy D; Towbin, Jeffrey A; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.

  11. Cardiac Metabolic Pathways Affected in the Mouse Model of Barth Syndrome

    PubMed Central

    Huang, Yan; Powers, Corey; Madala, Satish K.; Greis, Kenneth D.; Haffey, Wendy D.; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Javadov, Sabzali; Strauss, Arnold W.; Khuchua, Zaza

    2015-01-01

    Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F0F1-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS. PMID:26030409

  12. 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

  13. Automatic facial responses to affective stimuli in high-functioning adults with autism spectrum disorder.

    PubMed

    Mathersul, Danielle; McDonald, Skye; Rushby, Jacqueline A

    2013-01-17

    Individuals with autism spectrum disorder (ASD) demonstrate atypical behavioural responses to affective stimuli, although the underlying mechanisms remain unclear. Investigating automatic responses to these stimuli may help elucidate these mechanisms. 18 high-functioning adults with ASDs and 18 typically developing controls viewed 54 extreme pleasant (erotica), extreme unpleasant (mutilations), and non-social neutral images from the International Affective Picture System (IAPS). Two-thirds of images received an acoustic startle probe 3s post-picture onset. Facial electromyography (EMG) activity (orbicularis, zygomaticus, corrugator), skin conductance (SCR) and cardiac responses were recorded. The adults with ASDs demonstrated typical affective startle modulation and automatic facial EMG responses but atypical autonomic (SCRs and cardiac) responses, suggesting a failure to orient to, or a deliberate effort to disconnect from, socially relevant stimuli (erotica, mutilations). These results have implications for neural systems known to underlie affective processes, including the orbitofrontal cortex and amygdala. PMID:23142408

  14. Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture

    PubMed Central

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Miraldi, Fabio; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation. Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells. Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production. Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures. PMID:27340620

  15. Respiratory, metabolic and cardiac functions are altered by disinhibition of subregions of the medial prefrontal cortex

    PubMed Central

    Hassan, Sarah F; Cornish, Jennifer L; Goodchild, Ann K

    2013-01-01

    The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however, little is known about whether this region influences respiratory or metabolic outflows. The aim of this study was to describe simultaneous changes in respiratory, metabolic and cardiovascular functions evoked by disinhibition of the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane-anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A receptor antagonist) into 90 sites in the mPFC at 0.72–4.00 mm from bregma. Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown adipose tissue temperatures were measured. Novel findings included disturbances to respiratory rhythm evoked from all subregions of the mPFC. Injections into the cingulate cortex evoked reductions in central respiratory function exclusively, whereas in ventral sites, particularly the infralimbic region, increases in respiratory drive and frequency, and metabolic and cardiac outflows were evoked. Disinhibition of sites in surrounding regions revealed that the LSN could evoke cardiovascular changes accompanied by distinct oscillations in SNA, as well as increases in respiratory amplitude. We show that activation of neurons within the mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site-dependent manner. This study has implications with respect to the altered PFC neuronal activity seen in stress-related and mental health disorders, and suggests how basic physiological systems may be affected. PMID:24042503

  16. 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

  17. 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

  18. Emotion Risk-Factor in Patients With Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study)

    PubMed Central

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghaei, Abbas

    2016-01-01

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases. PMID:26234976

  19. Emotion Risk-Factor in Patients with Cardiac Diseases: The Role of Cognitive Emotion Regulation Strategies, Positive Affect and Negative Affect (A Case-Control Study).

    PubMed

    Bahremand, Mostafa; Alikhani, Mostafa; Zakiei, Ali; Janjani, Parisa; Aghei, Abbas

    2015-05-17

    Application of psychological interventions is essential in classic treatments for patient with cardiac diseases. The present study compared cognitive emotion regulation strategies, positive affect, and negative affect for cardiac patients with healthy subjects. This study was a case-control study. Fifty subjects were selected using convenient sampling method from cardiac (coronary artery disease) patients presenting in Imam Ali medical center of Kermanshah, Iran in the spring 2013. Fifty subjects accompanied the patients to the medical center, selected as control group, did not have any history of cardiac diseases. For collecting data, the cognitive emotion regulation questionnaire and positive and negative affect scales were used. For data analysis, multivariate analysis of variance (MANOVA) Was applied using the SPSS statistical software (ver. 19.0). In all cognitive emotion regulation strategies, there was a significant difference between the two groups. A significant difference was also detected regarding positive affect between the two groups, but no significant difference was found regarding negative affect. We found as a result that, having poor emotion regulation strategies is a risk factor for developing heart diseases.

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

    PubMed

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

    2015-01-01

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

  1. Near death experiences, cognitive function and psychological outcomes of surviving cardiac arrest.

    PubMed

    Parnia, S; Spearpoint, K; Fenwick, P B

    2007-08-01

    Cardiac arrest is associated with a number of cognitive processes as well as long term psychological outcomes. Recent studies have indicated that approximately 10-20% of cardiac arrest survivors report cognitive processes, including the ability to recall specific details of their resuscitation from the period of cardiac arrest. In addition it has been demonstrated that these cognitive processes are consistent with the previously described near death experience and that those who have these experiences are left with long term positive life enhancing effects. There have also been numerous studies that have indicated that although the quality of life for cardiac arrest survivors is generally good, some are left with long term cognitive impairments as well as psychological sequelae such as post-traumatic stress disorder. This paper will review near death experiences, cognitive function and psychological outcomes in survivors of cardiac arrest.

  2. 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.

  3. Adult c-kit(pos) cardiac stem cells are necessary and sufficient for functional cardiac regeneration and repair.

    PubMed

    Ellison, Georgina M; Vicinanza, Carla; Smith, Andrew J; Aquila, Iolanda; Leone, Angelo; Waring, Cheryl D; Henning, Beverley J; Stirparo, Giuliano Giuseppe; Papait, Roberto; Scarfò, Marzia; Agosti, Valter; Viglietto, Giuseppe; Condorelli, Gianluigi; Indolfi, Ciro; Ottolenghi, Sergio; Torella, Daniele; Nadal-Ginard, Bernardo

    2013-08-15

    The epidemic of heart failure has stimulated interest in understanding cardiac regeneration. Evidence has been reported supporting regeneration via transplantation of multiple cell types, as well as replication of postmitotic cardiomyocytes. In addition, the adult myocardium harbors endogenous c-kit(pos) cardiac stem cells (eCSCs), whose relevance for regeneration is controversial. Here, using different rodent models of diffuse myocardial damage causing acute heart failure, we show that eCSCs restore cardiac function by regenerating lost cardiomyocytes. Ablation of the eCSC abolishes regeneration and functional recovery. The regenerative process is completely restored by replacing the ablated eCSCs with the progeny of one eCSC. eCSCs recovered from the host and recloned retain their regenerative potential in vivo and in vitro. After regeneration, selective suicide of these exogenous CSCs and their progeny abolishes regeneration, severely impairing ventricular performance. These data show that c-kit(pos) eCSCs are necessary and sufficient for the regeneration and repair of myocardial damage. PMID:23953114

  4. Modelling of an oesophageal electrode for cardiac function tomography.

    PubMed

    Tehrani, J Nasehi; Jin, C; McEwan, A L

    2012-01-01

    There is a need in critical care units for continuous cardiopulmonary monitoring techniques. ECG gated electrical impedance tomography is able to localize the impedance variations occurring during the cardiac cycle. This method is a safe, inexpensive and potentially fast technique for cardiac output imaging but the spatial resolution is presently low, particularly for central locations such as the heart. Many parameters including noise deteriorate the reconstruction result. One of the main obstacles in cardiac imaging at the heart location is the high impedance of lungs and muscles on the dorsal and posterior side of body. In this study we are investigating improvements of the measurement and initial conductivity estimation of the internal electrode by modelling an internal electrode inside the esophagus. We consider 16 electrodes connected around a cylindrical mesh. With the random noise level set near 0.05% of the signal we evaluated the Graz consensus reconstruction algorithm for electrical impedance tomography. The modelling and simulation results showed that the quality of the target in reconstructed images was improved by up to 5 times for amplitude response, position error, resolution, shape deformation and ringing effects with perturbations located in cardiac related positions when using an internal electrode.

  5. 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

  6. The evolutionary functions of cardiac NOS/NO in vertebrates tracked by fish and amphibian paradigms.

    PubMed

    Imbrogno, Sandra; Tota, Bruno; Gattuso, Alfonsina

    2011-06-30

    During early ectotherm vertebrate evolution the heart was redesigned as a high pressure pump adapted to perfuse larger body sizes. To compensate the consequent higher organ complexity and heterogeneity (ventricular myoarchitecture and blood supply), conceivably the three principal cardiac cell components, the endocardium, the contractile myocardium and the epicardium recruited and diversified the cardiac NOS system for functioning not only as a major modulator, but also as a spatio-temporal integrator of heart function. In the context of NOS isoform evolution, we will use fish and amphibian paradigms to illustrate major aspects of cardiac spatial and temporal integration achieved by the NOS/NO systems. This may reveal a primordial cardiac NOS/NO function, allocating it in a wider biological framework than so far envisioned.

  7. 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

  8. 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

  9. Cardiac tamponade in a neonate: a dreadful condition--need for functional echo.

    PubMed

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

    2014-12-22

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

  10. Effect of Depression and Sertraline Treatment on Cardiac Function in Female Nonhuman Primates

    PubMed Central

    Groban, Leanne; Kitzman, Dalane W.; Register, Thomas C.; Shively, Carol A.

    2014-01-01

    Objective Depression is a proposed risk factor for heart failure based largely on epidemiological data; little experimental data is available addressing this hypothesis. Methods Depression was evaluated in relation to cardiac structural and functional phenotypes assessed by transthoracic echocardiography in 42 adult female cynomolgus monkeys that consumed a Western-like diet for 3 years. Half of the monkeys were treated with the SSRI sertraline HCl for 18 months and depressive behavior was assessed for 12 months prior to echocardiography. Results Depressed monkeys (the 19/42 with depressive behavior rates above the mean rate) had higher HRs (171±4.1 vs 152±6.1), and smaller BSA (0.13±0.003 vs 0.15±0.004). Cardiac measures showed lower LV end systolic dimension (0.75±0.05 vs 0.89±0.04), LV systolic (0.76±0.08 vs 1.2±0.11) and diastolic (2.4±0.23 vs 3.4±0.26) volumes, and left atrial volumes (1.15±0.14 vs 1.75±0.12) in depressed versus nondepressed monkeys (p’s <0.05). Doppler profiles of depressed monkeys indicated greater myocardial relaxation (higher e′ and higher e′/a′ ratio) and lower filling pressures (lower E/e′) compared to nondepressed monkeys (p’s<0.05). Although treatment with sertraline reduced HR (150±5.8 vs 171±4.8) and modestly increased chamber dimensions (left ventricular end systolic dimension: 0.91±0.05 vs 0.74±0.03; left ventricular end diastolic dimension, BSA adjusted 1.69±0.05 vs 1.47±0.06) (p’s<0.05), it did not overtly affect systolic or diastolic function (p’s >0.10). Conclusions These data suggest that behavioral depression in female primates is accompanied by differences in cardiac function, although not in ways classically associated with subclinical heart failure. SSRIs show promise in supporting heart function by reducing HR and perhaps improving LV filling, however further investigation is needed to confirm this hypothesis. PMID:24470133

  11. Is Combination Therapy for Chronic Hepatitis C Toxic for Cardiac Function?

    PubMed Central

    Almawardy, Ramzy; Elhammady, Walid; Mousa, Nasser; Abotaleb, Sherif

    2012-01-01

    Background Many types of cardiovascular complications such as; cardiac arrhythmias, impaired cardiac function, myocardial ischemia and decreased left ventricular function, have been attributed to interferon therapy. Objectives The aim of this study was to evaluate the effects of combination therapy pegylated interferon and ribavirin on left ventricular systolic and diastolic functions in patients with a chronic hepatitis C infection. Patients and Methods A total of 120 patients, eligible for hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin, were included in this study. All patients underwent a full cardiovascular baseline examination including; detailed medical history, thorough clinical examination, 12 lead electrocardiogram (ECG), and echocardiography. A cardiac evaluation was performed at the beginning and six months after starting combination therapy. Results No significant changes regarding cardiac symptoms including; shortness of breath, cough, palpitations, chest pain and hypertension, were found during or six months after starting the combined therapy. ECG findings showed statistically non-significant decreases in the QT interval, while corrected QT showed statistically non-significant increases six months after beginning combined therapy, when compared to their values before treatment. Also with regard to the echocardiography findings, there was no statistically significant difference found between any of the echocardiography parameters six months after starting combined therapy compared to their values before treatment. Conclusions The results of our study suggest that, combination therapy does not cause a significant deterioration in cardiac function in patients with a chronic hepatitis C infection, and it may be used safely in patients without cardiac disease. PMID:23105944

  12. 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.

  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. 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.

  15. Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.

    PubMed

    Hamilton, Jasmine L; Hatef, Azadeh; Imran ul-Haq, Muhammad; Nair, Neelima; Unniappan, Suraj; Kizhakkedathu, Jayachandran N

    2014-01-01

    Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity.

  16. Clinically Approved Iron Chelators Influence Zebrafish Mortality, Hatching Morphology and Cardiac Function

    PubMed Central

    Hamilton, Jasmine L.; Hatef, Azadeh; Imran ul-haq, Muhammad; Nair, Neelima; Unniappan, Suraj; Kizhakkedathu, Jayachandran N.

    2014-01-01

    Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos. In this study, we took advantage of the rapid development and transparency of the zebrafish embryo, Danio rerio to assess and compare the toxicity of iron chelators. All three iron chelators described above were delivered to zebrafish embryos by direct soaking and their effects on mortality, hatching and developmental morphology were monitored for 96 hpf. To determine whether toxicity was specific to embryos, we examined the effects of chelator exposure via intra peritoneal injection on the cardiac function and gene expression in adult zebrafish. Chelators varied significantly in their effects on embryo mortality, hatching and morphology. While none of the embryos or adults exposed to DFO were negatively affected, ICL -treated embryos and adults differed significantly from controls, and L1 exerted toxic effects in embryos alone. ICL-670 significantly increased the mortality of embryos treated with doses of 0.25 mM or higher and also affected embryo morphology, causing curvature of larvae treated with concentrations above 0.5 mM. ICL-670 exposure (10 µL of 0.1 mM injection) also significantly increased the heart rate and cardiac output of adult zebrafish. While L1 exposure did not cause toxicity in adults, it did cause morphological defects in embryos at 0.5 mM. This study provides first evidence on iron chelator toxicity in early development and will help to guide our approach on better understanding the mechanism of iron chelator toxicity. PMID:25329065

  17. Steroid Receptor Coactivator-2 Is a Dual Regulator of Cardiac Transcription Factor Function*

    PubMed Central

    Reineke, Erin L.; Benham, Ashley; Soibam, Benjamin; Stashi, Erin; Taegtmeyer, Heinrich; Entman, Mark L.; Schwartz, Robert J.; O'Malley, Bert W.

    2014-01-01

    We have previously demonstrated the potential role of steroid receptor coactivator-2 (SRC-2) as a co-regulator in the transcription of critical molecules modulating cardiac function and metabolism in normal and stressed hearts. The present study seeks to extend the previous information by demonstrating SRC-2 fulfills this role by serving as a critical coactivator for the transcription and activity of critical transcription factors known to control cardiac growth and metabolism as well as in their downstream signaling. This knowledge broadens our understanding of the mechanism by which SRC-2 acts in normal and stressed hearts and allows further investigation of the transcriptional modifications mediating different types and degrees of cardiac stress. Moreover, the genetic manipulation of SRC-2 in this study is specific for the heart and thereby eliminating potential indirect effects of SRC-2 deletion in other organs. We have shown that SRC-2 is critical to transcriptional control modulated by MEF2, GATA-4, and Tbx5, thereby enhancing gene expression associated with cardiac growth. Additionally, we describe SRC-2 as a novel regulator of PPARα expression, thus controlling critical steps in metabolic gene expression. We conclude that through regulation of cardiac transcription factor expression and activity, SRC-2 is a critical transcriptional regulator of genes important for cardiac growth, structure, and metabolism, three of the main pathways altered during the cardiac stress response. PMID:24811170

  18. Steroid receptor coactivator-2 is a dual regulator of cardiac transcription factor function.

    PubMed

    Reineke, Erin L; Benham, Ashley; Soibam, Benjamin; Stashi, Erin; Taegtmeyer, Heinrich; Entman, Mark L; Schwartz, Robert J; O'Malley, Bert W

    2014-06-20

    We have previously demonstrated the potential role of steroid receptor coactivator-2 (SRC-2) as a co-regulator in the transcription of critical molecules modulating cardiac function and metabolism in normal and stressed hearts. The present study seeks to extend the previous information by demonstrating SRC-2 fulfills this role by serving as a critical coactivator for the transcription and activity of critical transcription factors known to control cardiac growth and metabolism as well as in their downstream signaling. This knowledge broadens our understanding of the mechanism by which SRC-2 acts in normal and stressed hearts and allows further investigation of the transcriptional modifications mediating different types and degrees of cardiac stress. Moreover, the genetic manipulation of SRC-2 in this study is specific for the heart and thereby eliminating potential indirect effects of SRC-2 deletion in other organs. We have shown that SRC-2 is critical to transcriptional control modulated by MEF2, GATA-4, and Tbx5, thereby enhancing gene expression associated with cardiac growth. Additionally, we describe SRC-2 as a novel regulator of PPARα expression, thus controlling critical steps in metabolic gene expression. We conclude that through regulation of cardiac transcription factor expression and activity, SRC-2 is a critical transcriptional regulator of genes important for cardiac growth, structure, and metabolism, three of the main pathways altered during the cardiac stress response. PMID:24811170

  19. Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism.

    PubMed

    Sassoon, Daniel J; Goodwill, Adam G; Noblet, Jillian N; Conteh, Abass M; Herring, B Paul; McClintick, Jeanette N; Tune, Johnathan D; Mather, Kieren J

    2016-07-01

    This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca(2+) binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion. PMID:27234258

  20. Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

    PubMed

    Cordes, Dietmar; Nandy, Rajesh R; Schafer, Scott; Wager, Tor D

    2014-04-01

    It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord areas are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac- and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal. PMID:24355483

  1. Hypoxia signaling controls postnatal changes in cardiac mitochondrial morphology and function.

    PubMed

    Neary, Marianne T; Ng, Keat-Eng; Ludtmann, Marthe H R; Hall, Andrew R; Piotrowska, Izabela; Ong, Sang-Bing; Hausenloy, Derek J; Mohun, Timothy J; Abramov, Andrey Y; Breckenridge, Ross A

    2014-09-01

    Fetal cardiomyocyte adaptation to low levels of oxygen in utero is incompletely understood, and is of interest as hypoxia tolerance is lost after birth, leading to vulnerability of adult cardiomyocytes. It is known that cardiac mitochondrial morphology, number and function change significantly following birth, although the underlying molecular mechanisms and physiological stimuli are undefined. Here we show that the decrease in cardiomyocyte HIF-signaling in cardiomyocytes immediately after birth acts as a physiological switch driving mitochondrial fusion and increased postnatal mitochondrial biogenesis. We also investigated mechanisms of ATP generation in embryonic cardiac mitochondria. We found that embryonic cardiac cardiomyocytes rely on both glycolysis and the tricarboxylic acid cycle to generate ATP, and that the balance between these two metabolic pathways in the heart is controlled around birth by the reduction in HIF signaling. We therefore propose that the increase in ambient oxygen encountered by the neonate at birth acts as a key physiological stimulus to cardiac mitochondrial adaptation.

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

    PubMed Central

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

    2009-01-01

    Normal cardiac function requires dynamic modulation of contraction. β1 adrenergic-induced protein kinase A (PKA) phosphorylation of cardiac myosin binding protein C (cMyBP-C) may regulate crossbridge kinetics to modulate contraction. We tested this idea with mechanical measurements and echocardiography in a mouse model lacking three PKA sites on cMyBP-C, i.e., cMyBP-C(t3SA). We developed the model by transgenic expression of mutant cMyBP-C with Ser to Ala mutations on the cMyBP-C knock-out (KO) 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, i.e., 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, i.e., stretch activation. The rate constants of relaxation, krel (s−1), and delayed force development, kdf (s−1), in the stretch activation response are indicators of crossbridge cycling kinetics. cMyBP-C(t3SA) myocardium had baseline krel and kdf similar to WT myocardium, but unlike WT, krel and kdf 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 echocardiagraphic 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

  3. 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

  4. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function.

    PubMed

    Sadhukhan, Sushabhan; Liu, Xiaojing; Ryu, Dongryeol; Nelson, Ornella D; Stupinski, John A; Li, Zhi; Chen, Wei; Zhang, Sheng; Weiss, Robert S; Locasale, Jason W; Auwerx, Johan; Lin, Hening

    2016-04-19

    Cellular metabolites, such as acyl-CoA, can modify proteins, leading to protein posttranslational modifications (PTMs). One such PTM is lysine succinylation, which is regulated by sirtuin 5 (SIRT5). Although numerous proteins are modified by lysine succinylation, the physiological significance of lysine succinylation and SIRT5 remains elusive. Here, by profiling acyl-CoA molecules in various mouse tissues, we have discovered that different tissues have different acyl-CoA profiles and that succinyl-CoA is the most abundant acyl-CoA molecule in the heart. This interesting observation has prompted us to examine protein lysine succinylation in different mouse tissues in the presence and absence of SIRT5. Protein lysine succinylation predominantly accumulates in the heart whenSirt5is deleted. Using proteomic studies, we have identified many cardiac proteins regulated by SIRT5. Our data suggest that ECHA, a protein involved in fatty acid oxidation, is a major enzyme that is regulated by SIRT5 and affects heart function.Sirt5knockout (KO) mice have lower ECHA activity, increased long-chain acyl-CoAs, and decreased ATP in the heart under fasting conditions.Sirt5KO mice develop hypertrophic cardiomyopathy, as evident from the increased heart weight relative to body weight, as well as reduced shortening and ejection fractions. These findings establish that regulating heart metabolism and function is a major physiological function of lysine succinylation and SIRT5. PMID:27051063

  5. Measurement of cardiac function using pressure–volume conductance catheter technique in mice and rats

    PubMed Central

    Pacher, Pál; Nagayama, Takahiro; Mukhopadhyay, Partha; Bátkai, Sándor; Kass, David A

    2008-01-01

    Ventricular pressure–volume relationships have become well established as the most rigorous and comprehensive ways to assess intact heart function. Thanks to advances in miniature sensor technology, this approach has been successfully translated to small rodents, allowing for detailed characterization of cardiovascular function in genetically engineered mice, testing effects of pharmacotherapies and studying disease conditions. This method is unique for providing measures of left ventricular (LV) performance that are more specific to the heart and less affected by vascular loading conditions. Here we present descriptions and movies for procedures employing this method (anesthesia, intubation and surgical techniques, calibrations). We also provide examples of hemodynamics measurements obtained from normal mice/rats, and from animals with cardiac hypertrophy/heart failure, and describe values for various useful load-dependent and load-independent indexes of LV function obtained using different types of anesthesia. The completion of the protocol takes 1–4 h (depending on the experimental design/end points). PMID:18772869

  6. Tetradecylthioacetic acid increases fat metabolism and improves cardiac function in experimental heart failure.

    PubMed

    Øie, Erik; Berge, Rolf K; Ueland, Thor; Dahl, Christen P; Edvardsen, Thor; Beitnes, Jan Otto; Bohov, Pavol; Aukrust, Pål; Yndestad, Arne

    2013-02-01

    Changes in myocardial metabolism, including a shift from fatty acid to glucose utilization and changes in fatty acid availability and composition are characteristics of heart failure development. Tetradecylthioacetic acid (TTA) is a fatty acid analogue lacking the ability to undergo mitochondrial β-oxidation. TTA promotes hepatic proliferation of mitochondria and peroxisomes and also decreases serum triglycerides and cholesterol in animals. We investigated the effect of TTA, in combination with a high-fat or regular diet, in a rat model of post-myocardial infarction heart failure. TTA had a beneficial effect on cardiac function in post-myocardial infarction heart failure without affecting myocardial remodeling. These effects of TTA on myocardial function were accompanied by decreased free fatty acids in plasma, increased myocardial proportion of n-3 polyunsaturated fatty acids (PUFA) and a decreased proportion of n-6 PUFA. Myocardial enzyme gene expression during TTA treatment suggested that the increase in n-3 PUFA could reflect increased n-3 PUFA synthesis and inadequately increased n-3 PUFA β-oxidation. Based on our data, it is unlikely that the changes are secondary to alterations in other tissues as plasma and liver showed an opposite pattern with decreased n-3 PUFA during TTA treatment. The present study suggests that TTA may improve myocardial function in heart failure, potentially involving its ability to decrease the availability of FFA and increase the myocardial proportion of n-3 PUFA. PMID:23266898

  7. 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…

  8. Cardiac Structure and Function in Weight Trainers Runners, and Runner/Weight Trainers.

    ERIC Educational Resources Information Center

    Elias, Barbara A.; And Others

    1991-01-01

    Study compared cardiac structure and function in adult male weight trainers, runners, and those who did both. Results indicate men who run or weight train and run have similar heart structural and functional characteristics and greater relative internal diameter and left ventricular wall thickness than men who only weight train. (SM)

  9. The genetic basis of cardiac function: dissection by zebrafish (Danio rerio) screens.

    PubMed Central

    Warren, K S; Wu, J C; Pinet, F; Fishman, M C

    2000-01-01

    The vertebrate heart differs from chordate ancestors both structurally and functionally. Genetic units of form, termed 'modules', are identifiable by mutation, both in zebrafish and mouse, and correspond to features recently acquired in evolution, such as the ventricular chamber or endothelial lining of the vessels and heart. Zebrafish (Danio rerio) genetic screens have provided a reasonably inclusive set of such genes. Normal cardiac function may also be disrupted by single-gene mutations in zebrafish. Individual mutations may perturb contractility or rhythm generation. The zebrafish mutations which principally disturb cardiac contractility fall into two broad phenotypic categories, 'dilated' and 'hypertrophic'. Interestingly, these correspond to the two primary types of heart failure in humans. These disorders of early cardiac function provide candidate genes to be examined in complex human heart diseases, including arrhythmias and heart failure. PMID:11128987

  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. Gravity Reception and Cardiac Function in the Spider

    NASA Technical Reports Server (NTRS)

    Finck, A.

    1985-01-01

    The following features of the arachnid gravity system were studied. (1) the absolute threshold to hyper-gz is quite low indicating fine proprioreceptive properties of the lyriform organ, the Gz/vibration detector; (2) the neurogenic heart of the spider is a good dependent variable for assessing its behavior to Gz and other stimuli which produce mechanical effects on the exoskeleton; (3) Not only is the cardiac response useful but it is now understood to be an integral part of the system which compensates for the consequences of gravity in the spider (an hydraulic leg extension); and (4) a theoretical model was proposed in which a mechanical amplifier, the leg lever, converts a weak force (at the tarsus) to a strong force (at the patella), capable of compressing the exoskeleton and consequently the lyriform receptor.

  12. Effect of dispersed crude oil on cardiac function in seabass Dicentrarchus labrax.

    PubMed

    Tissier, Florine; Dussauze, Matthieu; Lefloch, Nina; Theron, Michael; Lemaire, Philippe; Le Floch, Stéphane; Pichavant-Rafini, Karine

    2015-09-01

    In this study, the impact of dispersed oil was assessed in Dicentrarchus labrax, a fish frequently used as an oil contamination indicator species. Fish were exposed for 48h to (mechanically and chemically) dispersed oil and dispersant alone. The impact of these exposure conditions was assessed on cardiac function by measuring (i) the contraction strength, the contraction and the relaxation speeds (ii) the cardiac energy metabolism using respirometry on permeabilized cardiac fibers. Compared to control, the increase of polycyclic aromatic metabolites observed in the bile indicated oil contamination in our fish. Following 48h of oil exposure at realistic oil concentrations, alterations of cardiac performances were observed. A decrease in contraction strength, contraction and relaxation speeds was observed in the presence of oil without effect of dispersant on these three parameters. Looking at cardiac energy metabolism, dispersant alone decreases all the activity of the respiratory chain and increases the proton leak. From these results, it appears that the observed decrease in cardiac performance in fish exposed to oil was not linked to a decrease in energy availability. PMID:25950135

  13. Preserved recovery of cardiac function following ischemia-reperfusion in mice lacking SIRT3.

    PubMed

    Koentges, Christoph; Pfeil, Katharina; Meyer-Steenbuck, Maximilian; Lother, Achim; Hoffmann, Michael M; Odening, Katja E; Hein, Lutz; Bode, Christoph; Bugger, Heiko

    2016-01-01

    Lack of the mitochondrial deacetylase sirtuin 3 (SIRT3) impairs mitochondrial function and increases the susceptibility to induction of the mitochondrial permeability transition pore. Because these alterations contribute to myocardial ischemia-reperfusion (IR) injury, we hypothesized that SIRT3 deficiency may increase cardiac injury following myocardial IR. Hearts of 10-week-old mice were perfused in the isolated working mode and subjected to 17.5 min of global no-flow ischemia, followed by 30 min of reperfusion. Measurements before ischemia revealed a decrease in cardiac power (-20%) and rate pressure product (-15%) in SIRT3(-/-) mice. Mitochondrial state 3 respiration (-15%), ATP synthesis (-39%), and ATP/O ratios (-29%) were decreased in hearts of SIRT3(-/-) mice. However, percent recovery of cardiac power (WT 94% ± 9%; SIRT3(-/-) 89% ± 9%) and rate pressure product (WT 89% ± 16%; SIRT3(-/-) 96% ± 3%) following IR was similar in both groups. Myocardial infarct size was not increased in SIRT3(-/-) mice following permanent ligation of the left anterior descending coronary artery (LAD). Left ventricular pressure and dP/dtmax, and mitochondrial respiration and ATP synthesis were not different between groups following LAD ligation. Thus, despite pre-existing defects in cardiac function and mitochondrial respiratory capacity in SIRT3(-/-) mice, SIRT3 deficiency does not additionally impair cardiac function following IR or following myocardial infarction.

  14. Spatial Variation and Resuscitation Process Affecting Survival after Out-of-Hospital Cardiac Arrests (OHCA)

    PubMed Central

    Chen, Chien-Chou; Chen, Chao-Wen; Ho, Chi-Kung; Liu, I-Chuan; Lin, Bo-Cheng; Chan, Ta-Chien

    2015-01-01

    Background Ambulance response times and resuscitation efforts are critical predictors of the survival rate after out-of-hospital cardiac arrests (OHCA). On the other hand, rural-urban differences in the OHCA survival rates are an important public health issue. Methods We retrospectively reviewed the January 2011–December 2013 OHCA registry data of Kaohsiung City, Taiwan. With particular focus on geospatial variables, we aimed to unveil risk factors predicting the overall OHCA survival until hospital admission. Spatial analysis, network analysis, and the Kriging method by using geographic information systems were applied to analyze spatial variations and calculate the transport distance. Logistic regression was used to identify the risk factors for OHCA survival. Results Among the 4,957 patients, the overall OHCA survival to hospital admission was 16.5%. In the multivariate analysis, female sex (adjusted odds ratio:, AOR, 1.24 [1.06–1.45]), events in public areas (AOR: 1.30 [1.05–1.61]), exposure to automated external defibrillator (AED) shock (AOR: 1.70 [1.30–2.23]), use of laryngeal mask airway (LMA) (AOR: 1.35 [1.16–1.58]), non-trauma patients (AOR: 1.41 [1.04–1.90]), ambulance bypassed the closest hospital (AOR: 1.28 [1.07–1.53]), and OHCA within the high population density areas (AOR: 1.89 [1.55–2.32]) were positively associated with improved OHCA survival. By contrast, a prolonged total emergency medical services (EMS) time interval was negatively associated with OHCA survival (AOR: 0.98 [0.96–0.99]). Conclusions Resuscitative efforts, such as AED or LMA use, and a short total EMS time interval improved OHCA outcomes in emergency departments. The spatial heterogeneity of emergency medical resources between rural and urban areas might affect survival rate. PMID:26659851

  15. The Circadian Clock Maintains Cardiac Function by Regulating Mitochondrial Metabolism in Mice

    PubMed Central

    Kohsaka, Akira; Das, Partha; Hashimoto, Izumi; Nakao, Tomomi; Deguchi, Yoko; Gouraud, Sabine S.; Waki, Hidefumi; Muragaki, Yasuteru; Maeda, Masanobu

    2014-01-01

    Cardiac function is highly dependent on oxidative energy, which is produced by mitochondrial respiration. Defects in mitochondrial function are associated with both structural and functional abnormalities in the heart. Here, we show that heart-specific ablation of the circadian clock gene Bmal1 results in cardiac mitochondrial defects that include morphological changes and functional abnormalities, such as reduced enzymatic activities within the respiratory complex. Mice without cardiac Bmal1 function show a significant decrease in the expression of genes associated with the fatty acid oxidative pathway, the tricarboxylic acid cycle, and the mitochondrial respiratory chain in the heart and develop severe progressive heart failure with age. Importantly, similar changes in gene expression related to mitochondrial oxidative metabolism are also observed in C57BL/6J mice subjected to chronic reversal of the light-dark cycle; thus, they show disrupted circadian rhythmicity. These findings indicate that the circadian clock system plays an important role in regulating mitochondrial metabolism and thereby maintains cardiac function. PMID:25389966

  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. 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.

  18. Post-translational modification of cardiac proteasomes: functional delineation enabled by proteomics

    PubMed Central

    Scruggs, Sarah B.; Zong, Nobel C.; Wang, Ding; Stefani, Enrico

    2012-01-01

    Proteasomes are ubiquitously expressed multicatalytic complexes that serve as key regulators of protein homeostasis. There are several lines of evidence indicating that proteasomes exist in heterogeneous subpopulations in cardiac muscle, differentiated, in part, by post-translational modifications (PTMs). PTMs regulate numerous facets of proteasome function, including catalytic activities, complex assembly, interactions with associating partners, subcellular localization, substrate preference, and complex turnover. Classical technologies used to identify PTMs on proteasomes have lacked the ability to determine site specificity, quantify stoichiometry, and perform large-scale, multi-PTM analysis. Recent advancements in proteomic technologies have largely overcome these limitations. We present here a discussion on the importance of PTMs in modulating proteasome function in cardiac physiology and pathophysiology, followed by the presentation of a state-of-the-art proteomic workflow for identifying and quantifying PTMs of cardiac proteasomes. PMID:22523251

  19. 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.

  20. 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.

  1. Functional and structural impact of pirfenidone on the alterations of cardiac disease and diabetes mellitus.

    PubMed

    Avila, Guillermo; Osornio-Garduño, Diana Stephanie; Ríos-Pérez, Erick Benjamín; Ramos-Mondragón, Roberto

    2014-11-01

    A synthetic compound, termed pirfenidone (PFD), is considered promising for the treatment of cardiac disease. It leads to beneficial effects in animal models of diabetes mellitus (DM); as well as in heart attack, atrial fibrillation, muscular dystrophy, and diabetic cardiomyopathy (DC). The latter is a result of alterations linked to metabolic syndrome as they promote cardiac hypertrophy, fibrosis and contractile dysfunction. Although reduced level of fibrosis and stiffness represent an essential step in the mechanism of PFD action, a wide range of functional effects might also contribute to the therapeutic benefits. For example, PFD stimulates L-type voltage-gated Ca(2+) channels (LTCCs), which are pivotal for a process known as excitation-contraction coupling (ECC). Recent evidence suggests that these two types of actions - namely structural and functional - aid in treating both cardiac disease and DM. This view is supported by the fact that in DC, for example, systolic dysfunction arises from both cardiac stiffness linked to fibrosis and down-regulation of ECC. Thus, not surprisingly, clinical trials have been conducted with PFD in the settings of DM, for treating not only cardiac but also renal disease. This review presents all these concepts, along with the possible mechanisms and pathophysiological consequences.

  2. Attenuated muscle metaboreflex-induced increases in cardiac function in hypertension.

    PubMed

    Sala-Mercado, Javier A; Spranger, Marty D; Abu-Hamdah, Rania; Kaur, Jasdeep; Coutsos, Matthew; Stayer, Douglas; Augustyniak, Robert A; O'Leary, Donal S

    2013-11-15

    Sympathoactivation may be excessive during exercise in subjects with hypertension, leading to increased susceptibility to adverse cardiovascular events, including arrhythmias, infarction, stroke, and sudden cardiac death. The muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting marked increases in sympathetic activity during exercise. We used conscious, chronically instrumented dogs trained to run on a motor-driven treadmill to investigate the effects of hypertension on the mechanisms of the muscle metaboreflex. Experiments were performed before and 30.9 ± 4.2 days after induction of hypertension, which was induced via partial, unilateral renal artery occlusion. After induction of hypertension, resting mean arterial pressure was significantly elevated from 98.2 ± 2.6 to 141.9 ± 7.4 mmHg. The hypertension was caused by elevated total peripheral resistance. Although cardiac output was not significantly different at rest or during exercise after induction of hypertension, the rise in cardiac output with muscle metaboreflex activation was significantly reduced in hypertension. Metaboreflex-induced increases in left ventricular function were also depressed. These attenuated cardiac responses caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude that the ability of the muscle metaboreflex to elicit increases in cardiac function is impaired in hypertension, which may contribute to exercise intolerance.

  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.

  4. 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.

  5. 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

  6. Overexpressing superoxide dismutase 2 induces a supernormal cardiac function by enhancing redox-dependent mitochondrial function and metabolic dilation.

    PubMed

    Kang, Patrick T; Chen, Chwen-Lih; Ohanyan, Vahagn; Luther, Daniel J; Meszaros, J Gary; Chilian, William M; Chen, Yeong-Renn

    2015-11-01

    During heightened cardiac work, O2 consumption by the heart benefits energy production via mitochondria. However, some electrons leak from the respiratory chain and yield superoxide, which is rapidly metabolized into H2O2 by SOD2. To understand the systemic effects of the metabolic dilator, H2O2, we studied mice with cardiac-specific SOD2 overexpression (SOD2-tg), which increases the H2O2 produced by cardiac mitochondria. Contrast echocardiography was employed to evaluate cardiac function, indicating that SOD2-tg had a significantly greater ejection fraction and a lower mean arterial pressure (MAP) that was partially normalized by intravenous injection of catalase. Norepinephrine-mediated myocardial blood flow (MBF) was significantly enhanced in SOD2-tg mice. Coupling of MBF to the double product (Heart Rate×MAP) was increased in SOD2-tg mice, indicating that the metabolic dilator, "spilled" over, inducing systemic vasodilation. The hypothesis that SOD2 overexpression effectively enhances mitochondrial function was further evaluated. Mitochondria of SOD2-tg mice had a decreased state 3 oxygen consumption rate, but maintained the same ATP production flux under the basal and L-NAME treatment conditions, indicating a higher bioenergetic efficiency. SOD2-tg mitochondria produced less superoxide, and had lower redox activity in converting cyclic hydroxylamine to stable nitroxide, and a lower GSSG concentration. EPR analysis of the isolated mitochondria showed a significant decrease in semiquinones at the SOD2-tg Qi site. These results support a more reductive physiological setting in the SOD2-tg murine heart. Cardiac mitochondria exhibited no significant differences in the respiratory control index between WT and SOD2-tg. We conclude that SOD2 overexpression in myocytes enhances mitochondrial function and metabolic vasodilation, leading to a phenotype of supernormal cardiac function.

  7. Redox Control of Cardiac Excitability

    PubMed Central

    Aggarwal, Nitin T.

    2013-01-01

    Abstract Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation. Antioxid. Redox Signal. 18, 432–468. PMID:22897788

  8. 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

  9. 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

  10. Inspiratory Muscle Training and Functional Capacity in Patients Undergoing Cardiac Surgery

    PubMed Central

    Cordeiro, André Luiz Lisboa; de Melo, Thiago Araújo; Neves, Daniela; Luna, Julianne; Esquivel, Mateus Souza; Guimarães, André Raimundo França; Borges, Daniel Lago; Petto, Jefferson

    2016-01-01

    Introduction Cardiac surgery is a highly complex procedure which generates worsening of lung function and decreased inspiratory muscle strength. The inspiratory muscle training becomes effective for muscle strengthening and can improve functional capacity. Objective To investigate the effect of inspiratory muscle training on functional capacity submaximal and inspiratory muscle strength in patients undergoing cardiac surgery. Methods This is a clinical randomized controlled trial with patients undergoing cardiac surgery at Instituto Nobre de Cardiologia. Patients were divided into two groups: control group and training. Preoperatively, were assessed the maximum inspiratory pressure and the distance covered in a 6-minute walk test. From the third postoperative day, the control group was managed according to the routine of the unit while the training group underwent daily protocol of respiratory muscle training until the day of discharge. Results 50 patients, 27 (54%) males were included, with a mean age of 56.7±13.9 years. After the analysis, the training group had significant increase in maximum inspiratory pressure (69.5±14.9 vs. 83.1±19.1 cmH2O, P=0.0073) and 6-minute walk test (422.4±102.8 vs. 502.4±112.8 m, P=0.0031). Conclusion We conclude that inspiratory muscle training was effective in improving functional capacity submaximal and inspiratory muscle strength in this sample of patients undergoing cardiac surgery. PMID:27556313

  11. 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…

  12. 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,…

  13. 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.

