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Sample records for adult murine heart

  1. Assessment of DNA synthesis in Islet-1{sup +} cells in the adult murine heart

    SciTech Connect

    Weinberger, Florian Mehrkens, Dennis Starbatty, Jutta Nicol, Philipp Eschenhagen, Thomas

    2015-01-02

    Highlights: • Islet-1 was expressed in the adult heart. • Islet-1-positive cells did not proliferate in the adult heart. • Sinoatrial node cells did not proliferate in the adult heart. - Abstract: Rationale: Islet-1 positive (Islet-1{sup +}) cardiac progenitor cells give rise to the right ventricle, atria and outflow tract during murine cardiac development. In the adult heart Islet-1 expression is limited to parasympathetic neurons, few cardiomyocytes, smooth muscle cells, within the proximal aorta and pulmonary artery and sinoatrial node cells. Its role in these cells is unknown. Here we tested the hypothesis that Islet-1{sup +} cells retain proliferative activity and may therefore play a role in regenerating specialized regions in the heart. Methods and results: DNA synthesis was analyzed by the incorporation of tritiated thymidine ({sup 3}H-thymidine) in Isl-1-nLacZ mice, a transgenic model with an insertion of a nuclear beta-galactosidase in the Islet-1 locus. Mice received daily injections of {sup 3}H-thymidine for 5 days. DNA synthesis was visualized throughout the heart by dipping autoradiography of cryosections. Colocalization of an nLacZ-signal and silver grains would indicate DNA synthesis in Islet-1{sup +} cells. Whereas Islet{sup −} non-myocyte nuclei were regularly marked by accumulation of silver grains, colocalization with nLacZ-signals was not detected in >25,000 cells analyzed. Conclusions: Islet-1{sup +} cells are quiescent in the adult heart, suggesting that, under normal conditions, even pacemaking cells do not proliferate at higher rates than normal cardiac myocytes.

  2. Alternatively activated macrophages determine repair of the infarcted adult murine heart

    PubMed Central

    Shiraishi, Manabu; Shintani, Yasunori; Shintani, Yusuke; Ishida, Hidekazu; Saba, Rie; Yamaguchi, Atsushi; Adachi, Hideo; Yashiro, Kenta

    2016-01-01

    Alternatively activated (also known as M2) macrophages are involved in the repair of various types of organs. However, the contribution of M2 macrophages to cardiac repair after myocardial infarction (MI) remains to be fully characterized. Here, we identified CD206+F4/80+CD11b+ M2-like macrophages in the murine heart and demonstrated that this cell population predominantly increases in the infarct area and exhibits strengthened reparative abilities after MI. We evaluated mice lacking the kinase TRIB1 (Trib1–/–), which exhibit a selective depletion of M2 macrophages after MI. Compared with control animals, Trib1–/– mice had a catastrophic prognosis, with frequent cardiac rupture, as the result of markedly reduced collagen fibril formation in the infarct area due to impaired fibroblast activation. The decreased tissue repair observed in Trib1–/– mice was entirely rescued by an external supply of M2-like macrophages. Furthermore, IL-1α and osteopontin were suggested to be mediators of M2-like macrophage–induced fibroblast activation. In addition, IL-4 administration achieved a targeted increase in the number of M2-like macrophages and enhanced the post-MI prognosis of WT mice, corresponding with amplified fibroblast activation and formation of more supportive fibrous tissues in the infarcts. Together, these data demonstrate that M2-like macrophages critically determine the repair of infarcted adult murine heart by regulating fibroblast activation and suggest that IL-4 is a potential biological drug for treating MI. PMID:27140396

  3. Brain Derived Neurotrophic Factor Contributes to the Cardiogenic Potential of Adult Resident Progenitor Cells in Failing Murine Heart

    PubMed Central

    Samal, Rasmita; Ameling, Sabine; Dhople, Vishnu; Sappa, Praveen Kumar; Wenzel, Kristin; Völker, Uwe; Felix, Stephan B.; Hammer, Elke; Könemann, Stephanie

    2015-01-01

    Aims Resident cardiac progenitor cells show homing properties when injected into the injured but not to the healthy myocardium. The molecular background behind this difference in behavior needs to be studied to elucidate how adult progenitor cells can restore cardiac function of the damaged myocardium. Since the brain derived neurotrophic factor (BDNF) moderates cardioprotection in injured hearts, we focused on delineating its regulatory role in the damaged myocardium. Methods and Results Comparative gene expression profiling of freshly isolated undifferentiated Sca-1 progenitor cells derived either from heart failure transgenic αMHC-CyclinT1/Gαq overexpressing mice or wildtype littermates revealed transcriptional variations. Bdnf expression was up regulated 5-fold during heart failure which was verified by qRT-PCR and confirmed at protein level. The migratory capacity of Sca-1 cells from transgenic hearts was improved by 15% in the presence of 25ng/ml BDNF. Furthermore, BDNF-mediated effects on Sca-1 cells were studied via pulsed Stable Isotope Labeling of Amino acids in Cell Culture (pSILAC) proteomics approach. After BDNF treatment significant differences between newly synthesized proteins in Sca-1 cells from control and transgenic hearts were observed for CDK1, SRRT, HDGF, and MAP2K3 which are known to regulate cell cycle, survival and differentiation. Moreover BDNF repressed the proliferation of Sca-1 cells from transgenic hearts. Conclusion Comparative profiling of resident Sca-1 cells revealed elevated BDNF levels in the failing heart. Exogenous BDNF (i) stimulated migration, which might improve the homing ability of Sca-1 cells derived from the failing heart and (ii) repressed the cell cycle progression suggesting its potency to ameliorate heart failure. PMID:25799225

  4. Adult Congenital Heart Association

    MedlinePlus

    ... survivable, manageable, yet in the routine years between infancy and adulthood, sometimes forgettable. The Adult Congenital Heart ... understand the continuum of the disease from its infancy. The Adult Congential Heart Association brings together valuable ...

  5. Adult Congenital Heart Association

    MedlinePlus

    ... to ACHA Search The futures of adults with congenital heart disease made brighter by their pasts Get Involved 2016 ... conference theme is "The Changing Landscape of Adult Congenital Heart Disease." Join Us Help us improve the quality of ...

  6. Adults with Congenital Heart Defects

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Web Booklet: Adults With Congenital Heart Defects Updated:Apr ... topic from the list below to learn more. Web Booklet: Adults With Congenital Heart Defects Introduction Introduction: ...

  7. Analysis of cardiomyocyte movement in the developing murine heart

    SciTech Connect

    Hashimoto, Hisayuki; Yuasa, Shinsuke; Tabata, Hidenori; Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto; Nakajima, Kazunori; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Fukuda, Keiichi

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  8. Isolation and expansion of adult cardiac stem/progenitor cells in the form of cardiospheres from human cardiac biopsies and murine hearts.

    PubMed

    Chimenti, Isotta; Gaetani, Roberto; Barile, Lucio; Forte, Elvira; Ionta, Vittoria; Angelini, Francesco; Frati, Giacomo; Messina, Elisa; Giacomello, Alessandro

    2012-01-01

    The successful isolation and ex vivo expansion of resident cardiac stem/progenitor cells from human heart biopsies has allowed us to study their biological characteristics and their applications in therapeutic approaches for the repair of ischemic/infarcted heart, the preparation of tissue-engineered cardiac grafts and, possibly, the design of cellular kits for drug screening applications. From the first publication of the original method in 2004, several adjustments and slight changes have been introduced to optimize and adjust the procedure to the evolving experimental and translational needs. Moreover, due to the wide applicability of such a method (which is based on the exploitation of intrinsic functional properties of cells with regenerative properties that are present in most tissues), the key steps of this procedure have been used to derive several kinds of tissue-specific adult stem cells for preclinical or clinical purposes.In order to define the original procedure, complete with the up-to-date modifications introduced through the years, an exhaustive description of the current protocol is performed in this chapter, with particular attention in highlighting critical steps and troubleshoots. The procedure described here consists of modular steps, that could be employed to derive cells from any kind of tissue biopsy, and needs to be considered the gold standard of all the so-called "explant methods" or "cardiosphere methods," and it represents a milestone in the clinical translation of autologous cell therapy. PMID:22610568

  9. Measurement and interpretation of electrocardiographic QT intervals in murine hearts.

    PubMed

    Zhang, Yanmin; Wu, JingJing; King, James H; Huang, Christopher L-H; Fraser, James A

    2014-06-01

    Alterations in ECG QT intervals correlate with the risk of potentially fatal arrhythmias, for which transgenic murine hearts are becoming increasingly useful experimental models. However, QT intervals are poorly defined in murine ECGs. As a consequence, several different techniques have been used to measure murine QT intervals. The present work develops a consistent measure of the murine QT interval that correlates with changes in the duration of ventricular myocyte action potentials (APs). Volume-conducted ECGs were compared with simultaneously recorded APs, obtained using floating intracellular microelectrodes in Langendorff-perfused mouse hearts. QT intervals were measured from the onset of the QRS complex. The interval, Q-APR90, measured to the time at 90% AP recovery, was compared with two measures of the QT interval. QT1 was measured to the recovery of the ECG trace to the isoelectric baseline for entirely positive T-waves or to the trough of any negative T-wave undershoot. QT2-used extensively in previous studies-was measured to the return of any ECG trough to the isoelectric baseline. QT1, but not QT2, closely correlated with changes in Q-APR90. These findings were confirmed over a range of pacing rates, in low K(+) concentration solutions, and in Scn5a+/ΔKPQ hearts used to model human long QT syndrome. Application of this method in whole anesthetized mice similarly demonstrated a prolonged corrected QT (QTc) in Scn5a+/ΔKPQ hearts. We therefore describe a robust method for the determination of QT and QTc intervals that correlate with the duration of ventricular myocyte APs in murine hearts. PMID:24705556

  10. Analysis of cardiomyocyte movement in the developing murine heart.

    PubMed

    Hashimoto, Hisayuki; Yuasa, Shinsuke; Tabata, Hidenori; Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto; Nakajima, Kazunori; Sakaue-Sawano, Asako; Miyawaki, Atsushi; Fukuda, Keiichi

    2015-09-01

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. PMID:26168730

  11. Health in adults with congenital heart disease.

    PubMed

    Cuypers, Judith A A E; Utens, Elisabeth M W J; Roos-Hesselink, Jolien W

    2016-09-01

    Since the introduction of cardiac surgery, the prospects for children born with a cardiac defect have improved spectacularly. Many reach adulthood and the population of adults with congenital heart disease is increasing and ageing. However, repair of congenital heart disease does not mean cure. Many adults with congenital heart disease encounter late complications. Late morbidity can be related to the congenital heart defect itself, but may also be the consequence of the surgical or medical treatment or longstanding alterations in hemodynamics, neurodevelopment and psychosocial development. This narrative review describes the cardiac and non-cardiac long-term morbidity in the adult population with congenital heart disease. PMID:27451323

  12. Histone methylations in heart development, congenital and adult heart diseases

    PubMed Central

    Zhang, Qing-Jun; Liu, Zhi-Ping

    2015-01-01

    Heart development comprises myocyte specification, differentiation and cardiac morphogenesis. These processes are regulated by a group of core cardiac transcription factors in a coordinated temporal and spatial manner. Histone methylation is an emerging epigenetic mechanism for regulating gene transcription. Interplay among cardiac transcription factors and histone lysine modifiers plays important role in heart development. Aberrant expression and mutation of the histone lysine modifiers during development and in adult life can cause either embryonic lethality or congenital heart diseases, and influences the response of adult hearts to pathological stresses. In this review, we describe current body of literature on the role of several common histone methylations and their modifying enzymes in heart development, congenital and adult heart diseases. PMID:25942538

  13. Heart Failure in Older Adults.

    PubMed

    Butrous, Hoda; Hummel, Scott L

    2016-09-01

    Heart failure (HF) is a leading cause of morbidity, hospitalization, and mortality in older adults and a growing public health problem placing a huge financial burden on the health care system. Many challenges exist in the assessment and management of HF in geriatric patients, who often have coexisting multimorbidity, polypharmacy, cognitive impairment, and frailty. These complex "geriatric domains" greatly affect physical and functional status as well as long-term clinical outcomes. Geriatric patients have been under-represented in major HF clinical trials. Nonetheless, available data suggest that guideline-based medical and device therapies improve morbidity and mortality. Nonpharmacologic strategies, such as exercise training and dietary interventions, are an active area of research. Targeted geriatric evaluation, including functional and cognitive assessment, can improve risk stratification and guide management in older patients with HF. Clinical trials that enroll older patients with multiple morbidities and HF and evaluate functional status and quality of life in addition to mortality and cardiovascular morbidity should be encouraged to guide management of this age group. PMID:27476982

  14. Hippo signaling impedes adult heart regeneration

    PubMed Central

    Heallen, Todd; Morikawa, Yuka; Leach, John; Tao, Ge; Willerson, James T.; Johnson, Randy L.; Martin, James F.

    2013-01-01

    Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but it has not been studied postnatally or in fully mature adult cardiomyocytes. Here, we investigated Hippo signaling in adult cardiomyocyte renewal and regeneration. We found that unstressed Hippo-deficient adult mouse cardiomyocytes re-enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after adult myocardial infarction as well as after postnatal day eight (P8) cardiac apex resection and P8 myocardial infarction. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. Our findings reveal that Hippo signaling is an endogenous repressor of adult cardiomyocyte renewal and regeneration. Targeting the Hippo pathway in human disease might be beneficial for the treatment of heart disease. PMID:24255096

  15. Multimorbidity in Older Adults with Heart Failure.

    PubMed

    Dharmarajan, Kumar; Dunlay, Shannon M

    2016-05-01

    Multimorbidity is common among older adults with heart failure and creates diagnostic and management challenges. Diagnosis of heart failure may be difficult, as many conditions commonly found in older persons produce dyspnea, exercise intolerance, fatigue, and weakness; no singular pathognomonic finding or diagnostic test differentiates them from one another. Treatment may also be complicated, as multimorbidity creates high potential for drug-disease and drug-drug interactions in settings of polypharmacy. The authors suggest that management of multimorbid older persons with heart failure be patient, rather than disease-focused, to best meet patients' unique health goals and minimize risk from excessive or poorly-coordinated treatments. PMID:27113146

  16. Heart Failure in Adult Congenital Heart Disease: Nonpharmacologic Treatment Strategies.

    PubMed

    LeMond, Lisa; Mai, Tuan; Broberg, Craig S; Muralidaran, Ashok; Burchill, Luke J

    2015-11-01

    In early stages, heart failure (HF) in adult congenital heart disease (ACHD) remains an elusive diagnosis. Many ACHD patients seem well-compensated owing to chronic physical and psychological adaptations. HF biomarkers and cardiopulmonary exercise tests are often markedly abnormal, although patients report stable health and good quality of life. Treatment differs from acquired HF. Evidence for effective drug therapy in ACHD-related HF is lacking. Residual ventricular, valvular, and vascular abnormalities contribute to HF pathophysiology, leading to an emphasis on nonpharmacologic treatment strategies. This article reviews emerging perspectives on nonpharmacologic treatment strategies, including catheter-based interventions, surgical correction, and palliative care. PMID:26471822

  17. Optical pacing of the adult rabbit heart.

    PubMed

    Jenkins, Michael W; Wang, Y T; Doughman, Y Q; Watanabe, M; Cheng, Y; Rollins, A M

    2013-01-01

    Optical pacing has been demonstrated to be a viable alternative to electrical pacing in embryonic hearts. In this study, the feasibility of optically pacing an adult rabbit heart was explored. Hearts from adult New Zealand White rabbits (n = 9) were excised, cannulated and perfused on a modified Langendorff apparatus. Pulsed laser light (λ = 1851 nm) was directed to either the left or right atrium through a multimode optical fiber. An ECG signal from the left ventricle and a trigger pulse from the laser were recorded simultaneously to determine when capture was achieved. Successful optical pacing was demonstrated by obtaining pacing capture, stopping, then recapturing as well as by varying the pacing frequency. Stimulation thresholds measured at various pulse durations suggested that longer pulses (8 ms) had a lower energy capture threshold. To determine whether optical pacing caused damage, two hearts were perfused with 30 µM of propidium iodide and analyzed histologically. A small number of cells near the stimulation site had compromised cell membranes, which probably limited the time duration over which pacing was maintained. Here, short-term optical pacing (few minutes duration) is demonstrated in the adult rabbit heart for the first time. Future studies will be directed to optimize optical pacing parameters to decrease stimulation thresholds and may enable longer-term pacing. PMID:24049683

  18. Sex Suffers for Younger Adults After Heart Attack

    MedlinePlus

    ... 160722.html Sex Suffers for Younger Adults After Heart Attack Lack of interest a complaint of many women ... WEDNESDAY, Aug. 31, 2016 (HealthDay News) -- After a heart attack, many younger adults experience sexual difficulties -- and women ...

  19. TCDD Inhibits Heart Regeneration in Adult Zebrafish

    PubMed Central

    Hofsteen, Peter; Mehta, Vatsal; Heideman, Warren

    2013-01-01

    Normal adult zebrafish can completely regenerate lost myocardium following partial amputation of the ventricle apex. We report that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) significantly impairs this regeneration. Adult male zebrafish were injected with vehicle (control) or TCDD (70ng/g, ip) 1 day prior to partial amputation of the ventricle apex. Gross observation and histological analysis of the amputated heart at 21 days postamputation revealed that TCDD-exposed fish had not progressed beyond the initial clot formation stage, whereas the vehicle control fish showed substantial recovery and almost complete resolution of the formed clot. In contrast, hearts that were not surgically wounded showed no signs of TCDD toxicity. Striking features in the TCDD-exposed hearts were the absence of the normal sheath of new tissue enveloping the wound and the absence of intense cell proliferation at the site of the wound. In addition, the patterns of collagen deposition at the wound site were different between the TCDD and vehicle groups. Because the receptor for TCDD is the aryl hydrocarbon receptor ligand-activated transcriptional regulator, we examined the effects of TCDD exposure on gene expression in the ventricle using DNA microarrays. Samples were collected just prior to amputation and at 6h and 7 days postamputation. TCDD-pretreated hearts had dysregulated expression of genes involved in heart function, tissue regeneration, cell growth, and extracellular matrix. Because embryonic, but not adult, hearts are major targets for TCDD-induced cardiotoxicity, we speculate that the need for embryonic-like cells in regeneration is connected with the effects of TCDD in inhibiting the response to wounding. PMID:23204111

  20. Origin of Cardiomyocytes in the Adult Heart

    PubMed Central

    Leri, Annarosa; Rota, Marcello; Pasqualini, Francesco S.; Goichberg, Polina; Anversa, Piero

    2014-01-01

    This review article discusses the mechanisms of cardiomyogenesis in the adult heart. They include the reentry of cardiomyocytes into the cell cycle; dedifferentiation of preexisting cardiomyocytes which assume an immature replicating cell phenotype; transdifferentiation of hematopoietic stem cells into cardiomyocytes; and cardiomyocytes derived from activation and lineage specification of resident cardiac stem cells. The recognition of the origin of cardiomyocytes is of critical importance for the development of strategies capable of enhancing the growth response of the myocardium; in fact, cell therapy for the decompensated heart has to be based on the acquisition of this fundamental biological knowledge. PMID:25552694

  1. Adult congenital heart disease and pulmonary arterial hypertension: the Texas Adult Congenital Heart Program experience.

    PubMed

    Franklin, Wayne J; Parekh, Dhaval R; Safdar, Zeenat

    2011-11-01

    Congenital heart disease (CHD) is a common structural defect of the heart or major blood vessels. Patients with adult congenital heart disease (ACHD) have medical needs that are distinct from those of pediatric patients with CHD, and the transition into adult health care is important for management of the patient with ACHD. A large proportion of patients with CHD develop diseases and complications associated with the long-term stress of intracardiac shunts. Pulmonary arterial hypertension (PAH) is a significant complication of some CHD lesions. The treatment of these patients remains challenging due to their combined heart and lung disease, and multidisciplinary care is ofen necessitated for a variety of secondary conditions. A number of treatment options are available for the management of PAH associated with CHD, including prostanoids, phosphodiesterase type-5 inhibitors, and endothelin receptor antagonists. This article discusses the diagnosis and management of such ACHD patients with PAH. PMID:22104452

  2. The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping

    PubMed Central

    Liao, Ronglih; Podesser, Bruno K.

    2012-01-01

    The isolated retrograde-perfused Langendorff heart and the isolated ejecting heart have, over many decades, resulted in fundamental discoveries that form the underpinnings of our current understanding of the biology and physiology of the heart. These two experimental methodologies have proven invaluable in studying pharmacological effects on myocardial function, metabolism, and vascular reactivity and in the investigation of clinically relevant disease states such as ischemia-reperfusion injury, diabetes, obesity, and heart failure. With the advent of the genomics era, the isolated mouse heart preparation has gained prominence as an ex vivo research tool for investigators studying the impact of gene modification in the intact heart. This review summarizes the historical development of the isolated heart and provides a practical guide for the establishment of the Langendorff and ejecting heart preparations with a particular emphasis on the murine heart. In addition, current applications and novel methods of recording cardiovascular parameters in the isolated heart preparation will be discussed. With continued advances in methodological recordings, the isolated mouse heart preparation will remain physiologically relevant for the foreseeable future, serving as an integral bridge between in vitro assays and in vivo approaches. PMID:22636675

  3. Accelerated self-gated UTE MRI of the murine heart

    NASA Astrophysics Data System (ADS)

    Motaal, Abdallah G.; Noorman, Nils; De Graaf, Wolter L.; Florack, Luc J.; Nicolay, Klaas; Strijkers, Gustav J.

    2014-03-01

    We introduce a new protocol to obtain radial Ultra-Short TE (UTE) MRI Cine of the beating mouse heart within reasonable measurement time. The method is based on a self-gated UTE with golden angle radial acquisition and compressed sensing reconstruction. The stochastic nature of the retrospective triggering acquisition scheme produces an under-sampled and random kt-space filling that allows for compressed sensing reconstruction, hence reducing scan time. As a standard, an intragate multislice FLASH sequence with an acquisition time of 4.5 min per slice was used to produce standard Cine movies of 4 mice hearts with 15 frames per cardiac cycle. The proposed self-gated sequence is used to produce Cine movies with short echo time. The total scan time was 11 min per slice. 6 slices were planned to cover the heart from the base to the apex. 2X, 4X and 6X under-sampled k-spaces cine movies were produced from 2, 1 and 0.7 min data acquisitions for each slice. The accelerated cine movies of the mouse hearts were successfully reconstructed with a compressed sensing algorithm. Compared to the FLASH cine images, the UTE images showed much less flow artifacts due to the short echo time. Besides, the accelerated movies had high image quality and the undersampling artifacts were effectively removed. Left ventricular functional parameters derived from the standard and the accelerated cine movies were nearly identical.

  4. Evaluation of Adults With Congenital Heart Disease.

    PubMed

    Graziani, Francesca; Delogu, Angelica Bibiana

    2016-03-01

    The clinical approach to adults with congenital heart diseases (ACHDs) is unique in cardiovascular medicine because these patients encompass a broad range of presentations. Each patient, despite having similar diagnosis, will be anatomically and physiologically unlike others within ACHD population, in relation to the type of repair, age at repair, associated defects, with specific long-term risk factors and complications. Furthermore, as many patients will not complain of symptoms, clinical evaluation and diagnostic testing must also be based on the underlying main diagnostic category, with complete standardized lesion-specific clinical protocols, investigating all known risk factors specific for each congenital heart disease and performed as part of screening for significant long-term complications. The first part of this review will focus on clinical history, physical examination, and the most important diagnostic testing in ACHD population. The second part of the article will focus on some clinical issues we have to face in our daily practice, such as heart failure, cyanosis, and pulmonary hypertension. Furthermore, as survival rates of ACHD population continue to improve and patients with this condition live longer, we will briefly report on a new clinical concern regarding the impact of acquired morbidities like coronary artery disease that appear to be of greater importance in defining outcome in older patients with ACHD. PMID:26957402

  5. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    MedlinePlus

    ... Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  6. CTGF/CCN2 Postconditioning Increases Tolerance of Murine Hearts towards Ischemia-Reperfusion Injury

    PubMed Central

    Kaasbøll, Ole Jørgen; Moe, Ingvild Tronstad; Ahmed, Mohammad Shakil; Stang, Espen; Hagelin, Else Marie Valbjørn; Attramadal, Håvard

    2016-01-01

    Background and Purpose Previous studies of ischemia-reperfusion injury (IRI) in hearts from mice with cardiac-restricted overexpression of CCN2 have shown that CCN2 increases tolerance towards IRI. The objectives of this study were to investigate to what extent post-ischemic administration of recombinant human CCN2 (rhCCN2) would limit infarct size and improve functional recovery and what signaling pathways are involved. Experimental Approach Isolated mice hearts were perfused ad modum Langendorff, subjected to no-flow, global ischemia, and subsequently, exposed to mammalian cell derived, full-length (38-40kDa) rhCCN2 (250 nM) or vehicle during the first 15 min of a 60 min reperfusion period. Key Results Post-ischemic administration of rhCCN2 resulted in attenuation of infarct size from 58 ± 4% to 34 ± 2% (p < 0.001) which was abrogated by concomitant administration of the PI3 kinase inhibitor LY294002 (45 ± 3% vs. 50 ± 3%, ns). In congruence with reduction of infarct size rhCCN2 also improved recovery of left ventricular developed pressure (p < 0.05). Western blot analyses of extracts of ex vivo-perfused murine hearts also revealed that rhCCN2 evoked concentration-dependent increase of cardiac phospho-GSK3β (serine-9) contents. Conclusions and Implications We demonstrate that post-ischemic administration of rhCCN2 increases the tolerance of ex vivo-perfused murine hearts to IRI. Mechanistically, this postconditioning effect of rhCCN2 appeared to be mediated by activation of the reperfusion injury salvage kinase pathway as demonstrated by sensitivity to PI3 kinase inhibition and increased CCN2-induced phosphorylation of GSK3β (Ser-9). Thus, the rationale for testing rhCCN2-mediated post-ischemic conditioning of the heart in more complex models is established. PMID:26872261

  7. Explant culture of adult zebrafish hearts for epicardial regeneration studies.

    PubMed

    Cao, Jingli; Poss, Kenneth D

    2016-05-01

    Here we describe how to culture adult zebrafish hearts as explants and study the regeneration of epicardial tissue ex vivo, as a means to identify therapeutic targets for heart disease. Uninjured or injured adult hearts are excised, washed and cultured in an incubator with gentle agitation. Heart explants can be prepared within 2 h, and they can be maintained in culture for 30 d or longer. If explants are prepared from appropriate transgenic lines, dynamic behaviors of epicardial cells can be monitored by live imaging using stereofluorescence microscopy. We also describe ex vivo procedures for genetic ablation of the epicardium, cell proliferation assays, tissue grafts and bead grafts. Basic cell culture and surgical skills are required to carry out this protocol. Unlike existing protocols for culturing isolated zebrafish epicardial cells on matrices, procedures described here maintain epicardial cells on an intact cardiac surface, thereby better supporting in vivo cell behaviors. Our protocols complement and extend in vivo studies of heart regeneration. PMID:27055096

  8. The emerging adult population with congenital heart disease.

    PubMed

    Williams, William G.; Webb, Gary D.

    2000-01-01

    The successes in managing infants and children with congenital heart disease have led to an emerging population of adult patients. As we enter this new century, the majority of patients with congenital heart disease will be adults, not children. It is important to maintain our commitment for continuing care to the emerging adult population. Psycho-social issues, including employment and pregnancy counseling, are required as well as the ongoing need for medical and occasionally surgical intervention. The health care system needs to develop supra-regional tertiary referral centers for care of these patients and provide information sharing and support for community-based physicians interested in the welfare of the adult with congenital heart disease. Copyright 2000 by W.B. Saunders Company PMID:11486200

  9. Optical projection tomography permits efficient assessment of infarct volume in the murine heart postmyocardial infarction

    PubMed Central

    Zhao, X.; Wu, J.; Gray, C. D.; McGregor, K.; Rossi, A. G.; Morrison, H.; Jansen, M. A.

    2015-01-01

    The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective, and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion-fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. Two-dimensional infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r2 = 0.99, P < 0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (r2 = 0.7608, P < 0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a nondestructive, efficient, and accurate approach for routine in vitro assessment of murine myocardial infarct volume. PMID:26071543

  10. Mending broken hearts: cardiac development as a basis for adult heart regeneration and repair

    PubMed Central

    Xin, Mei; Olson, Eric N.; Bassel-Duby, Rhonda

    2013-01-01

    As the adult mammalian heart has limited potential for regeneration and repair, the loss of cardiomyocytes during injury and disease can result in heart failure and death. The cellular processes and regulatory mechanisms involved in heart growth and development can be exploited to repair the injured adult heart through ‘reawakening’ pathways that are active during embryogenesis. Heart function has been restored in rodents by reprogramming non-myocytes into cardiomyocytes, by expressing transcription factors (GATA4, HAND2, myocyte-specific enhancer factor 2C (MEF2C) and T-box 5 (TBX5)) and microRNAs (miR-1, miR-133, miR-208 and miR-499) that control cardiomyocyte identity. Stimulating cardiomyocyte dedifferentiation and proliferation by activating mitotic signalling pathways involved in embryonic heart growth represents a complementary approach for heart regeneration and repair. Recent advances in understanding the mechanistic basis of heart development offer exciting opportunities for effective therapies for heart failure. PMID:23839576

  11. In vivo 2D mapping of impaired murine cardiac energetics in NO-induced heart failure.

    PubMed

    Flögel, Ulrich; Jacoby, Christoph; Gödecke, Axel; Schrader, Jürgen

    2007-01-01

    (31)P MRS studies in humans have shown that an impairment of cardiac energetics is characteristic of heart failure. Although numerous transgenic mouse models with a heart-failure phenotype have been generated, current methods to analyze murine high-energy phosphates (HEPs) in vivo are hampered by limited spatial resolution. Using acquisition-weighted 2D (31)P chemical shift imaging (CSI) at 9.4 Tesla, we were able to acquire (31)P MR spectra over the entire thorax of the mouse with high spatial resolution in defined regions of the heart (the anterior, lateral, posterior, and septal walls) within a reasonable acquisition time of about 75 min. Analysis of a transgenic cardiomyopathy model (double mutant: cardiospecific inducible nitric oxide synthase (iNOS) overexpression and lack of myoglobin (tg-iNOS(+)/myo(-/-)) revealed that cardiac dysfunction in the mutant was associated with an impaired energy state (phosphocreatine (PCr)/adenosine triphosphate (ATP) 1.54 +/- 0.18) over the entire left ventricle (LV; wild-type (WT): PCr/ATP 2.06 +/- 0.22, N = 5, P < 0.05), indicating that in the absence of efficient cytosolic NO scavenging, iNOS-derived NO critically interferes with the respiratory chain. In vivo data were validated against (31)P MR spectra of perchloric acid extracts (PCr/ATP: 1.87 +/- 0.21 (WT), 1.39 +/- 0.17 (tg-iNOS(+)/myo(-/-), N = 5, P < 0.05). Future applications will substantially benefit studies on the cause-and-effect relationship between cardiac energetics and function in other genetically well-defined models of heart failure. PMID:17139621

  12. The Role of Beta-Blocker in Heart Failure in Adults with Congenital Heart Disease.

    PubMed

    Norozi, Kambiz

    2014-01-01

    Thanks to the enormous progress in the field of cardiac surgery and paediatric cardiology since the mid of 20th century, more and more children with congenital heart defects reach the adulthood. This on the other hand encounter physician and patients various problems due to late complications after the heart surgery like congestive heart failure, arrhythmia and sudden death. One of the challenging area is the medical management of heart failure in these patients with complex anatomy and hemodynamics. The lack of evidence of the effectiveness of the anti congestive medications in this population in from of large randomized controlled trials, makes it difficult to establish universally accepted therapy guidelines. In this article we will review the evidence of the beta-blockers in heart failure in patients with congenital heart disease. Also we will discuss the mechanisms of heart failure in this patient's cohort and will review the literature with respect to the use of neurohormonal antagonists in congenital heart disease. There is an urgent need to initiate well-designed clinical trials to prove if the positive results of neurohormonal blockade in acquired heart failure in adults can be translated in patients with congenital heart disease. PMID:25198738

  13. Hope in elderly adults with chronic heart failure. Concept analysis

    PubMed Central

    Caboral, Meriam F.; Evangelista, Lorraine S.; Whetsell, Martha V.

    2015-01-01

    This topic review employed Walker and Avant’s method of concept analysis to explore the construct of hope in elderly adults with chronic heart failure. The articles analyzed revealed that hope, as the belief of the occurrence of a positive result without any guarantee that it will be produced, is necessary for the survival and wellbeing of the elderly adults enduring this disease. PMID:26321777

  14. The Murine Model of Mucopolysaccharidosis IIIB Develops Cardiopathies over Time Leading to Heart Failure

    PubMed Central

    De Pasquale, Valeria; Cocchiaro, Pasquale; Paciello, Orlando; Avallone, Luigi; Belfiore, Maria Paola; Iacobellis, Francesca; Di Napoli, Daniele; Magliulo, Fabio; Perrino, Cinzia; Trimarco, Bruno; Esposito, Giovanni; Di Natale, Paola; Pavone, Luigi Michele

    2015-01-01

    Mucopolysaccharidosis (MPS) IIIB is a lysosomal disease due to the deficiency of the enzyme α-N-acetylglucosaminidase (NAGLU) required for heparan sulfate (HS) degradation. The disease is characterized by mild somatic features and severe neurological disorders. Very little is known on the cardiac dysfunctions in MPS IIIB. In this study, we used the murine model of MPS IIIB (NAGLU knockout mice, NAGLU-/-) in order to investigate the cardiac involvement in the disease. Echocardiographic analysis showed a marked increase in left ventricular (LV) mass, reduced cardiac function and valvular defects in NAGLU-/- mice as compared to wild-type (WT) littermates. The NAGLU-/- mice exhibited a significant increase in aortic and mitral annulus dimension with a progressive elongation and thickening of anterior mitral valve leaflet. A severe mitral regurgitation with reduction in mitral inflow E-wave-to-A-wave ratio was observed in 32-week-old NAGLU-/- mice. Compared to WT mice, NAGLU-/- mice exhibited a significantly lower survival with increased mortality observed in particular after 25 weeks of age. Histopathological analysis revealed a significant increase of myocardial fiber vacuolization, accumulation of HS in the myocardial vacuoles, recruitment of inflammatory cells and collagen deposition within the myocardium, and an increase of LV fibrosis in NAGLU-/- mice compared to WT mice. Biochemical analysis of heart samples from affected mice showed increased expression levels of cardiac failure hallmarks such as calcium/calmodulin-dependent protein kinase II, connexin43, α-smooth muscle actin, α-actinin, atrial and brain natriuretic peptides, and myosin heavy polypeptide 7. Furthermore, heart samples from NAGLU-/- mice showed enhanced expression of the lysosome-associated membrane protein-2 (LAMP2), and the autophagic markers Beclin1 and LC3 isoform II (LC3-II). Overall, our findings demonstrate that NAGLU-/- mice develop heart disease, valvular abnormalities and cardiac

  15. Advances in the Care of Adults With Congenital Heart Disease.

    PubMed

    Nasr, Viviane G; Kussman, Barry D

    2015-09-01

    The significant decline in mortality among children and adolescents with congenital heart disease (CHD) is associated with an increasing prevalence of CHD in adults, particularly those with moderate to severe defects. As a significant percentage of adolescents and young adults are lost to follow-up in the transition from pediatric to adult care, they may present for elective procedures with substantial CHD-associated morbidity. In addition to the specific cardiac defect, the procedures performed, and the current pathophysiological status, several factors should be considered when managing the adult with CHD. These include the type of setting (adult vs pediatric institution); surgeon (pediatric vs adult cardiac surgeon); coexisting diseases associated with CHD, such as coronary artery disease, hepatic dysfunction, renal dysfunction, cerebrovascular accidents, myopathy, and coagulation disorders; acquired diseases of aging; pregnancy; and psychosocial functioning. The current status of the management of common and important congenital cardiac defects is also described. PMID:25542866

  16. [Adult patients with congenital heart disease].

    PubMed

    Grabitz, R G; Kaemmerer, H; Mohr, F-W

    2013-01-01

    Unlike a few decades ago, today most patients with congenital heart disease reach adulthood after intervention or reparative surgery. As complete correction is generally not possible, a patient population with great complexity and a particular challenge to medical management is rising and a regular follow-up is mandatory. The aim of care is the timely recognition of residual or associated problems. Frequency and intensity of follow-up examinations depend on type and complexity of the lesion. The standard repertoire at follow-up consists of a specific history, clinical examination, ECG, Holter-monitoring, exercise tests, and echocardiography. Depending on the indication, cardio-MRI, CT scan, and sophisticated cardiac catheterization may become necessary. Long-term complications like rhythm disturbances, pulmonary hypertension, or heart failure are frequent, despite optimal care. Acute complications like arrhythmias, infective endocarditis, cerebral events, cerebral abscesses, aortic dissection, pulmonary embolism, and bleeding have to be recognized early and treated appropriately. Additional focus has to be placed on counseling and management of noncardiac disease and surgery, pregnancy and delivery, exercise at work and in private life, driving, and insurance issues. Training and certification of physicians as well as the establishment of specialized centers will help to ensure high quality health care for the affected patient population. PMID:23318541

  17. Congenital Heart Defects in Adults : A Field Guide for Cardiologists

    PubMed Central

    Romfh, Anitra; Pluchinotta, Francesca Romana; Porayette, Prashob; Valente, Anne Marie; Sanders, Stephen P.

    2013-01-01

    Advances in cardiology and cardiac surgery allow a large proportion of patients with congenital heart defects to survive into adulthood. These patients frequently develop complications characteristic of the defect or its treatment. Consequently, adult cardiologists participating in the care of these patients need a working knowledge of the more common defects. Occasionally, patients with congenital heart defects such as atrial septal defect, Ebstein anomaly or physiologically corrected transposition of the great arteries present for the first time in adulthood. More often patients previously treated in pediatric cardiology centers have transitioned to adult congenital heart disease centers for ongoing care. Some of the more important defects in this category are tetralogy of Fallot, transposition of the great arteries, functionally single ventricle defects, and coarctation. Through this field guide, we provide an overview of the anatomy of selected defects commonly seen in an adult congenital practice using pathology specimens and clinical imaging studies. In addition, we describe the physiology, clinical presentation to the adult cardiologist, possible complications, treatment options, and outcomes. PMID:24294540

  18. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  19. Optical mapping of the electrical activity of isolated adult zebrafish hearts: acute effects of temperature

    PubMed Central

    Lin, Eric; Ribeiro, Amanda; Ding, Weiguang; Hove-Madsen, Leif; Sarunic, Marinko V.; Beg, Mirza Faisal

    2014-01-01

    The zebrafish (Danio rerio) has emerged as an important model for developmental cardiovascular (CV) biology; however, little is known about the cardiac function of the adult zebrafish enabling it to be used as a model of teleost CV biology. Here, we describe electrophysiological parameters, such as heart rate (HR), action potential duration (APD), and atrioventricular (AV) delay, in the zebrafish heart over a range of physiological temperatures (18–28°C). Hearts were isolated and incubated in a potentiometric dye, RH-237, enabling electrical activity assessment in several distinct regions of the heart simultaneously. Integration of a rapid thermoelectric cooling system facilitated the investigation of acute changes in temperature on critical electrophysiological parameters in the zebrafish heart. While intrinsic HR varied considerably between fish, the ex vivo preparation exhibited impressively stable HRs and sinus rhythm for more than 5 h, with a mean HR of 158 ± 9 bpm (means ± SE; n = 20) at 28°C. Atrial and ventricular APDs at 50% repolarization (APD50) were 33 ± 1 ms and 98 ± 2 ms, respectively. Excitation originated in the atrium, and there was an AV delay of 61 ± 3 ms prior to activation of the ventricle at 28°C. APD and AV delay varied between hearts beating at unique HRs; however, APD and AV delay did not appear to be statistically dependent on intrinsic basal HR, likely due to the innate beat-to-beat variability within each heart. As hearts were cooled to 18°C (by 1°C increments), HR decreased by ∼40%, and atrial and ventricular APD50 increased by a factor of ∼3 and 2, respectively. The increase in APD with cooling was disproportionate at different levels of repolarization, indicating unique temperature sensitivities for ion currents at different phases of the action potential. The effect of temperature was more apparent at lower levels of repolarization and, as a whole, the atrial APD was the cardiac parameter most affected by acute

  20. Assessing structural and functional responses of murine hearts to acute and sustained β-adrenergic stimulation in vivo

    PubMed Central

    Puhl, Sarah-Lena; Weeks, Kate L.; Ranieri, Antonella; Avkiran, Metin

    2016-01-01

    Introduction Given the importance of β-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo. Methods Echocardiography was performed in naïve and stressed (isoprenaline; 30 μg/g/day s.c. for up to 14 days) mice, in the absence or presence of acute β-adrenergic stimulation (dobutamine 0.75 μg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically. Results In naïve mice, acute β-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p < 0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p < 0.05)) by 3 days, with little further change at 14 days. In contrast, increases in LVEF and LVFS were seen only at 14 days (p < 0.05). Discussion We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained β-adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced. PMID:26836145

  1. Self-Management of Heart Disease in Older Adults.

    PubMed

    Huynh-Hohnbaum, Anh-Luu T; Marshall, Lia; Villa, Valentine M; Lee, Gi

    2015-01-01

    The American Heart Association estimates that 81% of people who die of coronary heart disease are 65 years old or older. The leading risk health behaviors include physical inactivity, poor diet, smoking, and binge drinking. Using the 2011-2012 California Health Interview Survey (CHIS), this study looked at how self-management, which includes a plan developed by a medical professional and the confidence to manage one's disease, may decrease negative risk behaviors in older adults. The presence of a plan and increased self-efficacy decreased engagement in negative dietary behaviors and low physical activity. Implications for strategies that address heart disease and self-management are discussed. PMID:26566582

  2. Ghrelin signaling in heart remodeling of adult obese mice.

    PubMed

    Lacerda-Miranda, Glauciane; Soares, Vivian M; Vieira, Anatalia K G; Lessa, Juliana G; Rodrigues-Cunha, Alessandra C S; Cortez, Erika; Garcia-Souza, Erica P; Moura, Anibal S

    2012-05-01

    Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology, content and phosphorilation of cardiac proteins: ghrelin receptor (growth hormone secretagogue receptor 1a, GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK) and actin were achieved by Western blotting. GHSR-1a gene expression was analyzed by Real Time-PCR. We observed hyperglycemia and higher liver and visceral fat weight in obese when compared to control group. Obese mice presented a marked increase in heart weight/tibia length, indicating an enlarged heart size or a remodeling process. Obese mice had increased GHSR-1a content and expression in the heart associated to PI3K content and increased AKT content and phosphorylation. In contrast, AMPK content and phosphorylation in heart was not different between experimental groups. Ghrelin plasma levels in obese group were decreased when compared to control group. Our data suggest that remodeled myocardial in adult obese mice overnourished in early life are associated with higher phosphorylation of GHSR-1a, PI3K and AKT but not with AMPK. PMID:22407166

  3. Upper thermal limits of the hearts of Arctic cod Boreogadus saida: adults compared with larvae.

    PubMed

    Drost, H E; Fisher, J; Randall, F; Kent, D; Carmack, E C; Farrell, A P

    2016-02-01

    Wild adult and reared larval Boreogadus saida were acclimated to 3·5° C before testing their cardiac response to acute warming. Heart rate transition temperatures during warming were similar for adult and larval hearts, except that the maximum temperature for heart rate was 3° C warmer for adults. Thus, in a rapidly warming Arctic Ocean, the upper temperature limit for larval rather than adult B. saida appears more likely to dictate the southern range of the species. PMID:26608719

  4. Preconditioning boosts regenerative programmes in the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Sallin, Pauline; Jaźwińska, Anna

    2016-01-01

    During preconditioning, exposure to a non-lethal harmful stimulus triggers a body-wide increase of survival and pro-regenerative programmes that enable the organism to better withstand the deleterious effects of subsequent injuries. This phenomenon has first been described in the mammalian heart, where it leads to a reduction of infarct size and limits the dysfunction of the injured organ. Despite its important clinical outcome, the actual mechanisms underlying preconditioning-induced cardioprotection remain unclear. Here, we describe two independent models of cardiac preconditioning in the adult zebrafish. As noxious stimuli, we used either a thoracotomy procedure or an induction of sterile inflammation by intraperitoneal injection of immunogenic particles. Similar to mammalian preconditioning, the zebrafish heart displayed increased expression of cardioprotective genes in response to these stimuli. As zebrafish cardiomyocytes have an endogenous proliferative capacity, preconditioning further elevated the re-entry into the cell cycle in the intact heart. This enhanced cycling activity led to a long-term modification of the myocardium architecture. Importantly, the protected phenotype brought beneficial effects for heart regeneration within one week after cryoinjury, such as a more effective cell-cycle reentry, enhanced reactivation of embryonic gene expression at the injury border, and improved cell survival shortly after injury. This study reveals that exposure to antecedent stimuli induces adaptive responses that render the fish more efficient in the activation of the regenerative programmes following heart damage. Our results open a new field of research by providing the adult zebrafish as a model system to study remote cardiac preconditioning. PMID:27440423

  5. Sildenafil ameliorates left ventricular T-tubule remodeling in a pressure overload-induced murine heart failure model

    PubMed Central

    Huang, Chun-kai; Chen, Bi-yi; Guo, Ang; Chen, Rong; Zhu, Yan-qi; Kutschke, William; Hong, Jiang; Song, Long-sheng

    2016-01-01

    Aim: Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, has been shown to exert beneficial effects in heart failure. The purpose of this study was to test whether sildenafil suppressed transverse-tubule (T-tubule) remodeling in left ventricular (LV) failure and thereby providing the therapeutic benefits. Methods: A pressure overload-induced murine heart failure model was established in mice by thoracic aortic banding (TAB). One day after TAB, the mice received sildenafil (100 mg·kg−1·d−1, sc) or saline for 5 weeks. At the end of treatment, echocardiography was used to examine LV function. Then the intact hearts were dissected out and placed in Langendorff-perfusion chamber for in situ confocal imaging of T-tubule ultrastructure from epicardial myocytes. Results: TAB surgery resulted in heart failure accompanied by remarkable T-tubule remodeling. Sildenafil treatment significantly attenuated TAB-induced cardiac hypertrophy and congestive heart failure, improved LV contractile function, and preserved T-tubule integrity in LV cardiomyocytes. But sildenafil treatment did not significantly affect the chamber dilation. The integrity of LV T-tubule structure was correlated with cardiac hypertrophy (R2=0.74, P<0.01) and global LV function (R2=0.47, P<0.01). Conclusion: Sildenafil effectively ameliorates LV T-tubule remodeling in TAB mice, revealing a novel mechanism underlying the therapeutic benefits of sildenafil in heart failure. PMID:26972492

  6. Stem cell niches in the adult mouse heart

    PubMed Central

    Urbanek, Konrad; Cesselli, Daniela; Rota, Marcello; Nascimbene, Angelo; De Angelis, Antonella; Hosoda, Toru; Bearzi, Claudia; Boni, Alessandro; Bolli, Roberto; Kajstura, Jan; Anversa, Piero; Leri, Annarosa

    2006-01-01

    Cardiac stem cells (CSCs) have been identified in the adult heart, but the microenvironment that protects the slow-cycling, undifferentiated, and self-renewing CSCs remains to be determined. We report that the myocardium possesses interstitial structures with the architectural organization of stem cell niches that harbor long-term BrdU-retaining cells. The recognition of long-term label-retaining cells provides functional evidence of resident CSCs in the myocardium, indicating that the heart is an organ regulated by a stem cell compartment. Cardiac niches contain CSCs and lineage-committed cells, which are connected to supporting cells represented by myocytes and fibroblasts. Connexins and cadherins form gap and adherens junctions at the interface of CSCs–lineage-committed cells and supporting cells. The undifferentiated state of CSCs is coupled with the expression of α4-integrin, which colocalizes with the α2-chain of laminin and fibronectin. CSCs divide symmetrically and asymmetrically, but asymmetric division predominates, and the replicating CSC gives rise to one daughter CSC and one daughter committed cell. By this mechanism of growth kinetics, the pool of primitive CSCs is preserved, and a myocyte progeny is generated together with endothelial and smooth muscle cells. Thus, CSCs regulate myocyte turnover that is heterogeneous across the heart, faster at the apex and atria, and slower at the base–midregion of the ventricle. PMID:16754876

  7. Harnessing fetal and adult genetic reprograming for therapy of heart disease

    PubMed Central

    Nandi, Shyam Sundar; Mishra, Paras Kumar

    2015-01-01

    Heart is the first organ formed during organogenesis. The fetal heart undergoes several structural and functional modifications to form the four-chambered mammalian heart. The adult heart shows different adaptations during compensatory and decompensatory heart failure. However, one common adaptation in the pathological heart is fetal reprogramming, where the adult heart expresses several genes and miRNAs which are active in the fetal stage. The fetal reprogramming in the failing heart raises several questions, such as whether the switch of adult to fetal genetic programming is an adaptive response to cope with adverse remodeling of the heart, does the expression of fetal genes protect the heart during compensatory and/or decompensatory heart failure, does repressing the fetal gene in the failing heart is protective to the heart? To answer these questions, we need to understand the expression of genes and miRNAs that are reprogrammed in the failing heart. In view of this, we provided an overview of differentially expressed genes and miRNAs, and their regulation in this review. Further, we elaborated novel strategies for a plausible future therapy of cardiovascular diseases. PMID:25879081

  8. 3D Printing to Guide Ventricular Assist Device Placement in Adults With Congenital Heart Disease and Heart Failure.

    PubMed

    Farooqi, Kanwal M; Saeed, Omar; Zaidi, Ali; Sanz, Javier; Nielsen, James C; Hsu, Daphne T; Jorde, Ulrich P

    2016-04-01

    As the population of adults with congenital heart disease continues to grow, so does the number of these patients with heart failure. Ventricular assist devices are underutilized in adults with congenital heart disease due to their complex anatomic arrangements and physiology. Advanced imaging techniques that may increase the utilization of mechanical circulatory support in this population must be explored. Three-dimensional printing offers individualized structural models that would enable pre-surgical planning of cannula and device placement in adults with congenital cardiac disease and heart failure who are candidates for such therapies. We present a review of relevant cardiac anomalies, cases in which such models could be utilized, and some background on the cost and procedure associated with this process. PMID:27033018

  9. Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program

    ERIC Educational Resources Information Center

    Todorova, Irina L. G.; Tejada, Shirley; Castaneda-Sceppa, Carmen

    2014-01-01

    Background: Puerto Ricans are the second largest Hispanic group in the United States, and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. Purpose: To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being…

  10. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart

    PubMed Central

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D.; van den Hoff, Maurice J. B.; Butte, Manish J.; Yang, Phillip C.; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2016-01-01

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID:26375005

  11. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart.

    PubMed

    Wei, Ke; Serpooshan, Vahid; Hurtado, Cecilia; Diez-Cuñado, Marta; Zhao, Mingming; Maruyama, Sonomi; Zhu, Wenhong; Fajardo, Giovanni; Noseda, Michela; Nakamura, Kazuto; Tian, Xueying; Liu, Qiaozhen; Wang, Andrew; Matsuura, Yuka; Bushway, Paul; Cai, Wenqing; Savchenko, Alex; Mahmoudi, Morteza; Schneider, Michael D; van den Hoff, Maurice J B; Butte, Manish J; Yang, Phillip C; Walsh, Kenneth; Zhou, Bin; Bernstein, Daniel; Mercola, Mark; Ruiz-Lozano, Pilar

    2015-09-24

    The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans. PMID:26375005

  12. Social burden and lifestyle in adults with congenital heart disease.

    PubMed

    Zomer, A Carla; Vaartjes, Ilonca; Uiterwaal, Cuno S P; van der Velde, Enno T; Sieswerda, Gert-Jan T; Wajon, Elly M C; Plomp, Koos; van Bergen, Paul F M; Verheugt, Carianne L; Krivka, Eva; de Vries, Cees J; Lok, Dirk J A; Grobbee, Diederick E; Mulder, Barbara J M

    2012-06-01

    We aimed to evaluate how the presence and severity of congenital heart disease (CHD) influence social life and lifestyle in adult patients. A random sample (n = 1,496) from the CONgenital CORvitia (n = 11,047), the Dutch national registry of adult patients with CHD, completed a questionnaire on educational attainment, employment and marital statuses, and lifestyle (response 76%). The Utrecht Health Project provided a large reference group (n = 6,810) of unaffected subjects. Logistic regression models were used for subgroup analyses and to adjust for age, gender, and socioeconomic status where appropriate. Of all patients 51.5% were men (median age 39 years, interquartile range 29 to 51) with mild (46%), moderate (44%), and severe (10%) CHD. Young (<40-year-old) patients with CHD were more likely to have achieved a lower education (adjusted odds ratios [ORs] 1.6 for men and 1.9 for women, p <0.05 for the 2 comparisons), significantly more often unemployed (adjusted ORs 5.9 and 2.0 for men and women, respectively), and less likely to be in a relationship compared to the reference group (adjusted ORs 8.5 for men and 4.5 for women). These poorer outcomes were seen in all severity groups. Overall, the CHD population smoked less (adjusted OR 0.5, p <0.05), had more sports participation (adjusted OR 1.2, p <0.05), and had less obesity (adjusted OR 0.7, p <0.05) than the reference group. In conclusion, there was a substantial social disadvantage in adult patients with CHD, which was seen in all severity groups and primarily in young men. In contrast, adults with CHD had healthier lifestyles compared to the reference group. PMID:22444325

  13. Label-Retaining Cells in the Adult Murine Salivary Glands Possess Characteristics of Adult Progenitor Cells

    PubMed Central

    Chibly, Alejandro M.; Querin, Lauren; Harris, Zoey; Limesand, Kirsten H.

    2014-01-01

    Radiotherapy is the primary treatment for patients with head and neck cancer, which account for roughly 500,000 annual cases worldwide. Dysfunction of the salivary glands and associated conditions like xerostomia and dysphagia are often developed by these patients, greatly diminishing their life quality. Current preventative and palliative care fail to deliver an improvement in the quality of life, thus accentuating the need for regenerative therapies. In this study, a model of label retaining cells (LRCs) in murine salivary glands was developed, in which LRCs demonstrated proliferative potential and possessed markers of putative salivary progenitors. Mice were labeled with 5-Ethynyl-2′-deoxyuridine (EdU) at postnatal day 10 and chased for 8 weeks. Tissue sections from salivary glands obtained at the end of chase demonstrated co-localization between LRCs and the salivary progenitor markers keratin 5 and keratin 14, as well as kit mRNA, indicating that LRCs encompass a heterogeneous population of salivary progenitors. Proliferative potential of LRCs was demonstrated by a sphere assay, in which LRCs were found in primary and secondary spheres and they co-localized with the proliferation marker Ki67 throughout sphere formation. Surprisingly, LRCs were shown to be radio-resistant and evade apoptosis following radiation treatment. The clinical significance of these findings lie in the potential of this model to study the mechanisms that prevent salivary progenitors from maintaining homeostasis upon exposure to radiation, which will in turn facilitate the development of regenerative therapies for salivary gland dysfunction. PMID:25238060

  14. Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway.

    PubMed

    Han, Dong; Huang, Wei; Li, Xiang; Gao, Lei; Su, Tao; Li, Xiujuan; Ma, Sai; Liu, Tong; Li, Congye; Chen, Jiangwei; Gao, Erhe; Cao, Feng

    2016-03-01

    Mesenchymal stem cells (MSCs)-based therapy provides a promising therapy for the ischemic heart disease (IHD). However, engrafted MSCs are subjected to acute cell death in the ischemic microenvironment, characterized by excessive inflammation and oxidative stress in the host's infarcted myocardium. Melatonin, an indole, which is produced by many organs including pineal gland, has been shown to protect bone marrow MSCs against apoptosis although the mechanism of action remains elusive. Using a murine model of myocardial infarction (MI), this study was designed to evaluate the impact of melatonin on adipose-derived mesenchymal stem cells (AD-MSCs)-based therapy for MI and the underlying mechanism involved with a focus on silent information regulator 1(SIRT1) signaling. Our results demonstrated that melatonin promoted functional survival of AD-MSCs in infarcted heart and provoked a synergetic effect with AD-MSCs to restore heart function. This in vivo effect of melatonin was associated with alleviated inflammation, apoptosis, and oxidative stress in infarcted heart. In vitro studies revealed that melatonin exert cytoprotective effects on AD-MSCs against hypoxia/serum deprivation (H/SD) injury via attenuating inflammation, apoptosis, and oxidative stress. Mechanistically, melatonin enhanced SIRT1 signaling, which was accompanied with the increased expression of anti-apoptotic protein Bcl2, and decreased the expression of Ac-FoxO1, Ac-p53, Ac-NF-ΚB, and Bax. Taken together, our findings indicated that melatonin facilitated AD-MSCs-based therapy in MI, possibly through promoting survival of AD-MSCs via SIRT1 signaling. Our data support the promise of melatonin as a novel strategy to improve MSC-based therapy for IHD, possibly through SIRT1 signaling evocation. PMID:26607398

  15. Identification and enrichment of colony-forming cells from the adult murine pituitary

    SciTech Connect

    Lepore, D.A.; Roeszler, K.; Wagner, J.; Ross, S.A.; Bauer, K.; Thomas, P.Q. , E-Mail: paul.thomas@mcri.edu.au

    2005-08-01

    Stem and progenitor cells have been identified in many adult tissues including bone marrow, the central nervous system, and skin. While there is direct evidence to indicate the activity of a progenitor cell population in the pituitary gland, this putative subpopulation has not yet been identified. Herein we describe the isolation and characterization of a novel clonogenic cell type in the adult murine pituitary, which we have termed Pituitary Colony-Forming Cells (PCFCs). PCFCs constitute 0.2% of pituitary cells, and generate heterogeneous colonies from single cells. PCFCs exhibit variable proliferative potential, and may exceed 11 population doublings in 14 days. Enrichment of PCFCs to 61.5-fold with 100% recovery can be obtained through the active uptake of the fluorescent dipeptide, {beta}-Ala-Lys-N{epsilon}-AMCA. PCFCs are mostly contained within the large, agranular subpopulation of AMCA{sup +} cells, and constitute 28% of this fraction, corresponding to 140.5-fold enrichment. Interestingly, the AMCA{sup +} population contains rare cells that are GH{sup +} or PRL{sup +}. GH{sup +} cells were also identified in PCFC single cell colonies, suggesting that PCFCs have the potential to differentiate into GH{sup +} cells. Together, these data show that the pituitary contains a rare clonogenic population which may correspond to the somatotrope/lactotrope progenitors suggested by previous experiments.

  16. Long-Term Survival of Photoreceptors Transplanted into the Adult Murine Neural Retina Requires Immune Modulation

    PubMed Central

    West, Emma L.; Pearson, Rachael A.; Barker, Susie E.; Luhmann, Ulrich F. O.; Maclaren, Robert E.; Barber, Amanda C.; Duran, Yanai; Smith, Alexander J.; Sowden, Jane C.; Ali, Robin R.

    2012-01-01

    Stem cell therapy presents an opportunity to replace photoreceptors that are lost as a result of inherited and age-related degenerative disease. We have previously shown that murine postmitotic rod photoreceptor precursor cells, identified by expression of the rod-specific transcription factor Nrl, are able to migrate into and integrate within the adult murine neural retina. However, their long-term survival has yet to be determined. Here, we found that integrated Nrl.gfp+ve photoreceptors were present up to 12 months post-transplantation, albeit in significantly reduced numbers. Surviving cells had rod-like morphology, including inner/outer segments and spherule synapses. In a minority of eyes, we observed an early, marked reduction in integrated photoreceptors within 1 month post-transplantation, which correlated with increased numbers of amoeboid macrophages, indicating acute loss of transplanted cells due to an inflammatory response. In the majority of transplants, similar numbers of integrated cells were observed between 1 and 2 months post-transplantation. By 4 months, however, we observed a significant decrease in integrated cell survival. Macrophages and T cells were present around the transplantation site, indicating a chronic immune response. Immune suppression of recipients significantly increased transplanted photoreceptor survival, indicating that the loss observed in unsuppressed recipients resulted from T cell-mediated host immune responses. Thus, if immune responses are modulated, correctly integrated transplanted photoreceptors can survive for extended periods of time in hosts with partially mismatched H-2 haplotypes. These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective. PMID:20857496

  17. Report of the National Heart, Lung, and Blood Institute Working Group on research in adult congenital heart disease.

    PubMed

    Williams, Roberta G; Pearson, Gail D; Barst, Robyn J; Child, John S; del Nido, Pedro; Gersony, Welton M; Kuehl, Karen S; Landzberg, Michael J; Myerson, Merle; Neish, Steven R; Sahn, David J; Verstappen, Amy; Warnes, Carole A; Webb, Catherine L

    2006-02-21

    The Working Group on research in adult congenital heart disease (ACHD) was convened in September 2004 under the sponsorship of National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases, National Institutes of Health, Department of Health and Human Services, to make recommendations on research needs. The purpose of the Working Group was to advise the NHLBI on the current state of the science in ACHD and barriers to optimal clinical care, and to make specific recommendations for overcoming those barriers. The members of the Working Group were chosen to provide expert input on a broad range of research issues from both scientific and lay perspectives. The Working Group reviewed data on the epidemiology of ACHD, long-term outcomes of complex cardiovascular malformations, issues in assessing morphology and function with current imaging techniques, surgical and catheter-based interventions, management of related conditions including pregnancy and arrhythmias, quality of life, and informatics. After research and training barriers were discussed, the Working Group recommended outreach and educational programs for adults with congenital heart disease, a network of specialized adult congenital heart disease regional centers, technology development to support advances in imaging and modeling of abnormal structure and function, and a consensus on appropriate training for physicians to provide care for adults with congenital heart disease. PMID:16487831

  18. The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins

    PubMed Central

    Sebastian, Sonia; Ang, Richard; Abramowitz, Joel; Weinstein, Lee S.; Chen, Min; Ludwig, Andreas; Birnbaumer, Lutz

    2013-01-01

    Reciprocal physiological modulation of heart rate is controlled by the sympathetic and parasympathetic systems acting on the sinoatrial (SA) node. However, there is little direct in vivo work examining the role of stimulatory and inhibitory G protein signaling in the SA node. Thus, we designed a study to examine the role of the stimulatory (Gαs) and inhibitory G protein (Gαi2) in in vivo heart rate regulation in the SA node in the mouse. We studied mice with conditional deletion of Gαs and Gαi2 in the conduction system using cre-loxP technology. We crossed mice in which cre recombinase expression was driven by a tamoxifen-inducible conduction system-specific construct with “Gαs floxed” and “Gαi2 floxed” mice. We studied the heart rate responses of adult mice compared with littermate controls by using radiotelemetry before and after administration of tamoxifen. The mice with conditional deletion of Gαs and Gαi2 had a loss of diurnal variation and were bradycardic or tachycardic, respectively, in the daytime. In mice with conditional deletion of Gαs, there was a selective loss of low-frequency power, while with deletion of Gαi2, there was a loss of high-frequency power in power spectral analysis of heart rate variability. There was no evidence of pathological arrhythmia. Pharmacological modulation of heart rate by isoprenaline was impaired in the Gαs mice, but a muscarinic agonist was still able to slow the heart rate in Gαi2 mice. We conclude that Gαs- and Gαi2-mediated signaling in the sinoatrial node is important in the reciprocal regulation of heart rate through the autonomic nervous system. PMID:23697798

  19. Matrix metalloproteinases as candidate biomarkers in adults with congenital heart disease.

    PubMed

    Baggen, Vivan J M; Eindhoven, Jannet A; van den Bosch, Annemien E; Witsenburg, Maarten; Cuypers, Judith A A E; Langstraat, Jannette S; Boersma, Eric; Roos-Hesselink, Jolien W

    2016-07-01

    Context Matrix metalloproteinases (MMPs) are associated with diastolic dysfunction and heart failure in acquired heart disease. Objective To investigate the role of MMPs as novel biomarkers in clinically stable adults with congenital heart disease. Methods We measured serum MMP-2, -3, -9 and tissue inhibitor of matrix metalloproteinase-1 in 425 patients and analysed the association with cardiac function and exercise capacity. Results MMP-2 was significantly associated with exercise capacity, ventilatory efficiency and left ventricular deceleration time, independently of age, sex, body surface area and NT-proBNP. Conclusion MMP-2 may provide new information in the clinical evaluation of adults with congenital heart disease. PMID:26983903

  20. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium

    PubMed Central

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J.; Abreu Paiva, Marta S.; Habib, Josef; Macaulay, Iain; de Smith, Adam J.; al-Beidh, Farah; Sampson, Robert; Lumbers, R. Thomas; Rao, Pulivarthi; Harding, Sian E.; Blakemore, Alexandra I. F.; Eirik Jacobsen, Sten; Barahona, Mauricio; Schneider, Michael D.