  14. GRK2 – A Link Between Myocardial Contractile Function and Cardiac Metabolism

    PubMed Central

    Woodall, Meryl C.; Ciccarelli, Michele; Woodall, Benjamin P.; Koch, Walter J.

    2014-01-01

    Heart failure (HF) causes a tremendous burden on the worldwide healthcare system, affecting more than 23 million people. There are many cardiovascular disorders that contribute to the development of HF and multiple risk factors that accelerate its occurrence, but regardless of its underlying cause, HF is characterized by a marked decrease in myocardial contractility and loss of pump function. One biomarker molecule consistently shown to be upregulated in human HF and several animal models is G protein-coupled receptor (GPCR) kinase 2 (GRK2), a kinase originally discovered to be involved in GPCR desensitization, especially β-adrenergic receptors (βARs). Indeed, higher levels of GRK2 can impair βAR-mediated inotropic reserve and its inhibition or molecular reduction has shown to improve pump function in several animal models including a pre-clinical pig model of HF. Recently, non-classical roles for GRK2 in cardiovascular disease have been described, including negative regulation of insulin signaling, a role in myocyte cell survival and apoptotic signaling, and it has been shown to be localized in/on mitochondria. These new roles of GRK2 suggest that GRK2 may be a nodal link in the myocyte, influencing both cardiac contractile function and cell metabolism and survival and contributing to HF independent of its canonical role on GPCR desensitization. In this review, classical and non-classical roles for GRK2 will be discussed, focusing on recently discovered roles for GRK2 in cardiomyocyte metabolism and the effects that these roles may have on myocardial contractile function and HF development. PMID:24812353

  15. Optimal hematologic variables for oxygen transport, including P50, hemoglobin cooperativity, hematocrit, acid-base status, and cardiac function.

    PubMed

    Winslow, R M

    1988-01-01

    The two important blood properties that affect O2 delivery are the O2 equilibrium curve (OEC) and blood viscosity with its subsequent effect on flow (cardiac output). To quantitate these properties blood OEC's were analyzed in terms of the Adair 4-step oxygenation model and the resulting parameters were used to construct a computer nomogram to reproduce the OEC at any combination of effectors that regulate P50 (pH, PCO2, and 2,3-DPG). In this way, the P50 could be changed systematically and the effects on overall O2 transport could be studied. Hematocrit-viscosity-cardiac output relationships were taken from the literature and validated using data from human subjects with various pathological states and high-altitude natives. A model was then developed, using the Bohr integration, to predict the O2 transport function of blood under a variety of conditions including exercise and hypoxia. The results indicate that the optimal hematocrit is about 43-45%, even in hypoxia. The optimal P50, however, depends on the availability of O2: a high P50 is not necessarily beneficial in hypoxia and high cardiac output states. This model and general approach should prove useful in the design of blood substitutes.

  16. 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.

  17. c-Myc Alters Substrate Utilization and O-GlcNAc Protein Posttranslational Modifications without Altering Cardiac Function during Early Aortic Constriction

    PubMed Central

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.

    2015-01-01

    Hypertrophic stimuli cause transcription of the proto-oncogene c-Myc (Myc). Prior work showed that myocardial knockout of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we assessed the interplay between Myc, substrate oxidation and cardiac function during early pressure overload hypertrophy. Mice with cardiac specific, inducible Myc knockout (MycKO-TAC) and non-transgenic littermates (Cont-TAC) were subjected to transverse aortic constriction (TAC; n = 7/group). Additional groups underwent sham surgery (Cont-Sham and MycKO-Sham, n = 5 per group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. In sham hearts, Myc knockout did not affect cardiac function or substrate preferences for the citric acid cycle. However, Myc knockout altered fractional contributions during TAC. The unlabeled fractional contribution increased in MycKO-TAC versus Cont-TAC, whereas ketone and free fatty acid fractional contributions decreased. Additionally, protein posttranslational modifications by O-GlcNAc were significantly greater in Cont-TAC versus both Cont-Sham and MycKO-TAC. In conclusion, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy, which may regulate Myc-induced metabolic changes. PMID:26266538

  18. 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

  19. The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery

    PubMed Central

    Bozhinovska, Marija; Taleska, Gordana; Fabian, Andrej; Šoštarič, Maja

    2016-01-01

    The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP) channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes. PMID:27703584

  20. 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

  1. Intramyocardial Delivery of Notch Ligand-Containing Hydrogels Improves Cardiac Function and Angiogenesis Following Infarction

    PubMed Central

    Boopathy, Archana V.; Martinez, Mario D.; Smith, Amanda Walker; Brown, Milton E.; García, Andrés J.

    2015-01-01

    Myocardial infarction (MI) is the leading cause of death worldwide. Notch1 signaling plays a critical role in cardiac development, in survival, cardiogenic lineage commitment, differentiation of cardiac stem/progenitor cells, and in regenerative responses following myocardial injury. The objective of this study was the evaluation of the therapeutic effect of delivering the Notch ligand-containing hydrogels in a rat model of MI. Self-assembling peptide (SAP) hydrogels were functionalized with a peptide mimic of the Notch1 ligand Jagged1 (RJ). In rats subjected to experimental MI, delivery of RJ-containing hydrogel to the infarcted heart resulted in improvement in cardiac function back to sham-operated levels. A significant decrease in fibrosis and an increase in the endothelial vessel area and Ki67 expression were also observed in rats treated with the RJ hydrogels compared to untreated rats or rats treated with unmodified or scrambled peptide hydrogels. This study demonstrates the functional benefit of Notch1-activating peptide delivered in SAP hydrogels for cardiac repair. PMID:25982380

  2. 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.

  3. 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.

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

    PubMed Central

    Kopp, Zachary A.; Hsieh, Jo-Lin; Li, Andrew; Wang, William; Bhatt, Dhelni T.; Lee, Angela; Kim, Sae Yeon; Fan, David; Shah, Veevek; Siddiqui, Emaad; Ragam, Radhika; Park, Kristen; Ardeshna, Dev; Park, Kunwoo; Wu, Rachel; Parikh, Hardik; Parikh, Ayush; Lin, Yuh-Ru; Park, Yongkyu

    2015-01-01

    Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment. PMID:26399365

  5. Cross talk between cardiac myocytes and fibroblasts: from multiscale investigative approaches to mechanisms and functional consequences

    PubMed Central

    Zhang, P.; Su, J.

    2012-01-01

    The heart is comprised of a syncytium of cardiac myocytes (CM) and surrounding nonmyocytes, the majority of which are cardiac fibroblasts (CF). CM and CF are highly interspersed in the myocardium with one CM being surrounded by one or more CF. Bidirectional cross talk between CM and CF plays important roles in determining cardiac mechanical and electrical function in both normal and diseased hearts. Genetically engineered animal models and in vitro studies have provided evidence that CM and CF can regulate each other's function. Their cross talk contributes to structural and electrical remodeling in both atria and ventricles and appears to be involved in the pathogenesis of various heart diseases that lead to heart failure and arrhythmia disorders. Mechanisms of CM-CF cross talk, which are not yet fully understood, include release of paracrine factors, direct cell-cell interactions via gap junctions and potentially adherens junctions and nanotubes, and cell interactions with the extracellular matrix. In this article, we provide an overview of the existing multiscale experimental and computational approaches for the investigation of cross talk between CM and CF and review recent progress in our understanding of the functional consequences and underlying mechanisms. Targeting cross talk between CM and CF could potentially be used therapeutically for the modulation of the cardiac remodeling response in the diseased heart and may lead to new strategies for the treatment of heart failure or rhythm disturbances. PMID:23064834

  6. 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.

  7. 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

  8. Environmentally persistent free radicals decrease cardiac function and increase pulmonary artery pressure

    PubMed Central

    Mahne, Sarah; Chuang, Gin C.; Pankey, Edward; Kiruri, Lucy; Kadowitz, Philip J.; Dellinger, Barry

    2012-01-01

    Epidemiological studies have consistently linked inhalation of particulate matter (PM) to increased cardiac morbidity and mortality, especially in at risk populations. However, few studies have examined the effect of PM on baseline cardiac function in otherwise healthy individuals. In addition, airborne PM contain environmentally persistent free radicals (EPFR) capable of redox cycling in biological systems. The purpose of this study was to determine whether nose-only inhalation of EPFRs (20 min/day for 7 days) could decrease baseline left ventricular function in healthy male Sprague-Dawley rats. The model EPFR tested was 1,2-dichlorobenzene chemisorbed to 0.2-μm-diameter silica/CuO particles at 230°C (DCB230). Inhalation of vehicle or silica particles served as controls. Twenty-four hours after the last exposure, rats were anesthetized (isoflurane) and ventilated (3 l/min), and left ventricular function was assessed using pressure-volume catheters. Compared with controls, inhalation of DCB230 significantly decreased baseline stroke volume, cardiac output, and stroke work. End-diastolic volume and end-diastolic pressure were also significantly reduced; however, ventricular contractility and relaxation were not changed. DCB230 also significantly increased pulmonary arterial pressure and produced hyperplasia in small pulmonary arteries. Plasma levels of C-reactive protein were significantly increased by exposure to DCB230, as were levels of heme oxygenase-1 and SOD2 in the left ventricle. Together, these data show that inhalation of EPFRs, but not silica particles, decreases baseline cardiac function in healthy rats by decreasing cardiac filling, secondary to increased pulmonary resistance. These EPFRs also produced systemic inflammation and increased oxidative stress markers in the left ventricle. PMID:22942180

  9. Effects of acute and chronic sunitinib treatment on cardiac function and calcium/calmodulin-dependent protein kinase II

    PubMed Central

    Mooney, L; Skinner, M; Coker, S J; Currie, S

    2015-01-01

    Background and Purpose Calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) is an important regulator of cardiac contractile function and dysfunction and may be an unwanted secondary target for anti-cancer drugs such as sunitinib and imatinib that have been reported to alter cardiac performance. This study aimed to determine whether anti-cancer kinase inhibitors may affect CaMKII activity and expression when administered in vivo. Experimental Approach Cardiovascular haemodynamics in response to acute and chronic sunitinib treatment, and chronic imatinib treatment, were assessed in guinea pigs and the effects compared with those of the known positive and negative inotropes, isoprenaline and verapamil. Parallel studies from the same animals assessed CaMKIIδ expression and CaMKII activity following drug treatments. Key Results Acute administration of sunitinib decreased left ventricular (LV) dP/dtmax. Acute administration of isoprenaline increased LVdP/dtmax dose-dependently, while LVdP/dtmax was decreased by verapamil. CaMKII activity was decreased by acute administration of sunitinib and was increased by acute administration of isoprenaline, and decreased by acute administration of verapamil. CaMKIIδ expression following all acute treatments remained unchanged. Chronic imatinib and sunitinib treatments did not alter fractional shortening; however, both CaMKIIδ expression and CaMKII activity were significantly increased. Chronic administration of isoprenaline and verapamil decreased LV fractional shortening with parallel increases in CaMKIIδ expression and CaMKII activity. Conclusions and Implications Chronic sunitinib and imatinib treatment increased CaMKIIδ expression and CaMKII activity. As these compounds are associated with cardiac dysfunction, increased CaMKII expression could be an early indication of cellular cardiotoxicity marking potential progression of cardiac contractile dysfunction. PMID:26040813

  10. Copper sulfate affects Nile tilapia (Oreochromis niloticus) cardiomyocytes structure and contractile function.

    PubMed

    de Andrade Waldemarin, Kátia Cristina; Alves, Rosiane Nascimento; Beletti, Marcelo Emílio; Rantin, Francisco Tadeu; Kalinin, Ana Lúcia

    2012-04-01

    Copper sulfate (CuSO(4))is an inorganic chemical product worldwide used as an algaecide and a fungicide in aquaculture and agriculture and being discharged into freshwater environments where it can affect the freshwater fauna, especially fishes. The impact of copper on fish cardiac function was analyzed in two groups of Nile tilapias, Oreochromis niloticus (control group and group exposed to 1 mg l(-1) of CuSO(4) for 96 h). Structural and ultra-structural changes were studied and related to perturbations of the inotropic and chronotropic responses of ventricle strips. Fish of Cu exposed group did not show significant alterations in the medium diameter and in the percentage of collagen in the cardiac myocytes when evaluated through the light microscope. However, the ultrastructural analysis revealed cellular swelling followed by mitochondrial swelling. The myofibrils did not show significant variations among groups. Force contraction was significantly decreased, and rates of time to tension increase (contraction) and decrease (relaxation) were significantly augmented after copper exposure. The results suggest that the copper sulfate impairs the oxidative mitochondrial function and consequently alters the cardiac performance of this species.

  11. 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

  12. 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

  13. 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

  14. Interparental relationship dynamics and cardiac vagal functioning in infancy.

    PubMed

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

    2010-12-01

    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 5 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

  15. 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

  16. Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.

    PubMed

    Ekholm, Eeva; Rantanen, Virpi; Syvänen, Kari; Jalonen, Jarmo; Antila, Kari; Salminen, Eeva

    2002-04-01

    The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.

  17. 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

  18. 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.

  19. Sexually dimorphic adaptation of cardiac function: roles of epoxyeicosatrienoic acid and peroxisome proliferator-activated receptors.

    PubMed

    Qin, Jun; Le, Yicong; Froogh, Ghezal; Kandhi, Sharath; Jiang, Houli; Luo, Meng; Sun, Dong; Huang, An

    2016-06-01

    Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET-mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and sEH-KO than WT mice. All hearts displayed a dose-dependent decrease in coronary resistance and increase in cardiac contractility, represented as developed tension in response to increases in preload. These responses were also significantly greater in females than males, and sEH-KO than WT 14,15-EEZE abolished the sex-induced (F vs. M) and transgenic model-dependent (KO vs. WT) differences in the cardiac contractility, confirming an EET-driven response. Compared with M-WT controls, F-WT hearts expressed downregulation of sEH, associated with increased EETs and reduced DHETs, a pattern comparable to that observed in sEH-KO hearts. Coincidentally, F-WT and sEH-KO hearts exhibited increased PPARα expression, but comparable expression of eNOS, PPARβ, and EET synthases. In conclusion, female-specific downregulation of sEH initiates an EET-dependent adaptation of cardiac function, characterized by increased coronary flow via reduction in vascular resistance, and promotion of cardiac contractility, a response that could be further intensified by PPARα.

  20. Thioredoxin-2 Inhibits Mitochondrial ROS Generation and ASK1 Activity to Maintain Cardiac Function

    PubMed Central

    Huang, Qunhua; Zhou, Huanjiao Jenny; Zhang, Haifeng; Huang, Yan; Hinojosa-Kirschenbaum, Ford; Fan, Peidong; Yao, Lina; Belardinelli, Luiz; Tellides, George; Giordano, Frank J.; Budas, Grant R.; Min, Wang

    2015-01-01

    Background Thioredoxin 2 (Trx2) is a key mitochondrial protein which regulates cellular redox and survival by suppressing mitochondrial ROS generation and by inhibiting apoptosis stress kinase-1 (ASK1)-dependent apoptotic signaling. To date, the role of the mitochondrial Trx2 system in heart failure pathogenesis has not been investigated. Methods and Results Western blot and histological analysis revealed that Trx2 protein expression levels were reduced in hearts from patients with dilated cardiomyopathy (DCM), with a concomitant increase in increased ASK1 phosphorylation/activity. Cardiac-specific Trx2 knockout mice (Trx2-cKO). Trx2-cKO mice develop spontaneous DCM at 1 month of age with increased heart size, reduced ventricular wall thickness, and a progressive decline in left ventricular (LV) contractile function, resulting in mortality due to heart failure by ~4 months of age. The progressive decline in cardiac function observed in Trx2-cKO mice was accompanied by disruption of mitochondrial ultrastructure, mitochondrial membrane depolarization, increased mitochondrial ROS generation and reduced ATP production, correlating with increased ASK1 signaling and increased cardiomyocyte apoptosis. Chronic administration of a highly selective ASK1 inhibitor improved cardiac phenotype and reduced maladaptive LV remodeling with significant reductions in oxidative stress, apoptosis, fibrosis and cardiac failure. Cellular data from Trx2-deficient cardiomyocytes demonstrated that ASK1 inhibition reduced apoptosis and reduced mitochondrial ROS generation. Conclusions Our data support an essential role for mitochondrial Trx2 in preserving cardiac function by suppressing mitochondrial ROS production and ASK1-dependent apoptosis. Inhibition of ASK1 represents a promising therapeutic strategy for the treatment of dilated cardiomyopathy and heart failure. PMID:25628390

  1. Mechanism of estrogen-mediated improvement in cardiac function after trauma-hemorrhage: p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels.

    PubMed

    Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Ya-Ching; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

    2008-10-01

    Both p38 mitogen-activated protein kinase (p38) activation and protein kinase B (Akt) activation have been reported to regulate glucose transport during myocardial I/R. An increase in cardiac glycogen levels prevents myocardial injury in the ischemic or stressed heart. Although studies have shown that 17"-estradiol (E2)-mediated improvement in cardiac function after trauma-hemorrhage is via p38 activation, it remains unknown whether p38/Akt plays any role in regulation of cardiac glycogen levels under these conditions. To study this, male rats underwent trauma-hemorrhage(mean blood pressure, x40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats (n=6 per group) were treated with vehicle, E2 (1 mg/kg body weight), the p38 inhibitor SB203580 (2 mg/kg body weight), or E2 and SB203580. Various parameters were measured at 2 h after resuscitation. One-way ANOVA and Tukey test were used for statistical analysis, and differences were considered significant at P<0.05. The depressed cardiac function after trauma-hemorrhage was restored by E2 treatment (P<0.05). Administration of E2 after trauma-hemorrhage also normalized the p38/Akt phosphorylation, which was associated with restoration of cardiac glycogen, glycogen synthase kinase 3"activation, glucose transporter 4 translocation, and increased hexokinase II levels (all parameters, P<0.05). Inhibition of the p38 pathway abolished the E2-induced restoration in above parameters after trauma-hemorrhage. These results suggest that p38-dependent normalization of cardiac Akt phosphorylation and glycogen levels plays an important role in E2-mediated restoration of cardiac function after trauma-hemorrhage.

  2. Iron overload, cardiac and other factors affecting pregnancy in thalassemia major.

    PubMed

    Tsironi, Maria; Karagiorga, Markissia; Aessopos, Athanasios

    2010-06-01

    The reproductive thalassemic population is growing older and doctors confront the challenge of the thalassemic pregnancy. Pregnancy is characterized by dynamic multiple system changes, resulting in increased basal oxygen consumption, changes in energy substrate use by different organs and increased susceptibility to oxidative stress, while homozygous transfusion-dependent beta-thalassemia (beta-thal) patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload. Pregnant thalassemic patients require significantly larger amount of total blood transfusion during pregnancy and iron overload increases the oxidative stress of pregnancy, while the risk for cardiovascular events, in a high cardiac output state, is augmented and chelation treatment is generally avoided due to the potential teratogenicity. Pregnancy in thalassemia major should be considered high risk, and be cared for by an expert team with special caution and sensitivity.

  3. 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

  4. Three-dimensional dynamic functional mapping of cardiac mechanics

    NASA Astrophysics Data System (ADS)

    Taratorin, Alexander M.; Sideman, Samuel; Beyar, R.

    1993-07-01

    The heart is an organ which functions by a periodic change of the three dimensional (3D) spatially distributed parameters; malfunctions of the heart's operating systems are manifested by changes of the spatio-temporal heart shape dynamics. This paper attempts to present a set of image analysis tools aimed at a thorough study of the left ventricular (LV) shape-function relationship based on Cine-CT data. Data processing methodologies aimed at analysis and interpretation of the dynamic 3D LV shape, thickening and motion are described. These include the computerized detection of the LV boundaries, dynamic reconstruction of 3D LV shape, the LV shape parameters and their spatio-temporal evolution. The procedures are demonstrated using Cine-CT images of the human LV is normal and pathological cases.

  5. 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.

  6. [Cardiac function and the skin microcirculation in acromegaly].

    PubMed

    Bach, R; Leicht, E; Langer, H J; Hartenstein, R; Jung, F; Berg, G; Schätzer-Klotz, D; Bonaventura, K; Schieffer, H; Weinges, K F

    1992-03-27

    The microcirculation was measured by nail-fold capillary video microscopy in 21 patients (12 men, 9 women; mean age 54.7 [29-74] years) with acromegaly. Levels of growth hormone (12.0-71.7 microU/ml) and of somatomedin C (2.4-10.5 IU/ml) were elevated in 10 patients, despite preceding treatment. Eleven patients had an increase in myocardial thickness and nine had impairment of left ventricular function, although only slight in most. Left ventricular hypertrophy was demonstrable even in the absence of hypertension. No patient had evidence of coronary heart disease. Nail-fold capillary video microscopy (capillary density, torque index, reactive hyperaemia, epidermal blood flow) failed to distinguish between successfully treated patients and those with persistently elevated growth hormone concentrations or disease duration of over 5 years. There was no evidence of inadequate capillary blood flow as a cause of abnormal function in hypertrophied organs.

  7. 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

  8. Subject specific BOLD fMRI respiratory and cardiac response functions obtained from global signal.

    PubMed

    Falahpour, Maryam; Refai, Hazem; Bodurka, Jerzy

    2013-05-15

    Subtle changes in either breathing pattern or cardiac pulse rate alter blood oxygen level dependent functional magnetic resonance imaging signal (BOLD fMRI). This is problematic because such fluctuations could possibly not be related to underlying neuronal activations of interest but instead the source of physiological noise. Several methods have been proposed to eliminate physiological noise in BOLD fMRI data. One such method is to derive a template based on average multi-subject data for respiratory response function (RRF) and cardiac response function (CRF) by simultaneously utilizing an external recording of cardiac and respiratory waveforms with the fMRI. Standard templates can then be used to model, map, and remove respiration and cardiac fluctuations from fMRI data. Utilizing these does not, however, account for intra-subject variations in physiological response. Thus, performing a more individualized approach for single subject physiological noise correction becomes more desirable, especially for clinical purposes. Here we propose a novel approach that employs subject-specific RRF and CRF response functions obtained from the whole brain or brain tissue-specific global signals (GS). Averaging multiple voxels in global signal computation ensures physiological noise dominance over thermal and system noise in even high-spatial-resolution fMRI data, making the GS suitable for deriving robust estimations of both RRF and CRF for individual subjects. Using these individualized response functions instead of standard templates based on multi-subject averages judiciously removes physiological noise from the data, assuming that there is minimal neuronal contribution in the derived individualized filters. Subject-specific physiological response functions obtained from the GS better maps individuals' physiological characteristics.

  9. Preserved endothelium-dependent dilatation of the coronary microvasculature at the early phase of diabetes mellitus despite the increased oxidative stress and depressed cardiac mechanical function ex vivo

    PubMed Central

    2013-01-01

    Background There has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved. Materials and methods Zucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated. Results Zucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels. Conclusions The presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart. PMID

  10. Value of postoperative assessment of cardiac allograft function by transesophageal echocardiography.

    PubMed

    Kaye, D M; Bergin, P; Buckland, M; Esmore, D

    1994-01-01

    Heart transplantation now provides an acceptable therapy for patients with severe end-stage heart disease. Although patient outcome has significantly improved both early and late after heart transplantation, early morbidity and mortality continues to affect overall survival and may be unpredictable. In an attempt to identify factors that may assist in predicting early outcome after orthotopic heart transplantation, we assessed allograft function in 16 patients in the immediate postoperative period, 30 minutes after weaning from cardiopulmonary bypass by measuring the fractional shortening of the left ventricle with transesophageal echocardiography. In addition, standard hemodynamic indexes of allograft function (arterial blood pressure, pulmonary capillary wedge pressure, mean pulmonary artery pressure, and cardiac output) were obtained at this early time point. Early outcome was assessed by the duration and peak dose of inotrope support required after transplantation, requirement for mechanical support, and the duration of stay in the intensive care unit. Left ventricular fractional shortening 30 minutes after cardiopulmonary bypass was significantly lower in those patients requiring inotropic support (28.4% +/- 4.6% versus 43.7% +/- 3.5%, p < 0.05), whereas hemodynamic variables failed to distinguish these groups. In those patients requiring inotropes, there was a significant negative correlation of fractional shortening with the peak dose (r = -0.87, p < 0.01) and the duration of inotropic support (r = -0.62, p < 0.05). The total ischemic time of the allograft (206 +/- 22 minutes, range 77 to 359) did not correlate with the subsequent fractional shortening, but patients requiring inotrope support after the operation had significantly longer ischemic times (259 +/- 22 versus 138 +/- 22 minutes, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  11. [THE ENERGY FUNCTION OF RAT CARDIAC MITOCHONDRIA UNDER ARTIFICIAL HYPOBIOSIS].

    PubMed

    Melnytchuk, S D; Khyzhnyak, S V; Morozova, V S; Stepanova, L I; Umanskaya, A A; Voitsitsky, V M

    2015-01-01

    We investigated the energy activity of mitochondria from rat cardiomyocytes under the artificial carbon dioxide hypobiosis, which led to physiological changes in the organism (the decrease of body temperature, the reduction of heart rate, etc.). The respiratory and phosphorylation activities in mitochondria of cardiomyocytes is reduced when using two oxidation substrates (succinate and malate), which characterize the rate of the oxygen consumption by the mitochondria. The partial uncoupling of the oxidation and phosphorylation processes when using the malate unlike succinate was established. The activity of NADH-KoQ-oxidoreductase (complex I of the respiratory chain) is inhibited, but the activities of succinate dehydrogenase and cytochrome oxidase don't change. Probably, the priority of the succinate use under the artificial hypobiosis provides the support of the mitochondria functional activity on a sufficient energy level. It is evidenced by the ATP-synthetase activity. The modifications of the structural and functional state of the inner mitochondria membrane of the cardiomyocytes are directed to the adaptation under the artificial carbon dioxide hypobiosis. PMID:26387156

  12. Benefit Finding in Cardiac Patients: Relationships with Emotional Well-Being and Resources after Controlling for Physical Functional Impairment.

    PubMed

    Sanjuán, Pilar; García-Zamora, Cristina; Ruiz, M Ángeles; Rueda, Beatriz; Arranz, Henar; Castro, Almudena

    2016-01-01

    Benefit finding (BF) is defined as the individual's perception of positive change as a result of coping with an adverse life event. The beneficial effects of BF on well-being could be because BF favors the improvement of resources like self-efficacy, social support and effective coping. The main objective of this longitudinal 8 week study was to explore, in a sample of cardiac patients (n = 51), the combined contribution of BF and these resources to the positive affect. Moreover, we wanted to check whether these resources were derived from BF or, on the contrary, these resources were antecedents of BF. Results showed that after controlling for functional capacity, only effective coping could predict the positive affect at Time 1 (β = .32, p < .05), while the BF predicted it at Time 2 (β = .23, p < .001). Only social support predicted BF (β = .26, p < .05), but not the opposite. We discussed the desirability of promoting these processes to improve the emotional state of cardiac patients. PMID:27641065

  13. 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-stimulation.

  14. 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

  15. Effect of monomeric adiponectin on cardiac function and perfusion in anesthetized pig.

    PubMed

    Grossini, Elena; Prodam, Flavia; Walker, Gillian Elisabeth; Sigaudo, Lorenzo; Farruggio, Serena; Bellofatto, Kevin; Marotta, Patrizia; Molinari, Claudio; Mary, David; Bona, Gianni; Vacca, Giovanni

    2014-07-01

    Adiponectin, the most abundant adipokine released by adipose tissue, appears to play an important role in the regulation of vascular endothelial and cardiac function. To date, however, the physiological effects of human monomeric adiponectin on the coronary vasculature and myocardial systo-diastolic function, as well as on parasympathetic/sympathetic involvement and nitric oxide (NO) release, have not yet been investigated. Thus, we planned to determine the primary in vivo effects of human monomeric adiponectin on coronary blood flow and cardiac contractility/relaxation and the related role of autonomic nervous system, adiponectin receptors, and NO. In 30 anesthetized pigs, human monomeric adiponectin was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure, and the effects on coronary blood flow, left ventricular systo-diastolic function, myocardial oxygen metabolism, and NO release were examined. The mechanisms of the observed hemodynamic responses were also analyzed by repeating the highest dose of human monomeric adiponectin infusion after autonomic nervous system and NO blockade, and after specific adiponectin 1 receptor antagonist administration. Intracoronary human monomeric adiponectin caused dose-related increases of coronary blood flow and cardiac function. Those effects were accompanied by increased coronary NO release and coronary adiponectin levels. Moreover, the vascular effects of the peptide were prevented by blockade of β2-adrenoceptors and NO synthase, whereas all effects of human monomeric adiponectin were prevented by adiponectin 1 receptor inhibitor. In conclusion, human monomeric adiponectin primarily increased coronary blood flow and cardiac systo-diastolic function through the involvement of specific receptors, β2-adrenoceptors, and NO release.

  16. Altered right ventricular contractile pattern after cardiac surgery: monitoring of septal function is essential.

    PubMed

    Nguyen, Tin; Cao, Long; Movahed, Assad

    2014-10-01

    Assessment of right ventricular (RV) function is important in the management of various forms of cardiovascular disease. Accurately assessing RV volume and systolic function is a challenge in day-to-day clinical practice due to its complex geometry. Tricuspid annular plane systolic excursion (TAPSE) and systolic excursion velocity (S') have been reviewed to further assess their suitability and objectivity in evaluating RV function. Multiple studies have validated their diagnostic and prognostic values in numerous pathologic conditions. Diminished longitudinal contraction after cardiothoracic surgery is a well-known phenomenon, but it is not well validated. Despite significant reduction in RV performance along the long-axis assessed by TAPSE and S' after cardiac surgery, RV ejection fractions did not change as well as the left ventricular parameters and exercise capacity. RV contractile patterns were markedly altered with decreased longitudinal shortening and increased transverse shortening, which are likely resulted from the septal damage during cardiac surgery. The septum is essential for RV performance due to its oblique fiber orientation. This allows ventricular twisting, which is a vital mechanism against increased pulmonary vascular resistance. The septum function along with TAPSE and S' should be adequately assessed during cardiac surgery, and evidence of septal dysfunction should lead to reevaluation of myocardial protection methods. PMID:24919944

  17. 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.

  18. 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.

  19. Altered right ventricular contractile pattern after cardiac surgery: monitoring of septal function is essential.

    PubMed

    Nguyen, Tin; Cao, Long; Movahed, Assad

    2014-10-01

    Assessment of right ventricular (RV) function is important in the management of various forms of cardiovascular disease. Accurately assessing RV volume and systolic function is a challenge in day-to-day clinical practice due to its complex geometry. Tricuspid annular plane systolic excursion (TAPSE) and systolic excursion velocity (S') have been reviewed to further assess their suitability and objectivity in evaluating RV function. Multiple studies have validated their diagnostic and prognostic values in numerous pathologic conditions. Diminished longitudinal contraction after cardiothoracic surgery is a well-known phenomenon, but it is not well validated. Despite significant reduction in RV performance along the long-axis assessed by TAPSE and S' after cardiac surgery, RV ejection fractions did not change as well as the left ventricular parameters and exercise capacity. RV contractile patterns were markedly altered with decreased longitudinal shortening and increased transverse shortening, which are likely resulted from the septal damage during cardiac surgery. The septum is essential for RV performance due to its oblique fiber orientation. This allows ventricular twisting, which is a vital mechanism against increased pulmonary vascular resistance. The septum function along with TAPSE and S' should be adequately assessed during cardiac surgery, and evidence of septal dysfunction should lead to reevaluation of myocardial protection methods.

  20. 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.

  1. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    SciTech Connect

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.

  2. c-Myc alters substrate utilization and O-GlcNAc protein posttranslational modifications without altering cardiac function during early aortic constriction

    DOE PAGES

    Ledee, Dolena; Smith, Lincoln; Bruce, Margaret; Kajimoto, Masaki; Isern, Nancy; Portman, Michael A.; Olson, Aaron K.; Bertrand, Luc

    2015-08-12

    Pressure overload cardiac hypertrophy alters substrate metabolism. Prior work showed that myocardial inactivation of c-Myc (Myc) attenuated hypertrophy and decreased expression of metabolic genes after aortic constriction. Accordingly, we hypothesize that Myc regulates substrate preferences for the citric acid cycle during pressure overload hypertrophy from transverse aortic constriction (TAC) and that these metabolic changes impact cardiac function and growth. To test this hypothesis, we subjected mice with cardiac specific, inducible Myc inactivation (MycKO-TAC) and non-transgenic littermates (Cont-TAC) to transverse aortic constriction (TAC; n=7/group). A separate group underwent sham surgery (Sham, n=5). After two weeks, function was measured in isolated workingmore » hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with 13C labeled mixed fatty acids, lactate, ketone bodies and unlabeled glucose and insulin. Cardiac function was similar between groups after TAC although +dP/dT and -dP/dT trended towards improvement in MycKO-TAC versus Cont-TAC. Compared to Sham, Cont-TAC had increased free fatty acid fractional contribution with a concurrent decrease in unlabeled (predominately glucose) contribution. The changes in free fatty acid and unlabeled fractional contributions were abrogated by Myc inactivation during TAC (MycKO-TAC). Additionally, protein posttranslational modification by O-GlcNAc was significantly greater in Cont-TAC versus both Sham and MycKO-TAC. Lastly, Myc alters substrate preferences for the citric acid cycle during early pressure overload hypertrophy without negatively affecting cardiac function. Myc also affects protein posttranslational modifications by O-GlcNAc during hypertrophy.« less

  3. Nebulette knockout mice have normal cardiac function, but show Z-line widening and up-regulation of cardiac stress markers

    PubMed Central

    Mastrototaro, Giuseppina; Liang, Xingqun; Li, Xiaodong; Carullo, Pierluigi; Piroddi, Nicoletta; Tesi, Chiara; Gu, Yusu; Dalton, Nancy D.; Peterson, Kirk L.; Poggesi, Corrado; Sheikh, Farah; Chen, Ju; Bang, Marie-Louise

    2015-01-01

    Aims Nebulette is a 109 kDa modular protein localized in the sarcomeric Z-line of the heart. In vitro studies have suggested a role of nebulette in stabilizing the thin filament, and missense mutations in the nebulette gene were recently shown to be causative for dilated cardiomyopathy and endocardial fibroelastosis in human and mice. However, the role of nebulette in vivo has remained elusive. To provide insights into the function of nebulette in vivo, we generated and studied nebulette-deficient (nebl−/−) mice. Methods and results Nebl−/− mice were generated by replacement of exon 1 by Cre under the control of the endogenous nebulette promoter, allowing for lineage analysis using the ROSA26 Cre reporter strain. This revealed specific expression of nebulette in the heart, consistent with in situ hybridization results. Nebl−/− mice exhibited normal cardiac function both under basal conditions and in response to transaortic constriction as assessed by echocardiography and haemodynamic analyses. Furthermore, histological, IF, and western blot analysis showed no cardiac abnormalities in nebl−/− mice up to 8 months of age. In contrast, transmission electron microscopy showed Z-line widening starting from 5 months of age, suggesting that nebulette is important for the integrity of the Z-line. Furthermore, up-regulation of cardiac stress responsive genes suggests the presence of chronic cardiac stress in nebl−/− mice. Conclusion Nebulette is dispensable for normal cardiac function, although Z-line widening and up-regulation of cardiac stress markers were found in nebl−/− heart. These results suggest that the nebulette disease causing mutations have dominant gain-of-function effects. PMID:25987543

  4. Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures.

    PubMed

    Zhang, Wenhai; Li, Hong; Pan, Xiaohong

    2015-02-01

    Recent resting-state functional magnetic resonance imaging (fMRI) studies using graph theory metrics have revealed that the functional network of the human brain possesses small-world characteristics and comprises several functional hub regions. However, it is unclear how the affective functional network is organized in the brain during the processing of affective information. In this study, the fMRI data were collected from 25 healthy college students as they viewed a total of 81 positive, neutral, and negative pictures. The results indicated that affective functional networks exhibit weaker small-worldness properties with higher local efficiency, implying that local connections increase during viewing affective pictures. Moreover, positive and negative emotional processing exhibit dissociable functional hubs, emerging mainly in task-positive regions. These functional hubs, which are the centers of information processing, have nodal betweenness centrality values that are at least 1.5 times larger than the average betweenness centrality of the network. Positive affect scores correlated with the betweenness values of the right orbital frontal cortex (OFC) and the right putamen in the positive emotional network; negative affect scores correlated with the betweenness values of the left OFC and the left amygdala in the negative emotional network. The local efficiencies in the left superior and inferior parietal lobe correlated with subsequent arousal ratings of positive and negative pictures, respectively. These observations provide important evidence for the organizational principles of the human brain functional connectome during the processing of affective information.

  5. The neuronal control of cardiac functions in Molluscs.

    PubMed

    Kodirov, Sodikdjon A

    2011-10-01

    In this manuscript, I review the current and relevant classical studies on properties of the Mollusca heart and their central nervous system including ganglia, neurons, and nerves involved in cardiomodulation. Similar to mammalian brain hemispheres, these invertebrates possess symmetrical pairs of ganglia albeit visceral (only one) ganglion and the parietal ganglia (the right ganglion is bigger than the left one). Furthermore, there are two major regulatory drives into the compartments (pericard, auricle, and ventricle) and cardiomyocytes of the heart. These are the excitatory and inhibitory signals that originate from a few designated neurons and their putative neurotransmitters. Many of these neurons are well-identified, their specific locations within the corresponding ganglion are mapped, and some are termed as either heart excitatory (HE) or inhibitory (HI) cells. The remaining neurons are classified as cardio-regulatory, and their direct and indirect actions on the heart's function have been documented. The cardiovascular anatomy of frequently used experimental animals, Achatina, Aplysia, Helix, and Lymnaea is relatively simple. However, as in humans, it possesses all major components including even trabeculae and atrio-ventricular valves. Since the myocardial cells are enzymatically dispersible, multiple voltage dependent cationic currents in isolated cardiomyocytes are described. The latter include at least the A-type K(+), delayed rectifier K(+), TTX-sensitive Na(+), and L-type Ca(2+) channels.

  6. 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

  7. 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

  8. Cell–cell junction remodeling in the heart: Possible role in cardiac conduction system function and arrhythmias?

    PubMed Central

    Mezzano, Valeria; Sheikh, Farah

    2012-01-01

    Anchoring Cell–cell junctions (desmosomes, fascia adherens) play crucial roles in maintaining mechanical integrity of cardiac muscle cells and tissue. Genetic mutations and/or loss of critical components in these macromolecular structures are increasingly being associated with arrhythmogenic cardiomyopathies; however, their specific roles have been primarily attributed to effects within the working (ventricular) cardiac muscle. Growing evidence also points to a key role for anchoring Cell–cell junction components in cardiac muscle cells of the cardiac conduction system. This is not only evidenced by the molecular and ultra-structural presence of anchoring cell junctions in specific compartments/structures of the cardiac conduction system (sinoatrial node, atrioventricular node, His-Purkinje system), but also because conduction system-related arrhythmias can be found in humans and mouse models of cardiomyopathies harboring defects and/or mutations in key anchoring Cell–cell junction proteins. These studies emphasize the clinical need to understand the molecular and cellular role(s) for anchoring Cell–cell junctions in cardiac conduction system function and arrhythmias. This review will focus on (i) experimental findings that underline an important role for anchoring Cell–cell junctions in the cardiac conduction system, (ii) insights regarding involvement of these structures in age-related cardiac remodeling of the conduction system, (iii) summarizing available genetic mouse models that can target cardiac conduction system structures and (iv) implications of these findings on future therapies for arrhythmogenic heart diseases. PMID:22227473

  9. 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.

  10. 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

  11. 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

  12. Echocardiographic evaluation of the effects of dexmedetomidine on cardiac function during total intravenous anaesthesia.

    PubMed

    Lee, S H; Choi, Y S; Hong, G R; Oh, Y J

    2015-09-01

    The purpose of this study was to investigate the effects of dexmedetomidine on biventricular systolic and diastolic function using transoesophageal echocardiography. Cardiac function was assessed in 30 healthy patients who received total intravenous anaesthesia with propofol and remifentanil. The echocardiographic examinations were performed just before and 20, 40 and 60 min after dexmedetomidine or saline administration. Patients who received dexmedetomidine, compared with saline after 20 min, had a lower mean (SD) heart rate (56.7 (5.2) vs. 67.1 (7.1) beats.min(-1) ), higher systolic blood pressure (125.7 (18.9) vs. 109 (7.9) mmHg), and lower cardiac output (2.9 (0.5) vs. 3.7 (1.0) l.min(-1) ), respectively (all p < 0.05). In contrast, no changes were observed in biventricular systolic and diastolic indices in either group, and there were no inter-group differences at any time point. Dexmedetomidine, as an adjuvant to total intravenous anaesthesia, does not impair biventricular systolic and diastolic function in healthy patients, but decreases cardiac output by reducing heart rate.

  13. Effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats.

    PubMed

    Di Petta, Antonio; Simas, Rafael; Ferreira, Clebson L; Capelozzi, Vera L; Salemi, Vera M C; Moreira, Luiz F P; Sannomiya, Paulina

    2015-10-01

    Chronic obstructive pulmonary disease is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate the effects of the association of diabetes and pulmonary emphysema on cardiac structure and function in rats. Wistar rats were divided into control non-diabetic instilled with saline (CS) or elastase (CE), diabetic instilled with saline (DS) or elastase (DE), DE treated with insulin (DEI) groups and echocardiographic measurements, morphometric analyses of the heart and lungs, and survival analysis conducted 50 days after instillation. Diabetes mellitus was induced [alloxan, 42 mg/kg, intravenously (iv)] 10 days before the induction of emphysema (elastase, 0.25 IU/100 g). Rats were treated with NPH insulin (4 IU before elastase plus 2 IU/day, 50 days). Both CE and DE exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in right ventricular (RV) wall thickness (P = 0.0022), cavity area (P = 0.0001) and cardiomyocyte thickness (P = 0.0001). Diabetic saline group demonstrated a reduction in left ventricular (LV) wall, interventricular (IV) septum, cardiomyocyte thickness and an increase in cavity area, associated with a reduction in LV fractional shortening (P < 0.05), and an increase in LViv relaxation time (P < 0.05). Survival rate decreased from 80% in DS group to 40% in DE group. In conclusion, alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, even in the presence of insulin. Diabetes per se induced left ventricular dysfunction, which was less evident in the presence of RV hypertrophy. Survival rate was substantially reduced as a consequence, at least in part, of the coexistence of RV hypertrophy and diabetic cardiomyopathy.

  14. Dichloroacetate selectively improves cardiac function and metabolism in female and male rainbow trout.

    PubMed

    Battiprolu, Pavan K; Rodnick, Kenneth J

    2014-11-15

    Cardiac tissue from female rainbow trout demonstrates a sex-specific preference for exogenous glucose and glycolysis, impaired Ca(2+) handling, and a greater tolerance for hypoxia and reoxygenation than cardiac tissue from male rainbow trout. We tested the hypothesis that dichloroacetate (DCA), an activator of pyruvate dehydrogenase, enhances cardiac energy metabolism and Ca(2+) handling in female preparations and provide cardioprotection for hypoxic male tissue. Ventricle strips from sexually immature fish with very low (male) and nondetectable (female) plasma sex steroids were electrically paced in oxygenated or hypoxic Ringer solution with or without 1 mM DCA. In the presence of 5 mM glucose, aerobic tissue from male trout could be paced at a higher frequency (1.79 vs. 1.36 Hz) with lower resting tension and less contractile dysfunction than female tissue. At 0.5 Hz, DCA selectively reduced resting tension below baseline values and lactate efflux by 75% in aerobic female ventricle strips. DCA improved the functional recovery of developed twitch force, reduced lactate efflux by 50%, and doubled citrate in male preparations after hypoxia-reoxygenation. Independent of female sex steroids, reduced myocardial pyruvate dehydrogenase activity and impaired carbohydrate oxidation might explain the higher lactate efflux, compromised function of the sarcoplasmic reticulum, and reduced mechanical performance of aerobic female tissue. Elevated oxidative metabolism and reduced glycolysis might also underlie the beneficial effects of DCA on the mechanical recovery of male cardiac tissue after hypoxia-reoxygenation. These results support the use of rainbow trout as an experimental model of sex differences of cardiovascular energetics and function, with the potential for modifying metabolic phenotypes and cardioprotection independent of sex steroids. PMID:25217653

  15. Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function.

    PubMed

    McDermott-Roe, Chris; Ye, Junmei; Ahmed, Rizwan; Sun, Xi-Ming; Serafín, Anna; Ware, James; Bottolo, Leonardo; Muckett, Phil; Cañas, Xavier; Zhang, Jisheng; Rowe, Glenn C; Buchan, Rachel; Lu, Han; Braithwaite, Adam; Mancini, Massimiliano; Hauton, David; Martí, Ramon; García-Arumí, Elena; Hubner, Norbert; Jacob, Howard; Serikawa, Tadao; Zidek, Vaclav; Papousek, Frantisek; Kolar, Frantisek; Cardona, Maria; Ruiz-Meana, Marisol; García-Dorado, David; Comella, Joan X; Felkin, Leanne E; Barton, Paul J R; Arany, Zoltan; Pravenec, Michal; Petretto, Enrico; Sanchis, Daniel; Cook, Stuart A

    2011-10-05

    Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.

  16. Isolation and expansion of functionally-competent cardiac progenitor cells directly from heart biopsies

    PubMed Central

    Davis, Darryl R; Kizana, Eddy; Terrovitis, John; Barth, Andreas S.; Zhang, Yiqiang; Smith, Rachel Ruckdeschel; Miake, Junichiro; Marbán, Eduardo

    2010-01-01

    The adult heart contains reservoirs of progenitor cells that express embryonic and stem cell-related antigens. While these antigenically-purified cells are promising candidates for autologous cell therapy, clinical application is hampered by their limited abundance and tedious isolation methods. Methods that involve an intermediate cardiosphere-forming step have proven successful and are being tested clinically, but it is unclear whether the cardiosphere step is necessary. Accordingly, we investigated the molecular profile and functional benefit of cells that spontaneously emigrate from cardiac tissue in primary culture. Adult Wistar-Kyoto rat hearts were minced, digested and cultured as separate anatomical regions. Loosely-adherent cells that surround the plated tissue were harvested weekly for a total of five harvests. Genetic lineage tracing demonstrated that a small proportion of the direct outgrowth from cardiac samples originates from myocardial cells. This outgrowth contains sub-populations of cells expressing embryonic (SSEA-1) and stem cell-related antigens (c-Kit, abcg2) that varied with time in culture but not with the cardiac chamber of origin. This direct outgrowth, and its expanded progeny, underwent marked in vitro angiogenic/cardiogenic differentiation and cytokine secretion (IGF-1, VGEF). In vivo effects included long-term functional benefits as gauged by MRI following cell injection in a rat model of myocardial infarction. Outgrowth cells afforded equivalent functional benefits to cardiosphere-derived cells, which require more processing steps to manufacture. These results provide the basis for a simplified and efficient process to generate autologous cardiac progenitor cells (and mesenchymal supporting cells) to augment clinically-relevant approaches for myocardial repair. PMID:20211627

  17. Mathematical Models Based on Transfer Functions to Estimate Tissue Temperature During RF Cardiac Ablation in Real Time

    PubMed Central

    Alba-Martínez, Jose; Trujillo, Macarena; Blasco-Gimenez, Ramon; Berjano, Enrique

    2012-01-01

    Radiofrequency cardiac ablation (RFCA) has been used to treat certain types of cardiac arrhythmias by producing a thermal lesion. Even though a tissue temperature higher than 50ºC is required to destroy the target, thermal mapping is not currently used during RFCA. Our aim was thus to develop mathematical models capable of estimating tissue temperature from tissue characteristics acquired or estimated at the beginning of the procedure (electrical conductivity, thermal conductivity, specific heat and density) and the applied voltage at any time. Biological tissue was considered as a system with an input (applied voltage) and output (tissue temperature), and so the mathematical models were based on transfer functions relating these variables. We used theoretical models based on finite element method to verify the mathematical models. Firstly, we solved finite element models to identify the transfer functions between the temperature at a depth of 4 mm and a constant applied voltage using a 7Fr and 4 mm electrode. The results showed that the relationships can be expressed as first-order transfer functions. Changes in electrical conductivity only affected the static gain of the system, while specific heat variations produced a change in the dynamic system response. In contrast, variations in thermal conductivity modified both the static gain and the dynamic system response. Finally, to assess the performance of the transfer functions obtained, we conducted a new set of computer simulations using a controlled temperature protocol and considering the temperature dependence of the thermal and electrical conductivities, i.e. conditions closer to those found in clinical use. The results showed that the difference between the values estimated from transfer functions and the temperatures obtained from finite element models was less than 4ºC, which suggests that the proposed method could be used to estimate tissue temperature in real time. PMID:22715345

  18. Intravital imaging of cardiac function at the single-cell level

    PubMed Central

    Aguirre, Aaron D.; Vinegoni, Claudio; Sebas, Matt; Weissleder, Ralph

    2014-01-01

    Knowledge of cardiomyocyte biology is limited by the lack of methods to interrogate single-cell physiology in vivo. Here we show that contracting myocytes can indeed be imaged with optical microscopy at high temporal and spatial resolution in the beating murine heart, allowing visualization of individual sarcomeres and measurement of the single cardiomyocyte contractile cycle. Collectively, this has been enabled by efficient tissue stabilization, a prospective real-time cardiac gating approach, an image processing algorithm for motion-artifact-free imaging throughout the cardiac cycle, and a fluorescent membrane staining protocol. Quantification of cardiomyocyte contractile function in vivo opens many possibilities for investigating myocardial disease and therapeutic intervention at the cellular level. PMID:25053815

  19. Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation.

    PubMed

    Spartera, Marco; Galderisi, Maurizio; Mele, Donato; Cameli, Matteo; D'Andrea, Antonello; Rossi, Andrea; Mondillo, Sergio; Novo, Giuseppina; Esposito, Roberta; D'Ascenzi, Flavio; Montisci, Roberta; Gallina, Sabina; Margonato, Alberto; Agricola, Eustachio

    2016-05-01

    Functional mitral regurgitation (FMR) is a common complication of left ventricle (LV) dysfunction and remodelling. Recently, it has been recognized as an independent prognostic factor in both ischaemic and non-ischaemic LV dysfunctions. In this review article, we discuss the mechanisms through which cardiac dyssynchrony is involved in FMR pathophysiologic cascade and how cardiac resynchronization therapy (CRT) can have therapeutic effects on FMR by reverting specific dyssynchrony pathways. We analyse recent clinical trials focusing on CRT impact on FMR in 'real-world' patients, the limits and future perspectives that could eventually generate new predictors of CRT response in terms of FMR reduction. Finally, we propose a practical diagnostic and therapeutic strategy for the management of symptomatic patients with severe LV dysfunction and concomitant 'prognostic' FMR.

  20. Impact of dispersed fuel oil on cardiac mitochondrial function in polar cod Boreogadus saida.

    PubMed

    Dussauze, Matthieu; Camus, Lionel; Le Floch, Stéphane; Pichavant-Rafini, Karine; Geraudie, Perrine; Coquillé, Nathalie; Amérand, Aline; Lemaire, Philippe; Theron, Michael

    2014-12-01

    In this study, impact of dispersed oil on cardiac mitochondrial function was assessed in a key species of Arctic marine ecosystem, the polar cod Boreogadus saida. Mature polar cod were exposed during 48 h to dispersed oil (mechanically and chemically) and dispersants alone. The increase observed in ethoxyresorufin-O-deethylase activity and polycyclic aromatic hydrocarbon metabolites in bile indicated no difference in contamination level between fish exposed to chemical or mechanical dispersion of oil. Oil induced alterations of O2 consumption of permeabilised cardiac fibres showing inhibitions of complexes I and IV of the respiratory chain. Oil did not induce any modification of mitochondrial proton leak. Dispersants did not induce alteration of mitochondrial activity and did not increase oil toxicity. These data suggest that oil exposure may limit the fitness of polar cod and consequently could lead to major disruption in the energy flow of polar ecosystem.

  1. Teaching cardiac autonomic function dynamics employing the Valsalva (Valsalva-Weber) maneuver.

    PubMed

    Junqueira, Luiz Fernando

    2008-03-01

    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, and some guidelines are established for simple application of the maneuver in a teaching or research laboratory setting. These include the hemodynamic and cardiac autonomic mechanisms involved, technical aspects such as the intensity and duration of the expiratory straining, frequency of maneuver sessions, training and posture of the individuals tested, different time- and grade change-dependent indexes of heart interval variation, and clinical application of the maneuver.

  2. Impact of aortocaval shunt flow on cardiac and renal function in unilateral nephrectomized rats

    PubMed Central

    Wu, Jie; Cheng, Zhong; Zhang, Mingjing; Zhu, Pengfei; Gu, Ye

    2016-01-01

    We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-α, IL-6, IL-1β, TGF-β and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model. PMID:27279232

  3. N-cadherin haploinsufficiency affects cardiac gap junctions and arrhythmic susceptibility

    PubMed Central

    Li, Jifen; Levin, Mark D; Xiong, Yanming; Petrenko, Nataliya; Patel, Vickas V.; Radice, Glenn L.

    2008-01-01

    Cardiac-specific deletion of the murine gene (Cdh2) encoding the cell adhesion molecule, N-cadherin, results in disassembly of the intercalated disc (ICD) structure and sudden arrhythmic death. Connexin 43 (Cx43)-containing gap junctions are significantly reduced in the heart after depleting N-cadherin, therefore we hypothesized that animals expressing half the normal levels of N-cadherin would exhibit an intermediate phenotype. We examined the effect of N-cadherin haploinsufficiency on Cx43 expression and susceptibility to induced arrhythmias in mice either wild-type or heterozygous for the Cx43 (Gja1)-null allele. An increase in hypophosphorylated Cx43 accompanied by a modest decrease in total Cx43 protein levels was observed in the N-cadherin heterozygous mice. Consistent with these findings N-cadherin heterozygotes exhibited increased susceptibility to ventricular arrhythmias compared to wild-type mice. Quantitative immunofluorescence microscopy revealed a reduction in size of large Cx43-containing plaques in the N-cadherin heterozygous animals compared to wild-type. Gap junctions were further decreased in number and size in the N-cad/Cx43 compound heterozygous mice with increased arrhythmic susceptibility compared to the single mutants. The scaffold protein, ZO-1, was reduced at the ICD in N-cadherin heterozygous cardiomyocytes providing a possible explanation for the reduction in Cx43 plaque size. These data provide further support for the intimate relationship between N-cadherin and Cx43 in the heart, and suggest that germline mutations in the human N-cadherin (Cdh2) gene may predispose patients to increased risk of cardiac arrhythmias. PMID:18201716

  4. Effect of exercise on cardiac autonomic function in females with rheumatoid arthritis.

    PubMed

    Janse van Rensburg, Dina C; Ker, James A; Grant, Catharina C; Fletcher, Lizelle

    2012-08-01

    The objective of this study is to evaluate the effect of exercise on cardiac autonomic function as measured by short-term heart rate variability (HRV) in females suffering from rheumatoid arthritis (RA). Females with confirmed RA were randomly assigned to an exercise group (RAE) and a sedentary group (RAC). RAE was required to train under supervision two to three times per week, for 3 months. Three techniques (time domain, frequency domain and Poincaré plot analyses) were used to measure HRV at baseline and study completion. At baseline, RAC (n = 18) had a significantly higher variability compared to RAE (n = 19) for most HRV indicators. At study completion, the variables showing significant changes (p = 0.01 to 0.05) favoured RAE in all instances. Wilcoxon signed rank tests were performed to assess changes within groups from start to end. RAE showed significant improvement for most of the standing variables, including measurements of combined autonomic influence, e.g. SDRR (p = 0.002) and variables indicating only vagal influence, e.g. pNN50 (p = 0.014). RAC mostly deteriorated with emphasis on variables measuring vagal influence (RMSSD, pNN50, SD1 and HF (ms(2)). Study results indicated that 12 weeks of exercise intervention had a positive effect on cardiac autonomic function as measured by short-term HRV, in females with RA. Several of the standing variables indicated improved vagal influence on the heart rate. Exercise can thus potentially be used as an instrument to improve cardiac health in a patient group known for increased cardiac morbidity.

  5. Akt2 Knockout Alleviates Prolonged Caloric Restriction-Induced Change in Cardiac Contractile Function through Regulation of Autophagy

    PubMed Central

    Zhang, Yingmei; Han, Xuefeng; Hu, Nan; Huff, Anna F.; Gao, Feng; Ren, Jun

    2014-01-01

    Caloric restriction leads to changes in heart geometry and function although the underlying mechanism remains elusive. Autophagy, a conserved pathway for degradation of intracellular proteins and organelles, preserves energy and nutrient in the face of caloric insufficiency. This study was designed to examine the role of Akt2 in prolonged caloric restriction-induced change in cardiac homeostasis and the underlying mechanism(s) involved. Wild-type (WT) and Akt2 knockout mice were caloric restricted (by 40%) for 30 weeks. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, autophagy and its regulatory proteins were evaluated. Caloric restriction compromised echocardiographic indices (decreased left ventricular mass, left ventricular diameters and cardiac output), cardiomyocyte contractile and intracellular Ca2+ properties associated with dampened SERCA2a phosphorylation, upregulated phospholamban and autophagy (Beclin-1, Atg7, LC3BII-to-LC3BI ratio), increased autophagy adaptor protein p62, elevated phosphorylation of AMPK, Akt2 and the Akt downstream signal molecule TSC2, the effects of which with the exception of autophagy protein markers (Beclin-1, Atg7, LC3B) and AMPK were mitigated or significantly alleviated by Akt2 knockout. Lysosomal inhibition using bafilomycin A1 negated Akt2 knockout-induced protective effect on p62. Evaluation of downstream signaling molecules of Akt and AMPK including mTOR and ULK1 revealed that caloric restriction suppressed and promoted phosphorylation of mTOR and ULK1, respectively, without affecting total mTOR and ULK1 expression. Akt2 knockout significantly augmented caloric restriction-induced responses on mTOR and ULK1. Taken together, these data suggest a beneficial role of Akt2 knockout in preservation of cardiac homeostasis against prolonged caloric restriction-induced pathological changes possibly through facilitating autophagy. PMID:24368095

  6. Effects of freeze-dried red wine on cardiac function and ECG of the Langendorff-perfused rat heart.

    PubMed

    Ferrara, Antonella; Fusi, Fabio; Gorelli, Beatrice; Sgaragli, Giampietro; Saponara, Simona

    2014-02-01

    The effect of freeze-dried red wine (FDRW) on cardiac function and electrocardiogram (ECG) in Langendorff-isolated rat hearts was investigated. FDRW significantly decreased left ventricular pressure and coronary perfusion pressure, the latter being dependent on the activation of both phosphatidylinositol 3-kinase and eNOS. FDRW did not affect the QRS and QT interval in the ECG, although at 56 μg of gallic acid equivalents/mL, it prolonged PQ interval and induced a second-degree atrioventricular block in 3 out of 6 hearts. This is the first study demonstrating that at concentrations resembling a moderate consumption of red wine, FDRW exhibited negative inotropic and coronary vasodilating activity leaving unaltered ECG, whereas at very high concentrations, it induced arrhythmogenic effects.

  7. Cardiac Sarcoidosis

    MedlinePlus

    ... is Cardiac Sarcoidosis? Sarcoidosis is a poorly understood disease that commonly affects the lungs. It can also involve the lymph nodes, liver, spleen, eyes, skin, bones, salivary glands and heart. ...

  8. The PKD Inhibitor CID755673 Enhances Cardiac Function in Diabetic db/db Mice

    PubMed Central

    Venardos, Kylie; De Jong, Kirstie A.; Elkamie, Mansour; Connor, Timothy; McGee, Sean L.

    2015-01-01

    The development of diabetic cardiomyopathy is a key contributor to heart failure and mortality in obesity and type 2 diabetes (T2D). Current therapeutic interventions for T2D have limited impact on the development of diabetic cardiomyopathy. Clearly, new therapies are urgently needed. A potential therapeutic target is protein kinase D (PKD), which is activated by metabolic insults and implicated in the regulation of cardiac metabolism, contractility and hypertrophy. We therefore hypothesised that PKD inhibition would enhance cardiac function in T2D mice. We first validated the obese and T2D db/db mouse as a model of early stage diabetic cardiomyopathy, which was characterised by both diastolic and systolic dysfunction, without overt alterations in left ventricular morphology. These functional characteristics were also associated with increased PKD2 phosphorylation in the fed state and a gene expression signature characteristic of PKD activation. Acute administration of the PKD inhibitor CID755673 to normal mice reduced both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 administration to T2D db/db mice for two weeks reduced expression of the gene expression signature of PKD activation, enhanced indices of both diastolic and systolic left ventricular function and was associated with reduced heart weight. These alterations in cardiac function were independent of changes in glucose homeostasis, insulin action and body composition. These findings suggest that PKD inhibition could be an effective strategy to enhance heart function in obese and diabetic patients and provide an impetus for further mechanistic investigations into the role of PKD in diabetic cardiomyopathy. PMID:25798941

  9. Assessment of cardiac and pulmonary function in children with juvenile idiopathic arthritis.

    PubMed

    Alkady, Eman A M; Helmy, Hatem A R; Mohamed-Hussein, Aliaë A R

    2012-01-01

    Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disorder of childhood. It is a group of diseases characterized by chronic synovitis and associated with many extra-articular manifestations including cardiac and pulmonary involvement. Cardiac involvement as pericarditis, myocarditis and valvular disease is common in JIA. There are, however, few descriptions concerning systolic and diastolic functions of the left ventricle (LV) and the development of lung disease in children with JIA. The study was carried out to detect the cardiac and pulmonary involvement and to study the systolic and diastolic function of the left ventricle in a group of children with juvenile idiopathic arthritis. Forty-five children with JIA without any cardiac or pulmonary symptoms and 30 age- and sex-matched controls were included in the study. M-mode, two-dimensional and pulsed Doppler echocardiography (ECHO) was performed on 36 patients. Tissue Doppler ECHO examination was performed on 24 patients to assess systolic and diastolic functions of left ventricle. Pulmonary function tests: Forced vital capacity (FVC%), the predicted forced expiratory volume in the first second (FEV(1)%) and FEV(1)/FVC ratio and peak expiratory flow (PEF), total lung capacity (TLC) and residual volume (RV), carbon monoxide diffusing capacity of the lung (DLCO) and DLCO/alveolar volume (VA) were evaluated in 32 patients. Informed consent was obtained from all children's parents. The study protocol was approved by ethical committee of Faculty of Medicine, Assiut University. In this study, children with JIA had higher systolic and diastolic blood pressures, resting heart rate, left ventricle systolic size and volume (4.35 ± 0.68 vs. 3.92 ± 0.28, P value = 0.02). On Doppler and tissue Doppler analysis, the JIA group had lower peak early filling velocity (E, m/s), higher peak atrial filling velocity (A, m/s) and prolonged diastolic E and A waves deceleration times and isovolumic relaxation time

  10. Evolutionarily conserved intercalated disc protein Tmem65 regulates cardiac conduction and connexin 43 function.

    PubMed

    Sharma, Parveen; Abbasi, Cynthia; Lazic, Savo; Teng, Allen C T; Wang, Dingyan; Dubois, Nicole; Ignatchenko, Vladimir; Wong, Victoria; Liu, Jun; Araki, Toshiyuki; Tiburcy, Malte; Ackerley, Cameron; Zimmermann, Wolfram H; Hamilton, Robert; Sun, Yu; Liu, Peter P; Keller, Gordon; Stagljar, Igor; Scott, Ian C; Kislinger, Thomas; Gramolini, Anthony O

    2015-01-01

    Membrane proteins are crucial to heart function and development. Here we combine cationic silica-bead coating with shotgun proteomics to enrich for and identify plasma membrane-associated proteins from primary mouse neonatal and human fetal ventricular cardiomyocytes. We identify Tmem65 as a cardiac-enriched, intercalated disc protein that increases during development in both mouse and human hearts. Functional analysis of Tmem65 both in vitro using lentiviral shRNA-mediated knockdown in mouse cardiomyocytes and in vivo using morpholino-based knockdown in zebrafish show marked alterations in gap junction function and cardiac morphology. Molecular analyses suggest that Tmem65 interaction with connexin 43 (Cx43) is required for correct localization of Cx43 to the intercalated disc, since Tmem65 deletion results in marked internalization of Cx43, a shorter half-life through increased degradation, and loss of Cx43 function. Our data demonstrate that the membrane protein Tmem65 is an intercalated disc protein that interacts with and functionally regulates ventricular Cx43.

  11. Affect integration and reflective function: clarification of central conceptual issues.

    PubMed

    Solbakken, Ole André; Hansen, Roger Sandvik; Monsen, Jon Trygve

    2011-07-01

    The importance of affect regulation, modulation or integration for higher-order reflection and adequate functioning is increasingly emphasized across different therapeutic approaches and theories of change. These processes are probably central to any psychotherapeutic endeavor, whether explicitly conceptualized or not, and in recent years a number of therapeutic approaches have been developed that explicitly target them as a primary area of change. However, there still is important lack of clarity in the field regarding the understanding and operationalization of affect integration, particularly when it comes to specifying underlying mechanisms, the significance of different affect states, and the establishment of operational criteria for measurement. The conceptual relationship between affect integration and reflective function thus remains ambiguous. The present article addresses these topics, indicating ways in which a more complex and exhaustive understanding of integration of affect, cognition and behavior can be attained.

  12. How Does Maternal Employment Affect Children's Socioemotional Functioning?

    ERIC Educational Resources Information Center

    Lam, Gigi

    2015-01-01

    The maternal employment becomes an irreversible trend across the globe. The effect of maternal employment on children's socioemotional functioning is so pervasive that it warrants special attention to investigate into the issue. A trajectory of analytical framework of how maternal employment affects children's socioemotional functioning originates…

  13. Bone morphogenetic protein-10 induces cardiomyocyte proliferation and improves cardiac function after myocardial infarction.

    PubMed

    Sun, Lijun; Yu, Jing; Qi, Shun; Hao, Yuewen; Liu, Ying; Li, Zhenwu

    2014-11-01

    Heart disease is among the leading causes of death worldwide, and the limited proliferation of mammalian cardiomyocytes prevents heart regeneration in response to injury. Bone morphogenetic protein-10 (BMP10) exerts multiple roles in various developmental events; however, the effect of BMP10 and the underlying mechanism involved in cardiac repair remains unclear. After stimulation with the recombinant BMP10, an obvious dose-dependent cardiomyocyte proliferation and reentry of differentiated mammalian cardiomyocytes into the cell cycle was observed. Furthermore, BMP10 stimulation strikingly enhanced Tbx20 expression. Further analysis demonstrated that T-box 20 (Tbx20) was involved in BMP10-induced proliferation of differentiated cardiomyocytes as preconditioning with Tbx20 siRNA significantly attenuated BMP10-induced DNA synthesis. In vivo, BMP10 induced rat cardiomyocyte DNA synthesis and cytokinesis. After myocardial infarction (MI), BMP10 stimulated cardiomyocyte cell-cycle reentry and mitosis, resulting in the decrease of infarct size and improvement of cardiac repair. Taken together, these data indicated that BMP10 stimulated cardiomyocyte proliferation and repaired cardiac function after heart injury. Consequently, BMP10 may be a potential target for innovative strategies against heart failure.

  14. Cardiac structure and function in humans: a new cardiovascular physiology laboratory

    PubMed Central

    Song, Su; Burleson, Paul D.; Passo, Stanley; Messina, Edward J.; Levine, Norman; Thompson, Carl I.; Belloni, Francis L.; Recchia, Fabio A.; Ojaimi, Caroline; Kaley, Gabor

    2009-01-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another “hands-on” experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions. PMID:19745049

  15. Cardiac structure and function in humans: a new cardiovascular physiology laboratory.

    PubMed

    Song, Su; Burleson, Paul D; Passo, Stanley; Messina, Edward J; Levine, Norman; Thompson, Carl I; Belloni, Francis L; Recchia, Fabio A; Ojaimi, Caroline; Kaley, Gabor; Hintze, Thomas H

    2009-09-01

    As the traditional cardiovascular control laboratory has disappeared from the first-year medical school curriculum, we have recognized the need to develop another "hands-on" experience as a vehicle for wide-ranging discussions of cardiovascular control mechanisms. Using an echocardiograph, an automatic blood pressure cuff, and a reclining bicycle, we developed protocols to illustrate the changes in cardiac and vascular function that occur with changes in posture, venous return, and graded exercise. We use medical student volunteers and a professional echocardiographer to generate and acquire data, respectively. In small-group sessions, we developed an interactive approach to discuss the data and to make a large number of calculations from a limited number of measurements. The sequence of cardiac events and cardiac structure in vivo were illustrated with the volunteers lying down, standing, and then with their legs raised passively above the heart to increase venous return. Volunteers were then asked to peddle the bicycle to achieve steady-state heart rates of 110 and 150 beats/min. Data were collected in all these states, and calculations were performed and used as the basis of a small-group discussion to illustrate physiological principles. Information related to a surprisingly large number of cardiovascular control mechanisms was derived, and its relevance to cardiovascular dysfunction was explored. This communication describes our experience in developing a new cardiovascular control laboratory to reinforce didactic material presented in lectures and small-group sessions.

  16. On site assessment of cardiac function and neural regulation in amateur half marathon runners

    PubMed Central

    Dalla Vecchia, Laura; Traversi, Egidio; Porta, Alberto; Lucini, Daniela; Pagani, Massimo

    2014-01-01

    Objective Strenuous exercise variably modifies cardiovascular function. Only few data are available on intermediate levels of effort. We therefore planned a study in order to address the hypothesis that a half marathon distance would result in transient changes of cardiac mechanics, neural regulation and biochemical profile suggestive of a complex, integrated adaptation. Methods We enrolled 35 amateur athletes (42±7 years). Supine and standing heart rate variability and a complete echocardiographic evaluation were assessed on site after the completion of a half marathon (postrace) and about 1 month after (baseline). Biochemical tests were also measured postrace. Results Compared to baseline, the postrace left ventricular end-diastolic volume was smaller, peak velocity of E wave was lower, peak velocity of A wave higher, and accordingly the E/A ratio lower. The postrace heart and respiratory rate were higher and variance of RR interval lower, together with a clear shift towards a sympathetic predominance in supine position and a preserved response to orthostasis. At baseline, athletes were characterised by a lower, although still predominant, sympathetic drive with a preserved physiological response to standing. Conclusions Immediately after a half marathon there are clear marks that an elevated sympathetic cardiac drive outlasts the performance, together with decreased left ventricular diastolic volumes and slight modifications of the left ventricular filling pattern without additional signs of diastolic dysfunction or indices of transient left or right ventricular systolic abnormalities. Furthermore, no biochemical indices of any permanent cardiac damage were found. PMID:25332775

  17. Relationship of radionuclide indexes of cardiac function during interventions: volume loading, afterload stress, exercise, and pacing

    SciTech Connect

    Slutsky, R.A.

    1983-04-01

    We compared three radionuclide index of cardiac function: 1) the ejection fraction (EF), 2) the mean ejection rate (ER), and 3) the mean velocity of circumferential fiber shortening (MVCF) during volume loading, phenylephrine hydrochloride stress, exercise, and atrial pacing. All behaved in a similar (linear) fashion, allowing appropriate hemodynamic conclusions to be drawn using either index. During atrial pacing, the ejection fraction declined when velocity indexes increased, suggesting that the ejection fraction may not be a suitable index to characterize alterations in inotropic state during rapid alterations in heart rate, particular in the absence of angina pectoris. This may result from the reductions in cardiac volume for the duration of pacing, where the velocity index is preserved. In most circumstances excluding atrial pacing, ejection fraction during interventions is an adequate index of the change of myocardial contractile state. Overall, radionuclide angiography is an excellent technique to characterize acute hemodynamic interventions, with ejection fraction, in general, the simplest and most reliable of cardiac indexes during stress interventions.

  18. Investigation of the effect of high +Gz accelerations on human cardiac function.

    PubMed

    Jamshidi, M; Ahmadian, M T

    2013-11-01

    This study investigates the effect of body acceleration on human cardiac function. Finite element analysis is conducted to simulate geometrical and mechanical properties of human heart. Heart geometrical modeling in three-dimension is performed by segmentation of cardiac MRI images. The nonlinear mechanical behavior of myocardium is modeled by Mooney-Rivlin, Polynomial, Ogden and Yeoh hyperelastic material models. Stress-strain curves of myocardial tissue are obtained from experimental compression tests on bovine heart samples. The experimental results are employed for the evaluation of material coefficients by the nonlinear least squares method. Among hyperelastic models, the Yeoh model presents the best fit with experimental stress-strain curve and is used for finite element simulation of heart tissue. Obtained material coefficients are implemented into the constructed heart model and nonlinear finite element analysis is performed for different levels of acceleration in upward direction of vertical axis of body during the rapid filling phase of cardiac cycle. Based on the finite element analysis, ventricular volume change, stress and deformation of heart model are evaluated. It is revealed that when the body is subjected to high accelerations, structural changes in the heart reduce blood supply to body up to 7.2% at +6G.

  19. The effects of pre-pregnancy obesity on fetal cardiac functions.

    PubMed

    Ece, Ibrahim; Uner, Abdurrahman; Balli, Sevket; Kibar, Ayse Esin; Oflaz, Mehmet Burhan; Kurdoglu, Mertihan

    2014-06-01

    Obesity is a substantial public health problem with a rapidly increasing prevalence in numerous industrialized nations. The objective of this study was to evaluate the effects of maternal pre-pregnancy obesity on fetal cardiac functions. We studied 55 fetuses of obese mothers and 44 fetuses of healthy mothers at 26-38 weeks of gestation. Cardiac functions were evaluated by M-mode, pulsed-wave, and tissue Doppler echocardiography. The two groups were similar in terms of maternal age, gravidity, parity, gestational age, estimated birth weight, serum lipids, and systolic-diastolic blood pressure. Fetal heart rate, diameters of the aortic and pulmonary valve annulus, aortic and pulmonary peak systolic velocities, ventricular systolic function, and cardiothoracic ratio were similar in the two groups. Pulsed-wave Doppler-derived E/A ratios in the mitral and tricuspid valves were similar in the two groups. The deceleration time of early mitral inflow was prolonged in the fetuses of the obese mothers. In the interventricular septum, left ventricle posterior wall, and right ventricle free wall, the E a and A a were higher, and E a/A a ratios were significantly lower in the study group than in the control group. The E/E a ratio was higher in the obese group than in the control group. The isovolumic relaxation time and the right and left ventricle myocardial performance indices were higher in the fetuses of the obese mothers than in the fetuses of the healthy mothers. We believe that maternal obesity has an important influence on fetal cardiac diastolic functions.

  20. S100A1 gene therapy preserves in vivo cardiac function after myocardial infarction.

    PubMed

    Pleger, Sven T; Remppis, Andrew; Heidt, Beatrix; Völkers, Mirko; Chuprun, J Kurt; Kuhn, Matthew; Zhou, Rui-Hai; Gao, Erhe; Szabo, Gabor; Weichenhan, Dieter; Müller, Oliver J; Eckhart, Andrea D; Katus, Hugo A; Koch, Walter J; Most, Patrick

    2005-12-01

    Myocardial infarction (MI) represents an enormous clinical challenge as loss of myocardium due to ischemic injury is associated with compromised left ventricular (LV) function often leading to acute cardiac decompensation or chronic heart failure. S100A1 was recently identified as a positive inotropic regulator of myocardial contractility in vitro and in vivo. Here, we explore the strategy of myocardial S100A1 gene therapy either at the time of, or 2 h after, MI to preserve global heart function. Rats underwent cryothermia-induced MI and in vivo intracoronary delivery of adenoviral transgenes (4 x 10(10) pfu). Animals received saline (MI), the S100A1 adenovirus (MI/AdS100A1), a control adenovirus (MI/AdGFP), or a sham operation. S100A1 gene delivery preserved global in vivo LV function 1 week after MI. Preservation of LV function was due mainly to S100A1-mediated gain of contractility of the remaining, viable myocardium since contractile parameters and Ca(2+) transients of isolated MI/AdS100A1 myocytes were significantly enhanced compared to myocytes isolated from both MI/AdGFP and sham groups. Moreover, S100A1 gene therapy preserved the cardiac beta-adrenergic inotropic reserve, which was associated with the attenuation of GRK2 up-regulation. Also, S100A1 overexpression reduced cardiac hypertrophy 1 week post-MI. Overall, our data indicate that S100A1 gene therapy provides a potential novel treatment strategy to maintain contractile performance of the post-MI heart.

  1. Longitudinal changes of cardiac structure and function in CKD (CASCADE study).

    PubMed

    Cai, Qi-Zhe; Lu, Xiu-Zhang; Lu, Ye; Wang, Angela Yee-Moon

    2014-07-01

    Little is known regarding the natural longitudinal changes in cardiac structure and function in CKD. We hypothesized that baseline CKD stage is associated with progressive worsening in cardiac structure and function. We conducted a prospective longitudinal study, recruiting 300 patients with stages 3-5 CKD from a major regional tertiary center and university teaching hospital in Hong Kong. Baseline CKD stages were studied in relation to natural longitudinal changes in echocardiographic and tissue Doppler imaging-derived parameters. Over 1 year, the prevalence of left ventricular (LV) hypertrophy increased from 40.3% to 48.9%, median left atrial volume index increased 4.8 (interquartile range [IQR], 2.1, 7.7) ml/m(2) (P<0.001), peak systolic mitral annular velocity decreased 0.5 (IQR, -1.5, 0.5) cm/s (P<0.001), early diastolic mitral annular velocity decreased 0.5 (IQR, -1.5, 0.5) cm/s (P<0.001), and eGFR declined 2.0 (IQR, -5.0, 0.0) ml/min per 1.73 m(2). CKD stages 4 and 5 were associated with more baseline abnormalities in cardiac structure and function and predicted greater longitudinal progression in LV mass index (odds ratio [OR], 3.02; 95% confidence interval [95% CI], 1.39 to 6.58), volume index (OR, 2.58; 95% CI, 1.18 to 5.62), and left atrial volume index (OR, 2.61; 95% CI, 1.20 to 5.69) and worse diastolic dysfunction grade (OR, 3.17; 95% CI, 1.16 to 8.69) compared with stage 3a in the fully adjusted analysis. In conclusion, more advanced CKD at baseline may be associated with larger longitudinal increases in LV mass and volume and greater deterioration in diastolic function.

  2. Cardiac function and myocardial perfusion immediately following maximal treadmill exercise inside the MRI room

    PubMed Central

    Jekic, Mihaela; Foster, Eric L; Ballinger, Michelle R; Raman, Subha V; Simonetti, Orlando P

    2008-01-01

    Treadmill exercise stress testing is an essential tool in the prevention, detection, and treatment of a broad spectrum of cardiovascular disease. After maximal exercise, cardiac images at peak stress are typically acquired using nuclear scintigraphy or echocardiography, both of which have inherent limitations. Although CMR offers superior image quality, the lack of MRI-compatible exercise and monitoring equipment has prevented the realization of treadmill exercise CMR. It is critical to commence imaging as quickly as possible after exercise to capture exercise-induced cardiac wall motion abnormalities. We modified a commercial treadmill such that it could be safely positioned inside the MRI room to minimize the distance between the treadmill and the scan table. We optimized the treadmill exercise CMR protocol in 20 healthy volunteers and successfully imaged cardiac function and myocardial perfusion at peak stress, followed by viability imaging at rest. Imaging commenced an average of 30 seconds after maximal exercise. Real-time cine of seven slices with no breath-hold and no ECG-gating was completed within 45 seconds of exercise, immediately followed by stress perfusion imaging of three short-axis slices which showed an average time to peak enhancement within 57 seconds of exercise. We observed a 3.1-fold increase in cardiac output and a myocardial perfusion reserve index of 1.9, which agree with reported values for healthy subjects at peak stress. This study successfully demonstrates in-room treadmill exercise CMR in healthy volunteers, but confirmation of feasibility in patients with heart disease is still needed. PMID:18272005

  3. Effect of Actual and Simulated Microgravity on Cardiac Mass and Function in the Rat

    NASA Technical Reports Server (NTRS)

    Ray, Chester H.; Vasques, Marilyn; Miller, Todd H.; Wilkerson, M. Keith; Delp, Michael D.; Dalton, Bonnie (Technical Monitor)

    2001-01-01

    The purpose of this study was to test the hypothesis that exposure to actual or simulated microgravity induces cardiac atrophy in male Sprague-Dawley rats. For the microgravity study, rats were subdivided into four groups: Preflight (PF, n = 12); Flight (FL, n = 7); Flight Cage Simulation (SIM, n = 6), and Vivarium Control (VIV, n = 7). Animals in the FL group were exposed to 7 days of microgravity during the Spacelab 3 mission. Animals in the simulated microgravity study were subdivided into three groups: Control (CON, n = 20); 7 day hindlimb unloaded (7HU, n = 10); and 28 day unloaded (28HU, n = 19). In a subset of CON (n = 7) and 28HU (n = 6) rats, a catheter was advanced into the left ventricle to measure the rate of rise in ventricular pressure (+dP/dt) during standing as an estimate of cardiac contractility. After completion of their respective treatments, hearts were removed and weighed. Animals in the PF group were sacrificed 24 hr prior to launch while the FL group was sacrificed 11- 17 hr after landing. The SM and VIV groups were sacrificed 48 and 96 hr after the FL group, respectively. Heart mass was unchanged in adult animals exposed to 7 days of actual microgravity (PF 1.33 +/- .03 g; FL 1.32 +/- 0.02 g; SIM 1.28 +/- 0.04 g; VIV 1.35 +/- 0.04 g). Similarly, heart mass was unaltered with hinlimb unloading (CON 1.40 +/- 0.04 g; 7HU 1.35 +/- 0.06 g; 28HU 1.42 +/- 0.03 g). Hindlimb unloading also had no effect on myocardial contractility (CON 8055 +/- 385 mmHg/sec; 28HU 8545 +/- 755 mmHg/sec). These data suggest that cardiac atrophy does not occur following short-term exposure to microgravity, and that neither short- nor long-term simulated microgravity alter cardiac mass or function.