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT–PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα+ cells. Clonal progeny of single Sca1+ SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα− cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα+/CD31− cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα−/CD31+ cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem/progenitor cell. PMID:25980517

  1. PDGFRα demarcates the cardiogenic clonogenic Sca1+ stem/progenitor cell in adult murine myocardium.

    PubMed

    Noseda, Michela; Harada, Mutsuo; McSweeney, Sara; Leja, Thomas; Belian, Elisa; Stuckey, Daniel J; Abreu Paiva, Marta S; Habib, Josef; Macaulay, Iain; de Smith, Adam J; al-Beidh, Farah; Sampson, Robert; Lumbers, R Thomas; Rao, Pulivarthi; Harding, Sian E; Blakemore, Alexandra I F; Jacobsen, Sten Eirik; Barahona, Mauricio; Schneider, Michael D

    2015-01-01

    Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells. Clonal progeny of single Sca1(+) SP cells show cardiomyocyte, endothelial and smooth muscle lineage potential after cardiac grafting, augmenting cardiac function although durable engraftment is rare. PDGFRα(-) cells are characterized by Kdr/Flk1, Cdh5, CD31 and lack of clonogenicity. PDGFRα(+)/CD31(-) cells derive from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1, distinct from PDGFRα(-)/CD31(+) cells (Gata5 low; Flk1 and Tie2 high). Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1(+) stem/progenitor cell. PMID:25980517

  2. Mechanistic Target of Rapamycin (Mtor) Is Essential for Murine Embryonic Heart Development and Growth

    PubMed Central

    Zhu, Yi; Pires, Karla M. P.; Whitehead, Kevin J.; Olsen, Curtis D.; Wayment, Benjamin; Zhang, Yi Cheng; Bugger, Heiko; Ilkun, Olesya; Litwin, Sheldon E.; Thomas, George; Kozma, Sara C.; Abel, E. Dale

    2013-01-01

    Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using α myosin heavy chain (α-MHC) driven Cre recombinase. Initial mosaic expression of Cre between embryonic day (E) 10.5 and E11.5 eliminated a subset of cardiomyocytes with high Cre activity by apoptosis and reduced overall cardiac proliferative capacity. The remaining cardiomyocytes proliferated and expanded normally. However loss of 50% of cardiomyocytes defined a threshold that impairs the ability of the embryonic heart to sustain the embryo’s circulatory requirements. As a result 92% of embryos with cardiomyocyte Mtor deficiency died by the end of gestation. Thus Mtor is required for survival and proliferation of cardiomyocytes in the developing heart. PMID:23342106

  3. Risks and Benefits of Exercise Training in Adults With Congenital Heart Disease.

    PubMed

    Chaix, Marie-A; Marcotte, François; Dore, Annie; Mongeon, François-Pierre; Mondésert, Blandine; Mercier, Lise-Andrée; Khairy, Paul

    2016-04-01

    Exercise capacity in adults with various forms of congenital heart disease is substantially lower than that of the general population. Although the underlying congenital heart defect, and its sequelae, certainly contribute to observed exercise limitations, there is evidence suggesting that deconditioning and a sedentary lifestyle are important implicated factors. The prevalence of acquired cardiovascular comorbidities is on the increase in the aging population with congenital heart disease, such that obesity and a sedentary lifestyle confer increased risk. Health fears and misconceptions are common barriers to regular physical activity in adults with congenital heart disease, despite evidence linking lower functional capacity to poor outcomes, and data supporting the safety and efficacy of exercise in bestowing numerous physical and psychosocial rewards. With few exceptions, adults with congenital heart disease should be counselled to exercise regularly. In this contemporary review, we provide a practical approach to assessing adults with congenital heart disease before exercise training. We examine available evidence supporting the safety and benefits of exercise training. Risks associated with exercise training in adults with congenital heart disease are discussed, particularly with regard to sudden cardiac death. Finally, recommendations for exercise training are provided, with consideration for the type of congenital heart disease, the nature (ie, static vs dynamic) and intensity (ie, low, medium, high) of the physical activity, and associated factors such as systemic ventricular dysfunction and residual defects. Further research is required to determine optimal exercise regimens and to identify effective strategies to implement exercise training as a key determinant of healthy living. PMID:26868839

  4. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Bui, Albert D; Sprague, Lisanne; D'Souza, Manoranjan S

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. PMID:26683901

  5. Placing Advocacy at the Heart of Adult Education

    ERIC Educational Resources Information Center

    Taylor, Jackie

    2016-01-01

    Adult educators know that adults and families change their lives through adult education. Adult education also positively impacts a host of social and economic issues. Yet this fact is largely unknown or misunderstood by the general public. Resources have become increasingly scarce, while at the same time adult educators are asked to do more with…

  6. Expression of skeletal muscle sodium channel (Nav1.4) or connexin32 prevents reperfusion arrhythmias in murine heart

    PubMed Central

    Anyukhovsky, Evgeny P.; Sosunov, Eugene A.; Kryukova, Yelena N.; Prestia, Kevin; Ozgen, Nazira; Rivaud, Mathilde; Cohen, Ira S.; Robinson, Richard B.; Rosen, Michael R.

    2011-01-01

    Aims Acute myocardial ischaemia induces a decrease in resting membrane potential [which leads to reduction of action potential (AP) Vmax] and intracellular acidification (which closes gap junctions). Both contribute to conduction slowing. We hypothesized that ventricular expression of the skeletal muscle Na+ channel, Nav1.4 (which activates fully at low membrane potentials), or connexin32 (Cx32, which is less pH-sensitive than connexin43) would support conduction and be antiarrhythmic. We tested this hypothesis in a murine model of ischaemia and reperfusion arrhythmias. Methods and results Empty adenovirus (Sham) or adenoviral constructs expressing either SkM1 (gene encoding Nav1.4) or Cx32 genes were injected into the left ventricular wall. Four days later, ventricular tachycardia (VT) occurred during reperfusion following a 5 min coronary occlusion. In Nav1.4- and Cx32-expressing mice, VT incidence and duration were lower than in Sham (P < 0.05). In vitro multisite microelectrode mapping was performed in the superfused right ventricular wall. To simulate ischaemic conditions, [K+] in solution was increased to 10 mmol/L and/or pH was decreased to 6.0. Western blots revealed Cx32 and Nav1.4 expression in both ventricles. Nav1.4 APs showed higher Vmax and conduction velocity (CV) than Shams at normal and elevated [K+]. Exposure of tissue to acid solution reduced intracellular pH to 6.4. There was no difference in CV between Sham and Cx32 groups in control solution. Acid solution slowed CV in Sham (P < 0.05) but not in Cx32. Conclusion Nav1.4 or Cx32 expression preserved normal conduction in murine hearts and decreased the incidence of reperfusion VT. PMID:20823275

  7. Coxsackievirus and adenovirus receptor (CAR) mediates atrioventricular-node function and connexin 45 localization in the murine heart

    PubMed Central

    Lim, Byung-Kwan; Xiong, Dingding; Dorner, Andrea; Youn, Tae-Jin; Yung, Aaron; Liu, Taylor I.; Gu, Yusu; Dalton, Nancy D.; Wright, Adam T.; Evans, Sylvia M.; Chen, Ju; Peterson, Kirk L.; McCulloch, Andrew D.; Yajima, Toshitaka; Knowlton, Kirk U.

    2008-01-01

    The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein that belongs to the family of adhesion molecules. In the postnatal heart, it is localized predominantly at the intercalated disc, where its function is not known. Here, we demonstrate that a first degree or complete block of atrioventricular (AV) conduction developed in the absence of CAR in the adult mouse heart and that prolongation of AV conduction occurred in the embryonic heart of the global CAR-KO mouse. In the cardiac-specific CAR-KO (CAR-cKO) mouse, we observed the loss of connexin 45 localization to the cell-cell junctions of the AV node but preservation of connexin 40 and 43 in contracting myocardial cells and connexin 30.2 in the AV node. There was also a marked decrease in β-catenin and zonula occludens-1 (ZO-1) localization to the intercalated discs of CAR-cKO mouse hearts at 8 weeks before the mice developed cardiomyopathy at 21 weeks of age. We also found that CAR formed a complex with connexin 45 via its PSD-95/DigA/ZO-1–binding (PDZ-binding) motifs. We conclude that CAR expression is required for normal AV-node conduction and cardiac function. Furthermore, localization of connexin 45 at the AV-node cell-cell junction and of β-catenin and ZO-1 at the ventricular intercalated disc are dependent on CAR. PMID:18636119

  8. Nutrition and Cognition in Older Adults With Heart Failure: A Systematic Review.

    PubMed

    Stewart, Mara W; Traylor, Abigail C; Bratzke, Lisa C

    2015-11-01

    Cognitive impairment is commonly observed in older adults with heart failure; nutrition is a possible contributing factor. The purpose of the current systematic review is to examine the relationship between nutrition and cognition in older adults with heart failure. A literature review was performed through August 2015 that examined published, peer-reviewed studies from PubMed, PsycINFO, CINAHL, and Web of Science. Four articles were selected for inclusion. Findings revealed that poorer nutritional habits were associated with poorer attention, executive functioning, and memory in older adults with heart failure. Nutritional biomarkers, including anemia, hyponatremia, hypokalemia, hyperglycemia, and hypoalbuminemia, were also associated with cognitive impairment. More research is needed to explore the relationship between nutrition and cognition in this population. Descriptive studies will inform scientists as they design and test nutritional interventions to optimize cognitive function in older adults with heart failure. PMID:26505248

  9. Precursors of Hypertensive Heart Phenotype Develop in Healthy Adults

    PubMed Central

    de Marvao, Antonio; Dawes, Timothy J.W.; Shi, Wenzhe; Durighel, Giuliana; Rueckert, Daniel; Cook, Stuart A.; O’Regan, Declan P.

    2015-01-01

    Objectives This study used high-resolution 3-dimensional cardiac magnetic resonance to define the anatomical and functional left ventricular (LV) properties associated with increasing systolic blood pressure (SBP) in a drug-naïve cohort. Background LV hypertrophy and remodeling occur in response to hemodynamic stress but little is known about how these phenotypic changes are initiated in the general population. Methods In this study, 1,258 volunteers (54% women, mean age 40.6 ± 12.8 years) without self-reported cardiovascular disease underwent 3-dimensional cardiac magnetic resonance combined with computational modeling. The relationship between SBP and wall thickness (WT), relative WT, end-systolic wall stress (WS), and fractional wall thickening were analyzed using 3-dimensional regression models adjusted for body surface area, sex, race, age, and multiple testing. Significantly associated points in the LV model (p < 0.05) were identified and the relationship with SBP reported as mean β coefficients. Results There was a continuous relationship between SBP and asymmetric concentric hypertrophic adaptation of the septum and anterior wall that was associated with normalization of wall stress. In the lateral wall an increase in wall stress with rising SBP was not balanced by a commensurate hypertrophic relationship. In normotensives, SBP was positively associated with WT (β = 0.09) and relative WT (β = 0.07) in the septal and anterior walls, and this regional hypertrophic relationship was progressively stronger among pre-hypertensives (β = 0.10) and hypertensives (β = 0.30). Conclusions These findings show that the precursors of the hypertensive heart phenotype can be traced to healthy normotensive adults and that an independent and continuous relationship exists between adverse LV remodeling and SBP in a low-risk population. These adaptations show distinct regional variations with concentric hypertrophy of the septum and eccentric hypertrophy of the

  10. Expression of vascular endothelial growth factor (VEGF)-B and its receptor (VEGFR1) in murine heart, lung and kidney.

    PubMed

    Muhl, Lars; Moessinger, Christine; Adzemovic, Milena Z; Dijkstra, Marike H; Nilsson, Ingrid; Zeitelhofer, Manuel; Hagberg, Carolina E; Huusko, Jenni; Falkevall, Annelie; Ylä-Herttuala, Seppo; Eriksson, Ulf

    2016-07-01

    Metabolic diseases, such as obesity and diabetes, are a serious burden for the health system. Vascular endothelial growth factor (VEGF)-B has been shown to regulate tissue uptake and accumulation of fatty acids and is thus involved in these metabolic diseases. However, the cell-type-specific expression pattern of Vegfb and its receptor (VEGFR1, gene Flt1) remains unclear. We explore the expression of Vegfb and Flt1 in the murine heart, lung and kidney by utilizing β-galactosidase knock-in mouse models and combining the analysis of reporter gene expression and immunofluorescence microscopy. Furthermore, Flt1 heterozygous mice were analyzed with regard to muscular fatty acid accumulation and peripheral insulin sensitivity. Throughout the heart, Vegfb expression was found in cardiomyocytes with a postnatal ventricular shift corresponding to known changes in energy requirements. Vegfb expression was also found in the pulmonary myocardium of the lung and in renal epithelial cells of the thick ascending limb of Henle's loop, the connecting tubule and the collecting duct. In all analyzed organs, VEGFR1 expression was restricted to endothelial cells. We also show that reduced expression of VEGFR1 resulted in decreased cardiac fatty acid accumulation and increased peripheral insulin sensitivity, possibly as a result of attenuated VEGF-B/VEGFR1 signaling. Our data therefore support a tightly controlled, paracrine signaling mechanism of VEGF-B to VEGFR1. The identified cell-specific expression pattern of Vegfb and Flt1 might form the basis for the development of cell-type-targeted research models and contributes to the understanding of the physiological and pathological role of VEGF-B/VEGFR1 signaling. PMID:26928042

  11. Prevalence and correlates of heart disease among adults in Singapore.

    PubMed

    Picco, Louisa; Subramaniam, Mythily; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann

    2016-02-01

    Heart disease is one of the leading causes of morbidity and mortality worldwide and it has been well established that it is associated with both mental and physical conditions. This paper describes the prevalence of heart disease with mental disorders and other chronic physical conditions among the Singapore resident population. Data were from the Singapore Mental Health Study which was a representative, cross-sectional epidemiological survey undertaken with 6616 Singapore residents, between December 2009 and December 2010. The Composite International Diagnostic Interview Version 3.0 was used to establish the diagnosis of mental disorders, while a chronic medical conditions checklist was used to gather information on 15 physical conditions, including various forms of heart disease. Health-related quality of life was measured using the Euro-Quality of Life Scale (EQ-5D). The lifetime prevalence of heart disease was 2.8%. Socio-demographic correlates of heart disease included older age, Indian ethnicity, secondary education (vs. tertiary) and being economically inactive. After adjusting for socio-demographic variables and other comorbid physical and mental disorders, the prevalence of major depressive disorder and bipolar disorder were significantly higher among those with heart disease, as were diabetes, arthritis, kidney failure and lung disease. These findings highlight important associations between heart disease and various socio-demographic correlates, mental disorders and physical conditions. Given the high prevalence of mood disorders among heart disease patients, timely and appropriate screening and treatment of mental disorders among this group is essential. PMID:26957336

  12. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-01-01

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed. PMID:24476362

  13. Overweight Status, Obesity, and Risk Factors for Coronary Heart Disease in Adults with Intellectual Disability

    ERIC Educational Resources Information Center

    Henderson, C. Michael; Robinson, Laura M.; Davidson, Philip W.; Haveman, Meindert; Janicki, Matthew P.; Albertini, Giorgio

    2008-01-01

    Research indicates that adults with intellectual disabilities (ID) have high rates of overweight status/obesity (OSO). OSO is associated with several important risk factors for coronary heart disease (CHD). This study focused on assessing whether such risk factors are being identified in adults with ID who are receiving their healthcare in…

  14. Differential characteristics of heart, liver, and brain metastatic subsets of murine breast carcinoma.

    PubMed

    Erin, Nuray; Kale, Sule; Tanrıöver, Gamze; Köksoy, Sadi; Duymuş, Ozlem; Korcum, Aylin F

    2013-06-01

    Breast carcinoma is comprised of heterogeneous groups of cells with different metastatic potential. To develop effective therapeutic strategies targeting metastatic disease, it is crucial to understand the characteristics of breast cancer cells that enable metastasis to distant organs. 4THM breast carcinoma cells are the cells of 4T1 primary tumors that metastasized to the heart. Cells of 4THM tumors which metastasized to liver (4TLM) were previously isolated. Recently macroscopic brain metastasis in 4THM injected animals, were isolated to obtain a brain metastatic cell line (4TBM). Using an orthotopic mouse model differential characteristic of cells metastasized to heart (4THM), liver (4TLM), and brain (4TBM) were compared for ability to metastasize and expression of stem cell markers. We found that 4TLM cells produced significantly more lung and liver metastasis compared to 4TBM and 4THM cells. In vitro, proliferation as well as migration rate of 4TLM cells was also significantly higher than the other cell lines. Remarkably primary tumors formed by 4TLM cells expressed significant amounts of CD34, a marker for mesenchymal malignancies. Markers of epithelial-mesenchymal transition were expressed in all metastatic cells, but the degree of expression differed. Majorities of 4TLM, 4THM, and 4TBM cells were CD44+ CD24- whereas, 12 % of 4TLM cells also expressed membranous CD24. Conditioned mediums of non-metastatic 67NR breast tumors and cancer-associated fibroblasts inhibited growth of highly metastatic 4TLM cells. Malignant cells metastasized to brain were distinguished by membranous E-cadherin expression that was markedly higher in 4TBM cells grown as spheroids suggesting E-cadherin is required for brain metastasis. Differential features of heart, brain, and liver metastatic cells in a syngenic model was shown in this study for the first time. These findings not only provide a model to explore new treatment modalities, but also demonstrate differential features of

  15. Cardiomyogenic potential of c-kit+ expressing cells derived from neonatal and adult mouse hearts

    PubMed Central

    Zaruba, Marc-Michael; Soonpaa, Mark; Reuter, Sean; Field, Loren J.

    2010-01-01

    Summary Background c-kit is a receptor tyrosine kinase family member expressed in hematopoietic stem cells. c-kit is also transiently expressed in cardiomyocyte precursors during development, and in a rare cell population in the normal adult heart. Here, the cardiomyogenic potential of c-kit+ cells isolated from normal neonatal, normal adult and infarcted adult mouse hearts was evaluated. Methods and Results Magnetic activated cell sorting (MACS) was used to prepare c-kit+ cells from the hearts of ACT-EGFP/MHC-nLAC double transgenic mice. These animals exhibit widespread enhanced green fluorescent protein (EGFP) expression and cardiomyocyte-restricted nuclear β-galactosidase activity, thus permitting simultaneous tracking of cell survival and differentiation. A subset of the c-kit+ cells from double transgenic neonatal hearts acquired a cardiomyogenic phenotype when co-cultured with fetal cardiomyocytes (2.4% of all EGFP+ cells screened), but not when cultured alone or when co-cultured with mouse fibroblasts (0.03% and 0.05% of the EGFP+ cells screened, respectively). In contrast, c-kit+ cells from normal adult double transgenic hearts failed to undergo cardiomyogenic differentiation when co-cultured with non-transgenic fetal cardiomyocytes (>18,000 EGFP+ cells screened) or when transplanted into normal or infarcted adult mouse hearts (14 EGFP+ grafts examined). A single c-kit+ cell from an infarcted double transgenic adult heart was observed to acquire a cardiomyogenic phenotype in co-culture (>37,000 EGFP+ cells screened). Conclusions These data suggest that the ability of cardiac-resident c-kit+ cells to acquire a cardiomyogenic phenotype is subject to temporal limitations, or alternatively that the cardiomyogenic population is lost. Elucidation of the underlying molecular basis may permit robust cardiomyogenic induction in adult-derived cardiac c-kit+ cells. PMID:20421520

  16. Adult-Onset Asthma Might Raise Heart Risks

    MedlinePlus

    ... Heart Risks But shared risk factors, such as air pollution, might explain the connection, researchers say To use ... is often caused by different factors -- such as air pollution -- and often results in a more rapid decline ...

  17. The Proteome of Native Adult Müller Glial Cells From Murine Retina*

    PubMed Central

    Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca

    2016-01-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  18. The Proteome of Native Adult Müller Glial Cells From Murine Retina.

    PubMed

    Grosche, Antje; Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca; von Toerne, Christine; Merl-Pham, Juliane; Hauck, Stefanie M

    2016-02-01

    To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial

  19. Flecainide exerts paradoxical effects on sodium currents and atrial arrhythmia in murine RyR2-P2328S hearts

    PubMed Central

    Salvage, S C; King, J H; Chandrasekharan, K H; Jafferji, D I G; Guzadhur, L; Matthews, H R; Huang, C L-H; Fraser, J A

    2015-01-01

    Aims Cardiac ryanodine receptor mutations are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), and some, including RyR2-P2328S, also predispose to atrial fibrillation. Recent work associates reduced atrial Nav1.5 currents in homozygous RyR2-P2328S (RyR2S/S) mice with slowed conduction and increased arrhythmogenicity. Yet clinically, and in murine models, the Nav1.5 blocker flecainide reduces ventricular arrhythmogenicity in CPVT. We aimed to determine whether, and how, flecainide influences atrial arrhythmogenicity in RyR2S/S mice and their wild-type (WT) littermates. Methods We explored effects of 1 μm flecainide on WT and RyR2S/S atria. Arrhythmic incidence, action potential (AP) conduction velocity (CV), atrial effective refractory period (AERP) and AP wavelength (λ = CV × AERP) were measured using multi-electrode array recordings in Langendorff-perfused hearts; Na+ currents (INa) were recorded using loose patch clamping of superfused atria. Results RyR2S/S showed more frequent atrial arrhythmias, slower CV, reduced INa and unchanged AERP compared to WT. Flecainide was anti-arrhythmic in RyR2S/S but pro-arrhythmic in WT. It increased INa in RyR2S/S atria, whereas it reduced INa as expected in WT. It increased AERP while sparing CV in RyR2S/S, but reduced CV while sparing AERP in WT. Thus, RyR2S/S hearts have low λ relative to WT; flecainide then increases λ in RyR2S/S but decreases λ in WT. Conclusions Flecainide (1 μm) rescues the RyR2-P2328S atrial arrhythmogenic phenotype by restoring compromised INa and λ, changes recently attributed to increased sarcoplasmic reticular Ca2+ release. This contrasts with the increased arrhythmic incidence and reduced INa and λ with flecainide in WT. PMID:25850710

  20. Notch-independent RBPJ controls angiogenesis in the adult heart

    PubMed Central

    Díaz-Trelles, Ramón; Scimia, Maria Cecilia; Bushway, Paul; Tran, Danh; Monosov, Anna; Monosov, Edward; Peterson, Kirk; Rentschler, Stacey; Cabrales, Pedro; Ruiz-Lozano, Pilar; Mercola, Mark

    2016-01-01

    Increasing angiogenesis has long been considered a therapeutic target for improving heart function after injury such as acute myocardial infarction. However, gene, protein and cell therapies to increase microvascularization have not been successful, most likely because the studies failed to achieve regulated and concerted expression of pro-angiogenic and angiostatic factors needed to produce functional microvasculature. Here, we report that the transcription factor RBPJ is a homoeostatic repressor of multiple pro-angiogenic and angiostatic factor genes in cardiomyocytes. RBPJ controls angiogenic factor gene expression independently of Notch by antagonizing the activity of hypoxia-inducible factors (HIFs). In contrast to previous strategies, the cardiomyocyte-specific deletion of Rbpj increased microvascularization of the heart without adversely affecting cardiac structure or function even into old age. Furthermore, the loss of RBPJ in cardiomyocytes increased hypoxia tolerance, improved heart function and decreased pathological remodelling after myocardial infarction, suggesting that inhibiting RBPJ might be therapeutic for ischaemic injury. PMID:27357444

  1. Estimating Energy Expenditure from Heart Rate in Older Adults: A Case for Calibration

    PubMed Central

    Schrack, Jennifer A.; Zipunnikov, Vadim; Goldsmith, Jeff; Bandeen-Roche, Karen; Crainiceanu, Ciprian M.; Ferrucci, Luigi

    2014-01-01

    Background Accurate measurement of free-living energy expenditure is vital to understanding changes in energy metabolism with aging. The efficacy of heart rate as a surrogate for energy expenditure is rooted in the assumption of a linear function between heart rate and energy expenditure, but its validity and reliability in older adults remains unclear. Objective To assess the validity and reliability of the linear function between heart rate and energy expenditure in older adults using different levels of calibration. Design Heart rate and energy expenditure were assessed across five levels of exertion in 290 adults participating in the Baltimore Longitudinal Study of Aging. Correlation and random effects regression analyses assessed the linearity of the relationship between heart rate and energy expenditure and cross-validation models assessed predictive performance. Results Heart rate and energy expenditure were highly correlated (r = 0.98) and linear regardless of age or sex. Intra-person variability was low but inter-person variability was high, with substantial heterogeneity of the random intercept (s.d. = 0.372) despite similar slopes. Cross-validation models indicated individual calibration data substantially improves accuracy predictions of energy expenditure from heart rate, reducing the potential for considerable measurement bias. Although using five calibration measures provided the greatest reduction in the standard deviation of prediction errors (1.08 kcals/min), substantial improvement was also noted with two (0.75 kcals/min). Conclusion These findings indicate standard regression equations may be used to make population-level inferences when estimating energy expenditure from heart rate in older adults but caution should be exercised when making inferences at the individual level without proper calibration. PMID:24787146

  2. Ethanol consumption and early murine retrovirus infection influence liver, heart, and muscle levels of iron, zinc, and copper in C57BL/6 mice.

    PubMed

    Shahbazian, L M; Wood, S; Watson, R R

    1994-08-01

    The relative and combined roles of ethanol and murine acquired immunodeficiency syndrome (MAIDS) on the mineral status (Fe, Zn, and Cu) of liver (storage site), heart, muscle (nutrient mobile sites) were investigated. C57BL/6 mice were randomly assigned to four groups: (a) uninfected mice fed isocaloric, adequate nutrient diet (NRC), (b) uninfected mice fed the NRC diet with 25% of energy derived from ethanol, (c) LP-BM5 retrovirus-infected mice fed the isocaloric NRC diet, and (d) retrovirus-infected mice fed the NRC diet with 25% of its energy derived from ethanol. The levels of Cu and Zn levels in the liver did not significantly change as a result of ethanol consumption. However hepatic Zn concentration was increased significantly in retrovirus-infected mice. This may be correlated to the increase in their liver weight. Ethanol administration significantly increased Fe concentration in the liver, yet significantly decreased concentration of Cu in the heart. Retrovirus infection alone, which had not proceeded to murine AIDS, resulted in a significant increase in heart Cu and Zn concentration as compared with uninfected mice. Retrovirus infection in C57BL/6 mice significantly increased Fe and Zn level/g of muscle. Early retrovirus infection alters tissue micronutrient levels, and may thus contribute to immunological changes. PMID:7978111

  3. Telomerase expression confers cardioprotection in the adult mouse heart after acute myocardial infarction

    PubMed Central

    Serrano, Rosa; Tejera, Agueda; Ayuso, Eduard; Jimenez, Veronica; Formentini, Ivan; Bobadilla, Maria; Mizrahi, Jacques; de Martino, Alba; Gomez, Gonzalo; Pisano, David; Mulero, Francisca; Wollert, Kai C.; Bosch, Fatima; Blasco, Maria A.

    2016-01-01

    Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI. PMID:25519492

  4. Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family

    PubMed Central

    Porrello, Enzo R.; Mahmoud, Ahmed I.; Simpson, Emma; Johnson, Brett A.; Grinsfelder, David; Canseco, Diana; Mammen, Pradeep P.; Rothermel, Beverly A.; Olson, Eric N.; Sadek, Hesham A.

    2013-01-01

    We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity. PMID:23248315

  5. Isothiocyanates Ameliorate the Symptom of Heart Dysfunction and Mortality in a Murine AIDS Model by Inhibiting Apoptosis in the Left Ventricle

    PubMed Central

    Ho, Jin-Nyoung; Yoon, Ho-Geun; Park, Chang-Soo; Kim, Sunoh; Jun, Woojin; Choue, Ryowon

    2012-01-01

    Abstract Cardiac involvement has been reported in as many as 45–55% of patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS), and significant cardiac morbidity is reported in 6–7% of HIV patients. We investigated the inhibitory effects of isothiocyanates (ITCs) on heart dysfunction and mortality by regulating apoptosis in the left ventricle of the heart in a murine AIDS model. Mice were divided into six groups: an uninfected group, an untreated LP-BM5 retrovirus-infected group, and four LP-BM5 retrovirus-infected groups treated with one of four ITCs (sulforaphane [SUL], indolo[3,2-b]carbazole, benzyl isothiocyanate [BITC], or phenethyl isothiocyanate [PEITC]). After 16 weeks, the median survival time of the LP-BM5 retrovirus-infected mice was 87 days, whereas that of the uninfected control group and all ITC treatment groups was over 112 days. SUL, PEITC, and BITC significantly inhibited apoptosis in the left ventricle by increasing the Bcl-2/Bax ratio compared with LP-BM5-infected mice. In addition, SUL and PEITC suppressed inducible nitric oxide synthase (iNOS) expression at both the mRNA and protein levels in the left ventricle of heart tissue infected with the LP-BM5 retrovirus by inactivating cytoplasmic nuclear factor κB (NF-κB). In conclusion, LP-BM5 retrovirus infection was related to survival of murine AIDS mice, and NF-κB-mediated iNOS expression may be an important mediator of left ventricle dysfunction of the heart. Furthermore, certain ITCs may have the potential to improve AIDS-related heart dysfunction due to their inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB. PMID:22925072

  6. On-Pump Beating Heart Extraanatomical Ascending-Descending Aortic Bypass Using a Beating Heart Positioner in an Adult with Aortic Coarctation

    PubMed Central

    Gyoten, Takayuki; Nagura, Saori; Yamashita, Akio; Fukahara, Kazuaki; Kotoh, Keiju; Yoshimura, Naoki

    2016-01-01

    The prognosis of uncorrected aortic coarctation is poor due to development of heart failure. We performed an on-pump beating heart extraanatomical ascending-descending aortic bypass using a beating heart positioner in an adult with coarctation complicated by severe left ventricular hypertrophy. A 51-year-old woman was referred with severe hypertension. Computed tomography demonstrated severe distal aortic arch narrowing. Coarctation of the aorta was diagnosed. A posterior pericardial beating heart extraanatomical bypass via median sternotomy was performed from the ascending to descending aorta using a heart positioner. Her postoperative course was uneventful and blood pressure was normal on a low-dose beta-blocker. PMID:27087874

  7. Adult congenital heart disease: A paradigm of epidemiological change.

    PubMed

    Ntiloudi, Despοina; Giannakoulas, George; Parcharidou, Despοina; Panagiotidis, Theofilos; Gatzoulis, Michael A; Karvounis, Haralambos

    2016-09-01

    Increasing survival rates for patients with congenital heart disease (CHD) represent a major achievement of modern medicine. Despite incredible progress been made in diagnosis, follow-up, early treatment and management in adulthood, many patients are faced with long-term complications, such as arrhythmia, thromboembolism, heart failure, pulmonary hypertension, endocarditis and/or the need for reoperation. In parallel, half of the patients are female, most of childbearing age, and, thus warrant specialist reproductive counseling and appropriate obstetric care. It is not surprising therefore, that healthcare utilization has steadily increased for CHD in recent years. Furthermore, cardiology and other medical disciplines are now faced with new challenges, namely the provision of expert care and optimal, lifelong medical surveillance for these patients. PMID:27240150

  8. Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart

    PubMed Central

    de Preux Charles, Anne-Sophie; Bise, Thomas; Baier, Felix; Marro, Jan; Jaźwińska, Anna

    2016-01-01

    The adult heart is able to activate cardioprotective programmes and modifies its architecture in response to physiological or pathological changes. While mammalian cardiac remodelling often involves hypertrophic expansion, the adult zebrafish heart exploits hyperplastic growth. This capacity depends on the responsiveness of zebrafish cardiomyocytes to mitogenic signals throughout their entire life. Here, we have examined the role of inflammation on the stimulation of cell cycle activity in the context of heart preconditioning and regeneration. We used thoracotomy as a cardiac preconditioning model and cryoinjury as a model of cardiac infarction in the adult zebrafish. First, we performed a spatio-temporal characterization of leucocytes and cycling cardiac cells after thoracotomy. This analysis revealed a concomitance between the infiltration of inflammatory cells and the stimulation of the mitotic activity. However, decreasing the immune response using clodronate liposome injection, PLX3397 treatment or anti-inflammatory drugs surprisingly had no effect on the re-entry of cardiac cells into the cell cycle. In contrast, reducing inflammation using the same strategies after cryoinjury strongly impaired cardiac cell mitotic activity and the regenerative process. Taken together, our results show that, while the immune response is not necessary to induce cell-cycle activity in intact preconditioned hearts, inflammation is required for the regeneration of injured hearts in zebrafish. PMID:27440424

  9. A Statistically Enhanced Spectral Counting Approach to TCDD Cardiac Toxicity in the Adult Zebrafish Heart

    PubMed Central

    Zhang, Jiang; Lanham, Kevin A; Heideman, Warren; Peterson, Richard E.; Li, Lingjun

    2013-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant and teratogen that produces cardiac toxicity in the developing zebrafish. Here we adopted a label free quantitative proteomic approach based on normalized spectral abundance factor (NSAF) to investigate the disturbance of the cardiac proteome induced by TCDD in the adult zebrafish heart. The protein expression level changes between heart samples from TCDD treated and control zebrafish were systematically evaluated by a large scale MudPIT analysis which incorporated triplicate analyses for both control and TCDD exposed heart proteomic samples to overcome the data dependant variation in shotgun proteomic experiments and obtain a statistically significant protein dataset with improved quantification confidence. A total of 519 and 443 proteins were identified in hearts collected from control and TCDD treated zebrafish, respectively, among which 106 proteins showed statistically significant expression changes. After correcting for the experimental variation between replicate analyses by statistical evaluation, 55 proteins exhibited NSAF ratio above 2 and 43 proteins displayed NSAF ratio smaller than 0.5, with statistical significance by t-test (p < 0.05). The proteins identified as altered by TCDD encompass a wide range of biological functions including calcium handling, myocardium cell architecture, energy production and metabolism, mitochondrial homeostasis, and stress response. Collectively, our results indicate that TCDD exposure alters the adult zebrafish heart in a way that could result in cardiac hypertrophy and heart failure, and suggests a potential mechanism for the diastolic dysfunction observed in TCDD exposed embryos. PMID:23682714

  10. Understanding age-based transition needs: Perspectives from adolescents and adults with congenital heart disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to explore the transition process in congenital heart disease (CHD) care through the perceived needs and concerns of adolescents (pretransition) and the experiential insight from adults (post-transition), in order to inform future transition initiatives and information ...

  11. Metabolic Syndrome and Short-Term Heart Rate Variability in Adults with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Chang, Yaw-Wen; Lin, Jin-Ding; Chen, Wei-Liang; Yen, Chia-Feng; Loh, Ching-Hui; Fang, Wen-Hui; Wu, Li-Wei

    2012-01-01

    Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV…

  12. Lifestyle Modification for the Prevention of Morbidity and Mortality in Adult Congenital Heart Disease.

    PubMed

    Rosenthal, Todd M; Leung, Steven T; Ahmad, Raza; Young, Thomas; Lavie, Carl J; Moodie, Douglas S; Shah, Sangeeta

    2016-01-01

    Patients with adult congenital heart disease are now living longer due to the advancements in medicine. As such, these patients are now experiencing morbidities that are commonly seen in the general population such as myocardial infarction, heart failure, and arrhythmias. Often times these problems can be attributed to the underlying adult congenital heart disease; however, a patient making poor lifestyle choices only compounds their risk for these life-threatening comorbidities. The aim of this article is to propose recommendations for health care providers to follow with this specific patient population. These recommendations encompass the importance of proper caloric intake, methods of weight loss (including behavioral therapy, drugs, and surgeries), practical recommendations for physical activity, and the implications of substance abuse. Being proactive and addressing important lifestyle choices in this population can reduce comorbidities and, therefore, medical cost. PMID:26931766

  13. Conditional Ablation of Nonmuscle Myosin II-B Delineates Heart Defects in Adult Mice

    PubMed Central

    Ma, Xuefei; Takeda, Kazuyo; Singh, Aman; Yu, Zu-Xi; Zerfas, Patricia; Blount, Anthony; Liu, Chengyu; Towbin, Jeffrey A.; Schneider, Michael D.; Adelstein, Robert S.; Wei, Qize

    2009-01-01

    Rationale Germline ablation of the cytoskeletal protein nonmuscle myosin II-B (NMII-B) results in embryonic lethality with defects in both the brain and heart. Tissue specific ablation of NMII-B by a Cre-recombinase strategy should avoid embryonic lethality and permit study of the function of NMII-B in adult hearts. Objective To understand the function of NMII-B in adult mouse hearts and to see if the brain defects found in germline ablated mice influence cardiac development. Methods and Results We used a loxP/Cre-recombinase strategy to specifically ablate NMII-B in the brains or hearts of mice. Mice ablated for NMII-B in neural tissues, die between postnatal day 12 and 22 without showing cardiac defects. Mice deficient in NMII-B only in cardiac myocytes (BαMHC/BαMHC mice) do not show brain defects. However BαMHC/BαMHC mice display novel cardiac defects not seen in NMII-B germline ablated mice. Most of the BαMHC/BαMHC mice are born with enlarged cardiac myocytes some of which are multinucleated, reflecting a defect in cytokinesis. Between 6–10 months they develop a cardiomyopathy which includes interstitial fibrosis and infiltration of the myocardium and pericardium with inflammatory cells. Four of five BαMHC/BαMHC hearts develop marked widening of intercalated discs. Conclusion By avoiding the embryonic lethality found in germline-ablated mice we were able to study the function of NMII-B in adult mice and show that absence of NMII-B in cardiac myocytes results in cardiomyopathy in the adult heart. We also define a role for NMII-B in maintaining the integrity of intercalated discs. PMID:19815823

  14. Home health care with telemonitoring improves health status for older adults with heart failure.

    PubMed

    Madigan, Elizabeth; Schmotzer, Brian J; Struk, Cynthia J; DiCarlo, Christina M; Kikano, George; Piña, Ileana L; Boxer, Rebecca S

    2013-01-01

    Home telemonitoring can augment home health care services during a patient's transition from hospital to home. Home health care agencies commonly use telemonitors for patients with heart failure although studies have shown mixed results in the use of telemonitors to reduce rehospitalizations. This randomized trial investigated if older patients with heart failure admitted to home health care following a hospitalization would have a reduction in rehospitalizations and improved health status if they received telemonitoring. Patients were followed up to 180 days post-discharge from home health care services. Results showed no difference in the time to rehospitalization or emergency visit between those who received telemonitoring versus usual care. Older heart failure patients who received telemonitoring had better health status by home health care discharge than those who received usual care. Therefore, for older adults with heart failure, telemonitoring may be an important adjunct to home health care services to improve health status. PMID:23438509

  15. Cardiac regenerative potential of cardiosphere-derived cells from adult dog hearts

    PubMed Central

    Hensley, Michael Taylor; de Andrade, James; Keene, Bruce; Meurs, Kathryn; Tang, Junnan; Wang, Zegen; Caranasos, Thomas G; Piedrahita, Jorge; Li, Tao-Sheng; Cheng, Ke

    2015-01-01

    The regenerative potential of cardiosphere-derived cells (CDCs) for ischaemic heart disease has been demonstrated in mice, rats, pigs and a recently completed clinical trial. The regenerative potential of CDCs from dog hearts has yet to be tested. Here, we show that canine CDCs can be produced from adult dog hearts. These cells display similar phenotypes in comparison to previously studied CDCs derived from rodents and human beings. Canine CDCs can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in vitro. In addition, conditioned media from canine CDCs promote angiogenesis but inhibit cardiomyocyte death. In a doxorubicin-induced mouse model of dilated cardiomyopathy (DCM), intravenous infusion of canine CDCs improves cardiac function and decreases cardiac fibrosis. Histology revealed that injected canine CDCs engraft in the mouse heart and increase capillary density. Out study demonstrates the regenerative potential of canine CDCs in a mouse model of DCM. PMID:25854418

  16. Choosing Between MRI and CT Imaging in the Adult with Congenital Heart Disease.

    PubMed

    Bonnichsen, Crystal; Ammash, Naser

    2016-05-01

    Improvements in the outcomes of surgical and catheter-based interventions and medical therapy have led to a growing population of adult patients with congenital heart disease. Adult patients with previously undiagnosed congenital heart disease or those previously palliated or repaired may have challenging echocardiographic examinations. Understanding the distinct anatomic and hemodynamic features of the congenital anomaly and quantifying ventricular function and valvular dysfunction plays an important role in the management of these patients. Rapid advances in imaging technology with magnetic resonance imaging (MRI) and computed tomography angiography (CTA) allow for improved visualization of complex cardiac anatomy in the evaluation of this unique patient population. Although echocardiography remains the most widely used imaging tool to evaluate congenital heart disease, alternative and, at times, complimentary imaging modalities should be considered. When caring for adults with congenital heart disease, it is important to choose the proper imaging study that can answer the clinical question with the highest quality images, lowest risk to the patient, and in a cost-efficient manner. PMID:27002621

  17. Emerging Research Directions in Adult Congenital Heart Disease: A Report From an NHLBI/ACHA Working Group.

    PubMed

    Gurvitz, Michelle; Burns, Kristin M; Brindis, Ralph; Broberg, Craig S; Daniels, Curt J; Fuller, Stephanie M P N; Honein, Margaret A; Khairy, Paul; Kuehl, Karen S; Landzberg, Michael J; Mahle, William T; Mann, Douglas L; Marelli, Ariane; Newburger, Jane W; Pearson, Gail D; Starling, Randall C; Tringali, Glenn R; Valente, Anne Marie; Wu, Joseph C; Califf, Robert M

    2016-04-26

    Congenital heart disease (CHD) is the most common birth defect, affecting about 0.8% of live births. Advances in recent decades have allowed >85% of children with CHD to survive to adulthood, creating a growing population of adults with CHD. Little information exists regarding survival, demographics, late outcomes, and comorbidities in this emerging group, and multiple barriers impede research in adult CHD. The National Heart, Lung, and Blood Institute and the Adult Congenital Heart Association convened a multidisciplinary working group to identify high-impact research questions in adult CHD. This report summarizes the meeting discussions in the broad areas of CHD-related heart failure, vascular disease, and multisystem complications. High-priority subtopics identified included heart failure in tetralogy of Fallot, mechanical circulatory support/transplantation, sudden cardiac death, vascular outcomes in coarctation of the aorta, late outcomes in single-ventricle disease, cognitive and psychiatric issues, and pregnancy. PMID:27102511

  18. Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure.

    PubMed

    Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J; Yang, Jin; Donti, Taraka R; Harmancey, Romain; Vasquez, Hernan G; Graham, Brett H; Bellen, Hugo J; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y

    2015-01-01

    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. PMID:26356605

  19. Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure

    PubMed Central

    Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J.; Yang, Jin; Donti, Taraka R.; Harmancey, Romain; Vasquez, Hernan G.; Graham, Brett H.; Bellen, Hugo J.; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y.

    2015-01-01

    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy. PMID:26356605

  20. Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate responses to exercise in overweight adults.

    PubMed

    Ninio, Daniel M; Hill, Alison M; Howe, Peter R; Buckley, Jonathan D; Saint, David A

    2008-11-01

    Dietary fish oil supplementation and regular physical activity can improve outcomes in patients with established CVD. Exercise has been shown to improve heart rate variability (HRV), a predictor of cardiac death, but whether fish oil benefits HRV is controversial. Obese adults at risk of future coronary disease have impaired HRV and may benefit from these interventions. We evaluated the effect of DHA-rich tuna fish oil supplementation with and without regular exercise on HRV in sedentary, overweight adults with risk factors for coronary disease. In a randomised, double-blind, parallel comparison, sixty-five volunteers consumed 6 g fish oil/d (DHA 1.56 g/d, EPA 0.36 g/d) or sunflower-seed oil (placebo) for 12 weeks. Half of each oil group also undertook regular moderate physical activity (3 d/week for 45 min, at 75 % of age-predicted maximal heart rate (HR)). Resting HR and the HR response to submaximal exercise were measured at weeks 0, 6 and 12. In forty-six subjects, HRV was also assessed by power spectrum analysis of 20 min electrocardiogram recordings taken supine at baseline and 12 weeks. Fish oil supplementation improved HRV by increasing high-frequency power, representing parasympathetic activity, compared with placebo (P = 0.01; oil x time interaction). It also reduced HR at rest and during submaximal exercise (P = 0.008; oil x time interaction). There were no significant fish oil x exercise interactions. Dietary supplementation with DHA-rich fish oil reduced HR and modulated HRV in keeping with an improved parasympathetic-sympathetic balance in overweight adults with risk factors for future coronary disease. PMID:18339222

  1. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis.

    PubMed

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5'BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5'BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice. PMID

  2. Expression of slow skeletal TnI in adult mouse hearts confers metabolic protection to ischemia

    PubMed Central

    Pound, Kayla M.; Arteaga, Grace M.; Fasano, Mathew; Wilder, Tanganyika; Fischer, Susan K.; Warren, Chad M.; Wende, Adam R.; Farjah, Mariam; Abel, E. Dale; Solaro, R. John; Lewandowski, E. Douglas

    2011-01-01

    Changes in metabolic and myofilament phenotypes coincide in developing hearts. Posttranslational modification of sarcomere proteins influences contractility, affecting the energetic cost of contraction. However, metabolic adaptations to sarcomeric phenotypes are not well understood, particularly during pathophysiological stress. This study explored metabolic adaptations to expression of the fetal, slow skeletal muscle troponin I (ssTnI). Hearts expressing ssTnI exhibited no significant ATP loss during 5 minutes of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7 min ischemia TG-ssTnI hearts retained 80±12% of ATP vs. 49±6% in NTG (P<0.05). Hearts expressing ssTnI also had increased AMPK phosphorylation. The mechanism of ATP preservation was augmented glycolysis. Glycolytic end products (lactate and alanine) were 38% higher in TG-ssTnI than NTG at 2 min and 27% higher at 5 min. This additional glycolysis was supported exclusively by exogenous glucose, and not glycogen. Thus, expression of a fetal myofilament protein in adult mouse hearts induced elevated anaerobic ATP production during ischemia via metabolic adaptations consistent with the resistance to hypoxia of fetal hearts. The general findings hold important relevance to both our current understanding of the association between metabolic and contractile phenotypes and the potential for invoking cardioprotective mechanisms against ischemic stress. PMID:21640727

  3. The mitochondria-targeted anti-oxidant MitoQ decreases ischemia-reperfusion injury in a murine syngeneic heart transplant model

    PubMed Central

    Dare, Anna J.; Logan, Angela; Prime, Tracy A.; Rogatti, Sebastian; Goddard, Martin; Bolton, Eleanor M.; Bradley, J. Andrew; Pettigrew, Gavin J.; Murphy, Michael P.; Saeb-Parsy, Kourosh

    2015-01-01

    Background Free radical production and mitochondrial dysfunction during cardiac graft reperfusion is a major factor in post-transplant ischemia-reperfusion (IR) injury, an important underlying cause of primary graft dysfunction. We therefore assessed the efficacy of the mitochondria-targeted anti-oxidant MitoQ in reducing IR injury in a murine heterotopic cardiac transplant model. Methods Hearts from C57BL/6 donor mice were flushed with storage solution alone, solution containing the anti-oxidant MitoQ, or solution containing the non–anti-oxidant decyltriphenylphosphonium control and exposed to short (30 minutes) or prolonged (4 hour) cold preservation before transplantation. Grafts were transplanted into C57BL/6 recipients and analyzed for mitochondrial reactive oxygen species production, oxidative damage, serum troponin, beating score, and inflammatory markers 120 minutes or 24 hours post-transplant. Results MitoQ was taken up by the heart during cold storage. Prolonged cold preservation of donor hearts before IR increased IR injury (troponin I, beating score) and mitochondrial reactive oxygen species, mitochondrial DNA damage, protein carbonyls, and pro-inflammatory cytokine release 24 hours after transplant. Administration of MitoQ to the donor heart in the storage solution protected against this IR injury by blocking graft oxidative damage and dampening the early pro-inflammatory response in the recipient. Conclusions IR after heart transplantation results in mitochondrial oxidative damage that is potentiated by cold ischemia. Supplementing donor graft perfusion with the anti-oxidant MitoQ before transplantation should be studied further to reduce IR-related free radical production, the innate immune response to IR injury, and subsequent donor cardiac injury. PMID:26140808

  4. Real-Time Color-Flow CMR in Adults with Congenital Heart Disease

    PubMed Central

    de la Pena, Erasmo; Nguyen, Patricia K.; Nayak, Krishna S.; Yang, Phillip C.; Rosenthal, David N.; Hu, Bob S.; Pauly, John M.; McConnell, Michael V.

    2015-01-01

    CMR is valuable in the evaluation of congenital heart disease (CHD). Traditional flow imaging sequences involve cardiac and respiratory gating, increasing scan time and susceptibility to arrhythmias. We studied a real-time color-flow CMR system for the detection of flow abnormalities in 13 adults with CHD. All 16 congenital flow abnormalities previously detected by echocardiography were visualized using color-flow CMR, including atrial septal defects (n = 4), ventricular septal defects (n = 9), aortic coarctation (n = 1), Blalock-Taussig shunt (n = 1) and Fontan shunt (n = 1). Real-time color-flow CMR can identify intra- and extra-cardiac flow abnormalities in adults with congenital heart disease. PMID:17060103

  5. Global Gene Expression Profiling in PAI-1 Knockout Murine Heart and Kidney: Molecular Basis of Cardiac-Selective Fibrosis

    PubMed Central

    Ghosh, Asish K.; Murphy, Sheila B.; Kishore, Raj; Vaughan, Douglas E.

    2013-01-01

    Fibrosis is defined as an abnormal matrix remodeling due to excessive synthesis and accumulation of extracellular matrix proteins in tissues during wound healing or in response to chemical, mechanical and immunological stresses. At present, there is no effective therapy for organ fibrosis. Previous studies demonstrated that aged plasminogen activator inhibitor-1(PAI-1) knockout mice develop spontaneously cardiac-selective fibrosis without affecting any other organs. We hypothesized that differential expressions of profibrotic and antifibrotic genes in PAI-1 knockout hearts and unaffected organs lead to cardiac selective fibrosis. In order to address this prediction, we have used a genome-wide gene expression profiling of transcripts derived from aged PAI-1 knockout hearts and kidneys. The variations of global gene expression profiling were compared within four groups: wildtype heart vs. knockout heart; wildtype kidney vs. knockout kidney; knockout heart vs. knockout kidney and wildtype heart vs. wildtype kidney. Analysis of illumina-based microarray data revealed that several genes involved in different biological processes such as immune system processing, response to stress, cytokine signaling, cell proliferation, adhesion, migration, matrix organization and transcriptional regulation were affected in hearts and kidneys by the absence of PAI-1, a potent inhibitor of urokinase and tissue-type plasminogen activator. Importantly, the expressions of a number of genes, involved in profibrotic pathways including Ankrd1, Pi16, Egr1, Scx, Timp1, Timp2, Klf6, Loxl1 and Klotho, were deregulated in PAI-1 knockout hearts compared to wildtype hearts and PAI-1 knockout kidneys. While the levels of Ankrd1, Pi16 and Timp1 proteins were elevated during EndMT, the level of Timp4 protein was decreased. To our knowledge, this is the first comprehensive report on the influence of PAI-1 on global gene expression profiling in the heart and kidney and its implication in fibrogenesis and

  6. Quality of life and perceived health status in surviving adults with univentricular heart

    PubMed Central

    Saliba, Z; Butera, G; Bonnet, D; Bonhoeffer, P; Villain, E; Kachaner, J; Sidi, D; Iserin, L

    2001-01-01

    OBJECTIVE—To evaluate the quality of life in patients with univentricular heart and to determine the impact of sociodemographic and clinical characteristics.
DESIGN AND SETTING—Retrospective, cross sectional study conducted in a regional paediatric cardiology centre.
PATIENTS—The health records of 89 survivors with univentricular heart (median age 21 years; range 17-49 years) were reviewed. Sixty seven answered the Duke questionnaire. Sociodemographic and clinical variables were similar in the responders and non-responders. The impact of sociodemographic and clinical variables on individual Duke's measures was assessed.
RESULTS—The Duke scores of adults with univentricular heart were similar to the normal population. Cyanosis predicted a worse score for physical (p = 0.05) and perceived health measures (p = 0.02). A higher educational level predicted a better score for physical (p = 0.004), mental (p = 0.01), and general health measures (p = 0.02). Orthopaedic problems worsened the social score (p = 0.05). Psychosocial problems worsened the pain score (p = 0.04). In comparison with the other anatomical types, mitral atresia worsened the perceived health score (p = 0.02). Patients younger than 23 years scored better for almost all health and dysfunction measures.
CONCLUSIONS—Despite repeated interventions and other disease related everyday stresses, a selected group of adults with univentricular heart had a satisfying quality of life.


Keywords: congenital heart defect; quality of life; psychosocial problems; univentricular heart PMID:11410565

  7. Heart Rate Response During Underwater Treadmill Training in Adults with Incomplete Spinal Cord Injury

    PubMed Central

    Morgan, Don W.

    2015-01-01

    Background: Walking on a submerged treadmill can improve mobility in persons displaying lower limb muscle weakness and balance deficits. Little is known, however, regarding the effect of water treadmill exercise on cardiac performance in persons with incomplete spinal cord injury (iSCI). Objective: To assess heart rate response during underwater treadmill training (UTT) in adults with iSCI. Methods: Seven males and 4 females with iSCI (age = 48 ± 13 years; 5 ± 8 years after injury) completed 8 weeks of UTT (3 sessions per week; 3 walks per session) incorporating individually determined walking speeds, personalized levels of body weight unloading, and gradual, alternating increases in speed and duration. Heart rate was monitored during the last 15 seconds of the final 2 minutes of each walk. Results: Over the course of 3 biweekly periods in which walking speed remained constant, heart rate fell by 7% (7 ± 1 b•min-1; P < .001) in weeks 2 and 3, 14% (17 ± 6 b•min-1; P < .001) in weeks 4 and 5, and 17% (21 ± 11 b•min-1; P < .001) in weeks 6 and 7. Conclusion: In adults with iSCI, progressively greater absolute and relative reductions in submaximal exercise heart rate occurred after 2 months of UTT featuring a systematic increase in training volume. PMID:25762859

  8. Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARalpha in murine heart.

    PubMed

    Lu, Biao; Jiang, Yan J; Zhou, Yaling; Xu, Fred Y; Hatch, Grant M; Choy, Patrick C

    2005-01-15

    AGPAT (1-acyl-sn-glycerol 3-phosphate acyltransferase) exists in at least five isoforms in humans, termed as AGPAT1, AGPAT2, AGPAT3, AGPAT4 and AGPAT5. Although they catalyse the same biochemical reaction, their relative function, tissue expression and regulation are poorly understood. Linkage studies in humans have revealed that AGPAT2 contributes to glycerolipid synthesis and plays an important role in regulating lipid metabolism. We report the molecular cloning, tissue distribution, and enzyme characterization of mAGPATs (murine AGPATs) and regulation of cardiac mAGPATs by PPARalpha (peroxisome-proliferator-activated receptor alpha). mAGPATs demonstrated differential tissue expression profiles: mAGPAT1 and mAGPAT3 were ubiquitously expressed in most tissues, whereas mAGPAT2, mAGPAT4 and mAGPAT5 were expressed in a tissue-specific manner. mAGPAT2 expressed in in vitro transcription and translation reactions and in transfected COS-1 cells exhibited specificity for 1-acyl-sn-glycerol 3-phosphate. When amino acid sequences of five mAGPATs were compared, three highly conserved motifs were identified, including one novel motif/pattern KX2LX6GX12R. Cardiac mAGPAT activities were 25% lower (P<0.05) in PPARalpha null mice compared with wild-type. In addition, cardiac mAGPAT activities were 50% lower (P<0.05) in PPARalpha null mice fed clofibrate compared with clofibrate fed wild-type animals. This modulation of AGPAT activity was accompanied by significant enhancement/reduction of the mRNA levels of mAGPAT3/mAGPAT2 respectively. Finally, mRNA expression of cardiac mAGPAT3 appeared to be regulated by PPARalpha activation. We conclude that cardiac mAGPAT activity may be regulated by both the composition of mAGPAT isoforms and the levels of each isoform. PMID:15367102

  9. Improving Medication Knowledge among Older Adults with Heart Failure: A Patient-Centered Approach to Instruction Design

    ERIC Educational Resources Information Center

    Morrow, Daniel G.; Weiner, Michael; Young, James; Steinley, Douglas; Deer, Melissa; Murray, Michael D.

    2005-01-01

    Purpose: We investigated whether patient-centered instructions for chronic heart failure medications increase comprehension and memory for medication information in older adults diagnosed with chronic heart failure. Design and Methods: Patient-centered instructions for familiar and unfamiliar medications were compared with instructions for the…

  10. In Vitro Colony Assays for Characterizing Tri-potent Progenitor Cells Isolated from the Adult Murine Pancreas.

    PubMed

    Tremblay, Jacob R; LeBon, Jeanne M; Luo, Angela; Quijano, Janine C; Wedeken, Lena; Jou, Kevin; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2016-01-01

    Stem and progenitor cells from the adult pancreas could be a potential source of therapeutic beta-like cells for treating patients with type 1 diabetes. However, it is still unknown whether stem and progenitor cells exist in the adult pancreas. Research strategies using cre-lox lineage-tracing in adult mice have yielded results that either support or refute the idea that beta cells can be generated from the ducts, the presumed location where adult pancreatic progenitors may reside. These in vivo cre-lox lineage-tracing methods, however, cannot answer the questions of self-renewal and multi-lineage differentiation-two criteria necessary to define a stem cell. To begin addressing this technical gap, we devised 3-dimensional colony assays for pancreatic progenitors. Soon after our initial publication, other laboratories independently developed a similar, but not identical, method called the organoid assay. Compared to the organoid assay, our method employs methylcellulose, which forms viscous solutions that allow the inclusion of extracellular matrix proteins at low concentrations. The methylcellulose-containing assays permit easier detection and analyses of progenitor cells at the single-cell level, which are critical when progenitors constitute a small sub-population, as is the case for many adult organ stem cells. Together, results from several laboratories demonstrate in vitro self-renewal and multi-lineage differentiation of pancreatic progenitor-like cells from mice. The current protocols describe two methylcellulose-based colony assays to characterize mouse pancreatic progenitors; one contains a commercial preparation of murine extracellular matrix proteins and the other an artificial extracellular matrix protein known as a laminin hydrogel. The techniques shown here are 1) dissociation of the pancreas and sorting of CD133(+)Sox9/EGFP(+) ductal cells from adult mice, 2) single cell manipulation of the sorted cells, 3) single colony analyses using microfluidic q

  11. Fate Analysis of Adult Hippocampal Progenitors in a Murine Model of Fetal Alcohol Spectrum Disorder (FASD)

    PubMed Central

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreERT2/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access “drinking-in-the-dark” model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A–B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  12. Fate analysis of adult hippocampal progenitors in a murine model of fetal alcohol spectrum disorder (FASD).

    PubMed

    Kajimoto, Kenta; Allan, Andrea; Cunningham, Lee Anna

    2013-01-01

    Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and associated behavioral impairments that may be linked to disruptions in adult hippocampal neurogenesis. Social and physical enrichment has been proposed as a potential therapeutic approach toward reversing behavioral deficits associated with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In the present study, we utilized a genetic fate mapping approach in nestin-CreER(T2)/YFP bitransgenic mice to identify the stage-specific impact of prenatal alcohol exposure on the stepwise maturation of adult hippocampal progenitors. Using a limited alcohol access "drinking-in-the-dark" model of FASD, we confirm previous findings that moderate prenatal alcohol exposure has no effect on adult neurogenesis under standard housing conditions, but abolishes the neurogenic response to enriched environment (EE). Furthermore, we demonstrate that this effect is primarily due to failed EE-mediated survival of postmitotic neurons. Finally, we demonstrate that the neurogenic deficit is associated with impaired spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice in an A-B contextual discrimination task. These results identify a potential maturational stage-specific mechanism(s) underlying impaired neurogenic function in a preclinical model of FASD, and provide a basis for testing regulatory pathways in this model through conditional and inducible manipulation of gene expression in the adult hippocampal progenitor population. PMID:24040071

  13. Dietary Interventions for Heart Failure in Older Adults: Re-emergence of the Hedonic Shift

    PubMed Central

    Wessler, Jeffrey D.; Hummel, Scott L.; Maurer, Mathew S.

    2014-01-01

    Dietary non-adherence to sodium restriction is an important contribution to heart failure (HF) symptom burden, particularly in older adults. While knowledge, skills, and attitudes towards sodium restriction are important, sodium intake is closely linked to the ability to taste salt. The ‘hedonic shift’ occurs when sodium restriction induces changes in an individual’s salt taste that lower subsequent salt affinity. Older adults often have compromised salt taste and higher dietary salt affinity due to age-related changes. Older HF patients may have additional loss of salt taste and elevated salt appetite due to comorbid conditions, medication use, and micronutrient or electrolyte abnormalities, creating a significant barrier to dietary adherence. Induction of the hedonic shift has the potential to improve long-term dietary sodium restriction and significantly impact HF outcomes in older adults. PMID:25216615

  14. Hypocellularity in the Murine Model for Down Syndrome Ts65Dn Is Not Affected by Adult Neurogenesis

    PubMed Central

    López-Hidalgo, Rosa; Ballestín, Raul; Vega, Jessica; Blasco-Ibáñez, José M.; Crespo, Carlos; Gilabert-Juan, Javier; Nácher, Juan; Varea, Emilio

    2016-01-01

    Down syndrome (DS) is caused by the presence of an extra copy of the chromosome 21 and it is the most common aneuploidy producing intellectual disability. Neural mechanisms underlying this alteration may include defects in the formation of neuronal networks, information processing and brain plasticity. The murine model for DS, Ts65Dn, presents reduced adult neurogenesis. This reduction has been suggested to underlie the hypocellularity of the hippocampus as well as the deficit in olfactory learning in the Ts65Dn mice. Similar alterations have also been observed in individuals with DS. To determine whether the impairment in adult neurogenesis is, in fact, responsible for the hypocellularity in the hippocampus and physiology of the olfactory bulb, we have analyzed cell proliferation and neuronal maturation in the two major adult neurogenic niches in the Ts656Dn mice: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Additionally, we carried out a study to determine the survival rate and phenotypic fate of newly generated cells in both regions, injecting 5′BrdU and sacrificing the mice 21 days later, and analyzing the number and phenotype of the remaining 5′BrdU-positive cells. We observed a reduction in the number of proliferating (Ki67 positive) cells and immature (doublecortin positive) neurons in the subgranular and SVZ of Ts65Dn mice, but we did not observe changes in the number of surviving cells or in their phenotype. These data correlated with a lower number of apoptotic cells (cleaved caspase 3 positive) in Ts65Dn. We conclude that although adult Ts65Dn mice have a lower number of proliferating cells, it is compensated by a lower level of cell death. This higher survival rate in Ts65Dn produces a final number of mature cells similar to controls. Therefore, the reduction of adult neurogenesis cannot be held responsible for the neuronal hypocellularity in the hippocampus or for the olfactory learning deficit of Ts65Dn mice

  15. Adult cardiac fibroblast proliferation is modulated by calcium/calmodulin-dependent protein kinase II in normal and hypertrophied hearts.

    PubMed

    Martin, Tamara P; Lawan, Ahmed; Robinson, Emma; Grieve, David J; Plevin, Robin; Paul, Andrew; Currie, Susan

    2014-02-01

    Increased adult cardiac fibroblast proliferation results in an increased collagen deposition responsible for the fibrosis accompanying pathological remodelling of the heart. The mechanisms regulating cardiac fibroblast proliferation remain poorly understood. Using a minimally invasive transverse aortic banding (MTAB) mouse model of cardiac hypertrophy, we have assessed fibrosis and cardiac fibroblast proliferation. We have investigated whether calcium/calmodulin-dependent protein kinase IIδ (CaMKIIδ) regulates proliferation in fibroblasts isolated from normal and hypertrophied hearts. It is known that CaMKIIδ plays a central role in cardiac myocyte contractility, but nothing is known of its role in adult cardiac fibroblast function. The MTAB model used here produces extensive hypertrophy and fibrosis. CaMKIIδ protein expression and activity is upregulated in MTAB hearts and, specifically, in cardiac fibroblasts isolated from hypertrophied hearts. In response to angiotensin II, cardiac fibroblasts isolated from MTAB hearts show increased proliferation rates. Inhibition of CaMKII with autocamtide inhibitory peptide inhibits proliferation in cells isolated from both sham and MTAB hearts, with a significantly greater effect evident in MTAB cells. These results are the first to show selective upregulation of CaMKIIδ in adult cardiac fibroblasts following cardiac hypertrophy and to assign a previously unrecognised role to CaMKII in regulating adult cardiac fibroblast function in normal and diseased hearts. PMID:23881186

  16. The Relationship Between Nurse Staffing and 30-Day Readmission for Adults With Heart Failure

    PubMed Central

    Giuliano, Karen K.; Danesh, Valerie; Funk, Marjorie

    2016-01-01

    OBJECTIVE The purpose of this study was to better understand the relationship between nurse staffing and 30-day excess readmission ratios for patients with heart failure in the top US adult cardiology and heart surgery hospitals. BACKGROUND Heart failure is the most common cause of hospitalization for patients older than 65 years and is the most frequent diagnosis associated with 30-day hospital readmission in the United States. METHODS A secondary data analysis was conducted using nurse staffing data from 661 cardiology and heart surgery hospitals from the 2013 US News & World Report “Best Hospitals” survey. These data were combined with excess readmission ratios from the Centers for Medicare & Medicaid Services Hospital Compare database from 2013. An independent-samples t test was used to compare staffing (low/high) and excess hospital readmissions rates. RESULTS A significant difference (P = .021) was found between the low nurse staffing group (n = 358) and the high nurse staffing group (n = 303). Hospitals with a lower nurse staffing index had a significantly higher excess readmission rate. CONCLUSION These data provide further support to the body of research showing a positive relationship between nurse staffing and positive outcomes. PMID:26579974

  17. Life experiences and coping strategies in adults with congenital heart disease.

    PubMed

    Callus, E; Quadri, E; Compare, A; Tovo, A; Giamberti, A; Chessa, M

    2013-01-01

    Many adults with congenital heart disease (ACHD) have to face considerable psychosocial difficulties. The aim of this study was to explore the life experiences of ACHD patients, from when they become aware of having a condition, till after the open heart surgery they underwent. The study was conducted with the use of unstructured, in-depth interviews, performed on 11 patients (age ranging: 20 - 56 y) after they recovered from open heart surgery and a focus group, which included 16 participants (age ranging: 22 - 46 y). Both the interviews and the focus group were recorded, transcribed and analyzed according to Grounded Theory procedures. Our findings show that the condition of diversity is the core of the emotional experiences connected to ACHD. Feeling different and being perceived as being different are clearly interlinked and coping strategies adopted resulted as being influenced by this perception. This study also clearly outlines the importance of having an adequate perception of one's condition and the link between maladaptive coping strategies and an incorrect perception of one's heart condition. Results are discussed in order to promote psychosocial interventions within and outside of the hospital setting in order to improve the patients' emotional wellbeing. PMID:24516946

  18. Association between risk factors for coronary heart disease in schoolboys and adult mortality rates in the same localities.