  4. CARDIAC MICRO-CT FOR MORPHOLOGICAL AND FUNCTIONAL PHENOTYPING OF MLP NULL MICE

    PubMed Central

    Badea, Cristian T; Hedlund, Laurence W.; Boslego Mackel, Julie F.; Mao, Lan; Rockman, Howard A.; Johnson, G. Allan

    2009-01-01

    PURPOSE Investigate the use of micro-CT for morphological and functional phenotyping of MLP null mice and compare micro-CT with M-mode echocardiography. MATERIAL AND METHODS MLP null mice and controls were imaged using both micro-CT and M-mode echocardiography. For Micro-CT imaging, we used a custom built scanner. Following a single intravenous injection of a blood pool contrast agent (Fenestra™ VC) and using a cardio-respiratory gating, we acquired eight phases of the cardiac cycle (every 15 ms) and reconstructed 3D datasets with 94 micron isotropic resolution. Wall thickness and volumetric measurements of left ventricle were performed and cardiac function was estimated. RESULTS Micro-CT and M mode echocardiography showed both morphological and functional aspects that separate MLP null mice from controls. End Diastolic and Systolic Volumes were increased significantly 3 and 5 fold respectively in the MLP null versus controls. Ejection Fraction was reduced by an average of 32% in MLP null mice. The data analysis shows that two imaging modalities provided different results partly due to the difference in anesthesia regimes. Other sources of errors for micro-CT are also analyzed. CONCLUSION Micro-CT can provide the 4D data (3D isotropic volumes over time) required for morphological and functional phenotyping in mice. PMID:17711781

  5. Cardiac catheterization

    MedlinePlus

    Catheterization - cardiac; Heart catheterization; Angina - cardiac catheterization; CAD - cardiac catheterization; Coronary artery disease - cardiac catheterization; Heart valve - cardiac catheterization; Heart failure - ...

  6. A self-tuning effect of membership functions in a fuzzy-logic-based cardiac pacing system.

    PubMed

    Sugiura, T; Sugiura, N; Kazui, T; Harada, Y

    1998-01-01

    This paper describes a self-tuning method of membership functions in a fuzzy-logic-based cardiac pacing system and validates its feasibility in a double sensor system which has minute ventilation and oxygen saturation level as its guides for the rate regulation. Though the agreement between the pacing rates (fuzzy rates) calculated with three linguistic variables for each parameter and the target rates were not satisfactory, it was improved significantly by tuning the membership functions. Almost the same evaluated values with those obtained by using six linguistic variables for each parameter were obtained. Time required for the self-tuning process was about 40 s (386CPU, 20 MHz) which was fast enough for the system. The smaller number of linguistic labels results in a smaller number of rules, which is beneficial in implantable cardiac pacemakers with limited memory capacity. A fuzzy-logic-based cardiac pacing system is promising for the realization of custom-made cardiac pacemakers.

  7. Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function.

    PubMed

    Merx, Marc W; Gödecke, Axel; Flögel, Ulrich; Schrader, Jürgen

    2005-06-01

    Recent studies of myoglobin (Mb) knockout (myo-/-) mice have extended our understanding of Mb's diverse functions and have demonstrated a complex array of compensatory mechanisms. The present study was aimed at detailed analysis of cardiac function and exercise endurance in myo-/- mice and at providing evidence for Mb's functional relevance. Myo-/- isolated working hearts display decreased contractility (dP/dtmax 3883+/-351 vs. 4618+/-268 mmHg/sec, myo-/- vs. WT, P<0.005). Due to a shift in sympathetic/parasympathetic tone, heart rate is reduced in conscious myo mice-/- (615+/-33 vs. 645+/-27 bpm, myo-/- vs. WT, P<0.001). Oxygen consumption (VO2) under resting conditions (3082+/-413 vs. 4452+/-552 ml x kg(-1) x h(-1), myo-/- vs. WT, P<0.001) and exercise endurance, as determined by spiroergometry, are decreased (466+/-113 vs. 585+/-153 m, myo-/- vs. WT, P<0.01). Conscious myo-/- mice evaluated by echocardiography display lowered cardiac output (0.64+/-0.06 vs. 0.75+/-0.09 ml x min(-1) x g(-1), myo-/- vs. WT, P<0.001), impaired systolic shortening (60+/-3.5 vs. 65+/-4%, myo-/- vs. WT, P<0.001) and fail to respond to beta1-stimulation. Strikingly, the latter cardiac effects of Mb deficiency can be partially attenuated by NOS inhibition. Loss of Mb results in a distinct phenotype, even under resting conditions, and the importance of oxygen supply and nitric oxide scavenging by Mb is clearly demonstrated at the conscious animal level. PMID:15817640

  8. Cardiac Myosin Binding Protein-C Plays No Regulatory Role in Skeletal Muscle Structure and Function

    PubMed Central

    Lin, Brian; Govindan, Suresh; Lee, Kyounghwan; Zhao, Piming; Han, Renzhi; Runte, K. Elisabeth; Craig, Roger; Palmer, Bradley M.; Sadayappan, Sakthivel

    2013-01-01

    Myosin binding protein-C (MyBP-C) exists in three major isoforms: slow skeletal, fast skeletal, and cardiac. While cardiac MyBP-C (cMyBP-C) expression is restricted to the heart in the adult, it is transiently expressed in neonatal stages of some skeletal muscles. However, it is unclear whether this expression is necessary for the proper development and function of skeletal muscle. Our aim was to determine whether the absence of cMyBP-C alters the structure, function, or MyBP-C isoform expression in adult skeletal muscle using a cMyBP-C null mouse model (cMyBP-C(t/t)). Slow MyBP-C was expressed in both slow and fast skeletal muscles, whereas fast MyBP-C was mostly restricted to fast skeletal muscles. Expression of these isoforms was unaffected in skeletal muscle from cMyBP-C(t/t) mice. Slow and fast skeletal muscles in cMyBP-C(t/t) mice showed no histological or ultrastructural changes in comparison to the wild-type control. In addition, slow muscle twitch, tetanus tension, and susceptibility to injury were all similar to the wild-type controls. Interestingly, fMyBP-C expression was significantly increased in the cMyBP-C(t/t) hearts undergoing severe dilated cardiomyopathy, though this does not seem to prevent dysfunction. Additionally, expression of both slow and fast isoforms was increased in myopathic skeletal muscles. Our data demonstrate that i) MyBP-C isoforms are differentially regulated in both cardiac and skeletal muscles, ii) cMyBP-C is dispensable for the development of skeletal muscle with no functional or structural consequences in the adult myocyte, and iii) skeletal isoforms can transcomplement in the heart in the absence of cMyBP-C. PMID:23936073

  9. Oxygen supply and nitric oxide scavenging by myoglobin contribute to exercise endurance and cardiac function.

    PubMed

    Merx, Marc W; Gödecke, Axel; Flögel, Ulrich; Schrader, Jürgen

    2005-06-01

    Recent studies of myoglobin (Mb) knockout (myo-/-) mice have extended our understanding of Mb's diverse functions and have demonstrated a complex array of compensatory mechanisms. The present study was aimed at detailed analysis of cardiac function and exercise endurance in myo-/- mice and at providing evidence for Mb's functional relevance. Myo-/- isolated working hearts display decreased contractility (dP/dtmax 3883+/-351 vs. 4618+/-268 mmHg/sec, myo-/- vs. WT, P<0.005). Due to a shift in sympathetic/parasympathetic tone, heart rate is reduced in conscious myo mice-/- (615+/-33 vs. 645+/-27 bpm, myo-/- vs. WT, P<0.001). Oxygen consumption (VO2) under resting conditions (3082+/-413 vs. 4452+/-552 ml x kg(-1) x h(-1), myo-/- vs. WT, P<0.001) and exercise endurance, as determined by spiroergometry, are decreased (466+/-113 vs. 585+/-153 m, myo-/- vs. WT, P<0.01). Conscious myo-/- mice evaluated by echocardiography display lowered cardiac output (0.64+/-0.06 vs. 0.75+/-0.09 ml x min(-1) x g(-1), myo-/- vs. WT, P<0.001), impaired systolic shortening (60+/-3.5 vs. 65+/-4%, myo-/- vs. WT, P<0.001) and fail to respond to beta1-stimulation. Strikingly, the latter cardiac effects of Mb deficiency can be partially attenuated by NOS inhibition. Loss of Mb results in a distinct phenotype, even under resting conditions, and the importance of oxygen supply and nitric oxide scavenging by Mb is clearly demonstrated at the conscious animal level.

  10. [Research on Cardiac Structure and Function in the Overweight and Obese population and Influence Factors].

    PubMed

    Zhang, Yanmei; Han, Lina; Huang, He; Yu, Yerong; Li, Jiangbo; Liu, Xiaoqin

    2016-02-01

    In this study we performed Tissue Doppler Imaging (TDI), two-dimensional speckle tracking imaging (2D- STI) and three-dimensional speckle tracking imaging (3D-STI) on enrolled healthy, overweight and obese groups (34 subjects in each group), respectively, to analyze cardiac structure and its function. Compared with healthy group, global longitudinal strain (GLS), global circumferential strain (GCS), global area strain(GAS) and global radial strain (GRS) decreased progressively (P < 0.05). The ratio of early diastolic mitral inflow velocity to global early diastolic strain rate of left ventricle (E/e'sr) (r = 0.466, P < 0.001), GLS (r = 0.502, P < 0. 001), GCS (r = 0.426, P < 0.001), GAS (r = 0.535, P < 0.001) and GRS (r = -0.554, P < 0.001) were correlated with body mass index (BMI). E/e'sr (r = 0.37, P = 0.003), GLS (r = 0.455, P < 0.001), GCS (r = 0.282, P = 0.02), GAS (r = 0.412, P < 0.001) and GRS (r = -0.471, P < 0.001) were correlated with free fatty acid (FFA). Stepwise multiple linear regression revealed that BMI was independently correlated with E/e'sr, GLS, GCS, GAS and GRS. Waist to hip ratio (WHR) was independently correlated with GLS, GCS, GAS and GRS. FFA was independently correlated with E/e'sr (P < 0.05). The study showed that cardiac structure changed and impaired left ventricular global systolic and diastolic function in overweight and obes population. Moreover, BMI, WHR and FFA may be independent influence factors of cardiac function in overweight and obese population. PMID:27382752

  11. Adipose-derived stromal cell therapy improves cardiac function after coronary occlusion in rats.

    PubMed

    Bagno, Luiza L S; Werneck-de-Castro, João Pedro S; Oliveira, Patrícia F; Cunha-Abreu, Márcia S; Rocha, Nazareth N; Kasai-Brunswick, Taís H; Lago, Vivian M; Goldenberg, Regina C S; Campos-de-Carvalho, Antonio C

    2012-01-01

    Recent studies have identified adipose tissue as a new source of mesenchymal stem cells for therapy. The purpose of this study was to investigate the therapy with adipose-derived stromal cells (ASCs) in a rat model of healed myocardial infarction (MI). ASCs from inguinal subcutaneous adipose tissue of male Wistar rats were isolated by enzymatic digestion and filtration. Cells were then cultured until passage 3. Four weeks after ligation of the left coronary artery of female rats, a suspension of either 100 µl with phosphate-buffered saline (PBS) + Matrigel + 2 × 10(6) ASCs labeled with Hoechst (n = 11) or 100 µl of PBS + Matrigel (n = 10) was injected along the borders of the ventricular wall scar tissue. A sham-operated group (n = 5) was submitted to the same surgical procedure except permanent ligation of left coronary artery. Cardiac performance was assessed by electro- and echocardiogram. Echo was performed prior to injections (baseline, BL) and 6 weeks after injections (follow-up, FU), and values after treatment were normalized by values obtained before treatment. Hemodynamic measurements were performed 6 weeks after injections. All infarcted animals exhibited cardiac function impairment. Ejection fraction (EF), shortening fractional area (SFA), and left ventricular akinesia (LVA) were similar between infarcted groups before treatment. Six weeks after therapy, ASC group showed significant improvement in all three ECHO indices in comparison to vehicle group. In anesthetized animals dp/dt(+) was also significantly higher in ASCs when compared to vehicle. In agreement with functional improvement, scar area was diminished in the ASC group. We conclude that ASCs improve cardiac function in infarcted rats when administered directly to the myocardium. PMID:22472303

  12. The uncalibrated pulse contour cardiac output during off-pump coronary bypass surgery: performance in patients with a low cardiac output status and a reduced left ventricular function

    PubMed Central

    Jo, Youn Yi; Song, Jong Wook; Yoo, Young Chul; Park, Ji Young; Kwak, Young Lan

    2011-01-01

    Background We compared the continuous cardiac index measured by the FloTrac/Vigileo™ system (FCI) to that measured by a pulmonary artery catheter (CCI) with emphasis on the accuracy of the FCI in patients with a decreased left ventricular ejection fraction (LVEF) and a low cardiac output status during off-pump coronary bypass surgery (OPCAB). We also assessed the influence of several factors affecting the pulse contour, such as the mean arterial pressure (MAP), the systemic vascular resistance index (SVRI) and the use of norepinephrine. Methods Fifty patients who were undergoing OPCAB (30 patients with a LVEF ≥ 40%, 20 patients with a LVEF < 40%) were enrolled. The FCI and CCI were measured and we performed a Bland-Altman analysis. Subgroup analyses were done according to the LVEF (< 40%), the CCI (≤ 2.4 L/min/m), the MAP (60-80 mmHg), the SVRI (1,600-2,600 dyne/s/cm5/m2) and the use of norepinephrine. Results The FCI was reliable at all the time points of measurement with an overall bias and limit of agreement of -0.07 and 0.67 L/min/m2, respectively, resulting in a percentage error of 26.9%. The percentage errors in the patients with a decreased LVEF and in a low cardiac output status were 28.2% and 22.3%, respectively. However, the percentage error in the 91 data pairs outside the normal range of the SVRI was 40.2%. Conclusions The cardiac output measured by the FloTrac/Vigileo™ system was reliable even in patients with a decreased LVEF and in a low cardiac output status during OPCAB. Acceptable agreement was also noted during the period of heart displacement and grafting of the obtuse marginalis branch. PMID:21602972

  13. Cardiac function in total anomalous pulmonary venous return before and after surgery.

    PubMed

    Mathew, R; Thilenius, O G; Replogle, R L; Arcilla, R A

    1977-02-01

    Cardiac performance was evaluated in 12 infants with isolated total anomalous pulmonary venous return. Four had significant pulmonary venous obstruction and severe pulmonary hypertension (group A). Eight had no obvious venous obstruction, and the pulmonary pressures were lower (group B). In all subjects, right ventricular end-diastolic volume was increased (197% of predicted normal) and its ejection fraction was normal. Left ventricular volume was, generally speaking, still in the normal range (87% of predicted normal); however, its ejection fraction was reduced (0.57 vs normal of 0.73) and left ventricular output was low (3.08 L/min/m2 vs normal of 3.98). Left atrial volume was consistently small (53% of predicted normal) with an appendage of normal size. The infants in group A had smaller chamber volumes/m2 BSA than those in group B. Left atrial function was abnormal, characterized by reduced reservoir function and a greater role as "conduit" from right atrium to left ventricle. Left atrial size was not found to be critical in the surgical repair of TAPVR. Cardiac function is restored to normal following surgery.

  14. Effects of renal sympathetic denervation on cardiac systolic function after myocardial infarction in rats

    PubMed Central

    Guo, Jiqun; Zhou, Zhongxia; Li, Zhenzhen; Liu, Qian; Zhu, Guoqing; Shan, Qijun

    2016-01-01

    Abstract This study investigated the therapeutic effects of renal denervation on cardiac systolic function after myocardial infarction (MI) in rats and the mechanism involved. Fifty male SD rats were randomly assigned to the sham group (n = 15), the MI group (n = 20), and the MI plus renal denervation group (n = 15). MI was established through thoracotomic ligation of the anterior descending artery. Renal denervation was achieved by laparotomic stripping of the renal arterial adventitial sympathetic nerve, approximately 3 mm from the abdominal aorta. Left ventricular function and hemodynamics were measured several weeks following MI. The left ventricular systolic function of the MI group was significantly reduced and the systolic blood pressure (SBP) remarkably declined. In rats with MI treated with renal denervation, the left ventricular ejection fraction (EF), fractional shortening (FS) and SBP markedly improved compared with the MI group. However, heart rate and fibrosis decreased significantly. These findings suggest that renal denervation has therapeutic effects on post-MI cardiac dysfunction. These effects are associated with increased left ventricular ejection fraction (LVEF) and SBP, as well as reduced heart rate and fibrosis. This may represent a new approach to the treatment of post-MI remodeling and subsequent heart failure.

  15. Functional Coupling of Ca2+ Channels and Ryanodine Receptors in Cardiac Myocytes

    NASA Astrophysics Data System (ADS)

    Sham, James S. K.; Cleemann, Lars; Morad, Martin

    1995-01-01

    In skeletal muscle, dihydropyridine receptors are functionally coupled to ryanodine receptors of the sarcoplasmic reticulum in triadic or diadic junctional complexes. In cardiac muscle direct physical or functional couplings have not been demonstrated. We have tested the hypothesis of functional coupling of L-type Ca2+ channels and ryanodine receptors in rat cardiac myocytes by comparing the efficacies of Ca2+ in triggering Ca2+ release when the ion enters the cell via the Ca2+ channels or the Na^+/Ca2+ exchanger. Ca2+ transported through the Ca2+ channels was 20-160 times more effective than Ca2+ influx via the Na^+/Ca2+ exchanger in gating Ca2+ release from the sarcoplasmic reticulum, suggesting privileged communication between Ca2+ channels and ryanodine receptors. In support of this hypothesis we found that Ca2+ channels were inactivated by Ca2+ release from the sarcoplasmic reticulum, even though the myoplasmic Ca2+ concentrations were buffered with 10 mM EGTA. The data thus suggest privileged cross signaling between the dihydropyridine and ryanodine receptors such that Ca2+ flux through either the Ca2+ channel or the ryanodine receptor alters the gating kinetics of the other channel.

  16. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function

    PubMed Central

    Bibee, Kristin P.; Cheng, Ya-Jian; Ching, James K.; Marsh, Jon N.; Li, Allison J.; Keeling, Richard M.; Connolly, Anne M.; Golumbek, Paul T.; Myerson, Jacob W.; Hu, Grace; Chen, Junjie; Shannon, William D.; Lanza, Gregory M.; Weihl, Conrad C.; Wickline, Samuel A.

    2014-01-01

    Duchenne muscular dystrophy in boys progresses rapidly to severe impairment of muscle function and death in the second or third decade of life. Current supportive therapy with corticosteroids results in a modest increase in strength as a consequence of a general reduction in inflammation, albeit with potential untoward long-term side effects and ultimate failure of the agent to maintain strength. Here, we demonstrate that alternative approaches that rescue defective autophagy in mdx mice, a model of Duchenne muscular dystrophy, with the use of rapamycin-loaded nanoparticles induce a reproducible increase in both skeletal muscle strength and cardiac contractile performance that is not achievable with conventional oral rapamycin, even in pharmacological doses. This increase in physical performance occurs in both young and adult mice, and, surprisingly, even in aged wild-type mice, which sets the stage for consideration of systemic therapies to facilitate improved cell function by autophagic disposal of toxic byproducts of cell death and regeneration.—Bibee, K. P., Cheng, Y.-J., Ching, J. K., Marsh, J. N., Li, A. J., Keeling, R. M., Connolly, A. M., Golumbek, P. T., Myerson, J. W., Hu, G., Chen, J., Shannon, W. D., Lanza, G. M., Weihl, C. C., Wickline, S. A. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function. PMID:24500923

  17. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    PubMed

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged < or =50 years (n=10), and older men aged >50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; P<0.05 each). Although the age dependent impairment is thought to cause this depression, neither the per cent increase in EF nor the per cent decrease in VR in the older men was significantly different from that in the younger men. Post-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause. PMID:12673166

  18. Impaired cardiac response to exercise in post-menopausal women: relationship with peripheral vascular function.

    PubMed

    Yoshioka, J; Node, K; Hasegawa, S; Paul, A K; Mu, X; Maruyama, K; Nakatani, D; Kitakaze, M; Hori, M; Nishimura, T

    2003-04-01

    Endothelial dysfunction has been demonstrated in post-menopausal women. To assess the relationship between peripheral vascular reserve and cardiac function during exercise in post-menopausal women, 91 subjects, who had no ischaemic findings on myocardial SPECT, were assigned to four groups: pre-menopausal women (n=13), post-menopausal women (n=33), younger men aged < or =50 years (n=10), and older men aged >50 years (n=35). First-pass radionuclide angiography was performed before and during bicycle exercise to calculate ejection fraction (EF) and peripheral vascular resistance (VR). There were no differences in haemodynamic variables among the groups at baseline. The per cent increase in EF=(exercise EF - resting EF)x100/resting EF, and the per cent decrease in VR=(resting VR - exercise VR)x100/resting VR were depressed in the post-menopausal women (0.4+/-2% and 35+/-3%, respectively) compared to the pre-menopausal women (10+/-3% and 47+/-3%, respectively; P<0.05 each). Although the age dependent impairment is thought to cause this depression, neither the per cent increase in EF nor the per cent decrease in VR in the older men was significantly different from that in the younger men. Post-menopausal women exhibited depressed cardiac function during exercise, which may be related to the impairment of peripheral vascular function after menopause.

  19. Impact of Thoracic Surgery on Cardiac Morphology and Function in Small Animal Models of Heart Disease: A Cardiac MRI Study in Rats

    PubMed Central

    Nordbeck, Peter; Bönhof, Leoni; Hiller, Karl-Heinz; Voll, Sabine; Arias-Loza, Paula; Seidlmayer, Lea; Williams, Tatjana; Ye, Yu-Xiang; Gensler, Daniel; Pelzer, Theo; Ertl, Georg; Jakob, Peter M.

    2013-01-01

    Background Surgical procedures in small animal models of heart disease might evoke alterations in cardiac morphology and function. The aim of this study was to reveal and quantify such potential artificial early or long term effects in vivo, which might account for a significant bias in basic cardiovascular research, and, therefore, could potentially question the meaning of respective studies. Methods Female Wistar rats (n = 6 per group) were matched for weight and assorted for sham left coronary artery ligation or control. Cardiac morphology and function was then investigated in vivo by cine magnetic resonance imaging at 7 Tesla 1 and 8 weeks after the surgical procedure. The time course of metabolic and inflammatory blood parameters was determined in addition. Results Compared to healthy controls, rats after sham surgery showed a lower body weight both 1 week (267.5±10.6 vs. 317.0±11.3 g, n<0.05) and 8 weeks (317.0±21.1 vs. 358.7±22.4 g, n<0.05) after the intervention. Left and right ventricular morphology and function were not different in absolute measures in both groups 1 week after surgery. However, there was a confined difference in several cardiac parameters normalized to the body weight (bw), such as myocardial mass (2.19±0.30/0.83±0.13 vs. 1.85±0.22/0.70±0.07 mg left/right per g bw, p<0.05), or enddiastolic ventricular volume (1.31±0.36/1.21±0.31 vs. 1.14±0.20/1.07±0.17 µl left/right per g bw, p<0.05). Vice versa, after 8 weeks, cardiac masses, volumes, and output showed a trend for lower values in sham operated rats compared to controls in absolute measures (782.2±57.2/260.2±33.2 vs. 805.9±84.8/310.4±48.5 mg, p<0.05 for left/right ventricular mass), but not normalized to body weight. Matching these findings, blood testing revealed only minor inflammatory but prolonged metabolic changes after surgery not related to cardiac disease. Conclusion Cardio-thoracic surgical procedures in experimental myocardial infarction cause distinct

  20. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne Muscular Dystrophy

    PubMed Central

    Galindo, Cristi L.; Soslow, Jonathan H.; Brinkmeyer-Langford, Candice L.; Gupte, Manisha; Smith, Holly M.; Sengsayadeth, Seng; Sawyer, Douglas B.; Benson, D. Woodrow; Kornegay, Joe N.; Markham, Larry W.

    2016-01-01

    Background In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. Methods We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ months) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. Results We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. Conclusion These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively. PMID:26672735

  1. Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process.

    PubMed

    Avitabile, Daniele; Crespi, Alessia; Brioschi, Chiara; Parente, Valeria; Toietta, Gabriele; Devanna, Paolo; Baruscotti, Mirko; Truffa, Silvia; Scavone, Angela; Rusconi, Francesca; Biondi, Andrea; D'Alessandra, Yuri; Vigna, Elisa; Difrancesco, Dario; Pesce, Maurizio; Capogrossi, Maurizio C; Barbuti, Andrea

    2011-05-01

    The efficacy of cardiac repair by stem cell administration relies on a successful functional integration of injected cells into the host myocardium. Safety concerns have been raised about the possibility that stem cells may induce foci of arrhythmia in the ischemic myocardium. In a previous work (36), we showed that human cord blood CD34(+) cells, when cocultured on neonatal mouse cardiomyocytes, exhibit excitation-contraction coupling features similar to those of cardiomyocytes, even though no human genes were upregulated. The aims of the present work are to investigate whether human CD34(+) cells, isolated after 1 wk of coculture with neonatal ventricular myocytes, possess molecular and functional properties of cardiomyocytes and to discriminate, using a reporter gene system, whether cardiac differentiation derives from a (trans)differentiation or a cell fusion process. Umbilical cord blood CD34(+) cells were isolated by a magnetic cell sorting method, transduced with a lentiviral vector carrying the enhanced green fluorescent protein (EGFP) gene, and seeded onto primary cultures of spontaneously beating rat neonatal cardiomyocytes. Cocultured EGFP(+)/CD34(+)-derived cells were analyzed for their electrophysiological features at different time points. After 1 wk in coculture, EGFP(+) cells, in contact with cardiomyocytes, were spontaneously contracting and had a maximum diastolic potential (MDP) of -53.1 mV, while those that remained isolated from the surrounding myocytes did not contract and had a depolarized resting potential of -11.4 mV. Cells were then resuspended and cultured at low density to identify EGFP(+) progenitor cell derivatives. Under these conditions, we observed single EGFP(+) beating cells that had acquired an hyperpolarization-activated current typical of neonatal cardiomyocytes (EGFP(+) cells, -2.24 ± 0.89 pA/pF; myocytes, -1.99 ± 0.63 pA/pF, at -125 mV). To discriminate between cell autonomous differentiation and fusion, EGFP(+)/CD34

  2. The Effect of Acute Coronary Perfusion Change on Cardiac Function measured by Shear Wave Elasticity Imaging

    PubMed Central

    Vejdani-Jahromi, Maryam; Kiplagat, Annette; Trahey, Gregg E.; Wolf, Patrick D.

    2016-01-01

    The possibility of measuring cardiac function noninvasively has generated wide interest in elastography imaging techniques. Shear Wave Elasticity Imaging (SWEI) is an ultrasound-based elastography technique used to measure stiffness of tissues. While this technique has been studied extensively in static homogenous tissues such as liver, breast or prostate, there is still a significant need to study its capabilities to measure cardiac stiffness and function. In this research, we have studied the potential of SWEI to evaluate the coronary perfusion pressure effect on systolic and diastolic stiffness referred to as elastance and compliance of the heart. Five isolated rabbit hearts were used in this study in a Langendorff preparation. SWEI measurements of stiffness were recorded in two steps. In the first step, coronary perfusion was set to normal and then was reduced to half-normal. After 40 minutes of half-normal perfusion, it was returned to normal perfusion for the second step. SWEI velocity decreased from 6.003 m/s to 4.713 m/s in systole and from 1.948 m/s to 1.507 m/s in diastole in the first step. During the second step raising the perfusion to normal, SWEI stiffness showed an increase from 3.760 m/s to 5.468 m/s in systole and from 1.678 m/s to 2.156 m/s during diastole. Our results show that SWEI measurements of stiffness can characterize the cross talk between coronary perfusion and cardiac stiffness and also has the potential to measure compliance and elastance of the heart in systole and diastole. PMID:25571133

  3. Effects of depth and chest volume on cardiac function during breath-hold diving.

    PubMed

    Marabotti, Claudio; Scalzini, Alessandro; Cialoni, Danilo; Passera, Mirko; Ripoli, Andrea; L'Abbate, Antonio; Bedini, Remo

    2009-07-01

    Cardiac response to breath-hold diving in human beings is primarily characterized by the reduction of both heart rate and stroke volume. By underwater Doppler-echocardiography we observed a "restrictive/constrictive" left ventricular filling pattern compatible with the idea of chest squeeze and heart compression during diving. We hypothesized that underwater re-expansion of the chest would release heart constriction and normalize cardiac function. To this aim, 10 healthy male subjects (age 34.2 +/- 10.4) were evaluated by Doppler-echocardiography during breath-hold immersion at a depth of 10 m, before and after a single maximal inspiration from a SCUBA device. During the same session, all subjects were also studied at surface (full-body immersion) and at 5-m depth in order to better characterize the relationship of echo-Doppler pattern with depth. In comparison to surface immersion, 5-m deep diving was sufficient to reduce cardiac output (P = 0.042) and increase transmitral E-peak velocity (P < 0.001). These changes remained unaltered at a 10-m depth. Chest expansion at 10 m decreased left ventricular end-systolic volume (P = 0.024) and increased left ventricular stroke volume (P = 0.024). In addition, it decreased transmitral E-peak velocity (P = 0.012) and increased deceleration time of E-peak (P = 0.021). In conclusion the diving response, already evident during shallow diving (5 m) did not progress during deeper dives (10 m). The rapid improvement in systolic and diastolic function observed after lung volume expansion is congruous with the idea of a constrictive effect on the heart exerted by chest squeeze.

  4. Functional Cardiac Magnetic Resonance Imaging (MRI) in the Assessment of Myocardial Viability and Perfusion

    PubMed Central

    2003-01-01

    Executive Summary Objective The objective of this health technology policy assessment was to determine the effectiveness safety and cost-effectiveness of using functional cardiac magnetic resonance imaging (MRI) for the assessment of myocardial viability and perfusion in patients with coronary artery disease and left ventricular dysfunction. Results Functional MRI has become increasingly investigated as a noninvasive method for assessing myocardial viability and perfusion. Most patients in the published literature have mild to moderate impaired LV function. It is possible that the severity of LV dysfunction may be an important factor that can alter the diagnostic accuracy of imaging techniques. There is some evidence of comparable or better performance of functional cardiac MRI for the assessment of myocardial viability and perfusion compared with other imaging techniques. However limitations to most of the studies included: Functional cardiac MRI studies that assess myocardial viability and perfusion have had small sample sizes. Some studies assessed myocardial viability/perfusion in patients who had already undergone revascularization, or excluded patients with a prior MI (Schwitter et al., 2001). Lack of explicit detail of patient recruitment. Patients with LVEF >35%. Interstudy variability in post MI imaging time(including acute or chronic MI), when patients with a prior MI were included. Poor interobserver agreement (kappa statistic) in the interpretation of the results. Traditionally, 0.80 is considered “good”. Cardiac MRI measurement of myocardial perfusion to as an adjunct tool to help diagnose CAD (prior to a definitive coronary angiography) has also been examined in some studies, with methodological limitations, yielding comparable results. Many studies examining myocardial viability and perfusion report on the accuracy of imaging methods with limited data on long-term patient outcome and management. Kim et al. (2000) revealed that the transmural

  5. Bimodal biophotonic imaging of the structure-function relationship in cardiac tissue

    PubMed Central

    Hucker, William J.; Ripplinger, Crystal M.; Fleming, Christine P.; Fedorov, Vadim V.; Rollins, Andrew M.; Efimov, Igor R.

    2009-01-01

    The development of systems physiology is hampered by the limited ability to relate tissue structure and function in intact organs in vivo or in vitro. Here, we show the application of a bimodal biophotonic imaging approach that employs optical coherence tomography and fluorescent imaging to investigate the structure-function relationship at the tissue level in the heart. Reconstruction of cardiac excitation and structure was limited by the depth penetration of bimodal imaging to ∼2 mm in atrial tissue, and ∼1 mm in ventricular myocardium. The subcellular resolution of optical coherence tomography clearly demonstrated that microscopic fiber orientation governs the pattern of wave propagation in functionally characterized rabbit sinoatrial and atrioventricular nodal preparations and revealed structural heterogeneities contributing to ventricular arrhythmias. The combination of this bimodal biophotonic imaging approach with histology and/or immunohistochemistry can span multiple scales of resolution for the investigation of the molecular and structural determinants of intact tissue physiology. PMID:19021392

  6. Can Functional Cardiac Age be Predicted from ECG in a Normal Healthy Population

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd; Starc, Vito; Leban, Manja; Sinigoj, Petra; Vrhovec, Milos

    2011-01-01

    In a normal healthy population, we desired to determine the most age-dependent conventional and advanced ECG parameters. We hypothesized that changes in several ECG parameters might correlate with age and together reliably characterize the functional age of the heart. Methods: An initial study population of 313 apparently healthy subjects was ultimately reduced to 148 subjects (74 men, 84 women, in the range from 10 to 75 years of age) after exclusion criteria. In all subjects, ECG recordings (resting 5-minute 12-lead high frequency ECG) were evaluated via custom software programs to calculate up to 85 different conventional and advanced ECG parameters including beat-to-beat QT and RR variability, waveform complexity, and signal-averaged, high-frequency and spatial/spatiotemporal ECG parameters. The prediction of functional age was evaluated by multiple linear regression analysis using the best 5 univariate predictors. Results: Ignoring what were ultimately small differences between males and females, the functional age was found to be predicted (R2= 0.69, P < 0.001) from a linear combination of 5 independent variables: QRS elevation in the frontal plane (p<0.001), a new repolarization parameter QTcorr (p<0.001), mean high frequency QRS amplitude (p=0.009), the variability parameter % VLF of RRV (p=0.021) and the P-wave width (p=0.10). Here, QTcorr represents the correlation between the calculated QT and the measured QT signal. Conclusions: In apparently healthy subjects with normal conventional ECGs, functional cardiac age can be estimated by multiple linear regression analysis of mostly advanced ECG results. Because some parameters in the regression formula, such as QTcorr, high frequency QRS amplitude and P-wave width also change with disease in the same direction as with increased age, increased functional age of the heart may reflect subtle age-related pathologies in cardiac electrical function that are usually hidden on conventional ECG.

  7. 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

  8. Salvianolic acid B functioned as a competitive inhibitor of matrix metalloproteinase-9 and efficiently prevented cardiac remodeling

    PubMed Central

    2010-01-01

    Background Infarct-induced left ventricular (LV) remodeling is a deleterious consequence after acute myocardial infarction (MI) which may further advance to congestive heart failure. Therefore, new therapeutic strategies to attenuate the effects of LV remodeling are urgently needed. Salvianolic acid B (SalB) from Salviae mitiorrhizae, which has been widely used in China for the treatment of cardiovascular diseases, is a potential candidate for therapeutic intervention of LV remodeling targeting matrix metalloproteinase-9 (MMP-9). Results Molecular modeling and LIGPLOT analysis revealed in silico docking of SalB at the catalytic site of MMP-9. Following this lead, we expressed truncated MMP-9 which contains only the catalytic domain, and used this active protein for in-gel gelatin zymography, enzymatic analysis, and SalB binding by Biacore. Data generated from these assays indicated that SalB functioned as a competitive inhibitor of MMP-9. In our rat model for cardiac remodeling, western blot, echocardiography, hemodynamic measurement and histopathological detection were used to detect the effects and mechanism of SalB on cardio-protection. Our results showed that in MI rat, SalB selectively inhibited MMP-9 activities without affecting MMP-9 expression while no effect of SalB was seen on MMP-2. Moreover, SalB treatment in MI rat could efficiently increase left ventricle wall thickness, improve heart contractility, and decrease heart fibrosis. Conclusions As a competitive inhibitor of MMP-9, SalB presents significant effects on preventing LV structural damage and preserving cardiac function. Further studies to develop SalB and its analogues for their potential for cardioprotection in clinic are warranted. PMID:20735854

  9. Diastolic abnormalities in systemic sclerosis: evidence for associated defective cardiac functional reserve.

    PubMed Central

    Valentini, G; Vitale, D F; Giunta, A; Maione, S; Gerundo, G; Arnese, M; Tirri, E; Pelaggi, N; Giacummo, A; Tirri, G; Condorelli, M

    1996-01-01

    OBJECTIVE: To investigate the pattern of diastolic abnormalities in patients with systemic sclerosis (SSc) and the relationship between impaired ventricular filling and systolic function. METHODS: Twenty four patients with SSc underwent M-mode and two dimensional echocardiography using echo-Doppler and gated blood pool cardiac angiography, both at rest and after exercise. RESULTS: An impaired diastolic relaxation of the left ventricle was detected in 10 of the 24 patients with SSc. Left ventricular ejection fraction at rest in these 10 patients with impaired ventricular filling did not differ from that in the remaining 14 patients, but eight of the 10 failed to increase their ejection fraction during exercise, compared with two of the 14 with normal ventricular filling (p = 0.003). CONCLUSION: Impaired relaxation of the left ventricle is a recently described feature of scleroderma heart disease. Diastolic dysfunction in SSc could depend on myocardial fibrosis or myocardial ischaemia, or both. It was found to be associated with a defective cardiac functional reserve. However, its prognostic significance remains to be clarified. PMID:8774164

  10. Effect of fiber diameter on the assembly of functional 3D cardiac patches

    NASA Astrophysics Data System (ADS)

    Fleischer, Sharon; Miller, Jacob; Hurowitz, Haley; Shapira, Assaf; Dvir, Tal

    2015-07-01

    The cardiac ECM has a unique 3D structure responsible for tissue morphogenesis and strong contractions. It is divided into three fiber groups with specific roles and distinct dimensions; nanoscale endomysial fibers, perimysial fibers with a diameter of 1 μm, and epimysial fibers, which have a diameter of several micrometers. We report here on our work, where distinct 3D fibrous scaffolds, each of them recapitulating the dimension scales of a single fiber population in the heart matrix, were fabricated. We have assessed the mechanical properties of these scaffolds and the contribution of each fiber population to cardiomyocyte morphogenesis, tissue assembly and function. Our results show that the nanoscale fiber scaffolds were more elastic than the microscale scaffolds, however, cardiomyocytes cultured on microscale fiber scaffolds exhibited enhanced spreading and elongation, both on the single cell and on the engineered tissue levels. In addition, lower fibroblast proliferation rates were observed on these microscale topographies. Based on the collected data we have fabricated composite scaffolds containing micro and nanoscale fibers, promoting superior tissue morphogenesis without compromising tissue contraction. Cardiac tissues, engineered within these composite scaffolds exhibited superior function, including lower excitation threshold and stronger contraction forces than tissue engineered within the single-population fiber scaffolds.

  11. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review.

    PubMed

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R

    2015-07-01

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.

  12. Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

    PubMed

    Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

    2016-06-01

    Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P < 0.001). Mild right ventricular dilatation and grade I pulmonary hypertension were present in three (12 %) workers of the coke-making part, but none of the controls (P = 0.010). According to these results, occupational air pollution exposure in workers of the steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations. PMID:26946505

  13. Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component?

    PubMed Central

    Sears, Claire E; Ashley, Euan A; Casadei, Barbara

    2004-01-01

    Nitric oxide (NO) has been shown to regulate cardiac function, both in physiological conditions and in disease states. However, several aspects of NO signalling in the myocardium remain poorly understood. It is becoming increasingly apparent that the disparate functions ascribed to NO result from its generation by different isoforms of the NO synthase (NOS) enzyme, the varying subcellular localization and regulation of NOS isoforms and their effector proteins. Some apparently contrasting findings may have arisen from the use of non-isoform-specific inhibitors of NOS, and from the assumption that NO donors may be able to mimic the actions of endogenously produced NO. In recent years an at least partial explanation for some of the disagreements, although by no means all, may be found from studies that have focused on the role of the neuronal NOS (nNOS) isoform. These data have shown a key role for nNOS in the control of basal and adrenergically stimulated cardiac contractility and in the autonomic control of heart rate. Whether or not the role of nNOS carries implications for cardiovascular disease remains an intriguing possibility requiring future study. PMID:15306414

  14. Exposure to occupational air pollution and cardiac function in workers of the Esfahan Steel Industry, Iran.

    PubMed

    Golshahi, Jafar; Sadeghi, Masoumeh; Saqira, Mohammad; Zavar, Reihaneh; Sadeghifar, Mostafa; Roohafza, Hamidreza

    2016-06-01

    Air pollution is recognized as an important risk factor for cardiovascular disease. We investigated association of exposure to occupational air pollution and cardiac function in the workers of the steel industry. Fifty male workers of the agglomeration and coke-making parts of the Esfahan Steel Company were randomly selected (n = 50). Workers in the administrative parts were studied as controls (n = 50). Those with known history of hypertension, dyslipidemia, or diabetes, and active smokers were not included. Data of age, body mass index, employment duration, blood pressure, fasting blood sugar, and lipid profile were gathered. Echocardiography was performed to evaluate cardiac function. Left ventricular ejection fraction was lower in workers of the agglomeration/coke-making parts than in controls (mean difference = 5 to 5.5 %, P < 0.001). Mild right ventricular dilatation and grade I pulmonary hypertension were present in three (12 %) workers of the coke-making part, but none of the controls (P = 0.010). According to these results, occupational air pollution exposure in workers of the steel industry is associated with left heart systolic dysfunction. Possible right heart insults due to air pollution exposure warrant further investigations.

  15. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving.

    PubMed

    Shiels, H A; Galli, G L J; Block, B A

    2015-02-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation-contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca(2+) transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation-contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range.

  16. Strategies for the chemical and biological functionalization of scaffolds for cardiac tissue engineering: a review

    PubMed Central

    Tallawi, Marwa; Rosellini, Elisabetta; Barbani, Niccoletta; Cascone, Maria Grazia; Rai, Ranjana; Saint-Pierre, Guillaume; Boccaccini, Aldo R.

    2015-01-01

    The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed. PMID:26109634

  17. The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease.

    PubMed

    Townley-Tilson, W H Davin; Pi, Xinchun; Xie, Liang

    2015-01-01

    Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease.

  18. Morphological and Functional Evaluation of Quadricuspid Aortic Valves Using Cardiac Computed Tomography

    PubMed Central

    Song, Inyoung; Park, Jung Ah; Choi, Bo Hwa; Shin, Je Kyoun; Chee, Hyun Keun; Kim, Jun Seok

    2016-01-01

    Objective The aim of this study was to identify the morphological and functional characteristics of quadricuspid aortic valves (QAV) on cardiac computed tomography (CCT). Materials and Methods We retrospectively enrolled 11 patients with QAV. All patients underwent CCT and transthoracic echocardiography (TTE), and 7 patients underwent cardiovascular magnetic resonance (CMR). The presence and classification of QAV assessed by CCT was compared with that of TTE and intraoperative findings. The regurgitant orifice area (ROA) measured by CCT was compared with severity of aortic regurgitation (AR) by TTE and the regurgitant fraction (RF) by CMR. Results All of the patients had AR; 9 had pure AR, 1 had combined aortic stenosis and regurgitation, and 1 had combined subaortic stenosis and regurgitation. Two patients had a subaortic fibrotic membrane and 1 of them showed a subaortic stenosis. One QAV was misdiagnosed as tricuspid aortic valve on TTE. In accordance with the Hurwitz and Robert's classification, consensus was reached on the QAV classification between the CCT and TTE findings in 7 of 10 patients. The patients were classified as type A (n = 1), type B (n = 3), type C (n = 1), type D (n = 4), and type F (n = 2) on CCT. A very high correlation existed between ROA by CCT and RF by CMR (r = 0.99) but a good correlation existed between ROA by CCT and regurgitant severity by TTE (r = 0.62). Conclusion Cardiac computed tomography provides comprehensive anatomical and functional information about the QAV. PMID:27390538

  19. Cardiac function in an endothermic fish: cellular mechanisms for overcoming acute thermal challenges during diving

    PubMed Central

    Shiels, H. A.; Galli, G. L. J.; Block, B. A.

    2015-01-01

    Understanding the physiology of vertebrate thermal tolerance is critical for predicting how animals respond to climate change. Pacific bluefin tuna experience a wide range of ambient sea temperatures and occupy the largest geographical niche of all tunas. Their capacity to endure thermal challenge is due in part to enhanced expression and activity of key proteins involved in cardiac excitation–contraction coupling, which improve cardiomyocyte function and whole animal performance during temperature change. To define the cellular mechanisms that enable bluefin tuna hearts to function during acute temperature change, we investigated the performance of freshly isolated ventricular myocytes using confocal microscopy and electrophysiology. We demonstrate that acute cooling and warming (between 8 and 28°C) modulates the excitability of the cardiomyocyte by altering the action potential (AP) duration and the amplitude and kinetics of the cellular Ca2+ transient. We then explored the interactions between temperature, adrenergic stimulation and contraction frequency, and show that when these stressors are combined in a physiologically relevant way, they alter AP characteristics to stabilize excitation–contraction coupling across an acute 20°C temperature range. This allows the tuna heart to maintain consistent contraction and relaxation cycles during acute thermal challenges. We hypothesize that this cardiac capacity plays a key role in the bluefin tunas' niche expansion across a broad thermal and geographical range. PMID:25540278

  20. The Role of Oxygen Sensors, Hydroxylases, and HIF in Cardiac Function and Disease

    PubMed Central

    Townley-Tilson, W. H. Davin; Pi, Xinchun; Xie, Liang

    2015-01-01

    Ischemic heart disease is the leading cause of death worldwide. Oxygen-sensing proteins are critical components of the physiological response to hypoxia and reperfusion injury, but the role of oxygen and oxygen-mediated effects is complex in that they can be cardioprotective or deleterious to the cardiac tissue. Over 200 oxygen-sensing proteins mediate the effects of oxygen tension and use oxygen as a substrate for posttranslational modification of other proteins. Hydroxylases are an essential component of these oxygen-sensing proteins. While a major role of hydroxylases is regulating the transcription factor HIF, we investigate the increasing scope of hydroxylase substrates. This review discusses the importance of oxygen-mediated effects in the heart as well as how the field of oxygen-sensing proteins is expanding, providing a more complete picture into how these enzymes play a multifaceted role in cardiac function and disease. We also review how oxygen-sensing proteins and hydroxylase function could prove to be invaluable in drug design and therapeutic targets for heart disease. PMID:26491535

  1. A Meta-Analysis of Renal Function After Adult Cardiac Surgery With Pulsatile Perfusion.

    PubMed

    Nam, Myung Ji; Lim, Choon Hak; Kim, Hyun-Jung; Kim, Yong Hwi; Choi, Hyuk; Son, Ho Sung; Lim, Hae Ja; Sun, Kyung

    2015-09-01

    The aim of this meta-analysis was to determine whether pulsatile perfusion during cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 25, 2014. Meta-analysis was conducted to determine the effects of pulsatile perfusion on postoperative renal functions, as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving 674 patients that received pulsatile perfusion and 698 patients that received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Stratified analysis was performed according to effective pulsatility or unclear pulsatility of the pulsatile perfusion method in the presence of heterogeneity. NGAL levels were not significantly different between the pulsatile and nonpulsatile groups. However, patients in the pulsatile group had a significantly higher CrCl and lower Cr levels when the analysis was restricted to studies on effective pulsatile flow (P < 0.00001, respectively). The incidence of ARI was significantly lower in the pulsatile group (P < 0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative renal function.

  2. Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

    NASA Technical Reports Server (NTRS)

    Meck, Janice V.; Martin, David S.; D'Aunno, Dominick S.; Waters, Wendy W.

    2003-01-01

    Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

  3. Comparative impact of AAV and enzyme replacement therapy on respiratory and cardiac function in adult Pompe mice

    PubMed Central

    Falk, Darin J; Soustek, Meghan S; Todd, Adrian Gary; Mah, Cathryn S; Cloutier, Denise A; Kelley, Jeffry S; Clement, Nathalie; Fuller, David D; Byrne, Barry J

    2015-01-01

    Pompe disease is an autosomal recessive genetic disorder characterized by a deficiency of the enzyme responsible for degradation of lysosomal glycogen (acid α-glucosidase (GAA)). Cardiac dysfunction and respiratory muscle weakness are primary features of this disorder. To attenuate the progressive and rapid accumulation of glycogen resulting in cardiorespiratory dysfunction, adult Gaa–/– mice were administered a single systemic injection of rAAV2/9-DES-hGAA (AAV9-DES) or bimonthly injections of recombinant human GAA (enzyme replacement therapy (ERT)). Assessment of cardiac function and morphology was measured 1 and 3 months after initiation of treatment while whole-body plethysmography and diaphragmatic contractile function was evaluated at 3 months post-treatment in all groups. Gaa–/– animals receiving either AAV9-DES or ERT demonstrated a significant improvement in cardiac function and diaphragmatic contractile function as compared to control animals. AAV9-DES treatment resulted in a significant reduction in cardiac dimension (end diastolic left ventricular mass/gram wet weight; EDMc) at 3 months postinjection. Neither AAV nor ERT therapy altered minute ventilation during quiet breathing (eupnea). However, breathing frequency and expiratory time were significantly improved in AAV9-DES animals. These results indicate systemic delivery of either strategy improves cardiac function but AAV9-DES alone improves respiratory parameters at 3 months post-treatment in a murine model of Pompe disease. PMID:26029718

  4. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    PubMed Central

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by

  5. Electrocardiogram and cardiac function in a longitudinal study of copper deficiency in the Long-Evans rat

    SciTech Connect

    Zhiming Liao, Hamlin, R.; Medeiros, D.M. )

    1991-03-11

    Weanling Long-Evans rats were fed either copper-adequate or -restricted diets for varying periods of time up to 6 wk. Beginning at 2 wk after weaning, and weekly thereafter, 5 rats from each diet were evaluated for cardiac function and ECG activity and sacrificed. ECG traces revealed indications of cardiac failure at week 3 in rats fed the copper-restricted diet at which time concentric cardiac hypertrophy was evident. Prolonged P-R and Q-T intervals and greater QRS height and higher voltages were observed in copper-restricted rats. However, + and {minus} dP/dt max did not differ by diet copper treatment for any of the time intervals studied, nor was any notable difference in total left developed ventricular pressure apparent. These results suggest that the onset of cardiac dysfunction in copper deficiency is rapid, with both dysfunction and hypertrophy apparent within 3 weeks after copper restriction.

  6. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity

    PubMed Central

    Quevedo, Henry C.; Hatzistergos, Konstantinos E.; Oskouei, Behzad N.; Feigenbaum, Gary S.; Rodriguez, Jose E.; Valdes, David; Pattany, Pradip M.; Zambrano, Juan P.; Hu, Qinghua; McNiece, Ian; Heldman, Alan W.; Hare, Joshua M.

    2009-01-01

    The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC) remain highly controversial. Here we tested the hypothesis that MSCs regenerate chronically infarcted myocardium through mechanisms comprising long-term engraftment and trilineage differentiation. Twelve weeks after myocardial infarction, female swine received catheter-based transendocardial injections of either placebo (n = 4) or male allogeneic MSCs (200 million; n = 6). Animals underwent serial cardiac magnetic resonance imaging, and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos) cells with markers of cardiac, vascular muscle, and endothelial lineages. MSCs engrafted in infarct and border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4, Nkx2.5, and α-sarcomeric actin. In addition, Ypos MSCs exhibited vascular smooth muscle and endothelial cell differentiation, contributing to large and small vessel formation. Infarct size was reduced from 19.3 ± 1.7% to 13.9 ± 2.0% (P < 0.001), and ejection fraction (EF) increased from 35.0 ± 1.7% to 41.3 ± 2.7% (P < 0.05) in MSC but not placebo pigs over 12 weeks. This was accompanied by increases in regional contractility and myocardial blood flow (MBF), particularly in the infarct border zone. Importantly, MSC engraftment correlated with functional recovery in contractility (R = 0.85, P < 0.05) and MBF (R = 0.76, P < 0.01). Together these findings demonstrate long-term MSC survival, engraftment, and trilineage differentiation following transplantation into chronically scarred myocardium. MSCs are an adult stem cell with the capacity for cardiomyogenesis and vasculogenesis which contribute, at least in part, to their ability to repair chronically scarred myocardium. PMID:19666564

  7. Functional coupling with cardiac muscle promotes maturation of hPSC-derived sympathetic neurons

    PubMed Central

    Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang

    2016-01-01

    Summary Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B:eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties, and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX:eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040

  8. Bromocriptine for an acromegalic patient. Improvement in cardiac function and carpal tunnel syndrome.

    PubMed

    Luboshitzky, R; Barzilai, D

    1980-10-17

    A 64-year-old woman with active acromegaly of 33 years' duration, severe carpal tunnel syndrome, and subclinical heart disease was treated with bromocriptine mesylate. Within eight months of therapy, basal growth hormone (GH) levels decreased from 90.0 to 7.0 ng/mL, and hand volume was reduced from 375 to 295 mL. Concomitantly, echocardiographic studies showed normal left ventricular size and function. Electromyographic studies demonstrated normal function in both median nerves. Bromocriptine may correct cardiac dysfunction and carpal tunnel syndrome in acromegaly either by reduction of GH oversecretion or by a direct effect of bromocriptine on dopamine receptors in the heart and peripheral nerve endings.

  9. ECG and Navigator-Free 4D Whole-Heart Coronary MRA for Simultaneous Visualization of Cardiac Anatomy and Function

    PubMed Central

    Pang, Jianing; Sharif, Behzad; Fan, Zhaoyang; Bi, Xiaoming; Arsanjani, Reza; Berman, Daniel S.; Li, Debiao

    2014-01-01

    Purpose To develop a cardiac and respiratory self-gated 4D coronary MRA technique for simultaneous cardiac anatomy and function visualization. Methods A contrast-enhanced, ungated spoiled gradient echo sequence with self-gating (SG) and 3DPR trajectory was used for image acquisition. Data was retrospectively binned into different cardiac and respiratory phases based on information extracted from SG projections using principal component analysis. Each cardiac phase was reconstructed using a respiratory motion-corrected self-calibrating SENSE framework, and those belong to the quiescent period were retrospectively combined for coronary visualization. Healthy volunteer studies were conducted to evaluate the efficacy of the SG method, the accuracy of the left ventricle (LV) function parameters and the quality of coronary artery visualization. Results SG performed reliably for all subjects including one with poor ECG. The LV function parameters showed excellent agreement with those from a conventional cine protocol. For coronary imaging, the proposed method yielded comparable apparent SNR and coronary sharpness and lower apparent CNR on three subjects compared with an ECG and navigator-gated Cartesian protocol and an ECG-gated, respiratory motion-corrected 3DPR protocol. Conclusion A fully self-gated 4D whole-heart imaging technique was developed, potentially allowing cardiac anatomy and function assessment from a single measurement. PMID:25216287

  10. Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

    NASA Astrophysics Data System (ADS)

    Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

    2014-03-01

    Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume

  11. Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

    PubMed Central

    Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

    2015-01-01

    Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA – a cohort of asymptomatic patients; and b) DETERMINE – a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end

  12. Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption, but increase cardiac function more than proportionally☆

    PubMed Central

    Kyriacou, Andreas; Pabari, Punam A.; Mayet, Jamil; Peters, Nicholas S.; Davies, D. Wyn; Lim, P. Boon; Lefroy, David; Hughes, Alun D.; Kanagaratnam, Prapa; Francis, Darrel P.; I.Whinnett, Zachary

    2014-01-01

    Background The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown. Methods Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO2) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB). Results AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04. AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22. Mechanoenergetics at AV-40 were no different from LBBB. The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02). Conclusions Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”. PMID:24332598

  13. SUMO-1 gene transfer improves cardiac function in a large-animal model of heart failure.

    PubMed

    Tilemann, Lisa; Lee, Ahyoung; Ishikawa, Kiyotake; Aguero, Jaume; Rapti, Kleopatra; Santos-Gallego, Carlos; Kohlbrenner, Erik; Fish, Kenneth M; Kho, Changwon; Hajjar, Roger J

    2013-11-13

    Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice. In a previous study, we showed that SUMO-1 gene transfer substantially improved cardiac function in a murine model of pressure overload-induced HF. Toward clinical translation, we evaluated in this study the effects of SUMO-1 gene transfer in a swine model of ischemic HF. One month after balloon occlusion of the proximal left anterior descending artery followed by reperfusion, the animals were randomized to receive either SUMO-1 at two doses, SERCA2a, or both by adeno-associated vector type 1 (AAV1) gene transfer via antegrade coronary infusion. Control animals received saline infusions. After gene delivery, there was a significant increase in the maximum rate of pressure rise [dP/dt(max)] that was most pronounced in the group that received both SUMO-1 and SERCA2a. The left ventricular ejection fraction (LVEF) improved after high-dose SUMO-1 with or without SERCA2a gene delivery, whereas there was a decline in LVEF in the animals receiving saline. Furthermore, the dilatation of LV volumes was prevented in the treatment groups. SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.

  14. A generalized activating function for predicting virtual electrodes in cardiac tissue.

    PubMed Central

    Sobie, E A; Susil, R C; Tung, L

    1997-01-01

    To fully understand the mechanisms of defibrillation, it is critical to know how a given electrical stimulus causes membrane polarizations in cardiac tissue. We have extended the concept of the activating function, originally used to describe neuronal stimulation, to derive a new expression that identifies the sources that drive changes in transmembrane potential. Source terms, or virtual electrodes, consist of either second derivatives of extracellular potential weighted by intracellular conductivity or extracellular potential gradients weighted by derivatives of intracellular conductivity. The full response of passive tissue can be considered, in simple cases, to be a convolution of this "generalized activating function" with the impulse response of the tissue. Computer simulations of a two-dimensional sheet of passive myocardium under steady-state conditions demonstrate that this source term is useful for estimating the effects of applied electrical stimuli. The generalized activating function predicts oppositely polarized regions of tissue when unequally anisotropic tissue is point stimulated and a monopolar response when a point stimulus is applied to isotropic tissue. In the bulk of the myocardium, this new expression is helpful for understanding mechanisms by which virtual electrodes can be produced, such as the hypothetical "sawtooth" pattern of polarization, as well as polarization owing to regions of depressed conductivity, missing cells or clefts, changes in fiber diameter, or fiber curvature. In comparing solutions obtained with an assumed extracellular potential distribution to those with fully coupled intra- and extracellular domains, we find that the former provides a reliable estimate of the total solution. Thus the generalized activating function that we have derived provides a useful way of understanding virtual electrode effects in cardiac tissue. Images FIGURE 2 FIGURE 4 FIGURE 5 FIGURE 6 PMID:9284308

  15. Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons.

    PubMed

    Parsons, Rodney L; Barstow, Karen L; Scornik, Fabiana S

    2002-09-01

    Mudpuppy parasympathetic neurons exhibit spontaneous miniature hyperpolarizations (SMHs) that are generated by potassium currents, which are spontaneous miniature outward currents (SMOCs), flowing through clusters of large conductance voltage- and calcium (Ca(2+))-activated potassium (BK) channels. The underlying SMOCs are initiated by a Ca(2+)-induced Ca(2+) release (CICR) mechanism. Perforated-patch whole cell voltage recordings were used to determine whether activation of SMHs contributed to action potential (AP) repolarization or affected the latency to AP generation. Blockade of BK channels by iberiotoxin (IBX, 100 nM) slowed AP repolarization and increased AP duration. Treatment with omega-conotoxin GVIA (3 microM) or nifedipine (10 microM) to inhibit Ca(2+) influx through N- or L-type voltage-dependent calcium channels (VDCCs), respectively, also decreased the rate of AP repolarization and increased AP duration. Elimination of CICR by treatment with either thapsigargin (1 microM) or ryanodine (10 microM) produced no significant change in AP repolarization or duration. Blockade of BK channels with IBX and inhibition of N-type VDCCs with omega-conotoxin GVIA, but not inhibition of L-type VDCCs with nifedipine, decreased the latency of AP generation. A decrease in latency to AP generation occurred with elimination of SMHs by inhibition of CICR following treatment with thapsigargin. Ryanodine treatment decreased AP latency in three of six cells. Apamin (100 nM) had no affect on AP repolarization, duration, or latency to AP generation, but did decrease the hyperpolarizing afterpotential (HAP). Inhibition of L-type VDCCs by nifedipine also decreased HAP amplitude. Inhibition of CICR by either thapsigargin or ryanodine treatment increased the number of APs generated with long depolarizing current pulses, whereas exposure to IBX or omega-conotoxin GVIA depressed excitability. We conclude that CICR, the process responsible for SMH generation, represents a unique

  16. miR-300 mediates Bmi1 function and regulates differentiation in primitive cardiac progenitors

    PubMed Central

    Cruz, F M; Tomé, M; Bernal, J A; Bernad, A

    2015-01-01

    B lymphoma Mo-MLV insertion region 1 (Bmi1) is a polycomb-family transcriptional factor critical for self-renewal in many adult stem cells and human neoplasia. We sought to identify microRNAs regulated by Bmi1 that could play a role in multipotent cardiac progenitor cell (CPC) decisions. We found that miR-300, a poorly characterized microRNA mapping in the Dlk1-Dio3 microRNA cluster, was positively regulated by Bmi1 in CPCs. Forced expression of miR-300 in CPCs promoted an improved stemness signature with a significant increase in Oct4 levels, a reduction in senescence progression and an enhanced proliferative status via p19 activation and inhibition of p16 accumulation. Endothelial and cardiogenic differentiation were clearly compromised by sustained miR-300 expression. Additionally, RNA and protein analysis revealed a significant reduction in key cardiac transcription factors, including Nkx2.5 and Tbx5. Collectively, these results suggest that some functions attributed to Bmi1 are due to induction of miR-300, which decreases the cardiogenic differentiation potential of multipotent CPCs in vitro and promotes self-renewal. PMID:26512961

  17. Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

    PubMed

    Cho, P W; Levin, H R; Curtis, W E; Tsitlik, J E; DiNatale, J M; Kass, D A; Gardner, T J; Kunel, R W; Acker, M A

    1993-07-01

    Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

  18. Cardiac structure and function in women basketball athletes: seasonal variation and comparisons with nonathletic controls.

    PubMed

    Crouse, S F; Rohack, J J; Jacobsen, D J

    1992-12-01

    To characterize hypertrophy and quantify seasonal changes in cardiac structure and function of women collegiate basketball (BB) athletes (n = 15), echocardiographic (echo) measurements were made in the fall (FALL1), winter (WIN), and spring (SPR), then again during the subsequent fall (FALL2; n = 10). Comparisons were made to age-matched nonathletes (NA) measured during FALL1 (n = 22) and SPR (n = 5). Left ventricular (LV) internal dimension-diastole (LVIDd), LV end-diastolic volume (LVEDV), stroke volume (SV), LV mass (LVM), septal thickness (IVS), LV posterior wall thickness (LVPW), right ventricular (RV) internal dimension-diastole (RVIDd), and aortic root diameter (AOD) were significantly larger (12-70%) in the athletes; RVIDd-, LVEDV-, SV-, and LVM-index were also significantly greater (8-46%). From FALL1 to SPR measurement periods, LVIDd, RVIDd, LVEDV, SV, IVS, and LVM-index increased significantly (7-18%) in the athletes. Over the same period of time, LVIDd, LAD, AOD, LVEDV, and SV measured in the five NA subjects increased significantly. In the athletes, LVIDs, RVIDd, IVS, LVPW, and LVM decreased significantly (5-30%) from the SPR to FALL2 measurement period. These data characterize the general nature of the cardiac hypertrophy noted in women BB athletes compared to NA controls and show that distinct changes in heart structure corresponding to different periods of the competitive season can occur in these athletes.

  19. Cardiac cryolesions: factors affecting their size and a means of monitoring their formation.

    PubMed

    Markovitz, L J; Frame, L H; Josephson, M E; Hargrove, W C

    1988-11-01

    Twenty-seven endocardial cryolesions were created in mongrel dogs and analyzed to determine the effects on cryolesion size of both the initial myocardial temperature (37 degrees C versus 12 degrees C) and the pressure within the nitrous oxide delivery line (tank pressure of more than 700 pounds per square inch [psi] versus tank pressure of less than 700 psi). In addition, local myocardial temperatures were monitored to determine their utility in the intraoperative determination of the extent of cryothermic cell death. Cryolesion volume was significantly affected by both the initial myocardial temperature (p less than 0.001) and the line pressure (p = 0.014). In a 37 degrees C myocardium, the mean lesion volume ranged from 0.501 +/- 0.183 cc at line pressures lower than 700 psi to 0.839 +/- 0.258 cc at line pressures greater than 700 psi. In a 12 degrees C myocardium, the mean volume was 1.151 +/- 0.436 cc at line pressures lower than 700 psi and 1.361 +/- 0.288 cc at line pressures higher than 700 psi. A myocardial temperature of 0 degrees C occurs at the edge of the area of cell death. When analyzing the range from -5 degrees to +5 degrees C, the probability of a point at or lower than 0 degrees C falling inside the cryolesion is 84.2%. Monitoring intramyocardial temperature will predict the border of a cryolesion.

  20. A Tocotrienol-Enriched Formulation Protects against Radiation-Induced Changes in Cardiac Mitochondria without Modifying Late Cardiac Function or Structure

    PubMed Central

    Sridharan, Vijayalakshmi; Tripathi, Preeti; Aykin-Burns, Nukhet; Krager, Kimberly J; Sharma, Sunil K.; Moros, Eduardo G.; Melnyk, Stepan B.; Pavliv, Oleksandra; Hauer-Jensen, Martin; Boerma, Marjan

    2015-01-01

    Radiation-induced heart disease (RIHD) is a common and sometimes severe late side effect of radiation therapy for intrathoracic and chest wall tumors. We have previously shown that local heart irradiation in a rat model caused prolonged changes in mitochondrial respiration and increased susceptibility to mitochondrial permeability transition pore (mPTP) opening. Because tocotrienols are known to protect against oxidative stress-induced mitochondrial dysfunction, in this study, we examined the effects of tocotrienols on radiation-induced alterations in mitochondria, and structural and functional manifestations of RIHD. Male Sprague-Dawley rats received image-guided localized X irradiation to the heart to a total dose of 21 Gy. Twenty-four hours before irradiation, rats received a tocotrienol-enriched formulation or vehicle by oral gavage. Mitochondrial function and mitochondrial membrane parameters were studied at 2 weeks and 28 weeks after irradiation. In addition, cardiac function and histology were examined at 28 weeks. A single oral dose of the tocotrienol-enriched formulation preserved Bax/Bcl2 ratios and prevented mPTP opening and radiation-induced alterations in succinate-driven mitochondrial respiration. Nevertheless, the late effects of local heart irradiation pertaining to myocardial function and structure were not modified. Our studies suggest that a single dose of tocotrienols protects against radiation-induced mitochondrial changes, but these effects are not sufficient against long-term alterations in cardiac function or remodeling. PMID:25710576

  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. Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.

    PubMed

    Koshman, Yevgeniya E; Sternlicht, Mark D; Kim, Taehoon; O'Hara, Christopher P; Koczor, Christopher A; Lewis, William; Seeley, Todd W; Lipson, Kenneth E; Samarel, Allen M

    2015-12-01

    Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCε mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCε mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted.

  3. Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues

    PubMed Central

    Ravenscroft, Stephanie M.; Pointon, Amy; Williams, Awel W.; Cross, Michael J.; Sidaway, James E.

    2016-01-01

    The immature phenotype of stem cell derived cardiomyocytes is a significant barrier to their use in translational medicine and pre-clinical in vitro drug toxicity and pharmacological analysis. Here we have assessed the contribution of non-myocyte cells on the contractile function of co-cultured human embryonic stem cell derived cardiomyocytes (hESC-CMs) in spheroid microtissue format. Microtissues were formed using a scaffold free 96-well cell suspension method from hESC-CM cultured alone (CM microtissues) or in combination with human primary cardiac microvascular endothelial cells and cardiac fibroblasts (CMEF microtissues). Contractility was characterized with fluorescence and video-based edge detection. CMEF microtissues displayed greater Ca2+ transient amplitudes, enhanced spontaneous contraction rate and remarkably enhanced contractile function in response to both positive and negative inotropic drugs, suggesting a more mature contractile phenotype than CM microtissues. In addition, for several drugs the enhanced contractile response was not apparent when endothelial cell or fibroblasts from a non-cardiac tissue were used as the ancillary cells. Further evidence of maturity for CMEF microtissues was shown with increased expression of genes that encode proteins critical in cardiac Ca2+ handling (S100A1), sarcomere assembly (telethonin/TCAP) and β-adrenergic receptor signalling. Our data shows that compared with single cell-type cardiomyocyte in vitro models, CMEF microtissues are superior at predicting the inotropic effects of drugs, demonstrating the critical contribution of cardiac non-myocyte cells in mediating functional cardiotoxicity. PMID:27125969

  4. 8-Oxoguanine DNA glycosylase 1 (ogg1) maintains the function of cardiac progenitor cells during heart formation in zebrafish

    SciTech Connect

    Yan, Lifeng; Zhou, Yong; Yu, Shanhe; Ji, Guixiang; Liu, Wei; Gu, Aihua

    2013-11-15

    Genomic damage may devastate the potential of progenitor cells and consequently impair early organogenesis. We found that ogg1, a key enzyme initiating the base-excision repair, was enriched in the embryonic heart in zebrafish. So far, little is known about DNA repair in cardiogenesis. Here, we addressed the critical role of ogg1 in cardiogenesis for the first time. ogg1 mainly expressed in the anterior lateral plate mesoderm (ALPM), the primary heart tube, and subsequently the embryonic myocardium by in situ hybridisation. Loss of ogg1 resulted in severe cardiac morphogenesis and functional abnormalities, including the short heart length, arrhythmia, decreased cardiomyocytes and nkx2.5{sup +} cardiac progenitor cells. Moreover, the increased apoptosis and repressed proliferation of progenitor cells caused by ogg1 deficiency might contribute to the heart phenotype. The microarray analysis showed that the expression of genes involved in embryonic heart tube morphogenesis and heart structure were significantly changed due to the lack of ogg1. Among those, foxh1 is an important partner of ogg1 in the cardiac development in response to DNA damage. Our work demonstrates the requirement of ogg1 in cardiac progenitors and heart development in zebrafish. These findings may be helpful for understanding the aetiology of congenital cardiac deficits. - Highlights: • A key DNA repair enzyme ogg1 is expressed in the embryonic heart in zebrafish. • We found that ogg1 is essential for normal cardiac morphogenesis in zebrafish. • The production of embryonic cardiomyocytes requires appropriate ogg1 expression. • Ogg1 critically regulated proliferation of cardiac progenitor cells in zebrafish. • foxh1 is a partner of ogg1 in the cardiac development in response to DNA damage.

  5. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    SciTech Connect

    Guo, Hai-dong; Cui, Guo-hong; Yang, Jia-jun; Wang, Cun; Zhu, Jing; Zhang, Li-sheng; Jiang, Jun; Shao, Shui-jin

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  6. Carbon nanotubes instruct physiological growth and functionally mature syncytia: nongenetic engineering of cardiac myocytes.

    PubMed

    Martinelli, Valentina; Cellot, Giada; Toma, Francesca Maria; Long, Carlin S; Caldwell, John H; Zentilin, Lorena; Giacca, Mauro; Turco, Antonio; Prato, Maurizio; Ballerini, Laura; Mestroni, Luisa

    2013-07-23

    Myocardial tissue engineering currently represents one of the most realistic strategies for cardiac repair. We have recently discovered the ability of carbon nanotube scaffolds to promote cell division and maturation in cardiomyocytes. Here, we test the hypothesis that carbon nanotube scaffolds promote cardiomyocyte growth and maturation by altering the gene expression program, implementing the cell electrophysiological properties and improving networking and maturation of functional syncytia. In our study, we combine microscopy, biological and electrophysiological methodologies, and calcium imaging, to verify whether neonatal rat ventricular myocytes cultured on substrates of multiwall carbon nanotubes acquire a physiologically more mature phenotype compared to control (gelatin). We show that the carbon nanotube substrate stimulates the induction of a gene expression profile characteristic of terminal differentiation and physiological growth, with a 2-fold increase of α-myosin heavy chain (P < 0.001) and upregulation of sarcoplasmic reticulum Ca(2+) ATPase 2a. In contrast, markers of pathological hypertrophy remain unchanged (β-myosin heavy chain, skeletal α-actin, atrial natriuretic peptide). These modifications are paralleled by an increase of connexin-43 gene expression, gap junctions and functional syncytia. Moreover, carbon nanotubes appear to exert a protective effect against the pathologic stimulus of phenylephrine. Finally, cardiomyocytes on carbon nanotubes demonstrate a more mature electrophysiological phenotype of syncytia and intracellular calcium signaling. Thus, carbon nanotubes interacting with cardiomyocytes have the ability to promote physiological growth and functional maturation. These properties are unique in the current vexing field of tissue engineering, and offer unprecedented perspectives in the development of innovative therapies for cardiac repair.

  7. Echocardiographic Evaluation of Cardiac Function in Ischemic Rats: Value of M-Mode Echocardiography

    PubMed Central

    Darbandi Azar, Amir; Tavakoli, Fatemeh; Moladoust, Hassan; Zare, Asghar; Sadeghpour, Anita

    2014-01-01

    Background: Echocardiography is a well-established diagnostic tool for a safe, reproducible and accurate evaluation of cardiac anatomy, hemodynamics and function in clinical practice. Objectives: We sought to demonstrate the efficacy and feasibility of M-mode echocardiography to evaluate cardiac structure and function in normal and MI-induced adult rats. Materials and Methods: All animal procedures were approved by the ethics committee of Tehran University of Medical Sciences and the investigation conformed to the “Guide for the Care and Use of Laboratory Animals” published by the United States National Institutes of Health. Forty-eight male Wistar rats weighing 280-300 grams were obtained from a single breeding colony. The statistical analyses were performed using SPSS 20.0. Results: Echocardiographic measurements were possible in all rats before and after the operation. In our survey, we studied echocardiographic alterations in rats after MI induction. Changes can be seen in all echocardiographic mean values after myocardial infarction (MI), but significant decrease (P < 0.01) of Fractional shortening and Ejection Fraction as well as significant increase (P < 0.05) of end systolic diameter and systolic volume after left anterior descending coronary artery (LAD) ligation can be good signs of MI induction. Conclusions: In light of our results, it can be concluded that we succeeded in establishing a precise echocardiographic method to confidently assess the success of LAD ligation surgery in rats. It is feasible to thoroughly monitor the functional efficiency of regional therapeutic interventions such as intra-myocardial stem cell injection. PMID:25785251

  8. Aging Impairs Myocardial Fatty Acid and Ketone Oxidation and Modifies Cardiac Functional and Metabolic Responses to Insulin in Mice

    SciTech Connect

    Hyyti, Outi M.; Ledee, Dolena; Ning, Xue-Han; Ge, Ming; Portman, Michael A.

    2010-07-02

    Aging presumably initiates shifts in substrate oxidation mediated in part by changes in insulin sensitivity. Similar shifts occur with cardiac hypertrophy and may contribute to contractile dysfunction. We tested the hypothesis that aging modifies substrate utilization and alters insulin sensitivity in mouse heart when provided multiple substrates. In vivo cardiac function was measured with microtipped pressure transducers in the left ventricle from control (4–6 mo) and aged (22–24 mo) mice. Cardiac function was also measured in isolated working hearts along with substrate and anaplerotic fractional contributions to the citric acid cycle (CAC) by using perfusate containing 13C-labeled free fatty acids (FFA), acetoacetate, lactate, and unlabeled glucose. Stroke volume and cardiac output were diminished in aged mice in vivo, but pressure development was preserved. Systolic and diastolic functions were maintained in aged isolated hearts. Insulin prompted an increase in systolic function in aged hearts, resulting in an increase in cardiac efficiency. FFA and ketone flux were present but were markedly impaired in aged hearts. These changes in myocardial substrate utilization corresponded to alterations in circulating lipids, thyroid hormone, and reductions in protein expression for peroxisome proliferator-activated receptor (PPAR)α and pyruvate dehydrogenase kinase (PDK)4. Insulin further suppressed FFA oxidation in the aged. Insulin stimulation of anaplerosis in control hearts was absent in the aged. The aged heart shows metabolic plasticity by accessing multiple substrates to maintain function. However, fatty acid oxidation capacity is limited. Impaired insulin-stimulated anaplerosis may contribute to elevated cardiac efficiency, but may also limit response to acute stress through depletion of CAC intermediates.

  9. 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.

    PubMed

    Frunza, Olga; Russo, Ilaria; Saxena, Amit; Shinde, Arti V; Humeres, Claudio; Hanif, Waqas; Rai, Vikrant; Su, Ya; Frangogiannis, Nikolaos G

    2016-05-01

    The β-galactoside-binding animal lectin galectin-3 is predominantly expressed by activated macrophages and is a promising biomarker for patients with heart failure. Galectin-3 regulates inflammatory and fibrotic responses; however, its role in cardiac remodeling remains unclear. We hypothesized that galectin-3 may be up-regulated in the pressure-overloaded myocardium and regulate hypertrophy and fibrosis. In normal mouse myocardium, galectin-3 was constitutively expressed in macrophages and was localized in atrial but not ventricular cardiomyocytes. In a mouse model of transverse aortic constriction, galectin-3 expression was markedly up-regulated in the pressure-overloaded myocardium. Early up-regulation of galectin-3 was localized in subpopulations of macrophages and myofibroblasts; however, after 7 to 28 days of transverse aortic constriction, a subset of cardiomyocytes in fibrotic areas contained large amounts of galectin-3. In vitro, cytokine stimulation suppressed galectin-3 synthesis by macrophages and cardiac fibroblasts. Correlation studies revealed that cardiomyocyte- but not macrophage-specific galectin-3 localization was associated with adverse remodeling and dysfunction. Galectin-3 knockout mice exhibited accelerated cardiac hypertrophy after 7 days of pressure overload, whereas female galectin-3 knockouts had delayed dilation after 28 days of transverse aortic constriction. However, galectin-3 loss did not affect survival, systolic and diastolic dysfunction, cardiac fibrosis, and cardiomyocyte hypertrophy in the pressure-overloaded heart. Despite its potential role as a prognostic biomarker, galectin-3 is not a critical modulator of cardiac fibrosis but may delay the hypertrophic response. PMID:26948424

  10. Cognitive function in the affective disorders: a prospective study.

    PubMed

    Bulbena, A; Berrios, G E

    1993-01-01

    A prospective, controlled study of 50 subjects confirmed claims that major depression or mania may cause temporary disorders of attention, memory, visuo-spatial function, and choice reaction time, and cause-independently of medication-the appearance of glabellar tap, positive hand-face test, nuchocephalic reflex, and graphesthesia. On follow-up, all these phenomena either disappeared or markedly improved. Age and age of onset, but not pre-morbid intelligence or history of ECT, seemed to modulate the severity of the cognitive impairment. Presence of delusions predicted poor (but reversible) visuo-spatial function. Cognitive impairment accompanied by reversible soft neurological signs was more marked but patients thus affected surprisingly showed lower depressive scores; this was interpreted as representing a secondary, 'organic' form of affective disorder (i.e. a behavioural phenocopy of depression) characterised by a reduced capacity to experience depressive symptoms and by little improvement at follow-up.

  11. The impact of non-severe burn injury on cardiac function and long-term cardiovascular pathology

    PubMed Central

    O’Halloran, Emily; Shah, Amit; Dembo, Lawrence; Hool, Livia; Viola, Helena; Grey, Christine; Boyd, James; O’Neill, Tomas; Wood, Fiona; Duke, Janine; Fear, Mark

    2016-01-01

    Severe burn injury significantly affects cardiovascular function for up to 3 years. However, whether this leads to long-term pathology is unknown. The impact of non-severe burn injury, which accounts for over 80% of admissions in developed countries, has not been investigated. Using a rodent model of non-severe burn injury with subsequent echocardiography we showed significantly increased left ventricular end systolic diameter (LVESD) and ventricular wall thickness at up to 3 months post-injury. Use of propranolol abrogated the changes in cardiac measures observed. Subsequently we investigated changes in a patient cohort with non-severe injury. Echocardiography measured at baseline and at 3 months post-injury showed increased LVESD at 3 months and significantly decreased posterior wall diameter. Finally, 32 years of Western Australian hospital records were used to investigate the incidence of cardiovascular disease admissions after burn injury. People who had experienced a burn had increased hospital admissions and length of stay for cardiovascular diseases when compared to a matched uninjured cohort. This study presents animal, patient and population data that strongly suggest non-severe burn injury has significant effects on cardiovascular function and long-term morbidity in some burn patients. Identification of patients at risk will promote better intervention and outcomes for burn patients. PMID:27694999

  12. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.