    PubMed Central

    Freeman, W; Weir, D C; Whitehead, J E; Rogers, D I; Sapiano, S B; Floyd, C A; Kirk, P M; Stalker, C R; Field, N J; Cayton, R M

    1990-01-01

    Risk factors for coronary heart disease were compared in fifth year boys (15-16 years old) from two schools that were chosen from localities with a fourfold difference in adult mortality from coronary heart disease. One school was in an underprivileged urban locality in the area of increased incidence of heart disease ('high risk') and the other in a semi-rural affluent locality with an incidence of heart disease similar to the national average ('low risk'). Smoking, hypertension, hypercholesterolaemia, obesity, physical fitness, and inactivity were evaluated as risk factors for coronary heart disease. Smoking, increased body fat, poor diet, and physical inactivity were found increased among pupils from the school in the high risk area compared with those in the low risk area. Lipids, maximum oxygen uptake, and hypertension were similar in both schools. The risk of coronary heart disease seems to reflect the adult mortality rates in the area. To reduce the overall incidence of coronary heart disease, health education should be directed towards prevention of smoking, improving diets, and increasing amounts of activity among school children, with special attention directed toward children in regions where there is a high mortality from coronary heart disease among adults. PMID:2301987

  19. December 2014 HeartWeek issue of cardiology in the young: highlights of HeartWeek 2014: diseases of the cardiac valves from the foetus to the adult.

    PubMed

    Jacobs, Jeffrey P

    2014-12-01

    This December Issue of Cardiology in the Young represents the 12th annual publication generated from the two meetings that compose "HeartWeek in Florida". "HeartWeek in Florida", the joint collaborative project sponsored by the Cardiac Center at the Children's Hospital of Philadelphia, Pennsylvania, together with Johns Hopkins All Children's Heart Institute of Saint Petersburg, Florida, averages over 1000 attendees every year and is now recognised as one of the major planks of continuing medical and nursing education for those working in the fields of diagnosis and treatment of cardiac disease in the foetus, neonate, infant, child, and adult. "HeartWeek in Florida" combines the International Symposium on Congenital Heart Disease, organised by All Children's Hospital and Johns Hopkins Medicine and entering its 15th year, with the Annual Postgraduate Course in Pediatric Cardiovascular Disease, organised by The Children's Hospital of Philadelphia and entering its 18th year. This December, 2014 Issue of Cardiology in the Young features highlights of Johns Hopkins All Children's Heart Institute's 14th Annual International Symposium on Congenital Heart Disease, which was held at the Renaissance Vinoy Resort & Golf Club, Saint Petersburg, Florida, from 15-18 February, 2014. This Symposium was co-sponsored by The American Association for Thoracic Surgery (AATS) and had as its special focus " Diseases of the Cardiac Valves from the Fetus to the Adult ". We acknowledge the tremendous contributions made to paediatric and congenital cardiac care by Duke Cameron and Joel Brenner, and therefore we dedicate this December, 2014 HeartWeek Issue of Cardiology in the Young to them. Duke Cameron is Professor of Surgery at Johns Hopkins University and Cardiac Surgeon-in-Charge at The Johns Hopkins Hospital. Joel Brenner is Professor of Pediatrics at Johns Hopkins University and Director of the Taussig Heart Center at Bloomberg Children's Center, The Johns Hopkins Hospital. Together

  20. What is the Best Measure of Daytime Sleepiness in Adults with Heart Failure?

    PubMed Central

    Riegel, Barbara; Hanlon, Alexandra L.; Zhang, Xuemei; Fleck, Desiree; Sayers, Steven L.; Goldberg, Lee R.; Weintraub, William S.

    2014-01-01

    Purpose To identify the best screening measure of daytime sleepiness in adults with heart failure (HF). Data sources 280 adults with HF completed the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, and a single Likert item measuring daytime sleepiness. The sensitivity and specificity of these self-report measures were assessed in relation to a measure of daytime dysfunction from poor sleep quality. Conclusions Only 16% of the sample reported significant daytime dysfunction due to poor sleep quality. Those reporting daytime dysfunction were likely to be younger (p<0.001), to be unmarried (p=0.002), to have New York Heart Association (NYHA) functional class IV HF (p=0.015), and to report low income (p=0.006) and fewer hours of sleep (p=0.015). The measure of daytime sleepiness that was most sensitive to daytime dysfunction was a single Likert item measured on a 10-point (1–10) scale. Patients with a score ≥ 4 were 2.4 times more likely to have daytime dysfunction than those with a score <4. Implications for practice Complaints of daytime dysfunction due to poor sleep are not common in adults with HF. Routine use of a single question about daytime sleepiness can help nurse practitioners to identify those HF patients with significant sleep issues that may require further screening. PMID:24170569

  1. Ablating hedgehog signaling in tenocytes during development impairs biomechanics and matrix organization of the adult murine patellar tendon enthesis

    PubMed Central

    Aschbacher‐Smith, Lindsey; Lu, Yinhui; Dyment, Nathaniel A.; Liu, Chia‐Feng; Liu, Han; Wylie, Chris; Rao, Marepalli; Shearn, Jason T.; Rowe, David W.; Kadler, Karl E.; Jiang, Rulang; Butler, David L.

    2015-01-01

    ABSTRACT Restoring the native structure of the tendon enthesis, where collagen fibers of the midsubstance are integrated within a fibrocartilaginous structure, is problematic following injury. As current surgical methods fail to restore this region adequately, engineers, biologists, and clinicians are working to understand how this structure forms as a prerequisite to improving repair outcomes. We recently reported on the role of Indian hedgehog (Ihh), a novel enthesis marker, in regulating early postnatal enthesis formation. Here, we investigate how inactivating the Hh pathway in tendon cells affects adult (12‐week) murine patellar tendon (PT) enthesis mechanics, fibrocartilage morphology, and collagen fiber organization. We show that ablating Hh signaling resulted in greater than 100% increased failure insertion strain (0.10 v. 0.05 mm/mm, p<0.01) as well as sub‐failure biomechanical deficiencies. Although collagen fiber orientation appears overtly normal in the midsubstance, ablating Hh signaling reduces mineralized fibrocartilage by 32%, leading to less collagen embedded within mineralized tissue. Ablating Hh signaling also caused collagen fibers to coalesce at the insertion, which may explain in part the increased strains. These results indicate that Ihh signaling plays a critical role in the mineralization process of fibrocartilaginous entheses and may be a novel therapeutic to promote tendon‐to‐bone healing. © 2015 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 33:1142–1151, 2015. PMID:25807894

  2. Wnts are dispensable for differentiation and self-renewal of adult murine hematopoietic stem cells

    PubMed Central

    Kabiri, Zahra; Numata, Akihiko; Kawasaki, Akira; Tenen, Daniel G.

    2015-01-01

    Wnt signaling controls early embryonic hematopoiesis and dysregulated β-catenin is implicated in leukemia. However, the role of Wnts and their source in adult hematopoiesis is still unclear, and is clinically important as upstream Wnt inhibitors enter clinical trials. We blocked Wnt secretion in hematopoietic lineages by targeting Porcn, a membrane-bound O-acyltransferase that is indispensable for the activity and secretion of all vertebrate Wnts. Surprisingly, deletion of Porcn in Rosa-CreERT2/PorcnDel, MX1-Cre/PorcnDel, and Vav-Cre/PorcnDel mice had no effects on proliferation, differentiation, or self-renewal of adult hematopoietic stem cells. Targeting Wnt secretion in the bone marrow niche by treatment with a PORCN inhibitor, C59, similarly had no effect on hematopoiesis. These results exclude a role for hematopoietic PORCN-dependent Wnts in adult hematopoiesis. Clinical use of upstream Wnt inhibitors is not likely to be limited by effects on hematopoiesis. PMID:26089398

  3. Advanced Echocardiography in Adult Zebrafish Reveals Delayed Recovery of Heart Function after Myocardial Cryoinjury

    PubMed Central

    Kossack, Mandy; Juergensen, Lonny; Fuchs, Dieter; Katus, Hugo A.; Hassel, David

    2015-01-01

    Translucent zebrafish larvae represent an established model to analyze genetics of cardiac development and human cardiac disease. More recently adult zebrafish are utilized to evaluate mechanisms of cardiac regeneration and by benefiting from recent genome editing technologies, including TALEN and CRISPR, adult zebrafish are emerging as a valuable in vivo model to evaluate novel disease genes and specifically validate disease causing mutations and their underlying pathomechanisms. However, methods to sensitively and non-invasively assess cardiac morphology and performance in adult zebrafish are still limited. We here present a standardized examination protocol to broadly assess cardiac performance in adult zebrafish by advancing conventional echocardiography with modern speckle-tracking analyses. This allows accurate detection of changes in cardiac performance and further enables highly sensitive assessment of regional myocardial motion and deformation in high spatio-temporal resolution. Combining conventional echocardiography measurements with radial and longitudinal velocity, displacement, strain, strain rate and myocardial wall delay rates after myocardial cryoinjury permitted to non-invasively determine injury dimensions and to longitudinally follow functional recovery during cardiac regeneration. We show that functional recovery of cryoinjured hearts occurs in three distinct phases. Importantly, the regeneration process after cryoinjury extends far beyond the proposed 45 days described for ventricular resection with reconstitution of myocardial performance up to 180 days post-injury (dpi). The imaging modalities evaluated here allow sensitive cardiac phenotyping and contribute to further establish adult zebrafish as valuable cardiac disease model beyond the larval developmental stage. PMID:25853735

  4. Impaired Transcriptional Response of the Murine Heart to Cigarette Smoke in the Setting of High Fat Diet and Obesity

    SciTech Connect

    Tilton, Susan C.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Mikheev, Vladimir B.; Lee, K. M.; Corley, Richard A.; Pounds, Joel G.; Bigelow, Diana J.

    2013-07-01

    Smoking and obesity are each well-established risk factors for cardiovascular heart disease, which together impose earlier onset and greater severity of disease. To identify early signaling events in the response of the heart to cigarette smoke exposure within the setting of obesity, we exposed normal weight and high fat diet-induced obese (DIO) C57BL/6 mice to repeated inhaled doses of mainstream (MS) or sidestream (SS) cigarette smoke administered over a two week period, monitoring effects on both cardiac and pulmonary transcriptomes. MS smoke (250 μg wet total particulate matter (WTPM)/L, 5 h/day) exposures elicited robust cellular and molecular inflammatory responses in the lung with 1466 differentially expressed pulmonary genes (p < 0.01) in normal weight animals and a much-attenuated response (463 genes) in the hearts of the same animals. In contrast, exposures to SS smoke (85 μg WTPM/L) with a CO concentration equivalent to that of MS smoke (250 CO ppm) induced a weak pulmonary response (328 genes) but an extensive cardiac response (1590 genes). SS smoke and to a lesser extent MS smoke preferentially elicited hypoxia- and stress-responsive genes as well as genes predicting early changes of vascular smooth muscle and endothelium, precursors of cardiovascular disease. The most sensitive smoke-induced cardiac transcriptional changes of normal weight mice were largely absent in DIO mice after smoke exposure, while genes involved in fatty acid utilization were unaffected. At the same time, smoke exposure suppressed multiple proteome maintenance genes induced in the hearts of DIO mice. Together, these results underscore the sensitivity of the heart to SS smoke and reveal adaptive responses in healthy individuals that are absent in the setting of high fat diet and obesity.

  5. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Colín-Castelán, Dannia; Ramírez-Santos, Jesús; Gutiérrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. PMID:26492830

  6. Pharmacological analysis of epithelial chloride secretion mechanisms in adult murine airways.

    PubMed

    Gianotti, Ambra; Ferrera, Loretta; Philp, Amber R; Caci, Emanuela; Zegarra-Moran, Olga; Galietta, Luis J V; Flores, Carlos A

    2016-06-15

    Defective epithelial chloride secretion occurs in humans with cystic fibrosis (CF), a genetic defect due to loss of function of CFTR, a cAMP-activated chloride channel. In the airways, absence of an active CFTR causes a severe lung disease. In mice, genetic ablation of CFTR function does not result in similar lung pathology. This may be due to the expression of an alternative chloride channel which is activated by calcium. The most probable protein performing this function is TMEM16A, a calcium-activated chloride channel (CaCC). Our aim was to assess the relative contribution of CFTR and TMEM16A to chloride secretion in adult mouse trachea. For this purpose we tested pharmacological inhibitors of chloride channels in normal and CF mice. The amplitude of the cAMP-activated current was similar in both types of animals and was not affected by a selective CFTR inhibitor. In contrast, a CaCC inhibitor (CaCCinh-A01) strongly blocked the cAMP-activated current as well as the calcium-activated chloride secretion triggered by apical UTP. Although control experiments revealed that CaCCinh-A01 also shows inhibitory activity on CFTR, our results indicate that transepithelial chloride secretion in adult mouse trachea is independent of CFTR and that another channel, possibly TMEM16A, performs both cAMP- and calcium-activated chloride transport. The prevalent function of a non-CFTR channel may explain the absence of a defect in chloride transport in CF mice. PMID:27063443

  7. Prenatal exposure to lipopolysaccharide results in myocardial remodelling in adult murine offspring

    PubMed Central

    2013-01-01

    Background The epigenetic plasticity hypothesis indicates that pregnancy exposure may result in adult-onset diseases, including hypertension, diabetes and cardiovascular disease, in offspring. In a previous study, we discovered that prenatal exposure to inflammatory stimulants, such as lipopolysaccharides (LPS), could lead to hypertension in adult rat offspring. In the present study, we further demonstrate that maternal inflammation induces cardiac hypertrophy and dysfunction via ectopic over-expression of nuclear transcription factor κB (NF- κB), and pyrrolidine dithiocarbamate (PDTC) can protect cardiac function by reducing maternal inflammation. Methods Pregnant SD rats were randomly divided into three groups and intraperitoneally injected with a vehicle, LPS (0.79 mg/kg), or LPS (0.79 mg/kg) plus PDTC (100 mg/kg) at 8 to 12 days of gestation. The offspring were raised until 4 and 8 months old, at which point an echocardiographic study was performed. The left ventricular (LV) mass index and apoptosis were examined. Results At 4 months of age, the LPS offspring exhibited augmented posterior wall thickness. These rats displayed left ventricle (LV) hypertrophy and LV diastolic dysfunction as well as a higher apoptotic index, a higher level of Bax and a lower level of Bcl-2 at 8 months of age. The protein levels of NF-κB (p65) in the myocardium of the offspring were measured at this time. NF-κB protein levels were higher in the myocardium of LPS offspring. The offspring that were prenatally treated with PDTC displayed improved signs of blood pressure (BP) and LV hypertrophy. Conclusions Maternal inflammation can induce cardiac hypertrophy in offspring during aging accompanied with hypertension emergence and can be rescued by the maternal administration of PDTC (the inhibitor of NF-κB). PMID:24764457

  8. Toxoplasma gondii Myocarditis after Adult Heart Transplantation: Successful Prophylaxis with Pyrimethamine

    PubMed Central

    Strabelli, Tania Mara V.; Siciliano, Rinaldo Focaccia; Vidal Campos, Silvia; Bianchi Castelli, Jussara; Bacal, Fernando; Bocchi, Edimar A.; Uip, David E.

    2012-01-01

    Toxoplasma gondii primary infection/reactivation after solid organ transplantation is a serious complication, due to the high mortality rate following disseminated disease. We performed a retrospective study of all cases of T. gondii infections in 436 adult patients who had received an orthotopic cardiac transplant at our Institution from May 1968 to January 2011. Six patients (1.3%) developed T. gondii infection/reactivation in the post-operative period. All infections/reactivations occurred before 1996, when no standardized toxoplasmosis prophylactic regimen or co-trimoxazole prophylaxis was used. Starting with the 112th heart transplant, oral pyrimethamine 75 mg/day was used for seronegative transplant recipients whose donors were seropositive or unknown. Two patients (33.3%) presented with disseminated toxoplasmosis infection, and all patients (100%) had myocarditis. Five patients (83.3%) were seronegative before transplant and one patient did not have pre-transplant serology available. Median time for infection onset was 131 days following transplantation. Three patients (50%) died due to toxoplasmosis infection. After 1996, we did not observe any additional cases of T. gondii infection/reactivation. In conclusion, toxoplasmosis in heart allographs was more frequent among seronegative heart recipients, and oral pyrimethamine was highly effective for the prevention of T. gondii infection in this population. PMID:23209479

  9. Challenges Caring for Adults With Congenital Heart Disease in Pediatric Settings: How Nurses Can Aid in the Transition.

    PubMed

    Anton, Kristin

    2016-08-01

    As surgery for complex congenital heart disease is becoming more advanced, an increasing number of patients are surviving into adulthood, yet many of these adult patients remain in the pediatric hospital system. Caring for adult patients is often a challenge for pediatric nurses, because the nurses have less experience and comfort with adult care, medications, comorbid conditions, and rehabilitation techniques. As these patients age, the increased risk of complications and comorbid conditions from their heart disease may complicate their care further. Although these patients are admitted on a pediatric unit, nurses can aid in promoting their independence and help prepare them to transition into the adult medical system. Nurses, the comprehensive medical teams, and patients' families can all effectively influence the process of preparing these patients for transition to adult care. PMID:27481810

  10. Increased Mitochondrial Pro-oxidant Activity Mediates Up-regulation of Complex I S-glutathionylation via Protein Thiyl Radical in the Murine Heart of eNOS−/−

    PubMed Central

    Kang, Patrick T.; Chen, Chwen-Lih; Chen, Yeong-Renn

    2014-01-01

    In response to oxidative stress, mitochondrial Complex I is reversibly S-glutathionylated. We hypothesized that protein S-glutathionylation (PrSSG) of Complex I is mediated by a kinetic mechanism involving reactive protein thiyl radical (PrS•) and GSH in vivo. Previous studies have shown that in vitro S-glutathionylation of isolated Complex I at the 51 kDa and 75 kDa subunits was detected under the conditions of •O2− production, and mass spectrometry confirmed that formation of Complex I PrS• mediates PrSSG. Exposure of myocytes to menadione resulted in enhanced Complex I PrSSG and PrS• (Kang et al Free Radical Biol. Med. 2012; 52: 962–73). In this investigation, we tested our hypothesis in the murine heart of eNOS−/−. The eNOS−/− mouse is known to be hypertensive and develops the pathological phenotype of progressive cardiac hypertrophy. The mitochondria isolated from the eNOS−/− myocardium exhibited a marked dysfunction with impaired state 3 respiration, a declining respiratory control index, and decreasing enzymatic activities of ETC components. Further biochemical analysis and EPR measurement indicated defective aconitase activity, a marked increase in •O2− generation activity, and a more oxidized physiological setting. These results suggest increasing prooxidant activity and subsequent oxidative stress in the mitochondria of the eNOS−/− murine heart. When Complex I from the mitochondria of the eNOS−/− murine heart was analyzed by immuno-spin trapping and probed with anti-GSH antibody, both PrS• and PrSSG of Complex I were significantly enhanced. Overexpression of SOD2 in the murine heart dramatically diminished the detected PrS•, supporting the conclusion that mediation of Complex I PrSSG by oxidative stress-induced PrS• is a unique pathway for the redox regulation of mitochondrial function in vivo. PMID:25445401

  11. Perspectives of Puerto Rican Adults about Heart Health and a Potential Community Program

    PubMed Central

    Todorova, Irina L.G.; Tejada, Shirley; Castaneda-Sceppa, Carmen

    2015-01-01

    Background Puerto Ricans are the second largest Hispanic group in the U.S. and older adults have significant health disparities. Educational programs that address heart disease risk for this population have rarely been developed and implemented. Purpose To address this gap, the Heart Healthy Initiative for Puerto Rican adults is being developed. To develop it as a participatory program, the community members were asked about their perspectives. Methods Five focus groups with 28 participants, aged 45–60, were conducted, transcribed and analyzed using Thematic Analysis. In-depth analysis of meanings of health promoting behaviors, in the context of cultural beliefs and values was carried out. Results The following themes were identified: Health as balance and integration; Health as connection of self, connection with others; Cultural meanings of lifestyle choices; Stresses and struggles. Participants suggested that the program should have significant variety and a holistic perspective, be sensitive to different needs and motivations, stimulate mutual understanding and shared cultural meanings. Discussion The program needs to support lifestyle changes which maximally preserve traditions and to introduce multi-level changes. Translation to Health Education Practice The identified cultural meanings of diet, physical activity and relationships were taken into account to develop the educational curriculum. PMID:26161165

  12. Glomerular parietal epithelial cells of adult murine kidney undergo EMT to generate cells with traits of renal progenitors.

    PubMed

    Swetha, G; Chandra, Vikash; Phadnis, Smruti; Bhonde, Ramesh

    2011-02-01

    Glomerular parietal epithelial cells (GPECs) are known to revert to embryonic phenotype in response to renal injury. However, the mechanism of de-differentiation in GPECs and the underlying cellular processes are not fully understood. In the present study, we show that cultured GPECs of adult murine kidney undergo epithelial-mesenchymal transition (EMT) to generate cells, which express CD24, CD44 and CD29 surface antigens. Characterization by qRT-PCR and immunostaining of these clonogenic cells demonstrate that they exhibit metastable phenotype with co-expression of both epithelial (cytokeratin-18) and mesenchymal (vimentin) markers. Transcript analysis by qRT-PCR revealed high expression of metanephric mesenchymal (Pax-2, WT-1, Six-1, Eya-1, GDNF) and uteric bud (Hoxb-7, C-Ret) genes in these cells, indicating their bipotent progenitor status. Incubation of GPECs with EMT blocker Prostaglandin E2, resulted in low expression of renal progenitor markers reflecting the correlation between EMT and acquired stemness in these cells. Additional in vitro renal commitment assays confirmed their functional staminality. When injected into E13.5 kidney rudiments, the cells incorporated into the developing kidney primordia and co-culture with E13.5 spinal cord resulted in branching and tubulogenesis in these cells. When implanted under renal capsule of unilaterally nephrectomized mice, these cells differentiated into immature glomeruli and vascular ducts. Our study demonstrates that EMT plays a major role in imparting plasticity to terminally differentiated GPECs by producing metastable cells with traits of kidney progenitors. The present study would improve our understanding on epithelial cell plasticity, furthering our knowledge of its role in renal repair and regeneration. PMID:19840197

  13. Guidelines and protocols for cardiovascular magnetic resonance in children and adults with congenital heart disease: SCMR expert consensus group on congenital heart disease

    PubMed Central

    2013-01-01

    Cardiovascular magnetic resonance (CMR) has taken on an increasingly important role in the diagnostic evaluation and pre-procedural planning for patients with congenital heart disease. This article provides guidelines for the performance of CMR in children and adults with congenital heart disease. The first portion addresses preparation for the examination and safety issues, the second describes the primary techniques used in an examination, and the third provides disease-specific protocols. Variations in practice are highlighted and expert consensus recommendations are provided. Indications and appropriate use criteria for CMR examination are not specifically addressed. PMID:23763839

  14. Prenatal cocaine exposure increases heart susceptibility to ischaemia–reperfusion injury in adult male but not female rats

    PubMed Central

    Bae, Soochan; Gilbert, Raymond D; Ducsay, Charles A; Zhang, Lubo

    2005-01-01

    The present study tested the hypothesis that prenatal cocaine exposure differentially regulates heart susceptibility to ischaemia–reperfusion (I/R) injury in adult offspring male and female rats. Pregnant rats were administered intraperitoneally either saline or cocaine (15 mg kg−1) twice daily from day 15 to day 21 of gestational age. There were no differences in maternal weight gain and birth weight between the two groups. Hearts were isolated from 2-month-old male and female offspring and were subjected to I/R (25 min/60 min) in a Langendorff preparation. Preischaemic values of left ventricular (LV) function were the same between the saline control and cocaine-treated hearts for both male and female rats. Prenatal cocaine exposure significantly increased I/R-induced myocardial apoptosis and infarct size, and significantly attenuated the postischaemic recovery of LV function in adult male offspring. In contrast, cocaine did not affect I/R-induced injury and postischaemic recovery of LV function in the female hearts. There was a significant decrease in PKCɛ and phospho-PKCɛ levels in LV in the male, but not female, offspring exposed to cocaine before birth. These results suggest that prenatal cocaine exposure causes a sex-specific increase in heart susceptibility to I/R injury in adult male offspring, and the decreased PKCɛ gene expression in the male heart may play an important role. PMID:15677681

  15. Trends in Heart Disease Mortality among Mississippi Adults over Three Decades, 1980-2013

    PubMed Central

    2016-01-01

    Heart disease (HD) remains the leading cause of death among Mississippians; however, despite the importance of the condition, trends in HD mortality in Mississippi have not been adequately explored. This study examined trends in HD mortality among adults in Mississippi from 1980 through 2013 and further examined these trends by race and sex. We used data from Mississippi Vital Statistics (1980–2013) to calculate age-adjusted HD mortality rates for Mississippians age 25 or older. Cases were identified using underlying cause of death codes from the International Classification of Diseases, Ninth Revision (ICD-9: 390–398, 402, 404–429) and Tenth Revision (ICD-10), including I00-I09, I11, I13, and I20-I51. Joinpoint software was used to calculate the average annual percent change in HD mortality rates for the overall population and by race and sex. Overall, the age-adjusted HD mortality rate among Mississippi adults decreased by 36.5% between 1980 and 2013, with an average annual percent change of -1.60% (95% CI -2.00 to -1.30). This trend varied across subgroups: HD mortality rates experienced an average annual change of -1.34% (95% CI -1.98 to -0.69) for black adults; -1.60% (95% CI -1.74 to -1.46) for white adults; -1.30% (95% CI -1.50 to -1.10) for all women, and -1.90% (95% -2.20 to -1.50) for all men. From 1980 to 2013, there was a continuous decrease in HD mortality among adult Mississippians. However, the magnitude of this reduction differed by race and sex. PMID:27518895

  16. Left ventricular function in adult patients with atrial septal defect: implication for development of heart failure after transcatheter closure.

    PubMed

    Masutani, Satoshi; Senzaki, Hideaki

    2011-11-01

    Despite advances in device closure for atrial septal defect (ASD), post-closure heart failure observed in adult patients remains a clinical problem. Although right heart volume overload is the fundamental pathophysiology in ASD, the post-closure heart failure characterized by acute pulmonary congestion is likely because of age-related left ventricular diastolic dysfunction, which is manifested by acute volume loading with ASD closure. Aging also appears to play important roles in the pathophysiology of heart failure through several mechanisms other than diastolic dysfunction, including ventricular systolic and vascular stiffening and increased incidence of comorbidities that significantly affect cardiovascular function. Recent studies suggested that accurate assessment of preclosure diastolic function, such as test ASD occlusion, may help identify high-risk patients for post-closure heart failure. Anti-heart failure therapy before device closure or the use of fenestrated device appears to be effective in preventing post-closure heart failure in the high-risk patients. However, the long-term outcome of such patients remains to be elucidated. Future studies are warranted to construct an algorithm to identify and treat patients at high risk for heart failure after device closure of ASD. PMID:22041334

  17. Prognostic and Therapeutic Implications of Frailty in Older Adults with Heart Failure.

    PubMed

    Goldfarb, Michael; Sheppard, Richard; Afilalo, Jonathan

    2015-11-01

    Frailty is increasingly recognized in older adults with cardiovascular disease, particularly in those with heart failure (HF). A growing body of evidence has shown that frailty has a negative effect on survival, hospitalizations, disability, and quality of life. Beyond frailty, additional domains captured by a comprehensive geriatric assessment contribute incremental value in predicting outcomes and identifying treatment targets. Exercise training is ideally suited to this setting as it can concomitantly improve physical frailty and HF symptoms. Multidisciplinary disease management programs offer a number of benefits for frail HF patients; invasive procedures carry a higher risk of morbidity than in non-frail counterparts, and evidence-based drugs and devices have an uncertain value and warrant further research. While more data accrues, difficult therapeutic decisions should be individualized using a shared patient-centered decision making approach. PMID:26346250

  18. Contribution of Major Lifestyle Risk Factors for Incident Heart Failure in Older Adults

    PubMed Central

    Del Gobbo, Liana C.; Kalantarian, Shadi; Imamura, Fumiaki; Lemaitre, Rozenn; Siscovick, David S.; Psaty, Bruce M.; Mozaffarian, Dariush

    2015-01-01

    Objectives The goal of this study was to determine the relative contribution of major lifestyle factors on the development of heart failure (HF) in older adults. Background HF incurs high morbidity, mortality, and health care costs among adults ≥65 years of age, which is the most rapidly growing segment of the U.S. population. Methods We prospectively investigated separate and combined associations of lifestyle risk factors with incident HF (1,380 cases) over 21.5 years among 4,490 men and women in the Cardiovascular Health Study, which is a community-based cohort of older adults. Lifestyle factors included 4 dietary patterns (Alternative Healthy Eating Index, Dietary Approaches to Stop Hypertension, an American Heart Association 2020 dietary goals score, and a Biologic pattern, which was constructed using previous knowledge of cardiovascular disease dietary risk factors), 4 physical activity metrics (exercise intensity, walking pace, energy expended in leisure activity, and walking distance), alcohol intake, smoking, and obesity. Results No dietary pattern was associated with developing HF (p > 0.05). Walking pace and leisure activity were associated with a 26% and 22% lower risk of HF, respectively (pace >3 mph vs. <2 mph; hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; leisure activity ≥845 kcal/week vs. <845 kcal/week; HR: 0.78; 95% CI: 0.69 to 0.87). Modest alcohol intake, maintaining a body mass index <30 kg/m2, and not smoking were also independently associated with a lower risk of HF. Participants with ≥4 healthy lifestyle factors had a 45% (HR: 0.55; 95% CI: 0.42 to 0.74) lower risk of HF. Heterogeneity by age, sex, cardiovascular disease, hypertension medication use, and diabetes was not observed. Conclusions Among older U.S. adults, physical activity, modest alcohol intake, avoiding obesity, and not smoking, but not dietary patterns, were associated with a lower risk of HF. PMID:26160366

  19. Knowledge Management in Cardiac Surgery: The Second Tehran Heart Center Adult Cardiac Surgery Database Report

    PubMed Central

    Abbasi, Kyomars; Karimi, Abbasali; Abbasi, Seyed Hesameddin; Ahmadi, Seyed Hossein; Davoodi, Saeed; Babamahmoodi, Abdolreza; Movahedi, Namdar; Salehiomran, Abbas; Shirzad, Mahmood; Bina, Peyvand

    2012-01-01

    Background: The Adult Cardiac Surgery Databank (ACSD) of Tehran Heart Center was established in 2002 with a view to providing clinical prediction rules for outcomes of cardiac procedures, developing risk score systems, and devising clinical guidelines. This is a general analysis of the collected data. Methods: All the patients referred to Tehran Heart Center for any kind of heart surgery between 2002 and 2008 were included, and their demographic, medical, clinical, operative, and postoperative data were gathered. This report presents general information as well as in-hospital mortality rates regarding all the cardiac procedures performed in the above time period. Results: There were 24959 procedures performed: 19663 (78.8%) isolated coronary artery bypass grafting surgeries (CABGs); 1492 (6.0%) isolated valve surgeries; 1437 (5.8%) CABGs concomitant with other procedures; 832 (3.3%) CABGs combined with valve surgeries; 722 (2.9%) valve surgeries concomitant with other procedures; 545 (2.2%) surgeries other than CABG or valve surgery; and 267 (1.1%) CABGs concomitant with valve and other types of surgery. The overall mortality was 205 (1.04%), with the lowest mortality rate (0.47%) in the isolated CABGs and the highest (4.49%) in the CABGs concomitant with valve surgeries and other types of surgery. Meanwhile, the overall mortality rate was higher in the female patients than in the males (1.90% vs. 0.74%, respectively). Conclusion: Isolated CABG was the most prevalent procedure at our center with the lowest mortality rate. However, the overall mortality was more prevalent in our female patients. This database can serve as a platform for the participation of the other countries in the region in the creation of a regional ACSD. PMID:23304179

  20. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  1. 31P-NMR studies of isolated adult heart cells: effect of myoglobin inactivation.

    PubMed

    Gupta, R K; Wittenberg, B A

    1991-10-01

    31P nuclear magnetic resonance (NMR) studies of isolated adult rat heart cells revealed that the cells maintained high-energy phosphates for up to 6 h in polyamide hollow fibers perfused with well-oxygenated nutrient medium. Glucose plus pyruvate superfused heart cells maintained [phosphocreatine]/[ATP] at 1.4 +/- 0.1, internal pH at 7.09 +/- 0.04 (external pH = 7.25), and intracellular free Mg2+ at 0.51 +/- 0.04 mM. In glucose-containing media, hypoxia was accompanied by a reversible decrease in intracellular ATP and phosphocreatine of approximately 50% and 80%, respectively, while the intracellular free Mg2+ was reversibly increased by 40%. However, inhibition of glycolysis by iodoacetate in aerobic pyruvate-containing medium did not significantly alter high-energy phosphate content. Inactivation of intracellular myoglobin with 1-2 mM sodium nitrite, which reduces the steady-state respiratory oxygen consumption rate by 30%, caused a significant (30%) decrease in intracellular phosphocreatine peak, which was reversed upon removal of sodium nitrite. The nitrite-induced decrease in phosphocreatine was also observed in iodoacetate-treated myocytes but not in oligomycin-treated cells. These results indicate that functional myoglobin enhances high-energy phosphate synthesis in well-oxygenated myocytes. PMID:1928397

  2. Health Care Costs for Adults With Congenital Heart Disease in the United States 2002 to 2012.

    PubMed

    Briston, David A; Bradley, Elisa A; Sabanayagam, Aarthi; Zaidi, Ali N

    2016-08-15

    More adults than children with congenital heart disease (CHD) are alive today. Few studies have evaluated adult congenital heart disease (ACHD) health care utilization in the United States. Data from the National Inpatient Sample from 2002 to 2012, using International Classification of Diseases, Ninth Revision, codes for moderate and complex CHD were analyzed. Hospital discharges, total billed and reimbursed amounts, length of stay, and gender/age disparities were evaluated. There was an increase in CHD discharges (moderate CHD: 4,742 vs 6,545; severe CHD: 807 vs 1,115) and total billed and reimbursed dollar amounts across all CHD (billed: $2.7 vs $7.0 billion, 155% increase; reimbursed: $1.3 vs $2.3 billion, 99% increase) and in the ACHD subgroup (billed: $543 million vs $1.5 billion, 178% increase; reimbursed: $221 vs $433 million, 95% increase). Women comprised more discharges in 2002 but not in 2012 (men:women, 2002: 6,503 vs 7,805; 2012: 7,715 vs 7,200, p = 0.39). Gender-based billed amounts followed similar trends (2002: $263 vs $280 million; 2012: $845 vs $662 million, p = 0.006) as did reimbursements (2002: $108 vs $114 million; 2012: $243 vs $190 million, p = 0.008). All age subgroups demonstrated increased health care expenditures, including the >44 versus 18- to 44-year-old age subgroup (billed: $618 vs $347 million, p <0.001; reimbursed: $136 vs $75 million, p <0.001). Our results reveal increased ACHD billed and reimbursed amounts and hospital discharges with a shift in gender-based ACHD hospitalizations: men now account for more hospitalizations in the United States. In conclusion, increased health care expenditure in older patients with ACHD is likely to increase further as health care system use and costs continue to grow. PMID:27476099

  3. Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults.

    PubMed

    Bianchim, M S; Sperandio, E F; Martinhão, G S; Matheus, A C; Lauria, V T; da Silva, R P; Spadari, R C; Gagliardi, A R T; Arantes, R L; Romiti, M; Dourado, V Z

    2016-03-01

    The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders. PMID:26840706

  4. Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

    PubMed

    Elder, Robert W; George, Roshan P; McCabe, Nancy M; Rodriguez Iii, Fred H; Book, Wendy M; Mahle, William T; Kirk, Allan D

    2015-10-01

    Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change. PMID:25916315

  5. Optimal Cutoff Points of Anthropometric Parameters to Identify High Coronary Heart Disease Risk in Korean Adults

    PubMed Central

    2016-01-01

    Several published studies have reported the need to change the cutoff points of anthropometric indices for obesity. We therefore conducted a cross-sectional study to estimate anthropometric cutoff points predicting high coronary heart disease (CHD) risk in Korean adults. We analyzed the Korean National Health and Nutrition Examination Survey data from 2007 to 2010. A total of 21,399 subjects aged 20 to 79 yr were included in this study (9,204 men and 12,195 women). We calculated the 10-yr Framingham coronary heart disease risk score for all individuals. We then estimated receiver-operating characteristic (ROC) curves for body mass index (BMI), waist circumference, and waist-to-height ratio to predict a 10-yr CHD risk of 20% or more. For sensitivity analysis, we conducted the same analysis for a 10-yr CHD risk of 10% or more. For a CHD risk of 20% or more, the area under the curve of waist-to-height ratio was the highest, followed by waist circumference and BMI. The optimal cutoff points in men and women were 22.7 kg/m2 and 23.3 kg/m2 for BMI, 83.2 cm and 79.7 cm for waist circumference, and 0.50 and 0.52 for waist-to-height ratio, respectively. In sensitivity analysis, the results were the same as those reported above except for BMI in women. Our results support the re-classification of anthropometric indices and suggest the clinical use of waist-to-height ratio as a marker for obesity in Korean adults. PMID:26770039

  6. Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults

    PubMed Central

    Bianchim, M.S.; Sperandio, E.F.; Martinhão, G.S.; Matheus, A.C.; Lauria, V.T.; da Silva, R.P.; Spadari, R.C.; Gagliardi, A.R.T.; Arantes, R.L.; Romiti, M.; Dourado, V.Z.

    2016-01-01

    The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R 2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders. PMID:26840706

  7. Paleolithic nutrition improves plasma lipid concentrations of hypercholesterolemic adults to a greater extent than traditional heart-healthy dietary recommendations.

    PubMed

    Pastore, Robert L; Brooks, Judith T; Carbone, John W

    2015-06-01

    Recent research suggests that traditional grain-based heart-healthy diet recommendations, which replace dietary saturated fat with carbohydrate and reduce total fat intake, may result in unfavorable plasma lipid ratios, with reduced high-density lipoprotein (HDL) and an elevation of low-density lipoprotein (LDL) and triacylglycerols (TG). The current study tested the hypothesis that a grain-free Paleolithic diet would induce weight loss and improve plasma total cholesterol, HDL, LDL, and TG concentrations in nondiabetic adults with hyperlipidemia to a greater extent than a grain-based heart-healthy diet, based on the recommendations of the American Heart Association. Twenty volunteers (10 male and 10 female) aged 40 to 62 years were selected based on diagnosis of hypercholesterolemia. Volunteers were not taking any cholesterol-lowering medications and adhered to a traditional heart-healthy diet for 4 months, followed by a Paleolithic diet for 4 months. Regression analysis was used to determine whether change in body weight contributed to observed changes in plasma lipid concentrations. Differences in dietary intakes and plasma lipid measures were assessed using repeated-measures analysis of variance. Four months of Paleolithic nutrition significantly lowered (P < .001) mean total cholesterol, LDL, and TG and increased (P < .001) HDL, independent of changes in body weight, relative to both baseline and the traditional heart-healthy diet. Paleolithic nutrition offers promising potential for nutritional management of hyperlipidemia in adults whose lipid profiles have not improved after following more traditional heart-healthy dietary recommendations. PMID:26003334

  8. Outcomes of a Telehealth Intervention for Homebound Older Adults with Heart or Chronic Respiratory Failure: A Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Gellis, Zvi D.; Kenaley, Bonnie; McGinty, Jean; Bardelli, Ellen; Davitt, Joan; Ten Have, Thomas

    2012-01-01

    Purpose: Telehealth care is emerging as a viable intervention model to treat complex chronic conditions, such as heart failure (HF) and chronic obstructive pulmonary disease (COPD), and to engage older adults in self-care disease management. Design and Methods: We report on a randomized controlled trial examining the impact of a multifaceted…

  9. The Effects of Various Comfort Food on Heart Coherence in Adults

    PubMed Central

    Joseph, Madeline Matar; McIntosh, Mark S.; Joseph, Christine Marie

    2014-01-01

    Background: Some of the nutrients in food are precursors to neurotransmitters, accounting for its effects on mood. Heart coherence (HC), which relates to the optimal psycho-physiological conditions for human body functions, is affected by a person's emotional status. Objectives: (1) To determine the effects of various comfort food on HC and heart rate (HR) in adult females 20 to 50 years of age and (2) to evaluate if body mass index (BMI) has an effect on HC and HR when eating various comfort foods. Methods: The researcher obtained consent from participants after explaining the project. The subjects' height and weight were measured using standardized methods to calculate their BMI. Participants sat in a comfortable chair in a quiet area with a clipped earpiece to measure their heart rate variability (HRV), HR, and HC. Each participant was asked about their favorite comfort food (sweet vs salty). First, the participant imagined eating her favorite comfort food (IFCF) and then was asked to imagine her non-favorite comfort food (INFCF). Finally, the participant ate her favorite comfort food (EFCF) and then ate her non-favorite comfort food (ENFCF). HC scores were recorded in three categories (low, medium, and high) in these four settings. Results: A total of 20 participants completed the study. Paired student's t-tests were used to assess whether the means of the compared groups were statistically different. The data demonstrated that there was a higher HC when participants ate their favorite comfort food than when they ate the non-favorite comfort food (t=−2.912, P<.01) and a higher HC when eating a favorite comfort food than when imaging eating a favorite comfort food (t=−.2408, P<.01). The participants' BMI had a positive correlation between the BMI and low HC (when one increases, the other increases as well) when imagining eating a favorite comfort food (r =.475, P<.05). There was a negative correlation between BMI and medium HC (when one increases, the other

  10. Plasma vitamin B12, methylmalonic acid and heart rate variability in healthy young Indian adults.

    PubMed

    Sucharita, Sambashivaiah; Sowmya, Sharma; Thomas, Tinku; Kurpad, Anura V; Vaz, Mario

    2013-01-01

    Prevalence of vitamin B12 deficiency in the Indian population is not known, however; it is considered to be higher than in the Western population. Vitamin B12 deficiency is generally diagnosed by the plasma vitamin B12 level. Metabolites of vitamin B12 such as homocysteine (Hcy) and methylmalonic acid (MMA) are considered to be better markers to diagnose vitamin B12 deficiency at the tissue level. Autonomic neuropathy in vitamin B12 deficiency appears to precede other neurological signs. One of the recent techniques to evaluate autonomic neuropathy is heart rate variability (HRV). We evaluated 14 healthy young adults to explore the association of plasma vitamin B12, MMA, and Hcy levels with HRV. Resting lead II ECG was recorded and power spectral analyses were performed. Plasma MMA level was significantly and negatively correlated with the log-transformed low frequency (r = - 0.74, p = 0.002) and total power spectra (r = - 0.55, p = 0.03) of HRV in absolute units. Low frequency (LF) (r = - 0.56, p = 0.03) and high frequency (HF) (r = 0.57, p = 0.03), when represented in normalized units, were also correlated significantly with plasma MMA. In summary, plasma MMA but not vitamin B12 was significantly associated with HRV indices in a young adult population, suggesting that a tissue-level marker of vitamin B12 deficiency is more closely correlated with functional changes. PMID:24846903

  11. Ambient fine particles modify heart rate variability in young healthy adults.

    PubMed

    Vallejo, Maite; Ruiz, Silvia; Hermosillo, Antonio G; Borja-Aburto, Víctor H; Cárdenas, Manuel

    2006-03-01

    Particulate air pollution has been related with cardiopulmonary morbidity and mortality. Recent studies have shown that an increase in particulate matter (PM)(2.5) ambient concentrations was associated with a decrease in heart rate variability (HRV) in the elderly with cardiovascular conditions, which could increase the risk of death. In order to assess if this association could also be observed in young adults, we studied 40 young healthy residents of the Mexico City Metropolitan Area (MCMA) who underwent 13 h Holter electrocardiographic and PM(2.5) personal monitoring. HRV was evaluated in time domain: the standard deviation of normal RR intervals (SDNN) and the percentage of differences between adjacent normal RR intervals larger than 50 ms (pNN50). In multivariate analysis with mixed effects models, a significant negative association of pNN50 with PM(2.5) accumulative exposure was found. An increase in 30 microg/m(3) of the average PM(2.5) personal exposure in the previous 2 h decreased the pNN50 in 0.08% (P=0.01). This observation revealed an acute effect related to environmental exposure to PM(2.5) with regard to HRV in normal youngsters. The long-term health consequences of this association in young healthy adults remain to be clarified. PMID:16151470

  12. Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Complex congenital cardiac lesions

    PubMed Central

    Silversides, Candice K; Oechslin, Erwin; Schwerzmann, Markus; Muhll, Isabelle Vonder; Khairy, Paul; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Warnes, Carole; Therrien, Judith

    2010-01-01

    With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger’s syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org. PMID:20352139

  13. Differential mRNA expression and glucocorticoid-mediated regulation of TRPM6 and TRPM7 in the heart and kidney throughout murine pregnancy and development.

    PubMed

    Cuffe, James S M; Steane, Sarah; Moritz, Karen M; Paravicini, Tamara M

    2015-01-01

    The transient receptor potential (TRP) channels TRPM6 and TRPM7 are critically involved in maintaining whole body and cellular Mg2+ homeostasis and ensuring the normal function of organs such as the heart and kidney. However, we do not know how the expression of TRPM6 and TPRM7 in these organs changes throughout fetal development and adult life, and whether this expression can be hormonally regulated. This study determined the ontogeny of TRPM6 and TRPM7 mRNA expression from mid-gestation through to adulthood in the mouse. In a second series of experiments, we examined how maternal administration of the glucocorticoids corticosterone and dexamethasone between embryonic days 12.5-15 affected TRPM6 and TRPM7 channel mRNA expression in the mother and fetus. Whilst renal TRPM7 expression was relatively constant throughout development, renal TRPM6 expression was markedly upregulated after birth. In contrast, cardiac TRPM7 expression was 2-4 fold higher in the fetus than in the adult. Surprisingly, TRPM6 expression was detected in the fetal heart (qPCR and in situ hybridization). Glucocorticoid administration during gestation increased fetal cardiac expression of both channels without affecting renal expression. In contrast, in the dam renal TRPM6 and TRPM7 expression was increased by glucocorticoids with no change in the cardiac channel expression. These data suggest that TRPM6 and TRPM7 channels are important in organogenesis, and that elevated maternal glucocorticoid levels can alter the expression of these channels. This suggests that perturbations in hormonal regulatory systems during pregnancy may adversely impact upon normal fetal development, at least in part by altering expression of TRPM channels. PMID:25692682

  14. The care of adults with congenital heart disease across the globe: Current assessment and future perspective: A position statement from the International Society for Adult Congenital Heart Disease (ISACHD).

    PubMed

    Webb, Gary; Mulder, Barbara J; Aboulhosn, Jamil; Daniels, Curt J; Elizari, Maria Amalia; Hong, Gu; Horlick, Eric; Landzberg, Michael J; Marelli, Ariane J; O'Donnell, Clare P; Oechslin, Erwin N; Pearson, Dorothy D; Pieper, Els P G; Saxena, Anita; Schwerzmann, Markus; Stout, Karen K; Warnes, Carole A; Khairy, Paul

    2015-09-15

    The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD. PMID:26056966

  15. Strategies to Enhance the Effectiveness of Adult Stem Cell Therapy for Ischemic Heart Diseases Affecting the Elderly Patients

    PubMed Central

    Khatiwala, Roshni

    2016-01-01

    Myocardial infarctions and chronic ischemic heart disease both commonly and disproportionately affect elderly patients more than any other patient population. Despite available treatments, heart tissue is often permanently damaged as a result of cardiac injury. This review aims to summarize recent literature proposing the use of modified autologous adult stem cells to promote healing of post-infarct cardiac tissue. This novel cellular treatment involves isolation of adult stem cells from the patient, in vitro manipulation of these stem cells, and subsequent transplantation back into the patient’s own heart to accelerate healing. One of the hindrances affecting this process is that cardiac issues are increasingly common in elderly patients, and stem cells recovered from their tissues tend to be pre-senescent or already in senescence. As a result, harsh in vitro manipulations can cause the aged stem cells to undergo massive in vivo apoptosis after transplantation. The consensus in literature is that inhibition or reversal of senescence onset in adult stem cells would be of utmost benefit. In fact, it is believed that this strategy may lower stem cell mortality and coerce aged stem cells into adopting more resilient phenotypes similar to that of their younger counterparts. This review will discuss a selection of the most efficient and most-recent strategies used experimentally to enhance the effectiveness of current stem cell therapies for ischemic heart diseases. PMID:26779896

  16. Abnormal Heart Rate Turbulence Predicts Cardiac Mortality in Low, Intermediate and High Risk Older Adults

    PubMed Central

    Stein, Phyllis K.; Barzilay, Joshua I.

    2011-01-01

    Introduction We examined whether heart rate turbulence (HRT) adds to traditional risk factors for cardiac mortality in older adults at low, intermediate and high risk. Methods and Results N=1298, age ≥65 years, with 24-hour Holter recordings were studied. HRT, which quantifies heart rate response to ventricular premature contractions, was categorized as: both turbulence onset (TO) and turbulence slope (TS) normal; TO abnormal; TS abnormal; or both abnormal. Independent risks for cardiac mortality associated with HRT or, for comparison, elevated C-reactive protein (CRP) (>3.0 mg/L), were calculated using Cox regression analysis adjusted for traditional cardiovascular disease risk factors and stratified by the presence of no, isolated subclinical (i.e., intermediate risk) or clinical CVD. Having both TS and TO abnormal compared to both normal was associated with cardiac mortality in the low risk group [HR 7.9, 95% CI 2.8–22.5, (p<0.001)]. In the high and intermediate risk groups, abnormal TS and TO ([HR 2.2, 95% CI 1.5–4.0, p=0.016] and [HR 2.7, 95% CI 1.2–5.9, p=0.012]), respectively, were also significantly associated with cardiac mortality. In contrast, elevated CRP was associated with increased cardiac mortality risk only in low risk individuals [HR 2.5, 95% CI 1.3–5.1, p=0.009]. In the low risk group, the c-statistic was 0.706 for the base model, 0.725 for the base model with CRP, and 0.767 for the base model with HRT. Conclusions Abnormal HRT independently adds to risk stratification of low, intermediate and high risk individuals but appears to add especially to the stratification of those considered at low risk. PMID:21134026

  17. Hypoxia/Reoxygenation Cardiac Injury and Regeneration in Zebrafish Adult Heart

    PubMed Central

    Pompilio, Giulio; Verduci, Lorena; Colombo, Gualtiero I.; Milano, Giuseppina; Guerrini, Uliano; Squadroni, Lidia; Cotelli, Franco; Pozzoli, Ombretta; Capogrossi, Maurizio C.

    2013-01-01

    Aims the adult zebrafish heart regenerates spontaneously after injury and has been used to study the mechanisms of cardiac repair. However, no zebrafish model is available that mimics ischemic injury in mammalian heart. We developed and characterized zebrafish cardiac injury induced by hypoxia/reoxygenation (H/R) and the regeneration that followed it. Methods and Results adult zebrafish were kept either in hypoxic (H) or normoxic control (C) water for 15 min; thereafter fishes were returned to C water. Within 2–6 hours (h) after reoxygenation there was evidence of cardiac oxidative stress by dihydroethidium fluorescence and protein nitrosylation, as well as of inflammation. We used Tg(cmlc2:nucDsRed) transgenic zebrafish to identify myocardial cell nuclei. Cardiomyocyte apoptosis and necrosis were evidenced by TUNEL and Acridine Orange (AO) staining, respectively; 18 h after H/R, 9.9±2.6% of myocardial cell nuclei were TUNEL+ and 15.0±2.5% were AO+. At the 30-day (d) time point myocardial cell death was back to baseline (n = 3 at each time point). We evaluated cardiomyocyte proliferation by Phospho Histone H3 (pHH3) or Proliferating Cell Nuclear Antigen (PCNA) expression. Cardiomyocyte proliferation was apparent 18–24 h after H/R, it achieved its peak 3–7d later, and was back to baseline at 30d. 7d after H/R 17.4±2.3% of all cardiomyocytes were pHH3+ and 7.4±0.6% were PCNA+ (n = 3 at each time point). Cardiac function was assessed by 2D-echocardiography and Ventricular Diastolic and Systolic Areas were used to compute Fractional Area Change (FAC). FAC decreased from 29.3±2.0% in normoxia to 16.4±1.8% at 18 h after H/R; one month later ventricular function was back to baseline (n = 12 at each time point). Conclusions zebrafish exposed to H/R exhibit evidence of cardiac oxidative stress and inflammation, myocardial cell death and proliferation. The initial decrease in ventricular function is followed by full recovery. This model more closely

  18. Three-dimensional scaffolds of fetal decellularized hearts exhibit enhanced potential to support cardiac cells in comparison to the adult.

    PubMed

    Silva, A C; Rodrigues, S C; Caldeira, J; Nunes, A M; Sampaio-Pinto, V; Resende, T P; Oliveira, M J; Barbosa, M A; Thorsteinsdóttir, S; Nascimento, D S; Pinto-do-Ó, P

    2016-10-01

    A main challenge in cardiac tissue engineering is the limited data on microenvironmental cues that sustain survival, proliferation and functional proficiency of cardiac cells. The aim of our study was to evaluate the potential of fetal (E18) and adult myocardial extracellular matrix (ECM) to support cardiac cells. Acellular three-dimensional (3D) bioscaffolds were obtained by parallel decellularization of fetal- and adult-heart explants thereby ensuring reliable comparison. Acellular scaffolds retained main constituents of the cardiac ECM including distinctive biochemical and structural meshwork features of the native equivalents. In vitro, fetal and adult ECM-matrices supported 3D culture of heart-derived Sca-1(+) progenitors and of neonatal cardiomyocytes, which migrated toward the center of the scaffold and displayed elongated morphology and excellent viability. At the culture end-point, more Sca-1(+) cells and cardiomyocytes were found adhered and inside fetal bioscaffolds, compared to the adult. Higher repopulation yields of Sca-1(+) cells on fetal ECM relied on β1-integrin independent mitogenic signals. Sca-1(+) cells on fetal bioscaffolds showed a gene expression profile that anticipates the synthesis of a permissive microenvironment for cardiomyogenesis. Our findings demonstrate the superior potential of the 3D fetal microenvironment to support and instruct cardiac cells. This knowledge should be integrated in the design of next-generation biomimetic materials for heart repair. PMID:27424216

  19. cap alpha. -skeletal and. cap alpha. -cardiac actin genes are coexpressed in adult human skeletal muscle and heart

    SciTech Connect

    Gunning, P.; Ponte, P.; Blau, H.; Kedes, L.

    1983-11-01

    The authors determined the actin isotypes encoded by 30 actin cDNA clones previously isolated from an adult human muscle cDNA library. Using 3' untranslated region probes, derived from ..cap alpha.. skeletal, ..beta..- and ..gamma..-actin cDNAs and from an ..cap alpha..-cardiac actin genomic clone, they showed that 28 of the cDNAs correspond to ..cap alpha..-skeletal actin transcripts. Unexpectedly, however, the remaining two cDNA clones proved to derive from ..cap alpha..-cardiac actin mRNA. Sequence analysis confirmed that the two skeletal muscle ..cap alpha..-cardiac actin cDNAs are derived from transcripts of the cloned ..cap alpha..-cardiac actin gene. Comparison of total actin mRNA levels in adult skeletal muscle and adult heart revealed that the steady-state levels in skeletal muscle are about twofold greater, per microgram of total cellular RNA, than those in heart. Thus, in skeletal muscle and in heart, both of the sarcomeric actin mRNA isotypes are quite abundant transcripts. They conclude that ..cap alpha..-skeletal and ..cap alpha..-cardiac actin genes are coexpressed as an actin pair in human adult striated muscles. Since the smooth-muscle actins (aortic and stomach) and the cytoplasmic actins (..beta.. and ..gamma..) are known to be coexpressed in smooth muscle and nonmuscle cells, respectively, they postulate that coexpression of actin pairs may be a common feature of mammalian actin gene expression in all tissues.

  20. Brain Volumetrics, Regional Cortical Thickness and Radiographic Findings in Adults with Cyanotic Congenital Heart Disease☆

    PubMed Central

    Cordina, Rachael; Grieve, Stuart; Barnett, Michael; Lagopoulos, Jim; Malitz, Nathan; Celermajer, David S.

    2014-01-01

    Background Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized. Hypothesis We hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes. Methods Ten adults with chronic cyanosis from CHD (40 ± 4 years) and mean oxygen saturations of 82 ± 2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects. Results Five of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8 ± 2). Quantitative MRI revealed evidence of extensive generalized WM and gray matter (GM) volumetric loss; global GM volume was reduced in cyanosed subjects (630 ± 16 vs. 696 ± 14 mL in controls, p = 0.01) as was global WM volume (471 ± 10 vs. 564 ± 18 mL, p = 0.003). Ventricular cerebrospinal fluid volume was increased (35 ± 10 vs. 26 ± 5 mL, p = 0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p ≤ 0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R = − 0.89, p = 0.009), high sensitivity C-reactive protein (R = − 0

  1. Exergaming in older adults: A scoping review and implementation potential for patients with heart failure

    PubMed Central

    Jaarsma, Tiny; Strömberg, Anna

    2014-01-01

    Background: Physical activity can improve exercise capacity, quality of life and reduce mortality and hospitalization in patients with heart failure (HF). Adherence to exercise recommendations in patients with HF is low. The use of exercise games (exergames) might be a way to encourage patients with HF to exercise especially those who may be reluctant to more traditional forms of exercise. No studies have been conducted on patients with HF and exergames. Aim: This scoping review focuses on the feasibility and influence of exergames on physical activity in older adults, aiming to target certain characteristics that are important for patients with HF to become more physically active. Methods: A literature search was undertaken in August 2012 in the databases PsychInfo, PUBMED, Scopus, Web of Science and CINAHL. Included studies evaluated the influence of exergaming on physical activity in older adults. Articles were excluded if they focused on rehabilitation of specific limbs, improving specific tasks or describing no intervention. Fifty articles were found, 11 were included in the analysis. Results: Exergaming was described as safe and feasible, and resulted in more energy expenditure compared to rest. Participants experienced improved balance and reported improved cognitive function after exergaming. Participants enjoyed playing the exergames, their depressive symptoms decreased, and they reported improved quality of life and empowerment. Exergames made them feel more connected with their family members, especially their grandchildren. Conclusion: Although this research field is small and under development, exergaming might be promising in order to enhance physical activity in patients with HF. However, further testing is needed. PMID:24198306

  2. An evaluation of a specialist nursing service for adult patients with congenital heart disease.

    PubMed

    Hatchett, Richard; McLaren, Susan; Corrigan, Philomena; Filer, Lynda

    2015-10-01

    The purpose of this study was to evaluate grown-up congenital heart (GUCH) patients' experiences and satisfaction with the delivery of a nurse specialist service, including perceived priorities and recommendations for future service delivery. A service evaluation utilizing descriptive, cross-sectional survey principles was conducted over a 2 year period. Postal questionnaires were sent to three patient cohorts (general adult n = 747; pregnancy n = 202; learning disability n = 72). Quantitative data were analysed using descriptive statistics. The majority of respondents were satisfied with the nursing care provided, including information provision, time made available to discuss needs, emotional support, well-being, self-management and symptom distress. Priority areas included timely information and advice; specialist knowledge and expertise; effective care coordination, monitoring and support. Accessibility, contact and responsiveness were dominant. A majority of patients agreed that their first, second and third-rated priorities had been met. Findings identified strong commitment, support and satisfaction with the GUCH nurse specialist service. PMID:25307531

  3. Towards regenerating the mammalian heart: challenges in evaluating experimentally induced adult mammalian cardiomyocyte proliferation.

    PubMed

    Zebrowski, David C; Becker, Robert; Engel, Felix B

    2016-05-01

    In recent years, there has been a dramatic increase in research aimed at regenerating the mammalian heart by promoting endogenous cardiomyocyte proliferation. Despite many encouraging successes, it remains unclear if we are any closer to achieving levels of mammalian cardiomyocyte proliferation for regeneration as seen during zebrafish regeneration. Furthermore, current cardiac regenerative approaches do not clarify whether the induced cardiomyocyte proliferation is an epiphenomena or responsible for the observed improvement in cardiac function. Moreover, due to the lack of standardized protocols to determine cardiomyocyte proliferation in vivo, it remains unclear if one mammalian regenerative factor is more effective than another. Here, we discuss current methods to identify and evaluate factors for the induction of cardiomyocyte proliferation and challenges therein. Addressing challenges in evaluating adult cardiomyocyte proliferation will assist in determining 1) which regenerative factors should be pursued in large animal studies; 2) if a particular level of cell cycle regulation presents a better therapeutic target than another (e.g., mitogenic receptors vs. cyclins); and 3) which combinatorial approaches offer the greatest likelihood of success. As more and more regenerative studies come to pass, progress will require a system that not only can evaluate efficacy in an objective manner but can also consolidate observations in a meaningful way. PMID:26921436

  4. MicroRNA Clusters in the Adult Mouse Heart: Age-Associated Changes

    PubMed Central

    Zhang, Xiaomin; Azhar, Gohar; Williams, Emmanuel D.; Rogers, Steven C.; Wei, Jeanne Y.

    2015-01-01

    The microRNAs and microRNA clusters have been implicated in normal cardiac development and also disease, including cardiac hypertrophy, cardiomyopathy, heart failure, and arrhythmias. Since a microRNA cluster has from two to dozens of microRNAs, the expression of a microRNA cluster could have a substantial impact on its target genes. In the present study, the configuration and distribution of microRNA clusters in the mouse genome were examined at various inter-microRNA distances. Three important microRNA clusters that are significantly impacted during adult cardiac aging, the miR-17-92, miR-106a-363, and miR-106b-25, were also examined in terms of their genomic location, RNA transcript character, sequence homology, and their relationship with the corresponding microRNA families. Multiple microRNAs derived from the three clusters potentially target various protein components of the cdc42-SRF signaling pathway, which regulates cytoskeleton dynamics associated with cardiac structure and function. The data indicate that aging impacted the expression of both guide and passenger strands of the microRNA clusters; nutrient stress also affected the expression of the three microRNA clusters. The miR-17-92, miR-106a-363, and miR-106b-25 clusters are likely to impact the Cdc42-SRF signaling pathway and thereby affect cardiac morphology and function during pathological conditions and the aging process. PMID:26221604

  5. Predictors of Objectively Measured Medication Nonadherence in Adults with Heart Failure

    PubMed Central

    Riegel, Barbara; Lee, Christopher S.; Ratcliffe, Sarah J.; De Geest, Sabina; Potashnik, Sheryl; Patey, Megan; Sayers, Steven L.; Goldberg, Lee R.; Weintraub, William S.

    2012-01-01

    Background Medication nonadherence rates are high. The factors predicting nonadherence in heart failure (HF) remain unclear. Methods and Results A sample of 202 adults with HF was enrolled from the Northeastern U.S. and followed for 6 months. Specific aims were to describe the types of objectively measured medication nonadherence (e.g. taking, timing, dosing, drug holidays) and to identify contributors to nonadherence 6 months after enrollment. Latent growth mixture modeling (GMM) was used to identify distinct trajectories of adherence. Indicators of the five World Health Organization (WHO) dimensions of adherence (socioeconomic, condition, therapy, patient, and health care system) were tested to identify contributors to nonadherence. Two distinct trajectories were identified and labeled persistent adherence (77.8%) and steep decline (22.3%). Three contributors to the steep decline in adherence were identified. Participants with lapses in attention (adjusted odds ratio (OR) = 2.65, p=0.023), those with excessive daytime sleepiness (OR = 2.51, p=0.037), and those with two or more medication dosings per day (OR = 2.59, p=0.016) were more likely to have a steep decline in adherence over time than to have persistent adherence. Conclusions Two distinct patterns of adherence were identified. Three potentially modifiable contributors to nonadherence have been identified. PMID:22647773

  6. Reversibility of electrophysiological changes induced by chronic high-altitude hypoxia in adult rat heart.

    PubMed

    Chouabe, C; Amsellem, J; Espinosa, L; Ribaux, P; Blaineau, S; Mégas, P; Bonvallet, R

    2002-04-01

    Recent studies indicate that regression of left ventricular hypertrophy normalizes membrane ionic current abnormalities. This work was designed to determine whether regression of right ventricular hypertrophy induced by permanent high-altitude exposure (4,500 m, 20 days) in adult rats also normalizes changes of ventricular myocyte electrophysiology. According to the current data, prolonged action potential, decreased transient outward current density, and increased inward sodium/calcium exchange current density normalized 20 days after the end of altitude exposure, whereas right ventricular hypertrophy evidenced by both the right ventricular weight-to-heart weight ratio and the right ventricular free wall thickness measurement normalized 40 days after the end of altitude exposure. This morphological normalization occurred at both the level of muscular tissue, as shown by the decrease toward control values of some myocyte parameters (perimeter, capacitance, and width), and the level of the interstitial collagenous connective tissue. In the chronic high-altitude hypoxia model, the regression of right ventricular hypertrophy would not be a prerequisite for normalization of ventricular electrophysiological abnormalities. PMID:11893582

  7. Acquired deficiency of tafazzin in the adult heart: Impact on mitochondrial function and response to cardiac injury.

    PubMed

    Szczepanek, Karol; Allegood, Jeremy; Aluri, Hema; Hu, Ying; Chen, Qun; Lesnefsky, Edward J

    2016-04-01

    The content and composition of cardiolipin (CL) is critical for preservation of mitochondrial oxidative phosphorylation (OXPHOS) and inner membrane integrity. Tafazzin (Taz) is an enzyme responsible for remodeling of immature CL containing mixed acyl groups into the mature tetralinoleyl form (C18:2)4-CL. We hypothesized that acquired defects in Taz in the mature heart would impact remodeling of CL and augment cardiac injury. The role of acquired Taz deficiency was studied using the inducible Taz knockdown (TazKD) mouse. Taz-specific shRNA is induced by doxycycline (DOX). One day of DOX intake decreased Taz mRNA in the heart to 20% vs. DOX-treated WT. Knockdown was initiated at an adult age and was stable during long term feeding. CL phenotype was assessed by (C18:2)4-CL content and was reduced 40% vs. WT at two months of DOX. TazKD showed increased production of reactive oxygen species and increased susceptibility to permeability transition pore opening at baseline. However, OXPHOS measured using the rate of oxygen consumption was unchanged in the setting of acquired Taz deficiency. Infarct size, measured in isolated buffer-perfused Langendorff hearts following 25min. Stop flow ischemia and 60min. Reperfusion was not altered in TazKD hearts. Thus, impaired Taz-function with onset at adult age does not enhance susceptibility to ischemia-reperfusion injury. PMID:26692032

  8. Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3.