    PubMed

    Coleman, Matthew A; Sasi, Sharath P; Onufrak, Jillian; Natarajan, Mohan; Manickam, Krishnan; Schwab, John; Muralidharan, Sujatha; Peterson, Leif E; Alekseyev, Yuriy O; Yan, Xinhua; Goukassian, David A

    2015-12-01

    There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers.

  13. Low-dose radiation affects cardiac physiology: gene networks and molecular signaling in cardiomyocytes.

    PubMed

    Coleman, Matthew A; Sasi, Sharath P; Onufrak, Jillian; Natarajan, Mohan; Manickam, Krishnan; Schwab, John; Muralidharan, Sujatha; Peterson, Leif E; Alekseyev, Yuriy O; Yan, Xinhua; Goukassian, David A

    2015-12-01

    There are 160,000 cancer patients worldwide treated with particle radiotherapy (RT). With the advent of proton, and high (H) charge (Z) and energy (E) HZE ionizing particle RT, the cardiovascular diseases risk estimates are uncertain. In addition, future deep space exploratory-type missions will expose humans to unknown but low doses of particle irradiation (IR). We examined molecular responses using transcriptome profiling in left ventricular murine cardiomyocytes isolated from mice that were exposed to 90 cGy, 1 GeV proton ((1)H) and 15 cGy, 1 GeV/nucleon iron ((56)Fe) over 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the IR response and time after exposure, with (56)Fe-IR showing the greatest level of gene modulation. (1)H-IR showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses, and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Validation of the signal transduction network by protein analysis and gel shift assay showed that particle IR clearly regulates a long-lived signaling mechanism for ERK1/2, p38 MAPK signaling and identified NFATc4, GATA4, STAT3, and NF-κB as regulators of the response at specific time points. These data suggest that the molecular responses and gene expression to (56)Fe-IR in cardiomyocytes are unique and long-lasting. Our study may have significant implications for the efforts of National Aeronautics and Space Administration to develop heart disease risk estimates for astronauts and for patients receiving conventional and particle RT via identification of specific HZE-IR molecular markers. PMID:26408534

  14. Gestational exposure to diethylstilbestrol alters cardiac structure/function, protein expression and DNA methylation in adult male mice progeny

    SciTech Connect

    Haddad, Rami; Kasneci, Amanda; Mepham, Kathryn; Sebag, Igal A.; and others

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0 μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5–14.5. At 3 months, male progeny were left sedentary or were swim trained for 4 weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. -- Highlights: ► Gestational DES changes cardiac SERCA2a and CASQ2 expression. ► Echocardiography identified systolic dysfunction and increased diastolic relaxation. ► DES

  15. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment

    SciTech Connect

    Iso, Yoshitaka; Spees, Jeffrey L.; E-mail: Jeffrey.Spees@uvm.edu; Serrano, Claudia; Bakondi, Benjamin; Pochampally, Radhika; Song, Yao-Hua; Sobel, Burton E.; Delafontaine, Patrick; Prockop, Darwin J. . E-mail: dprocko@tulane.edu

    2007-03-16

    The aim of this study was to determine whether intravenously administered multipotent stromal cells from human bone marrow (hMSCs) can improve cardiac function after myocardial infarction (MI) without long-term engraftment and therefore whether transitory paracrine effects or secreted factors are responsible for the benefit conferred. hMSCs were injected systemically into immunodeficient mice with acute MI. Cardiac function and fibrosis after MI in the hMSC-treated group were significantly improved compared with controls. However, despite the cardiac improvement, there was no evident hMSC engraftment in the heart 3 weeks after MI. Microarray assays and ELISAs demonstrated that multiple protective factors were expressed and secreted from the hMSCs in culture. Factors secreted by hMSCs prevented cell death of cultured cardiomyocytes and endothelial cells under conditions that mimicked tissue ischemia. The favorable effects of hMSCs appear to reflect the impact of secreted factors rather than engraftment, differentiation, or cell fusion.

  16. Identification and Functional Characterization of a Novel CACNA1C-Mediated Cardiac Disorder Characterized by Prolonged QT Intervals with Hypertrophic Cardiomyopathy, Congenital Heart Defects, and Sudden Cardiac Death

    PubMed Central

    Boczek, Nicole J.; Ye, Dan; Jin, Fang; Tester, David J.; Huseby, April; Bos, J. Martijn; Johnson, Aaron J.; Kanter, Ronald; Ackerman, Michael J.

    2016-01-01

    Background A portion of sudden cardiac deaths (SCD) can be attributed to structural heart diseases such as hypertrophic cardiomyopathy (HCM) or cardiac channelopathies such as long QT syndrome (LQTS); however, the underlying molecular mechanisms are quite distinct. Here, we identify a novel CACNA1C missense mutation with mixed loss-of-function/gain-of-function responsible for a complex phenotype of LQTS, HCM, SCD, and congenital heart defects (CHDs). Methods and Results Whole exome sequencing (WES) in combination with Ingenuity Variant Analysis was completed on three affected individuals and one unaffected individual from a large pedigree with concomitant LQTS, HCM, and CHDs and identified a novel CACNA1C mutation, p.Arg518Cys, as the most likely candidate mutation. Mutational analysis of exon 12 of CACNA1C was completed on 5 additional patients with a similar phenotype of LQTS plus a personal or family history of HCM-like phenotypes, and identified two additional pedigrees with mutations at the same position, p.Arg518Cys/His. Whole cell patch clamp technique was used to assess the electrophysiological effects of the identified mutations in CaV1.2, and revealed a complex phenotype, including loss of current density and inactivation in combination with increased window and late current. Conclusions Through WES and expanded cohort screening, we identified a novel genetic substrate p.Arg518Cys/His-CACNA1C, in patients with a complex phenotype including LQTS, HCM, and CHDs annotated as cardiac-only Timothy syndrome. Our electrophysiological studies, identification of mutations at the same amino acid position in multiple pedigrees, and co-segregation with disease in these pedigrees provides evidence that p.Arg518Cys/His is the pathogenic substrate for the observed phenotype. PMID:26253506

  17. Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

    PubMed Central

    Zhang, Ying; Ma, Xiao-juan; Guo, Chun-yu; Wang, Ming-ming; Kou, Na; Qu, Hua; Mao, Hui-min; Shi, Da-zhuo

    2016-01-01

    Aim: We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME). Methods: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses. Results: Pretreatment with the combination of ligustrazine (27 mg·kg−1·d−1) and berberine (90 mg·kg−1·d−1) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg−1·d−1). Conclusion: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects. PMID:26924290

  18. Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction

    SciTech Connect

    Muthu, Priya; Wang, Li; Yuan, Chen-Ching; Kazmierczak, Katarzyna; Huang, Wenrui; Hernandez, Olga M.; Kawai, Masataka; Irving, Thomas C.; Szczesna-Cordary, Danuta

    2012-04-02

    The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-{Delta}43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing ({approx} 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I{sub 1,1}/I{sub 1,0}, indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-{Delta}43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-{Delta}43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

  19. Using models of the myocyte for functional interpretation of cardiac proteomic data

    PubMed Central

    Winslow, Raimond L; Cortassa, Sonia; Greenstein, Joseph L

    2005-01-01

    There has been significant progress towards the development of highly integrative computational models of the cardiac myocyte over the past decade. Models now incorporate descriptions of voltage-gated ionic currents and membrane transporters, mechanisms of calcium-induced calcium release and intracellular calcium cycling, mitochondrial ATP production and its coupling to energy-requiring membrane transport processes and mechanisms of force generation. There is an extensive literature documenting both the reconstructive and predictive abilities of these models and there is no question that an interplay between quantitative modelling and experimental investigation has become a central component of modern cardiovascular research. As data regarding the cardiovascular proteome in both health and disease emerge, integrative models of the myocyte are becoming useful tools for interpreting the functional significance of changes in protein expression and post-translational modifications (PTMs). Data of particular importance include information on: (a) changes of expressed protein level, (b) changes of protein PTMs, (c) protein localization, and (d) protein–protein interactions, as it is often possible to incorporate and interpret the functional significance of such findings using computational models. We provide two examples of how models may be used in this fashion. In the first example, we show how information on altered expression of the sarcoplasmic reticulum Ca2+-ATPase, when interpreted through the use of a computational model, has provided key insights into fundamental mechanisms regulating cardiac action potential duration. In the second example, we show how information on the effects of phosphorylation of L-type Ca2+ channels, when interpreted through the use of a model, provides insights on how this post-translational modification alters the properties of excitation–contraction coupling and risk for arrhythmia. PMID:15611013

  20. Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy

    PubMed Central

    Sulaiman, M.; Matta, M. J.; Sunderesan, N. R.; Periasamy, M.; Gupta, M.

    2010-01-01

    Reduced sarcoplasmic calcium ATPase (SERCA2a) expression has been shown to play a significant role in the cardiac dysfunction in diabetic cardiomyopathy. The mechanism of SERCA2a repression is, however, not known. This study was designed to examine the effect of resveratrol (RSV), a potent activator of SIRT1, on cardiac function and SERCA2a expression in chronic type 1 diabetes. Adult male mice were injected with streptozotocin (STZ) and fed with either a regular diet or a diet enriched with RSV. STZ administration produced progressive decline in cardiac function, associated with markedly reduced SERCA2a and SIRT1 protein levels and increased collagen deposition; RSV treatment to these mice had a tremendous beneficial effect both in terms of improving SERCA2a expression and on cardiac function. In cultured cardiomyocytes, RSV restored SERCA2 promoter activity, which was otherwise highly repressed in high-glucose media. Protective effects of RSV were found to be dependent on its ability to activate Silent information regulator (SIRT) 1. In cardiomyocytes, overexpression of SIRT1 was found sufficient to activate SERCA2 promoter in a dose-dependent manner. In contrast, pretreatment of cardiomyocytes with SIRT1 antagonist, splitomycin, blocked these beneficial effects of RSV. In addition, SIRT1 knockout (+/−) mice were also found to be more sensitive to STZ-induced decline in SERCA2a mRNA. The data demonstrate that, in chronic diabetes, 1) the enzymatic activity of cardiac SIRT1 is reduced, which contributes to reduced expression of SERCA2a and 2) through activation of SIRT1, RSV enhances expression of SERCA2a and improves cardiac function. PMID:20008278

  1. Disruption of Ah Receptor Signaling during Mouse Development Leads to Abnormal Cardiac Structure and Function in the Adult

    PubMed Central

    Carreira, Vinicius S.; Fan, Yunxia; Kurita, Hisaka; Wang, Qin; Ko, Chia-I; Naticchioni, Mindi; Jiang, Min; Koch, Sheryl; Zhang, Xiang; Biesiada, Jacek; Medvedovic, Mario; Xia, Ying; Rubinstein, Jack; Puga, Alvaro

    2015-01-01

    The Developmental Origins of Health and Disease (DOHaD) Theory proposes that the environment encountered during fetal life and infancy permanently shapes tissue physiology and homeostasis such that damage resulting from maternal stress, poor nutrition or exposure to environmental agents may be at the heart of adult onset disease. Interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by exposure in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, causes structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. To test if embryonic effects progress into an adult phenotype, we investigated whether Ahr ablation or TCDD exposure in utero resulted in cardiac abnormalities in adult mice long after removal of the agent. Ten-months old adult Ahr-/- and in utero TCDD-exposed Ahr+/+ mice showed sexually dimorphic abnormal cardiovascular phenotypes characterized by echocardiographic findings of hypertrophy, ventricular dilation and increased heart weight, resting heart rate and systolic and mean blood pressure, and decreased exercise tolerance. Underlying these effects, genes in signaling networks related to cardiac hypertrophy and mitochondrial function were differentially expressed. Cardiac dysfunction in mouse embryos resulting from AHR signaling disruption seems to progress into abnormal cardiac structure and function that predispose adults to cardiac disease, but while embryonic dysfunction is equally robust in males and females, the adult abnormalities are more prevalent in females, with the highest severity in Ahr-/- females. The findings reported here underscore the conclusion that AHR signaling in the developing heart is one potential target of environmental factors associated with cardiovascular disease. PMID:26555816

  2. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  3. β-Adrenergic receptor desensitization in man: insight into post-exercise attenuation of cardiac function

    PubMed Central

    Hart, Emma; Dawson, Ellen; Rasmussen, Peter; George, Keith; Secher, Niels H; Whyte, Greg; Shave, Rob

    2006-01-01

    Desensitization of the β-adrenoreceptors (β-AR) may contribute to a post-exercise reduction in left ventricular (LV) function. However, attenuation of the chronotropic and inotropic responses to a β-AR agonist may depend upon alterations in parasympathetic tone. Furthermore, changes in cardiac output Q˙ and LV diastolic function in response to a β-AR agonist, pre- to post-prolonged exercise, remain unclear. Seven trained males (mean ± s.d., age 27 ± 6 years) performed 4 h of ergometer rowing. Peak heart rate (HR) and LV systolic and diastolic functional responses to incremental isoproterenol (isoprenaline) infusion (2, 4 and 6 μg kg min−1) were assessed after vagal blockade (glycopyrrolate, 1.2 mg). LV systolic function was assessed by the pressure/volume ratio (systolic blood pressure/end systolic volume) and Q˙, whilst diastolic function was evaluated as peak early and late transmitral filling velocities. Following exercise, the pressure/volume ratio decreased by 25% (P < 0.05), whereas Q˙ was unchanged (P > 0.05). The early/late filling ratio was reduced by 36% after exercise, due to an elevation in late LV filling (P < 0.01). The increase in HR response to isoproterenol infusion was blunted post-exercise at both 4 and 6 μg kg min−1 (127 ± 7 and 132 ± 6 beats min−1) compared with pre-exercise (138 ± 8 and 141 ± 12 beats min−1, P < 0.05). Additionally, the pressure/volume ratio and Q˙ were blunted post-exercise in response to isoproterenol (P < 0.05). In contrast, diastolic function was similar before and after exercise during isoproterenol infusion (P > 0.05). Desensitization of the β-AR contributes to an attenuated left ventricular systolic but not diastolic function following prolonged exercise. PMID:16973702

  4. Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction.

    PubMed

    Zentilin, Lorena; Puligadda, Uday; Lionetti, Vincenzo; Zacchigna, Serena; Collesi, Chiara; Pattarini, Lucia; Ruozi, Giulia; Camporesi, Silvia; Sinagra, Gianfranco; Pepe, Martino; Recchia, Fabio A; Giacca, Mauro

    2010-05-01

    Mounting evidence indicates that the function of members of the vascular endothelial growth factor (VEGF) family extends beyond blood vessel formation. Here, we show that the prolonged intramyocardial expression of VEGF-A(165) and VEGF-B(167) on adeno-associated virus-mediated gene delivery determined a marked improvement in cardiac function after myocardial infarction in rats, by promoting cardiac contractility, preserving viable cardiac tissue, and preventing remodeling of the left ventricle (LV) over time. Consistent with this functional outcome, animals treated with both factors showed diminished fibrosis and increased contractile myocardium, which were more pronounced after expression of the selective VEGF receptor-1 (VEGFR-1) ligand VEGF-B, in the absence of significant induction of angiogenesis. We found that cardiomyocytes expressed VEGFR-1, VEGFR-2, and neuropilin-1 and that, in particular, VEGFR-1 was specifically up-regulated in hypoxia and on exposure to oxidative stress. VEGF-B exerted powerful antiapoptotic effect in both cultured cardiomyocytes and after myocardial infarction in vivo. Finally, VEGFR-1 activation by VEGF-B was found to elicit a peculiar gene expression profile proper of the compensatory, hypertrophic response, consisting in activation of alphaMHC and repression of betaMHC and skeletal alpha-actin, and an increase in SERCA2a, RYR, PGC1alpha, and cardiac natriuretic peptide transcripts, both in cultured cardiomyocytes and in infarcted hearts. The finding that VEGFR-1 activation by VEGF-B prevents loss of cardiac mass and promotes maintenance of cardiac contractility over time has obvious therapeutic implications.

  5. The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice

    PubMed Central

    Fallavollita, James A.

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in-vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6-month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice. PMID:26808526

  6. The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice.

    PubMed

    Chaudhari, Milind R; Fallavollita, James A; Farkas, Gaspar A

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in-vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6-month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice. PMID:26808526

  7. Evaluation of cardiac functions of cirrhotic children using serum brain natriuretic peptide and tissue Doppler imaging

    PubMed Central

    Fattouh, Aya M; El-Shabrawi, Mortada H; Mahmoud, Enas H; Ahmed, Wafaa O

    2016-01-01

    Background: Cirrhotic cardiomyopathy (CCM) is described as the presence of cardiac dysfunction in cirrhotic patients. In children with chronic liver disease, CCM has been very rarely investigated. The Aim of the Study: Is to evaluate the cardiac function of cirrhotic children to identify those with CCM. Patients and Methods: Fifty-two cirrhotic patients and 53 age and sex matched controls were assessed using serum brain-type natriuretic peptide (BNP), conventional echocardiography, and tissue Doppler imaging. Results: Patients’ mean ages were 7.66 ± 4.16 years (vs. 6.88 ± 3.04 years for the controls). The study included 27 males and 25 females (28 and 25 respectively for the controls). Patients had larger left atrium and right ventricle (RV) (P value 0.05) and increased LV posterior wall thickness than controls (P value 0.04). They had higher late atrial diastolic filling velocity (A) of tricuspid valve (TV) inflow (0.59 ± 0.17 vs. 0.5 ± 0.1 m/s, P < 0.001) and lower ratios between the early diastolic filling velocity (E) and A wave velocity (E/A) of both mitral valve and TV inflow (1.7 ± 0.35 vs. 1.87 ± 0.34 and 1.3 ± 0.3 vs. 1.5 ± 0.3, P < 0.005 and 0.0008, respectively). Patients had significantly longer isovolumic relaxation time of LV (45.5 ± 11.1 vs. 40.5 ± 7.7 ms P 0.008), higher late diastolic peak myocardial velocity (A’) (11.8 ± 3.6 vs. 9.5 ± 2.7 ms, P 0.0003) and systolic velocity (S’) of the RV (14.5 ± 2.7 vs. 13.2 ± 2.9, P 0.01) and significantly higher myocardial performance index of both LV and RV (P 0.001 and 0.01). BNP levels were significantly higher in cases than controls (5.25 ng/l vs. 3.75 ng/l, P < 0.04) and was correlated with the E wave velocity of the TV (r 0.004) and the E/E’ ratio of the RV (r 0.001). None of the clinical or laboratory data were correlated with the BNP level. Conclusion Cirrhotic children have cardiac dysfunction mainly in the form of diastolic dysfunction. There is a need that CCM be more accurately

  8. EFFECTS OF INSTILLATION OF RESIDUAL OIL FLY ASH ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

    EPA Science Inventory


    EFFECTS OF INSTILLED RESIDUAL OIL FLY ASH (ROFA) ON INDICES OF CARDIAC, PULMONARY, AND THERMOREGULATORY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. LB Wichers1, JP Nolan2, UP Kodavanti2, MCJ Schladweiler2, R Hauser3, DW Winsett2, DL Costa2, and WP Watkinson2. 1UNC Sch...

  9. Assessment of cardiac function using myocardial perfusion imaging technique on SPECT with 99mTc sestamibi

    NASA Astrophysics Data System (ADS)

    Gani, M. R. A.; Nazir, F.; Pawiro, S. A.; Soejoko, D. S.

    2016-03-01

    Suspicion on coronary heart disease can be confirmed by observing the function of left ventricle cardiac muscle with Myocardial Perfusion Imaging techniques. The function perfusion itself is indicated by the uptake of radiopharmaceutical tracer. The 31 patients were studied undergoing the MPI examination on Gatot Soebroto Hospital using 99mTc-sestamibi radiopharmaceutical with stress and rest conditions. Stress was stimulated by physical exercise or pharmacological agent. After two hours, the patient did rest condition on the same day. The difference of uptake percentage between stress and rest conditions will be used to determine the malfunction of perfusion due to ischemic or infarct. Degradation of cardiac function was determined based on the image-based assessment of five segments of left ventricle cardiac. As a result, 8 (25.8%) patients had normal myocardial perfusion and 11 (35.5%) patients suspected for having partial ischemia. Total ischemia occurred to 8 (25.8%) patients with reversible and irreversible ischemia and the remaining 4 (12.9%) patients for partial infarct with characteristic the percentage of perfusion ≤50%. It is concluded that MPI technique of image-based assessment on uptake percentage difference between stress and rest conditions can be employed to predict abnormal perfusion as complementary information to diagnose the cardiac function.

  10. Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder.

    PubMed

    Friedrich, Corinna; Rinné, Susanne; Zumhagen, Sven; Kiper, Aytug K; Silbernagel, Nicole; Netter, Michael F; Stallmeyer, Birgit; Schulze-Bahr, Eric; Decher, Niels

    2014-06-27

    Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene.

  11. Gain-of-function mutation in TASK-4 channels and severe cardiac conduction disorder

    PubMed Central

    Friedrich, Corinna; Rinné, Susanne; Zumhagen, Sven; Kiper, Aytug K; Silbernagel, Nicole; Netter, Michael F; Stallmeyer, Birgit; Schulze-Bahr, Eric; Decher, Niels

    2014-01-01

    Analyzing a patient with progressive and severe cardiac conduction disorder combined with idiopathic ventricular fibrillation (IVF), we identified a splice site mutation in the sodium channel gene SCN5A. Due to the severe phenotype, we performed whole-exome sequencing (WES) and identified an additional mutation in the KCNK17 gene encoding the K2P potassium channel TASK-4. The heterozygous change (c.262G>A) resulted in the p.Gly88Arg mutation in the first extracellular pore loop. Mutant TASK-4 channels generated threefold increased currents, while surface expression was unchanged, indicating enhanced conductivity. When co-expressed with wild-type channels, the gain-of-function by G88R was conferred in a dominant-active manner. We demonstrate that KCNK17 is strongly expressed in human Purkinje cells and that overexpression of G88R leads to a hyperpolarization and strong slowing of the upstroke velocity of spontaneously beating HL-1 cells. Thus, we propose that a gain-of-function by TASK-4 in the conduction system might aggravate slowed conductivity by the loss of sodium channel function. Moreover, WES supports a second hit-hypothesis in severe arrhythmia cases and identified KCNK17 as a novel arrhythmia gene. PMID:24972929

  12. Factors affecting sexual function in menopause: A review article.

    PubMed

    Nazarpour, Soheila; Simbar, Masoumeh; Tehrani, Fahimeh Ramezani

    2016-08-01

    This study aimed to systematically review the articles on factors affecting sexual function during menopause. Searching articles indexed in Pubmed, Science Direct, Iranmedex, EMBASE, Scopus, and Scientific Information Database databases, a total number of 42 studies published between 2003 and 2013 were selected. Age, estrogen deficiency, type of menopause, chronic medical problems, partner's sex problems, severity of menopause symptoms, dystocia history, and health status were the physical factors influencing sexual function of menopausal women. There were conflicting results regarding the amount of androgens, hormonal therapy, exercise/physical activity, and obstetric history. In the mental-emotional area, all studies confirmed the impact of depression and anxiety. Social factors, including smoking, alcohol consumption, the quality of relationship with husband, partner's loyalty, sexual knowledge, access to health care, a history of divorce or the death of a husband, living apart from a spouse, and a negative understanding of women's health were found to affect sexual function; however, there were conflicting results regarding the effects of education, occupation, socioeconomic status, marital duration, and frequency of sexual intercourse. PMID:27590367

  13. Microbial composition affects the functioning of estuarine sediments

    PubMed Central

    Reed, Heather E; Martiny, Jennifer BH

    2013-01-01

    Although microorganisms largely drive many ecosystem processes, the relationship between microbial composition and their functioning remains unclear. To tease apart the effects of composition and the environment directly, microbial composition must be manipulated and maintained, ideally in a natural ecosystem. In this study, we aimed to test whether variability in microbial composition affects functional processes in a field setting, by reciprocally transplanting riverbed sediments between low- and high-salinity locations along the Nonesuch River (Maine, USA). We placed the sediments into microbial ‘cages' to prevent the migration of microorganisms, while allowing the sediments to experience the abiotic conditions of the surroundings. We performed two experiments, short- (1 week) and long-term (7 weeks) reciprocal transplants, after which we assayed a variety of functional processes in the cages. In both experiments, we examined the composition of bacteria generally (targeting the 16S rDNA gene) and sulfate-reducing bacteria (SRB) specifically (targeting the dsrAB gene) using terminal restriction fragment length polymorphism (T-RFLP). In the short-term experiment, sediment processes (CO2 production, CH4 flux, nitrification and enzyme activities) depended on both the sediment's origin (reflecting differences in microbial composition between salt and freshwater sediments) and the surrounding environment. In the long-term experiment, general bacterial composition (but not SRB composition) shifted in response to their new environment, and this composition was significantly correlated with sediment functioning. Further, sediment origin had a diminished effect, relative to the short-term experiment, on sediment processes. Overall, this study provides direct evidence that microbial composition directly affects functional processes in these sediments. PMID:23235294

  14. Myocardial performance index is sensitive to changes in cardiac contractility, but is also affected by vascular load condition.

    PubMed

    Uemura, Kazunori; Kawada, Toru; Zheng, Can; Li, Meihua; Shishido, Toshiaki; Sugimachi, Masaru

    2013-01-01

    Myocardial performance index (MPI), or Tei index, is measured by Doppler echocardiography in clinical practice. MPI has been shown to be useful in evaluating left ventricular (LV) performance and predicting prognosis in cardiac patients. However, the effects of LV load and contractile states on MPI remain to be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure-volume relationship with use of sonomicrometry and catheter-tip manometry. MPI was determined from the time derivative of LV volume and pressure. LV end-systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV end-diastolic volume (Ved) were used as indices of LV contractility, afterload and preload, respectively. Hemodynamic conditions were varied over wide ranges [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing cardiovascular agents, by inducing ischemic heart failure and by electrical atrial pacing. Multiple linear regression analysis of pooled data (66 data sets) indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg · ml(-1), p<0.0001, standard partial regression coefficient (β) =-0.66], Ea (3.6-21.9 mmHg · ml(-1), p<0.001, β = 0.4) and Ved (11-100 ml, p<0.0001, β = -0.69). MPI directly correlated with the time constant of isovolumic relaxation (19-66 ms, p<0.05), but not with HR or LV diastolic-stiffness (all p>0.1). Theoretical analysis also indicated that MPI decreases following the increases in LV contractility and in preload, while it increases in response to an increase in LV afterload. We conclude that MPI sensitively detects changes in LV contractility. However, MPI is also affected by changes in LV afterload and preload. PMID:24109782

  15. Live dynamic OCT imaging of cardiac structure and function in mouse embryos with 43 Hz direct volumetric data acquisition

    NASA Astrophysics Data System (ADS)

    Wang, Shang; Singh, Manmohan; Lopez, Andrew L.; Wu, Chen; Raghunathan, Raksha; Schill, Alexander; Li, Jiasong; Larin, Kirill V.; Larina, Irina V.

    2016-03-01

    Efficient phenotyping of cardiac dynamics in live mouse embryos has significant implications on understanding of early mammalian heart development and congenital cardiac defects. Recent studies established optical coherence tomography (OCT) as a powerful tool for live embryonic heart imaging in various animal models. However, current four-dimensional (4D) OCT imaging of the beating embryonic heart largely relies on gated data acquisition or postacquisition synchronization, which brings errors when cardiac cycles lack perfect periodicity and is time consuming and computationally expensive. Here, we report direct 4D OCT imaging of the structure and function of cardiac dynamics in live mouse embryos achieved by employing a Fourier domain mode-locking swept laser source that enables ~1.5 MHz A-line rate. Through utilizing both forward and backward scans of a resonant mirror, we obtained a ~6.4 kHz frame rate, which allows for a direct volumetric data acquisition speed of ~43 Hz, around 20 times of the early-stage mouse embryonic heart rate. Our experiments were performed on mouse embryos at embryonic day 9.5. Time-resolved 3D cardiodynamics clearly shows the heart structure in motion. We present analysis of cardiac wall movement and its velocity from the primitive atrium and ventricle. Our results suggest that the combination of ultrahigh-speed OCT imaging with live embryo culture could be a useful embryonic heart phenotyping approach for mouse mutants modeling human congenital heart diseases.

  16. The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

    PubMed Central

    Desjardins, Cody A.; Naya, Francisco J.

    2016-01-01

    Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2) transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart. PMID:27630998

  17. The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

    PubMed Central

    Desjardins, Cody A.; Naya, Francisco J.

    2016-01-01

    Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2) transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart.

  18. Waon therapy improves quality of life as well as cardiac function and exercise capacity in patients with chronic heart failure.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Fukui, Yasutaka; Ihori, Hiroyuki; Ohori, Takashi; Fujii, Nozomu; Inoue, Hiroshi

    2015-01-01

    Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity.

  19. Plasmid-based transient human stromal cell-derived factor-1 gene transfer improves cardiac function in chronic heart failure

    PubMed Central

    Sundararaman, S; Miller, T J; Pastore, J M; Kiedrowski, M; Aras, R; Penn, M S

    2011-01-01

    We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy. PMID:21472007

  20. Waon therapy improves quality of life as well as cardiac function and exercise capacity in patients with chronic heart failure.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Fukui, Yasutaka; Ihori, Hiroyuki; Ohori, Takashi; Fujii, Nozomu; Inoue, Hiroshi

    2015-01-01

    Waon therapy (WT), which in Japanese means soothing warmth, is a repeated sauna therapy that improves cardiac and vascular endothelial function in patients with chronic heart failure (CHF). We investigated whether WT could improve the quality of life (QOL) of CHF patients in addition to improving cardiac function and exercise capacity.A total of 49 CHF patients (69 ± 14 years old) were treated with a 60°C far infrared-ray dry sauna bath for 15 minutes and then kept in a bed covered with blankets for 30 minutes once a day for 3 weeks. At baseline and 3 weeks after starting WT, cardiac function, 6-minute walk distance (6MWD), flow mediated dilation (FMD) of the brachial artery, and SF36-QOL scores were determined.WT significantly improved left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), 6MWD, and FMD (3.6 ± 2.3 to 5.1 ± 2.8%, P < 0.01). Moreover, WT significantly improved not only the physical (PC) but also mental component (MC) of the QOL scores. WT-induced improvement of PC was negatively correlated with changes in BNP (r = -0.327, P < 0.05), but MC improvement was not related directly to changes in BNP, LVEF, or 6MWD. WT-induced changes in MC were not parallel to PC improvement.WT improved QOL as well as cardiac function and exercise capacity in patients with CHF. Mental QOL improved independently of WT-induced improvement of cardiac function and exercise capacity. PMID:25740582

  1. Cardiac function is preserved following 4 weeks of voluntary wheel running in a rodent model of chronic kidney disease

    PubMed Central

    Kuczmarski, James M.; Martens, Christopher R.; Kim, Jahyun; Lennon-Edwards, Shannon L.

    2014-01-01

    The purpose of this investigation was to determine the effect of 4 wk of voluntary wheel running on cardiac performance in the 5/6 ablation-infarction (AI) rat model of chronic kidney disease (CKD). We hypothesized that voluntary wheel running would be effective in preserving cardiac function in AI. Male Sprague-Dawley rats were divided into three study groups: 1) sham, sedentary nondiseased control; 2) AI-SED, sedentary AI; and 3) AI-WR, wheel-running AI. Animals were maintained over a total period of 8 wk following AI and sham surgery. The 8-wk period included 4 wk of disease development followed by a 4-wk voluntary wheel-running intervention/sedentary control period. Cardiac performance was assessed using an isolated working heart preparation. Left ventricular (LV) tissue was used for biochemical tissue analysis. In addition, soleus muscle citrate synthase activity was measured. AI-WR rats performed a low volume of exercise, running an average of 13 ± 2 km, which resulted in citrate synthase activity not different from that in sham animals. Isolated AI-SED hearts demonstrated impaired cardiac performance at baseline and in response to preload/afterload manipulations. Conversely, cardiac function was preserved in AI-WR vs. sham hearts. LV nitrite + nitrate and expression of LV nitric oxide (NO) synthase isoforms 2 and 3 in AI-WR were not different from those of sham rats. In addition, LV H2O2 in AI-WR was similar to that of sham and associated with increased expression of LV superoxide-dismutase-2 and glutathione peroxidase-1/2. The findings of the current study suggest that a low-volume exercise intervention is sufficient to maintain cardiac performance in rats with CKD, potentially through a mechanism related to improved redox homeostasis and increased NO. PMID:25059238

  2. Cardiac-Restricted Expression of VCP/TER94 RNAi or Disease Alleles Perturbs Drosophila Heart Structure and Impairs Function

    PubMed Central

    Viswanathan, Meera C.; Blice-Baum, Anna C.; Sang, Tzu-Kang; Cammarato, Anthony

    2016-01-01

    Valosin-containing protein (VCP) is a highly conserved mechanoenzyme that helps maintain protein homeostasis in all cells and serves specialized functions in distinct cell types. In skeletal muscle, it is critical for myofibrillogenesis and atrophy. However, little is known about VCP's role(s) in the heart. Its functional diversity is determined by differential binding of distinct cofactors/adapters, which is likely disrupted during disease. VCP mutations cause multisystem proteinopathy (MSP), a pleiotropic degenerative disorder that involves inclusion body myopathy. MSP patients display progressive muscle weakness. They also exhibit cardiomyopathy and die from cardiac and respiratory failure, which are consistent with critical myocardial roles for the enzyme. Nonetheless, efficient models to interrogate VCP in cardiac muscle remain underdeveloped and poorly studied. Here, we investigated the significance of VCP and mutant VCP in the Drosophila heart. Cardiac-restricted RNAi-mediated knockdown of TER94, the Drosophila VCP homolog, severely perturbed myofibrillar organization and heart function in adult flies. Furthermore, expression of MSP disease-causing alleles engendered cardiomyopathy in adults and structural defects in embryonic hearts. Drosophila may therefore serve as a valuable model for examining role(s) of VCP in cardiogenesis and for identifying novel heart-specific VCP interactions, which when disrupted via mutation, contribute to or elicit cardiac pathology. PMID:27500162

  3. Combining wet and dry research: experience with model development for cardiac mechano-electric structure-function studies

    PubMed Central

    Quinn, T. Alexander; Kohl, Peter

    2013-01-01

    Since the development of the first mathematical cardiac cell model 50 years ago, computational modelling has become an increasingly powerful tool for the analysis of data and for the integration of information related to complex cardiac behaviour. Current models build on decades of iteration between experiment and theory, representing a collective understanding of cardiac function. All models, whether computational, experimental, or conceptual, are simplified representations of reality and, like tools in a toolbox, suitable for specific applications. Their range of applicability can be explored (and expanded) by iterative combination of ‘wet’ and ‘dry’ investigation, where experimental or clinical data are used to first build and then validate computational models (allowing integration of previous findings, quantitative assessment of conceptual models, and projection across relevant spatial and temporal scales), while computational simulations are utilized for plausibility assessment, hypotheses-generation, and prediction (thereby defining further experimental research targets). When implemented effectively, this combined wet/dry research approach can support the development of a more complete and cohesive understanding of integrated biological function. This review illustrates the utility of such an approach, based on recent examples of multi-scale studies of cardiac structure and mechano-electric function. PMID:23334215

  4. Cardiac Microvascular Barrier Function Mediates the Protection of Tongxinluo against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Qi, Kang; Li, Lujin; Li, Xiangdong; Zhao, Jinglin; Wang, Yang; You, Shijie; Hu, Fenghuan; Zhang, Haitao; Cheng, Yutong; Kang, Sheng; Cui, Hehe; Duan, Lian; Jin, Chen; Zheng, Qingshan; Yang, Yuejin

    2015-01-01

    Objective Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network. Materials and Methods To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed. Results Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI. Conclusions Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC. PMID:25781461

  5. Cardiac Autonomic Function in Patients With Ankylosing Spondylitis: A Case-Control Study.

    PubMed

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

    2016-05-01

    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.

  6. Affecting Rhomboid-3 Function Causes a Dilated Heart in Adult Drosophila

    PubMed Central

    Yu, Lin; Lee, Teresa; Lin, Na; Wolf, Matthew J.

    2010-01-01

    Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT) can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF)–like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz–EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest that an

  7. Neuropsychological, Academic, and Adaptive Functioning in Children Who Survive In-Hospital Cardiac Arrest and Resuscitation.

    ERIC Educational Resources Information Center

    Morris, Robin D.; And Others

    1993-01-01

    This study of 25 children, ages 2-15, who survived a cardiac arrest while hospitalized, found that a majority of subjects exhibited low-average to deficient levels of performance on neuropsychologic, achievement, and adaptive behavior measures. Duration of cardiac arrest and a medical risk score were significantly correlated with decreased…

  8. Connecting Teratogen-Induced Congenital Heart Defects to Neural Crest Cells and Their Effect on Cardiac Function

    PubMed Central

    Karunamuni, Ganga H.; Ma, Pei; Gu, Shi; Rollins, Andrew M.; Jenkins, Michael W.; Watanabe, Michiko

    2014-01-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest is in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies. PMID:25220155

  9. Connecting teratogen-induced congenital heart defects to neural crest cells and their effect on cardiac function.

    PubMed

    Karunamuni, Ganga H; Ma, Pei; Gu, Shi; Rollins, Andrew M; Jenkins, Michael W; Watanabe, Michiko

    2014-09-01

    Neural crest cells play many key roles in embryonic development, as demonstrated by the abnormalities that result from their specific absence or dysfunction. Unfortunately, these key cells are particularly sensitive to abnormalities in various intrinsic and extrinsic factors, such as genetic deletions or ethanol-exposure that lead to morbidity and mortality for organisms. This review discusses the role identified for a segment of neural crest in regulating the morphogenesis of the heart and associated great vessels. The paradox is that their derivatives constitute a small proportion of cells to the cardiovascular system. Findings supporting that these cells impact early cardiac function raises the interesting possibility that they indirectly control cardiovascular development at least partially through regulating function. Making connections between insults to the neural crest, cardiac function, and morphogenesis is more approachable with technological advances. Expanding our understanding of early functional consequences could be useful in improving diagnosis and testing therapies.

  10. Functional Coupling with Cardiac Muscle Promotes Maturation of hPSC-Derived Sympathetic Neurons.

    PubMed

    Oh, Yohan; Cho, Gun-Sik; Li, Zhe; Hong, Ingie; Zhu, Renjun; Kim, Min-Jeong; Kim, Yong Jun; Tampakakis, Emmanouil; Tung, Leslie; Huganir, Richard; Dong, Xinzhong; Kwon, Chulan; Lee, Gabsang

    2016-07-01

    Neurons derived from human pluripotent stem cells (hPSCs) are powerful tools for studying human neural development and diseases. Robust functional coupling of hPSC-derived neurons with target tissues in vitro is essential for modeling intercellular physiology in a dish and to further translational studies, but it has proven difficult to achieve. Here, we derive sympathetic neurons from hPSCs and show that they can form physical and functional connections with cardiac muscle cells. Using multiple hPSC reporter lines, we recapitulated human autonomic neuron development in vitro and successfully isolated PHOX2B::eGFP+ neurons that exhibit sympathetic marker expression and electrophysiological properties and norepinephrine secretion. Upon pharmacologic and optogenetic manipulation, PHOX2B::eGFP+ neurons controlled beating rates of cardiomyocytes, and the physical interactions between these cells increased neuronal maturation. This study provides a foundation for human sympathetic neuron specification and for hPSC-based neuronal control of organs in a dish. PMID:27320040

  11. Effect of Yoga on migraine: A comprehensive study using clinical profile and cardiac autonomic functions

    PubMed Central

    Kisan, Ravikiran; Sujan, MU; Adoor, Meghana; Rao, Raghavendra; Nalini, A; Kutty, Bindu M; Chindanda Murthy, BT; Raju, TR; Sathyaprabha, TN

    2014-01-01

    Context and Aims: Migraine is an episodic disabling headache requiring long-term management. Migraine management through Yoga therapy would reduce the medication cost with positive health benefits. Yoga has shown to improve the quality of life, reduce the episode of headache and medication. The aim of the present study was to evaluate the efficacy of Yoga as an adjuvant therapy in migraine patients by assessing clinical outcome and autonomic functions tests. Subjects and Methods: Migraine patients were randomly given either conventional care (n = 30) or Yoga with conventional care (n = 30). Yoga group received Yoga practice session for 5 days a week for 6 weeks along with conventional care. Clinical assessment (frequency, intensity of headache and headache impact) and autonomic function test were done at baseline and at the end of the intervention. Results: Yoga with conventional care and convention care groups showed significant improvement in clinical variables, but it was better with Yoga therapy. Improvement in the vagal tone along with reduced sympathetic activity was observed in patients with migraine receiving Yoga as adjuvant therapy. Conclusions: Intervention showed significant clinical improvement in both groups. Headache frequency and intensity were reduced more in Yoga with conventional care than the conventional care group alone. Furthermore, Yoga therapy enhanced the vagal tone and decreased the sympathetic drive, hence improving the cardiac autonomic balance. Thus, Yoga therapy can be effectively incorporated as an adjuvant therapy in migraine patients. PMID:25035622

  12. Lifelong exposure to bisphenol a alters cardiac structure/function, protein expression, and DNA methylation in adult mice.