    PubMed

    Thomas, Glyn; Gurung, Iman S; Killeen, Matthew J; Hakim, Parvez; Goddard, Catharine A; Mahaut-Smith, Martyn P; Colledge, William H; Grace, Andrew A; Huang, Christopher L-H

    2007-01-01

    Ventricular arrhythmogenesis in long QT 3 syndrome (LQT3) involves both triggered activity and re-entrant excitation arising from delayed ventricular repolarization. Effects of specific L-type Ca2+ channel antagonism were explored in a gain-of-function murine LQT3 model produced by a DeltaKPQ 1505-1507 deletion in the SCN5A gene. Monophasic action potentials (MAPs) were recorded from epicardial and endocardial surfaces of intact, Langendorff-perfused Scn5a+/Delta hearts. In untreated Scn5a+/Delta hearts, epicardial action potential duration at 90% repolarization (APD90) was 60.0 +/- 0.9 ms compared with 46.9 +/- 1.6 ms in untreated wild-type (WT) hearts (P < 0.05; n = 5). The corresponding endocardial APD(90) values were 52.0 +/- 0.7 ms and 53.7 +/- 1.6 ms in Scn5a+/Delta and WT hearts, respectively (P > 0.05; n = 5). Epicardial early afterdepolarizations (EADs), often accompanied by spontaneous ventricular tachycardia (VT), occurred in 100% of MAPs from Scn5a+/Delta but not in any WT hearts (n = 10). However, EAD occurrence was reduced to 62 +/- 7.1%, 44 +/- 9.7%, 10 +/- 10% and 0% of MAPs following perfusion with 10 nm, 100 nm, 300 nm and 1 mum nifedipine, respectively (P < 0.05; n = 5), giving an effective IC50 concentration of 79.3 nm. Programmed electrical stimulation (PES) induced VT in all five Scn5a+/Delta hearts (n = 5) but not in any WT hearts (n = 5). However, repeat PES induced VT in 3, 2, 2 and 0 out of 5 Scn5a+/Delta hearts following perfusion with 10 nm, 100 nm, 300 nm and 1 mum nifedipine, respectively. Patch clamp studies in isolated ventricular myocytes from Scn5a+/Delta and WT hearts confirmed that nifedipine (300 nm) completely suppressed the inward Ca2+ current but had no effect on inward Na+ currents. No significant effects were seen on epicardial APD90, endocardial APD90 or ventricular effective refractory period in Scn5a+/Delta and WT hearts following perfusion with nifedipine at 1 nm, 10 nm, 100 nm, 300 nm and 1 microm nifedipine

  9. Knowledge of heart attack and stroke symptomology: a cross-sectional comparison of rural and non-rural US adults

    PubMed Central

    2012-01-01

    Background Understanding the signs and symptoms of heart attacks and strokes are important not only in saving lives, but also in preserving quality of life. Findings from recent research have yielded that the prevalence of cardiovascular disease risk factors are higher in rural populations, suggesting that adults living in rural locales may be at higher risk for heart attack and/or stroke. Knowledge of heart attack and stroke symptomology as well as calling 911 for a suspected heart attack or stroke are essential first steps in seeking care. This study sought to examine the knowledge of heart attack and stroke symptoms among rural adults in comparison to non-rural adults living in the U.S. Methods Using multivariate techniques, a cross-sectional analysis of an amalgamated multi-year Behavioral Risk Factor Surveillance Survey (BRFSS) database was performed. The dependent variable for this analysis was low heart attack and stroke knowledge score. The covariates for the analysis were: age, sex, race/ethnicity, annual household income, attained education, health insurance status, having a health care provider (HCP), timing of last routine medical check-up, medical care deferment because of cost, self-defined health status and geographic locale. Results The weighted n for this study overall was 103,262,115 U.S. adults > =18 years of age. Approximately 22.0% of these respondents were U.S. adults living in rural locales. Logistic regression analysis revealed that those U.S. adults who had low composite heart attack and stroke knowledge scores were more likely to be rural (OR = 1.218 95%CI 1.216-1.219) rather than non-rural residents. Furthermore, those with low scores were more likely to be: male (OR = 1.353 95%CI 1.352-1.354), >65 years of age (OR = 1.369 95%CI 1.368-1.371), African American (OR = 1.892 95%CI 1.889-1.894), not educated beyond high school (OR = 1.400 955CI 1.399-1.402), uninsured (OR = 1.308 95%CI 1.3-6-1.310), without a HCP

  10. Grown-up congenital heart (GUCH) disease: current needs and provision of service for adolescents and adults with congenital heart disease in the UK

    PubMed Central

    2002-01-01

    The size of the national population of patients with grown-up congenital heart disease (GUCH) is uncertain, but since 80–85% of patients born with congenital heart disease now survive to adulthood (age 16 years), an annual increase of 2500 can be anticipated according to birth rate. Organisation of medical care is haphazard with only three of 18 cardiac surgical centres operating on over 30 cases per annum and only two established specialised units fully equipped and staffed. Not all grown-ups with congenital heart disease require the same level of expertise; 20–25% are complex, rare, etc, and require life long expert supervision and/or intervention; a further 35–40% require access to expert consultation. The rest, about 40%, have simple or cured diseases and need little or no specialist expertise. The size of the population needing expertise is small in comparison to coronary and hypertensive disease, aging, and increasing in complexity. It requires expert cardiac surgery and specialised medical cardiology, intensive care, electrophysiology, imaging and interventions, "at risk" pregnancy services, connection to transplant services familiar with their basic problem, clinical nurse specialist advisors, and trained nurses. An integrated national service is described with 4–6 specialist units established within adult cardiology, ideally in relation or proximity to university hospital/departments in appropriate geographic location, based in association with established paediatric cardiac surgical centres with designated inpatient and outpatient facilities for grown-up patients with congenital heart disease. Specialist units should accept responsibility for educating the profession, training the specialists, cooperative research, receiving patients "out of region", sharing particular skills between each other, and they must liaise with other services and trusts in the health service, particularly specified outpatient clinics in district and regional centres. Not

  11. Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations From the Heart Failure Society of America Guideline Committee.

    PubMed

    Colvin, Monica; Sweitzer, Nancy K; Albert, Nancy M; Krishnamani, Rajan; Rich, Michael W; Stough, Wendy Gattis; Walsh, Mary Norine; Westlake Canary, Cheryl A; Allen, Larry A; Bonnell, Mark R; Carson, Peter E; Chan, Michael C; Dickinson, Michael G; Dries, Daniel L; Ewald, Gregory A; Fang, James C; Hernandez, Adrian F; Hershberger, Ray E; Katz, Stuart D; Moore, Stephanie; Rodgers, Jo E; Rogers, Joseph G; Vest, Amanda R; Whellan, David J; Givertz, Michael M

    2015-08-01

    The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients. PMID:26051012

  12. Changing practice of cardiac surgery in adult patients with congenital heart disease

    PubMed Central

    Srinathan, S K; Bonser, R S; Sethia, B; Thorne, S A; Brawn, W J; Barron, D J

    2005-01-01

    Objectives: To review 13 years’ data from a unit for grown ups with congenital heart disease (GUCH) to understand the change in surgical practice. Methods: Records were reviewed of patients over 16 years of age undergoing surgery between 1 January 1990 and 31 December 2002 in a dedicated GUCH unit. Patients with atrial septal defects were included but not those with Marfan’s syndrome or undergoing a first procedure for bicuspid aortic valves. Three equal time periods of 52 months were analysed. Results: Of 474 operations performed, 162 (34.2%) were repeat operations. The percentage of repeat operations increased from 24.8% (41 of 165) in January 1990–April 1994 to 49.7% (74 of 149) in September 1998–December 2002. Mortality was 6.3% (n  =  30). The median age decreased from 25.4 years (interquartile range 18.7) in January 1990–April 1994 to 23.9 (interquartile range 17.3) in September 1998–December 2002 (p  =  0.04). The proportion of patients with a “simple” diagnosis decreased from 45.4% (74 or 165) in January 1990–April 1994 to 27.5% (41 of 149) in September 1998–December 2002 (p  =  0.013). Pulmonary valve replacements in operated tetralogy of Fallot increased from one case in January 1990–April 1994 to 23 cases in September 1998–December 2002 and conduit replacement increased from five cases to 17. However, secundum atrial septal defect closures decreased from 35 cases to 14 (p < 0.0001). The estimated cost (not including salaries and prosthetics) incurred by an adult patient with congenital heart disease was £2290 compared with £2641 for a patient undergoing coronary artery bypass grafting. Conclusion: Despite the impact of interventional cardiology, the total number of surgical procedures remained unchanged. The complexity of the cases increased particularly with repeat surgery. Nevertheless, the patients do well with low mortality and the inpatient costs remain comparable with costs of surgery for acquired disease. PMID

  13. Continuous Multi-Parameter Heart Rate Variability Analysis Heralds Onset of Sepsis in Adults

    PubMed Central

    Ahmad, Saif; Ramsay, Tim; Huebsch, Lothar; Flanagan, Sarah; McDiarmid, Sheryl; Batkin, Izmail; McIntyre, Lauralyn; Sundaresan, Sudhir R.; Maziak, Donna E.; Shamji, Farid M.; Hebert, Paul; Fergusson, Dean; Tinmouth, Alan; Seely, Andrew J. E.

    2009-01-01

    Background Early diagnosis of sepsis enables timely resuscitation and antibiotics and prevents subsequent morbidity and mortality. Clinical approaches relying on point-in-time analysis of vital signs or lab values are often insensitive, non-specific and late diagnostic markers of sepsis. Exploring otherwise hidden information within intervals-in-time, heart rate variability (HRV) has been documented to be both altered in the presence of sepsis, and correlated with its severity. We hypothesized that by continuously tracking individual patient HRV over time in patients as they develop sepsis, we would demonstrate reduced HRV in association with the onset of sepsis. Methodology/Principal Findings We monitored heart rate continuously in adult bone marrow transplant (BMT) patients (n = 21) beginning a day before their BMT and continuing until recovery or withdrawal (12±4 days). We characterized HRV continuously over time with a panel of time, frequency, complexity, and scale-invariant domain techniques. We defined baseline HRV as mean variability for the first 24 h of monitoring and studied individual and population average percentage change (from baseline) over time in diverse HRV metrics, in comparison with the time of clinical diagnosis and treatment of sepsis (defined as systemic inflammatory response syndrome along with clinically suspected infection requiring treatment). Of the 21 patients enrolled, 4 patients withdrew, leaving 17 patients who completed the study. Fourteen patients developed sepsis requiring antibiotic therapy, whereas 3 did not. On average, for 12 out of 14 infected patients, a significant (25%) reduction prior to the clinical diagnosis and treatment of sepsis was observed in standard deviation, root mean square successive difference, sample and multiscale entropy, fast Fourier transform, detrended fluctuation analysis, and wavelet variability metrics. For infected patients (n = 14), wavelet HRV demonstrated a 25% drop from baseline 35 h

  14. Murine heterotopic heart transplant technique.

    PubMed

    Plenter, Robert J; Grazia, Todd J

    2014-01-01

    It is now over forty years since this technique was first reported by Corry, Wynn and Russell. Although it took some years for other labs to become proficient in and utilize this technique, it is now widely used by many laboratories around the world. A significant refinement to the original technique was developed and reported in 2001 by Niimi. Described here are the techniques that have evolved over more than a decade in the hands of three surgeons (Plenter, Grazia, Pietra) in our center. These techniques are now being passed on to a younger generation of surgeons and researchers. Based largely on the Niimi experience, the procedures used have evolved in the fine details - details which we will endeavor to relate here in such a way that others may be able to use this very useful model. Like Niimi, we have found that a video aid to learning is a priceless resource for the beginner. PMID:25046118

  15. Concise review: The role of C-kit expressing cells in heart repair at the neonatal and adult stage.

    PubMed

    Hesse, Michael; Fleischmann, Bernd K; Kotlikoff, Michael I

    2014-07-01

    Ischemic heart disease is the number one cause of morbidity and mortality in the developed world due to the inability of the heart to replace lost myocytes. The cause of postinfarction myogenic failure has been a subject of intense scientific investigation and much controversy. Recent data indicate a brief perinatal developmental window exists during which postinfarction myogenesis, and substantial heart regeneration, occurs. By contrast, repair of an equivalent injury of the adult heart results in prominent revascularization without myogenesis. Here, we review recent experiments on neonatal postinjury myogenesis, examine the mechanistic hypotheses of dedifferentiation and precursor expansion, and discuss experiments indicating that postinfarction revascularization derives primarily from cardiac vascular precursors. These data have profound consequences for the understanding of human heart repair, as they address the long standing question as to whether human postinfarction myogenic failure is due to the loss of precursors existent at the neonatal stage or to a context-dependent inhibition of these precursors within the infarct, and suggest strategies for the recapitulation of neonatal myogenic capacity and the augmentation of revascularization. PMID:24585704

  16. Predictors of Left Ventricular Dilatation in Young Adults (from the Bogalusa Heart Study)

    PubMed Central

    Haji, Showkat A.; Ulusoy, Rifat Eralp; Patel, Dharmendrakumar A.; Srinivasan, Sathanur R.; Chen, Wei; Delafontaine, Patrice; Berenson, Gerald S.

    2011-01-01

    Left ventricular (LV) dilatation may be an early sign of cardiac decompensation progressing to LV dysfunction. Determinants of LV dilatation in young asymptomatic adults are unknown. Five hundred six asymptomatic subjects (mean age 32 ± 3 years) enrolled in the Bogalusa Heart Study underwent echocardiographic examination. LV dilatation (LV end-diastolic diameter >5.5 cm) as measured by M-mode echocardiography was found in 31 subjects (6%). Subjects with LV dilatation had greater body mass indexes (32 ± 9 vs 27 ± 6 kg/m2, p <0.0001), systolic (119 ± 15 vs 112 ± 12 mm Hg, p = 0.007) and diastolic (79 ± 12 vs 75 ± 9 mm Hg, p = 0.04) blood pressures, and LV mass (230 ± 50 vs 123 ± 39 g, p <0.0001). Age, gender, race, and metabolic parameters (glucose, insulin, and lipoprotein levels) did not differ significantly between the subjects with and without LV dilatation. After correction for age, gender, and race differences, adulthood obesity (body mass index >30 kg/m2) was associated with a threefold odds ratio (2.9, 95% confidence interval 1.4 to 6.1), and hypertension (defined as per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) was also associated with a threefold odds ratio (3.0, 95% confidence interval 1.2 to 7.1) for an increased incidence of LV dilatation. There was an incremental increase in LV end-diastolic dimension depending on the presence of hypertension or obesity, and subjects with obesity and hypertension in adulthood had the greatest degree of LV end-diastolic dimensions. In multiple regression analyses, body mass index in childhood was the only significant predictor of LV dilatation in adulthood (odds ratio 1.47, 95% confidence interval 1.03 to 2.09). In conclusion, obesity beginning in childhood and obesity and hypertension in young adulthood are predictors of LV dilatation in an otherwise healthy young adult population. PMID:17056336

  17. Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second-signal requirements.

    PubMed Central

    McDouall, R M; Page, C S; Hafizi, S; Yacoub, M H; Rose, M L

    1996-01-01

    Human endothelial cells have been shown to be capable of causing direct allostimulation of T cells. However, the majority of immunological studies of human endothelial cells have been performed on cells of fetal origin. Here we use endothelial cells isolated from the adult human heart, both large vessel (coronary artery, pulmonary artery and aorta) and also microvascular. We have examined the ability of all these endothelial cells to cause direct allostimulation of T cells, and show that purified CD4+ T cells can proliferate in response to adult human heart endothelial cells, the response being dependent on pretreatment of the endothelial cells with interferon-gamma (IFN-gamma) and inhibited by anti-HLA-DR monoclonal antibody. The proliferative responses of CD8+ T cells to adult but not fetal endothelial cells was inconsistent and weak. Proliferative responses were not blocked by CTLA4-Ig, which inhibits T-cell responses to "classical' antigen-presenting cells (APC), but > 50% inhibition was achieved with monoclonal antibody to lymphocyte function-associated antigen-3 (LFA-3). These results show that adult human cardiovascular endothelial cells are capable of causing allostimulation of resting CD4+ T cells, using a different second signal to classical APC. In view of these findings endothelial cells should be considered as APC following solid organ transplantation. PMID:8943718

  18. Dietary carbohydrates, refined grains, glycemic load, and risk of coronary heart disease in Chinese adults.

    PubMed

    Yu, Danxia; Shu, Xiao-Ou; Li, Honglan; Xiang, Yong-Bing; Yang, Gong; Gao, Yu-Tang; Zheng, Wei; Zhang, Xianglan

    2013-11-15

    The potential long-term association between carbohydrate intake and the risk of coronary heart disease (CHD) remains unclear, especially among populations who habitually have high-carbohydrate diets. We prospectively examined intakes of carbohydrates and staple grains as well as glycemic index and glycemic load in relation to CHD among 117,366 Chinese women and men (40-74 years of age) without history of diabetes, CHD, stroke, or cancer at baseline in Shanghai, China. Diet was assessed using validated food frequency questionnaires. Incident CHD cases were ascertained during follow-ups (in women, the mean was 9.8 years and in men, the mean was 5.4 years) and confirmed by medical records. Carbohydrate intake accounted for 67.5% of the total energy intake in women and 68.5% in men. Seventy percent of total carbohydrates came from white rice and 17% were from refined wheat products. Positive associations between carbohydrate intakess and CHD were found in both sexes (all P for heterogeneity > 0.35). The combined multivariate-adjusted hazard ratios for the lowest to highest quartiles of carbohydrate intake, respectively, were 1.00, 1.38, 2.03, and 2.88 (95% confidence interval: 1.44, 5.78; P for trend = 0.001). The combined hazard ratios comparing the highest quartile with the lowest were 1.80 (95% confidence interval: 1.01, 3.17) for refined grains and 1.87 (95% confidence interval: 1.00, 3.53) for glycemic load (both P for trend = 0.03). High carbohydrate intake, mainly from refined grains, is associated with increased CHD risk in Chinese adults. PMID:24008907

  19. Posture and Gender Differentially Affect Heart Rate Variability of Symptomatic Mitral Valve Prolapse and Normal Adults

    PubMed Central

    Chang, Chien-Jung; Chen, Ya-Chu; Lee, Chih-Hsien; Yang, Ing-Fang; Yang, Ten-Fang

    2016-01-01

    Background Heart rate variability (HRV) has been shown to be a useful measure of autonomic activity in healthy and mitral valve prolapsed (MVP) subjects. However, the effects of posture and gender on HRV in symptomatic MVP and normal adults had not been elucidated in Taiwan. Methods A total of 118 MVP patients (7 males, 39 ± 7 years old; and 111 females, 42 ± 13 years old) and 148 healthy control (54 males, 28 ± 4 years old; and 94 females, 26 ± 6 years old) were investigated. The diagnosis of MVP was confirmed by cross-sectional echocardiography. A locally developed Taiwanese machine was used to record the HRV parameters for MVP and control groups in three stationary positions. Thereafter, the HRV time-domain parameters, and the frequency-domain parameters derived from fast Fourier transform or autoregressive methods were analyzed. Results The MVP group showed a decrease in time domain parameters and obtunded postural effects on frequency domain parameters moreso than the control group. Though the parasympathetic tone was dominant in female (higher RMSSD, nHF and lower nLF vs. male), the sympathetic outflow was higher in MVP female (lower SDNN, NN50 and higher nLF vs. normal female). While the parasympathetic activity was lower in male, sympathetic outflow was dominant in MVP male (lower nHF and higher nLF vs. normal male). Conclusions Both MVP female and male subjects had elevated levels of sympathetic outflow. The obtunded postural effects on frequency domain measures testified to the autonomic dysregulation of MVP subjects. PMID:27471360

  20. Lesion-Specific Factors Contributing to Inhospital Costs in Adults With Congenital Heart Disease.

    PubMed

    Cedars, Ari M; Burns, Sara; Novak, Eric L; Amin, Amit P

    2016-06-01

    The population of adults with congenital heart disease (ACHD) in the United States is growing rapidly with concomitant increases in care costs. We sought to define the variables having the greatest influence on annual cost of inpatient care in patients with ACHD in the United States. To do so, we conducted a retrospective analysis of admissions in patients >18 years old with a 3-digit International Classification of Disease, Ninth Revision, code of 745 to 747 from the State Inpatient Databases of Arkansas (2008 to 2010), California (2003 to 2012), Florida (2005 to 2012), Hawaii (2006 to 2010), Nebraska (2003 to 2011), and New York (2005 to 2012). We selected variables we believed would have the greatest effect on care costs and built a series of multivariable regression models grouping patients by congenital lesion to examine the relative contribution of the specified variables to total annual inpatient cost. We analyzed a total of 68,314 patients aged 57 ± 18.6 years, 51% of whom were women. The multivariable regression model had an overall R(2) of 0.35. Readmission was responsible for 10.3% of annual inpatient cost among all patients with ACHD and had the greatest effect on inpatient care cost for each congenital lesion except Eisenmenger syndrome and conotruncal abnormalities, for both of which it was the second most significant contributor. Other major contributors to annual inpatient care costs included length of stay and operative procedures. In conclusion, rehospitalization is the most significant contributor to annual inpatient cost for individual patients with ACHD in the United States, regardless of underlying anatomy. PMID:27079214

  1. Transcatheter interventions for multiple lesions in adults with congenital heart disease

    PubMed Central

    Hamid, Tahir; Clarke, Bernard; Mahadevan, Vaikom

    2012-01-01

    Recent advances in diagnosis, surgery and interventional management have significantly changed the quality of life of patients with congenital heart disease. Historically, congenital heart disease patients with multiple cardiac lesions have been referred for surgery; however, with the advent of newer technologies and expertise, transcatheter treatment has evolved as an alternative option. A series of patients who underwent interventional procedures for multiple congenital heart disease lesions with excellent procedural and medium-term outcomes is reported. PMID:22826648

  2. Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan

    PubMed Central

    2014-01-01

    Background The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE) in adult congenital heart disease (ConHD) patients in Taiwan. Methods From the National Health Insurance Research Database (1997-2010), adult patients (≥18 years) with ConHD were identified and compared to non-ConHD control patients. The primary end point was the incidence of MACE. Cox proportional hazards models were used to compute hazard ratios as estimates for multivariate adjusted relative risks with or without adjusting for age and sex. Results A total of 3,267 adult patients with ConHD were identified between 2000 and 2003 with a median follow-up of 11 years till December 31, 2010. The five most common types of ConHD were atrial septal defects, ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, and pulmonary stenosis. Overall, the incidence of MACE was 4.0-fold higher in the ConHD group compared with the controls. After adjustment for age and gender, the patients with ConHD had an increased risk of heart failure, malignant dysrhythmia, acute coronary syndrome, and stroke. The adult ConHD patients had a decreased life-long risk of MACE if they received surgical correction, especially in the patients with atrial septal defects. Conclusions After a median of 11 years of follow-up, the Taiwanese patients with ConHD were at an increased risk of life-long cardiovascular MACE, including heart failure, stroke, acute coronary syndrome, and malignant dysrhythmia. Surgical correction may help to decrease long-term MACE in ConHD patients, especially those with ASD. PMID:24655794

  3. In utero and early life exposure to diesel exhaust air pollution increases adult susceptibility to heart failure in mice

    PubMed Central

    2013-01-01

    Background Fine particulate air pollution (PM2.5) is a global health concern, as exposure to PM2.5 has consistently been found to be associated with increased cardiovascular morbidity and mortality. Although adult exposure to traffic related PM2.5, which is largely derived from diesel exhaust (DE), has been associated with increased cardiac hypertrophy, there are limited investigations into the potential effect of in utero and early life exposure on adult susceptibility to heart disease. In this study, we investigate the effect of in utero and early life exposure to DE on adult susceptibility to heart failure. Methods Female C57BL/6 J mice were exposed to either filtered air (FA) or DE for 3 weeks (≈300 μg/m3 PM2.5 for 6 hours/day, 5 days/week) and then introduced to male breeders for timed matings. Female mice were exposed to either FA or DE throughout pregnancy and until offspring were 3 weeks of age. Offspring were then transferred to either FA or DE for an additional 8 weeks of exposure. At 12 weeks of age, male offspring underwent a baseline echocardiographic assessment, followed by a sham or transverse aortic constriction (TAC) surgery to induce pressure overload. Following sacrifice three weeks post surgery, ventricles were processed for histology to assess myocardial fibrosis and individual cardiomyocyte hypertrophy. mRNA from lung tissue was isolated to measure expression of inflammatory cytokines IL6 and TNFα. Results We observed that mice exposed to DE during in utero and early life development have significantly increased susceptibility to cardiac hypertrophy, systolic failure, myocardial fibrosis, and pulmonary congestion following TAC surgery compared to FA control, or adult DE exposed mice. In utero and early life DE exposure also strongly modified the inflammatory cytokine response in the adult lung. Conclusions We conclude that exposure to diesel exhaust air pollution during in utero and early life development in mice increases adult

  4. Heart failure - home monitoring

    MedlinePlus

    ... Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice ... Cardiovascular Nursing; American Heart Association Council on Clinical ... Heart Association Council on Nutrition, Physical Activity, ...

  5. High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts

    PubMed Central

    Kang, Bong Jin; Park, Jinhyoung; Kim, Jieun; Kim, Hyung Ham; Lee, Changyang; Hwang, Jae Youn; Lien, Ching-Ling; Shung, K. Kirk

    2015-01-01

    Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s−1 with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation. PMID:25505135

  6. Comparative effects of oral chlorpyrifos exposure on cholinesterase activity and muscarinic receptor binding in neonatal and adult rat heart.

    PubMed

    Howard, Marcia D; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N

    2007-09-01

    Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M(2) muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M(2) receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor-mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M(2) receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age-related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac cholinesterase (ChE) activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1x LD(10): neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1x LD(10), relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (approximately 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC(50) values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that

  7. Comparative Effects of Oral Chlorpyrifos Exposure on Cholinesterase Activity and Muscarinic Receptor Binding in Neonatal and Adult Rat Heart

    PubMed Central

    Howard, Marcia D.; Mirajkar, Nikita; Karanth, Subramanya; Pope, Carey N.

    2010-01-01

    Organophosphorus (OP) pesticides elicit acute toxicity by inhibiting acetylcholinesterase (AChE), the enzyme responsible for inactivating acetylcholine (ACh) at cholinergic synapses. A number of OP toxicants have also been reported to interact directly with muscarinic receptors, in particular the M2 muscarinic subtype. Parasympathetic innervation to the heart primarily regulates cardiac function by activating M2 receptors in the sinus node, atrial-ventricular node and conducting tissues. Thus, OP insecticides can potentially influence cardiac function in a receptor–mediated manner indirectly by inhibiting acetylcholinesterase and directly by binding to muscarinic M2 receptors. Young animals are generally more sensitive than adults to the acute toxicity of OP insecticides and age related differences in potency of direct binding to muscarinic receptors by some OP toxicants have been reported. We thus compared the effects of the common OP insecticide chlorpyrifos (CPF) on functional signs of toxicity and cardiac ChE activity and muscarinic receptor binding in neonatal and adult rats. Dosages were based on acute lethality (i.e., 0.5 and 1 × LD10: neonates, 7.5 and 15 mg/kg; adults, 68 and 136 mg/kg). Dose- and time-related changes in body weight and cholinergic signs of toxicity (involuntary movements) were noted in both age groups. With 1 × LD10, relatively similar maximal reductions in ChE activity (95%) and muscarinic receptor binding (≈ 30%) were noted, but receptor binding reductions appeared earlier in adults and were more prolonged in neonates. In vitro inhibition studies indicated that ChE in neonatal tissues was markedly more sensitive to inhibition by the active metabolite of chlorpyrifos (i.e., chlorpyrifos oxon, CPO) than enzyme in adult tissues (IC50 values: neonates, 17 nM; adults, 200 nM). Chelation of free calcium with EDTA had relatively little effect on in vitro cholinesterase inhibition, suggesting that differential A-esterase activity was not

  8. Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts.

    PubMed

    Lin, Xianming; O'Malley, Heather; Chen, Chunling; Auerbach, David; Foster, Monique; Shekhar, Akshay; Zhang, Mingliang; Coetzee, William; Jalife, José; Fishman, Glenn I; Isom, Lori; Delmar, Mario

    2014-08-15

    Na(+) current (INa) is determined not only by the properties of the pore-forming voltage-gated Na(+) channel (VGSC) α subunit, but also by the integrated function of a molecular aggregate (the VGSC complex) that includes the VGSC β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including cases of Brugada syndrome and sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null mouse models to understand better the relation between Scn1b expression, and cardiac electrical function. Using a combination of macropatch and scanning ion conductance microscopy we show that loss of Scn1b in juvenile null animals resulted in increased tetrodotoxin-sensitive INa but only in the cell midsection, even before full T-tubule formation; the latter occurred concurrent with increased message abundance for the neuronal Scn3a mRNA, suggesting increased abundance of tetrodotoxin-sensitive NaV1.3 protein and yet its exclusion from the region of the intercalated disc. Ventricular myocytes from cardiac-specific adult Scn1b null animals showed increased Scn3a message, prolonged action potential repolarization, presence of delayed after-depolarizations and triggered beats, delayed Ca(2+) transients and frequent spontaneous Ca(2+) release events and at the whole heart level, increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca(2+) homeostasis were prevented by 100 nm tetrodotoxin. Our results suggest that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na(+) channel α subunit, can be partly consequent to disrupted intracellular Ca(2+) homeostasis in ventricular myocytes. PMID:25128572

  9. The Drosophila Hand gene is required for remodeling of the developing adult heart and midgut during metamorphosis

    PubMed Central

    Lo, Patrick C.H.; Zaffran, Stéphane; Sénatore, Sébastien; Frasch, Manfred

    2007-01-01

    The Hand proteins of the bHLH family of transcriptional factors play critical roles in vertebrate cardiogenesis. In Drosophila, the single orthologous Hand gene is expressed in the developing embryonic dorsal vessel (heart), lymph glands, circular visceral musculature, and a subset of CNS cells. We demonstrate that the absence of Hand activity causes semilethality during the early larval instars. The dorsal vessel and midgut musculature are unaffected in null mutant embryos, but in a large fraction the lymph glands are missing. However, homozygous adult flies lacking Hand possess morphologically abnormal dorsal vessels characterized by a disorganized myofibrillar structure, reduced systolic and diastolic diameter, abnormal heartbeat contractions, and suffer from premature lethality. In addition, their midguts are highly deformed; in the most severe cases, there is midgut blockage and a massive excess of ectopic peritrophic membrane tubules exiting a rupture in an anterior midgut bulge. Nevertheless, the visceral musculature appears to be relatively normal. Based on these phenotypes, we conclude that the expression of the Drosophila Hand gene in the dorsal vessel and circular visceral muscles is mainly required during pupal stages, when Hand participates in the proper hormone-dependent remodeling of the larval aorta into the adult heart and in the normal morphogenesis of the adult midgut endoderm during metamorphosis. PMID:17904115

  10. Effect of Fasting Blood Glucose Level on Heart Rate Variability of Healthy Young Adults

    PubMed Central

    Lutfi, Mohamed Faisal; Elhakeem, Ramaze Farouke

    2016-01-01

    Background Previous studies reported increased risk of cardiac events in subjects with fasting blood glucose (FBG) levels lower than the diagnostic threshold of diabetes mellitus. However, whether increased cardiac events in those with upper normal FBG is secondary to the shift of their cardiac sympathovagal balance towards sympathetic predominance is unknown. Aims To assess the association between FBG levels and cardiac autonomic modulation (CAM) in euglycaemic healthy subjects based on heart rate variability (HRV) derived indices. Subjects and Methods The study enrolled 42 healthy young adults. Following sociodemographic and clinical assessment, blood samples were collected to measure FBG levels. Five minutes ECG recordings were performed to all participants to obtain frequency domain HRV measurements, namely the natural logarithm (Ln) of total power (LnTP), very low frequency (LnVLF), low frequency (LnLF) and high frequency (LnHF), low frequency/ high frequency ratio (LnLF/HF), normalized low frequency (LF Norm) and high frequency (HF Norm). Results FBG levels correlated positively with LnHF (r = 0.33, P = 0.031) and HF Norm (r = 0.35, P = 0.025) and negatively with LF Norm (r = -0.35, P = 0.025) and LnLF/HF (r = -0.33, P = 0.035). LnHF and HF Norm were significantly decreased in subjects with the lower (4.00 (1.34) ms2/Hz and 33.12 (11.94) n.u) compared to those with the upper FBG quartile (5.64 (1.63) ms2/Hz and 49.43 (17.73) n.u, P = 0.013 and 0.032 respectively). LF Norm and LnLF/HF were significantly increased in subjects with the lower (66.88 (11.94) n.u and 0.73 (0.53)) compared to those with the higher FBG quartile (50.58 (17.83) n.u and 0.03 (0.79), P = 0.032 and 0.038 respectively). Conclusion The present study is the first to demonstrate that rise of blood glucose concentration, within physiological range, is associated with higher parasympathetic, but lower sympathetic CAM. Further researches are needed to set out the glycemic threshold beyond which

  11. S-Nitrosoglutathione Reductase Deficiency Enhances the Proliferative Expansion of Adult Heart Progenitors and Myocytes Post Myocardial Infarction

    PubMed Central

    Hatzistergos, Konstantinos E; Paulino, Ellena C; Dulce, Raul A; Takeuchi, Lauro M; Bellio, Michael A; Kulandavelu, Shathiyah; Cao, Yenong; Balkan, Wayne; Kanashiro-Takeuchi, Rosemeire M; Hare, Joshua M

    2015-01-01

    Background Mammalian heart regenerative activity is lost before adulthood but increases after cardiac injury. Cardiac repair mechanisms, which involve both endogenous cardiac stem cells (CSCs) and cardiomyocyte cell-cycle reentry, are inadequate to achieve full recovery after myocardial infarction (MI). Mice deficient in S-nitrosoglutathione reductase (GSNOR−⁄−), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI. Here, we tested the hypothesis that GSNOR activity modulates cardiac cell proliferation in the post-MI adult heart. Methods and Results GSNOR−⁄− and C57Bl6/J (wild-type [WT]) mice were subjected to sham operation (n=3 GSNOR−⁄−; n=3 WT) or MI (n=41 GSNOR−⁄−; n=65 WT). Compared with WT,GSNOR−⁄− mice exhibited improved survival, cardiac performance, and architecture after MI, as demonstrated by higher ejection fraction (P<0.05), lower endocardial volumes (P<0.001), and diminished scar size (P<0.05). In addition, cardiomyocytes from post-MI GSNOR−⁄− hearts exhibited faster calcium decay and sarcomeric relaxation times (P<0.001). Immunophenotypic analysis illustrated that post-MI GSNOR−⁄− hearts demonstrated enhanced neovascularization (P<0.001), c-kit+ CSC abundance (P=0.013), and a ≈3-fold increase in proliferation of adult cardiomyocytes and c-kit+/CD45− CSCs (P<0.0001 and P=0.023, respectively) as measured by using 5-bromodeoxyuridine. Conclusions Loss of GSNOR confers enhanced post-MI cardiac regenerative activity, characterized by enhanced turnover of cardiomyocytes and CSCs. Endogenous denitrosylases exert an inhibitory effect over cardiac repair mechanisms and therefore represents a potential novel therapeutic target. PMID:26178404

  12. Prior Hospitalization and the Risk of Heart Attack in Older Adults: A 12-Year Prospective Study of Medicare Beneficiaries

    PubMed Central

    Bentler, Suzanne E.; Liu, Li; Jones, Michael P.; Kaskie, Brian; Hockenberry, Jason; Chrischilles, Elizabeth A.; Wright, Kara B.; Geweke, John F.; Obrizan, Maksym; Ohsfeldt, Robert L.; Rosenthal, Gary E.; Wallace, Robert B.

    2010-01-01

    Background. We investigated whether prior hospitalization was a risk factor for heart attacks among older adults in the survey on Assets and Health Dynamics among the Oldest Old. Methods. Baseline (1993–1994) interview data were linked to 1993–2005 Medicare claims for 5,511 self-respondents aged 70 years and older and not enrolled in managed Medicare. Primary hospital International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) 410.xx discharge codes identified postbaseline hospitalizations for acute myocardial infarctions (AMIs). Participants were censored at death or postbaseline managed Medicare enrollment. Traditional risk factors and other covariates were included. Recent postbaseline non-AMI hospitalizations (ie, prior hospitalizations) were indicated by a time-dependent marker, and sensitivity analyses identified their peak effect. Results. The total number of person-years of surveillance was 44,740 with a mean of 8.1 (median = 9.1) per person. Overall, 483 participants (8.8%) suffered postbaseline heart attacks, with 423 participants (7.7%) having their first-ever AMI. As expected, significant traditional risk factors were sex (men); race (whites); marital status (never being married); education (noncollege); geography (living in the South); and reporting a baseline history of angina, arthritis, diabetes, and heart disease. Risk factors were similar for both any postbaseline and first-ever postbaseline AMI analyses. The time-dependent recent non-AMI hospitalization marker did not alter the effects of the traditional risk factors but increased AMI risk by 366% (adjusted hazards ratio = 4.66, p < .0001). Discussion. Our results suggest that some small percentage (<3%) of heart attacks among older adults might be prevented if effective short-term postdischarge planning and monitoring interventions were developed and implemented. PMID:20106961

  13. Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration.

    PubMed

    Phinney, Donald G; Baddoo, Melody; Dutreil, Maria; Gaupp, Dina; Lai, Wen Tzu; Isakova, Iryna A

    2006-06-01

    Mesenchymal stem cells (MSCs) have demonstrated efficacy as cellular vectors for treating a variety of nervous system disorders. Nevertheless, few studies have quantified MSC engraftment levels or explored the mechanisms that promote their survival and migration in nervous tissue. In this study, we compared the engraftment kinetics and anatomical distribution of murine, male MSCs injected intracranially into neonatal versus adult female mice using a real-time PCR assay that targets the mouse SRY gene. These analyses revealed that MSCs exhibited low but equivalent engraftment levels in the central nervous system (CNS) of neonatal and adult transplant recipients at 12 days post-injection. However, MSC engraftment levels were significantly greater at 60 and 150 days post-transplantation in neonates as compared to adults. Despite these differences, engrafted MSCs were widely distributed along the neuraxis of the CNS in both transplant groups. Collectively, these data indicate that proliferation, but not engraftment and migration, of MSCs in brain are regulated by the host microenvironment. Using a genomics approach, we also identified MSC subpopulations that express neural adhesion proteins and receptors that regulate neuronal cell migration in brain, including cadherin 2, neurexin 1, ninjurin 1, neogenin 1, neuropilin 2, and roundabout homolog 1 and 4. Functional studies indicate these proteins confer cell adhesion and migration of MSCs in response to the appropriate chemoattractant. On the basis of these findings, we conclude that the unique molecular composition of MSC subpopulations imparts to them an inherent capacity to engraft and migrate in brain. These subpopulations may represent more potent cellular vectors for treating CNS disorders. PMID:16846379

  14. Chronic hemodynamic unloading regulates the morphologic development of newborn mouse hearts transplanted into the ear of isogeneic adult mice.

    PubMed Central

    Rossi, M. A.

    1992-01-01

    The morphologic development of newborn mouse hearts transplanted into the pinna of the ears of isogeneic adult mice was assessed in comparison to in situ ventricular myocardium of recipients. The grafted hearts became vascularized from the auricular artery at the base of the ear, and although these preparations appeared not to be intrinsically innervated, most of them showed grossly visible pulsatile activity. Since they were not subjected to hemodynamic load due to working against a pressure gradient, this technique provided an interesting experimental model for studies on the growth of chronically unloaded tissue. The ultrastructure of the myocardium from neonatal mouse hearts, which were fixed immediately after dissection, revealed no differences in comparison to previously published observations. By 2 months, there was virtually no change in the myocardial cell size as compared with newborn mouse cardiac tissue. The heterotopic hearts showed a mature ultrastructural appearance, with parallel bands of myofibrils alternating with rows of mitochondria and differentiated intercalated discs comparable to in situ myocardium. The interstitial space was widened due to fibrous tissue, with activated fibroblasts and a few mononuclear cells. In contrast, by 6 months after transplantation, the heterotopic myocardium showed a dispersion of the measured cell diameter of myocytes, with atrophy of a certain population of cells and hypertrophy in others; nevertheless, the mean cell diameter was similar to that observed in 2-month grafts. The myocytes showed significant dissociation from each other in fibrous tissue and a cellular infiltrate composed predominantly of mononuclear cells, and greater variability of the parallel arrangement of cells. They often contained myofibrils coursing in different directions rather than in parallel. Normal-sized or predominantly atrophic degenerated myocytes, characterized by a wide variety of ultrastructural alterations, were present. By 12

  15. Coronary Arteries in Childhood Heart Disease: Implications for Management of Young Adults

    PubMed Central

    Baraona, Fernando; Valente, Anne Marie; Porayette, Prashob; Pluchinotta, Francesca Romana; Sanders, Stephen P.

    2013-01-01

    Survival of patients with congenital heart defects has improved dramatically. Many will undergo interventional catheter or surgical procedures later in life. Others will develop atherosclerotic or post-surgical coronary heart disease. The coronary artery anatomy in patients with congenital heart disease differs substantially from that seen in the structurally normal heart. This has implications for diagnostic procedures as well as interventions. The unique epicardial course seen in some defects could impair interpretation of coronary angiograms. Interventional procedures, especially at the base of the heart, risk injuring unusually placed coronary arteries so that coronary artery anatomy must be delineated thoroughly prior to the procedure. In this review, we will describe the variants of coronary artery anatomy and their implications for interventional and surgical treatment and for sudden death during late follow-up in several types of congenital heart defects including: tetralogy of Fallot, truncus arteriosus, transposition of the great arteries, double outlet right ventricle, congenitally corrected transposition of the great arteries and defects with functionally one ventricle. We will also discuss the coronary abnormalities seen in Kawasaki disease. PMID:24294539

  16. Short-term acute effects of gutkha chewing on heart rate variability among young adults: A cross-sectional study

    PubMed Central

    Itagi, Afreen Begum H; Arora, Dimple; Patil, Navin A; Bailwad, Sandeep Anant; Yunus, GY; Goel, Ankit

    2016-01-01

    Background and Objectives: An increase in the consumption of smokeless tobacco has been noticed among high school, college students, and adults. Despite the antiquity and popularity of chewing tobacco in India, its effects have not been investigated systematically in humans. The aim of this study was to investigate acute effects of gutkha chewing on heart rate variability (HRV) among healthy young adults. Materials and Methods: A total of 60 young adult males were included in the study. Each individual was asked to chew tobacco and subjected to HRV analysis. HRV analysis using short-term electrocardiogram recording was used to measure HRV parameters before gutkha chewing and at 5, 15, and 30 min after chewing tobacco. One-way analysis of variance and paired t-test was used to assess changes over time. Results: There was a significant increase in heart rate (HR) during tobacco chewing. Mean HR at baseline measured 73.0 ± 6.2 bpm. There was a rise in mean HR to 83.7 ± 9.1 bpm at 5 min during tobacco chewing and gradual reduction to baseline observed after 15 min followed by no significant change till 30 min. The normalized low-frequency power and LF/high-frequency (HF) power ratio were elevated after 5 min; however, normalized HF power was reduced after 5 min tobacco chewing. Conclusion: Gutkha is closely associated with traditional cardiovascular risk factors as detected by a transient enhancing sympathetic activity during tobacco chewing in the form of increased HRV parameters or an imbalance between sympathetic and parasympathetic neural activity among healthy young adults. PMID:26958522

  17. Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

    PubMed Central

    Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

    2016-01-01

    Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ± 7 years) were compared to 25 healthy age- and gender-matched controls. Assessments included a maximal treadmill test for peak oxygen uptake (VO2peak), oxygen uptake kinetics at onset of and on recovery from a submaximal treadmill test, functional mobility testing [Get Up and Go (GUG), Comfortable Gait Speed (CGS), Unipedal Stance (US)], and self-reported physical activity (PA). Results Compared to controls, HF had worse performance on GUG, CGS, and US, greater delays in submaximal oxygen uptake kinetics, and lower PA. In controls, VO2peak was more strongly associated with functional mobility and PA than submaximal oxygen uptake kinetics. In HF patients, submaximal oxygen uptake kinetics were similarly associated with GUG and CGS as VO2peak, but weakly associated with PA. Conclusions Based on their mobility performance, older HF patients with reduced ejection fraction are at risk for adverse functional outcomes. In this population, submaximal oxygen uptake measures may be equivalent to VO2 peak in predicting functional mobility, and in addition to being more feasible, may provide better insight into how aerobic function relates to mobility in older adults with HF. PMID:27594875

  18. Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type.

    PubMed

    Camerota, Filippo; Castori, Marco; Celletti, Claudia; Colotto, Marco; Amato, Silvia; Colella, Alessandra; Curione, Mario; Danese, Chiara

    2014-07-01

    Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome, hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue disorders strongly associating with pain, fatigue and other secondary aspects. Though not considered a diagnostic criterion for most EDS subtypes, cardiovascular involvement is a well-known complication in EDS. A case-control study was carried out on 28 adults with JHS/EDS-HT diagnosed according to current criteria, compared to 29 healthy subjects evaluating resting electrocardiographic (ECG), 24-h ECG and resting heart ultrasound data. Results obtained in the ECG studies showed a moderate excess in duration of the PR interval and P wave, an excess of heart conduction and rate abnormalities and an increased rate of mitral and tricuspid valve insufficiency often complicating with "true" mitral valve prolapse in the ecocardiographic study. These variable ECG subclinical anomalies reported in our sample may represent the resting surrogate of such a subnormal cardiovascular response to postural changes that are known to be present in patients with JHS/EDS-HT. Our findings indicate the usefulness of a full cardiologic evaluation of adults with JHS/EDS-HT for the correct management. PMID:24752348

  19. Combined triaxial accelerometry and heart rate telemetry for the physiological characterization of Latin dance in non-professional adults.

    PubMed

    Domene, Pablo A; Easton, Chris

    2014-03-01

    The purpose of this study was to value calibrate, cross-validate, and determine the reliability of a combined triaxial accelerometry and heart rate telemetry technique for characterizing the physiological and physical activity parameters of Latin dance. Twenty-two non-professional adult Latin dancers attended two laboratory-based dance trials each. After familiarization and a standardized warm-up, a multi-stage (3 x 5-minute) incremental (based on song tempo) Afro-Cuban salsa choreography was performed while following a video displayed on a projection screen. Data were collected with a portable indirect calorimeter, a heart rate telemeter, and wrist-, hip-, and ankle-mounted ActiGraph GT3X+ accelerometers. Prediction equations for energy expenditure and step count were value calibrated using forced entry multiple regression and cross-validated using a delete-one jackknife approach with additional Bland-Altman analysis. The average dance intensity reached 6.09 ± 0.96 kcal/kg/h and demanded 45.9 ± 11.3% of the heart rate reserve. Predictive ability of the derived models was satisfactory, where R(2) = 0.80; SEE = 0.44 kcal/kg/h and R(2) = 0.74; SEE = 3 step/min for energy expenditure and step count, respectively. Dependent t-tests indicated no differences between predicted and measured values for both energy expenditure (t65 = -0.25, p = 0.80) and step count (t65 = -0.89, p = 0.38). The 95% limits of agreement for energy expenditure and step count were -0.98 to 0.95 kcal/kg/h and -7 to 7 step/min, respectively. Latin dance to salsa music elicits physiological responses representative of moderate to vigorous physical activity, and a wrist-worn accelerometer with simultaneous heart rate measurement constitutes a valid and reliable technique for the prediction of energy expenditure and step count during Latin dance. PMID:24568801

  20. Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves

    PubMed Central

    van Geemen, Daphne; Soares, Ana L. F.; Oomen, Pim J. A.; Driessen-Mol, Anita; Janssen-van den Broek, Marloes W. J. T.; van den Bogaerdt, Antoon J.; Bogers, Ad J. J. C.; Goumans, Marie-José T. H.; Baaijens, Frank P. T.; Bouten, Carlijn V. C.

    2016-01-01

    There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation–but more pronounced in aortic valves–the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age. PMID:26867221

  1. Influence of hospital volume and outcomes of adult structural heart procedures.

    PubMed

    Panaich, Sidakpal S; Patel, Nilay; Arora, Shilpkumar; Patel, Nileshkumar J; Patel, Samir V; Savani, Chirag; Singh, Vikas; Sonani, Rajesh; Deshmukh, Abhishek; Cleman, Michael; Mangi, Abeel; Forrest, John K; Badheka, Apurva O

    2016-04-26

    Hospital volume is regarded amongst many in the medical community as an important quality metric. This is especially true in more complicated and less commonly performed procedures such as structural heart disease interventions. Seminal work on hospital volume relationships was done by Luft et al more than 4 decades ago, when they demonstrated that hospitals performing > 200 surgical procedures a year had 25%-41% lower mortality than those performing fewer procedures. Numerous volume-outcome studies have since been done for varied surgical procedures. An old adage "practice makes perfect" indicating superior operator and institutional experience at higher volume hospitals is believed to primarily contribute to the volume outcome relationship. Compelling evidence from a slew of recent publications has also highlighted the role of hospital volume in predicting superior post-procedural outcomes following structural heart disease interventions. These included transcatheter aortic valve repair, transcatheter mitral valve repair, septal ablation and septal myectomy for hypertrophic obstructive cardiomyopathy, left atrial appendage closure and atrial septal defect/patent foramen ovale closure. This is especially important since these structural heart interventions are relatively complex with evolving technology and a steep learning curve. The benefit was demonstrated both in lower mortality and complications as well as better economics in terms of lower length of stay and hospitalization costs seen at high volume centers. We present an overview of the available literature that underscores the importance of hospital volume in complex structural heart disease interventions. PMID:27152142

  2. When Hearts, Hands, and Feet Trump Brains: Centralist versus Peripheralist Responses in Children and Adults

    ERIC Educational Resources Information Center

    Winer, Gerald A.; Cottrell, Jane E.; Bica, Lori A.

    2009-01-01

    A series of studies examined the presence of centralist versus peripheralist responding about the physical location of psychological processes. Centralists respond that processes such as cognition and emotion are a function of the brain. Peripheralists respond that such processes are located in other parts of the body, such as the heart. Although…

  3. Influence of hospital volume and outcomes of adult structural heart procedures

    PubMed Central

    Panaich, Sidakpal S; Patel, Nilay; Arora, Shilpkumar; Patel, Nileshkumar J; Patel, Samir V; Savani, Chirag; Singh, Vikas; Sonani, Rajesh; Deshmukh, Abhishek; Cleman, Michael; Mangi, Abeel; Forrest, John K; Badheka, Apurva O

    2016-01-01

    Hospital volume is regarded amongst many in the medical community as an important quality metric. This is especially true in more complicated and less commonly performed procedures such as structural heart disease interventions. Seminal work on hospital volume relationships was done by Luft et al more than 4 decades ago, when they demonstrated that hospitals performing > 200 surgical procedures a year had 25%-41% lower mortality than those performing fewer procedures. Numerous volume-outcome studies have since been done for varied surgical procedures. An old adage “practice makes perfect” indicating superior operator and institutional experience at higher volume hospitals is believed to primarily contribute to the volume outcome relationship. Compelling evidence from a slew of recent publications has also highlighted the role of hospital volume in predicting superior post-procedural outcomes following structural heart disease interventions. These included transcatheter aortic valve repair, transcatheter mitral valve repair, septal ablation and septal myectomy for hypertrophic obstructive cardiomyopathy, left atrial appendage closure and atrial septal defect/patent foramen ovale closure. This is especially important since these structural heart interventions are relatively complex with evolving technology and a steep learning curve. The benefit was demonstrated both in lower mortality and complications as well as better economics in terms of lower length of stay and hospitalization costs seen at high volume centers. We present an overview of the available literature that underscores the importance of hospital volume in complex structural heart disease interventions. PMID:27152142

  4. The adult Göttingen minipig as a model for chronic heart failure after myocardial infarction: focus on cardiovascular imaging and regenerative therapies.

    PubMed

    Schuleri, Karl H; Boyle, Andrew J; Centola, Marco; Amado, Luciano C; Evers, Robert; Zimmet, Jeffrey M; Evers, Kristine S; Ostbye, Katherine M; Scorpio, Diana G; Hare, Joshua M; Lardo, Albert C

    2008-12-01

    Porcine models have become increasingly popular in cardiovascular research. The standard farm pig rapidly increases in body weight and size, potentially confounding serial measurements of cardiac function and morphology. We developed an adult porcine model that does not show physiologic increases in heart mass during the study period and is suitable for long-term study. We compared adult minipigs with the commonly used adolescent Yorkshire swine. Myocardial infarction was induced in adult Göttingen minipigs and adolescent Yorkshire swine by occlusion of the left anterior descending coronary artery followed by reperfusion. At 8 wk after infarction, the left ventricular ejection fraction was 34.1 +/- 2.3% in minipigs and 30.7 +/- 2.0% in Yorkshire swine. The left ventricular end-diastolic mass in Yorkshire pigs assessed by magnetic resonance imaging increased 17 +/- 5 g, from 42.6 +/- 4.3 g at week 1 after infarction to 52.8 +/- 6.6 g at week 8, whereas it remained unchanged in minipigs. Cardiac anatomy and physiology in adult minipigs were evaluated invasively by angiography and noninvasively by Multidetector Computed Tomography and by Magnetic Resonance Imaging at 1.5 T and 3 T prior to myocardial infarction and during folow-up. This porcine heart failure model is reproducible, mimics the pathophysiology in patients who have experienced myocardial infarction, and is suitable for imaging studies. New heart failure therapies and devices can be tested preclinically in this adult animal model of chronic heart failure. PMID:19149414

  5. The 2-Minute Step Test is Independently Associated with Cognitive Function in Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Raz, Naftali; Cohen, Ronald; Sweet, Lawrence H.; Colbert, Lisa H.; Josephson, Richard; Waechter, Donna; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Background and Aims Cognitive impairment is common in persons with heart failure (HF), and measures like the 6-minute walk test (6MWT) are known to correspond to level of impairment. The 2-minute step test (2MST) has been suggested as a more practical alternative to the 6MWT, though no study has examined whether it is associated with cognitive impairment in persons with HF. This study examined whether the 2MST is associated with cognitive function in older adults with HF. Methods Older adults with HF (N = 145; 68.97±9.31 years) completed the 2MST and a neuropsychological test battery that assessed function in multiple cognitive domains. Results Consistent with past work, HF patients exhibited high rates of cognitive impairment. Hierarchical regression analyses adjusting for demographic and medical characteistics found that the 2MST accounted for unique variance in global cognitive function (ΔR2 = .09, p < .001), executive function (ΔR2 = .03, p < .05), and language (ΔR2 = .10, p < .001). A trend emerged for attention (ΔR2 = .02, p = .09), Follow-up tests indicated that better 2MST performance was significantly correlated with better global, attention, executive, and language test performance. Conclusion The current results indicate that the 2MST is associated with cognitive function in older adults with HF. Further work is needed to clarify underlying mechanisms for this association and the value of implementing the 2MST during routine visits. PMID:22182711

  6. Scn1b deletion leads to increased tetrodotoxin-sensitive sodium current, altered intracellular calcium homeostasis and arrhythmias in murine hearts

    PubMed Central

    Lin, Xianming; O'Malley, Heather; Chen, Chunling; Auerbach, David; Foster, Monique; Shekhar, Akshay; Zhang, Mingliang; Coetzee, William; Jalife, José; Fishman, Glenn I; Isom, Lori; Delmar, Mario

    2015-01-01

    Na+ current (INa) is determined not only by the properties of the pore-forming voltage-gated Na+ channel (VGSC) α subunit, but also by the integrated function of a molecular aggregate (the VGSC complex) that includes the VGSC β subunit family. Mutations or rare variants in Scn1b (encoding the β1 and β1B subunits) have been associated with various inherited arrhythmogenic syndromes, including cases of Brugada syndrome and sudden unexpected death in patients with epilepsy. Here, we have used Scn1b null mouse models to understand better the relation between Scn1b expression, and cardiac electrical function. Using a combination of macropatch and scanning ion conductance microscopy we show that loss of Scn1b in juvenile null animals resulted in increased tetrodotoxin-sensitive INa but only in the cell midsection, even before full T-tubule formation; the latter occurred concurrent with increased message abundance for the neuronal Scn3a mRNA, suggesting increased abundance of tetrodotoxin-sensitive NaV1.3 protein and yet its exclusion from the region of the intercalated disc. Ventricular myocytes from cardiac-specific adult Scn1b null animals showed increased Scn3a message, prolonged action potential repolarization, presence of delayed after-depolarizations and triggered beats, delayed Ca2+ transients and frequent spontaneous Ca2+ release events and at the whole heart level, increased susceptibility to polymorphic ventricular arrhythmias. Most alterations in Ca2+ homeostasis were prevented by 100 nm tetrodotoxin. Our results suggest that life-threatening arrhythmias in patients with mutations in Scn1b, a gene classically defined as ancillary to the Na+ channel α subunit, can be partly consequent to disrupted intracellular Ca2+ homeostasis in ventricular myocytes. Key points Na+ current (INa) results from the integrated function of a molecular aggregate (the voltage-gated Na+ channel complex) that includes the β subunit family. Mutations or rare variants in Scn1b

  7. The future direction of the adult heart allocation system in the United States.

    PubMed

    Meyer, D M; Rogers, J G; Edwards, L B; Callahan, E R; Webber, S A; Johnson, M R; Vega, J D; Zucker, M J; Cleveland, J C

    2015-01-01

    Ensuring equitable and fair organ allocation is a central charge of the United Network for Organ Sharing (UNOS) as the Organ Procurement and Transplantation Network (OPTN) through its contract with the Department of Health and Human Services (DHHS). The OPTN/UNOS Board initiated a reassessment of the current allocation system. This paper describes the efforts of the OPTN/UNOS Heart Subcommittee, acting on behalf of the OPTN/UNOS Thoracic Organ Transplantation Committee, to modify the current allocation system. The Subcommittee assessed the limitations of the current three-tiered system, outcomes of patients with status exceptions, emerging ventricular assist device (VAD) population, options for improved geographic sharing and status of potentially disenfranchised groups. They analyzed waiting list and posttransplant mortality rates of a contemporary cohort of patient groups at risk, in collaboration with the Scientific Registry of Transplant Recipients to develop a proposed multi-tiered allocation scheme. This proposal provides a framework for simulation modeling to project whether candidates would have better waitlist survival in the revised allocation system, and whether posttransplant survival would remain stable. The tiers are subject to change, based on further analysis by the Heart Subcommittee and will lead to the development of a more effective and equitable heart allocation system. PMID:25534445

  8. Subcutaneous implantable cardioverter defibrillators in children, young adults and patients with congenital heart disease.

    PubMed

    Bordachar, Pierre; Marquié, Christelle; Pospiech, Thomas; Pasquié, Jean-Luc; Jalal, Zakaria; Haissaguerre, Michel; Thambo, Jean-Benoit

    2016-01-15

    The demonstration of severe complications in patients implanted with a transvenous implantable cardioverter defibrillator (ICD) has led to the development of devices equipped with a subcutaneous lead. This new technique offers numerous advantages but also certain disadvantages. Various studies or anecdotal clinical cases have specifically been conducted with this subcutaneous defibrillation system in children and/or patients with congenital heart disease. Results of these studies suggest: 1) a high feasibility despite being limited by a selection process that excludes patients requiring permanent pacing and patients declared ineligible during pre-screening; 2) good efficacy of electrical shocks in reducing induced or spontaneous ventricular arrhythmias; 3) in this specific subset of patients, 2 types of complications have been particularly described: a risk of device exteriorization and infection, and a large number of inappropriate therapies primarily related to T-wave oversensing. The subcutaneous ICD could therefore constitute the gold standard for patients with complex congenital heart disease with no venous access to the heart or with a persistent shunt increasing the risk of systemic emboli as well as in young patients with channelopathy or hypertrophic cardiomyopathy not requiring long-term pacing. Technological change (reduction in device size, better differentiation between R- and T-waves, possibility of pacing if device coupled with a leadless pacemaker) could reduce the limitations and complications and thereby increase the indications in this sub-group of patients. PMID:26519678

  9. Ah receptor expression in cardiomyocytes protects adult female mice from heart dysfunction induced by TCDD exposure.

    PubMed

    Kurita, Hisaka; Carreira, Vinicius S; Fan, Yunxia; Jiang, Min; Naticchioni, Mindi; Koch, Sheryl; Rubinstein, Jack; Puga, Alvaro

    2016-04-29

    Epidemiological studies in humans and experimental work in rodents suggest that exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a persistent environmental toxicant, is associated with incidence of heart disease. Although TCDD toxicity depends by and large on the aryl hydrocarbon receptor (AHR), the role of the cardiac AHR in TCDD induced cardiovascular disease is not well defined. To determine whether the Ahr gene mediates disruption of heart function by TCDD, we generated a cardiomyocyte-specific Ahr knockout mouse by crossing Ahr(fx/fx) mice with βMhc:cre/+ mice, in which expression of Cre recombinase is driven by the promoter of the βMhc (myosin heavy chain-beta) gene. Starting at three months of age, mice with cardiomyocyte-specific Ahr ablation were exposed to 1μg/kg/week of TCDD or control vehicle by oral gavage for an additional three months. Relative to unexposed controls, TCDD-exposure induced cardiomyocyte Ahr-independent changes in males but not females, including a significant increase in body weight, blood pressure, and cardiac hypertrophy and a decrease in cardiac ejection fraction. TCDD exposure also induced cardiomyocyte Ahr-dependent changes in fibrosis and calcium signaling gene expression in both males and females. TCDD exposure appears to cause sexually dimorphic effects on heart function and induce fibrosis and changes in calcium signaling in both males and females through activation of the cardiomyocyte-specific Ahr. PMID:27163630

  10. The intercellular organization of the two muscular systems in the adult salmonid heart, the compact and the spongy myocardium.

    PubMed

    Pieperhoff, Sebastian; Bennett, William; Farrell, Anthony Peter

    2009-11-01

    The ventricle of the salmonid heart consists of an outer compact layer of circumferentially arranged cardiomyocytes encasing a spongy myocardium that spans the lumen of the ventricle with a fine arrangement of muscular trabeculae. While many studies have detailed the anatomical structure of fish hearts, few have considered how these two cardiac muscle architectures are attached to form a functional working unit. The present study considers how the spindle-like cardiomyocytes, unlike the more rectangular structure of adult mammalian cardiomyocytes, form perpendicular connections between the two muscle layers that withstand the mechanical forces generated during cardiac systole and permit a simultaneous, coordinated contraction of both ventricular components. Therefore, hearts of rainbow trout (Oncorhynchus mykiss) and sockeye salmon (Oncorhynchus nerka) were investigated in detail using scanning electron microscopy (SEM) and various light microscopic techniques. In contrast to earlier suggestions, we found no evidence for a distinct connective tissue layer between the two muscle architectures that might 'glue' together the compact and the spongy myocardium. Instead, the contact layer between the compact and the spongy myocardium was characterized by a significantly higher amount of desmosome-like (D) and fascia adhaerens-like (FA) adhering junctions compared with either region alone. In addition, we observed that the trabeculae form muscular sheets of fairly uniform thickness and variable width rather than thick cylinders of variable diameter. This sheet-like trabecular anatomy would minimize diffusion distance while maximizing the area of contact between the trabecular muscle and the venous blood as well as the muscle tension generated by a single trabecular sheet. PMID:19627390

  11. [2012 -- the year of success in the 20 year-old adult heart transplant program of Hungary].

    PubMed

    Szabolcs, Zoltán; Hartyánszky, István; Hüttl, Tivadar; Fazekas, Levente; Balogh, Orsolya; Becker, Dávid; Soós, Pál; Varga, Tamás; Paulovich, Erzsébet; Németh, Endre; Rácz, Kristóf; Horkay, Ferenc; Merkely, Béla

    2013-06-01

    The Hungarian adult heart transplant program, which started in 1992, has changed gradually in the past 20 years. After the early enthusiasm of the first cases it changed significantly and it became an organized programme. However, low donation activity and moderate referral numbers to the national transplant waiting list slowed down the process therefore, heart transplant numbers did not fulfill expectations in the early years. After a moderate increase in 2007 transplant numbers have dropped again until recently when Hungary partially joined Eurotransplant network. Excess fundamental resources allocated to cardiac transplantation by health care professionals and reorganizing transplant coordination as well as logistics forced dramatic changes in clinical management. In 2011 and 2012 major structural changes had been made at Semmelweis University. The newly established transplant intensive care unit and the initiation of mechanical circulatory support and assist device programme increased transplant numbers by 131% compared to previous years, as well as it resulted an 86.63% 30-day survival rate, hence last year was the most successful year of cardiac transplantation ever. PMID:23708987

  12. The effect of maternal low-protein diet on the heart of adult offspring: role of mitochondria and oxidative stress.

    PubMed

    Nascimento, Luciana; Freitas, Cristiane M; Silva-Filho, Reginaldo; Leite, Ana Catarina R; Silva, Alessandra B; da Silva, Aline Isabel; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; Maia, Maria Bernadete Souza; Fernandes, Mariana P; Lagranha, Claudia

    2014-08-01

    Protein restriction during perinatal and early postnatal development is associated with a greater incidence of disease in the adult, such arterial hypertension. The aim in the present study was to investigate the effect of maternal low-protein diet on mitochondrial oxidative phosphorylation capacity, mitochondrial reactive oxygen species (ROS) formation, antioxidant levels (enzymatic and nonenzymatic), and oxidative stress levels on the heart of the adult offspring. Pregnant Wistar rats received either 17% casein (normal protein, NP) or 8% casein (low protein, LP) throughout pregnancy and lactation. After weaning male progeny of these NP or LP fed rats, females were maintained on commercial chow (Labina-Purina). At 100 days post-birth, the male rats were sacrificed and heart tissue was harvested and stored at -80 °C. Our results show that restricting protein consumption in pregnant females induced decreased mitochondrial oxidative phosphorylation capacity (51% reduction in ADP-stimulated oxygen consumption and 49.5% reduction in respiratory control ratio) in their progeny when compared with NP group. In addition, maternal low-protein diet induced a significant decrease in enzymatic antioxidant capacity (37.8% decrease in superoxide dismutase activity; 42% decrease in catalase activity; 44.8% decrease in glutathione-S-transferase activity; 47.9% decrease in glutathione reductase; 25.7% decrease in glucose-6 phosphate dehydrogenase) and glutathione level (34.8% decrease) when compared with control. From these findings, we hypothesize that an increased production of ROS and decrease in antioxidant activity levels induced by protein restriction during development could potentiate the progression of metabolic and cardiac diseases in adulthood. PMID:24905448

  13. Real-time MRI-guided right heart catheterization in adults using passive catheters

    PubMed Central

    Ratnayaka, Kanishka; Faranesh, Anthony Z.; Hansen, Michael S.; Stine, Annette M.; Halabi, Majdi; Barbash, Israel M.; Schenke, William H.; Wright, Victor J.; Grant, Laurie P.; Kellman, Peter; Kocaturk, Ozgur; Lederman, Robert J.