    PubMed

    Patel, Bhavini B; Raad, Mohamad; Sebag, Igal A; Chalifour, Lorraine E

    2013-05-01

    Bisphenol A (BPA) is an estrogenizing endocrine disruptor compound of concern. Our objective was to test whether lifelong BPA would impact cardiac structure/function, calcium homeostasis protein expression, and the DNA methylation of cardiac genes. We delivered 0.5 and 5.0 µg/kg/day BPA lifelong from gestation day 11 or 200 µg/kg/day from gestation day 11 to postnatal day 21 via the drinking water to C57bl/6n mice. BPA 5.0 males and females had increased body weight, body mass index, body surface area, and adiposity. Echocardiography identified concentric remodeling in all BPA-treated males. Systolic and diastolic cardiac functions were essentially similar, but lifelong BPA enhanced male and reduced female sex-specific differences in velocity of circumferential shortening and ascending aorta velocity time integral. Diastolic blood pressure was increased in all BPA females. The calcium homeostasis proteins sarcoendoplasmic reticulum ATPase 2a (SERCA2a), sodium calcium exchanger-1, phospholamban (PLB), phospho-PLB, and calsequestrin 2 are important for contraction and relaxation. Changes in their expression suggest increased calcium mobility in males and reduced calcium mobility in females supporting the cardiac function changes. DNA methyltransferase 3a expression was increased in all BPA males and BPA 0.5 females and reduced in BPA 200 females. Global DNA methylation was increased in BPA 0.5 males and reduced in BPA 0.5 females. BPA induced sex-specific altered DNA methylation in specific CpG pairs in the calsequestrin 2 CpG island. These results suggest that continual exposure to BPA impacts cardiac structure/function, protein expression, and epigenetic DNA methylation marks in males and females.

  13. Echocardiographic evaluation of pulmonary venous blood flow and cardiac function changes during one-lung ventilation

    PubMed Central

    Lee, Su Hyun; Kim, Namo; Kim, Hyun IL; Oh, Young Jun

    2015-01-01

    Objectives: The intra-pulmonary shunt induced by one-lung ventilation (OLV), is alleviated by increased pulmonary blood flow by gravitational redistribution and hypoxic pulmonary vasoconstriction. We investigated the changes of pulmonary venous blood flow (PVBF) and biventricular function during OLV with echocardiography. And the correlation between PVBF and intra-pulmonary shunt fraction (Qs/Qt) was evaluated. Methods: PVBF of the left upper pulmonary vein and cardiac function were measured with echocardiography in twenty-five patients who underwent elective thoracic surgery in left lateral decubitus. Qs/Qt and PaO2 were measured with blood gas analysis. Data was obtained at 10 min after two-lung ventilation in supine (TLV-S) and lateral decubitus position (TLV-L), and at 10, 20 and 30 min after OLV in lateral decubitus position (OLV-10, -20 and -30). Results: There were significant changes in PVBF among TLV-S, TLV-L and OLV-10 (959.5±280.8, 1416.9±489.7 and 1999.9±670.5 ml/min; P<0.05, respectively). There were not differences in PVBF, Qs/Qt and PaO2 among OLV-10, -20 and -30. There were an inverse correlation between percent change of PVBF and change of Qs/Qt (r2 = 0.5; P<0.0001) and positive correlations between the percent change of PVBF and change of PaO2 (r2 = 0.4; P<0.0001) during OLV over TLV-L. No significant changes in biventricular systolic and diastolic function were observed during positional change and OLV. Conclusions: A remarkable change of PVBF relevant to gravitational distribution and hypoxic pulmonary vasoconstriction was proved by echocardiography. And PVBF changes could represent the changes of Qs/Qt and PaO2 during OLV. However, biventricular function was not impaired during OLV. PMID:26550232

  14. Acute Radiation Effects on Cardiac Function Detected by Strain Rate Imaging in Breast Cancer Patients

    SciTech Connect

    Erven, Katrien; Jurcut, Ruxandra; Weltens, Caroline; Giusca, Sorin; Ector, Joris; Wildiers, Hans; Van den Bogaert, Walter; Voigt, Jens-Uwe

    2011-04-01

    Purpose: To investigate the occurrence of early radiation-induced changes in regional cardiac function using strain rate imaging (SRI) by tissue Doppler echocardiography. Methods and Materials: We included 20 left-sided and 10 right-sided breast cancer patients receiving radiotherapy (RT) to the breast or chest wall. Standard echocardiography and SRI were performed before RT (baseline), immediately after RT (post-RT), and at 2 months follow-up (FUP) after RT. Regional strain (S) and strain rate (SR) values were obtained from all 18 left ventricular (LV) segments. Data were compared to the regional radiation dose. Results: A reduction in S was observed post-RT and at FUP in left-sided patients (S{sub post-RT}: -17.6 {+-} 1.5%, and S{sub FUP}: -17.4 {+-} 2.3%, vs. S{sub baseline}: -19.5 {+-} 2.1%, p < 0.001) but not in right-sided patients. Within the left-sided patient group, S and SR were significantly reduced after RT in apical LV segments (S{sub post-RT}: -15.3 {+-} 2.5%, and S{sub FUP}: -14.3 {+-} 3.7%, vs. S{sub baseline}: -19.3 {+-} 3.0%, p < 0.01; and SR{sub post-RT}: -1.06 {+-} 0.15 s {sup -1}, and SR{sub FUP}: -1.16 {+-} 0.28 s {sup -1}, vs. SR{sub baseline}: -1.29 {+-} 0.27s {sup -1}, p = 0.01), but not in mid- or basal segments. Furthermore, we observed that segments exposed to more than 3 Gy showed a significant decrease in S after RT (S{sub post-RT}: -16.1 {+-} 1.6%, and S{sub FUP}: -15.8 {+-} 3.4%, vs. S{sub baseline}: -18.9 {+-} 2.6%, p < 0.001). This could not be observed in segments receiving less than 3 Gy. Conclusions: SRI shows a dose-related regional decrease in myocardial function after RT. It might be a useful tool in the evaluation of modern RT techniques, with respect to cardiac toxicity.

  15. Cardiac function in BRCA1/2 mutation carriers with history of breast cancer treated with anthracyclines.

    PubMed

    Barac, Ana; Lynce, Filipa; Smith, Karen L; Mete, Mihriye; Shara, Nawar M; Asch, Federico M; Nardacci, Madeline P; Wray, Lynette; Herbolsheimer, Pia; Nunes, Raquel A; Swain, Sandra M; Warren, Robert; Peshkin, Beth N; Isaacs, Claudine

    2016-01-01

    Animal data suggest that defects in BRCA1/2 genes significantly increase the risk of heart failure and mortality in mice exposed to doxorubicine. Women with BRCA1/2 mutations who develop breast cancer (BC) may receive anthracyclines but their risk of cardiac dysfunction has not been investigated. Our study tested the hypothesis that women with history of BRCA1/2 mutation-associated BC treated with anthracyclines have impaired parameters of cardiac function compared to similarly treated women with history of sporadic BC. Women with history of BC and anthracycline treatment underwent an echocardiographic exam for assessment of primary outcomes, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). The sample size of 81 provided 79 % power with two-sided two-sample t test and alpha of 0.05 to detect a clinically meaningful difference in cardiac function of absolute 5 % points difference for LVEF and 2 % points difference for GLS. Of 81 normotensive participants, 39 were BRCA1/2 mutation carriers and 42 in the sporadic group. Mean age was 50 ± 9 years in both groups (P = 0.99) but BRCA1/2 mutation carriers had longer anthracycline treatment-to-enrollment time (7.5 ± 5.3 vs. 4.2 ± 3.3 years, P = 0.001). There were no significant differences in LVEF (P = 0.227) or GLS (P = 0.53) between the groups. LVEF was normal in 91 % of women and subclinical cardiac dysfunction defined as absolute GLS value <18.9 % was seen in 4 (10 %) BRCA1/2 mutation carriers and 7 (17 %) sporadic participants. In this first prospective examination of cardiac function in BRCA1/2 mutation carriers, we found no significant differences in sensitive echocardiographic parameters of cardiac function between BRCA1/2 mutation carriers and women with history of sporadic BC who received anthracycline treatment. In contrast to laboratory animal data, our findings indicate lack of elevated cardiac risk with the use of standard-doses of adjuvant anthracyclines in treatment of BRCA1

  16. Cardiac mitochondrial function and tissue remodelling are improved by a non-antihypertensive dose of enalapril in spontaneously hypertensive rats.

    PubMed

    Piotrkowski, Barbara; Koch, Osvaldo R; De Cavanagh, Elena M V; Fraga, César G

    2009-04-01

    Renal and cardiac benefits of renin-angiotensin system inhibition exceed blood pressure (BP) reduction and seem to involve mitochondrial function. It has been shown that RAS inhibition prevented mitochondrial dysfunction in spontaneously hypertensive rats (SHR) kidneys. Here, it is investigated whether a non-antihypertensive enalapril dose protects cardiac tissue and mitochondria function. Three-month-old SHR received water containing enalapril (10 mg/kg/day, SHR+Enal) or no additions (SHR-C) for 5 months. Wistar-Kyoto rats (WKY) were normotensive controls. At month 5, BP was similar in SHR+Enal and SHR-C. In SHR+Enal and WKY, heart weight and myocardial fibrosis were lower than in SHR-C. Matrix metalloprotease-2 activity was lower in SHR+Enal with respect to SHR-C and WKY. In SHR+Enal and WKY, NADH/cytochrome c oxidoreductase activity, eNOS protein and activity and mtNOS activity were higher and Mn-SOD activity was lower than in SHR-C. In summary, enalapril at a non-antihypertensive dose prevented cardiac hypertrophy and modifies parameters of cardiac mitochondrial dysfunction in SHR. PMID:19296328

  17. Embryonic caffeine exposure acts via A1 adenosine receptors to alter adult cardiac function and DNA methylation in mice.

    PubMed

    Buscariollo, Daniela L; Fang, Xiefan; Greenwood, Victoria; Xue, Huiling; Rivkees, Scott A; Wendler, Christopher C

    2014-01-01

    Evidence indicates that disruption of normal prenatal development influences an individual's risk of developing obesity and cardiovascular disease as an adult. Thus, understanding how in utero exposure to chemical agents leads to increased susceptibility to adult diseases is a critical health related issue. Our aim was to determine whether adenosine A1 receptors (A1ARs) mediate the long-term effects of in utero caffeine exposure on cardiac function and whether these long-term effects are the result of changes in DNA methylation patterns in adult hearts. Pregnant A1AR knockout mice were treated with caffeine (20 mg/kg) or vehicle (0.09% NaCl) i.p. at embryonic day 8.5. This caffeine treatment results in serum levels equivalent to the consumption of 2-4 cups of coffee in humans. After dams gave birth, offspring were examined at 8-10 weeks of age. A1AR+/+ offspring treated in utero with caffeine were 10% heavier than vehicle controls. Using echocardiography, we observed altered cardiac function and morphology in adult mice exposed to caffeine in utero. Caffeine treatment decreased cardiac output by 11% and increased left ventricular wall thickness by 29% during diastole. Using DNA methylation arrays, we identified altered DNA methylation patterns in A1AR+/+ caffeine treated hearts, including 7719 differentially methylated regions (DMRs) within the genome and an overall decrease in DNA methylation of 26%. Analysis of genes associated with DMRs revealed that many are associated with cardiac hypertrophy. These data demonstrate that A1ARs mediate in utero caffeine effects on cardiac function and growth and that caffeine exposure leads to changes in DNA methylation.

  18. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    PubMed Central

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2015-01-01

    The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (IncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of IncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated IncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived IncRNAs. PMID:25149110

  19. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    DOE PAGES

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; et al

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Throughmore » a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.« less

  20. Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease

    SciTech Connect

    Ounzain, Samir; Pezzuto, Iole; Micheletti, Rudi; Burdet, Frédéric; Sheta, Razan; Nemir, Mohamed; Gonzales, Christine; Sarre, Alexandre; Alexanian, Michael; Blow, Matthew J.; May, Dalit; Johnson, Rory; Dauvillier, Jérôme; Pennacchio, Len A.; Pedrazzini, Thierry

    2014-08-19

    We report here that the key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

  1. Bisphenol A affects androgen receptor function via multiple mechanisms.

    PubMed

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B Alex; Jetten, Anton M; Austin, Christopher P; Tice, Raymond R

    2013-05-25

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR.

  2. Bisphenol A affects androgen receptor function via multiple mechanisms

    PubMed Central

    Teng, Christina; Goodwin, Bonnie; Shockley, Keith; Xia, Menghang; Huang, Ruili; Norris, John; Merrick, B. Alex; Jetten, Anton M.; Austin, Christopher, P.; Tice, Raymond R.

    2013-01-01

    Bisphenol A (BPA), is a well-known endocrine disruptor compound (EDC) that affects the normal development and function of the female and male reproductive system, however the mechanisms of action remain unclear. To investigate the molecular mechanisms of how BPA may affect ten different nuclear receptors, stable cell lines containing individual nuclear receptor ligand binding domain (LBD)-linked to the β-Gal reporter were examined by a quantitative high throughput screening (qHTS) format in the Tox21 Screening Program of the NIH. The results showed that two receptors, estrogen receptor alpha (ERα) and androgen receptor (AR), are affected by BPA in opposite direction. To confirm the observed effects of BPA on ERα and AR, we performed transient transfection experiments with full-length receptors and their corresponding response elements linked to luciferase reporters. We also included in this study two BPA analogs, bisphenol AF (BPAF) and bisphenol S (BPS). As seen in African green monkey kidney CV1 cells, the present study confirmed that BPA and BPAF act as ERα agonists (half maximal effective concentration EC50 of 10-100 nM) and as AR antagonists (half maximal inhibitory concentration IC50 of 1-2 μM). Both BPA and BPAF antagonized AR function via competitive inhibition of the action of synthetic androgen R1881. BPS with lower estrogenic activity (EC50 of 2.2 μM), did not compete with R1881 for AR binding, when tested at 30 μM. Finally, the effects of BPA were also evaluated in a nuclear translocation assays using EGPF-tagged receptors. Similar to 17β-estradiol (E2) which was used as control, BPA was able to enhance ERα nuclear foci formation but at a 100-fold higher concentration. Although BPA was able to bind AR, the nuclear translocation was reduced. Furthermore, BPA was unable to induce functional foci in the nuclei and is consistent with the transient transfection study that BPA is unable to activate AR. PMID:23562765

  3. Mechano-sensitivity of cardiac pacemaker function: Pathophysiological relevance, experimental implications, and conceptual integration with other mechanisms of rhythmicity

    PubMed Central

    Quinn, T. Alexander; Kohl, Peter

    2012-01-01

    Cardiac pacemaker cells exhibit spontaneous, rhythmic electrical excitation, termed automaticity. This automatic initiation of action potentials requires spontaneous diastolic depolarisation, whose rate determines normal rhythm generation in the heart. Pacemaker mechanisms have been split recently into: (i) cyclic changes in trans-sarcolemmal ion flows (termed the ‘membrane-clock’), and (ii) rhythmic intracellular calcium cycling (the ‘calcium-clock’). These two ‘clocks’ undoubtedly interact, as trans-sarcolemmal currents involved in pacemaking include calcium-carrying mechanisms, while intracellular calcium cycling requires trans-sarcolemmal ion flux as the mechanism by which it affects membrane potential. The split into separate ‘clocks’ is, therefore, somewhat arbitrary. Nonetheless, the ‘clock’ metaphor has been conceptually stimulating, in particular since there is evidence to support the view that either ‘clock’ could be sufficient in principle to set the rate of pacemaker activation. Of course, the same has also been shown for sub-sets of ‘membrane-clock’ ion currents, illustrating the redundancy of mechanisms involved in maintaining such basic functionality as the heartbeat, a theme that is common for vital physiological systems. Following the conceptual path of identifying individual groups of sub-mechanisms, it is important to remember that the heart is able to adapt pacemaker rate to changes in haemodynamic load, even after isolation or transplantation, and on a beat-by-beat basis. Neither the ‘membrane-’ nor the ‘calcium-clock’ do, as such, inherently account for this rapid adaptation to circulatory demand (cellular Ca2+ balance changes over multiple beats, while variation of sarcolemmal ion channel presence takes even longer). This suggests that a third set of mechanisms must be involved in setting the pace. These mechanisms are characterised by their sensitivity to the cyclically changing mechanical environment, and

  4. Cardiac myosin-binding protein-C is a critical mediator of diastolic function.

    PubMed

    Tong, Carl W; Nair, Nandini A; Doersch, Karen M; Liu, Yang; Rosas, Paola C

    2014-03-01

    Diastolic dysfunction prominently contributes to heart failure with preserved ejection fraction (HFpEF). Owing partly to inadequate understanding, HFpEF does not have any effective treatments. Cardiac myosin-binding protein-C (cMyBP-C), a component of the thick filament of heart muscle that can modulate cross-bridge attachment/detachment cycling process by its phosphorylation status, appears to be involved in the diastolic dysfunction associated with HFpEF. In patients, cMyBP-C mutations are associated with diastolic dysfunction even in the absence of hypertrophy. cMyBP-C deletion mouse models recapitulate diastolic dysfunction despite in vitro evidence of uninhibited cross-bridge cycling. Reduced phosphorylation of cMyBP-C is also associated with diastolic dysfunction in patients. Mouse models of reduced cMyBP-C phosphorylation exhibit diastolic dysfunction while cMyBP-C phosphorylation mimetic mouse models show enhanced diastolic function. Thus, cMyBP-C phosphorylation mediates diastolic function. Experimental results of both cMyBP-C deletion and reduced cMyBP-C phosphorylation causing diastolic dysfunction suggest that cMyBP-C phosphorylation level modulates cross-bridge detachment rate in relation to ongoing attachment rate to mediate relaxation. Consequently, alteration in cMyBP-C regulation of cross-bridge detachment is a key mechanism that causes diastolic dysfunction. Regardless of the exact molecular mechanism, ample clinical and experimental data show that cMyBP-C is a critical mediator of diastolic function. Furthermore, targeting cMyBP-C phosphorylation holds potential as a future treatment for diastolic dysfunction. PMID:24442121

  5. Cardiac morphology and function in patients with and without residual diuresis on hemodialysis.

    PubMed

    Araujo, Salustiano; Lemes, Helton P; Cunha, Danny A; Queiroz, Vinicius S; Nascimento, Daniela D; Ferreira Filho, Sebastião Rodrigues

    2011-03-01

    In patients with chronic renal failure on hemodialysis, left ventricular hypertrophy is related to the increase in total peripheral vascular resistance and volume overload. The presence of residual diuresis enables greater control of the volemia of these. We evaluated the morpho-functional changes of the left ventricle in patients with chronic kidney disease on hemodyalisis treatment with and without residual diuresis. A total of 31 non diabetic patients were studied and they were divided into two groups: with residual diuresis (RD+) (n = 17) and without residual diuresis (RD-) (n = 14). In both groups, RD+ vs. RD-, using data from a Doppler echocardiogram differences were found, respectively, in the cardiac index (3.9 ± 0.2 vs. 3.0 ± 0.2 L/min/m²; p = 0.0056), systolic index (54 ± 2.9 vs. 45 ± 3.3 mL/b/m²; p = 0.04), end diastolic volume (141 ± 6.7 vs. 112 ± 7.6 mL; p = 0.008), end diastolic diameter (52 ± 0.7 vs. 48 ± 1.1 mm; p = 0.0072) and total peripheral resistance index (1121 ± 56 vs. 1529 ± 111 dyne.sec.cm-5; p = 0.001). RD+ had lower relative wall thickness than RD- (0.38 ± 0.01 vs. 0.45 ± 0.01; p = 0.0008). The ejection fraction and the left ventricular mass index were similar in both groups. The urinary 24-hour volume correlated with the relative wall thickness (r = -0.42; p = 0.0186) and with peripheral resistance index (r = -0.48; p = 0.0059). In conclusion, there were distinct ventricular geometric patterns and different functional performances between RD+ and RD- groups. The presence of residual diuresis can be responsible by these modifications in systolic function.

  6. Impaired Cerebrovascular Function in Coronary Artery Disease Patients and Recovery Following Cardiac Rehabilitation

    PubMed Central

    Anazodo, Udunna C.; Shoemaker, J. K.; Suskin, Neville; Ssali, Tracy; Wang, Danny J. J.; St. Lawrence, Keith S.

    2016-01-01

    Coronary artery disease (CAD) poses a risk to the cerebrovascular function of older adults and has been linked to impaired cognitive abilities. Using magnetic resonance perfusion imaging, we investigated changes in resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to hypercapnia in 34 CAD patients and 21 age-matched controls. Gray matter volume (GMV) images were acquired and used as a confounding variable to separate changes in structure from function. Compared to healthy controls, CAD patients demonstrated reduced CBF in the superior frontal, anterior cingulate (AC), insular, pre- and post-central gyri, middle temporal, and superior temporal regions. Subsequent analysis of these regions demonstrated decreased CVR in the AC, insula, post-central and superior frontal regions. Except in the superior frontal and precentral regions, regional reductions in CBF and CVR were identified in brain areas where no detectable reductions in GMV were observed, demonstrating that these vascular changes were independent of brain atrophy. Because aerobic fitness training can improve brain function, potential changes in regional CBF were investigated in the CAD patients after completion of a 6-months exercise-based cardiac rehabilitation program. Increased CBF was observed in the bilateral AC, as well as recovery of CBF in the dorsal aspect of the right AC, where the magnitude of increased CBF was roughly equal to the reduction in CBF at baseline compared to controls. These exercise-related improvements in CBF in the AC is intriguing given the role of this area in cognitive processing and regulation of cardiovascular autonomic control. PMID:26779011

  7. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood

    PubMed Central

    Shoykhet, Michael; Middleton, Jason W.

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  8. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood

    PubMed Central

    Shoykhet, Michael; Middleton, Jason W.

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  9. Cardiac Arrest-Induced Global Brain Hypoxia-Ischemia during Development Affects Spontaneous Activity Organization in Rat Sensory and Motor Thalamocortical Circuits during Adulthood.

    PubMed

    Shoykhet, Michael; Middleton, Jason W

    2016-01-01

    Normal maturation of sensory information processing in the cortex requires patterned synaptic activity during developmentally regulated critical periods. During early development, spontaneous synaptic activity establishes required patterns of synaptic input, and during later development it influences patterns of sensory experience-dependent neuronal firing. Thalamocortical neurons occupy a critical position in regulating the flow of patterned sensory information from the periphery to the cortex. Abnormal thalamocortical inputs may permanently affect the organization and function of cortical neuronal circuits, especially if they occur during a critical developmental window. We examined the effect of cardiac arrest (CA)-associated global brain hypoxia-ischemia in developing rats on spontaneous and evoked firing of somatosensory thalamocortical neurons and on large-scale correlations in the motor thalamocortical circuit. The mean spontaneous and sensory-evoked firing rate activity and variability were higher in CA injured rats. Furthermore, spontaneous and sensory-evoked activity and variability were correlated in uninjured rats, but not correlated in neurons from CA rats. Abnormal activity patterns of ventroposterior medial nucleus (VPm) neurons persisted into adulthood. Additionally, we found that neurons in the entopeduncular nucleus (EPN) in the basal ganglia had lower firing rates yet had higher variability and higher levels of burst firing after injury. Correlated levels of power in local field potentials (LFPs) between the EPN and the motor cortex (MCx) were also disrupted by injury. Our findings indicate that hypoxic-ischemic injury during development leads to abnormal spontaneous and sensory stimulus-evoked input patterns from thalamus to cortex. Abnormal thalamic inputs likely permanently and detrimentally affect the organization of cortical circuitry and processing of sensory information. Hypoxic-ischemic injury also leads to abnormal single neuron and

  10. Cardiac autonomic functions and the emergence of violence in a highly realistic model of social conflict in humans

    PubMed Central

    Haller, Jozsef; Raczkevy-Deak, Gabriella; Gyimesine, Katalin P.; Szakmary, Andras; Farkas, Istvan; Vegh, Jozsef

    2014-01-01

    Among the multitude of factors that can transform human social interactions into violent conflicts, biological features received much attention in recent years as correlates of decision making and aggressiveness especially in critical situations. We present here a highly realistic new model of human aggression and violence, where genuine acts of aggression are readily performed and which at the same time allows the parallel recording of biological concomitants. Particularly, we studied police officers trained at the International Training Centre (Budapest, Hungary), who are prepared to perform operations under extreme conditions of stress. We found that aggressive arousal can transform a basically peaceful social encounter into a violent conflict. Autonomic recordings show that this change is accompanied by increased heart rates, which was associated earlier with reduced cognitive complexity of perceptions (“attentional myopia”) and promotes a bias toward hostile attributions and aggression. We also observed reduced heart rate variability in violent subjects, which is believed to signal a poor functioning of prefrontal-subcortical inhibitory circuits and reduces self-control. Importantly, these autonomic particularities were observed already at the beginning of social encounters i.e., before aggressive acts were initiated, suggesting that individual characteristics of the stress-response define the way in which social pressure affects social behavior, particularly the way in which this develops into violence. Taken together, these findings suggest that cardiac autonomic functions are valuable external symptoms of internal motivational states and decision making processes, and raise the possibility that behavior under social pressure can be predicted by the individual characteristics of stress responsiveness. PMID:25374519

  11. Can lifestyle modification affect men’s erectile function?

    PubMed Central

    Hehemann, Marah C.

    2016-01-01

    Erectile dysfunction (ED) is a common condition affecting millions of men worldwide. The pathophysiology and epidemiologic links between ED and risk factors for cardiovascular disease (CVD) are well-established. Lifestyle modifications such as smoking cessation, weight reduction, dietary modification, physical activity, and psychological stress reduction have been increasingly recognized as foundational to the prevention and treatment of ED. The aim of this review is to outline behavioral choices which may increase ones risk of developing ED, to present relevant studies addressing lifestyle factors correlated with ED, and to highlight proposed mechanisms for intervention aimed at improving erectile function in men with ED. These recommendations can provide a framework for counseling patients with ED about lifestyle modification. PMID:27141445

  12. Alteration of cardiac autonomic function in patients with newly diagnosed epilepsy.

    PubMed

    Goit, Rajesh K; Jha, Santosh K; Pant, Bhawana N

    2016-06-01

    The aim of the study was to determine if heart rate variability (HRV) showed any changes in patients with newly diagnosed epilepsy in comparison with controls. Sixty-five patients with epilepsy (38 males and 27 females), aged 30-50 years, who had never previously received treatment with antiepileptic drugs were eligible for inclusion in this study. Resting electrocardiogram (ECG) at spontaneous respiration was recorded for 5 min in supine position. Time-domain analysis, frequency-domain analysis, and Poincare plot of HRV were recorded from ECG In time-domain measures, the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD) and percentage of consecutive RR intervals that differ by more than 50 msec (pNN50) were significantly less in patients with epilepsy. In frequency-domain measures, high frequency [(HF) msec(2)], HF (nu), and low frequency [LF (msec(2))] were significantly less in patients with epilepsy while LF (nu) and LF/HF were significantly high in patients with epilepsy. In Poincare plot, standard deviation perpendicular to line of Poincare plot (SD1) and standard deviation along the line of entity in Poincare plot (SD2) were significantly less in patients with epilepsy. Our results suggest that epileptic patients have an impact on the cardiac autonomic function as measured by HRV.

  13. TGF-{beta}{sub 1}-induced cardiac myofibroblasts are nonproliferating functional cells carrying DNA damages

    SciTech Connect

    Petrov, Victor V. Pelt, Jos F. van; Vermeesch, Joris R.; Van Duppen, Viktor J.; Vekemans, Katrien; Fagard, Robert H.; Lijnen, Paul J.

    2008-04-15

    TGF-{beta}{sub 1} induces differentiation and total inhibition of cardiac MyoFb cell division and DNA synthesis. These effects of TGF-{beta}{sub 1} are irreversible. Inhibition of MyoFb proliferation is accompanied with the expression of Smad1, Mad1, p15Ink4B and total inhibition of telomerase activity. Surprisingly, TGF-{beta}{sub 1}-activated MyoFbs are growth-arrested not only at G1-phase but also at S-phase of the cell cycle. Staining with TUNEL indicates that these cells carry DNA damages. However, the absolute majority of MyoFbs are non-apoptotic cells as established with two apoptosis-specific methods, flow cytometry and caspase-dependent cleavage of cytokeratin 18. Expression in MyoFbs of proliferative cell nuclear antigen even in the absence of serum confirms that these MyoFbs perform repair of DNA damages. These results suggest that TGF-{beta}{sub 1}-activated MyoFbs can be growth-arrested by two checkpoints, the G1/S checkpoint, which prevents cells from entering S-phase and the intra-S checkpoint, which is activated by encountering DNA damage during the S phase or by unrepaired damage that escapes the G1/S checkpoint. Despite carrying of the DNA damages TGF-{beta}{sub 1}-activated MyoFbs are highly functional cells producing lysyl oxidase and contracting the collagen matrix.

  14. Astragalus polysaccharide improves cardiac function in doxorubicin-induced cardiomyopathy through ROS-p38 signaling

    PubMed Central

    Zhou, Liangliang; Chen, Lanping; Wang, Jing; Deng, Yijun

    2015-01-01

    Doxorubicin (DOX) is widely used as an antitumor agent, but it is significantly challenged by clinical workers due to the severe and acute cardiotoxitity. Astragalus polysaccharide (APS) is characterized by an anti-inflammation and anti-oxidant features. In the current study, we explored the effects and specific mechanisms of APS on DOX-induced-cardiomyopathy in mouse primary myocardial cells. To explore the effect of DOX on ROS production, DHE staining and flow cytometry analysis were used in primary cardiomyocytes treated with 1 μM DOX for 24 h. MTT assay was applied to determine the effect of DOX on cell viability. The effects of DOX on rat cardiomyocytes apoptosis by Hoechst staining and annexin V-PI staining, while caspase3 activity was determined using an assay kit. Two-dimensional echocardiography of rats was performed to determine left ventricular fraction and relative wall thickness. Activation of p38 and Akt was analyzed using western blot. ROS production was significantly enhanced by DOX stimulation in primary cardiomyocytes. DOX reduced rat cardiomyocytes viability in a time- and dose-dependent manner. DOX induced apoptosis in rat cardiomyocytes via activation of caspase-3. Cardiac function was significantly impaired by enhanced p38 activation. APS treatment reduced DOX-induced rat cardiomyocytes apoptosis by decreasing ROS production. To conclude, APS reduced DOX-induced cell apoptosis and ROS production by reduced activation of p38 signaling pathway. PMID:26885153

  15. Cardiovascular anatomy and cardiac function in the air-breathing swamp eel (Monopterus albus).

    PubMed

    Iversen, Nina K; Lauridsen, Henrik; Do, Thi Thanh Huong; Nguyen, Van Cong; Gesser, Hans; Buchanan, Rasmus; Bayley, Mark; Pedersen, Michael; Wang, Tobias

    2013-01-01

    Monopterus albus, a swamp eel inhabiting the freshwaters of South East Asia, relies on an extensive vascularisation of the buccal cavity, pharynx and anterior oesophagus for gas exchange, while the gills are much reduced. In the present study we describe the macro-circulation in the cephalic region and the vascularisation of the buccal cavity of M. albus using vascular fillings and micro-computed tomography (μCT). We also show that M. albus has the capacity to use the buccal cavity for aquatic gas exchange, being able to maintain normal arterial blood gas composition, blood pressure, heart rate and cardiac output throughout 10h of forced submergence. M. albus therefore can be characterised as a facultative air-breather. Because M. albus aestivates for many months in moist mud during the dry season we characterised in vivo cardiovascular function during exposure to anoxia as well as the effects of anoxia on in vitro contractility of strip preparations from atria and ventricle. Both studies revealed a low anoxia tolerance, rendering it unlikely that M. albus can survive prolonged exposure to anoxia.

  16. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  17. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing. PMID:20336685

  18. Functional roles affect diversity-succession relationships for boreal beetles.

    PubMed

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of "functional" groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience.

  19. Functional characterization of CaVα2δ mutations associated with sudden cardiac death.

    PubMed

    Bourdin, Benoîte; Shakeri, Behzad; Tétreault, Marie-Philippe; Sauvé, Rémy; Lesage, Sylvie; Parent, Lucie

    2015-01-30

    L-type Ca(2+) channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30-33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca(2+) currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. PMID:25527503

  20. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  1. To what extent does urbanisation affect fragmented grassland functioning?

    PubMed

    van der Walt, L; Cilliers, S S; Kellner, K; Du Toit, M J; Tongway, D

    2015-03-15

    Urbanisation creates altered environments characterised by increased human habitation, impermeable surfaces, artificial structures, landscape fragmentation, habitat loss, resulting in different resource loss pathways. The vulnerable Rand Highveld Grassland vegetation unit in the Tlokwe Municipal area, South Africa, has been extensively affected and transformed by urbanisation, agriculture, and mining. Grassland fragments in urban areas are often considered to be less species rich and less functional than in the more untransformed or "natural" exurban environments, and are therefore seldom a priority for conservation. Furthermore, urban grassland fragments are often being more intensely managed than exurban areas, such as consistent mowing in open urban areas. Four urbanisation measures acting as indicators for patterns and processes associated with urban areas were calculated for matrix areas surrounding each selected grassland fragment to quantify the position of each grassland remnant along an urbanisation gradient. The grassland fragments were objectively classified into two classes of urbanisation, namely "exurban" and "urban" based on the urbanisation measure values. Grazing was recorded in some exurban grasslands and mowing in some urban grassland fragments. Unmanaged grassland fragments were present in both urban and exurban areas. Fine-scale biophysical landscape function was determined by executing the Landscape Function Analysis (LFA) method. LFA assesses fine-scale landscape patchiness (entailing resource conserving potential and erosion resistance) and 11 soil surface indicators to produce three main LFA parameters (stability, infiltration, and nutrient cycling), which indicates how well a system is functioning in terms of fine-scale biophysical soil processes and characteristics. The aim of this study was to determine the effects of urbanisation and associated management practices on fine-scale biophysical landscape function of urban and exurban

  2. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction.

    PubMed

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×10(6) or 1x10(6) cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×10(6) CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved

  3. Gelatin Hydrogel Enhances the Engraftment of Transplanted Cardiomyocytes and Angiogenesis to Ameliorate Cardiac Function after Myocardial Infarction

    PubMed Central

    Nakajima, Kazuaki; Fujita, Jun; Matsui, Makoto; Tohyama, Shugo; Tamura, Noriko; Kanazawa, Hideaki; Seki, Tomohisa; Kishino, Yoshikazu; Hirano, Akinori; Okada, Marina; Tabei, Ryota; Sano, Motoaki; Goto, Shinya; Tabata, Yasuhiko; Fukuda, Keiichi

    2015-01-01

    Cell transplantation therapy will mean a breakthrough in resolving the donor shortage in cardiac transplantation. Cardiomyocyte (CM) transplantation, however, has been relatively inefficient in restoring cardiac function after myocardial infarction (MI) due to low engraftment of transplanted CM. In order to ameliorate engraftment of CM, the novel transplantation strategy must be invented. Gelatin hydrogel (GH) is a biodegradable water-soluble polymer gel. Gelatin is made of collagen. Although we observed that collagen strongly induced the aggregation of platelets to potentially cause coronary microembolization, GH did not enhance thrombogenicity. Therefore, GH is a suitable biomaterial in the cell therapy after heart failure. To assess the effect of GH on the improvement of cardiac function, fetal rat CM (5×106 or 1x106 cells) were transplanted with GH (10 mg/ml) to infarcted hearts. We compared this group with sham operated rats, CM in phosphate buffered saline (PBS), only PBS, and only GH-transplanted groups. Three weeks after transplantation, cardiac function was evaluated by echocardiography. The echocardiography confirmed that transplantation of 5×106 CM with GH significantly improved cardiac systolic function, compared with the CM+PBS group (fractional area change: 75.1±3.4% vs. 60.7±5.9%, p<0.05), only PBS, and only GH groups (60.1±6.5%, 65.0±2.8%, p<0.05). Pathological analyses demonstrated that in the CM+GH group, CM were efficiently engrafted in infarcted myocardium (p<0.01) and angiogenesis was significantly enhanced (p<0.05) in both central and peripheral areas of the scar. Moreover, quantitative RT-PCR revealed that angiogenic cytokines, such as basic fibroblast growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were significantly enriched in the CM+GH group (p<0.05). Here, we report that GH confined the CM effectively in infarcted myocardium after transplantation, and that CM transplanted with GH improved cardiac

  4. Inhalation of Photochemically Altered Urban Mixtures Depresses Cardiac Function in Mice

    EPA Science Inventory

    Rationale: Epidemiological studies have indicated an association between urban air pollution exposure and cardiovascular morbidity and mortality. The present study was designed to evaluate the cardiac effects of inhaled photochemical products in urban mixtures in a murine model. ...

  5. Integrating Negative Affect Measures in a Measurement Model: Assessing the Function of Negative Affect as Interference to Self-Regulation

    ERIC Educational Resources Information Center

    Magno, Carlo

    2010-01-01

    The present study investigated the composition of negative affect and its function as inhibitory to thought processes such as self-regulation. Negative affect in the present study were composed of anxiety, worry, thought suppression, and fear of negative evaluation. These four factors were selected based on the criteria of negative affect by…

  6. Amino-functionalization of carbon nanotubes by using a factorial design: human cardiac troponin T immunosensing application.

    PubMed

    Freitas, Tatianny A; Mattos, Alessandra B; Silva, Bárbara V M; Dutra, Rosa F

    2014-01-01

    A simple amino-functionalization method for carbon nanotubes and its application in an electrochemical immunosensor for detection of the human cardiac troponin T are described. Amino-functionalized carbon nanotubes allow oriented antibodies immobilization via their Fc regions, improving the performance of an immunosensor. Herein multiwalled carbon nanotubes were amino-functionalized by using the ethylenediamine reagent and assays were designed by fractional factorial study associated with Doehlert matrix. Structural modifications in the carbon nanotubes were confirmed by Fourier transform infrared spectroscopy. After amino-functionalization the carbon nanotubes were attached to screen-printed carbon electrode and a sandwich-type immunoassay was performed for measuring the cardiac troponin T. The electrochemical measurements were obtained through hydrogen peroxide reaction with peroxidase conjugated to the secondary antibody. Under optimal conditions, troponin T immunosensor was evaluated in serum samples, which showed a broad linear range (0.02 to 0.32 ng mL(-1)) and a low limit of detection, 0.016 ng mL(-1). This amino platform can be properly used as clinical tool for cardiac troponin T detection in the acute myocardial infarction diagnosis.

  7. Influence of different anesthetic and analgesic methods on early cognitive function of elderly patients receiving non-cardiac surgery

    PubMed Central

    Wang, Yong; Zhang, Jie; Zhang, Shuijun

    2016-01-01

    Objective: To discuss over influence of two different anesthetic and analgesic methods on early cognitive function of elderly patients who received non-cardiac surgery. Methods: Two hundred and six elderly patients who underwent non-cardiac surgery were selected as research subjects. They were randomly divided into observation group (103 cases) and control group (103 cases). Patients in observation group were given combined spinal and epidural anesthesia and epidural analgesia, while patients in control group adopted general anesthesia and intravenous analgesia. Neurological function test was carried out one day before surgery and on the 7th day after surgery. Moreover, changes of postoperative pain degree, neuropsychological function and cognitive function were observed and compared. Results: On the 7th day after surgery, incidence of cognition impairment in observation group and control group was 48.50% (50/103 cases) and 44.70% (46/103 cases), and difference between groups had no statistical significance. Visual Analogue Scale (VAS) Score of observation group was much lower than control group in the 12th, 24th and 48th h after surgery (p < 0.05). Logistic regression analysis suggested that, short education years and general surgery were independent risk factors for early cognition impairment. Conclusion: About 46.60% elderly patients undergoing non-cardiac surgery developed cognition impairment, but influence of different anesthetic and analgesic methods on incidence of postoperative cognition impairment of elderly patients had no significant difference. PMID:27182242

  8. Amino-Functionalization of Carbon Nanotubes by Using a Factorial Design: Human Cardiac Troponin T Immunosensing Application

    PubMed Central

    Freitas, Tatianny A.; Mattos, Alessandra B.; Silva, Bárbara V. M.; Dutra, Rosa F.