    2013-01-01

    Aims Real-time MRI creates images with superb tissue contrast that may enable radiation-free catheterization. Simple procedures are the first step towards novel interventional procedures. We aim to perform comprehensive transfemoral diagnostic right heart catheterization in an unselected cohort of patients entirely using MRI guidance. Methods and results We performed X-ray and MRI-guided transfemoral right heart catheterization in consecutive patients undergoing clinical cardiac catheterization. We sampled both cavae and both pulmonary arteries. We compared success rate, time to perform key steps, and catheter visibility among X-ray and MRI procedures using air-filled or gadolinium-filled balloon-tipped catheters. Sixteen subjects (four with shunt, nine with coronary artery disease, three with other) underwent paired X-ray and MRI catheterization. Complete guidewire-free catheterization was possible in 15 of 16 under both. MRI using gadolinium-filled balloons was at least as successful as X-ray in all procedure steps, more successful than MRI using air-filled balloons, and better than both in entering the left pulmonary artery. Total catheterization time and individual procedure steps required approximately the same amount of time irrespective of image guidance modality. Catheter conspicuity was best under X-ray and next-best using gadolinium-filled MRI balloons. Conclusion In this early experience, comprehensive transfemoral right heart catheterization appears feasible using only MRI for imaging guidance. Gadolinium-filled balloon catheters were more conspicuous than air-filled ones. Further workflow and device enhancement are necessary for clinical adoption. PMID:22855740

  14. Eating Patterns and Overweight Status in Young Adults: The Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have focused on the association between eating patterns and obesity. However, the findings have not been consistent. The goal of the present study was to identify the eating patterns associated with overweight among young adults aged 19-28 years (n = 504) in Bogalusa, Louisiana. Fo...

  15. Dietary & health predictors associated with overweight & obesity in young adults: the Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We examined independent associations between diet and lifestyle behaviors; differences in markers of cardiovascular disease (CVD), and type 2 diabetes mellitus (T2DM); and self-reported health problems among normal weight (NW); overweight (OW), and obese (OB) young adults. Cross-sectional data on pa...

  16. The Adult Congenital and Pediatric Cardiology Section: increasing the opportunities for the congenital heart disease community within the American College of Cardiology.

    PubMed

    Martin, Gerard R; Mitchell, Stephanie; Beekman, Robert H; Feinstein, Jeffrey A; Jenkins, Kathy J; Landzberg, Michael; Webb, Gary

    2012-01-01

    The Adult Congenital and Pediatric Cardiology (AC/PC) Section was established to develop a clear voice within the American College of Cardiology and address the myriad issues facing the congenital heart disease profession. The Section is governed by the AC/PC Council, which includes pediatric cardiologists, adult congenital cardiologists, a cardiac care associate, and a fellow-in-training member. The Council is responsible for bidirectional communication between the College's Board of Trustees and the AC/PC Section members. Since its founding in 2004, Section objectives have been defined by the College's mission: to advocate for quality cardiovascular care through education, research promotion, and the development and application of standards and guidelines and to influence health care policy. The pillars of the College-advocacy, quality, education, and member engagement-serve as the defining template for the Section's strategy. The Section has developed work groups in advocacy, clinical practice, education and training, quality, and publications. A separate leadership group has been developed for adult congenital heart disease. Work groups are open to all Section members. Recognition of the importance of lifelong care in congenital heart disease led Section leaders to incorporate pediatric cardiology and adult congenital heart disease content into each of the work groups. There are more than 1,200 Section members, with nearly 400 members actively contributing to Section activities. This article outlines Section efforts to date and highlights significant successes to date. PMID:22192673

  17. Dietary, lifestyle, and health correlates of overweight and obesity in adults 19 to 39 years of age: The Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diet and lifestyle factors of young adults and their relationship to health risk factors are understudied. Data from the Bogalusa Heart Study population (n = 1214; 19-39 years; 74.1% white; 60.8% female) were used to study associations of lifestyle, health risk factors, and reported health problems ...

  18. Cardiac-targeting magnetic lipoplex delivery of SH-IGF1R plasmid attenuate norepinephrine-induced cardiac hypertrophy in murine heart.

    PubMed

    Xu, Yiping; Li, Xuebiao; Kong, Minjian; Jiang, Daming; Dong, Aiqiang; Shen, Zhonghua; Duan, Qunjun

    2014-01-01

    Recent studies have demonstrated a number of molecular mechanisms contributing to the initiation of cardiac hypertrophy response to pressure overload. IGF1R (insulin-like growth factor-1 receptor), an important oncogene, is overexpressed in hypertrophic heart and mediates the hypertrophic pathology process. In this study, we applied with liposomal magnetofection that potentiated gene transfection by applying an external magnetic field to enhance its transfection efficiency. Liposomal magnetofection provided high efficiency in transgene expression in vivo. In vivo, IGF1R-specific-shRNA (small-hairpin RNA) by magnetofection inhibited IGF1R protein expression by 72.2 ± 6.8, 80.7 ± 9.6 and 84.5 ± 5.6%, at 24, 48 and 72 h, respectively, after pGFPshIGF1R injection, indicating that liposomal magnetofection is a promising method that allows the targeting of gene therapy for heart failure. Furthermore, we found that the treated animals (liposomal magnetofection with shIGF1R) showed reduced septal and posterior wall thickness, reduced HW:BWs (heart weight-to-body weights) compared with controls. Moreover, we also found that liposomal magnetofection-based shIGF1R transfection decreased the expression level of p-ERK (phosphorylated extracellular-signal-regulated kinase)1/2, p-AKT1 (phosphorylated protein kinase B1) compared with untreated hearts. These results suggested that liposomal magnetofection-mediated IGF1R-specific-shRNA may be a promising method, and suppression the IGF1R expression inhibited norepinephrine-induced cardiac hypertrophic process via inhibiting PI3K (phosphoinositide 3-kinase)/AKT pathway. PMID:24965872

  19. Deletion of Kvβ1.1 subunit leads to electrical and haemodynamic changes causing cardiac hypertrophy in female murine hearts

    PubMed Central

    Tur, Jared; Chapalamadugu, Kalyan C.; Padawer, Timothy; Badole, Sachin L.; Kilfoil, Peter J.; Bhatnagar, Aruni; Tipparaju, Srinivas M.

    2016-01-01

    Cardiovascular disease is the leading cause of death and debility in women in the USA, and cardiac arrhythmias are a major concern. Voltage-gated potassium (Kv) channels along with the binding partners; Kvβ subunits are major regulators of the action potential (AP) shape and duration (APD). The regulation of Kv channels by the Kvβ1 subunit is unknown in female hearts. In the present study, we hypothesized that the Kvβ1 subunit is an important regulator of female cardiac physiology. To test this hypothesis, we ablated (knocked out; KO) the KCNAB1 isoform 1 (Kvβ1.1) subunit in mice and evaluated cardiac function and electrical activity by using ECG, monophasic action potential recordings and echocardiography. Our results showed that the female Kvβ1.1 KO mice developed cardiac hypertrophy, and the hearts were structurally different, with enlargement and increased area. The electrical derangements caused by Kvβ1.1 KO in female mice included long QTc and QRS intervals along with increased APD (APD20–90% repolarization). The male Kvβ1.1 KO mice did not develop cardiac hypertrophy, but they showed long QTc and prolonged APD. Molecular analysis showed that several genes that support cardiac hypertrophy were significantly altered in Kvβ1.1 KO female hearts. In particular, myosin heavy chain αexpression was significantly elevated in Kvβ1.1 KO mouse heart. Using a small interfering RNA strategy, we identified that knockdown of Kvβ1 increases myosin heavy chain αexpression in H9C2 cells. Collectively, changes in molecular and cell signalling pathways clearly point towards a distinct electrical and structural remodelling consistent with cardiac hypertrophy in the Kvβ1.1 KO female mice. PMID:27038296

  20. Cardiac-targeting magnetic lipoplex delivery of SH-IGF1R plasmid attenuate norepinephrine-induced cardiac hypertrophy in murine heart

    PubMed Central

    Xu, Yiping; Li, Xuebiao; Kong, Minjian; Jiang, Daming; Dong, Aiqiang; Shen, Zhonghua; Duan, Qunjun

    2014-01-01

    Recent studies have demonstrated a number of molecular mechanisms contributing to the initiation of cardiac hypertrophy response to pressure overload. IGF1R (insulin-like growth factor-1 receptor), an important oncogene, is overexpressed in hypertrophic heart and mediates the hypertrophic pathology process. In this study, we applied with liposomal magnetofection that potentiated gene transfection by applying an external magnetic field to enhance its transfection efficiency. Liposomal magnetofection provided high efficiency in transgene expression in vivo. In vivo, IGF1R-specific-shRNA (small-hairpin RNA) by magnetofection inhibited IGF1R protein expression by 72.2±6.8, 80.7±9.6 and 84.5±5.6%, at 24, 48 and 72 h, respectively, after pGFPshIGF1R injection, indicating that liposomal magnetofection is a promising method that allows the targeting of gene therapy for heart failure. Furthermore, we found that the treated animals (liposomal magnetofection with shIGF1R) showed reduced septal and posterior wall thickness, reduced HW:BWs (heart weight-to-body weights) compared with controls. Moreover, we also found that liposomal magnetofection-based shIGF1R transfection decreased the expression level of p-ERK (phosphorylated extracellular-signal-regulated kinase)1/2, p-AKT1 (phosphorylated protein kinase B1) compared with untreated hearts. These results suggested that liposomal magnetofection-mediated IGF1R-specific-shRNA may be a promising method, and suppression the IGF1R expression inhibited norepinephrine-induced cardiac hypertrophic process via inhibiting PI3K (phosphoinositide 3-kinase)/AKT pathway. PMID:24965872

  1. The Unsteady Mainstay of the Family: Now Adult Children's Retrospective View on Social Support in Relation to Their Parent's Heart Transplantation

    PubMed Central

    Ågren, Susanna; Rönning, Helén

    2014-01-01

    The needs for support among children with a seriously ill parent, who is waiting for heart transplantation, are unknown today. The aim was to describe now adult children's experiences of social support in relation to a parent's heart transplant during childhood. Nine females and four males were interviewed. The median age for the children was 18 at the transplantation and their parents had been ill before for 18 months (median) and on waiting list for 161 days (mean). Three categories emerged: health care professionals' approaches, family and friends' approaches, and society approaches. Our results show that there was lack of support for children of heart transplantation patients. Support in the shape of information was in most cases provided by the sick or healthy parent. It is of great clinical importance to develop psychosocial support programs for children with a seriously ill parent waiting for heart transplantation (before, during, and after surgery). PMID:25431662

  2. Frequency distribution analysis of activation times and regional fibrosis in murine Scn5a+/− hearts: The effects of ageing and sex

    PubMed Central

    Jeevaratnam, Kamalan; Rewbury, Rebecca; Zhang, Yanmin; Guzadhur, Laila; Grace, Andrew A.; Lei, Ming; Huang, Christopher L.-H.

    2012-01-01

    Both Brugada Syndrome (BrS) and progressive cardiac conduction defect (PCCD) are associated respectively with diffuse and discrete alterations in conduction pathways affected by ageing and sex. This study assessed for contributions of such processes to the mechanism of conduction changes in Scn5a+/− and WT hearts stratified by age (3 and 12 months) and sex. In vivo electrocardiographic chest-lead assessment demonstrated greater incidences of bundle branch block in all Scn5a+/− mice compared to WT. Frequency analysis of right ventricular (RV) epicardial activation obtained from a 64-channel multi-electrode array demonstrated greater prominence of late conducting components in Scn5a+/− compared to WT male, and in male compared to female Scn5a+/− following stratification by genotype and sex. Similar differences were observed between old male Scn5a+/− and young male Scn5a+/−, old female Scn5a+/−, and old male WT, following stratification by genotype, age and sex. These findings directly correlated with histomorphometric assessment of regional fibrosis in both septa and free walls preferentially involving the RV. We demonstrate complex alterations in conduction distributions suggesting a conversion of normal to slow-conducting tissue, modulated by ageing and sex, coupled with fibrosis in Scn5a+/− hearts. These features suggest an overlap between pathophysiological processes related to BrS and PCCD in Scn5a+/− hearts. PMID:22968175

  3. Murine Typhus

    PubMed Central

    Dzul-Rosado, Karla R; Zavala Velázquez, Jorge Ernesto; Zavala-Castro, Jorge

    2012-01-01

    Rickettsia typhi: is an intracellular bacteria who causes murine typhus. His importance is reflected in the high frequency founding specific antibodies against Rickettsia typhi in several worldwide seroepidemiological studies, the seroprevalence ranging between 3-36%. Natural reservoirs of R. typhi are rats (some species belonging the Rattus Genus) and fleas (Xenopsylla cheopis) are his vector. This infection is associated with overcrowding, pollution and poor hygiene. Typically presents fever, headache, rash on trunk and extremities, in some cases may occur organ-specific complications, affecting liver, kidney, lung or brain. Initially the disease is very similar to other diseases, is very common to confuse the murine typhus with Dengue fever, therefore, ignorance of the disease is a factor related to complications or non-specific treatments for the resolution of this infection. This paper presents the most relevant information to consider about the rickettsiosis caused by Rickettsia typhi. PMID:24893060

  4. Mortality Resulting From Congenital Heart Disease Among Children and Adults in the United States, 1999 to 2006

    PubMed Central

    Gilboa, Suzanne M.; Salemi, Jason L.; Nembhard, Wendy N.; Fixler, David E.; Correa, Adolfo

    2016-01-01

    Background Previous reports suggest that mortality resulting from congenital heart disease (CHD) among infants and young children has been decreasing. There is little population-based information on CHD mortality trends and patterns among older children and adults. Methods and Results We used data from death certificates filed in the United States from 1999 to 2006 to calculate annual CHD mortality by age at death, race-ethnicity, and sex. To calculate mortality rates for individuals ≥1 year of age, population counts from the US Census were used in the denominator; for infant mortality, live birth counts were used. From 1999 to 2006, there were 41 494 CHD-related deaths and 27 960 deaths resulting from CHD (age-standardized mortality rates, 1.78 and 1.20 per 100 000, respectively). During this period, mortality resulting from CHD declined 24.1% overall. Mortality resulting from CHD significantly declined among all race-ethnicities studied. However, disparities persisted; overall and among infants, mortality resulting from CHD was consistently higher among non-Hispanic blacks compared with non-Hispanic whites. Infant mortality accounted for 48.1% of all mortality resulting from CHD; among those who survived the first year of life, 76.1% of deaths occurred during adulthood (≥18 years of age). Conclusions CHD mortality continued to decline among both children and adults; however, differences between race-ethnicities persisted. A large proportion of CHD-related mortality occurred during infancy, although significant CHD mortality occurred during adulthood, indicating the need for adult CHD specialty management. PMID:21098447

  5. Obesity as a Risk Factor for Poor Neurocognitive Outcomes in Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Gunstad, John

    2016-01-01

    Heart failure (HF) has reached epidemic proportions and is a significant contributor to poor outcomes. HF is an established risk factor for Alzheimer's disease, vascular dementia, and abnormalities on neuroimaging. Moreover, up to 80% of HF patients also exhibit milder impairments on cognitive tests assessing attention, executive function, memory, and language. The mechanisms of cognitive impairment in HF are not entirely clear and involve a combination of physiological processes that negatively impact the brain. Cerebral hypoperfusion and common comorbid conditions in HF are among the most commonly proposed contributors to poor neurocognitive outcomes in this population. Obesity is another likely risk factor for adverse brain changes and cognitive impairment in HF, as it is a known contributor to neurocognitive outcomes in healthy and patient samples. This paper reviews the literature on HF and cognitive function and introduces obesity as a significant risk factor for poor neurocognitive outcomes in this population. PMID:23743688

  6. Congenital heart defect - corrective surgery

    MedlinePlus

    ... born with one or more heart defects has congenital heart disease . Surgery is needed if the defect could harm ... 2008 Guidelines for the Management of Adults with Congenital Heart Disease: a report of the American College of Cardiology/ ...

  7. Coronary heart disease

    MedlinePlus

    ... adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice ... of the American Heart Association, American College of Cardiology, and American Society of Hypertension. Treatment of hypertension ...

  8. Arrhythmic substrate, slowed propagation and increased dispersion in conduction direction in the right ventricular outflow tract of murine Scn5a+/− hearts

    PubMed Central

    Zhang, Y; Guzadhur, L; Jeevaratnam, K; Salvage, S C; Matthews, G D K; Lammers, W J; Lei, M; Huang, C L-H; Fraser, J A

    2014-01-01

    Aim To test a hypothesis attributing arrhythmia in Brugada Syndrome to right ventricular (RV) outflow tract (RVOT) conduction abnormalities arising from Nav1.5 insufficiency and fibrotic change. Methods Arrhythmic properties of Langendorff-perfused Scn5a+/− and wild-type mouse hearts were correlated with ventricular effective refractory periods (VERPs), multi-electrode array (MEA) measurements of action potential (AP) conduction velocities and dispersions in conduction direction (CD), Nav1.5 expression levels, and fibrotic change, as measured at the RVOT and RV. Two-way anova was used to test for both independent and interacting effects of anatomical region and genotype on these parameters. Results Scn5a+/− hearts showed greater arrhythmic frequencies during programmed electrical stimulation at the RVOT but not the RV. The Scn5a+/− genotype caused an independent increase of VERP regardless of whether the recording site was the RVOT or RV. Effective AP conduction velocities (CV†s), derived from fitting regression planes to arrays of observed local activation times were reduced in Scn5a+/− hearts and at the RVOT independently. AP conduction velocity magnitudes derived by averaging MEA results from local vector analyses, CV*, were reduced by the Scn5a+/− genotype alone. In contrast, dispersions in conduction direction, were greater in the RVOT than the RV, when the atrioventricular node was used as the pacing site. The observed reductions in Nav1.5 expression were attributable to Scn5a+/−, whereas increased levels of fibrosis were associated with the RVOT. Conclusions The Scn5a+/− RVOT recapitulates clinical findings of increased arrhythmogenicity through reduced CV† reflecting reduced CV* attributable to reduced Nav1.5 expression and increased CD attributable to fibrosis. PMID:24913289

  9. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes

    PubMed Central

    Qian, Li; Huang, Yu; Spencer, C. Ian; Foley, Amy; Vedantham, Vasanth; Liu, Lei; Conway, Simon J.; Fu, Ji-dong; Srivastava, Deepak

    2012-01-01

    SUMMARY The reprogramming of adult cells into pluripotent cells or directly into alternative adult cell types holds great promise for regenerative medicine. We reported that cardiac fibroblasts, which represent 50% of the cells in the mammalian heart, can be directly reprogrammed to adult cardiomyocyte-like cells in vitro by the addition of Gata4, Mef2c and Tbx5 (GMT). Here, we use genetic lineage-tracing to show that resident non-myocytes in the murine heart can be reprogrammed into cardiomyocyte-like cells in vivo by local delivery of GMT after coronary ligation. Induced cardiomyocytes became bi-nucleate, assembled sarcomeres and had cardiomyocyte-like gene expression. Analysis of single cells revealed ventricular cardiomyocyte-like action potentials, beating upon electrical stimulation, and evidence of electrical coupling. In vivo delivery of GMT decreased infarct size and modestly attenuated cardiac dysfunction up to 3 months after coronary ligation. Delivery of the pro-angiogenic and fibroblast activating peptide, Thymosin β4, along with GMT, resulted in further improvements in scar area and cardiac function. These findings demonstrate that cardiac fibroblasts can be reprogrammed into cardiomyocyte-like cells in their native environment for potential regenerative purposes. PMID:22522929

  10. Gender and incidence of dementia in the Framingham Heart Study from mid-adult life

    PubMed Central

    Au, Rhoda; Preis, Sarah R; Wolf, Philip A; Dufouil, Carole; Seshadri, Sudha

    2014-01-01

    Background Gender-specific risks for dementia and Alzheimer's Disease (AD) starting in midlife remain largely unknown. Methods Prospectively ascertained dementia/AD and cause-specific mortality in Framingham Heart Study (FHS) participants was used to generate 10- to 50-year risk estimates of dementia/AD, based on the Kaplan-Meier method (Cumulative Incidence) or accounting for competing risk of death (lifetime risk, LTR). Results Overall, 777 incident dementia (601 AD) occurred in 7,901 participants (4,333 women) over 136,266 person-years. Whereas cumulative incidences were similar in women and men, LTRs were higher in women >85. LTR of dementia/AD at age 45 was 1 in 5 in women, 1 in 10 in men. Cardiovascular mortality was higher in men with rate ratios decreasing from ~6 at 45-54 to <2 after age 65. Conclusion Selective survival of men with a healthier cardiovascular risk profile and hence lower propensity to dementia might partly explain the higher LTR of dementia/AD in women. PMID:24418058

  11. Tai Chi Chuan modulates heart rate variability during abdominal breathing in elderly adults.

    PubMed

    Wei, Gao-Xia; Li, You-Fa; Yue, Xiao-Lin; Ma, Xiao; Chang, Yu-Kai; Yi, Long-Yan; Li, Jing-Cheng; Zuo, Xi-Nian

    2016-03-01

    Tai Chi Chuan (TCC) practice is currently intentionally applied in clinical populations, especially those with cardiovascular diseases because of its potential benefits on the autonomic nervous system. The long-term effect of TCC practice on heart rate variability (HRV) remains largely unknown. In this study, we recruited 23 TCC practitioners whose experience averaged approximately 21 years and 19 controls matched by age, sex and education to examine the effect of TCC practice on the autonomic nervous system during a resting state and during an abdominal breathing state. HRV was measured by traditional electrocardiogram (ECG) recording. The results showed that the low frequency, total power frequency, and normalized low frequency components and the low-frequency/high-frequency ratio were significantly higher, whereas the normalized high frequency was significantly lower in the TCC practitioners relative to controls during the abdominal breathing state. However, we did not detect any significant difference in the HRV measures during the resting state between the two groups. Additionally, TCC experience did not correlate with HRV components either in the abdominal state or the resting state in the TCC group. Considering all of these findings, we suggest that TCC improves vagal activity and the balance between sympathetic and parasympathetic activity during the relaxation state. This study also provides direct physiological evidence for the role of TCC practice in relaxation. PMID:26377754

  12. Dietary Patterns, Alcohol Consumption and Risk of Coronary Heart Disease in Adults: A Meta-Analysis

    PubMed Central

    Zhang, Xiao-Yan; Shu, Long; Si, Cai-Juan; Yu, Xiao-Long; Liao, Dan; Gao, Wei; Zhang, Lun; Zheng, Pei-Fen

    2015-01-01

    Previous studies reported the potential associations between dietary patterns and the risk of coronary heart disease (CHD) in adulthood, however a consistent perspective has not been established to date. Herein, we carried out this meta-analysis to evaluate the associations between dietary patterns and the risk of CHD. MEDLINE and EBSCO were searched for relevant articles published up to April 2015. A total of 35 articles (reporting 37 original studies) met the inclusion criteria and were included in the present meta-analysis. The decreased risk of CHD was shown for the highest compared with the lowest categories of healthy/prudent dietary patterns (odds ratio (OR) = 0.67; 95% confidence interval (CI): 0.60, 0.75; p < 0.00001) and alcohol consumption (OR = 0.68; 95% CI: 0.59, 0.78; p < 0.00001). There was evidence of an increased risk of CHD in the highest compared with the lowest categories of the unhealthy/Western-type dietary patterns (OR = 1.45; 95% CI: 1.05, 2.01; p = 0.02). The results of this meta-analysis indicate that different dietary patterns may be associated with the risk of CHD. PMID:26262641

  13. Outdoor Temperature, Heart Rate and Blood Pressure in Chinese Adults: Effect Modification by Individual Characteristics

    PubMed Central

    Madaniyazi, Lina; Zhou, Yong; Li, Shanshan; Williams, Gail; Jaakkola, Jouni J.K.; Liang, Xin; Liu, Yan; Wu, Shouling; Guo, Yuming

    2016-01-01

    We collected data from Kailuan cohort study from 2006 to 2011 to examine whether short-term effects of ambient temperature on heart rate (HR) and blood pressure (BP) are non-linear or linear, and their potential modifying factors. The HR, BP and individual information, including basic characteristics, life style, socio-economic characteristics and other characteristics, were collected for each participant. Daily mean temperature and relative humidity were collected. A regression model was used to evaluate associations of temperature with HR and BP, with a non-linear function for temperature. We also stratified the analyses in different groups divided by individual characteristics. 47,591 residents were recruited. The relationships of temperature with HR and BP were “V” shaped with thresholds ranging from 22 °C to 28 °C. Both cold and hot effects were observed on HR and BP. The differences of effect estimates were observed among the strata of individual characteristics. The effect estimate of temperature was higher among older people. The cold effect estimate was higher among people with lower Body Mass Index. However, the differences of effect estimates among other groups were inconsistent. These findings suggest both cold and hot temperatures may have short-term impacts on HR and BP. The individual characteristics could modify these relationships. PMID:26876040

  14. Effectiveness of Motivational Interviewing in Decreasing Hospital Readmission in Adults With Heart Failure and Multimorbidity.

    PubMed

    Riegel, Barbara; Masterson Creber, Ruth; Hill, Julia; Chittams, Jesse; Hoke, Linda

    2016-08-01

    Hospitalizations are common in heart failure (HF). Multimorbidity, defined as ≥2 comorbid conditions, drives many readmissions. The purpose of this pilot study was to test the effectiveness of motivational interviewing (MI) in decreasing these hospital readmissions. We enrolled 100 hospitalized HF patients into a randomized controlled trial, randomizing in a 2:1 ratio: intervention (n = 70) and control (n = 30). The intervention group received MI tailored to reports of self-care during one home visit and three to four follow-up phone calls. After 3 months, 34 participants had at least one hospital readmission. The proportion of patients readmitted for a condition unrelated to HF was lower in the intervention (7.1%) compared with the control group (30%, p = .003). Significant predictors of a non-HF readmission were intervention group, age, diabetes, and hemoglobin. Together, these variables explained 35% of the variance in multimorbidity readmissions. These preliminary results are promising in suggesting that MI may be an effective method of decreasing multimorbidity hospital readmissions in HF patients. PMID:26743119

  15. Risk Factors for Increased Hospital Resource Utilization and In-Hospital Mortality in Adults With Single Ventricle Congenital Heart Disease.

    PubMed

    Collins, Ronnie Thomas; Doshi, Pratik; Onukwube, Jennifer; Fram, Ricki Y; Robbins, James M

    2016-08-01

    Most patients with single ventricle congenital heart disease are now expected to survive to adulthood. Co-morbid medical conditions (CMCs) are common. We sought to identify risk factors for increased hospital resource utilization and in-hospital mortality in adults with single ventricle. We analyzed data from the 2001 to 2011 Nationwide Inpatient Sample database in patients aged ≥18 years admitted to nonteaching general hospitals (NTGHs), TGHs, and pediatric hospitals (PHs) with either hypoplastic left heart syndrome, tricuspid atresia or common ventricle. National estimates of hospitalizations were calculated. Elixhauser CMCs were identified. Length of stay (LOS), total hospital costs, and effect of CMCs were determined. Age was greater in NTGH (41.5 ± 1.3 years) than in TGH (32.8 ± 0.5) and PH (25.0 ± 0.6; p <0.0001). Adjusted LOS was shorter in NTGH (5.6 days) than in PH (9.7 days; p <0.0001). Adjusted costs were higher in PH ($56,671) than in TGH ($31,934) and NTGH ($18,255; p <0.0001). CMCs are associated with increased LOS (p <0.0001) and costs (p <0.0001). Risk factors for in-hospital mortality included increasing age (odds ratio [OR] 5.250, CI 2.825 to 9.758 for 45- to 64-year old vs 18- to 30-year old), male gender (OR 2.72, CI 1.804 to 4.103]), and the presence of CMC (OR 4.55, CI 2.193 to 9.436) for 2 vs none). No differences in mortality were found among NTGH, TGH, and PH. Cardiovascular procedures were more common in PH hospitalizations and were associated with higher costs and LOS. CMCs increase costs and mortality. In-hospital mortality is increased with age, male gender, and the presence of hypoplastic left heart syndrome. PMID:27291967

  16. Association of Age, Systolic Blood Pressure, and Heart Rate with Adult Morbidity and Mortality after Urgent Care Visits

    PubMed Central

    Hart, James; Woodruff, Michael; Joy, Elizabeth; Dalto, Joseph; Snow, Gregory; Srivastava, Rajendu; Isaacson, Brad; Allen, Todd

    2016-01-01

    Introduction Little data exists to help urgent care (UC) clinicians predict morbidity and mortality risk. Age, systolic blood pressure (SBP), and heart rate (HR) are easily obtainable and have been used in other settings to predict short-term risk of deterioration. We hypothesized that there is a relationship between advancing age, SBP, HR, and short-term health outcomes in the UC setting. Methods We collected retrospective data from 28 UC clinics and 22 hospitals in the Intermountain Healthcare system between years 2008–2013. Adult patients (≥18 years) were included if they had a unique UC visit and HR or SBP data. Three endpoints following UC visit were assessed: emergency department (ED) visit within three days, hospitalization within three days, and death within seven days. We analyzed associations between age, SBP, HR and endpoints using local regression with a binomial likelihood. Five age groups were chosen from previously published national surveys. Vital sign (VS) distributions were determined for each age group, and the central tendency was compared against previously published norms (90–120mmHg for SBP and 60–100bpm for HR.) Results A total of 1,720,207 encounters (714,339 unique patients) met the inclusion criteria; 51,446 encounters (2.99%) had ED visit within three days; 12,397 (0.72%) experienced hospitalization within three days; 302 (0.02%) died within seven days of UC visit. Heart rate and SBP combined with advanced age predicted the probability of ED visit (p<0.0001) and hospitalization (p<0.0001) following UC visit. Significant associations between advancing age and death (p<0.0001), and VS and death (p<0.0001) were observed. Odds ratios of risk were highest for elderly patients with lower SBP or higher HR. Observed distributions of SBP were higher than published normal ranges for all age groups. Conclusion Among adults seeking care in the UC, associations between HR and SBP and likelihood of ED visits and hospitalization were more

  17. Urinary Metals and Heart Rate Variability: A Cross-Sectional Study of Urban Adults in Wuhan, China

    PubMed Central

    Feng, Wei; He, Xiaosheng; Chen, Mu; Deng, Siyun; Qiu, Gaokun; Li, Xiaoliang; Liu, Chuanyao; Li, Jun; Deng, Qifei; Huang, Suli; Wang, Tian; Dai, Xiayun; Yang, Binyao; Yuan, Jing; He, Meian; Zhang, Xiaomin; Chen, Weihong; Kan, Haidong

    2014-01-01

    Background Epidemiological studies have suggested an association between external estimates of exposure to metals in air particles and altered heart rate variability (HRV). However, studies on the association between internal assessments of metals exposure and HRV are limited. Objectives The purpose of this study was to examine the potential association between urinary metals and HRV among residents of an urban community in Wuhan, China. Methods We performed a cross-sectional analysis of 23 urinary metals and 5-min HRV indices (SDNN, standard deviation of normal-to-normal intervals; r-MSSD, root mean square of successive differences in adjacent normal-to-normal intervals; LF, low frequency; HF, high frequency; TP, total power) using baseline data on 2,004 adult residents of Wuhan. Results After adjusting for other metals, creatinine, and other covariates, natural log-transformed urine titanium concentration was positively associated with all HRV indices (all p < 0.05). Moreover, we estimated negative associations between cadmium and r-MSSD, LF, HF, and TP; between lead and r-MSSD, HF, and TP; and between iron, copper, and arsenic and HF, SDNN, and LF, respectively, based on models adjusted for other metals, creatinine, and covariates (all p < 0.10). Several associations differed according to cardiovascular disease risk factors. For example, negative associations between cadmium and r-MSSD were stronger among participants ≤ 52 years of age (vs. > 52), current smokers (vs. nonsmokers), body mass index < 25 kg/m2 (vs. ≥ 25), and among those who were not hypertensive. Conclusions Urine concentrations of several metals were associated with HRV parameters in our cross-sectional study population. These findings need replication in other studies with adequate sample sizes. Citation Feng W, He X, Chen M, Deng S, Qiu G, Li X, Liu C, Li J, Deng Q, Huang S, Wang T, Dai X, Yang B, Yuan J, He M, Zhang X, Chen W, Kan H, Wu T. 2015. Urinary metals and heart rate variability: a

  18. Left heart bypass support with the Rotaflow Centrifugal Pump® as a bridge to decision and recovery in an adult.

    PubMed

    Kashiwa, Koichi; Nishimura, Takashi; Saito, Aya; Kubo, Hitoshi; Fukaya, Aoi; Tamai, Hisayoshi; Yambe, Tomoyuki; Kyo, Shunei; Ono, Minoru

    2012-06-01

    Since left heart bypass or biventricular circulatory assist with an extracorporeal centrifugal pump as a bridge to decision or recovery sometimes requires long-time support, the long-term durability of extracorporeal centrifugal pumps is crucial. The Rotaflow Centrifugal Pump(®) (MAQUET Cardiopulmonary AG, Hirrlingen, Germany) is one of the centrifugal pumps available for long-term use in Japan. However, there have been few reports of left heart bypass or biventricular circulatory support over the mid-term. This is a case report of left heart bypass support with the Rotaflow Centrifugal Pump(®) as a bridge to decision and recovery for an adult patient who could not be weaned from cardiopulmonary bypass and percutaneous cardiopulmonary support after cardiac surgery. We could confirm that the patient's consciousness level was normal; however, the patient could not be weaned from the left heart bypass support lasting 1 month. Therefore, the circulatory assist device was switched to the extracorporeal Nipro ventricular assist device (VAD). This time, left heart bypass support could be maintained for 30 days using a single Rotaflow Centrifugal Pump(®). There were no signs of hemolysis during left heart bypass support. The Rotaflow Centrifugal Pump(®) itself may be used as a device for a bridge to decision or recovery before using a VAD in cardiogenic shock patients. PMID:22358461

  19. Cardiac Rehabilitation is Associated with Lasting Improvements in Cognitive Function in Older Adults with Heart Failure

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Objective Heart failure (HF) is a known risk factor for cognitive impairment. Cardiac rehabilitation (CR) may attenuate poor neurocognitive outcomes in HF via improved physical fitness—a significant promoter of cognitive function. However, no study has examined the possible acute and lasting benefits of CR on cognitive function in persons with HF. Methods and Results 52 patients with HF completed a 12-week Phase II CR program. All participants were administered neuropsychological testing and completed a brief physical fitness assessment at baseline, completion of CR (i.e. 12-weeks), and 12-month follow-up. Repeated measures analyses showed a significant time effect for both attention/executive function and memory (p < 0.05). Attention/executive function performance increased from baseline to 12-weeks and these gains remained up to 12-months; memory was unchanged from baseline to 12-weeks, but then improved between the 12-week and 12-month time points. Physical fitness improved from baseline to 12-weeks and these benefits were maintained 12-months later. Changes in physical fitness and cognitive function over time did not reach a statistically significant association, though poorer physical fitness was associated with decreased cognitive performance at the baseline and 12-month time points. Conclusions CR is associated with both acute and lasting cognitive benefits in patients with HF. Prospective studies with extended follow-ups are needed to clarify the mechanisms that underpin cognitive improvements following CR (e.g., improved cerebral perfusion) and whether CR can ultimately reduce risk for cognitive decline and conditions like Alzheimer’s disease in HF. PMID:25181916

  20. [Early ambulation and rehabilitation following heart surgery from the viewpoint of the cardiologist for adults].

    PubMed

    Gleichmann, U; Körfer, R; Mannebach, H; Mommsen, S; Meffert, C; Mertens, H M

    1990-01-01

    Traditional concepts about the early phase of postoperative remobilization after cardiac surgery favor physical inactivity--as did earlier concepts for rehabilitation after myocardial infarction like the armchair treatment philosophy. For an overwhelming majority of our patients, however, this concept does not hold, according to our experience during the last decade. In contrast, we propose a model of stepwise mobilization and rehabilitation starting the first postoperative days. At the end of the first week most patients are able to climb staircases. In the second week group physical therapy can be started. At the 14th postoperative day, discharge from the surgical ward is warranted. During this step of early mobilization some exceptions have to be made and some special aspects have to be considered. Early mobilization must be postponed in patients with overt heart insufficiency, a low ejection fraction, complex ventricular arrhythmias or pericardial effusions. Cautious mobilization is also required in patients with mitral valve replacement and persistent elevation of pulmonary pressure and resistance. This holds also for patients with valve replacement during acute endocarditis, patients with repair of a dissecting aneurysm of the aorta and patients with perioperative myocardial infarction. The stage of early postoperative mobilization usually ends after the second week and is followed by the next step, the rehabilitation phase during weeks 3 to 6. The goals of the rehabilitation program are; increasing the physical fitness of the patient, thereby increasing his self-assurance and self-esteem; establishing a health-education program, increasing the patients health competence and his coping capacities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2082606

  1. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

    PubMed Central

    Saito, Isao; Hitsumoto, Shinichi; Maruyama, Koutatsu; Nishida, Wataru; Eguchi, Eri; Kato, Tadahiro; Kawamura, Ryoichi; Takata, Yasunori; Onuma, Hiroshi; Osawa, Haruhiko; Tanigawa, Takeshi

    2015-01-01

    Background Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt’s insulin sensitivity index (ISI). Pulse was recorded for 5 min, and time-domain heart rate variability (HRV) indices were calculated: the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive difference (RMSSD). Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power, and the LF:HF ratio. Results Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10). Conclusions Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals. PMID:26277879

  2. Delayed conduction and its implications in murine Scn5a+/− hearts: independent and interacting effects of genotype, age, and sex

    PubMed Central

    Poh Tee, Sui; Zhang, Yanmin; Rewbury, Rebecca; Guzadhur, Laila; Duehmke, Rudolf; Grace, Andrew A.; Lei, Ming; Huang, Christopher L.-H.

    2010-01-01

    We explored for relationships between SCN5A haploinsufficiency, implicated in clinical arrhythmogenicity, and right ventricular (RV) conduction disorders in Langendorff-perfused, male and female, and young (3 months) and old (>12 month old) Scn5a+/− and wild type (WT) hearts. The investigated conditions of genotype, age, and sex affected latencies but not repolarization time courses of RV monophasic action potentials. This prompted examination of the patterns of RV epicardial activation, its dispersion, and their interrelationships as possible arrhythmic mechanisms using a 64-channel, multi-electrode array. Mean ventricular activation times (T*MEAN), spatial dispersions (D*S) between recording channels/cardiac cycle, and maximum activation times (T*MAX) representing the slowest possible conduction in any given heart were all higher in old male Scn5a+/− compared with young male and old female Scn5a+/− and old male WT. Temporal dispersions (D*T) of recording channels were similarly higher in old male Scn5a+/− compared with old male WT. All groupings of D*T, D*S, and T*MAX nevertheless linearly correlated with T*MEAN, with indistinguishable slopes. The variates explored thus influence D*T, D*S, and T*MAX through actions on T*MEAN. These findings in turn correlated with increased levels of fibrosis in young male, young female, and old male Scn5a+/− compared with the corresponding WTs. We thus demonstrate for the first time independent and interacting effects of genotype, age, and sex on epicardial conduction and its dispersions at least partially attributable to fibrotic change, resulting in the greatest effects in old male Scn5a+/− in an absence of alterations in repolarization time courses. This directly implicates altered depolarization in the clinical arrhythmogenicity associated with Scn5a+/−. PMID:21127902

  3. Prevalence of Major Cardiovascular Risk Factors and Coronary Heart Disease in a Sample of Greek Adults: The Saronikos Study

    PubMed Central

    Gikas, Aristofanis; Lambadiari, Vaia; Sotiropoulos, Alexios; Panagiotakos, Demosthenes; Pappas, Stavros

    2016-01-01

    Background: Comprehensive data regarding prevalence of coronary heart disease (CHD) and associated factors in different geographical regions are very important to our understanding of global distribution and evolution of CHD. The aim of this study was to assess the current prevalence of self-reported risk factors and CHD in Greek adult population. Methods: A community-based cross-sectional study was conducted in May 2014, during an election day, among residents of Saronikos municipality (Attica region). Data were collected from face-to-face interviews. The study sample included 2636 subjects (men, 49.5%; mean age, 50.5; range 20-95 years), with similar age and sex distribution to the target population. Results: The age-standardized prevalence rates of five major risk factors were as follows: type 2 diabetes 11.1%, hypercholesterolemia (cholesterol>240 mg/dl or using cholesterol-lowering medication) 23.8%, hypertension 27.2%, current smoking 38.9% and physical inactivity 43%. Of the participants, only 21% were free of any of these factors. Clustering of two to five risk factors was more frequent among persons aged 50 years and older as compared with younger ones (60% vs 27%, P=0.000). The age-adjusted prevalence of CHD was 6.3% (in men, 8.9%; in women, 3.8%) and that of myocardial infarction was 3.6% (in men, 5.2%; in women, 2.1%). According to multivariate analysis age, gender, education level, obesity, diabetes, hypercholesterolemia, hypertension and ever smoking were strongly associated with CHD. Conclusion: Classic risk factors are highly prevalent and frequently clustered, especially in adults aged 50 years and older. These findings raise concerns about future trends of already increased rates of CHD. Multifactorial and integrated population-based interventions need to be applied to reduce the burden of cardiovascular conditions. PMID:27429668

  4. [Heart and vascular surgery interventions with hypothermic circulatory arrest in adults].

    PubMed

    Kipfer, B; Leupi, F; Althaus, U

    1990-10-01

    In the period between 1981 and 1988, 51 patients were operated on the thoracic aorta using the hypothermic circulatory arrest technique. 31 patients had a dissection of the thoracic aorta, in 16 cases, an aneurysm was the reason for the intervention. In addition, we used the hypothermic circulatory arrest for a thrombectomy in the aortic arch and two mitral-valve replacements. The following operations were performed: 14 x composite graft, 19 x supracoronar prosthesis (6 x with aortic valve replacement, 3 x with partial replacement of aortic arch), 17 operations were performed either for aortic arch or aorta descendens replacement. In our retrospective study, 7 courses were fata (14%), 3 patients had complications with residuals. Compared with a group of 105 patients operated on the thoracic aorta in the same period without circulatory arrest, we found no difference with regard to the lethality and morbidity. We conclude that the hypothermic circulatory arrest is a safe technique for selected problems in cardiovascular surgery in adults. PMID:2074178

  5. Reduced Heart Rate Variability Predicts Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes and Controls Without Diabetes

    PubMed Central

    Rodrigues, Ticiana C.; Ehrlich, James; Hunter, Cortney M.; Kinney, Gregory L.; Rewers, Marian

    2010-01-01

    Abstract Aim Reduced heart rate variability (HRV) is a manifestation of cardiac autonomic neuropathy, a known complication of type 1 diabetes (T1D). We evaluated whether HRV predicted coronary artery calcium (CAC) progression. Methods Subjects between 19 and 56 years of age with T1D or those without diabetes from the Coronary Artery Calcification in Type 1 Diabetes study underwent supine deep breathing 12-lead electrocardiograms. The SD of consecutive RR intervals was used as a measure of HRV. CAC was measured at two visits 6.0 ± 0.5 years apart. Progression of CAC was defined as an increase in square root transformed CAC volume of ≥2.5 mm3, excluding patients who had cardiovascular events during follow-up. Results Reduced HRV was associated with older age, higher hemoglobin A1c, elevated albuminuria, CAC volume at baseline, and increased fibrinogen. Higher HRV at baseline was associated with lower likelihood CAC progression (odds ratio = 0.71, 95% confidence interval 0.56–0.90, P = 0.005), and the adjustment for known cardiovascular risk factors did not change this strong association, including adjustment for inflammatory markers. Conclusions Reduced HRV predicted progression of CAC in adults with and without T1D. This association further supports the participation of autonomic neuropathy in the atherosclerosis process. PMID:21128843

  6. Proarrhythmia in a non-failing murine model of cardiac-specific Na+/Ca2+ exchanger overexpression: whole heart and cellular mechanisms

    PubMed Central

    Muszynski, Adam; Ruhe, Matthias; Bögeholz, N.; Schulte, Jan S.; Milberg, Peter; Mönnig, Gerold; Fabritz, Larissa; Goldhaber, Joshua I.; Breithardt, Günter; Schmitz, Wilhelm; Philipson, Kenneth D.; Eckardt, Lars; Kirchhof, Paulus; Müller, Frank U.

    2012-01-01

    The cardiac Na+/Ca2+ exchanger (NCX) generates an inward electrical current during SR-Ca2+ release, thus possibly promoting afterdepolarizations of the action potential (AP). We used transgenic mice 12.5 weeks or younger with cardiomyocyte-directed overexpression of NCX (NCX-Tg) to study the proarrhythmic potential and mechanisms of enhanced NCX activity. NCX-Tg exhibited normal echocardiographic left ventricular function and heart/body weight ratio, while the QT interval was prolonged in surface ECG recordings. Langendorff-perfused NCX-Tg, but not wild-type (WT) hearts, developed ventricular tachycardia. APs and ionic currents were measured in isolated cardiomyocytes. Cell capacitance was unaltered between groups. APs were prolonged in NCX-Tg versus WT myocytes along with voltage-activated K+ currents (Kv) not being reduced but even increased in amplitude. During abrupt changes in pacing cycle length, early afterdepolarizations (EADs) were frequently recorded in NCX-Tg but not in WT myocytes. Next to EADs, delayed afterdepolarizations (DAD) triggering spontaneous APs (sAPs) occurred in NCX-Tg but not in WT myocytes. To test whether sAPs were associated with spontaneous Ca2+ release (sCR), Ca2+ transients were recorded. Despite the absence of sAPs in WT, sCR was observed in myocytes of both genotypes suggesting a facilitated translation of sCR into DADs in NCX-Tg. Moreover, sCR was more frequent in NCX-Tg as compared to WT. Myocardial protein levels of Ca2+-handling proteins were not different between groups except the ryanodine receptor (RyR), which was increased in NCX-Tg versus WT. We conclude that NCX overexpression is proarrhythmic in a non-failing environment even in the absence of reduced KV. The underlying mechanisms are: (1) occurrence of EADs due to delayed repolarization; (2) facilitated translation from sCR into DADs; (3) proneness to sCR possibly caused by altered Ca2+ handling and/or increased RyR expression. PMID:22327339

  7. Developmental changes in Ca(2+)-uptake, Na+,Ca(2+)-exchange and Ca(2+)-ATPase in freshly isolated embryonic, newborn and adult chicken heart.

    PubMed

    Prakash, P; Meera, P; Tripathi, O

    1996-01-01

    Developmental changes in cellular Ca(2+)-transport mechanisms were studied in chick heart by determining cellular Ca(2+)-uptake and Na+,Ca(2+)-exchange activity in freshly isolated ventricular tissues of embryonic (5-18 days old), newborn (1-2 days old) and young adult (90-100 days old) heart by monitoring 45Ca influx. Ca(2+)-ATPase activity was determined in microsomal fractions at different stages of development. The Ca(2+)-uptake (per g wet tissue weight) increased with the development of embryonic as well as post-hatch chick heart, reaching a maximum in the young adult chicken. The overall increase in Ca(2+)-uptake, from embryonic day 5 to young-adult stage, was more than 3 fold. The Na+,Ca(2+)-exchange activity, determined as Na(+)-gradient-induced Ca(2+)-uptake in presence of either ouabain or zero [Na+]0, showed a 6-fold increase during development of heart from the embryonic day 5 to the young adult stage. Amiloride, an inhibitor of Na+,Ca(2+)-exchange, caused a dose-dependent reduction in a ouabain-induced rise in 45Ca influx at different stages of development. The inhibitory effect of amiloride was, however, greater during later stages of development. A progressive increase in Ca(2+)-ATPase activity was also seen during development. Ca(2+)-ATPase exhibited about a 4-fold increase in activity from embryonic day 7 to the young adult. The concomitant increase in Ca(2+)-uptake, Na+,Ca(2+)-exchange and Ca(2+)-ATPase activities suggests age-dependent changes in Ca(2+)-transport and storage systems of developing heart during embryogenesis and post-embryonic life. During embryogenesis the developmental increase in Na+,Ca(2+)-exchange activity was greater than that during post-hatch development of heart. However, the increase in Ca(2+)-ATPase activity was greater during post-hatch development than during embryogenesis. It is suggested that Na+,Ca(2+)-exchange and Ca(2+)-ATPase play a prominent role in maintaining cellular Ca2+ homeostasis during embryogenesis and

  8. Reliability and concurrent validity of a peripheral pulse oximeter and health-app system for the quantification of heart rate in healthy adults.

    PubMed

    Losa-Iglesias, Marta Elena; Becerro-de-Bengoa-Vallejo, Ricardo; Becerro-de-Bengoa-Losa, Klark Ricardo

    2016-06-01

    There are downloadable applications (Apps) for cell phones that can measure heart rate in a simple and painless manner. The aim of this study was to assess the reliability of this type of App for a Smartphone using an Android system, compared to the radial pulse and a portable pulse oximeter. We performed a pilot observational study of diagnostic accuracy, randomized in 46 healthy volunteers. The patients' demographic data and cardiac pulse were collected. Radial pulse was measured by palpation of the radial artery with three fingers at the wrist over the radius; a low-cost portable, liquid crystal display finger pulse oximeter; and a Heart Rate Plus for Samsung Galaxy Note®. This study demonstrated high reliability and consistency between systems with respect to the heart rate parameter of healthy adults using three systems. For all parameters, ICC was > 0.93, indicating excellent reliability. Moreover, CVME values for all parameters were between 1.66-4.06 %. We found significant correlation coefficients and no systematic differences between radial pulse palpation and pulse oximeter and a high precision. Low-cost pulse oximeter and App systems can serve as valid instruments for the assessment of heart rate in healthy adults. PMID:25038201

  9. Construction of a normalized directionally cloned cDNA library from adult heart and analysis of 3040 clones by partial sequencing.

    PubMed

    Tanaka, T; Ogiwara, A; Uchiyama, I; Takagi, T; Yazaki, Y; Nakamura, Y

    1996-07-01

    Large-scale sequencing of clones from cDNA libraries derived from specific tissues is a rapid and efficient way of discovering novel genes expressed in those tissues. However, because the heart is continually contracting and relaxing, it strongly expresses muscle-contractile genes and/or mitochondrial genes, a bias that reduces the efficiency of this method. To improve the efficiency of identifying novel genes expressed in the heart, we constructed a normalized directionally cloned cDNA library from adult heart and partially sequenced 3040 clones. Comparisons of these sequence data with known DNA sequences in the database revealed that 57.1% of the clones matched human genes already known, 23.4% were identical or almost identical to human expressed sequence tags (ESTs), 14.2% bore no significant homology to any sequences in the database, and 1.2% represented repetitive sequences. The remaining 4.1% showed some homology with known genes, and Northern blot analysis of several clones in this category revealed that most of them were expressed mainly in the heart and skeletal muscle. After redundancy was excluded, the 3040 clones accounted for 1395 distinctive ESTs, 446 of which exhibited no match to any known sequence. Our results suggest that our normalized library is less redundant than standard libraries and is a useful resource for cataloging genes expressed in the heart. PMID:8661126

  10. Dietary patterns associated with metabolic syndrome, sociodemographic and lifestyle factors in young adults: the Bogalusa Heart Study

    PubMed Central

    Deshmukh-Taskar, Priya R; O’Neil, Carol E; Nicklas, Theresa A; Yang, Su-Jau; Liu, Yan; Gustat, Jeanette; Berenson, Gerald S

    2009-01-01

    Objective To examine the association between dietary patterns (DP) and risk for metabolic syndrome (MetS); and to identify differences in DP by socio-economic, demographic and lifestyle factors. Design Dietary intake (from an FFQ), anthropometric/biochemical parameters and sociodemographic/lifestyle information (from a self-reported questionnaire) were evaluated, using a cross-sectional design. Statistical methods included principal component factor analysis, analysis of covariance and linear regression. All analyses were covariate-adjusted. Setting The Bogalusa Heart Study (1995–1996), USA. Subjects Young adults (19–39 years; n 995; 61 % females/39 % males; 80 % whites/20 % blacks) from a semi-rural southern US community were examined. Results The ‘Western Dietary Pattern’ (WDP) consisted of refined grains, French fries, high-fat dairy foods, cheese dishes, red meats, processed meats, eggs, snacks, sweets/desserts, sweetened beverages and condiments. The ‘Prudent Dietary Pattern’ (PDP) consisted of whole grains, legumes, vegetables, fruits, 100 % fruit juices, low-fat dairy products, poultry, clear soups and low-fat salad dressings. The DP explained 31 % of the dietary intake variance. Waist circumference (P = 0·02), triceps skinfold (P = 0·01), plasma insulin (P = 0·03), serum TAG (P = 0·05), and the occurrence of MetS (P = 0·03) were all inversely associated with PDP. Insulin sensitivity (P < 0·0005) was positively associated with PDP. Serum HDL cholesterol (P = 0·05) was inversely associated with WDP. Blacks consumed more servings from WDP than whites (P = 0·02). Females consumed more servings from PDP than males (P = 0·002). Those with >12 years of education consumed more servings from PDP than their counterparts (P < 0·0001). Current smokers consumed more servings from WDP than current non-smokers (P < 0·0001). Physically very active young adults consumed fewer servings from WDP than their sedentary counterparts (P = 0·02). Conclusions

  11. Predicting Stereoselective Disposition of Carvedilol in Adult and Pediatric Chronic Heart Failure Patients by Incorporating Pathophysiological Changes in Organ Blood Flows-A Physiologically Based Pharmacokinetic Approach.

    PubMed

    Rasool, Muhammad Fawad; Khalil, Feras; Läer, Stephanie

    2016-07-01

    Chronic heart failure (CHF) is a systemic low perfusion syndrome resulting from impairment in the pumping function of the heart. The decrease in blood supply to body organs can potentially affect the pharmacokinetics (PK) of the drugs being administered. Carvedilol is administered as a racemic mixture and undergoes extensive stereoselective first pass metabolism. For such a drug, the pathophysiological changes occurring in CHF can have a profound impact on PK, and thus the resulting pharmacodynamic response, of both enantiomers. The aim of the current work was to predict stereoselective disposition of carvedilol after incorporating the pathophysiological changes in CHF into a whole-body physiologically based PK model using Simcyp, and to scale that model to pediatric CHF patients on a physiologic basis to investigate whether the same changes in the adult model can also be adopted for children. The developed model has successfully described PK of carvedilol enantiomers in healthy adults and in patients after the incorporation of reduced organ blood flows, as seen by the visual predictive checks and the calculated observed/predicted ratios for all PK parameters of interest. In contrast to adults, pediatric patients up to 12 years of age were better described without the reductions in organ blood flow, whereas older pediatric patients were better described after incorporating organ blood flow reductions. These findings indicate that the incorporated blood flow reductions in the adult model cannot be directly adopted in pediatrics, at least for the young ones; however, to draw definite conclusions, more data are still needed. PMID:27068272

  12. Dietary patterns and cardiovascular risk factors in adolescents and young adults: the Northern Ireland Young Hearts Project.

    PubMed

    McCourt, Hannah J; Draffin, Claire R; Woodside, Jayne V; Cardwell, Chris R; Young, Ian S; Hunter, Steven J; Murray, Liam J; Boreham, Colin A; Gallagher, Alison M; Neville, Charlotte E; McKinley, Michelle C

    2014-11-28

    Dietary pattern (DP) analysis allows examination of the combined effects of nutrients and foods on the markers of CVD. Very few studies have examined these relationships during adolescence or young adulthood. Traditional CVD risk biomarkers were analysed in 12-15-year-olds (n 487; Young Hearts (YH)1) and again in the same individuals at 20-25 years of age (n 487; YH3). Based on 7 d diet histories, in the present study, DP analysis was performed using a posteriori principal component analysis for the YH3 cohort and the a priori Mediterranean Diet Score (MDS) was calculated for both YH1 and YH3 cohorts. In the a posteriori DP analysis, YH3 participants adhering most closely to the 'healthy' DP were found to have lower pulse wave velocity (PWV) and homocysteine concentrations, the 'sweet tooth' DP were found to have increased LDL concentrations, and decreased HDL concentrations, [corrected] the 'drinker/social' DP were found to have lower LDL and homocysteine concentrations, but exhibited a trend towards a higher TAG concentration, and finally the 'Western' DP were found to have elevated homocysteine and HDL concentrations. In the a priori dietary score analysis, YH3 participants adhering most closely to the Mediterranean diet were found to exhibit a trend towards a lower PWV. MDS did not track between YH1 and YH3, and nor was there a longitudinal relationship between the change in the MDS and the change in CVD risk biomarkers. In conclusion, cross-sectional analysis revealed that some associations between DP and CVD risk biomarkers were already evident in the young adult population, namely the association between the healthy DP (and the MDS) and PWV; however, no longitudinal associations were observed between these relatively short time periods. PMID:25234582

  13. “It’s a toss up between my hearing, my heart, and my hip”: Prioritizing and Accommodating Multiple Morbidities by Vulnerable Older Adults

    PubMed Central

    Leach, Corinne; Edwards, William

    2011-01-01

    Nearly three quarters of older adults have multiple morbidities (MM). This study investigated which morbidities older adults prioritize, why, and how they accommodate these conditions, focusing on elders with two or more chronic conditions and low socioeconomic status. Methods In-depth interviews were conducted with 41 older adults (most-being African American women from the southeastern U.S., with two or more chronic illnesses). Results Many participants reported worrying most about their heart disease, diabetes, and disability/mobility problems, and about their synergistic effects. Many worried that MMs might tip them into a downward spiral. Participants spent the most time and money on arthritis and diabetes. Few received help; when they did, relatives assisted with arthritis/ mobility, diabetes, and effects of stroke. Discussion Enhanced formal care coordination, increased use of technological innovations, and understanding elders’ priorities are necessary to improve self-care/management and quality of life. PMID:19202253

  14. Population normative data for the CERAD Word List and Victoria Stroop Test in younger- and middle-aged adults: Cross-sectional analyses from the Framingham Heart Study

    PubMed Central

    Hankee, Lisa D.; Preis, Sarah R.; Piers, Ryan J.; Beiser, Alexa S.; Devine, Sherral A.; Liu, Yulin; Seshadri, Sudha; Wolf, Philip A.; Au, Rhoda

    2016-01-01

    Objective To provide baseline normative data on tests of verbal memory and executive function for non-demented young to middle age adults. Methods The Consortium to Establish a Registry for Alzheimer’s Disease Word List task (CERAD-WL) and Victoria Stroop Test (VST) were administered to 3362 Framingham Heart Study (FHS) volunteer participants aged 24-78 years. Analyses of the effects of age, sex and education were conducted. Normative data on traditional measures and error responses are reported for each test. Results Traditional measures were significantly associated with both age and education in this younger-aged cohort. Error responses also evidenced significant age and education effects. Conclusion These data provide a normative comparison for assessment of verbal memory and executive functioning capabilities in young adults and may be utilized as a tool for preclinical studies of disease in younger aged adults. PMID:27410241

  15. Heart Health

    MedlinePlus

    ... Connected Home » Heart Health Heath and Aging Heart Health Your Heart Changes to Your Heart With ... are both taking steps toward heart health. Your Heart Your heart is a strong muscle about the ...

  16. Identification of novel mRNA transcripts of the nm23-M1 gene that are modulated during mouse embryo development and are differently expressed in adult murine tissues.

    PubMed

    Gervasi, F; Capozza, F; Bruno, T; Fanciulli, M; Lombardi, D

    1998-12-01

    The nm23-M1, a putative metastasis-suppressor gene, and its homologs are involved in development and differentiation. We have shown previously that in vitro neuronal cell proliferation and differentiation can be modulated by nm23-M1 expression levels. In the present study, by the yeast two-hybrid system, we have shown that, at the onset of mouse tissue differentiation, the Nm23-M1 protein forms either homodimers, or heterodimers with Nm23-M2. Furthermore, we have isolated two cDNA variants of the nm23-M1 gene in the 3'-untranslated region (UTR). The two variants related to novel mRNA transcripts that are modulated in mouse embryo and are differently expressed in adult murine tissues. PMID:9881672

  17. The CroHort study: cardiovascular behavioral risk factors in adults, school children and adolescents, hospitalized coronary heart disease patients, and cardio rehabilitation groups in Croatia.

    PubMed

    Milanović, Sanja Musić; Uhernik, Ana Ivicević; Dzakula, Aleksandar; Brborović, Ognjen; Poljicanin, Tamara; Fister, Kristina; Juresa, Vesna; Heim, Inge; Vrazić, Hrvoje; Bergovec, Mijo; Kern, Josipa; Vuletić, Silvije

    2012-01-01

    Based on repeated measurement of health behaviors the CroHort Study showed that health behavior explains a great deal more of class inequalities in mortality than observed in previous studies. These include decreasing prevalence of smoking and increase in obesity, hypertension and diabetes mellitus. The lowest prevalence of health risks was recorded among children and adolescents, followed by general adult population from the CroHort Study. Hospitalized coronary heart disease patients had higher risks prevalence than general population, while the highest prevalence of risks was recorded among patients in cardiac rehabilitation program. The higher levels of stress were associated to lower financial conditions, poorer social functioning and poorer mental health for both men and women. Higher levels of stress were also associated with heart problems, higher alcohol consumption in men while in women stress was associated to poorer general health, higher age and lower levels of education. PMID:22338783

  18. Postnatal consequences of prenatal cocaine exposure and myocardial apoptosis: does cocaine in utero imperil the adult heart?

    PubMed Central

    Feng, Qingping

    2005-01-01

    Cocaine use is common among pregnant women with a history of substance abuse, and has been shown to cause abnormalities in the heart during fetal and postnatal development. However, mechanisms underlying the detrimental effects of cocaine on the developing heart are not fully understood. In this issue, Bae and Zhang show that prenatal cocaine exposure increases the susceptibility of the postnatal heart to ischemia and reperfusion injury. Their results suggest that myocardial apoptosis induced by cocaine during fetal development may represent one of the mechanisms by which prenatal cocaine exposure exerts its long-term, deleterious consequences on postnatal cardiac function. PMID:15685202

  19. Heart Health - Brave Heart

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Brave Heart Past Issues / Winter 2009 Table of Contents For ... you can have a good life after a heart attack." Lifestyle Changes Surviving—and thriving—after such ...

  20. Association of Calcium Intake, Dairy Product Consumption with Overweight Status in Young Adults (1995-1996): The Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective is to examine the association between calcium intake and dairy product consumption with overweight and obesity in young adults. The sample used in this study consisted of 1306 young adults, ages 19–38 years, who participated in the 1995–1996 young adult survey. Analysis was performed w...

  1. Common Tests for Congenital Heart Defects

    MedlinePlus

    ... Heart Defect - Fetal Circulation • Care & Treatment • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

  2. Care and Treatment for Congenital Heart Defects

    MedlinePlus

    ... Physical Activity Recommendations for Heart Health • Tools & Resources Web Booklets on Congenital Heart Defects These online publications ... to you or your child’s defect and concerns. Web Booklet: Adults With Congenital Heart Defects Web Booklet: ...

  3. Heart transplant

    MedlinePlus

    ... 10 years. Alternative Names Cardiac transplant; Transplant - heart; Transplantation - heart Images Heart, section through the middle Heart, ... 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton ...

  4. Heart Failure

    MedlinePlus

    ... version of this page please turn Javascript on. Heart Failure What is Heart Failure? In heart failure, the heart cannot pump enough ... failure often experience tiredness and shortness of breath. Heart Failure is Serious Heart failure is a serious and ...

  5. Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1CreERT2 and GlastCreERT2 Murine Lines

    PubMed Central

    Yang, Sung M.; Alvarez, Diego D.

    2015-01-01

    Newly generated dentate granule cells (GCs) are relevant for input discrimination in the adult hippocampus. Yet, their precise contribution to information processing remains unclear. To address this question, it is essential to develop approaches to precisely label entire cohorts of adult-born GCs. In this work, we used genetically modified mice to allow conditional expression of tdTomato (Tom) in adult-born GCs and characterized their development and functional integration. Ascl1CreERT2;CAGfloxStopTom and GlastCreERT2;CAGfloxStopTom mice resulted in indelible expression of Tom in adult neural stem cells and their lineage upon tamoxifen induction. Whole-cell recordings were performed to measure intrinsic excitability, firing behavior, and afferent excitatory connectivity. Developing GCs were also staged by the expression of early and late neuronal markers. The slow development of adult-born GCs characterized here is consistent with previous reports using retroviral approaches that have revealed that a mature phenotype is typically achieved after 6–8 weeks. Our findings demonstrate that Ascl1CreERT2 and GlastCreERT2 mouse lines enable simple and reliable labeling of adult-born GC lineages within restricted time windows. Therefore, these mice greatly facilitate tagging new neurons and manipulating their activity, required for understanding adult neurogenesis in the context of network remodeling, learning, and behavior. SIGNIFICANCE STATEMENT Our study shows that Ascl1CreERT2 and GlastCreERT2 mice lines can be used to label large cohorts of adult-born dentate granule cells with excellent time resolution. Neurons labeled in this manner display developmental and functional profiles that are in full agreement with previous findings using thymidine analogs and retroviral labeling, thus providing an alternative approach to tackle fundamental questions on circuit remodeling. Because of the massive neuronal targeting and the simplicity of this method, genetic labeling will

  6. Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease.