    2014-01-01

    A simple amino-functionalization method for carbon nanotubes and its application in an electrochemical immunosensor for detection of the human cardiac troponin T are described. Amino-functionalized carbon nanotubes allow oriented antibodies immobilization via their Fc regions, improving the performance of an immunosensor. Herein multiwalled carbon nanotubes were amino-functionalized by using the ethylenediamine reagent and assays were designed by fractional factorial study associated with Doehlert matrix. Structural modifications in the carbon nanotubes were confirmed by Fourier transform infrared spectroscopy. After amino-functionalization the carbon nanotubes were attached to screen-printed carbon electrode and a sandwich-type immunoassay was performed for measuring the cardiac troponin T. The electrochemical measurements were obtained through hydrogen peroxide reaction with peroxidase conjugated to the secondary antibody. Under optimal conditions, troponin T immunosensor was evaluated in serum samples, which showed a broad linear range (0.02 to 0.32 ng mL−1) and a low limit of detection, 0.016 ng mL−1. This amino platform can be properly used as clinical tool for cardiac troponin T detection in the acute myocardial infarction diagnosis. PMID:25133185

  9. Residential Proximity to Major Roadways Is Not Associated with Cardiac Function in African Americans: Results from the Jackson Heart Study

    PubMed Central

    Weaver, Anne M.; Wellenius, Gregory A.; Wu, Wen-Chih; Hickson, DeMarc A.; Kamalesh, Masoor; Wang, Yi

    2016-01-01

    Cardiovascular disease (CVD), including heart failure, is a major cause of morbidity and mortality, particularly among African Americans. Exposure to ambient air pollution, such as that produced by vehicular traffic, is believed to be associated with heart failure, possibly by impairing cardiac function. We evaluated the cross-sectional association between residential proximity to major roads, a marker of long-term exposure to traffic-related pollution, and echocardiographic indicators of left and pulmonary vascular function in African Americans enrolled in the Jackson Heart Study (JHS): left ventricular ejection fraction, E-wave velocity, isovolumic relaxation time, left atrial diameter index, and pulmonary artery systolic pressure. We examined these associations using multivariable linear or logistic regression, adjusting for potential confounders. Of 4866 participants at study enrollment, 106 lived <150 m, 159 lived 150–299 m, 1161 lived 300–999 m, and 3440 lived ≥1000 m from a major roadway. We did not observe any associations between residential distance to major roads and these markers of cardiac function. Results were similar with additional adjustment for diabetes and hypertension, when considering varying definitions of major roadways, or when limiting analyses to those free from cardiovascular disease at baseline. Overall, we observed little evidence that residential proximity to major roads was associated with cardiac function among African Americans. PMID:27304962

  10. Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

    PubMed Central

    Ghayour Najafabadi, Mahboubeh; Rahbar Nikoukar, Laya; Memari, Amir; Ekhtiari, Hamed; Beygi, Sara

    2015-01-01

    We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes. PMID:26697263

  11. Hypertrophy, gene expression, and beating of neonatal cardiac myocytes are affected by microdomain heterogeneity in 3D

    PubMed Central

    Curtis, Matthew W.; Sharma, Sadhana; Desai, Tejal A.

    2011-01-01

    Cardiac myocytes are known to be influenced by the rigidity and topography of their physical microenvironment. It was hypothesized that 3D heterogeneity introduced by purely physical microdomains regulates cardiac myocyte size and contraction. This was tested in vitro using polymeric microstructures (G′=1.66 GPa) suspended with random orientation in 3D by a soft Matrigel matrix (G′=22.9 Pa). After 10 days of culture, the presence of 100 μm-long microstructures in 3D gels induced fold increases in neonatal rat ventricular myocyte size (1.61±0.06, p<0.01) and total protein/cell ratios (1.43± 0.08, p<0.05) that were comparable to those induced chemically by 50 μM phenylephrine treatment. Upon attachment to microstructures, individual myocytes also had larger cross-sectional areas (1.57±0.05, p<0.01) and higher average rates of spontaneous contraction (2.01±0.08, p<0.01) than unattached myocytes. Furthermore, the inclusion of microstructures in myocyte-seeded gels caused significant increases in the expression of beta-1 adrenergic receptor (β1-AR, 1.19±0.01), cardiac ankyrin repeat protein (CARP, 1.26±0.02), and sarcoplasmic reticulum calcium-ATPase (SERCA2, 1.59±0.12, p<0.05), genes implicated in hypertrophy and contractile activity. Together, the results demonstrate that cardiac myocyte behavior can be controlled through local 3D microdomains alone. This approach of defining physical cues as independent features may help to advance the elemental design considerations for scaffolds in cardiac tissue engineering and therapeutic microdevices. PMID:20668947

  12. Effect of mediastinal irradiation on cardiac function of patients treated during childhood and adolescence for Hodgkin's disease

    SciTech Connect

    Green, D.M.; Gingell, R.L.; Pearce, J.; Panahon, A.M.; Ghoorah, J.

    1987-02-01

    To determine the frequency of cardiac dysfunction in patients treated during childhood or adolescence with mediastinal irradiation for Hodgkin's disease (HD), 28 patients underwent cardiac evaluation 19 to 182 months (median, 90 months) after the completion of radiation therapy. No patient had symptoms of cardiac disease. All were normotensive. All patients had a normal cardiothoracic ratio. There were no abnormalities of voltage or rhythm in the ECGs. The left ventricular end diastolic volume was increased in 19.2% of patients, none of whom had evidence of impaired left ventricular function. The left ventricular ejection fraction (LVEF) was increased in 15.3% of patients. No patient had a decreased LVEF. Pericardial thickening was demonstrated on echocardiograms from 12 of 28 patients (42.9%). Thickening was more frequent among those patients observed for 72 or more months (47.1%; eight of 17) than among those with shorter periods of follow-up (36.4%; four of 11). This study demonstrates that cardiac dysfunction is an infrequent sequela of mediastinal irradiation following treatment using an equally weighted, anterior-posterior technique. Longitudinal study of these patients will be necessary to determine the clinical significance and evolution of the occult pericardial thickening that was identified.

  13. Cardiac magnetic resonance determinants of functional mitral regurgitation in ischemic and non ischemic left ventricular dysfunction.

    PubMed

    Fernández-Golfín, Covadonga; De Agustin, Alberto; Manzano, M Carmen; Bustos, Ana; Sánchez, Tibisay; Pérez de Isla, Leopoldo; Fuentes, Manuel; Macaya, Carlos; Zamorano, José

    2011-04-01

    Functional mitral regurgitation (FMR) is frequent in left ventricular (LV) dilatation/dysfunction. Echocardiographic predictors of FMR are known. However, cardiac magnetic resonance (CMR) predictors of FMR have not been fully addressed. The aim of the study was to evaluate CMR mitral valve (MV) parameters associated with FMR in ischemic and non ischemic LV dysfunction. 80 patients with LV ejection fraction below 45% and/or left ventricular dilatation of ischemic and non ischemic etiology were included. Cine-MR images (steady state free-precession) were acquired in a short-axis and 4 chambers views where MV evaluation was performed. Delayed enhancement was performed as well. Significant FMR was established as more than mild MR according to the echocardiographic report. Mean age was 59 years, males 79%. FMR was detected in 20 patients (25%) Significant differences were noted in LV functional parameters and in most MV parameters according to the presence of significant FMR. However, differences were noted between ischemic and non ischemic groups. In the first, differences in most MV parameters remained significant while in the non ischemic, only systolic and diastolic interpapillary muscle distance (1.60 vs. 2.19 cm, P = 0.001; 2. 51 vs. 3.04, P = 0.008) were predictors of FMR. FMR is associated with a more severe LV dilatation/dysfunction in the overall population. CMR MV parameters are associated with the presence of significant FMR and are different between ischemic and non ischemic patients. CMR evaluation of these patients may help in risk stratification as well as in surgical candidate selection.

  14. Eprosartan improves cardiac function in swine working heart model of ischemia-reperfusion injury

    PubMed Central

    Weymann, Alexander; Sabashnikov, Anton; Patil, Nikhil P.; Konertz, Wolfgang; Modersohn, Diethelm; Dohmen, Pascal M.

    2014-01-01

    Background Eprosartan is an angiotensin II receptor antagonist used as an antihypertensive. We sought to evaluate the regional effect of Eprosartan on postinfarct ventricular remodeling and myocardial function in an isolated swine working heart model of ischemia-reperfusion injury. Material/Methods 22 swine hearts were perfused with the Langendorff perfusion apparatus under standard experimental conditions. Myocardial ischemia was induced by a 10-min left anterior descending artery ligation. Hearts were reperfused with either saline (control group, n=11), or Eprosartan (treatment group, n=11). Left ventricular pressure (LVP) and regional heart parameters such as intramyocardial pressure (IMP), wall thickening rate (WTh), and pressure-length-loops (PLL) were measured at baseline and after 30 min of reperfusion. Results Measured parameters were statistically similar between the 2 groups at baseline. The administration of Eprosartan led to a significantly better recovery of IMP and WTh: 44.4±2.5 mmHg vs. 51.2±3.3 mmHg, p<0.001 and 3.8±0.4 μm vs. 4.4±0.3 μm, p=0.001, respectively. PLL were also significantly higher in the treatment group following reperfusion (21694±3259 units vs. 31267±3429 units, p<0.01). There was no difference in the LVP response to Eprosartan versus controls (63.6±3.0 mmHg vs. 62.5±3.1 mmHg, p=0.400). Conclusions Pre-treatment with Eprosartan is associated with a significant improvement in regional cardiac function under ischemic conditions. Pharmacological treatment with eprosartan may exert a direct cardioprotective effect on ischemic myocardium. PMID:24762635

  15. Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

    SciTech Connect

    McGhie, A.I.; Corbett, J.R.; Akers, M.S.; Kulkarni, P.; Sills, M.N.; Kremers, M.; Buja, L.M.; Durant-Reville, M.; Parkey, R.W.; Willerson, J.T. )

    1991-02-01

    The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.

  16. Correlations Between Echocardiographic Systolic and Diastolic Function with Cardiac Catheterization in Biventricular Congenital Heart Patients.

    PubMed

    Nadorlik, H; Stiver, C; Khan, S; Miao, Y; Holzer, R; Cheatham, J P; Cua, C L

    2016-04-01

    Newer echocardiographic techniques may allow for more accurate assessment of left ventricular (LV) function. Adult studies have correlated these echocardiographic measurements with invasive data, but minimal data exist in the pediatric congenital heart population. Purpose of this study was to evaluate which echocardiographic measurements correlated best with LV systolic and diastolic catheterization parameters. Patients with two-ventricle physiology who underwent simultaneous echocardiogram and cardiac catheterization were included. Images were obtained in the four-chamber view. LV systolic echocardiographic data included ejection fraction, displacement, tissue Doppler imaging (TDI) s' wave, global longitudinal strain, and strain rate (SR) s' wave. Diastolic echocardiographic data included mitral E and A waves, TDI e' and a' waves, and SRe' and SRa' waves. E/TDI e', TDI e'/TDI a', E/SRe', and SRe'/SRa' ratios were also calculated. Catheterization dP/dt was used as a marker for systolic function, and LV end-diastolic pressure (EDP) was used as a marker for diastolic function. Correlations of the echocardiographic and catheterization values were performed using Pearson correlation. Twenty-nine patients were included (14 females, 15 males). Median age at catheterization was 3.4 years (0.04-17.4 years). dP/dt was 1258 ± 353 mmHg/s, and LVEDP was 10.8 ± 2.4 mmHg. There were no significant correlations between catheterization dP/dt and systolic echocardiographic parameters. LVEDP correlated significantly with SRe' (r = -0.4, p = 0.03), SRa' (r = -0.4, p = 0.03), and E/SRe' (r = 0.5, p = 0.004). In pediatric congenital heart patients, catheterization dP/dt did not correlate with echocardiographic measurements of LV systolic function. Further studies are needed to determine which echocardiographic parameter best describes LV systolic function in this population. Strain rate analysis significantly correlated with LVEDP. Strain rate analysis should be considered as an

  17. Functional Roles Affect Diversity-Succession Relationships for Boreal Beetles

    PubMed Central

    Gibb, Heloise; Johansson, Therese; Stenbacka, Fredrik; Hjältén, Joakim

    2013-01-01

    Species diversity commonly increases with succession and this relationship is an important justification for conserving large areas of old-growth habitats. However, species with different ecological roles respond differently to succession. We examined the relationship between a range of diversity measures and time since disturbance for boreal forest beetles collected over a 285 year forest chronosequence. We compared responses of “functional” groups related to threat status, dependence on dead wood habitats, diet and the type of trap in which they were collected (indicative of the breadth of ecologies of species). We examined fits of commonly used rank-abundance models for each age class and traditional and derived diversity indices. Rank abundance distributions were closest to the Zipf-Mandelbrot distribution, suggesting little role for competition in structuring most assemblages. Diversity measures for most functional groups increased with succession, but differences in slopes were common. Evenness declined with succession; more so for red-listed species than common species. Saproxylic species increased in diversity with succession while non-saproxylic species did not. Slopes for fungivores were steeper than other diet groups, while detritivores were not strongly affected by succession. Species trapped using emergence traps (log specialists) responded more weakly to succession than those trapped using flight intercept traps (representing a broader set of ecologies). Species associated with microhabitats that accumulate with succession (fungi and dead wood) thus showed the strongest diversity responses to succession. These clear differences between functional group responses to forest succession should be considered in planning landscapes for optimum conservation value, particularly functional resilience. PMID:23977350

  18. Cardiac function and perfusion dynamics measured on a beat-by-beat basis in the live mouse using ultra-fast 4D optoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Ford, Steven J.; Deán-Ben, Xosé L.; Razansky, Daniel

    2015-03-01

    The fast heart rate (~7 Hz) of the mouse makes cardiac imaging and functional analysis difficult when studying mouse models of cardiovascular disease, and cannot be done truly in real-time and 3D using established imaging modalities. Optoacoustic imaging, on the other hand, provides ultra-fast imaging at up to 50 volumetric frames per second, allowing for acquisition of several frames per mouse cardiac cycle. In this study, we combined a recently-developed 3D optoacoustic imaging array with novel analytical techniques to assess cardiac function and perfusion dynamics of the mouse heart at high, 4D spatiotemporal resolution. In brief, the heart of an anesthetized mouse was imaged over a series of multiple volumetric frames. In another experiment, an intravenous bolus of indocyanine green (ICG) was injected and its distribution was subsequently imaged in the heart. Unique temporal features of the cardiac cycle and ICG distribution profiles were used to segment the heart from background and to assess cardiac function. The 3D nature of the experimental data allowed for determination of cardiac volumes at ~7-8 frames per mouse cardiac cycle, providing important cardiac function parameters (e.g., stroke volume, ejection fraction) on a beat-by-beat basis, which has been previously unachieved by any other cardiac imaging modality. Furthermore, ICG distribution dynamics allowed for the determination of pulmonary transit time and thus additional quantitative measures of cardiovascular function. This work demonstrates the potential for optoacoustic cardiac imaging and is expected to have a major contribution toward future preclinical studies of animal models of cardiovascular health and disease.

  19. In Utero Exposure to a Cardiac Teratogen Causes Reversible Deficits in Postnatal Cardiovascular Function, But Altered Adaptation to the Burden of Pregnancy.

    PubMed

    Aasa, Kristiina L; Maciver, Rebecca D; Ramchandani, Shyamlal; Adams, Michael A; Ozolinš, Terence R S

    2015-11-01

    Congenital heart defects (CHD) are the most common birth anomaly and while many resolve spontaneously by 1 year of age, the lifelong burden on survivors is poorly understood. Using a rat model of chemically induced CHD that resolve postnatally, we sought to characterize the postnatal changes in cardiac function, and to investigate whether resolved CHD affects the ability to adapt to the increased the cardiovascular (CV) burden of pregnancy. To generate rats with resolved CHD, pregnant rats were administered distilled water or dimethadione (DMO) [300 mg/kg b.i.d. on gestation day (gd) 9 and 10] and pups delivered naturally. To characterize structural and functional changes in the heart, treated and control offspring were scanned by echocardiography on postnatal day 4, 21, and 10-12 weeks. Radiotelemeters were implanted for continuous monitoring of hemodynamics. Females were mated and scanned by echocardiography on gd12 and gd18 during pregnancy. On gd18, maternal hearts were collected for structural and molecular assessment. Postnatal echocardiography revealed numerous structural and functional differences in treated offspring compared with control; however, these resolved by 10-12 weeks of age. The CV demand of pregnancy revealed differences between treated and control offspring with respect to mean arterial pressure, CV function, cardiac strain, and left ventricular gene expression. In utero exposure to DMO also affected the subsequent generation. Gd18 fetal and placental weights were increased in treated F2 offspring. This study demonstrates that in utero chemical exposure may permanently alter the capacity of the postnatal heart to adapt to pregnancy and this may have transgenerational effects.

  20. Life Course Socioeconomic Position: Associations with Cardiac Structure and Function at Age 60-64 Years in the 1946 British Birth Cohort

    PubMed Central

    Murray, Emily T.; Jones, Rebecca; Thomas, Claudia; Ghosh, Arjun K.; Sattar, Naveed; Deanfield, John; Hardy, Rebecca; Kuh, Diana; Hughes, Alun D.; Whincup, Peter

    2016-01-01

    Although it is recognized that risks of cardiovascular diseases associated with heart failure develop over the life course, no studies have reported whether life course socioeconomic inequalities exist for heart failure risk. The Medical Research Council’s National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and measures of cardiac structure [left ventricular (LV) mass index and relative wall thickness (RWT)] and function [systolic: ejection fraction (EF) and midwall fractional shortening (mFS); diastolic: left atrial (LA) volume, E/A ratio and E/e’ ratio)]. Different life course models were compared with a saturated model to ascertain the nature of the relationship between socioeconomic position across the life course and each cardiac marker. Findings showed that models where socioeconomic position accumulated over multiple time points in life provided the best fit for 3 of the 7 cardiac markers: childhood and early adulthood periods for the E/A ratio and E/e’ ratio, and all three life periods for LV mass index. These associations were attenuated by adjustment for adiposity, but were little affected by adjustment for other established or novel cardio-metabolic risk factors. There was no evidence of a relationship between socioeconomic position at any time point and RWT, EF, mFS or LA volume index. In conclusion, socioeconomic position across multiple points of the lifecourse, particularly earlier in life, is an important determinant of some measures of LV structure and function. BMI may be an important mediator of these associations. PMID:27031846

  1. Development of a patch type embedded cardiac function monitoring system using dual microprocessor for arrhythmia detection in heart disease patient.

    PubMed

    Jang, Yongwon; Noh, Hyung Wook; Lee, I B; Jung, Ji-Wook; Song, Yoonseon; Lee, Sooyeul; Kim, Seunghwan

    2012-01-01

    A patch type embedded cardiac function monitoring system was developed to detect arrhythmias such as PVC (Premature Ventricular Contraction), pause, ventricular fibrillation, and tachy/bradycardia. The overall system is composed of a main module including a dual processor and a Bluetooth telecommunication module. The dual microprocessor strategy minimizes power consumption and size, and guarantees the resources of embedded software programs. The developed software was verified with standard DB, and showed good performance.

  2. Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer.

    PubMed

    van den Boogaard, Malou; Wong, L Y Elaine; Tessadori, Federico; Bakker, Martijn L; Dreizehnter, Lisa K; Wakker, Vincent; Bezzina, Connie R; 't Hoen, Peter A C; Bakkers, Jeroen; Barnett, Phil; Christoffels, Vincent M

    2012-07-01

    The contraction pattern of the heart relies on the activation and conduction of the electrical impulse. Perturbations of cardiac conduction have been associated with congenital and acquired arrhythmias as well as cardiac arrest. The pattern of conduction depends on the regulation of heterogeneous gene expression by key transcription factors and transcriptional enhancers. Here, we assessed the genome-wide occupation of conduction system-regulating transcription factors TBX3, NKX2-5, and GATA4 and of enhancer-associated coactivator p300 in the mouse heart, uncovering cardiac enhancers throughout the genome. Many of the enhancers colocalized with ion channel genes repressed by TBX3, including the clustered sodium channel genes Scn5a, essential for cardiac function, and Scn10a. We identified 2 enhancers in the Scn5a/Scn10a locus, which were regulated by TBX3 and its family member and activator, TBX5, and are functionally conserved in humans. We also provided evidence that a SNP in the SCN10A enhancer associated with alterations in cardiac conduction patterns in humans disrupts TBX3/TBX5 binding and reduces the cardiac activity of the enhancer in vivo. Thus, the identification of key regulatory elements for cardiac conduction helps to explain how genetic variants in noncoding regulatory DNA sequences influence the regulation of cardiac conduction and the predisposition for cardiac arrhythmias. PMID:22706305

  3. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  4. The Effects of Tai Chi on the Renal and Cardiac Functions of Patients with Chronic Kidney and Cardiovascular Diseases

    PubMed Central

    Shi, Zhi-Min; Wen, Hai-Ping; Liu, Fu-Rong; Yao, Chun-Xia

    2014-01-01

    [Purpose] To assess the effects of Tai Chi on the renal and cardiac functions of patients with chronic kidney disease (CKD) and cardiovascular disease (CVD). [Subjects and Methods] Twenty-one patients with CKD and CVD were randomly divided into control and exercise groups. The exercise group performed Tai Chi training for 30 minutes three to five times a week for 12 weeks, while the control group did not. All patients’ renal and cardiac functions and blood lipid parameters were measured at baseline and after 12 weeks. [Results] The 12 weeks Tai Chi intervention improved the estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), and the high density lipoprotein (HDL) level, and decreased the serum creatintine (Scr) level, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and the total cholesterol (CH), triglyceride (TG) and low density lipoprotein (LDL) levels. The change in eGFR correlated negatively with the changes in CH, TG and LDL, and positively with the change in HDL. In addition, the change in SBP correlated positively with the changes in CH, TG and LDL, and negatively with the change in HDL. [Conclusion] Tai Chi training might improve the renal and cardiac functions of CKD and CVD patients via improved regulation of lipid metabolism. PMID:25435688

  5. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation.

    PubMed

    Homburger, Julian R; Green, Eric M; Caleshu, Colleen; Sunitha, Margaret S; Taylor, Rebecca E; Ruppel, Kathleen M; Metpally, Raghu Prasad Rao; Colan, Steven D; Michels, Michelle; Day, Sharlene M; Olivotto, Iacopo; Bustamante, Carlos D; Dewey, Frederick E; Ho, Carolyn Y; Spudich, James A; Ashley, Euan A

    2016-06-14

    Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

  6. Are Cardiac Autonomic Nervous System Activity and Perceived Stress Related to Functional Somatic Symptoms in Adolescents? The TRAILS Study

    PubMed Central

    Janssens, Karin A. M.; Riese, Harriëtte; Van Roon, Arie M.; Hunfeld, Joke A. M.; Groot, Paul F. C.; Oldehinkel, Albertine J.; Rosmalen, Judith G. M.

    2016-01-01

    Objective Stressors have been related to medically insufficiently explained or functional somatic symptoms (FSS). However, the underlying mechanism of this association is largely unclear. In the current study, we examined whether FSS are associated with different perceived stress and cardiac autonomic nervous system (ANS) levels during a standardized stressful situation, and whether these associations are symptom-specific. Methods We examined 715 adolescents (16.1 years, 51.3% girls) from the Dutch cohort study Tracking Adolescents’ Individual Lives Sample during the Groningen Social Stress Test (GSST). FSS were assessed by the Youth Self-Report, and clustered into a cluster of overtiredness, dizziness and musculoskeletal pain and a cluster of headache and gastrointestinal symptoms. Perceived stress levels (i.e. unpleasantness and arousal) were assessed by the Self-Assessment Manikin, and cardiac ANS activity by assessing heart rate variability (HRV-HF) and pre-ejection period (PEP). Perceived stress and cardiac ANS levels before, during, and after the GSST were studied as well as cardiac ANS reactivity. Linear regression analyses were used to examine the associations. Results Perceived arousal levels during (beta = 0.09, p = 0.04) and after (beta = 0.07, p = 0.047) the GSST, and perceived unpleasantness levels before (beta = 0.07, p = 0.048) and during (beta = 0.12, p = 0.001) the GSST were related to FSS during the past couple of months. The association between perceived stress and FSS was stronger for the FSS cluster of overtiredness, dizziness and musculoskeletal pain than for the cluster of headache and gastrointestinal symptoms. Neither ANS activity levels before, during, and after the GSST, nor maximal HF-HRV and PEP reactivity were related to FSS. Conclusions This study suggests that perceived stress levels during social stress are related to FSS, whereas cardiac ANS activity and reactivity are not related to FSS. PMID:27089394

  7. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    PubMed Central

    Homburger, Julian R.; Green, Eric M.; Caleshu, Colleen; Sunitha, Margaret S.; Taylor, Rebecca E.; Ruppel, Kathleen M.; Metpally, Raghu Prasad Rao; Colan, Steven D.; Michels, Michelle; Day, Sharlene M.; Olivotto, Iacopo; Bustamante, Carlos D.; Dewey, Frederick E.; Ho, Carolyn Y.; Spudich, James A.; Ashley, Euan A.

    2016-01-01

    Myosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac death. How specific myosin variants alter motor function or clinical expression of disease remains incompletely understood. Here, we combine structural models of myosin from multiple stages of its chemomechanical cycle, exome sequencing data from two population cohorts of 60,706 and 42,930 individuals, and genetic and phenotypic data from 2,913 patients with HCM to identify regions of disease enrichment within β-cardiac myosin. We first developed computational models of the human β-cardiac myosin protein before and after the myosin power stroke. Then, using a spatial scan statistic modified to analyze genetic variation in protein 3D space, we found significant enrichment of disease-associated variants in the converter, a kinetic domain that transduces force from the catalytic domain to the lever arm to accomplish the power stroke. Focusing our analysis on surface-exposed residues, we identified a larger region significantly enriched for disease-associated variants that contains both the converter domain and residues on a single flat surface on the myosin head described as the myosin mesa. Notably, patients with HCM with variants in the enriched regions have earlier disease onset than patients who have HCM with variants elsewhere. Our study provides a model for integrating protein structure, large-scale genetic sequencing, and detailed phenotypic data to reveal insight into time-shifted protein structures and genetic disease. PMID:27247418

  8. Functional Effect of Pim1 Depends upon Intracellular Localization in Human Cardiac Progenitor Cells.

    PubMed

    Samse, Kaitlen; Emathinger, Jacqueline; Hariharan, Nirmala; Quijada, Pearl; Ilves, Kelli; Völkers, Mirko; Ormachea, Lucia; De La Torre, Andrea; Orogo, Amabel M; Alvarez, Roberto; Din, Shabana; Mohsin, Sadia; Monsanto, Megan; Fischer, Kimberlee M; Dembitsky, Walter P; Gustafsson, Åsa B; Sussman, Mark A

    2015-05-29

    Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics.

  9. Influence of hydrotherapy on clinical and cardiac autonomic function in migraine patients

    PubMed Central

    Sujan, M. U.; Rao, M. Raghavendra; Kisan, Ravikiran; Abhishekh, Hulegar A.; Nalini, Atchayaram; Raju, Trichur R.; Sathyaprabha, T. N.

    2016-01-01

    Background: Migraine is associated with autonomic symptoms. The growing body of literature suggests that the dysfunctional autonomic nervous system might play a pivotal role in the pathogenesis of migraine. Thermal therapies have been hypothesized to modulate these changes and alleviate pain. However, data regarding the efficacy of hydrotherapy in migraine remain scant. We evaluated the effect of add on hydrotherapy procedure (a hot arm and foot bath with ice massage to head) in migraine patients. Methods: Forty chronic migraine patients fulfilling the International Classification of Headache Disorders II criteria were recruited from the neurology outpatient clinic. Patients were randomized to receive either hydrotherapy plus conventional pharmacological care (n = 20) or conventional medication only (n = 20). Hydrotherapy group received treatment with hot arm and foot bath (103°F to 110°F) and ice massage to head daily for 20 min for 45 days. Patients were assessed using headache impact test (HIT), visual analog scale for pain and cardiac autonomic function by heart rate variability (HRV) before and after intervention period. Results: There was a significant decrease in HIT score, frequency, and intensity of headaches following treatment in both the groups. However, it was more evident in add on hydrotherapy group compared to pharmacological treatment alone group. There was also significant improvement in the HRV parameters. In particular, there was a significant decrease in heart rate (P = 0.017), increase in high frequency (HF) (P = 0.014) and decrease in low frequency/HF ratio (P = 0.004) in add on hydrotherapy group. Conclusion: Our study shows that add on hydrotherapy enhanced the vagal tone in addition to reducing the frequency and intensity of headaches in migraine patients. PMID:26933356

  10. The structural and functional effects of the familial hypertrophic cardiomyopathy-linked cardiac troponin C mutation, L29Q

    PubMed Central

    Robertson, Ian M.; Sevrieva, Ivanka; Li, Monica X.; Irving, Malcolm; Sun, Yin-Biao; Sykes, Brian D.

    2015-01-01

    Familial hypertrophic cardiomyopathy (FHC) is characterized by severe abnormal cardiac muscle growth. The traditional view of disease progression in FHC is that an increase in the Ca2 +-sensitivity of cardiac muscle contraction ultimately leads to pathogenic myocardial remodeling, though recent studies suggest this may be an oversimplification. For example, FHC may be developed through altered signaling that prevents downstream regulation of contraction. The mutation L29Q, found in the Ca2 +-binding regulatory protein in heart muscle, cardiac troponin C (cTnC), has been linked to cardiac hypertrophy. However, reports on the functional effects of this mutation are conflicting, and our goal was to combine in vitro and in situ structural and functional data to elucidate its mechanism of action. We used nuclear magnetic resonance and circular dichroism to solve the structure and characterize the backbone dynamics and stability of the regulatory domain of cTnC with the L29Q mutation. The overall structure and dynamics of cTnC were unperturbed, although a slight rearrangement of site 1, an increase in backbone flexibility, and a small decrease in protein stability were observed. The structure and function of cTnC was also assessed in demembranated ventricular trabeculae using fluorescence for in situ structure. L29Q reduced the cooperativity of the Ca2 +-dependent structural change in cTnC in trabeculae under basal conditions and abolished the effect of force-generating myosin cross-bridges on this structural change. These effects could contribute to the pathogenesis of this mutation. PMID:26341255

  11. Cardiac Rehabilitation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Rehabilitation? Cardiac rehabilitation (rehab) is a medically supervised program ... be designed to meet your needs. The Cardiac Rehabilitation Team Cardiac rehab involves a long-term commitment ...

  12. Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content.

    PubMed

    Swanson, J E; Lokesh, B R; Kinsella, J E

    1989-03-01

    White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.

  13. Effect of hypokinesia on cardiac contractile function and nervous regulation of the heart

    NASA Technical Reports Server (NTRS)

    Meyerson, F. Z.; Kapelko, V. I.; Gorina, M. S.; Shchegolkov, A. N.; Larinov, N. P.

    1980-01-01

    Longterm hypokinesia caused cardiac deadaptation in rabbits, which resulted in the diminishing of the left ventricular rate of contraction and relaxation, joined later by decreased vascular resistance. As a results, the ejection rate as well as stroke volume and cardiac output were normal. The decrease of the relaxation speed was more obvious at a high heart rate and results in shortening of the diastolic pause and diminishing of cardiac output. Hearts of the hypokinetic animals were characterized by normal maximal pressure developed by a unit of muccardial mass aorta clamping, decreased adrenoreactivity, and increased cholinoreactivity. This complex of changes is contrary to changes observed in adaptation to exercise, but is similar to changes observed in compensatory hypertrophy of the heart.

  14. Cardiac Light-Sheet Fluorescent Microscopy for Multi-Scale and Rapid Imaging of Architecture and Function

    PubMed Central

    Fei, Peng; Lee, Juhyun; Packard, René R. Sevag; Sereti, Konstantina-Ioanna; Xu, Hao; Ma, Jianguo; Ding, Yichen; Kang, Hanul; Chen, Harrison; Sung, Kevin; Kulkarni, Rajan; Ardehali, Reza; Kuo, C.-C. Jay; Xu, Xiaolei; Ho, Chih-Ming; Hsiai, Tzung K.

    2016-01-01

    Light Sheet Fluorescence Microscopy (LSFM) enables multi-dimensional and multi-scale imaging via illuminating specimens with a separate thin sheet of laser. It allows rapid plane illumination for reduced photo-damage and superior axial resolution and contrast. We hereby demonstrate cardiac LSFM (c-LSFM) imaging to assess the functional architecture of zebrafish embryos with a retrospective cardiac synchronization algorithm for four-dimensional reconstruction (3-D space + time). By combining our approach with tissue clearing techniques, we reveal the entire cardiac structures and hypertrabeculation of adult zebrafish hearts in response to doxorubicin treatment. By integrating the resolution enhancement technique with c-LSFM to increase the resolving power under a large field-of-view, we demonstrate the use of low power objective to resolve the entire architecture of large-scale neonatal mouse hearts, revealing the helical orientation of individual myocardial fibers. Therefore, our c-LSFM imaging approach provides multi-scale visualization of architecture and function to drive cardiovascular research with translational implication in congenital heart diseases. PMID:26935567

  15. Controlled Release of Collagen-Binding SDF-1α Improves Cardiac Function after Myocardial Infarction by Recruiting Endogenous Stem Cells

    PubMed Central

    Sun, Jie; Zhao, Yannan; Li, Qingguo; Chen, Bing; Hou, Xianglin; Xiao, Zhifeng; Dai, Jianwu

    2016-01-01

    Stromal cell-derived factor-1α (SDF-1α) is a well-characterized chemokine that mobilizes stem cells homing to the ischemic heart, which is beneficial for cardiac regeneration. However, clinically administered native SDF-1α diffuses quickly, thus decreasing its local concentration, and results in side effects. Thus, a controlled release system for SDF-1α is required to produce an effective local concentration in the ischemic heart. In this study, we developed a recombinant chemokine, consisting of SDF-1α and a collagen-binding domain, which retains both the SDF-1α and collagen-binding activity (CBD-SDF-1α). In an in vitro assay, CBD-SDF-1α could specifically bind to a collagen gel and achieve sustained release. An intramyocardial injection of CBD-SDF-1α after acute myocardial infarction demonstrated that the protein was largely tethered in the ischemic area and that controlled release had been achieved. Furthermore, CBD-SDF-1α enhanced the recruitment of c-kit positive (c-kit+) stem cells, increased capillary density and improved cardiac function, whereas NAT-SDF-1α had no such beneficial effects. Our findings demonstrate that CBD-SDF-1α can specifically bind to collagen and achieve controlled release both in vitro and in vivo. Local delivery of this protein could mobilize endogenous stem cells homing to the ischemic heart and improve cardiac function after myocardial infarction. PMID:27226084

  16. Cardiac Light-Sheet Fluorescent Microscopy for Multi-Scale and Rapid Imaging of Architecture and Function.

    PubMed

    Fei, Peng; Lee, Juhyun; Packard, René R Sevag; Sereti, Konstantina-Ioanna; Xu, Hao; Ma, Jianguo; Ding, Yichen; Kang, Hanul; Chen, Harrison; Sung, Kevin; Kulkarni, Rajan; Ardehali, Reza; Kuo, C-C Jay; Xu, Xiaolei; Ho, Chih-Ming; Hsiai, Tzung K

    2016-01-01

    Light Sheet Fluorescence Microscopy (LSFM) enables multi-dimensional and multi-scale imaging via illuminating specimens with a separate thin sheet of laser. It allows rapid plane illumination for reduced photo-damage and superior axial resolution and contrast. We hereby demonstrate cardiac LSFM (c-LSFM) imaging to assess the functional architecture of zebrafish embryos with a retrospective cardiac synchronization algorithm for four-dimensional reconstruction (3-D space + time). By combining our approach with tissue clearing techniques, we reveal the entire cardiac structures and hypertrabeculation of adult zebrafish hearts in response to doxorubicin treatment. By integrating the resolution enhancement technique with c-LSFM to increase the resolving power under a large field-of-view, we demonstrate the use of low power objective to resolve the entire architecture of large-scale neonatal mouse hearts, revealing the helical orientation of individual myocardial fibers. Therefore, our c-LSFM imaging approach provides multi-scale visualization of architecture and function to drive cardiovascular research with translational implication in congenital heart diseases. PMID:26935567

  17. Cardiac Light-Sheet Fluorescent Microscopy for Multi-Scale and Rapid Imaging of Architecture and Function

    NASA Astrophysics Data System (ADS)

    Fei, Peng; Lee, Juhyun; Packard, René R. Sevag; Sereti, Konstantina-Ioanna; Xu, Hao; Ma, Jianguo; Ding, Yichen; Kang, Hanul; Chen, Harrison; Sung, Kevin; Kulkarni, Rajan; Ardehali, Reza; Kuo, C.-C. Jay; Xu, Xiaolei; Ho, Chih-Ming; Hsiai, Tzung K.

    2016-03-01

    Light Sheet Fluorescence Microscopy (LSFM) enables multi-dimensional and multi-scale imaging via illuminating specimens with a separate thin sheet of laser. It allows rapid plane illumination for reduced photo-damage and superior axial resolution and contrast. We hereby demonstrate cardiac LSFM (c-LSFM) imaging to assess the functional architecture of zebrafish embryos with a retrospective cardiac synchronization algorithm for four-dimensional reconstruction (3-D space + time). By combining our approach with tissue clearing techniques, we reveal the entire cardiac structures and hypertrabeculation of adult zebrafish hearts in response to doxorubicin treatment. By integrating the resolution enhancement technique with c-LSFM to increase the resolving power under a large field-of-view, we demonstrate the use of low power objective to resolve the entire architecture of large-scale neonatal mouse hearts, revealing the helical orientation of individual myocardial fibers. Therefore, our c-LSFM imaging approach provides multi-scale visualization of architecture and function to drive cardiovascular research with translational implication in congenital heart diseases.

  18. Pyruvate stabilizes electrocardiographic and hemodynamic function in pigs recovering from cardiac arrest

    PubMed Central

    Cherry, Brandon H; Nguyen, Anh Q; Hollrah, Roger A; Williams, Arthur G; Hoxha, Besim; Olivencia-Yurvati, Albert H

    2015-01-01

    Cardiac electromechanical dysfunction may compromise recovery of patients who are initially resuscitated from cardiac arrest, and effective treatments remain elusive. Pyruvate, a natural intermediary metabolite, energy substrate, and antioxidant, has been found to protect the heart from ischemia-reperfusion injury. This study tested the hypothesis that pyruvate-enriched resuscitation restores hemodynamic, metabolic, and electrolyte homeostasis following cardiac arrest. Forty-two Yorkshire swine underwent pacing-induced ventricular fibrillation and, after 6 min pre-intervention arrest, 4 min precordial compressions followed by transthoracic countershocks. After defibrillation and recovery of spontaneous circulation, the pigs were monitored for another 4 h. Sodium pyruvate or NaCl were infused i.v. (0.1 mmol·kg−1·min−1) throughout precordial compressions and the first 60 min recovery. In 8 of the 24 NaCl-infused swine, the first countershock converted ventricular fibrillation to pulseless electrical activity unresponsive to subsequent countershocks, but only 1 of 18 pyruvate-treated swine developed pulseless electrical activity (relative risk 0.17; 95% confidence interval 0.13–0.22). Pyruvate treatment also lowered the dosage of vasoconstrictor phenylephrine required to maintain systemic arterial pressure at 15–60 min recovery, hastened clearance of excess glucose, elevated arterial bicarbonate, and raised arterial pH; these statistically significant effects persisted up to 3 h after sodium pyruvate infusion, while infusion-induced hypernatremia subsided. These results demonstrate that pyruvate-enriched resuscitation achieves electrocardiographic and hemodynamic stability in swine during the initial recovery from cardiac arrest. Such metabolically based treatment may offer an effective strategy to support cardiac electromechanical recovery immediately after cardiac arrest. PMID:26088865

  19. Assay of muscarinic acetylcholine receptor function in cultured cardiac cells by stimulation of /sup 86/Rb+ efflux

    SciTech Connect

    Hunter, D.D.; Nathanson, N.M.

    1985-09-01

    An assay for the increase in potassium permeability mediated by muscarinic acetylcholine receptors (mAChR) in cultured cardiac cells is described, using the K+ ion substitute /sup 86/Rb+ as the tracer ion. Cardiac cells accumulate /sup 86/Rb+ from the extracellular medium in a Na+/K+ ATPase-dependent manner. Subsequent efflux of /sup 86/Rb+ in the absence and presence of muscarinic agonists follows kinetics similar to those previously reported for /sup 42/K+. The mAChR agonist carbamylcholine (carbachol) stimulated /sup 86/Rb+ efflux with an EC50 of 50 nM. The half-time for efflux is reduced by greater than 40% at maximally effective concentrations of agonist. Stimulation of /sup 86/Rb+ efflux by carbachol is blocked by the mAChR antagonist atropine with an IC50 of 15 nM. The stimulation of 86Rb+ efflux by carbachol is not affected by the presence