    PubMed

    Braitsch, Caitlin M; Kanisicak, Onur; van Berlo, Jop H; Molkentin, Jeffery D; Yutzey, Katherine E

    2013-12-01

    During embryonic heart development, the transcription factors Tcf21, Wt1, and Tbx18 regulate activation and differentiation of epicardium-derived cells, including fibroblast lineages. Expression of these epicardial progenitor factors and localization of cardiac fibrosis were examined in mouse models of cardiovascular disease and in human diseased hearts. Following ischemic injury in mice, epicardial fibrosis is apparent in the thickened layer of subepicardial cells that express Wt1, Tbx18, and Tcf21. Perivascular fibrosis with predominant expression of Tcf21, but not Wt1 or Tbx18, occurs in mouse models of pressure overload or hypertensive heart disease, but not following ischemic injury. Areas of interstitial fibrosis in ischemic and hypertensive hearts actively express Tcf21, Wt1, and Tbx18. In all areas of fibrosis, cells that express epicardial progenitor factors are distinct from CD45-positive immune cells. In human diseased hearts, differential expression of Tcf21, Wt1, and Tbx18 also is detected with epicardial, perivascular, and interstitial fibrosis, indicating conservation of reactivated developmental mechanisms in cardiac fibrosis in mice and humans. Together, these data provide evidence for distinct fibrogenic mechanisms that include Tcf21, separate from Wt1 and Tbx18, in different fibroblast populations in response to specific types of cardiac injury. PMID:24140724

  7. Assessment of the influence of age on the rate of heart rate decline after maximal exercise in non-athletic adult males.

    PubMed

    Dimkpa, U; Ibhazehiebo, K

    2009-01-01

    This study investigated the influence of age on heart rate (HR) decline after exercise in non-athletic adult males. One hundred and fourteen adult males (66 young, 25 +/- 6.26 years; 48 old, 53 +/- 8.54 years) participated in the study. Subjects performed maximum-effort ergometer exercise in incremental stages. HR was measured at rest and continuously monitored during and after exercise. Maximum oxygen uptake (VO(2max)) was measured during the exercise using respiratory gas analyser. Body mass index (BMI) was computed from weight and height measurements, while rating of perceived exertion (RPE) was obtained immediately after the exercise. Results indicated age differences in the rate of HR decline with the young presenting significantly higher %HR decline (P<0.001) than old adults at both levels of recovery. When linearly correlated with age, the rate of HR decline in 1 and 3 min indicated variances of (52%,56%) in young adults, and (54%,49%) in the old adults. After controlling for VO(2max), resting HR, BMI and RPE, the influence of age on rate of HR decline in the two phases of recovery disappeared in young. In the older adult group, it reduced greatly in the 1-min recovery (r(2) = 25%; P = 0.001) and disappeared in the 3-min recovery. Pattern of HR recovery did not differ between the two age groups while age threshold was observed in HR recovery in 1 min. In summary, the influence that age appeared to have on the rate of HR decline could not hold when factors affecting HR recovery were taken into account. PMID:19016813

  8. Isoform-Specific Modulation of Inflammation Induced by Adenoviral Mediated Delivery of Platelet-Derived Growth Factors in the Adult Mouse Heart

    PubMed Central

    Ylä-Herttuala, Seppo; Betsholtz, Christer; Andrae, Johanna

    2016-01-01

    Platelet-derived growth factors (PDGFs) are key regulators of mesenchymal cells in vertebrate development. To what extent PDGFs also exert beneficial homeostatic or reparative roles in adult organs, as opposed to adverse fibrogenic responses in pathology, are unclear. PDGF signaling plays critical roles during heart development, during which forced overexpression of PDGFs induces detrimental cardiac fibrosis; other studies have implicated PDGF signaling in post-infarct myocardial repair. Different PDGFs may exert different effects mediated through the two PDGF receptors (PDGFRα and PDGFRβ) in different cell types. Here, we assessed responses induced by five known PDGF isoforms in the adult mouse heart in the context of adenovirus vector-mediated inflammation. Our results show that different PDGFs have different, in some cases even opposing, effects. Strikingly, whereas the major PDGFRα agonists (PDGF-A and -C) decreased the amount of scar tissue and increased the numbers of PDGFRα-positive fibroblasts, PDGFRβ agonists either induced large scars with extensive inflammation (PDGF-B) or dampened the adenovirus-induced inflammation and produced a small and dense scar (PDGF-D). These results provide evidence for PDGF isoform-specific inflammation-modulating functions that may have therapeutic implications. They also illustrate a surprising complexity in the PDGF-mediated pathophysiological responses. PMID:27513343

  9. Single ventricle, bicuspid aorta and interatrial wall aneurysm as a rare complex adult congenital heart disease: a case report

    PubMed Central

    2009-01-01

    Background Single ventricle, bicuspid aortic valve and interatrial wall aneurysm in adulthood are a rare and unique case in medical literature. This presented case with congenital heart disease has never been treated surgically and clinical consequences seriously presented in adulthood. Case presentation A 27 year old man with complex congenital heart disease presented. At the age of six, the single ventricle was ultrasonographly diagnosed, but at age 27 clinical consequences started to be seriously present. We explored his history, clinical course, physical examination, laboratory findings, medical treatments and actual patient condition. Conclusion The possibilities for surgical evaluation are presented. PMID:19183494

  10. Changes in Coronary Heart Disease Risk Profile of Adults with Intellectual Disabilities following a Physical Activity Intervention

    ERIC Educational Resources Information Center

    Moss, S. J.

    2009-01-01

    Background: Regular physical activity is one of the modifiable risk factors for coronary heart disease (CHD). With an increasing age profile and similar patterns of morbidity to the general population, persons with intellectual disabilities (ID) and their caregivers would benefit from data that indicate CHD risk factors. Knowledge of the CHD risk…

  11. Impact of a Health Promotion Nurse Intervention on Disability and Health Care Costs among Elderly Adults with Heart Conditions

    ERIC Educational Resources Information Center

    Meng, Hongdao; Wamsley, Brenda R.; Eggert, Gerald M.; Van Nostrand, Joan F.

    2007-01-01

    Context: Patients with heart conditions in rural areas may have different responses to health promotion-disease Self-management interventions compared to their urban counterparts. Purpose: To estimate the impact of a multi-component health promotion nurse intervention on physical function and total health care expenditures among elderly adults…

  12. Percutaneous left-heart decompression during extracorporeal membrane oxygenation: an alternative to surgical and transeptal venting in adult patients.

    PubMed

    Avalli, Leonello; Maggioni, Elena; Sangalli, Fabio; Favini, Giorgio; Formica, Francesco; Fumagalli, Roberto

    2011-01-01

    Extracorporeal membrane oxygenation (ECMO) is often applied for acute cardiorespiratory failure. Left ventricular distension can compromise recovery of the failing heart. To overcome this complication, we describe a new technique to decompress the left heart through the insertion of a venting cannula in the pulmonary artery. A 43-year-old woman was connected to ECMO for refractory cardiogenic shock after left pneumonia and severe sepsis. Transesophageal echocardiography (TEE) revealed a large intraventricular clot. A 15F venous cannula was placed percutaneously in the pulmonary artery and connected to the venous limb of the ECMO circuit to decompress the left heart, and to prevent left ventricular ejection and potential embolization. After myocardial recovery, when the thrombus was judged as stable, the patient was weaned, and ECMO was removed on day 16. The patient was discharged from the cardiac surgery intensive care unit on day 30 and subsequently had an uneventful recovery. This new percutaneous approach represent a feasible and effective method to vent the left heart during ECMO, when it becomes necessary to reduce wall tension or to prevent ejection. PMID:21048495

  13. Lifestyle intervention improves heart rate recovery from exercise in adults with Type 2 diabetes: Results from the Look AHEAD Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined ...

  14. Lifestyle intervention improves heart rate recovery from exercise in adults with type 2 diabetes: Results from the Look AHEAD study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT), and (2) to determine the independent and combined...

  15. Episodic ozone exposure in adult and senescent Brown Norway rats: acute and delayed effect on heart rate, core temperature and motor activity.

    PubMed

    Gordon, C J; Johnstone, A F; Aydin, C; Phillips, P M; MacPhail, R C; Kodavanti, U P; Ledbetter, A D; Jarema, K A

    2014-06-01

    Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O₃) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T(c)) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O₃ (6 h/day of 1 ppm O₃ for 2 consecutive days/week for 13 weeks). Acute O₃ initially led to marked drops in HR and T(c). As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O₃. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O₃ exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O₃, adult and senescent rats exhibited an elevated T(c) and HR during the day but not at night, an effect that persisted for at least 48 h after O₃ exposure. MA was elevated in adults but not senescent rats during recovery from O₃. Overall, acute effects of O₃, including reductions in HR and T(c), were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T(c) with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O₃ in senescent rats may explain the relatively heightened physiological response to O₃ in younger rats. PMID:24779854

  16. A method for high purity intestinal epithelial cell culture from adult human and murine tissues for the investigation of innate immune function

    PubMed Central

    Graves, Christina L.; Harden, Scott W.; LaPato, Melissa; Nelson, Michael; Amador, Byron; Sorenson, Heather; Frazier, Charles J.; Wallet, Shannon M.

    2015-01-01

    Intestinal epithelial cells (IECs) serve as an important physiologic barrier between environmental antigens and the host intestinal immune system. Thus, IECs serve as a first line of defense and may act as sentinel cells during inflammatory insults. Despite recent renewed interest in IEC contributions to host immune function, the study of primary IEC has been hindered by lack of a robust culture technique, particularly for small intestinal and adult tissues. Here, a novel adaptation for culture of primary IEC is described for human duodenal organ donor tissue as well as duodenum and colon of adult mice. These epithelial cell cultures display characteristic phenotypes and are of high purity. In addition, the innate immune function of human primary IEC, specifically with regard to Toll-like receptor (TLR) expression and microbial ligand responsiveness, is contrasted with a commonly used intestinal epithelial cell line (HT-29). Specifically, TLR expression at the mRNA level and production of cytokine (IFNγ and TNFα) in response to TLR agonist stimulation is assessed. Differential expression of TLRs as well as innate immune responses to ligand stimulation is observed in human-derived cultures compared to that of HT-29. Thus, use of this adapted method to culture primary epithelial cells from adult human donors and from adult mice will allow for more appropriate studies of IECs as innate immune effectors. PMID:25193428

  17. Long-term Impact of Childhood Adiposity on Adult Metabolic Syndrome Is Modified by Insulin Resistance: The Bogalusa Heart Study

    PubMed Central

    Zhang, Huijie; Zhang, Tao; Li, Shengxu; Li, Ying; Hussain, Azad; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia A.; He, Jiang; Chen, Wei

    2015-01-01

    Childhood adiposity and insulin resistance are well-known risk factors for adult metabolic syndrome (MetS). This study aims to examine whether the association between childhood adiposity and adult MetS is modified by insulin resistance. The cohort consisted of 1,593 black and white subjects, aged 19–50 years at follow-up, who were examined 19 years apart on average as children and adults for MetS variables. The prevalence of adult MetS was compared between the insulin-sensitive obesity and insulin-resistant obesity groups in childhood. Adult MetS prevalence was higher in the insulin-resistant obesity group than in the insulin-sensitive obesity group (34.9% vs. 24.3%, p = 0.008). In multivariable logistic regression analyses adjusted for age, race, gender, and follow-up years, individuals with insulin-resistant obesity in childhood were 1.7 times (p = 0.011) more likely to have MetS 19 years later on average than those with insulin-sensitive obesity in childhood. Odds ratio did not differ significantly between blacks and whites (p = 0.724). ORs for the association of childhood BMI with adult MetS significantly increased with increasing tertiles of childhood HOMA (p < 0.001 for trend). These findings suggest that insulin resistance amplifies the association between childhood adiposity and adult MetS and underscore the importance of preventing both adiposity and insulin resistance in early life. PMID:26640243

  18. Type A behavior and its determinants in children, adolescents and young adults with and without parental coronary heart disease: a case-control study.

    PubMed

    Räikkönen, K; Keltikangas-Järvinen, L; Pietikäinen, M

    1991-01-01

    Healthy children, adolescents and young adults with parental coronary heart disease (CHD) (N = 78) were compared with their one-to-one matched controls without a parental CHD (N = 78) in terms of their psychological and behavioral characteristics. The variables adopted were Type A behavior, self-esteem, achievement striving, hyperactivity and social maladjustment. The results indicate a tendency for boys with parental CHD to be characterized by higher scores on Type A behavior, lower self-esteem and more intense striving for achievement compared to their matched controls. Girls with parental CHD differed from their matched controls in the predicted direction only in one respect: a higher level of hyperactivity was characteristic for cases. PMID:2046059

  19. Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes

    PubMed Central

    Graham, Evan Lee; Balla, Cristina; Franchino, Hannabeth; Melman, Yonathan

    2013-01-01

    The use of primary cardiomyocytes (CMs) in culture has provided a powerful complement to murine models of heart disease in advancing our understanding of heart disease. In particular, the ability to study ion homeostasis, ion channel function, cellular excitability and excitation-contraction coupling and their alterations in diseased conditions and by disease-causing mutations have led to significant insights into cardiac diseases. Furthermore, the lack of an adequate immortalized cell line to mimic adult CMs, and the limitations of neonatal CMs (which lack many of the structural and functional biomechanics characteristic of adult CMs) in culture have hampered our understanding of the complex interplay between signaling pathways, ion channels and contractile properties in the adult heart strengthening the importance of studying adult isolated cardiomyocytes. Here, we present methods for the isolation, culture, manipulation of gene expression by adenoviral-expressed proteins, and subsequent functional analysis of cardiomyocytes from the adult mouse. The use of these techniques will help to develop mechanistic insight into signaling pathways that regulate cellular excitability, Ca2+ dynamics and contractility and provide a much more physiologically relevant characterization of cardiovascular disease. PMID:24084584

  20. A Pilot Study of Brief Heart Rate Variability Biofeedback to Reduce Craving in Young Adult Men Receiving Inpatient Treatment for Substance Use Disorders

    PubMed Central

    Eddie, D.; Kim, C.; Lehrer, P.; Deneke, E.; Bates, M.E.

    2014-01-01

    The present pilot study investigated the implementation feasibility, and efficacy for reducing alcohol and drug craving, of a brief, 3-session heart rate variability biofeedback (HRV BFB) intervention added to a traditional 28-day substance abuse disorder (SUD) inpatient treatment program. Forty-eight young adult men received either treatment as usual (TAU) plus three sessions of HRV BFB training over three weeks, or TAU only. Participants receiving HRV BFB training were instructed to practice daily using a handheld HRV BFB device. HRV BFB training was well tolerated by participants and supported by treatment staff. Men receiving TAU + HRV BFB demonstrated a greater, medium effect size reduction in alcohol and drug craving compared to those receiving TAU only, although this difference did not reach statistical significance. In addition, an interaction effect was observed in analyses that accounted for baseline craving levels, wherein heart rate variability (HRV) levels at treatment entry were predictive of changes in craving in the TAU group only. Low baseline levels of HRV were associated with increases in craving, whereas higher baseline HRV levels were associated with greater decreases in craving from start to end of treatment. In the TAU + HRV BFB group, however, there was no such association. That is, HRV BFB appeared to dissociate individual differences in baseline HRV levels from changes in craving. Given that alcohol and drug craving often precipitates relapse, HRV BFB merits further study as an adjunct treatment to ameliorate craving experienced by persons with substance use disorders. PMID:25179673

  1. The Relationship Between Obstructive Sleep Apnea and Self-Reported Stroke or Coronary Heart Disease in Overweight and Obese Adults with Type 2 Diabetes Mellitus

    PubMed Central

    Rice, Thomas B.; Foster, Gary D.; Sanders, Mark H.; Unruh, Mark; Reboussin, David; Kuna, Samuel T.; Millman, Richard; Zammit, Gary; Wing, Rena R.; Wadden, Thomas A.; Kelley, David; Pi-Sunyer, Xavier; Newman, Anne B.

    2012-01-01

    Study Objectives: Type 2 diabetes mellitus (T2DM) and obstructive sleep apnea (OSA) are common, increasingly recognized as comorbid conditions, and individually implicated in the development of cardiovascular disease (CVD). We sought to determine the association between OSA and CVD in an overweight and obese population with T2DM. Design: Cross-sectional. Setting: Ancillary study to the Look AHEAD trial. Participants: Three hundred five participants of the Sleep AHEAD study who underwent unattended full polysomnography at home with measurement of the apnea-hypopnea index (AHI). Measurements and Results: Self-reported prevalent CVD was obtained at the initial assessment of the parent study and included a history of the following conditions: stroke, carotid endarterectomy, myocardial infarction, coronary artery bypass grafting, and percutaneous coronary intervention. Logistic regression was used to assess the association of OSA, measured continuously and categorically, with prevalent CVD. OSA was present (AHI ≥ 5) in 86% of the population, whereas the prevalence of all forms of CVD was just 14%. The AHI was associated with stroke with an adjusted odds ratio (95% confidence interval) of 2.57 (1.03, 6.42). Neither the continuously measured AHI nor the categories of OSA severity were significantly associated with the other forms of CVD assessed. Conclusions: We found suggestive evidence of a greater prevalence of stroke at greater values of the AHI. OSA was not associated with prevalent coronary heart disease in the Sleep AHEAD trial. Future studies should confirm the link between OSA and stroke and examine mechanisms that link OSA to stroke in adults with T2DM. Citation: Rice TB; Foster GD; Sanders MH; Unruh M; Reboussin D; Kuna ST; Millman R; Zammit G; Wing RR; Wadden TA; Kelley D; Pi-Sunyer X; Newman AB. The relationship between obstructive sleep apnea and self-reported stroke or coronary heart disease in overweight and obese adults with type 2 diabetes mellitus

  2. The effect of heart rate controlled low resistance circuit weight training and endurance training on maximal aerobic power in sedentary adults.

    PubMed

    Kaikkonen, H; Yrjämä, M; Siljander, E; Byman, P; Laukkanen, R

    2000-08-01

    The effects of a 12-week low resistance circuit weight training (CWT) on cardiovascular and muscular fitness were studied in 90 healthy sedentary adults. The subjects were randomized into three equally fit groups: CWT, Endurance (END) and Control (CON) according to their maximal aerobic power (VO2max). Both training groups exercised for 12 weeks, 3 days a week in sessions of 40 min, with a heart rate (HR) level of 70-80% HRmax. The CWT group trained with air resistance machines. Heart rate was controlled by setting the speed of movement. The END group walked, jogged, cross-country skied or cycled. The net differences (between pre- and posttraining changes) between the CWT and CON groups was statistically significant for VO2max (2.45 ml x min(-1) x kg(-1), 95% CI 1.1; 3.8), for abdominal muscles (3.7 reps, CI 0.3; 7.1), for push-ups (1.1 reps, CI 0.2; 2.1), and for kneeling (2.25 reps, CI 0.01; 4.5). The net difference (between pre- and posttraining changes) in the END and CON groups was statistically significant for VO2max (2.75 ml(-1) x min(-1) x kg(-1), 95% CI 0.9; 4.6), and kneeling (3.0 reps, CI 0.7; 5.3). Low resistance CWT with moderately hard HR level has effects comparable to an equal amount of endurance training on the cardiovascular fitness of sedentary adults. The CWT model was benefical also on muscular fitness. Based on the results, this type of exercise can be recommended for beginners because of its multilevel effects. PMID:10898265

  3. Incidence, etiology, and outcome of primary graft dysfunction in adult heart transplant recipients: a single-center experience in Japan.

    PubMed

    Seguchi, Osamu; Fujita, Tomoyuki; Murata, Yoshihiro; Sunami, Haruki; Sato, Takuma; Watanabe, Takuya; Nakajima, Seiko; Kuroda, Kensuke; Hisamatsu, Eriko; Sato, Takamasa; Yanase, Masanobu; Hata, Hiroki; Wada, Kyoichi; Ishibashi-Ueda, Hatsue; Kobayashi, Junjiro; Nakatani, Takeshi

    2016-04-01

    Donor and recipient characteristics, as well as donor-recipient matching, affect clinical outcomes after heart transplantation (HTx). This study aimed to clarify how donor and recipient characteristics affect the clinical course after HTx. The medical records of all the patients who underwent HTx at the National Cerebral and Cardiovascular Center from 1999 to 2014 were retrospectively reviewed. Sixty-one patients (48 males) underwent HTx. Six recipients (9.8 %) developed primary graft dysfunction (PGD) determined by criteria recently established at a consensus conference. Development of PGD was associated with high-dose inotropic support for the donor heart and a history of stroke in the recipient (p = 0.04 and p = 0.002, respectively). Recipients with PGD had higher right atrial pressure (RAP) and lower cardiac output (CO) compared with those without PGD at 6 months after HTx (RAP, 6.8 ± 3.6 vs. 2.8 ± 2.2 mmHg, p < 0.001; CO, 4.6 ± 0.8 l vs. 5.8 ± 1.2 l/min, p = 0.02). With respect to survival, patients with PGD had a 5-year survival rate equivalent to those without PGD (83.3 vs. 93.3 %, p = 0.23). High-dose inotropic support for the donor heart and a history of stroke in the recipient are significant predictive factors for the development of PGD. However, recipients with PGD demonstrate mid-term survival comparable to those without PGD. PMID:25682298

  4. Following your heart or your head: focusing on emotions versus information differentially influences the decisions of younger and older adults.

    PubMed

    Mikels, Joseph A; Löckenhoff, Corinna E; Maglio, Sam J; Goldstein, Mary K; Garber, Alan; Carstensen, Laura L

    2010-03-01

    Research on aging has indicated that whereas deliberative cognitive processes decline with age, emotional processes are relatively spared. To examine the implications of these divergent trajectories in the context of health care choices, we investigated whether instructional manipulations emphasizing a focus on feelings or details would have differential effects on decision quality among younger and older adults. We presented 60 younger and 60 older adults with health care choices that required them to hold in mind and consider multiple pieces of information. Instructional manipulations in the emotion-focus condition asked participants to focus on their emotional reactions to the options, report their feelings about the options, and then make a choice. In the information-focus condition, participants were instructed to focus on the specific attributes, report the details about the options, and then make a choice. In a control condition, no directives were given. Manipulation checks indicated that the instructions were successful in eliciting different modes of processing. Decision quality data indicate that younger adults performed better in the information-focus than in the control condition whereas older adults performed better in the emotion-focus and control conditions than in the information-focus condition. Findings support and extend extant theorizing on aging and decision making as well as suggest that interventions to improve decision-making quality should take the age of the decision maker into account. PMID:20350046

  5. Following Your Heart or Your Head: Focusing on Emotions Versus Information Differentially Influences the Decisions of Younger and Older Adults

    PubMed Central

    Mikels, Joseph A.; Löckenhoff, Corinna E.; Maglio, Sam J.; Goldstein, Mary K.; Garber, Alan; Carstensen, Laura L.

    2014-01-01

    Research on aging indicates that whereas deliberative cognitive processes decline with age, emotional processes are relatively spared. To examine the implications of these divergent trajectories in the context of healthcare choices, we investigated whether instructional manipulations emphasizing a focus on feelings or details would have differential effects on decision quality among younger and older adults. We presented 60 younger and 60 older adults with healthcare choices that required them to hold in mind and consider multiple pieces of information. Instructional manipulations in the emotion-focus condition asked participants to focus on their emotional reactions to the options, report their feelings about the options, and then make a choice. In the information-focus condition, participants were instructed to focus on the specific attributes, report the details about the options, and then make a choice. In a control condition, no directives were given. Manipulation checks indicated that the instructions were successful in eliciting different modes of processing. Decision quality data indicate that younger adults performed better in the information-focus than in the control condition whereas older adults performed better in the emotion-focus and control conditions than in the information-focus condition. Findings support and extend extant theorizing on aging and decision making as well as suggest that interventions to improve decision making quality should take the age of the decision maker into account. PMID:20350046

  6. "What I Feel in My Heart": Literacy Practices of and for the Self among Adults with Limited or No Schooling

    ERIC Educational Resources Information Center

    Perry, Kristen H.; Homan, Annie

    2014-01-01

    Through this international cross-case analysis of ethnographic literacy practices data, we investigated two questions: (1) In what literacy practices do adults with limited or no schooling engage for personal fulfillment? and (2) What do these practices reveal about the nature of literacy for individuals who are often characterized as illiterate?…

  7. Temporal Relationship Between Childhood Body Mass Index and Insulin and Its Impact on Adult Hypertension: The Bogalusa Heart Study.

    PubMed

    Zhang, Tao; Zhang, Huijie; Li, Ying; Sun, Dianjianyi; Li, Shengxu; Fernandez, Camilo; Qi, Lu; Harville, Emily; Bazzano, Lydia; He, Jiang; Xue, Fuzhong; Chen, Wei

    2016-09-01

    Although obesity and insulin resistance are closely correlated, their temporal sequences in early life and influence on adult hypertension are largely unknown. This study aims to delineate the temporal relationship patterns between body mass index (BMI) and insulin in childhood and their impact on adult hypertension. The longitudinal cohort consisted of 990 adults (630 whites and 360 blacks) who had BMI and fasting insulin measured twice 5.4 years apart in childhood (mean age, 10.5 years at baseline and 15.9 years at follow-up) and blood pressure measured 14.7 years later in adulthood (mean age, 30.5 years). Cross-lagged panel and mediation analysis models were used to examine the temporal relationship between childhood BMI and insulin and its impact on adult hypertension. After adjusting for age, race, sex, and follow-up years, the cross-lagged path coefficient (β=0.33; P<0.001) from baseline BMI to follow-up insulin was significantly greater than the path coefficient (β=-0.02; P>0.05) from baseline insulin to follow-up BMI in childhood with P<0.001 for the difference in βs. Blacks and whites showed similar patterns of the temporal relationship. The path coefficient (β=0.59; P<0.001) from BMI to insulin in the hypertensive group was significantly greater than that (β=0.24; P<0.001) in normotensive group, with P<0.001 for the difference in βs between these 2 groups. The mediation effect of childhood insulin on the childhood BMI-adult hypertension association was estimated at 21.1% (P<0.001). These findings provide evidence that higher BMI levels precede hyperinsulinemia during childhood, and this 1-directional relation plays a role in the development of hypertension. PMID:27432860

  8. Elk3 deficiency causes transient impairment in post-natal retinal vascular development and formation of tortuous arteries in adult murine retinae.

    PubMed

    Weinl, Christine; Wasylyk, Christine; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Beck, Susanne C; Riehle, Heidemarie; Stritt, Christine; Roux, Michel J; Seeliger, Mathias W; Wasylyk, Bohdan; Nordheim, Alfred

    2014-01-01

    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(-/-) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(-/-) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(-/-) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients. PMID:25203538

  9. Elk3 Deficiency Causes Transient Impairment in Post-Natal Retinal Vascular Development and Formation of Tortuous Arteries in Adult Murine Retinae

    PubMed Central

    Weinl, Christine; Wasylyk, Christine; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Beck, Susanne C.; Riehle, Heidemarie; Stritt, Christine; Roux, Michel J.; Seeliger, Mathias W.; Wasylyk, Bohdan; Nordheim, Alfred

    2014-01-01

    Serum Response Factor (SRF) fulfills essential roles in post-natal retinal angiogenesis and adult neovascularization. These functions have been attributed to the recruitment by SRF of the cofactors Myocardin-Related Transcription Factors MRTF-A and -B, but not the Ternary Complex Factors (TCFs) Elk1 and Elk4. The role of the third TCF, Elk3, remained unknown. We generated a new Elk3 knockout mouse line and showed that Elk3 had specific, non-redundant functions in the retinal vasculature. In Elk3(−/−) mice, post-natal retinal angiogenesis was transiently delayed until P8, after which it proceeded normally. Interestingly, tortuous arteries developed in Elk3(−/−) mice from the age of four weeks, and persisted into late adulthood. Tortuous vessels have been observed in human pathologies, e.g. in ROP and FEVR. These human disorders were linked to altered activities of vascular endothelial growth factor (VEGF) in the affected eyes. However, in Elk3(−/−) mice, we did not observe any changes in VEGF or several other potential confounding factors, including mural cell coverage and blood pressure. Instead, concurrent with the post-natal transient delay of radial outgrowth and the formation of adult tortuous arteries, Elk3-dependent effects on the expression of Angiopoietin/Tie-signalling components were observed. Moreover, in vitro microvessel sprouting and microtube formation from P10 and adult aortic ring explants were reduced. Collectively, these results indicate that Elk3 has distinct roles in maintaining retinal artery integrity. The Elk3 knockout mouse is presented as a new animal model to study retinal artery tortuousity in mice and human patients. PMID:25203538

  10. Usability Testing of an Internet-Based e-Counseling Platform for Adults With Chronic Heart Failure

    PubMed Central

    Surikova, Jelena; Liu, Sam; Ross, Heather; Mechetiuc, Teodora; Nolan, Robert P

    2015-01-01

    Background Chronic heart failure (CHF) is a major cause of hospitalization and mortality. In order to maintain heart function and quality of life, patients with CHF need to follow recommended self-care guidelines (ie, eating a heart healthy diet, exercising regularly, taking medications as prescribed, monitoring their symptoms, and living a smoke-free life). Yet, adherence to self-care is poor. We have developed an Internet-based e-Counseling platform, Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT), that aims to improve self-care adherence and quality of life in people with CHF. Before assessing the efficacy of this e-platform in a multisite, double-blind, randomized controlled trial, we evaluated the usability of the prototype website. Objective The objective of the study was to assess the usability of the CHF-CePPORT e-Counseling platform in terms of navigation, content, and layout. Methods CHF patients were purposively sampled from the Heart Function Clinic at the Peter Munk Cardiac Center, University Health Network, to participate in this study. We asked the consented participants to perform specific tasks on the website. These tasks included watching self-help videos and reviewing content as directed. Their interactions with the website were captured using the “think aloud” protocol. After completing the tasks, research personnel conducted a semi-structured interview with each participant to assess their experience with the website. Content analysis of the transcripts from the “think aloud” sessions and the interviews was conducted to identify themes related to navigation, content, and layout of the website. Descriptive statistics were used to summarize the satisfaction data. Results A total of 7 men and women (ages 39-77) participated in 2 iterative rounds of testing. Overall, all participants were very satisfied with the content and layout of the website. They reported that the content was helpful to

  11. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta.

    PubMed

    Panaroni, Cristina; Gioia, Roberta; Lupi, Anna; Besio, Roberta; Goldstein, Steven A; Kreider, Jaclynn; Leikin, Sergey; Vera, Juan Carlos; Mertz, Edward L; Perilli, Egon; Baruffaldi, Fabio; Villa, Isabella; Farina, Aurora; Casasco, Marco; Cetta, Giuseppe; Rossi, Antonio; Frattini, Annalisa; Marini, Joan C; Vezzoni, Paolo; Forlino, Antonella

    2009-07-01

    Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [alpha1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P < .05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases. PMID:19414862

  12. EphB2 and EphB3 play an important role in the lymphoid seeding of murine adult thymus.

    PubMed

    Alfaro, David; García-Ceca, Javier; Farias-de-Oliveira, Desio A; Terra-Granado, Eugenia; Montero-Herradón, Sara; Cotta-de-Almeida, Vinicius; Savino, Wilson; Zapata, Agustín

    2015-12-01

    Adult thymuses lacking either ephrin type B receptor 2 (EphB2) or EphB3, or expressing a truncated form of EphB2, the forward signal-deficient EphB2LacZ, have low numbers of early thymic progenitors (ETPs) and are colonized in vivo by reduced numbers of injected bone marrow (BM) lineage-negative (Lin(-)) cells. Hematopoietic progenitors from these EphB mutants showed decreased capacities to colonize wild type (WT) thymuses compared with WT precursors, with EphB2(-/-) cells exhibiting the greatest reduction. WT BM Lin(-) cells also showed decreased colonizing capacity into mutant thymuses. The reduction was also more severe in EphB2(-/-) host thymuses, with a less severe phenotype in the EphB2LacZ thymus. These results suggest a major function for forward signaling through EphB2 and, to a lesser extent, EphB3, in either colonizing progenitor cells or thymic stromal cells, for in vivo adult thymus recruitment. Furthermore, the altered expression of the molecules involved in thymic colonization that occurs in the mutant thymus correlates with the observed colonizing capacities of different mutant mice. Reduced production of CCL21 and CCL25 occurred in the thymus of the 3 EphB-deficient mice, but their expression, similar to that of P-selectin, on blood vessels, the method of entry of progenitor cells into the vascular thymus, only showed a significant reduction in EphB2(-/-) and EphB3(-/-) thymuses. Decreased migration into the EphB2(-/-) thymuses correlated also with reduced expression of both ephrinB1 and ephrinB2, without changes in the EphB2LacZ thymuses. In the EphB3(-/-) thymuses, only ephrinB1 expression appeared significantly diminished, confirming the relevance of forward signals mediated by the EphB2-ephrinB1 pair in cell recruitment into the adult thymus. PMID:25810451

  13. Bad Marriage, Broken Heart? Age and Gender Differences in the Link between Marital Quality and Cardiovascular Risks among Older Adults

    PubMed Central

    Liu, Hui; Waite, Linda

    2015-01-01

    Working from a life course perspective, we develop hypotheses about age and gender differences in the link between marital quality and cardiovascular risk and test them using data from the first two waves of the National Social Life, Health, and Aging Project. The analytic sample includes 459 married women and 739 married men (aged 57–85 in the first wave) who were interviewed in both waves. We apply Heckman-type corrections for selection bias due to mortality and marriage. Cardiovascular risk is measured as hypertension, rapid heart rate, C-reactive protein, and general cardiovascular events. Results suggest that changes in marital quality and cardiovascular risk are more closely related for older married people than for their younger counterparts; and that the link between marital quality and cardiovascular risk is more pronounced among women than among men at older ages. These findings fit with the gendered life course perspective and cumulative disadvantage framework. PMID:25413802

  14. Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation

    PubMed Central

    Choi, Nahyun; Zhang, Boyu; Zhang, Li; Ittmann, Michael; Xin, Li

    2012-01-01

    Summary The prostate epithelial lineage hierarchy and the cellular origin for prostate cancer remain inadequately defined. Using a lineage tracing approach, we show that adult rodent prostate basal and luminal cells are independently self-sustained in vivo. Disrupting the tumor suppressor Pten in either lineage led to prostate cancer initiation. However, the cellular composition and onset dynamics of the resulting tumors are distinctive. Prostate luminal cells are more responsive to Pten null-induced mitogenic signaling. In contrast, basal cells are resistant to direct transformation. Instead, loss of Pten activity induces the capability of basal cells to differentiate into transformation-competent luminal cells. Our study suggests that deregulation of epithelial differentiation is a critical step for the initiation of prostate cancers of basal cell origin. PMID:22340597

  15. Lifestyle Intervention Improves Heart Rate Recovery from Exercise in Adults with Type 2 Diabetes: Results from the Look AHEAD Study

    PubMed Central

    Ribisl, Paul M.; Gaussoin, Sarah A.; Lang, Wei; Bahnson, Judy; Connelly, Stephanie A.; Horton, Edward S.; Jakicic, John M.; Killean, Tina; Kitzman, Dalane W.; Knowler, William C.; Stewart, Kerry J.; Research Group, Look AHEAD

    2012-01-01

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45–76 years) who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI) with (DSE) upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P < 0.001) while mean fitness increased in ILI by 20.9% versus 5.8% in DSE (P < 0.001). At Year 1, all exercise and HRR variables in ILI improved (P < 0.0001) versus DSE: heart rate (HR) at rest was lower (72.8 ± 11.4 versus 77.7 ± 11.7 b/min), HR range was greater (57.7 ± 12.1 versus 53.1 ± 12.4 b/min), HR at 2 minutes was lower (89.3 ± 21.8 versus 93.0 ± 12.1 b/min), and HRR was greater (41.25 ± 22.0 versus 37.8 ± 12.5 b/min). Weight loss and fitness gain produced significant separate and independent improvements in HRR. PMID:23227314

  16. Lifestyle intervention improves heart rate recovery from exercise in adults with type 2 diabetes: results from the Look AHEAD study.

    PubMed

    Ribisl, Paul M; Gaussoin, Sarah A; Lang, Wei; Bahnson, Judy; Connelly, Stephanie A; Horton, Edward S; Jakicic, John M; Killean, Tina; Kitzman, Dalane W; Knowler, William C; Stewart, Kerry J

    2012-01-01

    The primary aims of this paper were (1) to evaluate the influence of intensive lifestyle weight loss and exercise intervention (ILI) compared with diabetes support and education (DSE) upon Heart Rate Recovery (HRR) from graded exercise testing (GXT) and (2) to determine the independent and combined effects of weight loss and fitness changes upon HRR. In 4503 participants (45-76 years) who completed 1 year of intervention, HRR was measured after a submaximal GXT to compare the influence of (ILI) with (DSE) upon HRR. Participants assigned to ILI lost an average 8.6% of their initial weight versus 0.7% in DSE group (P < 0.001) while mean fitness increased in ILI by 20.9% versus 5.8% in DSE (P < 0.001). At Year 1, all exercise and HRR variables in ILI improved (P < 0.0001) versus DSE: heart rate (HR) at rest was lower (72.8 ± 11.4 versus 77.7 ± 11.7 b/min), HR range was greater (57.7 ± 12.1 versus 53.1 ± 12.4 b/min), HR at 2 minutes was lower (89.3 ± 21.8 versus 93.0 ± 12.1 b/min), and HRR was greater (41.25 ± 22.0 versus 37.8 ± 12.5 b/min). Weight loss and fitness gain produced significant separate and independent improvements in HRR. PMID:23227314

  17. Vaccination of adult and newborn mice of a resistant strain (C57BL/6J) against challenge with leukemias induced by Moloney murine leukemia virus

    SciTech Connect

    Reif, A.E.

    1985-01-01

    Adult or newborn C57BL/6J mice were immunized with isogenic Moloney strain MuLV-induced leukemia cells irradiated with 10,000 rads or treated with low concentrations of formalin. Groups of immunized and control mice were challenged with a range of doses of viable leukemia cells, and tumor deaths were recorded for 90 days after challenge. Then, the doses of challenge cells which produced 50% tumor deaths were calculated for immunized and control mice. The logarithm of their ratio quantified the degree of protection provided by immunization. For adult C57BL/6J mice, a single immunization with MuLV-induced leukemia cells was not effective; either cells plus Bacillus Calmette-Guerin or Corynebacterium parvum, or else two immunizations with irradiated leukemia cells were needed to produce statistically significant increases in the values of the doses of challenge cells which produced 50% tumor deaths. Cross-protection was obtained by immunization with other isogenic MuLV-induced leukemias, but not by immunization with isogenic carcinogen-induced tumors or with an isogenic spontaneous leukemia. For newborn mice, a single injection of irradiated leukemia cells provided 1.3 to 1.5 logs of protection, and admixture of B. Calmette-Guerin or C. parvum increased this protection to 2.4 to 2.7 logs. Since irradiated and frozen-thawed MuLV-induced leukemia cells contained viable MuLV, leukemia cells treated with 0.5 or 1.0% formalin were tested as an alternative. A single injection of formalin-treated isogenic leukemia cells admixed with C. parvum provided between 1.7 and 2.8 logs of protection. These results demonstrate that a single vaccination of newborn animals against a highly antigenic virally induced leukemia produces strong protection against a subsequent challenge with viable leukemia cells.

  18. Cloning of murine ferrochelatase.

    PubMed Central

    Brenner, D A; Frasier, F

    1991-01-01

    Ferrochelatase (protoheme ferro-lyase, EC 4.99.1.1) catalyzes the last step in the heme biosynthetic pathway, the chelation of ferrous iron and protoporphyrin to form heme. The activity of ferrochelatase is deficient in the inherited disease protoporphyria. In this study, murine ferrochelatase cDNAs were obtained by screening cDNA libraries with an oligonucleotide probe. The derived amino acid sequence of murine ferrochelatase has 47% identity with the recently cloned Saccharomyces cerevisiae ferrochelatase, but it is not significantly similar to other published sequences. Results of Southern blotting are consistent with a single murine ferrochelatase gene, while Northern blotting demonstrates two ferrochelatase transcripts in all tissues examined. The ferrochelatase protein and mRNAs have different relative concentrations in different tissues. The cloning of murine ferrochelatase cDNAs provides the basis for future studies on ferrochelatase gene expression and on the identification of the molecular defect in protoporphyria. Images PMID:1704134

  19. Sense and antisense transcripts of the developmentally regulated murine hsp70.2 gene are expressed in distinct and only partially overlapping areas in the adult brain

    NASA Technical Reports Server (NTRS)

    Murashov, A. K.; Wolgemuth, D. J.

    1996-01-01

    We have examined the spatial pattern of expression of a member of the hsp70 gene family, hsp70.2, in the mouse central nervous system. Surprisingly, RNA blot analysis and in situ hybridization revealed abundant expression of an 'antisense' hsp70.2 transcript in several areas of adult mouse brain. Two different transcripts recognized by sense and antisense riboprobes for the hsp70.2 gene were expressed in distinct and only partially overlapping neuronal populations. RNA blot analysis revealed low levels of the 2.7 kb transcript of hsp70.2 in several areas of the brain, with highest signal in the hippocampus. Abundant expression of a slightly larger (approximately 2.8 kb) 'antisense' transcript was detected in several brain regions, notably in the brainstem, cerebellum, mesencephalic tectum, thalamus, cortex, and hippocampus. In situ hybridization revealed that the sense and antisense transcripts were both predominantly neuronal and localized to the same cell types in the granular layer of the cerebellum, trapezoid nucleus of the superior olivary complex, locus coeruleus and hippocampus. The hsp70.2 antisense transcripts were particularly abundant in the frontal cortex, dentate gyrus, subthalamic nucleus, zona incerta, superior and inferior colliculi, central gray, brainstem, and cerebellar Purkinje cells. Our findings have revealed a distinct cellular and spatial localization of both sense and antisense transcripts, demonstrating a new level of complexity in the function of the heat shock genes.

  20. Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25.

    PubMed

    Zhang, Zhuo; Zhang, Meili; Garmestani, Kayhan; Talanov, Vladimir S; Plascjak, Paul S; Beck, Barbara; Goldman, Carolyn; Brechbiel, Martin W; Waldmann, Thomas A

    2006-08-01

    Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 ((211)At)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 microCi (0.444 MBq) (211)At-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 microg weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta(2)mu) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 microCi (0.444 MBq) of (211)At-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody (211)At-11F11-treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining (211)At-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL. PMID:16569769

  1. Translating and Testing the ENABLE: CHF-PC Concurrent Palliative Care Model for Older Adults with Heart Failure and Their Family Caregivers

    PubMed Central

    Dionne-Odom, J. Nicholas; Kono, Alan; Frost, Jennifer; Jackson, Lisa; Ellis, Daphne; Ahmed, Ali; Azuero, Andres

    2014-01-01

    Abstract Background: Heart failure (HF) and palliative care (PC) organizations recommend early PC to improve the quality of life of patients living with HF. Objective: We conducted a two-phase formative evaluation study to translate a cancer-focused concurrent PC intervention into one that would be appropriate for rural-dwelling adults with New York Heart Association Class III-IV HF and their primary caregivers. Methods: Phase I: We tailored the intervention for an HF population via literature review, expert consultation, and clinician (N=15) small group interviews. Phase II: We enrolled 11 patient/caregiver dyads to assess intervention feasibility and satisfaction. We assessed participants' experiences and satisfaction after session/week three and session/week six via digitally recorded interviews. Clinician and participant interviews were transcribed and content analyzed. Outcome measures were evaluated for completion rates and effect sizes. Results: Phase I: Clinicians described barriers to initiating PC in HF, triggers for initiating PC, and suggestions for intervention improvement. Phase II: Participants were able to complete the majority of study sessions, measures, and interviews. Satisfaction interviews revealed the content to be relevant and comprehensive in addressing HF patient and caregiver primary concerns; however, participants unanimously suggested making the intervention available earlier in the illness trajectory. Efficacy measures demonstrated small to medium effect sizes. Conclusions: We tailored and demonstrated feasibility of providing an early, concurrent palliative care intervention to patients with advanced HF and their caregivers. Based on this experience we are now conducting an efficacy trial in a racially diverse sample. PMID:25072240

  2. Association of ambulatory heart rate and atherosclerosis risk factors with blood pressure in young non-hypertensive adults

    PubMed Central

    Cheng, Cynthia; Daskalakis, Constantine

    2016-01-01

    Objective The study objective was to assess the association between 24 h ambulatory heart rate (HR), atherosclerosis risk factors and blood pressure (BP) in young non-hypertensive patients. Methods We recruited 186 participants aged 18–45 years from a large urban academic Family Medicine outpatient practice, serving 40 000 individuals for this observational study. The main analyses were based on multiple linear regression, with mean 24 h BP (systolic BP (SBP) or diastolic BP (DBP)) as the outcomes, mean 24 h HR as the main predictor of interest, and controlling for age, gender, race, insulin sensitivity/resistance and endothelial function measured by strain gauge venous occlusion plethysmography. Results HR was independently associated with mean 24 h SBP and DBP (SBP and DBP: p=0.042 and 0.001, respectively). In our analyses, associations were markedly stronger for ambulatory compared with office BP measurements. Endothelial dysfunction was associated with higher SBP (p=0.013); plasminogen activator inhibitor-1 was significantly associated with both SBP and DBP (p=0.041 and 0.015, respectively), while insulin resistance was not associated with either SBP or DBP. Insulin resistance and C reactive protein were significant predictors of HR (p=0.013 and 0.007, respectively). Conclusions These findings suggest that HR may be a potential marker of elevated cardiovascular risk in young asymptomatic individuals, prior to the development of clinical hypertension or cardiovascular disease. PMID:26925242

  3. Prediabetes is not an independent risk factor for incident heart failure, other cardiovascular events or mortality in older adults: Findings from a population-based cohort study

    PubMed Central

    Deedwania, Prakash; Patel, Kanan; Fonarow, Gregg C.; Desai, Ravi V.; Zhang, Yan; Feller, Margaret A.; Ovalle, Fernando; Love, Thomas E.; Aban, Inmaculada B.; Mujib, Marjan; Ahmed, Mustafa I.; Anker, Stefan D.; Ahmed, Ali

    2013-01-01

    Background Whether prediabetes is an independent risk factor for incident heart failure (HF) in non-diabetic older adults remains unclear. Methods Of the 4602 Cardiovascular Health Study participants, age ≥ 65 years, without baseline HF and diabetes, 2157 had prediabetes, defined as fasting plasma glucose (FPG) 100–125 mg/dL. Propensity scores for prediabetes, estimated for each of the 4602 participants, were used to assemble a cohort of 1421 pairs of individuals with and without prediabetes, balanced on 44 baseline characteristics. Results Participants had a mean age of 73 years, 57% were women, and 13% African American. Incident HF occurred in 18% and 20% of matched participants with and without prediabetes, respectively (hazard ratio {HR} associated with prediabetes, 0.90; 95% confidence interval {CI}, 0.76–1.07; p = 0.239). Unadjusted and multivariable-adjusted HRs (95% CIs) for incident HF associated with prediabetes among 4602 pre-match participants were 1.22 (95% CI, 1.07–1.40; p = 0.003) and 0.98 (95% CI, 0.85–1.14; p = 0.826), respectively. Among matched individuals, prediabetes had no independent association with incident acute myocardial infarction (HR, 1.02; 95% CI, 0.81–1.28; p = 0.875), angina pectoris (HR, 0.93; 95% CI, 0.77–1.12; p = 0.451), stroke (HR, 0.86; 95% CI, 0.70–1.06; p = 0.151) or all-cause mortality (HR, 0.99; 95% CI, 0.88–1.11; p = 0.840). Conclusions We found no evidence that prediabetes is an independent risk factor for incident HF, other cardiovascular events or mortality in community-dwelling older adults. These findings question the wisdom of routine screening for prediabetes in older adults and targeted interventions to prevent adverse outcomes in older adults with prediabetes. PMID:23731526

  4. Epigenome-wide DNA methylation analysis implicates neuronal and inflammatory signaling pathways in adult murine hepatic tumorigenesis following perinatal exposure to bisphenol A.

    PubMed

    Weinhouse, Caren; Sartor, Maureen A; Faulk, Christopher; Anderson, Olivia S; Sant, Karilyn E; Harris, Craig; Dolinoy, Dana C

    2016-07-01

    Developmental exposure to the endocrine-active compound bisphenol A (BPA) has been linked to epigenotoxic and potential carcinogenic effects in rodent liver, prostate, and mammary glands. A dose-dependent increase in hepatic tumors in 10-month mice perinatally exposed to one of three doses of BPA (50 ng, 50 µg, or 50 mg BPA/kg chow) was previously reported. These tumors represent early-onset disease and lack classical sexual dimorphism in incidence. Here, adult epigenome-wide liver DNA methylation profiles to identify gene promoters associated with perinatal BPA exposure and disease in 10-month mice with and without liver tumors were investigated. Mice with hepatic tumors showed 12,822 (1.8%) probes with differential methylation as compared with non-tumor animals, of which 8,656 (67.5%) were hypomethylated. A significant enrichment of differential methylation in Gene Ontology (GO) terms and biological processes related to morphogenesis and development, and epigenomic alteration were observed. Pathway enrichment revealed a predominance of hypermethylated neuronal signaling pathways linked to energy regulation and metabolic function, supporting metabolic consequences in the liver via BPA-induced disruption of neuronal signaling pathways. Hypothesis-driven pathway analysis revealed mouse and human genes linked to BPA exposure related to intracellular Jak/STAT and MAPK signaling pathways. Taken together, these findings are indicators of the relevance of the hepatic tumor phenotype seen in BPA-exposed mice to human health. This work demonstrated that epigenome-wide discovery experiments in animal models were effective tools for identification and understanding of paralagous epimutations salient to human disease. Environ. Mol. Mutagen. 57:435-446, 2016. © 2016 Wiley Periodicals, Inc. PMID:27334623

  5. Systolic Blood Pressure Lower than Heart Rate upon Arrival at and Departure from the Emergency Department Indicates a Poor Outcome for Adult Trauma Patients

    PubMed Central

    Lai, Wei-Hung; Wu, Shao-Chun; Rau, Cheng-Shyuan; Kuo, Pao-Jen; Hsu, Shiun-Yuan; Chen, Yi-Chun; Hsieh, Hsiao-Yun; Hsieh, Ching-Hua

    2016-01-01

    Background: Hemorrhage is a leading cause of preventable trauma death. In this study, we used the reverse shock index (RSI), a ratio of systolic blood pressure (SBP) to heart rate (HR), to evaluate the hemodynamic stability of trauma patients. As an SBP lower than the HR (RSI < 1) may indicate hemodynamic instability, the objective of this study was to assess the associated complications in trauma patients with an RSI < 1 upon arrival at the emergency department (ED) (indicated as (A)RSI) and at the time of departure from the ED (indicated as (L)RSI) to the operative room or for admission. Methods: Data obtained from all 16,548 hospitalized patients recorded in the trauma registry system at a Level I trauma center between January 2009 and December 2013 were retrospectively reviewed. A total of 10,234 adult trauma patients aged ≥20 were enrolled and subsequently divided into four groups: Group I, (A)RSI ≥ 1 and (L)RSI ≥ 1 (n = 9827); Group II, (A)RSI ≥ 1 and (L)RSI < 1 (n = 76); Group III, (A)RSI < 1 and (L)RSI ≥ 1 (n = 251); and Group IV, (A)RSI < 1 and (L)RSI < 1 (n = 80). Pearson’s χ2 test, Fisher’s exact test, or independent Student’s t-test was conducted to compare trauma patients in Groups II, III, and IV with those in Group I. Results: Patients in Groups II, III, and IV had a higher injury severity score and underwent a higher number of procedures, including intubation, chest tube insertion, and blood transfusion, than Group I patients. Additionally, patients of these groups had increased hospital length of stay (16.3 days, 14.9 days, and 22.0 days, respectively), proportion of patients admitted to the intensive care unit (ICU) (48.7%, 43.0%, and 62.5%, respectively), and in-hospital mortality (19.7%, 7.6%, and 27.5%, respectively). Although the trauma patients who had a SBP < 90 mmHg either upon arrival at or departure from the ED also present a more severe injury and poor outcome, those patients who had a SBP ≥ 90 mmHg but an RSI < 1 had

  6. Impact of Adiposity on Incident Hypertension Is Modified by Insulin Resistance in Adults: Longitudinal Observation From the Bogalusa Heart Study.

    PubMed

    Zhang, Tao; Zhang, Huijie; Li, Shengxu; Li, Ying; Liu, Yaozhong; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia; He, Jiang; Chen, Wei

    2016-01-01

    Adiposity and insulin resistance are closely associated with hypertension. This study aims to investigate whether the association between adiposity and hypertension is modified by insulin resistance. The cohort consisted of 1624 middle-aged normotensive black and white adults aged 18 to 43 years at baseline who followed for 16 years on average. Overweight/obesity at baseline was defined as body mass index (BMI) ≥25, and insulin resistance was measured using homeostasis model assessment of insulin resistance. Prevalence of incident hypertension was compared between the insulin-sensitive adiposity and insulin-resistant adiposity groups. The prevalence of incident hypertension was higher in the insulin-resistant adiposity than in the insulin-sensitive adiposity group (32.1% versus 22.1%, P<0.001). In multivariable logistic analyses, adjusted for baseline age, race, sex, follow-up years, and smoking, baseline insulin-resistant obesity was associated with incident hypertension (odds ratio, 1.9; P=0.008). Odds ratios did not differ between blacks and whites (P=0.238). Of note, the odds ratios of BMI associated with hypertension significantly increased with increasing quartiles of baseline homeostasis model assessment (odds ratio, 1.3, 1.1, 1.5, and 2.5 in quartiles I, II, III, and IV, respectively; P=0.006 for trend). Slopes of increasing follow-up blood pressure with baseline BMI, measured as regression coefficients (β), were significantly greater in insulin-resistant than in insulin-sensitive individuals (β=0.74 versus β=0.35 for systolic blood pressure, P=0.004 for difference; β=0.51 versus β=0.23 for diastolic blood pressure, P=0.001 for difference). These findings suggest that insulin resistance has a synergistic effect on the obesity-hypertension association in young adults, indicating that the role of adiposity in the development of hypertension is modified by insulin resistance. PMID:26573703

  7. Prevalence, control and awareness of high blood pressure among Canadian adults. Canadian Heart Health Surveys Research Group.

    PubMed Central

    Joffres, M R; Hamet, P; Rabkin, S W; Gelskey, D; Hogan, K; Fodor, G

    1992-01-01

    OBJECTIVE: To estimate the prevalence and distribution of elevated blood pressure (BP) among Canadian adults and to determine the level of control, treatment, awareness and prevalence of other risk factors among adults with high BP. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registers in each province. For 20,582 subjects, BP was measured at least twice. Nurses administered a standard questionnaire and recorded two BP measurements using a standardized technique. Two further BP readings, anthropometric measurements and a blood specimen for lipid analysis were obtained from those subjects who attended a clinic. OUTCOME MEASURES: Mean values of systolic and diastolic BP, prevalence of elevated BP using different criteria, and prevalence of smoking, elevated blood cholesterol, body mass index, physical activity and presence of diabetes by high BP status are reported. MAIN RESULTS: Sixteen percent of men and 13% of women had diastolic BP of 90 mm Hg or greater or were on treatment (or both). About 26% of these subjects were unaware of their hypertension, 42% were being treated and their condition controlled, 16% were treated and not controlled, and 16% were neither treated nor controlled. Use of non-pharmacologic treatment of high BP with or without medication was low (22%). Hypertensive subjects showed a higher prevalence of elevated total cholesterol, high body mass index, diabetes and sedentary lifestyle than normotensive subjects. Most people with elevated BP were in the 90 to 95 mm Hg range for diastolic pressure and 140 to 160 mm Hg range for systolic pressure. Prevalence of high isolated systolic BP sharply increased in men (40%) and women (49%) 65 to 74 years old. CONCLUSIONS: The relatively low level of control of elevated BP calls for population and individual strategies, stressing a

  8. Microvolt T wave alternans in adults with congenital heart diseases characterized by right ventricle pathology or single ventricle physiology: a case control study

    PubMed Central

    2013-01-01

    Background Among adults with congenital heart diseases (CHD) evaluation of sudden cardiac death (SCD) risk remains a great challenge. Although microvolt T-wave alternans has been incorporated into SCD risk stratification algorithm, its role in adults with CHD still requires investigation. We sought to determine the incidence of MTWA in this specific group and its coincidence with ventricular arrhythmia (VA) and other clinical findings presumably associated with SCD. Methods A case–control study was performed in which 102 patients with CHD characterized by right ventricle pathology or single ventricle physiology (TGA, UVH, Ebstein’s anomaly, ccTGA, Eisenmenger syndrome, DORV, CAT, unoperated ToF) were compared to 45 age- and sex-matched controls. All subjects underwent spectral MTWA test, ambulatory ecg monitoring, cardiopulmonary test, BNP assessment. After excluding technically inadequate traces, the remaining MTWA results were classified as positive(+), negative(−) and indeterminate(ind). Due to similar prognostic significance MTWA(+) and (ind) were combined into a common group labeled ‘abnormal’. Results Abnormal MTWA was present more often in the study group, compared to controls (39.2% vs 2.3%, p = 0.00001). Sustained ventricular tachycardia (sVT) was observed more often among subjects with abnormal MTWA compared to MTWA(−): 19.4% vs 3.6%, p = 0.026. The patients with abnormal MTWA had a lower blood saturation (p = 0.047), more often were males (p = 0.031), had higher NYHA class (p = 0.04), worse cardiopulmonary parameters: %PeakVO2 (p = 0.034), %HRmax (p = 0.003). Factors proven to increase probability of abnormal MTWA on multivariate linear regression analysis were: sVT (OR = 20.7, p = 0.037) and male gender (OR = 15.9, p = 0.001); on univariate analysis: male gender (OR = 2.7, p = 0.021), presence of VA (OR = 2.6, p = 0.049), NYHA > I (OR = 2.06, p = 0.033), %HRmax (OR

  9. Fruit and Vegetable Intake and Risk of Coronary Heart Disease: Results from Prospective Cohort Studies of Chinese Adults in Shanghai

    PubMed Central

    Yu, Danxia; Zhang, Xianglan; Gao, Yu-Tang; Li, Honglan; Yang, Gong; Huang, Jie; Zheng, Wei; Xiang, Yong-Bing; Shu, Xiao-Ou

    2013-01-01

    Protective associations of fruit and vegetables against coronary heart disease (CHD) have been suggested in many epidemiological studies among Western populations. However, prospective data are lacking for Asian populations. We examined the associations of fruit and vegetable intake with incidence of CHD among 67,211 women (40–70 years) and 55,474 men (40–74 years) living in Shanghai, China. Food intake was assessed using validated food-frequency questionnaires through in-person interviews. Coronary events (nonfatal myocardial infarction or fatal CHD) were identified by biennial home visits and further confirmed by medical records review. During a mean follow-up of 9.8 and 5.4 years, 148 events in women and 217 events in men were documented and verified, respectively. After adjustment for potential confounders, women in the highest quartile of total fruit and vegetable intake (median: 814 g/d) had a hazard ratio (HR) for CHD of 0.62 (95% CI 0.38, 1.02) (P for trend=0.04) compared with those in the lowest quartile (median: 274 g/d). This association was primarily driven by fruits (the HR for the highest vs. the lowest intake in women: 0.62; 95% CI, 0.37, 1.03). The strength of the association was attenuated after further controlling for history of diabetes or hypertension. For men, no significant association was found for fruit and vegetable intake when analyzed either in combination or individually. Our findings suggest that a high consumption of fruits may reduce the risk of CHD in Chinese women. PMID:23866068

  10. Impact of multiple cardiovascular risk factors on femoral artery intima-media thickness in asymptomatic young adults (the Bogalusa Heart Study).

    PubMed

    Paul, Timir K; Srinivasan, Sathanur R; Chen, Wei; Li, Shengxu; Bond, M Gene; Tang, Rong; Berenson, Gerald S

    2005-02-15

    Femoral artery intima-media thickness (IMT), like carotid IMT, is a surrogate indicator of atherosclerotic coronary and peripheral vascular diseases in middle-aged and older adults. Although risk factors for coronary artery disease are also associated with increased IMT, especially as measured in carotid arteries, there is a paucity of information with respect to the femoral artery in this regard in the asymptomatic, younger adult population. This study examined the impact of multiple risk factors on the common femoral artery IMT as measured by B-mode ultrasonography in 1,080 black and white subjects aged 24 to 43 years (71% white and 43% men) enrolled in the Bogalusa Heart Study. Femoral IMT showed gender difference (men more than women, p = 0.001), but no racial difference. In a multivariate model, systolic blood pressure, age, male gender, cigarette smoking, and total cholesterol/high-density lipoprotein cholesterol ratios related independently, in that order, to IMT. Mean IMT increased with an increasing number of risk factors defined as values above the age-, race-, and gender-specific 75th percentile of systolic blood pressure, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, and insulin along with smoking status (p for trend = 0.003), with respective mean IMT values of 0.66, 0.69, 0.73, and 0.79 mm for 0, 1 to 2, 3, and 4 to 5 risk factors. The odds ratio for patients with >/=3 risk factors versus no risk factors having IMT in the top fifth percentile was 4.7 (p = 0.01). The observed adverse trend of increasing femoral IMT with an increasing number of risk factors in free-living, asymptomatic young subjects underscores the need for multiple risk factors profiling in early life. Further, ultrasonography of the femoral artery in conjunction with multiple risk factor profiling can be helpful in risk stratification. PMID:15695130

  11. Linking an Anxiety-Related Personality Trait to Cardiac Autonomic Regulation in Well-Defined Healthy Adults: Harm Avoidance and Resting Heart Rate Variability

    PubMed Central

    Kao, Lien-Cheng; Liu, Yu-Wen; Tzeng, Nian-Sheng; Kuo, Terry B. J.; Huang, San-Yuan

    2016-01-01

    Objective Anxiety trait, anxiety and depression states have all been reported to increase risks for cardiovascular disease (CVD), possibly through altering cardiac autonomic regulation. Our aim was to investigate whether the relationship between harm avoidance (HA, an anxiety-related personality trait) and cardiac autonomic regulation is independent of anxiety and depression states in healthy adults. Methods We recruited 535 physically and mentally healthy volunteers. Participants completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Tri-dimensional Personality Questionnaire. Participants were divided into high or low HA groups as discriminated by the quartile value. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV). We obtained the time and frequency-domain indices of HRV including variance (total HRV), the low-frequency power (LF; 0.05–0.15 Hz), which may reflect baroreflex function, the high-frequency power (HF; 0.15–0.40 Hz), which reflects cardiac parasympathetic activity, as well as the LF/HF ratio. Results The BDI and HA scores showed associations with HRV parameters. After adjustment for the BDI scores and other control variables, HA is still associated with reduced variance, LF and HF power. Compared with the participants with low HA, those with high HA displayed significant reductions in variance, LF and HF power and a significant increase in their LF/HF ratio. Conclusion This study highlights the independent role of HA in contributing to decreased autonomic cardiac regulation in healthy adults and provides a potential underlying mechanism for anxiety trait to confer increased risk for CVD. PMID:27482240

  12. Heart Disease and Asians and Pacific Islanders

    MedlinePlus

    ... American > Heart Disease Heart Disease and Asians and Pacific Islanders Overall, Asian American adults are less likely ... Disease Death Rates per 100,000 (2013) Asians/Pacific Islanders Non-Hispanic White Asians/Pacific Islanders /Non- ...

  13. Screening for Coronary Heart Disease with Electrocardiography

    MedlinePlus

    ... Force Recommendations Screening for Coronary Heart Disease with Electrocardiography The U.S. Preventive Services Task Force (Task Force) ... recommendations on Screening for Coronary Heart Disease with Electrocardiography . These recommendations are for adult men and women ...

  14. When a Heart Murmur Signals Valve Disease

    MedlinePlus

    ... in adults may be related to: Valve calcification Endocarditis Rheumatic fever In children, abnormal heart murmurs may ... Problem: Pulmonary Valve Regurgitation Heart Valves and Infective Endocarditis • Risks, Signs and Symptoms • Accurate Diagnosis • Treatment Options • ...

  15. Declines in Coronary Heart Disease Incidence and Mortality among Middle-Aged Adults with and without Diabetes

    PubMed Central

    Carson, April P.; Tanner, Rikki M.; Yun, Huifeng; Glasser, Stephen P.; Woolley, J. Michael; Thacker, Evan L.; Levitan, Emily B.; Farkouh, Michael E.; Rosenson, Robert S.; Brown, Todd M.; Howard, George; Safford, Monika M.; Muntner, Paul

    2014-01-01

    Purpose To investigate secular changes in CHD incidence and mortality among adults with and without diabetes and determine the effect of increased lipid-lowering medication use and reductions in low-density lipoprotein cholesterol (LDL-C) levels on these changes. Methods We analyzed data on participants aged 45–64 years from the Atherosclerosis Risk in Communities Study in 1987–1996 (early time period) and the Reasons for Geographic and Racial Differences in Stroke Study in 2003–2009 (late time period). Hazard ratios (HR) for the association of diabetes and time period with incident CHD and CHD mortality were obtained after adjustment for socio-demographics, cardiovascular risk factors, lipid-lowering medication use, and LDL-C. Results After multivariable adjustment, diabetes was associated with an increased CHD risk during the early (HR=1.99,95% CI=1.59,2.49) and late (HR=2.39,95% CI=1.69,3.35) time periods. CHD incidence and mortality declined between the early and late time periods for individuals with and without diabetes. Increased use of lipid-lowering medication and lower LDL-C explained 33.6% and 27.2% of the decline in CHD incidence and CHD mortality, respectively, for those with diabetes. Conclusions Although rates have declined, diabetes remains associated with an increased risk of CHD incidence and mortality, highlighting the need for continuing diabetes prevention and cardiovascular risk factor management. PMID:24970491

  16. The subependymal zone neurogenic niche: a beating heart in the centre of the brain: how plastic is adult neurogenesis? Opportunities for therapy and questions to be addressed.

    PubMed

    Kazanis, Ilias

    2009-11-01

    The mammalian brain is a remarkably complex organ comprising millions of neurons, glia and various other cell types. Its impressive cytoarchitecture led to the long standing belief that it is a structurally static organ and thus very sensitive to injury. However, an area of striking structural flexibility has been recently described at the centre of the brain. It is the subependymal zone of the lateral wall of the lateral ventricles. The subependymal zone--like a beating heart--continuously sends new cells to different areas of the brain: neurons to the olfactory bulbs and glial cells to the cortex and the corpus callosum. Interestingly, the generation and flow of cells changes in response to signals from anatomically remote areas of the brain or even from the external environment of the organism, therefore indicating that subependymal neurogenesis--as a system--is integrated in the overall homeostatic function of the brain. In this review, it will be attempted to describe the fundamental structural and functional characteristics of the subependymal neurogenic niche and to summarize the available evidence regarding its plasticity. Special focus is given on issues such as whether adult neural stem cells are activated after neurodegeneration, whether defects in neurogenesis contribute to neuropathological conditions and whether monitoring changes in neurogenic activity can have a diagnostic value. PMID:19773354

  17. The Association between Antidepressant Medications and Coronary Heart Disease in Brazil: A Cross-Sectional Analysis on the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil)

    PubMed Central

    Kemp, Andrew H.; Brunoni, Andre R.; Bittencourt, Marcio S.; Nunes, Maria A.; Benseñor, Isabela M.; Lotufo, Paulo A.

    2015-01-01

    Background: Recent studies have highlighted associations between use of antidepressant medications and coronary heart disease (CHD). Tricyclic antidepressants (TCA) are not recommended in patients with CHD as they may increase morbidity and mortality. However, this class of antidepressants is freely prescribed in public health pharmacies, while access to other classes of antidepressants is restricted in Brazil. Here, we examine the associations between antidepressant use and prevalent CHD in a large cohort from Brazil. Methods: Participants included 14,994 civil servants aged 35–74 years from the baseline assessment of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CHD (n = 710) included stable angina, myocardial infarction, and coronary revascularization. Univariate (unadjusted) and multivariate (adjusted) logistic regression analyses were conducted to estimate odds ratios and confidence intervals. Results: After full adjustment for covariates, TCA use (n = 156) was associated with a twofold increase in prevalent CHD, relative to non-use (n = 14,076). Additional sensitivity analysis revealed a threefold association for myocardial infarction (OR: 2.96, 95% CI: 1.41–6.21) and coronary revascularization (OR: 2.92, 95% CI: 1.28–6.66). There were no significant associations between antidepressant use and stable angina pectoris. Conclusion: Findings highlight a strong association between TCA use and prevalent CHD. While the cross-sectional design is an important limitation of the present study, findings have important implications for the treatment of cardiac patients in Brazil. PMID:25657993

  18. Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

    PubMed

    Krieger, Eric V; Leary, Peter J; Opotowsky, Alexander R

    2015-11-01

    Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patient's hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations. PMID:26471823

  19. Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society.

    PubMed

    Rich, Michael W; Chyun, Deborah A; Skolnick, Adam H; Alexander, Karen P; Forman, Daniel E; Kitzman, Dalane W; Maurer, Mathew S; McClurken, James B; Resnick, Barbara M; Shen, Win K; Tirschwell, David L

    2016-05-24

    The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The

  20. Knowledge Gaps in Cardiovascular Care of the Older Adult Population: A Scientific Statement From the American Heart Association, American College of Cardiology, and American Geriatrics Society.

    PubMed

    Rich, Michael W; Chyun, Deborah A; Skolnick, Adam H; Alexander, Karen P; Forman, Daniel E; Kitzman, Dalane W; Maurer, Mathew S; McClurken, James B; Resnick, Barbara M; Shen, Win K; Tirschwell, David L

    2016-05-24

    The incidence and prevalence of most cardiovascular disorders increase with age, and cardiovascular disease is the leading cause of death and major disability in adults ≥75 years of age; however, despite the large impact of cardiovascular disease on quality of life, morbidity, and mortality in older adults, patients aged ≥75 years have been markedly underrepresented in most major cardiovascular trials, and virtually all trials have excluded older patients with complex comorbidities, significant physical or cognitive disabilities, frailty, or residence in a nursing home or assisted living facility. As a result, current guidelines are unable to provide evidence-based recommendations for diagnosis and treatment of older patients typical of those encountered in routine clinical practice. The objectives of this scientific statement are to summarize current guideline recommendations as they apply to older adults, identify critical gaps in knowledge that preclude informed evidence-based decision making, and recommend future research to close existing knowledge gaps. To achieve these objectives, we conducted a detailed review of current American College of Cardiology/American Heart Association and American Stroke Association guidelines to identify content and recommendations that explicitly targeted older patients. We found that there is a pervasive lack of evidence to guide clinical decision making in older patients with cardiovascular disease, as well as a paucity of data on the impact of diagnostic and therapeutic interventions on key outcomes that are particularly important to older patients, such as quality of life, physical function, and maintenance of independence. Accordingly, there is a critical need for a multitude of large population-based studies and clinical trials that include a broad spectrum of older patients representative of those seen in clinical practice and that incorporate relevant outcomes important to older patients in the study design. The

  1. Open heart surgery

    MedlinePlus

    ... Heart bypass surgery (coronary artery bypass graft - CABG) Heart transplant Heart valve surgery Hypoplastic left heart repair Minimally ... Heart bypass surgery Heart bypass surgery - minimally invasive Heart transplant Heart valve surgery Hypoplastic left heart syndrome Patent ...

  2. Characterization of msim, a murine homologue of the Drosophila sim transcription factor

    SciTech Connect

    Moffett, P.; Reece, M.; Pelletier, J.

    1996-07-01

    Mutations in the Drosophila single-minded (sim) gene result in loss of precursor cells that give rise to midline cells of the embryonic central nervous system. During the course of an exon-trapping strategy aimed at identifying transcripts that contribute to the etiology and pathophysiology of Down syndrome, we identified a human exon from the Down syndrome, we identified a human exon from the Down syndrome critical region showing significantly homology to the Drosophila sim gene. Using a cross-hybridization approach, we have isolated a murine homolog of Drosophila sim gene, which we designated msim. Nucleotide and predicted amino acid sequence analyses of msim cDNA clones indicate the this gene encodes a member of the basic-helix-loop-helix class of transcription factors. The murine and Drosophila proteins share 88% residues within the basic-helix-loop helix domain, with an overall homology of 92%. In addition, the N-terminal domain of MSIM contains two PAS dimerization motifs also featured in the Drosophila sim gene product, as well as a small number of other transcription factors. Northern blot analysis of adult murine tissues revealed that the msim gene produces a single mRNA species of {approximately}4 kb expressed in a small number of tissues, with the highest levels in the kidneys and lower levels present in skeletal muscle, lung, testis, brain, and heart. In situ hybridization experiments demonstrate that msim is also expressed in early fetal development in the central nervous system and in cartilage primordia. The characteristics of the msim gene are consistent with its putative function as a transcriptional regulator. 51 refs., 6 figs., 1 tab.

  3. Characterization of msim, a murine homologue of the Drosophila sim transcription factor.

    PubMed

    Moffett, P; Dayo, M; Reece, M; McCormick, M K; Pelletier, J

    1996-07-01

    Mutations in the Drosophila single-minded (sim) gene result in loss of precursor cells that give rise to midline cells of the embryonic central nervous system. During the course of an exon-trapping strategy aimed at identifying transcripts that contribute to the etiology and pathophysiology of Down syndrome, we identified a human exon from the Down syndrome critical region showing significant homology to the Drosophila sim gene. Using a cross-hybridization approach, we have isolated a murine homolog of the Drosophila sim gene, which we designated msim. Nucleotide and predicted amino acid sequence analyses of msim cDNA clones indicate that this gene encodes a member of the basic-helix-loop-helix class of transcription factors. The murine and Drosophila proteins share 88% residues within the basic-helix-loop-helix domain, with an overall homology of 92%. In addition, the N-terminal domain of MSIM contains two PAS dimerization motifs also featured in the Drosophila sim gene product, as well as a small number of other transcription factors. Northern blot analysis of adult murine tissues revealed that the msim gene produces a single mRNA species of approximately 4 kb expressed in a small number of tissues, with the highest levels in the kidneys and lower levels present in skeletal muscle, lung, testis, brain, and heart. In situ hybridization experiments demonstrate that msim is also expressed in early fetal development in the central nervous system and in cartilage primordia. The characteristics of the msim gene are consistent with its putative function as a transcriptional regulator. PMID:8661115

  4. Heart Attack

    MedlinePlus

    ... attack treatment works best when it's given right after symptoms occur. Prompt treatment of a heart attack can help prevent or limit damage to the heart and prevent sudden death. Call 9-1-1 Right Away A heart ...

  5. Heart attack

    MedlinePlus

    ... infarction; Non-ST-elevation myocardial infarction; NSTEMI; CAD-heart attack; Coronary artery disease-heart attack ... made up of cholesterol and other cells. A heart attack may occur when: A tear in the ...

  6. Heart Block

    MedlinePlus

    ... Block Explore Heart Block What Is... Electrical System & EKG Results Types Causes Who Is at Risk Signs & ... heart block. Doctors use a test called an EKG (electrocardiogram) to help diagnose heart block. This test ...

  7. Heart Anatomy

    MedlinePlus

    ... Incredible Machine Bonus poster (PDF) The Human Heart Anatomy Blood The Conduction System The Coronary Arteries The ... of the Leg Vasculature of the Torso Heart anatomy illustrations and animations for grades K-6. Heart ...

  8. Heart attack

    MedlinePlus

    ... a heart attack take part in a cardiac rehabilitation program. ... al. eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2014: ...

  9. Metabolic Dyslipidemia and Risk of Coronary Heart Disease in 28,318 Adults With Diabetes Mellitus and Low-Density Lipoprotein Cholesterol <100 mg/dl.

    PubMed

    Rana, Jamal S; Liu, Jennifer Y; Moffet, Howard H; Solomon, Matthew D; Go, Alan S; Jaffe, Marc G; Karter, Andrew J

    2015-12-01

    The risk of future coronary heart disease (CHD) in subjects with diabetes and "metabolic dyslipidemia" (high triglyceride [TGs] and low high-density cholesterol levels) remains a matter of concern. Little is known regarding the risk of CHD for this phenotype with low-density lipoprotein cholesterol (LDL-C) levels <100 mg/dl. We analyzed a diabetes cohort of 28,318 members (aged 30 to 90 years) of Kaiser Permanente Northern California during 2002 to 2011 (192,356 person-years [p-y] follow-up), with LDL-C levels <100 mg/dl and without known CHD. We compared the incidence and hazard ratios (HRs) for CHD events in groups using Cox models: normal high-density lipoprotein (HDL) and TG (reference; n = 7,278, 25.7%); normal HDL and high TG (≥ 150 mg/dl; n = 4,484,15.8%); low HDL (≤ 50 mg/dl for women and ≤ 40 mg/dl for men) and normal TG (n = 4,048, 14.3%); low HDL and high TG (metabolic dyslipidemia; n = 12,508, 44%). Patients with metabolic dyslipidemia had the highest age-adjusted CHD events/1,000 p-y (12.7/1,000 p-y and 19.0/1,000 p-y for women and men, respectively). After multivariate adjustment for age, gender, ethnicity, hypertension, smoking, statin use, duration of diabetes, and hemoglobin A1c, we observed an increased CHD risk in women (HR 1.35, 95% confidence interval 1.14 to 1.60) and men (HR 1.62, 95% confidence interval 1.43 to 1.83) with metabolic dyslipidemia compared to those with normal HDL and TG. Even in subjects with an LDL-C <100 mg/dl, presence of metabolic dyslipidemia in adults with diabetes is associated with an increased risk of CHD. In conclusion, effective CHD prevention strategies are needed for adults with diabetes and metabolic dyslipidemia. PMID:26428026

  10. Relationship of Physical Activity and Healthy Eating with Mortality and Incident Heart Failure among Community-Dwelling Older Adults with Normal Body Mass Index

    PubMed Central

    Abdelmawgoud, Ahmed; Brown, Cynthia J.; Sui, Xuemei; Fonarow, Gregg C.; Kokkinos, Peter F.; Bittner, Vera; Aronow, Wilbert S.; Fletcher, Ross D.; Blair, Steven N.; Ahmed, Ali

    2016-01-01

    Aims Normal body mass index (BMI) is associated with lower mortality and may be achieved by physical activity (PA), healthy eating (HE), or both. We examined the association of PA and HE with mortality and incident heart failure (HF) among 2040 community-dwelling older adults aged ≥ 65 years with baseline BMI 18.5 to 24.99 kg/m2 during 13 years of follow-up in Cardiovascular Health Study. Methods and results Baseline PA was defined as ≥500 weekly metabolic equivalent task-minutes (MET-minutes) and HE as ≥5 daily servings of vegetable and fruit intake. Participants were categorized into 4 groups: (1) PA−/HE− (n=384); (2) PA+/HE− (n=992); (3) PA−/HE+ (n=162); and (4) PA+/HE+ (n=502). Participants had a mean age of 74 (±6) years, mean BMI of 22.6 (±1.5) kg/m2, 61% were women, and 4% African American. Compared with PA−/HE−, age-sex-race-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality for PA−/HE+, PA+/HE−, and PA+/HE+ groups were 0.96 (0.76–1.21), 0.61 (0.52–0.71) and 0.62 (0.52–0.75), respectively. These associations remained unchanged after multivariable adjustment and were similar for cardiovascular and non-cardiovascular mortalities. Respective demographic-adjusted HRs (95% Cis) for incident HF among 1954 participants without baseline HF were 1.21 (0.81–1.81), 0.71 (0.54–0.94) and 0.71 (0.51–0.98). These later associations lost significance after multivariable-adjustment. Conclusion Among community-dwelling older adults with normal BMI, physical activity, regardless of healthy eating, was associated with lower risk of mortality and incident HF, but healthy eating had no similar protective association in this cohort.

  11. Straight from the Heart

    ERIC Educational Resources Information Center

    Jonell, Lynne

    2010-01-01

    Every adult who reads to a child has seen what happens when a book speaks. For a time, the book becomes the child's beloved friend. It is asked for repeatedly and learned by heart. But books do more than speak to a child. Children use books to speak to adults. If one wants to understand a child's deepest emotions, take a look at the books they…

  12. Human and murine erythropoiesis

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Mohandas, Narla; Gallagher, Patrick G.

    2015-01-01

    Purpose of review Research into the fundamental mechanisms of erythropoiesis has provided critical insights into inherited and acquired disorders of the erythrocyte. Studies of human erythropoiesis have primarily utilized in-vitro systems, whereas murine models have provided insights from in-vivo studies. This report reviews recent insights into human and murine erythropoiesis gained from transcriptome-based analyses. Recent findings The availability of high-throughput genomic methodologies has allowed attainment of detailed gene expression data from cells at varying developmental and differentiation stages of erythropoiesis. Transcriptome analyses of human and murine reveal both stage and species-specific similarities and differences across terminal erythroid differentiation. Erythroid-specific long noncoding RNAs exhibit poor sequence conservation between human and mouse. Genome-wide analyses of alternative splicing reveal that complex, dynamic, stage-specific programs of alternative splicing program are utilized during terminal erythroid differentiation. Transcriptome data provide a significant resource for understanding mechanisms of normal and perturbed erythropoiesis. Understanding these processes will provide innovative strategies to detect, diagnose, prevent, and treat hematologic disease. Summary Understanding the shared and different mechanisms controlling human and murine erythropoiesis will allow investigators to leverage the best model system to provide insights in normal and perturbed erythropoiesis. PMID:25719574

  13. Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure.

    PubMed

    Angrisano, Tiziana; Schiattarella, Gabriele Giacomo; Keller, Simona; Pironti, Gianluigi; Florio, Ermanno; Magliulo, Fabio; Bottino, Roberta; Pero, Raffaela; Lembo, Francesca; Avvedimento, Enrico Vittorio; Esposito, Giovanni; Trimarco, Bruno; Chiariotti, Lorenzo; Perrino, Cinzia

    2014-01-01

    Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF). Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ATPase (SERCA-2A) and β-myosin-heavy chain (β-MHC) genes (Atp2a2 and Myh7, respectively) in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC). As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of β-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2) at lysine (K) 4 (H3K4me2) and K9 (H3K9me2), H3 trimethylation (me3) at K27 (H3K27me3) and dimethylation (me2) at K36 (H3K36me2). Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2) were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF. PMID:25181347

  14. Heart Attack

    MedlinePlus

    ... have a heart attack. About half of them die. Many people have permanent heart damage or die because they don't get help immediately. It's ... few hours causes the affected heart muscle to die. NIH: National Heart, Lung, and Blood Institute

  15. Heart Transplantation

    MedlinePlus

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  16. Heart Diseases

    MedlinePlus

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  17. Heart Diseases

    MedlinePlus

    ... re like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the U.S. ... disability. There are many different forms of heart disease. The most common cause of heart disease is ...

  18. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  19. Murine myocardium OCT imaging with a blood substitute

    NASA Astrophysics Data System (ADS)

    Kim, Jeehyun; Villard, Joseph W.; Lee, Ho; Feldman, Marc D.; Milner, Thomas E.

    2002-06-01

    Imaging of the in vivo murine myocardium using optical coherence tomography (OCT) is described. Application of conventional techniques (e.g. MRI, Ultrasound imaging) for imaging the murine myocardium is problematic because the wall thickness is less than 1.5mm (20g mouse), and the heart rate can be as high as six-hundred beats per minute. To acquire a real-time image of the murine myocardium, OCT can provide sufficient spatial resolution (10 micrometers ) and imaging speed (1000 A-Scans/s). Strong light scattering by blood in the heart causes significant light attenuation making delineation of the endocardium-chamber boundary problematic. By replacing whole blood in the mouse with an artificial blood substitute we demonstrate significant reduction of light scattering in the murine myocardium. The results indicate a significant reduction in light scattering as whole blood hematocrit is diminished below 5%. To measure thickness change of the myocardium during one cycle, a myocardium edge detection algorithm is developed and demonstrated.

  20. Keeping Hearts Pumping

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A collaboration between NASA, Dr. Michael DeBakey, Dr. George Noon, and MicroMed Technology, Inc., resulted in a life-saving heart pump for patients awaiting heart transplants. The MicroMed DeBakey VAD functions as a "bridge to heart transplant" by pumping blood throughout the body to keep critically ill patients alive until a donor heart is available. Weighing less than 4 ounces and measuring 1 inch by 3 inches, the pump is approximately one-tenth the size of other currently marketed pulsatile VADs. This makes it less invasive and ideal for smaller adults and children. Because of the pump's small size, less than 5 percent of the patients implanted developed device-related infections. It can operate up to 8 hours on batteries, giving patients the mobility to do normal, everyday activities.The MicroMed DeBakey VAD is a registered trademark of MicroMed Technology, Inc.

  1. Large-scale characterization of the murine cardiac proteome.

    PubMed

    Cosme, Jake; Emili, Andrew; Gramolini, Anthony O

    2013-01-01

    Cardiomyopathies are diseases of the heart that result in impaired cardiac muscle function. This dysfunction can progress to an inability to supply blood to the body. Cardiovascular diseases play a large role in overall global morbidity. Investigating the protein changes in the heart during disease can uncover pathophysiological mechanisms and potential therapeutic targets. Establishing a global protein expression "footprint" can facilitate more targeted studies of diseases of the heart.In the technical review presented here, we present methods to elucidate the heart's proteome through subfractionation of the cellular compartments to reduce sample complexity and improve detection of lower abundant proteins during multidimensional protein identification technology analysis. Analysis of the cytosolic, microsomal, and mitochondrial subproteomes separately in order to characterize the murine cardiac proteome is advantageous by simplifying complex cardiac protein mixtures. In combination with bioinformatic analysis and genome correlation, large-scale protein changes can be identified at the cellular compartment level in this animal model. PMID:23606244

  2. Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling.

    PubMed

    Bae, Soochan; Zhang, Lubo

    2005-12-01

    Previous studies have reported the sex differences in heart susceptibility to ischemia/reperfusion (I/R) injury, but the mechanisms are not understood. The present study tested the hypothesis that Akt and protein kinase C (PKC)epsilon play an important role in the sexual dimorphism of heart susceptibility to I/R injury. Isolated hearts from 2-month-old male and female rats were subjected to I/R in the Langendorff preparation. The postischemic recovery of left ventricular function was significantly better, and infarct size was significantly smaller in female (37.1 +/- 1.9%) than in male (48.3 +/- 2.3%) hearts after 25-min ischemia followed by 2-h reperfusion. Inhibition of phosphatidylinositol 3-kinase/Akt pathway by wortmannin or PKC by chelerythrine chloride before ischemia significantly reduced postischemic recovery and increased infarct size in female but not male hearts. There were no differences in myocardial protein levels of heat shock protein 70, Akt, and PKCepsilon, respectively, between male and female rats. However, the ratio of phosphorylated (p)-Akt/Akt (0.58 +/- 0.05 versus 0.22 +/- 0.04; P < 0.05) and p-PKCepsilon/PKCepsilon (0.35 +/- 0.03 versus 0.22 +/- 0.02; P < 0.05) was significantly higher in female than in male hearts. In addition, there were significant increases in p-Akt and p-PKCepsilon levels during reperfusion in female but not in male hearts. The results suggest that increased p-Akt and p-PKCepsilon levels in female hearts contribute to the gender-related differences in heart susceptibility to I/R and play an important role in cardioprotection against I/R injury in females. PMID:16099927

  3. Comparison of the EPIC Physical Activity Questionnaire with Combined Heart Rate and Movement Sensing in a Nationally Representative Sample of Older British Adults

    PubMed Central

    España-Romero, Vanesa; Golubic, Rajna; Martin, Kathryn R.; Hardy, Rebecca; Ekelund, Ulf; Kuh, Diana; Wareham, Nicholas J.; Cooper, Rachel; Brage, Soren

    2014-01-01

    Objectives To compare physical activity (PA) subcomponents from EPIC Physical Activity Questionnaire (EPAQ2) and combined heart rate and movement sensing in older adults. Methods Participants aged 60–64y from the MRC National Survey of Health and Development in Great Britain completed EPAQ2, which assesses self-report PA in 4 domains (leisure time, occupation, transportation and domestic life) during the past year and wore a combined sensor for 5 consecutive days. Estimates of PA energy expenditure (PAEE), sedentary behaviour, light (LPA) and moderate-to-vigorous PA (MVPA) were obtained from EPAQ2 and combined sensing and compared. Complete data were available in 1689 participants (52% women). Results EPAQ2 estimates of PAEE and MVPA were higher than objective estimates and sedentary time and LPA estimates were lower [bias (95% limits of agreement) in men and women were 32.3 (−61.5 to 122.6) and 29.0 (−39.2 to 94.6) kJ/kg/day for PAEE; −4.6 (−10.6 to 1.3) and −6.0 (−10.9 to −1.0) h/day for sedentary time; −171.8 (−454.5 to 110.8) and −60.4 (−367.5 to 246.6) min/day for LPA; 91.1 (−159.5 to 341.8) and 55.4 (−117.2 to 228.0) min/day for MVPA]. There were significant positive correlations between all self-reported and objectively assessed PA subcomponents (rho  = 0.12 to 0.36); the strongest were observed for MVPA (rho = 0.30 men; rho = 0.36 women) and PAEE (rho = 0.26 men; rho = 0.25 women). Conclusion EPAQ2 produces higher estimates of PAEE and MVPA and lower estimates of sedentary and LPA than objective assessment. However, both methodologies rank individuals similarly, suggesting that EPAQ2 may be used in etiological studies in this population. PMID:24516543

  4. Impaired Macrophage Migration Inhibitory Factor (MIF)-AMPK Activation and Ischemic Recovery in the Senescent Heart

    PubMed Central

    Ma, Heng; Wang, Jingying; Thomas, D Paul; Tong, Chao; Leng, Lin; Wang, Wenkui; Merk, Melanie; Zierow, Swen; Bernhagen, Jürgen; Ren, Jun; Bucala, Richard; Li, Ji

    2010-01-01

    Background Elderly patients are more sensitive to myocardial ischemia, which results in higher mortality. We investigated how aging impacts the cardioprotective AMP-activated protein kinase (AMPK) signaling pathway. Methods and Results Ischemic AMPK activation was impaired in aged compared to young murine hearts. The expression and secretion of the AMPK upstream regulator, macrophage migration inhibitory factor (MIF), were lower in aged compared to young adult hearts. Additionally, the levels of hypoxia-inducible factor 1α (HIF-1α), a known transcriptional activator of MIF, were reduced in aged compared to young hearts. Ischemia-induced AMPK activation in MIF knock-out (MIF KO) mice was blunted, leading to greater contractile dysfunction in MIF-deficient than in wild type (WT) hearts. Furthermore, intra-myocardial injection of adenovirus encoding MIF (Adv-MIF) in aged mice increased MIF expression and ischemic AMPK activation, and reduced infarct size. Conclusions An impaired MIF-AMPK activation response in senescence thus may be attributed to an aging-associated defect in the transcription factor for MIF, HIF-1α. In the clinical setting, impaired cardiac HIF-1α activation and consequent reduced MIF expression may play an important role in the increased susceptibility to myocardial ischemia observed in older cardiac patients. PMID:20606117

  5. Heart pacemaker

    MedlinePlus

    ... 1 ounce. Most pacemakers have 2 parts: The generator contains the battery and the information to control ... are wires that connect the heart to the generator and carry the electrical messages to the heart. ...

  6. Heart Health

    MedlinePlus

    ... nih.gov/Go4Life Heart Health Just like an engine makes a car go, your heart keeps your ... all at once —10-minute periods will do. Start by doing activities you enjoy—brisk walking, dancing, ...

  7. Heart Disease

    MedlinePlus

    ... with heart disease? What do my cholesterol and triglyceride numbers mean? How can I lower my cholesterol? ... weight Know your numbers (blood pressure, cholesterol, and triglycerides) You can reduce your chances of getting heart ...

  8. Heart Failure

    MedlinePlus

    ... arrhythmias) The use of toxic substances (such as alcohol or drug abuse) Congenital heart defect (a heart problem you were born with) Diabetes Thyroid problems Diagnosis & Tests How will my doctor know if I ...

  9. Heart palpitations

    MedlinePlus

    Heart palpitations can be due to: Anxiety, stress, panic attack, or fear Caffeine intake Nicotine intake Cocaine or other illegal drugs Diet pills Exercise Fever However, some palpitations are due to an abnormal heart rhythm, ...

  10. Heart Disease

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  11. Heart Attack

    MedlinePlus

    ... a million people in the U.S. have a heart attack. About half of them die. Many people have permanent heart damage or die because they don't get ... It's important to know the symptoms of a heart attack and call 9-1-1 if someone ...

  12. Pathophysiology of Heart Failure.

    PubMed

    Tanai, Edit; Frantz, Stefan

    2015-01-01

    Heart failure is considered an epidemic disease in the modern world affecting approximately 1% to 2% of adult population. It presents a multifactorial, systemic disease, in which--after cardiac injury--structural, neurohumoral, cellular, and molecular mechanisms are activated and act as a network to maintain physiological functioning. These coordinated, complex processes lead to excessive volume overload, increased sympathetic activity, circulation redistribution, and result in different, parallel developing clinical signs and symptoms. These signs and symptoms sum up to an unspecific clinical picture; thus invasive and noninvasive diagnostic tools are used to get an accurate diagnosis and to specify the underlying cause. The most important, outcome determining factor in heart failure is its constant progression. Constant optimizing of pharmatherapeutical regimes, novel targets, and fine regulation of these processes try to keep these compensatory mechanisms in a physiological range. Beside pharmacological therapy, interventional and surgical therapy options give new chances in the management of heart failure. For the optimization and establishment of these and novel therapeutical approaches, complete and comprehensive understanding of the underlying mechanisms is essentially needed. Besides diagnosis and treatment, efforts should be made for better prevention in heart failure by treatment of risk factors, or identifying and following risk groups. This summary of the pathophysiology of heart failure tries to give a compact overview of basic mechanisms and of the novel unfolding, progressive theory of heart failure to contribute to a more comprehensive knowledge of the disease. PMID:26756631

  13. Candy consumption in childhood is not predictive of weight, adiposity measures or cardiovascular risk factors in young adults: the Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are limited data available on the longitudinal relationship between candy consumption by children on weight and other cardiovascular risk factors (CVRF) in young adults. The present study investigated whether candy consumption in children was predictive of weight and CVRF in young adults. A lo...

  14. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID:26597703

  15. Hypoplastic left heart syndrome

    MedlinePlus

    HLHS; Congenital heart - hypoplastic left heart; Cyanotic heart disease - hypoplastic left heart ... Hypoplastic left heart is a rare type of congenital heart disease. It is more common in males than in females. As ...

  16. What's Love Got to Do with It?: Reflections on the Connection of Heart and Mind in Adult Learning

    ERIC Educational Resources Information Center

    Pond, Elizabeth K.

    2014-01-01

    As a psychotherapist and meditation instructor, this author was drawn to what mindfulness teachings say about function of mind and heart in learning. Sakyong Mipham (2003) teaches that the mind is naturally compassionate, open, and receptive. The question becomes, what prevents the arising of these inherent characteristics of love? These same…

  17. Relationship between N-Terminal Pro-Brain Natriuretic Peptide, Obesity and the Risk of Heart Failure in Middle-Aged German Adults

    PubMed Central

    Wirth, Janine; Buijsse, Brian; di Giuseppe, Romina; Fritsche, Andreas; Hense, Hans W.; Westphal, Sabine; Isermann, Berend; Boeing, Heiner; Weikert, Cornelia

    2014-01-01

    Background Both high concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and obesity are related to higher heart failure risk. However, inverse relationships between NT-proBNP and obesity have been reported. Therefore, it was investigated whether the association between NT-proBNP and the risk of heart failure differed according to obesity status. Methods A case-cohort study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, comprising a random sub-cohort (non-cases = 1,150, cases = 13, mean age: 50.5±9.0 years) and heart failure cases outside the sub-cohort (n = 197). Weighted Cox proportional hazards regression was used to examine the association between NT-proBNP and heart failure risk during a mean follow-up time of 8 years. Stratified analyses were performed according to obesity status as defined by body mass index (<30 kg/m2 versus ≥30 kg/m2). Results Overall, NT-proBNP was associated with higher risk of heart failure after multivariable adjustment (hazard ratio (HR) and 95% confidence interval (CI): 2.56 (1.49–4.41) for the top versus bottom tertile of NT-proBNP, ptrend:<0.01). In stratified analyses, the shape of association was linear in non-obese and U-shaped in obese participants: HRs (95%CI) from the first to the third tertile of NT-proBNP for non-obese: reference, 1.72 (0.85–3.49), 2.72 (1.42–5.22), and for obese: 3.29 (1.04–10.40), reference, 3.74 (1.52–9.21). Conclusions Although high circulating concentrations of NT-proBNP were positively associated with incident heart failure in the entire sample, the association differed according to obesity status. In obese, an increased risk of heart failure was also observed in those with low NT-proBNP concentrations. If confirmed, this observation warrants further investigation to understand underlying pathophysiological mechanisms. PMID:25423197

  18. Heart Failure

    MedlinePlus

    ... blood the way it should. It can affect one or both sides of the heart. The weakening of the heart's pumping ability causes Blood and fluid to back up into the lungs The buildup of fluid in the feet, ankles and legs - called edema Tiredness and shortness of breath Common causes of ...

  19. Having Heart.

    PubMed

    Cochrane, Christine

    2015-01-01

    A heart comes in many forms. This article shares the experience of behavioral health nurses caring for a suicidal patient who needs a heart. As a team, the nurses and their patient shared the journey of what it takes to achieve an optimum quality of life with a left ventricular assist device (LVAD) while battling mental illness. PMID:26731919

  20. Resident c-kit(+) cells in the heart are not cardiac stem cells.

    PubMed

    Sultana, Nishat; Zhang, Lu; Yan, Jianyun; Chen, Jiqiu; Cai, Weibin; Razzaque, Shegufta; Jeong, Dongtak; Sheng, Wei; Bu, Lei; Xu, Mingjiang; Huang, Guo-Ying; Hajjar, Roger J; Zhou, Bin; Moon, Anne; Cai, Chen-Leng

    2015-01-01

    Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. Previously, cardiac c-kit(+) cells were reported to be CSCs with a potential to become myocardial, endothelial and smooth muscle cells in vitro and after cardiac injury. Here we provide further insights into the nature of cardiac c-kit(+) cells. By targeting the c-kit locus with multiple reporter genes in mice, we find that c-kit expression rarely co-localizes with the expression of the cardiac progenitor and myogenic marker Nkx2.5, or that of the myocardial marker, cardiac troponin T (cTnT). Instead, c-kit predominantly labels a cardiac endothelial cell population in developing and adult hearts. After acute cardiac injury, c-kit(+) cells retain their endothelial identity and do not become myogenic progenitors or cardiomyocytes. Thus, our work strongly suggests that c-kit(+) cells in the murine heart are endothelial cells and not CSCs. PMID:26515110

  1. Resident c-kit+ cells in the heart are not cardiac stem cells

    PubMed Central

    Sultana, Nishat; Zhang, Lu; Yan, Jianyun; Chen, Jiqiu; Cai, Weibin; Razzaque, Shegufta; Jeong, Dongtak; Sheng, Wei; Bu, Lei; Xu, Mingjiang; Huang, Guo-Ying; Hajjar, Roger J.; Zhou, Bin; Moon, Anne; Cai, Chen-Leng

    2015-01-01

    Identifying a bona fide population of cardiac stem cells (CSCs) is a critical step for developing cell-based therapies for heart failure patients. Previously, cardiac c-kit+ cells were reported to be CSCs with a potential to become myocardial, endothelial and smooth muscle cells in vitro and after cardiac injury. Here we provide further insights into the nature of cardiac c-kit+ cells. By targeting the c-kit locus with multiple reporter genes in mice, we find that c-kit expression rarely co-localizes with the expression of the cardiac progenitor and myogenic marker Nkx2.5, or that of the myocardial marker, cardiac troponin T (cTnT). Instead, c-kit predominantly labels a cardiac endothelial cell population in developing and adult hearts. After acute cardiac injury, c-kit+ cells retain their endothelial identity and do not become myogenic progenitors or cardiomyocytes. Thus, our work strongly suggests that c-kit+ cells in the murine heart are endothelial cells and not CSCs. PMID:26515110

  2. Pulmonary Hypertension and Congenital Heart Disease.

    PubMed

    Roth, Todd S; Aboulhosn, Jamil A

    2016-08-01

    Pulmonary arterial hypertension in congenital heart disease (PAH-CHD) is a frequent complication in adults with congenital heart disease. Regardless of etiology, the optimal treatment strategy for this difficult population is challenging. The new frontier of targeted PAH therapies has demonstrated improved functional capacity in the various phenotypes of PAH-CHD, with work currently in progress scrutinizing outcomes. In those who fail conventional medical therapy, heart and heart-lung (block) transplantation become the final therapeutic options, with the role of ventricular assist devices and the total artificial heart still under investigation in this group. PMID:27443136

  3. Hospital-level variation in use of cardiovascular testing for adults with incident heart failure: Findings from the Cardiovascular Research Network PRESERVE Study

    PubMed Central

    Farmer, Steven A.; Lenzo, Justin; Magid, David J.; Gurwitz, Jerry H.; Smith, David H.; Hsu, Grace; Sung, Sue Hee; Go, Alan S.

    2014-01-01

    Objectives We aimed to characterize use of cardiovascular testing for patients with incident heart failure (HF) hospitalization participating in the NHLBI-sponsored Cardiovascular Research Network PRESERVE study. Background HF is a common cause of hospitalization, and testing and treatment patterns may differ substantially between providers. Testing choices have important implications for the cost and quality of care. Methods Crude and adjusted cardiovascular testing rates were calculated for each participating hospital. Cox proportional hazards regression models were used to examine hospital testing rates after adjustment for hospital-level patient case-mix. Results Of the 37,099 patients in the PRESERVE study, 5,878 patients were hospitalized with incident HF between 2005 and 2008. Of these, evidence of cardiovascular testing was available for 4,650 (79.1 %) over the time period between 14 days before the incident HF admission and ending six months following the incident discharge. We compared crude and adjusted cardiovascular testing rates at the hospital level because the vast majority of testing occurred during the incident HF hospitalization. Of patients for whom testing was performed, 4,085 (87.9%) had an echocardiogram, 4,345 (93.4%) had a systolic function assessment, and 1,714 (36.9%) had a coronary artery disease assessment. Crude and adjusted testing rates varied markedly across the profiled hospitals, for individual testing modalities (e.g., echocardiography, stress echocardiography, nuclear stress testing, and left heart catheterization) and for specific clinical indications (e.g., systolic function assessment and coronary artery disease assessment). Conclusions For patients with newly diagnosed heart failure, we did not observe widespread overuse of cardiovascular testing in the six months following incident HF hospitalization relative to existing HF guidelines. Variations in testing were greatest for assessment of ischemia, where testing guidelines

  4. Living with a Congenital Heart Defect

    MedlinePlus

    ... well the heart’s chambers and valves are working. Health Insurance and Employment Adults who have congenital heart defects ... carefully consider how changing jobs will affect their health insurance coverage. Some health plans have waiting periods or ...

  5. How Are Holes in the Heart Treated?

    MedlinePlus

    ... do. Those that do often are repaired during infancy or early childhood. Sometimes adults are treated for ... enlarged heart chambers are treated with surgery after infancy. However, most VSDs that require surgery are repaired ...

  6. Physical Activity and Public Health in Older Adults: Recommendation from the American College of Sports Medicine and the American Heart Association

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults. Participants: A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology. Evidence: The ...

  7. Heart CT scan

    MedlinePlus

    CAT scan - heart; Computed axial tomography scan - heart; Computed tomography scan - heart; Calcium scoring; Multi-detector CT scan - heart; Electron beam computed tomography - heart; Agaston score; Coronary calcium scan

  8. Coronary heart disease

    MedlinePlus

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... Coronary heart disease is the leading cause of death in the United States for men and women. Coronary heart ...

  9. Wine and heart health

    MedlinePlus

    Health and wine; Wine and heart disease; Preventing heart disease - wine; Preventing heart disease - alcohol ... more often just to lower your risk of heart disease. Heavier drinking can harm the heart and ...

  10. What Is Heart Failure?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...

  11. Hearts Wish.

    ERIC Educational Resources Information Center

    Jones, Lethonee A.

    1989-01-01

    Investigates characteristics and themes in 102 drawings by sexually abused children. Themes of the drawings included genitalia, the absence of specific body parts, phallic symbols, inappropriate smiles, distorted body images, kinetic activity, prominent hands and fingers, and hearts. (RJC)

  12. Heart palpitations

    MedlinePlus

    Heart palpitations can be due to: Anxiety, stress, panic attack, or fear Caffeine intake Nicotine intake Cocaine or other illegal drugs Diet pills Exercise Fever However, some palpitations are due ...

  13. Heart Failure

    MedlinePlus

    ... together. About Rise Above HF Rise Above Heart Failure seeks to increase the dialogue about HF and improve the lives of people affected by the condition through awareness, education and support. Through the initiative, AHA strives to ...

  14. Heart Transplant

    MedlinePlus

    ... Doctors remove the patient's heart by transecting the aorta , the main pulmonary artery and the superior and ... sewing together the recipient and donor vena cavae, aorta, pulmonary artery and left atrium. In patients with ...

  15. Heart MRI

    MedlinePlus

    ... an imaging method that uses powerful magnets and radio waves to create pictures of the heart. It does ... radiation involved in MRI. The magnetic fields and radio waves used during the scan have not been shown ...

  16. Heart Attack

    MedlinePlus

    ... lower “bad” cholesterol (also called LDL, or low-density lipoprotein) levels and may help increase “good” cholesterol (also called HDL, or high-density lipoprotein). If you have had a heart attack, ...

  17. Heart pacemaker

    MedlinePlus

    ... may not get enough oxygen. Symptoms may be light-headedness, tiredness, fainting spells, and shortness of breath. Some pacemakers can be used to stop a heart rate that is too fast ( tachycardia ) ...

  18. Heart transplant

    MedlinePlus

    ... have symptoms. You must take drugs that prevent transplant rejection for the rest of your life. You will ... heart transplant. The main problem, as with other transplants, is rejection. If rejection can be controlled, survival increases to ...

  19. Analysis of murine HOXA-2 activity in Drosophila melanogaster.

    PubMed

    Percival-Smith, A; Bondy, J A

    1999-01-01

    The murine HOXA-2 protein shares amino acid sequence similarity with Drosophila Proboscipedia (PB). In this paper, we test whether HOXA-2 and PB are functionally equivalent in Drosophila. In Drosophila, PB inhibits SCR activity required for larval T1 beard formation and adult tarsus formation and is required for maxillary palp and proboscis formation. HOXA-2 expressed from a heat-shock promoter weakly suppressed SCR activity required for T1 beard formation. But interestingly neither PB nor HOXA-2 expressed from a heat-shock promoter suppressed murine HOXA-5 activity, the murine SCR homologue, from inducing ectopic T1 beards in T2 and T3, indicating that HOXA-5 does not interact with PB. HOXA-2 activity expressed from the Tubulin alpha 1 promoter modified the pb null phenotype resulting in a proboscis-to-arista transformation, indicating that HOXA-2 was able to suppress SCR activity required for tarsus formation. However, HOXA-2 expressed from a Tubulin alpha 1 promoter was unable to direct maxillary palp determination when either ectopically expressed in the antenna or in the maxillary palp primordia of a pb null mutant. HOXA-2 was also unable to rescue pseudotrachea formation in a pb null mutant. These results indicate that the only activity that PB and HOXA-2 weakly share is the inhibition of SCR activity, and that murine HOXA-5 and Drosophila SCR do not share inhibition by PB activity. PMID:10322642

  20. Cloning and expression analysis of murine phospholipase D1.

    PubMed Central

    Colley, W C; Altshuller, Y M; Sue-Ling, C K; Copeland, N G; Gilbert, D J; Jenkins, N A; Branch, K D; Tsirka, S E; Bollag, R J; Bollag, W B; Frohman, M A

    1997-01-01

    Activation of phosphatidylcholine-specific phospholipase D(PLD) occurs as part of the complex signal-transduction cascade initiated by agonist stimulation of tyrosine kinase and G-protein-coupled receptors. A variety of mammalian PLD activities have been described, and cDNAs for two PLDs recently reported (human PLD1 and murine PLD2). We describe here the cloning and chromosomal localization of murine PLD1. Northern-blot hybridization and RNase protection analyses were used to examine the expression of murine PLD1 and PLD2 ina variety of cell lines and tissues. PLD1 and PLD2 were expressed in all RNA samples examined, although the absolute expression of each isoform varied, as well as the ratio of PLD1 to PLD2. Moreover, in situ hybridization of adult brain and murine embryo sections revealed high levels of expression of individual PLDs in some cell types and no detectable expression in others. Thus the two PLDs probably carry out distinct roles in restricted subsets of cells rather than ubiquitous roles in all cells. PMID:9307024

  1. Candy consumption in childhood is not predictive of weight, adiposity measures or cardiovascular risk factors in young adults: the Bogalusa Heart Study

    PubMed Central

    O’Neil, C. E.; Nicklas, T. A.; Liu, Y.; Berenson, G. S.

    2015-01-01

    Background There are limited data available on the longitudinal relationship between candy consumption by children on weight and other cardiovascular risk factors (CVRF) in young adults. The present study investigated whether candy consumption in children was predictive of weight and CVRF in young adults. Methods A longitudinal sample of children 10 years (n = 355; 61% females; 71% European Americans, 29% African Americans) who partici pated in cross sectional surveys from 1973 to 1984 (baseline) and in one of two surveys (follow ups) as young adults [19–38] years; mean (SD) = 23.6 (2.6) years] in Bogalusa, LA, were studied. Dietary data were collected using 24 h dietary recalls at baseline and at one follow up survey; a food frequency questionnaire was used in the other follow up survey. Candy consumers were those consuming any amount of candy. Candy con sumption was calculated (g day−1) from baseline 24 h dietary recalls, and was used as a covariate in the adjusted linear mixed models. Dependent variables included body mass index (BMI) and CVRF measured in young adults. Results At baseline, 92% of children reported consuming candy [46 (45) g day−1]; the percentage decreased to 67% [20 (30) g day−1] at fol low up. No longitudinal relationship was shown between baseline candy consumption and BMI or CVRF in young adults, suggesting that candy consumption was not predictive of health risks later in life. Conclusions The consumption of nutrient rich foods consistent with die tary recommendations is important, although modest amounts of candy can be added to the diet without potential adverse long term consequences to weight or CVRF. Additional studies are needed to confirm these results. PMID:24382141

  2. Inhibition of angiogenesis and murine tumour growth by laminarin sulphate.

    PubMed Central

    Hoffman, R.; Paper, D. H.; Donaldson, J.; Vogl, H.

    1996-01-01

    LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01). Images Figure 2 PMID:8630276

  3. Arrhythmias in Complex Congenital Heart Disease

    PubMed Central

    Hayward, Robert M.; Tseng, Zian H.

    2014-01-01

    Late after surgical repair of complex congenital heart disease, atrial arrhythmias are a major cause of morbidity, and ventricular arrhythmias and sudden cardiac death are a major cause of mortality. The six cases in this article highlight common challenges in the management of arrhythmias in the adult congenital heart disease population. PMID:25197326

  4. An Internet-Based Counseling Intervention With Email Reminders that Promotes Self-Care in Adults With Chronic Heart Failure: Randomized Controlled Trial Protocol

    PubMed Central

    Payne, Ada YM; Ross, Heather; White, Michel; D'Antono, Bianca; Chan, Sammy; Barr, Susan I; Gwadry-Sridhar, Femida; Nigam, Anil; Perreault, Sylvie; Farkouh, Michael; McDonald, Michael; Goodman, Jack; Thomas, Scott; Zieroth, Shelley; Isaac, Debra; Oh, Paul; Rajda, Miroslaw; Chen, Maggie; Eysenbach, Gunther; Liu, Sam; Zbib, Ahmad

    2014-01-01

    Background Chronic heart failure (CHF) is a public health priority. Its age-standardized prevalence has increased over the past decade. A major challenge for the management of CHF is to promote long-term adherence to self-care behaviors without overtaxing available health care resources. Counseling by multidisciplinary health care teams helps to improve adherence to self-care behaviors and to reduce the rate of death and hospitalization. In the absence of intervention, adherence to self-care is below recommended standards. Objective This trial aims to establish and evaluate a Canadian e-platform that will provide a core, standardized protocol of behavioral counseling and education to facilitate long-term adherence to self-care among patients with CHF. Methods Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT) is a multi-site, double blind, randomized controlled trial with a 2 parallel-group (e-Counseling + Usual Care vs e-Info Control + Usual Care) by 3 assessments (baseline, 4-, and 12-month) design. We will identify subjects with New York Heart Association Class II or III systolic heart failure from collaborating CHF clinics and then recruit them (n=278) by phone. Subjects will be randomized in blocks within each site (Toronto, Montreal, and Vancouver). The primary outcome will be improved quality of life, defined as an increased number of subjects with an improvement of ≥5 points on the summary score of the Kansas City Cardiomyopathy Questionnaire. We will also assess the following secondary outcomes: (1) diet habits, depression, anxiety, smoking history, stress level, and readiness for change using self-report questionnaires, (2) physical activity level, current smoking status, and vagal-heart rate modulation by physiological tests, and (3) exercise capacity, prognostic indicators of cardiovascular functioning, and medication adherence through medical chart review. The primary outcome will be analyzed using

  5. Carotenoid intakes, assessed by food-frequency questionnaires (FFQs), are associated with serum carotenoid concentrations in the Jackson Heart Study: validation of the Jackson Heart Study Delta NIRI Adult FFQs

    PubMed Central

    Talegawkar, Sameera A; Johnson, Elizabeth J; Carithers, Teresa C; Taylor, Herman A; Bogle, Margaret L; Tucker, Katherine L

    2009-01-01

    Objectives Intake and status of carotenoids have been associated with chronic disease. The objectives of this study were to examine the association between carotenoid intakes as measured by two regional food-frequency questionnaires (FFQs) and their corresponding measures in serum, and to report on dietary food sources of carotenoids in Jackson Heart Study (JHS) participants. Design Cross-sectional analysis of data for 402 African American men and women participating in the Diet and Physical Activity Sub-Study (DPASS) of the JHS. Results Mean serum carotenoid concentrations and intakes in this population were comparable to those reported for the general US population. After adjustment for covariates, correlations between serum and dietary measures of each carotenoid, for the average of the recalls (deattenuated), the short FFQ and the long FFQ, respectively, were: 0.37, 0.35 and 0.21 for α-carotene; 0.35, 0.26 and 0.28 for total (diet plus supplements) β-carotene; 0.25, 0.17 and 0.20 for dietary β-carotene; 0.42, 0.34 and 0.26 for β-cryptoxanthin; 0.33, 0.15 and 0.17 for lutein plus zeaxanthin; and 0.37, 0.19 and 0.14 for lycopene. Major dietary sources of α-carotene were orange vegetables; of β-carotene and lutein plus zeaxanthin, mustard, turnip and collard greens; of β-cryptoxanthin, orange juice; and of lycopene, tomato juice. Conclusions On average, carotenoid intakes and serum concentrations are not lower in this southern African American population than the general US population. The two regional FFQs developed for a southern US population and used as dietary assessment tools in the JHS appear to provide reasonably valid information for most of these carotenoids. PMID:18053294

  6. Heart Disease: Know Your Risk

    MedlinePlus

    ... active, and choosing good nutrition. Your Guide to Physical Activity and Your Heart - You know you should be more physically active. But are you confused, concerned, or just can't get started? This guide uses science-based information to help adults develop a safe ...

  7. Heart Disease and Stroke Prevention

    MedlinePlus

    ... active, and choosing good nutrition. Your Guide to Physical Activity and Your Heart - You know you should be more physically active. But are you confused, concerned, or just can't get started? This guide uses science-based information to help adults develop a safe ...

  8. Murine typhus in travelers returning from Indonesia.

    PubMed Central

    Parola, P.; Vogelaers, D.; Roure, C.; Janbon, F.; Raoult, D.

    1998-01-01

    We report the first three documented cases of murine typhus imported into Europe from Indonesia, discuss clues for the diagnosis of the disease, and urge that murine fever be considered in the diagnosis of febrile disease in travelers. PMID:9866749

  9. Antibacterial activity of recombinant murine beta interferon.

    PubMed Central

    Fujiki, T; Tanaka, A

    1988-01-01

    Recombinant murine beta interferon was protective and therapeutic for mice against Listeria monocytogenes infection in vivo. The recombinant murine beta interferon caused enhanced H2O2 release by macrophages in vivo, but not in vitro. PMID:3343048

  10. Myocardial hypoperfusion detected by cardiac computed tomography in an adult patient with heart failure after classic repair for corrected transposition of the great arteries.

    PubMed

    Okayama, Satoshi; Seno, Ayako; Soeda, Tsunenari; Takami, Yasuhiro; Horii, Manabu; Uemura, Shiro; Saito, Yoshihiko

    2011-08-01

    A 69-year-old male with a history of classic repair for corrected transposition of the great arteries (TGA) arrived at our hospital with dyspnoea upon exertion. Echocardiography revealed severe dilation and diffuse hypokinesis of the systemic ventricle without obvious valvular dysfunction. Cardiac computed tomography (CT) revealed no significant stenosis. However, the morphological right coronary artery (CA) on the left side was unequally distributed to the large systemic ventricle and was mostly obscured, especially on the anterior wall. A low attenuation area in the anterior wall of the systemic ventricle and prominent trabeculations suggested ischaemia or infarction. We considered that chronic myocardial hypoperfusion due to an inadequate coronary arterial supply was one cause of the exacerbated heart failure long after the classic repair. Cardiac CT is useful for evaluating the distribution of the CA and to predict blood supply to the myocardium in corrected TGA. PMID:21894815

  11. Attending religious services and its relationship with coronary heart disease and related risk factors in older adults: a qualitative study of church pastors' and parishioners' perspectives.

    PubMed

    Banerjee, Ananya Tina; Strachan, Patricia H; Boyle, Michael H; Anand, Sonia S; Oremus, Mark

    2014-12-01

    A qualitative study was undertaken to explain findings of a cross-sectional study of Canadian Community Health Survey (CCHS) 4.1 data showing older persons who attend religious services more than once a week, compared to persons who do not attend at all, have lower prevalences of coronary heart disease (CHD), diabetes and high blood pressure. Twelve semi-structured interviews with ordained pastors and three focus groups with older parishioners from Canadian churches were conducted. Interviews were transcribed and analyzed for emergent themes through a process of direct content analysis. All participants claimed that religious service attendance (RSA): (1) enhances mental health; (2) provides social support and activities; and (3) promotes health and lifestyle behaviours that lower CHD risk. These three themes appear to be underlying mechanisms that help to explain the inverse association between RSA and the prevalence of adverse health outcomes found in the CCHS 4.1 data. PMID:24132458

  12. Immunosuppressive effect of murine cytomegalovirus.

    PubMed Central

    Loh, L; Hudson, J B

    1980-01-01

    Murine cytomegalovirus suppressed the ability of spleen cells to respond to mitogens in vitro. The degree of suppression was proportional to the multiplicity of infection. This effect could not be explained by cytolysis of lymphocytes, an alteration in the kinetics of the response to mitogen, or a direct competition between virions and mitogen molecules for cell-surface receptors. Nor was it due to simple contact between cell and virus, since ultraviolet-inactivated murine cytomegalovirus failed to suppress the response to mitogens. Reconstitution experiments were performed which involved mixing various combinations of infected and uninfected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages and lymphocytes. Under these conditions, it was found that the infected macrophages had an impaired capacity to mediate the response ot T lymphocytes to concanavalin A. This suggests that murine cytomegalovirus may cause immunosuppression indirectly by interfering with macrophage function. PMID:6244228

  13. Usefulness of vascular stenting with and without transvenous pacing leads for vena caval obstruction among children and adults with repaired congenital heart disease.

    PubMed

    Kobayashi, Daisuke; Forbes, Thomas J; Turner, Daniel R; Singh, Harinder R; Karpawich, Peter P; Gowda, Srinath T

    2015-06-15

    Vena caval obstruction (VCO) is a common complication after vascular manipulation for congenital heart disease. Long-term efficacy of stent therapy for relief of VCO and long-term stent patency with and without intrastent transvenous pacing leads (TPLs) is not well described. This was a retrospective review of patients treated for VCO, including those who received intrastent TPLs, between 1995 and 2012. Patient demographics, diagnoses, vascular pressure gradients, and vessel diameters were analyzed. Forty-one patients (mean age 23.5 ± 10.3 years) with and without congenital heart disease underwent stent implantation, 26 of whom also received intrastent TPLs. Short-term stent implantation success in relieving obstructions was 93%. Poststent vascular pressure gradients and percentage vascular narrowing significantly improved (from 6.2 ± 4.5 to 1.1 ± 1.6 mm Hg and from 63.1 ± 19.5% to 18.0 ± 17.1%, respectively, p <0.05). On follow-up in 38 of 41 patients from 0.2 to 18 years (median 6.0), all survived; 6 (14%) required stent reintervention. Freedom from reintervention was 87% at 15 years. Patients with short-term procedural failure were at higher risk for stent reintervention. Among 27 patients with intrastent TPLs, freedom from reintervention was 96%. In 26 patients with follow-up catheterization, intrastent intimal proliferation was not significantly associated with TPL but was higher in the superior vena cava-innominate vein junction compared with other stent locations (p <0.05). In conclusion, stent therapy for VCO can be successfully and safely performed with good long-term results. Pre-pacing lead stent placement for VCO is effective in allowing TPL placement with encouraging long-term patency. PMID:25910527

  14. Methylation of inorganic arsenic by murine fetal tissue explants.

    PubMed

    Broka, Derrick; Ditzel, Eric; Quach, Stephanie; Camenisch, Todd D

    2016-07-01

    Although it is generally believed that the developing fetus is principally exposed to inorganic arsenic and the methylated metabolites from the maternal metabolism of arsenic, little is known about whether the developing embryo can autonomously metabolize arsenic. This study investigates inorganic arsenic methylation by murine embryonic organ cultures of the heart, lung, and liver. mRNA for AS3mt, the gene responsible for methylation of arsenic, was detected in all embryonic tissue types studied. In addition, methylated arsenic metabolites were generated by all three tissue types. The fetal liver explants yielded the most methylated arsenic metabolites (∼7% of total arsenic/48 h incubation) while the heart, and lung preparations produced slightly greater than 2% methylated metabolites. With all tissues the methylation proceeded mostly to the dimethylated arsenic species. This has profound implications for understanding arsenic-induced fetal toxicity, particularly if the methylated metabolites are produced autonomously by embryonic tissues. PMID:26446802

  15. The Murine Bladder Supports a Population of Stromal Sca-1+/CD34+/lin- Mesenchymal Stem Cells.

    PubMed

    Lilly, Meredith A; Kulkulka, Natalie A; Firmiss, Paula R; Ross, Michael J; Flum, Andrew S; Santos, Grace B Delos; Bowen, Diana K; Dettman, Robert W; Gong, Edward M

    2015-01-01

    Bladder fibrosis is an undesired end point of injury of obstruction and often renders the smooth muscle layer noncompliant. In many cases, the long-term effect of bladder fibrosis is renal failure. Despite our understanding of the progression of this disease, little is known about the cellular mechanisms that lead to a remodeled bladder wall. Resident stem (progenitor) cells have been identified in various organs such as the brain, heart and lung. These cells function normally during organ homeostasis, but become dysregulated after organ injury. Here, we aimed to characterize a mesenchymal progenitor cell population as a first step in understanding its role in bladder fibrosis. Using fluorescence activated cell sorting (FACS), we identified a Sca-1+/ CD34+/ lin- (PECAM-: CD45-: Ter119-) population in the adult murine bladder. These cells were localized to the stromal layer of the adult bladder and appeared by postnatal day 1. Cultured Sca-1+/ CD34+/ lin- bladder cells self-renewed, formed colonies and spontaneously differentiated into cells expressing smooth muscle genes. These cells differentiated into other mesenchymal lineages (chondrocytes, adipocytes and osteocytes) upon culture in induction medium. Both acute and partial obstruction of the bladder reduced expression of CD34 and changed localization of Sca-1 to the urothelium. Partial obstruction resulted in upregulation of fibrosis genes within the Sca-1+/CD34+/lin- population. Our data indicate a resident, mesenchymal stem cell population in the bladder that is altered by bladder obstruction. These findings provide new information about the cellular changes in the bladder that may be associated with bladder fibrosis. PMID:26540309

  16. The Murine Bladder Supports a Population of Stromal Sca-1+/CD34+/lin- Mesenchymal Stem Cells

    PubMed Central

    Lilly, Meredith A.; Kulkulka, Natalie A.; Firmiss, Paula R.; Ross, Michael J.; Flum, Andrew S.; Santos, Grace B. Delos; Bowen, Diana K.; Dettman, Robert W.; Gong, Edward M.

    2015-01-01

    Bladder fibrosis is an undesired end point of injury of obstruction and often renders the smooth muscle layer noncompliant. In many cases, the long-term effect of bladder fibrosis is renal failure. Despite our understanding of the progression of this disease, little is known about the cellular mechanisms that lead to a remodeled bladder wall. Resident stem (progenitor) cells have been identified in various organs such as the brain, heart and lung. These cells function normally during organ homeostasis, but become dysregulated after organ injury. Here, we aimed to characterize a mesenchymal progenitor cell population as a first step in understanding its role in bladder fibrosis. Using fluorescence activated cell sorting (FACS), we identified a Sca-1+/ CD34+/ lin- (PECAM-: CD45-: Ter119-) population in the adult murine bladder. These cells were localized to the stromal layer of the adult bladder and appeared by postnatal day 1. Cultured Sca-1+/ CD34+/ lin- bladder cells self-renewed, formed colonies and spontaneously differentiated into cells expressing smooth muscle genes. These cells differentiated into other mesenchymal lineages (chondrocytes, adipocytes and osteocytes) upon culture in induction medium. Both acute and partial obstruction of the bladder reduced expression of CD34 and changed localization of Sca-1 to the urothelium. Partial obstruction resulted in upregulation of fibrosis genes within the Sca-1+/CD34+/lin- population. Our data indicate a resident, mesenchymal stem cell population in the bladder that is altered by bladder obstruction. These findings provide new information about the cellular changes in the bladder that may be associated with bladder fibrosis. PMID:26540309

  17. Aging and Autophagy in the Heart.

    PubMed

    Shirakabe, Akihiro; Ikeda, Yoshiyuki; Sciarretta, Sebastiano; Zablocki, Daniela K; Sadoshima, Junichi

    2016-05-13

    The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Macroautophagy (hereafter referred to as autophagy) is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagy and autophagic flux are generally decreased in aging hearts, and murine autophagy loss-of-function models develop exacerbated cardiac dysfunction that is accompanied by the accumulation of misfolded proteins and dysfunctional organelles. On the contrary, stimulation of autophagy generally improves cardiac function in mouse models of protein aggregation by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged DNA, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart. Increasing lines of evidence suggest that autophagy is required for many mechanisms that mediate lifespan extension, such as caloric restriction, in various organisms. These results raise the exciting possibility that autophagy may play an important role in combating the adverse effects of aging in the heart. In this review, we discuss the role of autophagy in the heart during aging, how autophagy alleviates age-dependent changes in the heart, and how the level of autophagy in the aging heart can be restored. PMID:27174950

  18. The detection, treatment and control of high blood pressure in older British adults: cross-sectional findings from the British Women's Heart and Health Study and the British Regional Heart Study.

    PubMed

    Patel, R; Lawlor, D A; Whincup, P; Montaner, D; Papacosta, O; Brindle, P; Ebrahim, S

    2006-10-01

    Among older people, the detection and control of hypertension is particularly important to reduce cardiovascular disease risk. This cross-sectional survey aimed to describe the detection, treatment and control of hypertension in older British adults. A total of 3059 women and 3007 men aged 60-79 years were randomly selected from general practice age/sex registers in 24 British towns and examined from 1998 to 2001. Of these, 52.6% women and 47.9% men had at least one indicator of hypertension (high blood pressure on examination, or taking antihypertensive medication or recalled a doctor diagnosis of high blood pressure). Among women, 50% of those with any indication of hypertension were on treatment and 29% were well controlled, and among men 45% were on treatment and 16% were well controlled. With the exception of alcohol use in men (adjusted odds ratio 0.67 (0.46, 0.98)), socioeconomic factors, area of residence and behavioural risk factors were not associated with good control among those with hypertension in either sex. Of those on treatment, 20.7% of women and 28% of men were on two classes of antihypertensive medication and 3.5 and 4.9%, respectively, were on three or more classes of antihypertensive medication. Among those with a doctor diagnosis of hypertension and taking antihypertensive medication, the proportion with well controlled blood pressure did not differ between those on more than one antihypertensive and those on just one in either sex. We conclude that targets of good control are rarely met in older individuals, who would benefit from the associated reduction in cardiovascular disease risk. PMID:16855626

  19. Effect of Hepatitis C Positivity on Survival in Adult Patients Undergoing Heart Transplantation (from the United Network for Organ Sharing Database).

    PubMed

    Kumar, Sachin; Deo, Salil V; Altarabsheh, Salah E; Dunlay, Shannon M; Sarabu, Nagaraju; Sareyyupoglu, Basar; Elgudin, Yakov; Medalion, Benjamin; ElAmm, Chantal; Ginwalla, Mahazarin; Zacharias, Michael; Benatti, Rodolpho; Oliveira, Guilherme H; Kilic, Ahmet; Fonarow, Gregg C; Park, Soon J

    2016-07-01

    Concerns exist regarding orthotropic heart transplantation in hepatitis C virus (HCV) seropositive recipients. Thus, a national registry was accessed to evaluate early and late outcome in HCV seropositive recipients undergoing heart transplant. Retrospective analysis of the United Network for Organ Sharing registry (1991 to 2014) was performed to evaluate recipient profile and clinical outcome of patients with HCV seropositive (HCV +ve) and seronegative (HCV -ve). Adjusted results of early mortality and late survival were compared between cohorts. From 23,507 patients (mean age 52 years; 75% men), 481 (2%) were HCV +ve (mean age 52 years; 77% men). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3% to 2.7%; p = 0.2). The HCV +ve cohort had more African-American (22% vs 17%; p = 0.01), previous left ventricular assist device utilization (21% vs 14%; p <0.01) and more hepatitis B core Ag+ve recipients (17% vs 5%; p <0.01). However, both cohorts were comparable in terms of extracorporeal membrane oxygenator usage (p = 0.7), inotropic support (p = 0.2), intraaortic balloon pump (p = 0.7) support, serum creatinine (p = 0.7), and serum bilirubin (p = 0.7). Proportion of status 1A patients was similar (24% HCV + vs 21% HCV -); however, wait time for HCV +ve recipients were longer (mean 23 vs 19 days; p <0.01). Among donor variables, age (p = 0.8), hepatitis B status (p = 0.4), and Center for Diseases Control high-risk status (p = 0.9) were comparable in both cohorts. At a median follow-up of 4 years, 67% patients were alive, 28% died, and 1.1% were retransplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3% vs 72.9% and 43.2% vs 55% at 5 and 10 years; p <0.01), respectively. Late renal (odds ratio [OR] 1.2 [1 to 1.6]; p = 0.02) and liver dysfunction (odds ratio 4.5 [1.2 to 15.7]; p = 0.01) occurs more frequently in HCV +ve recipients. On adjusted analysis, HCV seropositivity is

  20. The association between dietary glycemic index, glycemic load and diet quality indices in Iranian adults: results from Isfahan Healthy Heart Program.

    PubMed

    Azadbakht, Leila; Mohammadifard, Noushin; Akhavanzanjani, Mohsen; Taheri, Marzieh; Golshahi, Jafar; Haghighatdoost, Fahimeh

    2016-01-01

    To assess the association between dietary glycemic index (GI), glycemic load (GL) and dietary quality indices in Iranian adults. This cross section was conducted among 1571 Iranian adults aged  ≥19 years. GI, GL and diet quality indices were estimated by 24-h recall and DDS was calculated using a validated 48-item food frequency questionnaire. Participants who were in the top tertile of GI had lower healthy eating index (HEI) (57.2 ± 7.8 versus 55.6 ± 8.7; p < 0.001), dietary diversity score (DDS) (3.6 ± 0.9 versus 3.3 ± 1.1; p < 0.001) and nutrient adequacy ratios (NARs) for Zn, Ca, vitamin C and B2. Individuals in the lowest tertile of GL had lower HEI, MAR and NARs for Zn, vitamin B2, B3, B6, B12, vitamin D. Both GI and GL were positively related to dietary diversity score (DED) (p < 0.001). The inverse associations for GI and GL with diet quality indices may suggest the relevance of carbohydrate source in determining the diet quality indices. PMID:26915989

  1. 2013 update on congenital heart disease, clinical cardiology, heart failure, and heart transplant.

    PubMed

    Subirana, M Teresa; Barón-Esquivias, Gonzalo; Manito, Nicolás; Oliver, José M; Ripoll, Tomás; Lambert, Jose Luis; Zunzunegui, José L; Bover, Ramon; García-Pinilla, José Manuel

    2014-03-01

    This article presents the most relevant developments in 2013 in 3 key areas of cardiology: congenital heart disease, clinical cardiology, and heart failure and transplant. Within the area of congenital heart disease, we reviewed contributions related to sudden death in adult congenital heart disease, the importance of specific echocardiographic parameters in assessing the systemic right ventricle, problems in patients with repaired tetralogy of Fallot and indication for pulmonary valve replacement, and confirmation of the role of specific factors in the selection of candidates for Fontan surgery. The most recent publications in clinical cardiology include a study by a European working group on correct diagnostic work-up in cardiomyopathies, studies on the cost-effectiveness of percutaneous aortic valve implantation, a consensus document on the management of type B aortic dissection, and guidelines on aortic valve and ascending aortic disease. The most noteworthy developments in heart failure and transplantation include new American guidelines on heart failure, therapeutic advances in acute heart failure (serelaxin), the management of comorbidities such as iron deficiency, risk assessment using new biomarkers, and advances in ventricular assist devices. PMID:24774396

  2. Systemic Trans-splicing adeno-associated viral delivery efficiently transduces the heart of adult mdx mouse, a model for duchenne muscular dystrophy.

    PubMed

    Ghosh, Arkasubhra; Yue, Yongping; Shin, Jin-Hong; Duan, Dongsheng

    2009-11-01

    Trans-splicing adeno-associated viral (tsAAV) vectors hold great promise for delivering large therapeutic genes. One potential application is in the treatment of Duchenne muscular dystrophy (DMD). In this case, it is necessary to transduce whole body muscle. We demonstrated body-wide AAV-9 tsAAV transduction in normal neonatal mice. However, it was not clear whether such an approach would work in diseased mice. In this study we delivered the AAV-9 alkaline phosphatase (AP) tsAAV vector (3 x 10(12) vector genome particles per vector per mouse, tail vein injection) to 2-month-old mdx mice, the most widely used DMD model. Four months later, we observed widespread AP expression in the heart. It reached the same level as we have seen in normal neonatal puppy. Interestingly, myocardial transduction correlated with beta-myosin heavy chain expression but not with LamR, the putative AAV-9 receptor. AP expression was also detected in various skeletal muscles but at levels much lower than in normal newborn mice. Despite the existing inflammatory milieu, we did not see any appreciable increase in CD4(+) and CD8(+) T cells and macrophages in striated muscles after systemic tsAAV infection. In summary, our results have paved the way for tsAAV-mediated gene therapy for Duchenne cardiomyopathy. PMID:19627234

  3. Antimicrobial proteins of murine macrophages.

    PubMed Central

    Hiemstra, P S; Eisenhauer, P B; Harwig, S S; van den Barselaar, M T; van Furth, R; Lehrer, R I

    1993-01-01

    Three murine microbicidal proteins (MUMPs) were purified from cells of the murine macrophage cell line RAW264.7 that had been activated by gamma interferon. Similar proteins were also present in nonactivated RAW264.7 cells, in cells of the murine macrophage cell line J774A.1, and in resident and activated murine peritoneal macrophages. MUMP-1, MUMP-2, and MUMP-3 killed Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Mycobacterium fortuitum, and Cryptococcus neoformans in vitro. MUMP-1 resembled an H1 histone but was unusual because its N-terminal residue (serine) was not N acetylated. Although MUMP-2 was N terminally blocked, its high lysine/arginine ratio and its reactivity with an antibody to H1 histones suggested that it also belonged to the H1 histone family. MUMP-3 was identical to histone H2B in 30 of 30 amino-terminal residues. Although the antimicrobial properties of histones have been recognized for decades, this is the first evidence that such proteins may endow the lysosomal apparatus of macrophages with nonoxidative antimicrobial potential. Other MUMPs, including some with a more restricted antimicrobial spectrum and one that appeared to be induced in RAW264.7 cells after gamma interferon stimulation, were noted but remain to be characterized. Images PMID:8514411

  4. Rising Blood Sugar Hitting More Obese Adults

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159853.html Rising Blood Sugar Hitting More Obese Adults To curb diabetes, researchers ... HealthDay News) -- Among obese American adults, control of blood sugar is worsening, leading to more diabetes and heart ...

  5. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  6. Heart Failure

    MedlinePlus

    ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and diabetes. It is more common in people who are 65 years old or older, African Americans, people who are overweight, and people who have ...

  7. Heart Truth

    MedlinePlus

    ... about women’s risk for heart disease―the #1 killer of women in the United States―and share ... t Care What You Wear—It's the #1 Killer of Women ® are registered trademarks of U.S. ...

  8. Women's Heart Disease: Heart Attack Symptoms

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Attack Symptoms Past Issues / Winter 2014 Table ... NHLBI has uncovered some of the causes of heart diseases and conditions, as well as ways to prevent ...

  9. After Heart Attack, New Threat: Heart Failure

    MedlinePlus

    ... of heart attack known as STEMI (ST elevation myocardial infarction). "Patients with ischemic heart disease are at the ... failure]. This includes those who have had a myocardial infarction, also called heart attack," Gho said. "Research studying ...

  10. Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Heart Disease: Symptoms, Diagnosis, Treatment Past Issues / Winter 2009 ... of this page please turn Javascript on. Most heart attacks happen when a clot in the coronary ...

  11. Heart Health: The Heart Truth Campaign 2009

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health The Heart Truth Campaign 2009 Past Issues / Winter 2009 Table ... one of the celebrities supporting this year's The Heart Truth campaign. Both R&B singer Ashanti (center) ...

  12. Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

    MedlinePlus

    ... Issues Cover Story Heart Health Heart Disease: Symptoms, Diagnosis, Treatment Past Issues / Winter 2009 Table of Contents ... or both arms, the neck, jaw, or stomach. Diagnosis Key heart tests include: Electrocardiogram (ECG or EKG) — ...

  13. Genetic Deletion of Uncoupling Protein 3 Exaggerates Apoptotic Cell Death in the Ischemic Heart Leading to Heart Failure

    PubMed Central

    Perrino, Cinzia; Schiattarella, Gabriele G.; Sannino, Anna; Pironti, Gianluigi; Petretta, Maria Piera; Cannavo, Alessandro; Gargiulo, Giuseppe; Ilardi, Federica; Magliulo, Fabio; Franzone, Anna; Carotenuto, Giuseppe; Serino, Federica; Altobelli, Giovanna G.; Cimini, Vincenzo; Cuocolo, Alberto; Lombardi, Assunta; Goglia, Fernando; Indolfi, Ciro; Trimarco, Bruno; Esposito, Giovanni

    2013-01-01

    Background Uncoupling protein 3 (ucp3) is a member of the mitochondrial anion carrier superfamily of proteins uncoupling mitochondrial respiration. In this study, we investigated the effects of ucp3 genetic deletion on mitochondrial function and cell survival under low oxygen conditions in vitro and in vivo. Methods and Results To test the effects of ucp3 deletion in vitro, murine embryonic fibroblasts and adult cardiomyocytes were isolated from wild‐type (WT, n=67) and ucp3 knockout mice (ucp3−/−, n=70). To test the effects of ucp3 genetic deletion in vivo, myocardial infarction (MI) was induced by permanent coronary artery ligation in WT and ucp3−/− mice. Compared with WT, ucp3−/− murine embryonic fibroblasts and cardiomyocytes exhibited mitochondrial dysfunction and increased mitochondrial reactive oxygen species generation and apoptotic cell death under hypoxic conditions in vitro (terminal deoxynucleotidyl transferase‐dUTP nick end labeling–positive nuclei: WT hypoxia, 70.3±1.2%; ucp3−/− hypoxia, 85.3±0.9%; P<0.05). After MI, despite similar areas at risk in the 2 groups, ucp3−/− hearts demonstrated a significantly larger infarct size compared with WT (infarct area/area at risk: WT, 48.2±3.7%; ucp3−/−, 65.0±2.9%; P<0.05). Eight weeks after MI, cardiac function was significantly decreased in ucp3−/− mice compared with WT (fractional shortening: WT MI, 42.7±3.1%; ucp3−/− MI, 24.4±2.9; P<0.05), and this was associated with heightened apoptotic cell death (terminal deoxynucleotidyl transferase‐dUTP nick end labeling–positive nuclei: WT MI, 0.7±0.04%; ucp3−/− MI, 1.1±0.09%, P<0.05). Conclusions Our data indicate that ucp3 levels regulate reactive oxygen species levels and cell survival during hypoxia, modulating infarct size in the ischemic heart. PMID:23688674

  14. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis

    SciTech Connect

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli–germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli–germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. - Highlights: • Intermittent treatment with BTZ caused fertility impairment in adult mice. • BTZ treatment elicited apoptosis during early phase of testicular recovery. • Up-regulation of oxidative stress by BTZ treatment

  15. Cell migration during heart regeneration in zebrafish.

    PubMed

    Tahara, Naoyuki; Brush, Michael; Kawakami, Yasuhiko

    2016-07-01

    Zebrafish possess the remarkable ability to regenerate injured hearts as adults, which contrasts the very limited ability in mammals. Although very limited, mammalian hearts do in fact have measurable levels of cardiomyocyte regeneration. Therefore, elucidating mechanisms of zebrafish heart regeneration would provide information of naturally occurring regeneration to potentially apply to mammalian studies, in addition to addressing this biologically interesting phenomenon in itself. Studies over the past 13 years have identified processes and mechanisms of heart regeneration in zebrafish. After heart injury, pre-existing cardiomyocytes dedifferentiate, enter the cell cycle, and repair the injured myocardium. This process requires interaction with epicardial cells, endocardial cells, and vascular endothelial cells. Epicardial cells envelope the heart, while endocardial cells make up the inner lining of the heart. They provide paracrine signals to cardiomyocytes to regenerate the injured myocardium, which is vascularized during heart regeneration. In addition, accumulating results suggest that local migration of these major cardiac cell types have roles in heart regeneration. In this review, we summarize the characteristics of various heart injury methods used in the research community and regeneration of the major cardiac cell types. Then, we discuss local migration of these cardiac cell types and immune cells during heart regeneration. Developmental Dynamics 245:774-787, 2016. © 2016 Wiley Periodicals, Inc. PMID:27085002

  16. Pediatric heart surgery - discharge

    MedlinePlus

    ... reduced appetite Alternate Names Congenital heart surgery - discharge; Patent ductus arteriosus ligation - discharge; Hypoplastic left heart repair - ... of the aorta Congenital heart defect - corrective surgery Patent ductus arteriosus Pediatric heart surgery Tetralogy of Fallot ...

  17. Problem: Heart Valve Regurgitation

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Problem: Heart Valve Regurgitation Updated:May 26,2016 What ... content was last reviewed May 2016. Heart Valve Problems and Disease • Home • About Heart Valves • Heart Valve ...

  18. Problem: Heart Valve Stenosis

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Problem: Heart Valve Stenosis Updated:Aug 10,2016 About ... content was last reviewed May 2016. Heart Valve Problems and Disease • Home • About Heart Valves • Heart Valve ...

  19. Heart attack first aid

    MedlinePlus

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...

  20. About Heart Attacks

    MedlinePlus

    ... survive. A heart attack occurs when the blood flow that brings oxygen to the heart muscle is severely reduced or ... survive. A heart attack occurs when the blood flow that brings oxygen to the heart muscle is severely reduced or ...

  1. Heart disease - resources

    MedlinePlus

    Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association -- www.heart.org Centers for Disease Control and Prevention -- www.cdc.gov/heartdisease

  2. What Causes Heart Block?

    MedlinePlus

    ... or inflammation of the heart muscle. Heart failure . Rheumatic (roo-MAT-ik) fever. Cardiomyopathy (KAR-de-o-mi-OP-a-the), or heart muscle diseases. Other diseases may increase the risk of heart ...

  3. Congenital heart disease

    MedlinePlus

    Congenital heart disease is a problem with the heart's structure and function that is present at birth. ... Congenital heart disease (CHD) can describe a number of different problems affecting the heart. It is the most common ...

  4. Heart CT scan

    MedlinePlus

    ... arteries to determine your risk for heart disease Congenital heart disease (heart problems that are present at birth) Problems ... Abnormal results may be due to: Aneurysm Congenital heart disease ... Narrowing of one or more coronary arteries (coronary artery ...

  5. Heart Attack Risk Assessment

    MedlinePlus

    ... Pressure Tools & Resources Stroke More Heart Attack Risk Assessment Updated:May 31,2016 We're sorry, but ... Can You Recognize a Heart Attack? Quiz Risk Assessment Patient Information Sheets: Heart Attack Heart Attack Personal ...

  6. Pediatric heart surgery

    MedlinePlus

    Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... after the baby is born. For others, your child may be able to safely wait for months ...

  7. Potential benefits of healthy food and lifestyle policies for reducing coronary heart disease mortality in Turkish adults by 2025: a modelling study

    PubMed Central

    Sahan, Ceyda; Sozmen, Kaan; Unal, Belgin; O'Flaherty, Martin; Critchley, Julia

    2016-01-01

    Objective This study uses a modelling approach to compare the potential impact of future risk factor scenarios relating to smoking, physical activity levels, dietary salt, saturated fat intake, mean body mass index (BMI) levels, diabetes prevalence and fruit and vegetable (F&V) consumption on future coronary heart disease (CHD) mortality in Turkey for year 2025. Design A CHD mortality model previously developed and validated in Turkey was extended to predict potential trends in CHD mortality from 2008 to 2025. Setting Using risk factor trends data from recent surveys as a baseline, we modelled alternative evidence-based future risk factor scenarios (modest/ideal scenarios). Probabilistic sensitivity analyses were conducted to account for uncertainties. Subject Projected populations in 2025 (aged 25–84) of 54 million in Turkey. Results Assuming lower mortality, modest policy changes in risk factors would result in ∼25 635 (range: 20 290–31 125) fewer CHD deaths in the year 2025; 35.6% attributed to reductions in salt consumption, 20.9% to falls in diabetes, 14.6% to declines in saturated fat intake and 13.6% to increase in F&V intake. In the ideal scenario, 45 950 (range: 36 780–55 450) CHD deaths could be prevented in 2025. Again, 33.2% of this would be attributed to reductions in salt reduction, 19.8% to increases in F&V intake, 16.7% to reductions in saturated fat intake and 14.0% to the fall in diabetes prevalence. Conclusions Only modest risk factor changes in salt, saturated/unsaturated fats and F&V intake could prevent around 16 000 CHD deaths in the year 2025 in Turkey, even assuming mortality continues to decline. Implementation of population-based, multisectoral interventions to reduce salt and saturated fat consumption and increase F&V consumption should be scaled up in Turkey. PMID:27388358

  8. Correlation of anthropometric indices with common cardiovascular risk factors in an urban adult population of Iran: data from Zanjan Healthy Heart Study.

    PubMed

    Mellati, Ali Awsat; Mousavinasab, Seyed Nouraddin; Sokhanvar, Sepide; Kazemi, Seyed Ali Naghi; Esmailli, Mohammad Hossain; Dinmohamadi, Hossain

    2009-01-01

    The purpose of this study was to determine the anthropometric index that best predicts common cardiovascular risk factors. A total of 2768 individuals (1310 men and 1458 women) aged 21-75 years with full relevant data from the Zanjan Healthy Heart Study (a prospective study in Zanjan and Abhar, two main cities of Zanjan Province, Iran) were recruited. Common cardiovascular risk factors (TG, TC, HDL-c, LDL-c, fast blood sugar, blood pressure), anthropometric indices (BMI, WC, WHR, WHtR) were measured using standard process, and their correlated classification was evaluated by partial correlation and Receiver Operator Characteristic (ROC) curve analysis. Area under curve (AUC) of WHtR was the largest for most (6 of 7) of the common cardiovascular risk factors in both men and women; followed by WC (4 of the 7 including ties) in men, while AUCs of three anthropometric indices (WC, BMI, WHR) were the same with the largest for 1 of 7 risk factors in women. These results show that the high prevalence of lipid profiles, as cardiovascular risk factors, need special attention, intervention and appropriate treatment. Consistence with other reports, WHtR is a better discriminator of cardiovascular risk factors compared with the other three indices (BMI, WC, and WHR). We determined its optimal cut-off point of 0.5 for both genders. However, due to differences in reported cut-off values across different ethnic groups, future research and longitudinal data is needed before reaching an internationally accepted simple and appropriate measure that could be effectively used in the clinical and epidemiological fields. PMID:19713181

  9. Statin under-use and low prevalence of LDL-C control among U.S. adults at high risk of coronary heart disease

    PubMed Central

    Gamboa, Christopher M.; Safford, Monika M.; Levitan, Emily B.; Mann, Devin M.; Yun, Huifeng; Glasser, Steve; Woolley, J. Michael; Rosenson, Robert; Farkouh, Michael; Muntner, Paul

    2014-01-01

    Background Statins reduce the risk of coronary heart disease (CHD) in individuals with a history of CHD or risk equivalents. A 10-year CHD risk >20% is considered a risk equivalent but is frequently not detected. Statin use and low density lipoprotein cholesterol (LDL-C) control were examined among participants with CHD or risk equivalents in the nationwide Reasons for Geographic and Racial Differences in Stroke (REGARDS) study (n=8,812). Methods Participants were categorized into 4 mutually exclusive groups: (1) history of CHD (n=4,025), (2) no history of CHD but with a history of stroke and/or abdominal aortic aneurysm (AAA) (n=946), (3) no history of CHD or stroke/AAA but with diabetes mellitus (n=3,134), or (4) no history of the conditions in (1) through (3) but with 10-year Framingham CHD risk score (FRS) >20% calculated using the ATP-III point scoring system (n=707). Results Statins were used by 58.4% of those in the CHD group and 41.7%, 40.4%, and 20.1% of those in the stroke/AAA, diabetes, and FRS>20% groups, respectively. Among those taking statins, 65.1% had LDL-C <100mg/dL, with no difference between the CHD, stroke/AAA, or diabetes groups. However, compared to those in the CHD group, LDL-C <100mg/dL was less common among participants in the FRS>20% group (multivariable adjusted prevalence ratio: 0.72; 95% CI: 0.62 – 0.85). Results were similar using the 2013 ACC/AHA cholesterol treatment guideline. Conclusions These data suggest many people with high CHD risk, especially those with a FRS>20%, do not receive guideline-concordant lipid-lowering therapy and do not achieve an LDL-C <100mg/dL. PMID:24892511

  10. Heart Disease in Women

    MedlinePlus

    ... United States, 1 in 4 women dies from heart disease. In fact, coronary heart disease (CHD)—the most common type of heart ... heart information http://womenshealth.gov/publications/our-publications/fact-sheet/heart-disease.html New Heart Guidelines Released; Talk to ...

  11. Pediatric heart surgery

    MedlinePlus

    Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... There are many kinds of heart defects. Some are minor, and others are more serious. Defects can occur inside the heart or in the large blood vessels ...

  12. Congenital Heart Disease: Causes, Diagnosis, Symptoms, and Treatments.

    PubMed

    Sun, RongRong; Liu, Min; Lu, Lei; Zheng, Yi; Zhang, Peiying

    2015-07-01

    The congenital heart disease includes abnormalities in heart structure that occur before birth. Such defects occur in the fetus while it is developing in the uterus during pregnancy. About 500,000 adults have congenital heart disease in USA (WebMD, Congenital heart defects medications, www.WebMD.com/heart-disease/tc/congenital-heart-defects-medications , 2014). 1 in every 100 children has defects in their heart due to genetic or chromosomal abnormalities, such as Down syndrome. The excessive alcohol consumption during pregnancy and use of medications, maternal viral infection, such as Rubella virus, measles (German), in the first trimester of pregnancy, all these are risk factors for congenital heart disease in children, and the risk increases if parent or sibling has a congenital heart defect. These are heart valves defects, atrial and ventricular septa defects, stenosis, the heart muscle abnormalities, and a hole inside wall of the heart which causes defect in blood circulation, heart failure, and eventual death. There are no particular symptoms of congenital heart disease, but shortness of breath and limited ability to do exercise, fatigue, abnormal sound of heart as heart murmur, which is diagnosed by a physician while listening to the heart beats. The echocardiogram or transesophageal echocardiogram, electrocardiogram, chest X-ray, cardiac catheterization, and MRI methods are used to detect congenital heart disease. Several medications are given depending on the severity of this disease, and catheter method and surgery are required for serious cases to repair heart valves or heart transplantation as in endocarditis. For genetic study, first DNA is extracted from blood followed by DNA sequence analysis and any defect in nucleotide sequence of DNA is determined. For congenital heart disease, genes in chromosome 1 show some defects in nucleotide sequence. In this review the causes, diagnosis, symptoms, and treatments of congenital heart disease are described

  13. Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

    PubMed Central

    Lv, Juanxiu; Zhang, Peiwen; Zhang, Yujuan; Kuang, Hanzhe; Cao, Li; Wu, Conglong; Jiang, Lin; Li, Dawei; Mao, Caiping

    2014-01-01

    Aims: Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin–angiotensin system (RAS) that may mediate cardiac cell death. Methods and Results: Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells. Conclusion: Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway. PMID:23690339

  14. Correlates of hot day air-conditioning use among middle-aged and older adults with chronic heart and lung diseases: the role of health beliefs and cues to action.

    PubMed

    Richard, Lucie; Kosatsky, Tom; Renouf, Annie

    2011-02-01

    Extreme ambient heat is a serious public health threat, especially for the elderly and persons with pre-existing health conditions. Although much of the excess mortality and morbidity associated with extreme heat is preventable, the adoption of effective preventive strategies is limited. The study reported here tested the predictive power of selected components of the Health Belief Model for air-conditioning (AC) use among 238 non-institutionalized middle-aged and older adults with chronic heart failure and/or chronic obstructive pulmonary disease living in Montréal, Canada. Respondents were recruited through clinics (response rate 71%) and interviews were conducted in their homes or by telephone. Results showed that 73% of participants reported having a home air conditioner. The average number of hours spent per 24-hour period in air-conditioned spaces during heat waves was 14.5 hours (SD = 9.4). Exploratory structural equation modeling showed that specific beliefs about the benefits of and drawbacks to AC as well as internal cues to action were predictive of its level of use, whereas the perceived severity of the effects of heat on health was not. The findings are discussed in light of the need to adequately support effective response to extreme heat in this vulnerable population. PMID:21068164

  15. Hypoxia and fetal heart development.

    PubMed

    Patterson, A J; Zhang, L

    2010-10-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation. PMID:20712587

  16. The proteasome inhibitor bortezomib induces testicular toxicity by upregulation of oxidative stress, AMP-activated protein kinase (AMPK) activation and deregulation of germ cell development in adult murine testis.

    PubMed

    Li, Wei; Fu, Jianfang; Zhang, Shun; Zhao, Jie; Xie, Nianlin; Cai, Guoqing

    2015-06-01

    Understanding how chemotherapeutic agents mediate testicular toxicity is crucial in light of compelling evidence that male infertility, one of the severe late side effects of intensive cancer treatment, occurs more often than they are expected to. Previous study demonstrated that bortezomib (BTZ), a 26S proteasome inhibitor used to treat refractory multiple myeloma (MM), exerts deleterious impacts on spermatogenesis in pubertal mice via unknown mechanisms. Here, we showed that intermittent treatment with BTZ resulted in fertility impairment in adult mice, evidenced by testicular atrophy, desquamation of immature germ cells and reduced caudal sperm storage. These deleterious effects may originate from the elevated apoptosis in distinct germ cells during the acute phase and the subsequent disruption of Sertoli-germ cell anchoring junctions (AJs) during the late recovery. Mechanistically, balance between AMP-activated protein kinase (AMPK) activation and Akt/ERK pathway appeared to be indispensable for AJ integrity during the late testicular recovery. Of particular interest, the upregulated testicular apoptosis and the following disturbance of Sertoli-germ cell interaction may both stem from the excessive oxidative stress elicited by BTZ exposure. We also provided the in vitro evidence that AMPK-dependent mechanisms counteract follicle-stimulating hormone (FSH) proliferative effects in BTZ-exposed Sertoli cells. Collectively, BTZ appeared to efficiently prevent germ cells from normal development via multiple mechanisms in adult mice. Employment of antioxidants and/or AMPK inhibitor may represent an attractive strategy of fertility preservation in male MM patients exposed to conventional BTZ therapy and warrants further investigation. PMID:25886977

  17. Heart Research

    NASA Technical Reports Server (NTRS)

    1991-01-01

    James Antaki and a group of researchers from the University of Pittsburgh School of Medicine used many elements of the Technology Utilization Program while looking for a way to visualize and track material points within the heart muscle. What they needed were tiny artificial "eggs" containing copper sulfate solution, small enough (about 2 mm in diameter) that they would not injure the heart, and large enough to be seen in Magnetic Resonance Imaging (MRI) images; they also had to be biocompatible and tough enough to withstand the beating of the muscle. The group could not make nor buy sufficient containers. After reading an article on microspheres in NASA Tech Briefs, and a complete set of reports on microencapsulation from the Jet Propulsion Laboratory (JPL), JPL put Antaki in touch with Dr.Taylor Wang of Vanderbilt University who helped construct the myocardial markers. The research is expected to lead to improved understanding of how the heart works and what takes place when it fails.

  18. Body mass index in early and middle adult life: prospective associations with myocardial infarction, stroke and diabetes over a 30-year period: the British Regional Heart Study

    PubMed Central

    Owen, Christopher G; Kapetanakis, Venediktos V; Rudnicka, Alicja R; Wathern, Andrea K; Lennon, Lucy; Papacosta, Olia; Cook, Derek G; Wannamethee, S Goya; Whincup, Peter H

    2015-01-01

    Objectives Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks. Design A prospective cohort study. Participants 7735 men with BMI measured in middle age (40–59 years) and BMI ascertained at 21 years from military records or participant recall. Primary and secondary outcome measures 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status. Results Among 4846 (63%) men (with complete data), a 1 kg/m2 higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m2 higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk. Conclusions Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke. PMID:26373398

  19. Older Adults and Mental Health

    MedlinePlus

    ... is a widely underrecognized and undertreated medical illness. Depression often co-occurs with other serious illnesses, such as heart disease, stroke, diabetes, cancer, and Parkinson's disease. Because many older adults face these illnesses as well as various social and ...

  20. The HEART Pathway Randomized Trial

    PubMed Central

    Mahler, Simon A.; Riley, Robert F.; Hiestand, Brian C.; Russell, Gregory B.; Hoekstra, James W.; Lefebvre, Cedric W.; Nicks, Bret A.; Cline, David M.; Askew, Kim L.; Elliott, Stephanie B.; Herrington, David M.; Burke, Gregory L.; Miller, Chadwick D.

    2015-01-01

    Background The HEART Pathway is a decision aid designed to identify emergency department patients with acute chest pain for early discharge. No randomized trials have compared the HEART Pathway with usual care. Methods and Results Adult emergency department patients with symptoms related to acute coronary syndrome without ST-elevation on ECG (n=282) were randomized to the HEART Pathway or usual care. In the HEART Pathway arm, emergency department providers used the HEART score, a validated decision aid, and troponin measures at 0 and 3 hours to identify patients for early discharge. Usual care was based on American College of Cardiology/American Heart Association guidelines. The primary outcome, objective cardiac testing (stress testing or angiography), and secondary outcomes, index length of stay, early discharge, and major adverse cardiac events (death, myocardial infarction, or coronary revascularization), were assessed at 30 days by phone interview and record review. Participants had a mean age of 53 years, 16% had previous myocardial infarction, and 6% (95% confidence interval, 3.6%–9.5%) had major adverse cardiac events within 30 days of randomization. Compared with usual care, use of the HEART Pathway decreased objective cardiac testing at 30 days by 12.1% (68.8% versus 56.7%; P=0.048) and length of stay by 12 hours (9.9 versus 21.9 hours; P=0.013) and increased early discharges by 21.3% (39.7% versus 18.4%; P<0.001). No patients identified for early discharge had major adverse cardiac events within 30 days. Conclusions The HEART Pathway reduces objective cardiac testing during 30 days, shortens length of stay, and increases early discharges. These important efficiency gains occurred without any patients identified for early discharge suffering MACE at 30 days. PMID:25737484

  1. Three-dimensional optical coherence tomography of the embryonic murine cardiovascular system

    NASA Astrophysics Data System (ADS)

    Luo, Wei; Marks, Daniel L.; Ralston, Tyler S.; Boppart, Stephen A.

    2006-03-01

    Optical coherence tomography (OCT) is an emerging high-resolution real-time biomedical imaging technology that has potential as a novel investigational tool in developmental biology and functional genomics. In this study, murine embryos and embryonic hearts are visualized with an OCT system capable of 2-µm axial and 15-µm lateral resolution and with real-time acquisition rates. We present, to our knowledge, the first sets of high-resolution 2- and 3-D OCT images that reveal the internal structures of the mammalian (murine) embryo (E10.5) and embryonic (E14.5 and E17.5) cardiovascular system. Strong correlations are observed between OCT images and corresponding hematoxylin- and eosin-stained histological sections. Real-time in vivo embryonic (E10.5) heart activity is captured by spectral-domain optical coherence tomography, processed, and displayed at a continuous rate of five frames per second. With the ability to obtain not only high-resolution anatomical data but also functional information during cardiovascular development, the OCT technology has the potential to visualize and quantify changes in murine development and in congenital and induced heart disease, as well as enable a wide range of basic in vitro and in vivo research studies in functional genomics.

  2. A Novel Population of Cells Expressing Both Hematopoietic and Mesenchymal Markers Is Present in the Normal Adult Bone Marrow and Is Augmented in a Murine Model of Marrow Fibrosis

    PubMed Central

    Ohishi, Masanobu; Ono, Wanida; Ono, Noriaki; Khatri, Richa; Marzia, Marilena; Baker, Emma K.; Root, Sierra H.; Wilson, Tremika Le-Shan; Iwamoto, Yukihide; Kronenberg, Henry M.; Aguila, Hector L.; Purton, Louise E.; Schipani, Ernestina

    2012-01-01

    Bone marrow (BM) fibrosis is a feature of severe hyperparathyroidism. Consistent with this observation, mice expressing constitutively active parathyroid hormone (PTH)/PTH-related peptide receptors (PPR) in osteoblasts (PPR*Tg) display BM fibrosis. To obtain insight into the nature of BM fibrosis in such a model, a double-mutant mouse expressing constitutively active PPR and green fluorescent protein (GFP) under the control of the type I collagen promoter (PPR*Tg/GFP) was generated. Confocal microscopy and flow cytometry revealed the presence of a cell population expressing GFP (GFP+) that was also positive for the hematopoietic marker CD45 in the BM of both PPR*Tg/GFP and control animals. This cell population was expanded in PPR*Tg/GFP. The existence of cells expressing both type I collagen and CD45 in the adult BM was confirmed by IHC and fluorescence-activated cell sorting. An analysis of total RNA extracted from sorted GFP+CD45+ cells showed that these cells produced type I collagen and PTH/PTH-related peptide receptor and receptor activator for NF-κB mRNAs, further supporting their features of being both mesenchymal and hematopoietic lineages. Similar cells, known as fibrocytes, are also present in pathological fibroses. Our findings, thus, indicate that the BM is a permissive microenvironment for the differentiation of fibrocyte-like cells and raise the possibility that these cells could contribute to the pathogenesis of BM fibrosis. PMID:22155108

  3. High-frame rate four dimensional optoacoustic tomography enables visualization of cardiovascular dynamics and mouse heart perfusion

    PubMed Central

    Deán-Ben, Xosé Luís; Ford, Steven James; Razansky, Daniel

    2015-01-01

    Functional imaging of mouse models of cardiac health and disease provides a major contribution to our fundamental understanding of the mammalian heart. However, imaging murine hearts presents significant challenges due to their small size and rapid heart rate. Here we demonstrate the feasibility of high-frame-rate, noninvasive optoacoustic imaging of the murine heart. The temporal resolution of 50 three-dimensional frames per second provides functional information at important phases of the cardiac cycle without the use of gating or other motion-reduction methods. Differentiation of the blood oxygenation state in the heart chambers was enabled by exploiting the wavelength dependence of optoacoustic signals. Real-time volumetric tracking of blood perfusion in the cardiac chambers was also evaluated using indocyanine green. Taken together, the newly-discovered capacities offer a unique tool set for in-vivo structural and functional imaging of the whole heart with high spatio-temporal resolution in all three dimensions. PMID:26130401

  4. [Heart transplantation].

    PubMed

    Fukushima, Norihide; Matsuda, Hikaru

    2005-11-01

    While nearly 4,000 patients undergo heart transplantation (HTx) every year in the world, only 27 HTx were performed since February, 1999, because of very strict Organ Transplantation Law in Japan. All were treated with triple immunosuppressive regimen. Although two patients died of infection 4 months and 4 years after HTx, respectively, 23 were discharged and 16 returned to work or go to school. New immunosuppressive drugs, such as sirolimus and everolimus, treatment of presensitized patients before transplantation using cyclophosphamide and intravenous globulin infusion, compact implantable left ventricular assist supports and the future of pediatric HTx in Japan are discussed. PMID:16277260

  5. Epicardium-Derived Heart Repair

    PubMed Central

    Smits, Anke M.; Riley, Paul R.

    2016-01-01

    In the last decade, cell replacement therapy has emerged as a potential approach to treat patients suffering from myocardial infarction (MI). The transplantation or local stimulation of progenitor cells with the ability to form new cardiac tissue provides a novel strategy to overcome the massive loss of myocardium after MI. In this regard the epicardium, the outer layer of the heart, is a tractable local progenitor cell population for therapeutic pursuit. The epicardium has a crucial role in formation of the embryonic heart. After activation and migration into the developing myocardium, epicardial cells differentiate into several cardiac cells types. Additionally, the epicardium provides instructive signals for the growth of the myocardium and coronary angiogenesis. In the adult heart, the epicardium is quiescent, but recent evidence suggests that it becomes reactivated upon damage and recapitulates at least part of its embryonic functions. In this review we provide an update on the current knowledge regarding the contribution of epicardial cells to the adult mammalian heart during the injury response.

  6. Impact of Heart Transplantation on Cheyne-Stokes Respiration in a Child

    PubMed Central

    Al-Saleh, Suhail; Kantor, Paul F.; Narang, Indra

    2016-01-01

    Sleep disordered breathing is well described in adults with heart failure but not in pediatric population. We describe a 13-year-old Caucasian male with severe heart failure related to dilated cardiomyopathy who demonstrated polysomnographic features of Cheyne-Stokes respiration, which completely resolved following cardiac transplantation. Cheyne-Stokes respiration in children with advanced heart failure and its resolution after heart transplant can be observed similar to adults. PMID:27127671

  7. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model.

    PubMed

    Bonfield, Tracey L; Koloze, Mary; Lennon, Donald P; Zuchowski, Brandon; Yang, Sung Eun; Caplan, Arnold I

    2010-12-01

    Allogeneic human mesenchymal stem cells (hMSCs) introduced intravenously can have profound anti-inflammatory activity resulting in suppression of graft vs. host disease as well as regenerative events in the case of stroke, infarct, spinal cord injury, meniscus regeneration, tendinitis, acute renal failure, and heart disease in human and animal models of these diseases. hMSCs produce bioactive factors that provide molecular cuing for: 1) immunosuppression of T cells; 2) antiscarring; 3) angiogenesis; 4) antiapoptosis; and 5) regeneration (i.e., mitotic for host-derived progenitor cells). Studies have shown that hMSCs have profound effects on the immune system and are well-tolerated and therapeutically active in immunocompetent rodent models of multiple sclerosis and stroke. Furthermore, intravenous administration of MSCs results in pulmonary localization. Asthma is a major debilitating pulmonary disease that impacts in excess of 150 million people in the world with uncontrolled asthma potentially leading to death. In addition, the socioeconomic impact of asthma-associated illnesses at the pediatric and adult level are in the millions of dollars in healthcare costs and lost days of work. hMSCs may provide a viable multiaction therapeutic for this inflammatory lung disease by secreting bioactive factors or directing cellular activity. Our studies show the effectiveness and specificity of the hMSCs on decreasing chronic airway inflammation associated with the murine ovalbumin model of asthma. In addition, the results from these studies verify the in vivo immunoeffectiveness of hMSCs in rodents and support the potential therapeutic use of hMSCs for the treatment of airway inflammation associated with chronic asthma. PMID:20817776

  8. Evaluation of antiobesity and cardioprotective effect of Gymnema sylvestre extract in murine model

    PubMed Central

    Kumar, Vinay; Bhandari, Uma; Tripathi, Chakra Dhar; Khanna, Geetika

    2012-01-01

    Objective: Obesity plays a central role in the insulin resistance syndrome, which is associated with hyperinsulinemia, hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of atherosclerotic cardiovascular disease. The present study was done to assess the effect of Gymnema sylvestre extract (GSE) in the high fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Materials and Methods: Adult male Wistar rats (150–200 g body weight) were used in this study. HFD was used to induce obesity. Body mass index, hemodynamic parameters, serum leptin, insulin, glucose, lipids, apolipoprotein levels, myocardial apoptosis, and antioxidant enzymes were assessed. Organ and visceral fat pad weights and histopathological studies were also carried out. Results: Oral feeding of HFD (20 g/day) for a period of 28 days resulted in a significant increase in body mass index, organ weights, visceral fat pad weight, cardiac caspase-3, cardiac DNA laddering (indicating apoptotic inter-nucleosomal DNA fragment), and lipid peroxide levels of cardiac tissues of rats. Further, mean arterial blood pressure, heart rate, serum leptin, insulin, LDH, LDL-C, total cholesterol, triglycerides, and apolipoprotein-B levels were enhanced significantly, whereas serum HDL-C, apoliporotein-A1 levels, and cardiac Na+ K+ ATPase, antioxidant enzymes levels were significantly decreased. Furthermore, treatment with standardized ethanolic GSE (200 m/kg/p.o.) for a period of 28 days resulted in significant reversal of above mentioned changes in the obese Wistar rats. Conclusion: The present study has demonstrated the significant antiobesity potential of GSE in murine model of obesity. PMID:23112423

  9. Heart Health for Women

    MedlinePlus

    ... signs of a heart attack. 1. Eat a heart healthy diet. The nutrition facts on the food label can help you make ... heart health for women . (PDF 190KB) Get the facts about heart attacks in women . Learn More About Heart Disease: ...

  10. Diabetic Heart Disease

    MedlinePlus

    ... be coronary heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ... Some people who have diabetic heart disease have no signs or symptoms of ...

  11. How the Heart Works

    MedlinePlus

    ... for the Public » Health Topics » How the Heart Works Explore How the Heart Works What Is... Anatomy Contraction Circulation Electrical System Heart ... Heart Disease Heart Valve Disease How the Lungs Work Send a link to NHLBI to someone by ...

  12. ▼ Sacubitril valsartan for heart failure.

    PubMed

    2016-06-01

    ▼ Sacubitril valsartan (Entresto-Novartis) is a new oral drug licensed for the treatment of symptomatic chronic heart failure in adults with reduced ejection fraction.(1) It is described as an angiotensin receptor neprilysin inhibitor and contains the neprilysin inhibitor, sacubitril and the angiotensin II receptor antagonist, valsartan.(1-3) Here, we review the evidence for sacubitril valsartan and consider its place in the management of heart failure. PMID:27284124

  13. The association between mood and anxiety disorders, and coronary heart disease in Brazil: a cross-sectional analysis on the Brazilian longitudinal study of adult health (ELSA-Brasil)

    PubMed Central

    Kemp, Andrew H.; Brunoni, Andre R.; Nunes, Maria A.; Santos, Itamar S.; Goulart, Alessandra C.; Ribeiro, Antonio L.; Benseñor, Isabela M.; Lotufo, Paulo A.

    2015-01-01

    Background: Associations between major depressive disorder (MDD) and coronary heart disease (CHD) have been established, and these associations increase risk of future morbidity and mortality. Prior research has been carried out in high-income countries. Here we examine associations between the mood and anxiety disorders, and CHD in a large cohort at baseline from Brazil, a country facing a variety of challenges that may affect these associations. Methods: Participants included 15,105 civil servants aged 35 to 74 at baseline (2008–2010) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). CHD (N = 721) included self-reported angina pectoris (n = 305), myocardial infarction (n = 259) and coronary revascularization (n = 239). Hierarchical logistic regression analyses were conducted to estimate odds ratios and confidence intervals. Results: Major findings indicate that comorbid MDD and anxiety disorders (n = 434) are associated with a threefold increase in CHD, MDD alone (n = 170) with a twofold increase in CHD, while generalized anxiety disorder alone (n = 1,394) and mixed anxiety and depression disorder (n = 1,844) – symptoms present, but diagnostic threshold not reached – are associated with a 1.5-fold increase in CHD, after full adjustment for covariates. Conclusion: The association with CHD is greatest in those with psychiatric comorbidity, while associations were also observed in MDD and generalized anxiety disorder without comorbidity. While findings are limited by the cross-sectional design of the study, given the known risks associated with comorbidity of the mood and anxiety disorders with CHD, findings reinforce the importance of comprehensive health assessment in Brazil. PMID:25762963

  14. Murine Typhus, Reunion, France, 2011–2013

    PubMed Central

    Camuset, Guillaume; Socolovschi, Cristina; Moiton, Marie-Pierre; Kuli, Barbara; Foucher, Aurélie; Poubeau, Patrice; Borgherini, Gianandrea; Wartel, Guillaume; Audin, Héla; Raoult, Didier; Filleul, Laurent; Parola, Philippe; Pagès, Fréderic

    2015-01-01

    Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin. PMID:25625653

  15. Holes in the Heart

    MedlinePlus

    ... page from the NHLBI on Twitter. What Are Holes in the Heart? Holes in the heart are simple congenital (kon-JEN- ... the heart. However, some babies are born with holes in the upper or lower septum. A hole ...

  16. Pediatric heart surgery - discharge

    MedlinePlus

    ... discharge; Heart valve surgery - children - discharge; Heart surgery - pediatric - discharge; Heart transplant - pediatric - discharge ... Keane JF, Lock JE, Fyler DC, eds. Nadas' Pediatric Cardiology . 2nd ed. St. Louis, MO; WB Saunders; ...

  17. Right heart ventriculography

    MedlinePlus

    Angiography - right heart ... moved forward into the right side of the heart. As the catheter is advanced, the doctor can ... is injected into the right side of the heart. It helps the cardiologist determine the size and ...

  18. Left heart catheterization

    MedlinePlus

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye will be injected into your ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  19. What Causes Heart Failure?

    MedlinePlus

    ... the heart, leading to heart failure. High Blood Pressure Blood pressure is the force of blood pushing against the ... weaken your heart and lead to plaque buildup. Blood pressure is considered high if it stays at or ...

  20. Heart Attack Recovery FAQs

    MedlinePlus

    ... Pressure High Blood Pressure Tools & Resources Stroke More Heart Attack Recovery FAQs Updated:Aug 24,2016 Most people ... recovery. View an animation of a heart attack . Heart Attack Recovery Questions and Answers What treatments will I ...

  1. Heart Murmurs (For Kids)

    MedlinePlus

    ... than normal. You also might get an electrocardiogram (EKG), which measures electrical activity of the heart. None ... MORE ON THIS TOPIC The Heart Getting an EKG (Video) Your Heart & Circulatory System Mitral Valve Prolapse ...

  2. Congenital Heart Information Network

    MedlinePlus

    ... heart defects. Important Notice The Congenital Heart Information Network website is temporarily out of service. Please join ... and Uwe Baemayr for The Congenital Heart Information Network Exempt organization under Section 501(c)3. Copyright © ...

  3. Heart failure - overview

    MedlinePlus

    ... Your heart muscle is stiff and does not fill up with blood easily. This is called diastolic heart failure. As the heart's pumping becomes less effective, blood may back up in other areas of the body. Fluid ...

  4. Heart and Down Syndrome

    MedlinePlus

    ... Associated Conditions » The Heart & Down Syndrome The Heart & Down Syndrome Abnormalities of the cardiovascular system are common in ... the Most Common Heart Defects in Children With Down Syndrome? The most common defects are Atrioventricular Septal Defect ( ...

  5. Pediatric heart transplantation

    PubMed Central

    Stiasny, Brian; Dave, Hitendu; Cavigelli-Brunner, Anna; Balmer, Christian; Kretschmar, Oliver; Bürki, Christoph; Klauwer, Dietrich; Hübler, Michael

    2015-01-01

    Pediatric heart transplantation (pHTx) represents a small (14%) but very important and particular part in the field of cardiac transplantation. This treatment has lifelong impact on children. To achieve the best short and especially long-term survival with adequate quality of life, which is of crucial importance for this young patient population, one has to realize and understand the differences with adult HTx. Indication for transplantation, waitlist management including ABO incompatible (ABOi) transplantation and immunosuppression differ. Although young transplant recipients are ultimately likely to be considered for re-transplantation. One has to distinguish between myopathy and complex congenital heart disease (CHD). The differences in anatomy and physiology make the surgical procedure much more complex and create unique challenges. These recipients need a well-organized and educated team with pediatric cardiologists and intensivists, including a high skilled surgeon, which is dedicated to pHTx. Therefore, these types of transplants are best concentrated in specialized centers to achieve promising outcome. PMID:25922739

  6. Mechanical signaling coordinates the embryonic heart

    NASA Astrophysics Data System (ADS)

    Chiou, Kevin; Rocks, Jason; Prosser, Benjamin; Discher, Dennis; Liu, Andrea

    The heart is an active material which relies on robust signaling mechanisms between cells in order to produce well-timed, coordinated beats. Heart tissue is composed primarily of active heart muscle cells (cardiomyocytes) embedded in a passive extracellular matrix. During a heartbeat, cardiomyocyte contractions are coordinated across the heart to form a wavefront that propagates through the tissue to pump blood. In the adult heart, this contractile wave is coordinated via intercellular electrical signaling.Here we present theoretical and experimental evidence for mechanical coordination of embryonic heartbeats. We model cardiomyocytes as mechanically excitable Eshelby inclusions embedded in an overdamped elastic-fluid biphasic medium. For physiological parameters, this model replicates recent experimental measurements of the contractile wavefront which are not captured by electrical signaling models. We additionally challenge our model by pharmacologically blocking gap junctions, inhibiting electrical signaling between myocytes. We find that while adult hearts stop beating almost immediately after gap junctions are blocked, embryonic hearts continue beating even at significantly higher concentrations, providing strong support for a mechanical signaling mechanism.

  7. Heart failure - medicines

    MedlinePlus

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  8. After Heart Attack, New Threat: Heart Failure

    MedlinePlus

    ... https://medlineplus.gov/news/fullstory_159007.html After Heart Attack, New Threat: Heart Failure 1 in 4 survivors develops this serious ... TUESDAY, May 24, 2016 (HealthDay News) -- Risk of heart failure appears high within a few years of ...

  9. The Association between Childhood Physical Abuse and Heart Disease in Adulthood: Findings from a Representative Community Sample

    ERIC Educational Resources Information Center

    Fuller-Thomson, Esme; Brennenstuhl, Sarah; Frank, John

    2010-01-01

    Objectives: Although, the relationship between childhood physical abuse and adult heart disease has been documented, very few studies have controlled for many of the known risk factors for heart disease. The objective of the current study, therefore, was to investigate the association between childhood physical abuse and adult heart disease while…

  10. Heart Failure: Unique to Older Adults

    MedlinePlus

    ... healthcare in various settings, such as the hospital, assisted living facility or at home. These situations can ... overeating. If you are feeling suicidal, call a suicide help line or your doctor, or go to ...

  11. Young at Heart: Tips for Older Adults

    MedlinePlus

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... diabetes, digestive and liver diseases, kidney diseases, weight control and nutrition, urologic diseases, endocrine and metabolic diseases, ...

  12. Heart regeneration in adult MRL mice

    PubMed Central

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-01-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10–20% for the MRL compared with 1–3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians. PMID:11493713

  13. Heart regeneration in adult MRL mice

    NASA Astrophysics Data System (ADS)

    Leferovich, John M.; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang-Ming; Zwas, Donna; Lankford, Edward B.; Heber-Katz, Ellen

    2001-08-01

    The reaction of cardiac tissue to acute injury involves interacting cascades of cellular and molecular responses that encompass inflammation, hormonal signaling, extracellular matrix remodeling, and compensatory adaptation of myocytes. Myocardial regeneration is observed in amphibians, whereas scar formation characterizes cardiac ventricular wound healing in a variety of mammalian injury models. We have previously shown that the MRL mouse strain has an extraordinary capacity to heal surgical wounds, a complex trait that maps to at least seven genetic loci. Here, we extend these studies to cardiac wounds and demonstrate that a severe transmural, cryogenically induced infarction of the right ventricle heals extensively within 60 days, with the restoration of normal myocardium and function. Scarring is markedly reduced in MRL mice compared with C57BL/6 mice, consistent with both the reduced hydroxyproline levels seen after injury and an elevated cardiomyocyte mitotic index of 10-20% for the MRL compared with 1-3% for the C57BL/6. The myocardial response to injury observed in these mice resembles the regenerative process seen in amphibians.

  14. Folliculin (Flcn) inactivation leads to murine cardiac hypertrophy through mTORC1 deregulation

    PubMed Central

    Hasumi, Yukiko; Baba, Masaya; Hasumi, Hisashi; Huang, Ying; Lang, Martin; Reindorf, Rachel; Oh, Hyoung-bin; Sciarretta, Sebastiano; Nagashima, Kunio; Haines, Diana C.; Schneider, Michael D.; Adelstein, Robert S.; Schmidt, Laura S.; Sadoshima, Junichi; Marston Linehan, W.

    2014-01-01

    Cardiac hypertrophy, an adaptive process that responds to increased wall stress, is characterized by the enlargement of cardiomyocytes and structural remodeling. It is stimulated by various growth signals, of which the mTORC1 pathway is a well-recognized source. Here, we show that loss of Flcn, a novel AMPK–mTOR interacting molecule, causes severe cardiac hypertrophy with deregulated energy homeostasis leading to dilated cardiomyopathy in mice. We found that mTORC1 activity was upregulated in Flcn-deficient hearts, and that rapamycin treatment significantly reduced heart mass and ameliorated cardiac dysfunction. Phospho-AMP-activated protein kinase (AMPK)-alpha (T172) was reduced in Flcn-deficient hearts and nonresponsive to various stimulations including metformin and AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide). ATP levels were elevated and mitochondrial function was increased in Flcn-deficient hearts, suggesting that excess energy resulting from up-regulated mitochondrial metabolism under Flcn deficiency might attenuate AMPK activation. Expression of Ppargc1a, a central molecule for mitochondrial metabolism, was increased in Flcn-deficient hearts and indeed, inactivation of Ppargc1a in Flcn-deficient hearts significantly reduced heart mass and prolonged survival. Ppargc1a inactivation restored phospho-AMPK-alpha levels and suppressed mTORC1 activity in Flcn-deficient hearts, suggesting that up-regulated Ppargc1a confers increased mitochondrial metabolism and excess energy, leading to inactivation of AMPK and activation of mTORC1. Rapamycin treatment did not affect the heart size of Flcn/Ppargc1a doubly inactivated hearts, further supporting the idea that Ppargc1a is the critical element leading to deregulation of the AMPK–mTOR-axis and resulting in cardiac hypertrophy under Flcn deficiency. These data support an important role for Flcn in cardiac homeostasis in the murine model. PMID:24908670

  15. Building and re-building the heart by cardiomyocyte proliferation.

    PubMed

    Foglia, Matthew J; Poss, Kenneth D

    2016-03-01

    The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration. PMID:26932668

  16. Heart murmurs and other sounds

    MedlinePlus

    Chest sounds - murmurs; Heart sounds - abnormal; Murmur - innocent; Innocent murmur; Systolic heart murmur; Diastolic heart murmur ... The heart has four chambers: Two upper chambers (atria) Two lower chambers (ventricles) The heart has valves that close ...

  17. Who Needs a Heart Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Heart Transplant? Most patients referred to heart transplant centers have ... for heart failure. Who Is Eligible for a Heart Transplant? The specialists at the heart transplant center will ...

  18. Who Needs Heart Surgery?

    MedlinePlus

    ... disease (CHD) Fix heart valves that don't work well Control abnormal heart rhythms Place medical devices Replace a damaged heart with a healthy one If other treatments—such as lifestyle changes, medicines, and medical ... surgeon will work with you to decide whether you need heart ...

  19. Advanced Heart Failure

    MedlinePlus

    ... High Blood Pressure Tools & Resources Stroke More Advanced Heart Failure Updated:Oct 8,2015 When heart failure (HF) ... content was last reviewed on 04/06/2015. Heart Failure • Home • About Heart Failure • Causes and Risks for ...

  20. Broken Heart Syndrome

    MedlinePlus

    ... heart attacks are caused by blockages and blood clots forming in the coronary arteries, which supply the heart with blood. If these ... who experience broken heart syndrome have fairly normal coronary arteries, without severe blockages or clots. The heart cells are “stunned” by stress hormones ...

  1. Heart Disease in Women | NIH MedlinePlus the Magazine

    MedlinePlus

    ... guide decisions about your heart health. In November, four clinical guidelines were released that focus on assessing risks to your heart, making lifestyle changes to reduce those risks, and managing elevated blood cholesterol and body weight in adults. The guidelines were released by the ...

  2. "Heart" and Self in Old Age: A Chinese Model.

    ERIC Educational Resources Information Center

    Shiang, Julia

    The relationship between Chinese-Americans and their elderly parents is examined in the context of the Chinese concept of "heart." The Chinese word "heart" expresses a concept central to the dynamics of family transactions and especially to the relationship of elderly parents to adult children. Chinese culture is not a physically or verbally…

  3. IL-10 regulates murine lupus.

    PubMed

    Yin, Zhinan; Bahtiyar, Gul; Zhang, Na; Liu, Lanzhen; Zhu, Ping; Robert, Marie E; McNiff, Jennifer; Madaio, Michael P; Craft, Joe

    2002-08-15

    MRL/MpJ-Tnfrsf6(lpr) (MRL/MpJ-Fas(lpr); MRL-Fas(lpr)) mice develop a spontaneous lupus syndrome closely resembling human systemic lupus erythematosus. To define the role of IL-10 in the regulation of murine lupus, IL-10 gene-deficient (IL-10(-/-)) MRL-Fas(lpr) (MRL-Fas(lpr) IL-10(-/-)) mice were generated and their disease phenotype was compared with littermates with one or two copies of an intact IL-10 locus (MRL-Fas(lpr) IL-10(+/-) and MRL-Fas(lpr) IL-10(+/+) mice, respectively). MRL-Fas(lpr) IL-10(-/-) mice developed severe lupus, with earlier appearance of skin lesions, increased lymphadenopathy, more severe glomerulonephritis, and higher mortality than their IL-10-intact littermate controls. The increased severity of lupus in MRL-Fas(lpr) IL-10(-/-) mice was closely associated with enhanced IFN-gamma production by both CD4(+) and CD8(+) cells and increased serum concentration of IgG2a anti-dsDNA autoantibodies. The protective effect of IL-10 in this lupus model was further supported by the observation that administration of rIL-10 reduced IgG2a anti-dsDNA autoantibody production in wild-type MRL-Fas(lpr) animals. In summary, our results provide evidence that IL-10 can down-modulate murine lupus through inhibition of pathogenic Th1 cytokine responses. Modulation of the level of IL-10 may be of potential therapeutic benefit for human lupus. PMID:12165544

  4. Heart Disease Risk Factors You Can Control

    MedlinePlus

    ... to talk to your doctor. Your Guide to Physical Activity and Your Heart - You know you should be more physically active. But are you confused, concerned, or just can't get started? This guide uses science-based information to help adults develop a safe ...

  5. Cardiac progenitor cells for heart repair

    PubMed Central

    Le, TYL; Chong, JJH

    2016-01-01

    Stem cell therapy is being investigated as an innovative and promising strategy to restore cardiac function in patients with heart failure. Several stem cell populations, including adult (multipotent) stem cells from developed organs and tissues, have been tested for cardiac repair with encouraging clinical and pre-clinical results. The heart has been traditionally considered a post-mitotic organ, however, this view has recently changed with the identification of stem/progenitor cells residing within the adult heart. Given their cardiac developmental origins, these endogenous cardiac progenitor cells (CPCs) may represent better candidates for cardiac cell therapy compared with stem cells from other organs such as the bone marrow and adipose tissue. This brief review will outline current research into CPC populations and their cardiac repair/regenerative potential. PMID:27551540

  6. Impact of valves in a biomechanical heart model assisting failing hearts.

    PubMed

    Guldner, Norbert W; Klapproth, Peter; Margaritoff, Petra R J; Noel, Ralf; Sievers, Hans H; Grossherr, Martin

    2009-12-01

    Experimental valveless muscular blood pumps (biomechanical hearts) in goats can pump more than 1 L.min(-1), but due to a high pendulum volume, no significant flow contribution to the circulation is gained. Thus valved and valveless biomechanical hearts were compared for efficacy. Heart failure was induced in 5 adult Bore goats by repeated intracoronary embolization. A valved and balloon-equipped pumping chamber was integrated into the descending aorta, simulating standard biomechanical circulatory support. The valveless biomechanical heart supported a failing heart with a baseline cardiac output of 2,670 +/- 710 mL.min(-1) by contributing additional flow of 113 +/- 37 mL.min(-1). The biomechanical heart model incorporating an outlet valve offered an additional 304 +/- 126 mL.min(-1), and the use of 2 valves significantly enhanced pulmonary blood flow by 1,235 +/- 526 mL.min(-1). The use of 2 valves in biomechanical hearts seems to be essential to achieve adequate circulatory support. Double-valved biomechanical hearts driven by an appropriate skeletal muscle ventricle may contribute to the therapy of heart failure. PMID:20026534

  7. Mitochondrial Dynamics in Heart Disease

    PubMed Central

    Dorn, Gerald W

    2012-01-01

    Mitochondrial fission and fusion have been observed, and their importance revealed, in almost every tissue and cell type except adult cardiac myocytes. As each human heart is uniquely dependent upon mitochondria to generate massive amounts of ATP that fuel its approximately 38 million contractions per year, it seems odd that cardiac myocytes are the sole exception to the general rule that mitochondrial dynamism is important to function. Here, I briefly review the mechanisms for mitochondrial fusion and fission and examine current data that dispel the previous notion that mitochondrial fusion is dispensable in the heart. Rare and generally overlooked examples of cardiomyopathies linked either to naturally-occurring mutations or to experimentally-induced mutagenesis of mitochondrial fusion/fission genes are described. New findings from genetically targeted Drosophila and mouse models wherein mitochondrial fusion deficiency has specifically been induced in cardiac myocytes are discussed. PMID:22450031

  8. [Indications for surgery for valvular heart disease].

    PubMed

    Halbach, Marcel; Wahlers, Thorsten; Baldus, Stephan; Rudolph, Volker

    2015-11-01

    Due to the demographic change, chronic valvular heart disease becomes increasingly important - especially age-related primary diseases of the aortic and mitral valve as well as secondary diseases of the mitral and tricuspid valve caused by other age-related cardiac disorders. Medical treatment is limited to symptom relief by use of diuretics. Specific drugs or drugs with a prognostic benefit are not available. Thus, valve repair or replacement are the key options for treatment of relevant valvular heart disease. While open heart surgery was the only approach for a long time, interventional, catheter-based therapies have evolved in the last decade. This article describes up-to-date recommendations on indications for surgery for the most prevalent valvular heart diseases in adults - aortic stenosis, and aortic, mitral and tricuspid regurgitation). PMID:26583817

  9. Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.

    PubMed Central

    Woods, Andrew M; Wang, Who W; Shaw, David M; Ward, Christopher M; Carroll, Miles W; Rees, Buddug R; Stern, Peter L

    2002-01-01

    Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development. PMID:12003637

  10. Characterization of the murine 5T4 oncofoetal antigen: a target for immunotherapy in cancer.

    PubMed

    Woods, Andrew M; Wang, Who W; Shaw, David M; Ward, Christopher M; Carroll, Miles W; Rees, Buddug R; Stern, Peter L

    2002-08-15

    Human 5T4 oncofoetal antigen defined by the murine 5T4 monoclonal antibody is a highly glycosylated protein expressed by trophoblast and a few specialized adult epithelia. Up-regulation of 5T4 expression in some cancers is associated with poor clinical outcome; overexpression of human 5T4 cDNA in epithelial cells can alter their morphology and motility, supporting a role for such functions in cancer and development. A murine model to study 5T4 biology and tumour immunology would be useful. The production of m5T4-specific antibodies, their use in establishing transfected cells and documenting their biological properties in vitro are described. A rat monoclonal antibody specific for mouse 5T4 molecules by ELISA, flow cytometry, immunohistochemistry and immunoprecipitation was isolated and epitope mapped. Similar to its human counterpart, murine 5T4 antigen is a 72 kDa glycoprotein (immunoprecipitation and Western blot analysis) and exhibits punctate cell surface expression, dependent upon the integrity of the actin cytoskeleton. Likewise, overexpression of autologous murine 5T4 by B16 F10 melanoma cells and A9 L fibroblasts accentuates the 5T4 phenotype, which is characterized by a spindle-like morphology, increased motility, and reduced adhesion and proliferation rate. Immunohistochemical analysis of adult mouse tissues shows a restricted pattern of expression similar to that of human 5T4 antigen. The murine 5T4 antigen-expressing cell lines and antibody reagents are now being used to explore novel immunotherapies in pre-clinical models and the biology of 5T4 in development. PMID:12003637

  11. Genetic testing in congenital heart disease: ethical considerations.

    PubMed

    Lin, Kimberly Y; D'Alessandro, Lisa C A; Goldmuntz, Elizabeth

    2013-01-01

    On March 16, 2012, the Ethics of the Heart 2012: Ethical and Policy Challenges in Pediatric and Adult Congenital Heart Disease Conference took place in Philadelphia, Pennsylvania. The first session focused on the ethics surrounding genetic testing in patients with congenital heart disease. Summarized here is the introductory presentation given by Dr Elizabeth Goldmuntz entitled "The Role of Genetic Testing in Congenital Heart Disease," followed by a case presentation given by Dr Lisa D'Alessandro. The case and the panel discussion that ensued highlight several ethical principles and challenges in this unique patient population. PMID:23799755

  12. Apoptosis in irradiated murine tumors.

    PubMed

    Stephens, L C; Ang, K K; Schultheiss, T E; Milas, L; Meyn, R E

    1991-09-01

    Early radiation responses of transplantable murine ovarian (OCaI) and hepatocellular (HCaI) carcinomas were examined at 6, 24, 48, 96, and 144 h after single photon doses of 25, 35, or 45 Gy. Previous studies using tumor growth delay and tumor radiocurability assays had shown OCaI tumors to be relatively radiosensitive and HCaI tumors to be radioresistant. At 6 h, approximately 20% of nuclei in OCaI tumors showed aberrations characteristic of cell death by apoptosis. This contrasted to an incidence of 3% in HCaI tumors. Mitotic activity was eliminated in OCaI tumors but was only transiently suppressed in HCaI tumors. At 24-96 h, OCaI tumors continued to display apoptosis and progressive necrosis, whereas HCaI tumors responded by exhibiting marked pleomorphism. Factors other than mitotic activity may influence tumor radiosensitivity, and one of these may be susceptibility to induction of apoptosis (programmed cell death), because this was a prominent early radiation response by the radiosensitive OCaI tumors. PMID:1886987

  13. Chemoimmunotherapy of murine bladder cancer.

    PubMed

    Stogdill, B J; Lamm, D L; Livingston, R B

    1981-11-01

    The lethality of invasive transitional cell carcinoma (TCC) has prompted a search for effective, minimally toxic, adjuvant therapy. Such agents were evaluated in a murine bladder cancer (MBT2) model which parallels the clinical disease. One hundred C3H/He mice were inoculated i.d. with 2.5 x 10(4) viable MBT2 tumor cells and randomized to receive either normal saline (control), cis-Platinum (CPT), cyclophosphamide (CY), methotrexate (MTX), BCG, (CY + MTX), or (CY + MTX + BCG). Chemotherapy was given intraperitoneally weekly starting on day 7 after inoculation. Immunotherapy was given intralesionally on days 1 and 10 only. All mice were treated for 5 weeks followed by 5 weeks of observation. At 5 weeks, tumors of mice receiving cyclophosphamide alone or either of the combinations of therapy were smaller (P less than 0.01) than tumors of controls or other single agents alone. Each regimen increased survival, but only the combination regimen increase survival significantly (P less than 0.01). In the doses and schedule used in this model. Combination chemotherapy and chemoimmunotherapy significantly delay tumor growth and increase duration of survival (P less than 0.01) when compared with controls or single agent groups. PMID:7298287

  14. Healthy Family 2009: Practicing Healthy Adult Living

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