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Sample records for isolated adult cardiac

  1. Isolation and Culture of Adult Mouse Cardiomyocytes for Cell Signaling and in vitro Cardiac Hypertrophy

    PubMed Central

    Li, Daxiang; Wu, Jian; Bai, Yan; Zhao, Xiaochen; Liu, Lijun

    2014-01-01

    Technological advances have made genetically modified mice, including transgenic and gene knockout mice, an essential tool in many research fields. Adult cardiomyocytes are widely accepted as a good model for cardiac cellular physiology and pathophysiology, as well as for pharmaceutical intervention. Genetically modified mice preclude the need for complicated cardiomyocyte infection processes to generate the desired genotype, which are inefficient due to cardiomyocytes’ terminal differentiation. Isolation and culture of high quantity and quality functional cardiomyocytes will dramatically benefit cardiovascular research and provide an important tool for cell signaling transduction research and drug development. Here, we describe a well-established method for isolation of adult mouse cardiomyocytes that can be implemented with little training. The mouse heart is excised and cannulated to an isolated heart system, then perfused with a calcium-free and high potassium buffer followed by type II collagenase digestion in Langendorff retrograde perfusion mode. This protocol yields a consistent result for the collection of functional adult mouse cardiomyocytes from a variety of genetically modified mice. PMID:24894542

  2. 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.

  3. 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

  4. Effects of pressure- or volume-overload hypertrophy on passive stiffness in isolated adult cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Kato, S.; Koide, M.; Cooper, G. 4th; Zile, M. R.

    1996-01-01

    It has been hypothesized that the changes in myocardial stiffness induced by chronic hemodynamic overloading are dependent on changes in the passive stiffness of the cardiac muscle cell (cardiocyte). However, no previous studies have examined the passive constitutive properties of cardiocytes isolated from animals with myocardial hypertrophy. Accordingly, changes in relative passive stiffness of cardiocytes isolated from animals with chronic pressure- or volume-overload hypertrophy were determined by examining the effects of anisosmotic stress on cardiocyte size. Anisosmotic stress was produced by altering superfusate osmolarity. Hypertrophied cardiocytes were enzymatically isolated from 16 adult cats with right ventricular (RV) pressure-overload hypertrophy induced by pulmonary artery banding (PAB) and from 6 adult cats with RV volume-overload hypertrophy induced by creating an atrial septal defect (ASD). Left ventricular (LV) cardiocytes from each cat served as nonhypertrophied, normally loaded, same-animal controls. Superfusate osmolarity was decreased from 305 +/- 3 to 135 +/- 5 mosM and increased to 645 +/- 4 mosM. During anisosmotic stress, there were no significant differences between hypertrophied RV and normal LV cardiocytes in pressure overload PAB cats with respect to percent change in cardiocyte area (47 +/- 2% in RV vs. 48 +/- 2% in LV), diameter (46 +/- 3% in RV vs. 48 +/- 2% in LV), or length (2.4 +/- 0.2% in RV vs. 2.0 +/- 0.3% in LV), or sarcomere length (1.5 +/- 0.1% in RV vs. 1.3 +/- 0.3% in LV). Likewise, there were no significant differences in cardiocyte strain between hypertrophied RV and normal LV cardiocytes from ASD cats. In conclusion, chronic pressure-overload hypertrophy and chronic volume-overload hypertrophy did not alter the cardiocyte response to anisosmotic stress. Thus chronic overload hypertrophy did not alter relative passive cardiocyte stiffness.

  5. Cardiac Rehabilitation in Older Adults.

    PubMed

    Schopfer, David W; Forman, Daniel E

    2016-09-01

    The biology of aging and the pathophysiology of cardiovascular disease (CVD) overlap, with the effect that CVD is endemic in the growing population of older adults. Moreover, CVD in older adults is usually complicated by age-related complexities, including multimorbidity, polypharmacy, frailty, and other intricacies that add to the risks of ambiguous symptoms, deconditioning, iatrogenesis, falls, disability, and other challenges. Cardiac rehabilitation (CR) is a comprehensive lifestyle program that can have particular benefit for older patients with cardiovascular conditions. Although CR was originally designed primarily as an exercise training program for younger adults after a myocardial infarction or coronary artery bypass surgery, it has evolved as a comprehensive lifestyle program (promoting physical activity as well as education, diet, risk reduction, and adherence) for a broader range of CVD (coronary heart disease, heart failure, and valvular heart disease). It provides a valuable opportunity to address and moderate many of the challenges pertinent for the large and growing population of older adults with CVD. Cardiac rehabilitation promotes physical function (cardiorespiratory fitness as well as strength and balance) that helps overcome disease and deconditioning as well as related vulnerabilities such as disability, frailty, and falls. Similarly, CR facilitates education, monitoring, and guidance to reduce iatrogenesis and promote adherence. Furthermore, CR fosters cognition, socialization, and independence in older patients. Yet despite all its conceptual benefits, CR is significantly underused in older populations. This review discusses benefits and the paradoxical underuse of CR, as well as evolving models of care that may achieve greater application and efficacy. PMID:27297002

  6. Modeling the isolated cardiac myocyte.

    PubMed

    Puglisi, Jose L; Wang, Fei; Bers, Donald M

    2004-01-01

    Computer modeling of cardiac myocytes has flourished in recent years. Models have evolved from mathematical descriptions of ionic channels alone to more sophisticated formulations that include calcium transport mechanisms, ATP production and metabolic pathways. The increased complexity is fueled by the new data available in the field. The continuous production of experimental data has led to the evolution of increasingly refined descriptions of the phenomena by modelers. Integrating the numerous systems involved in cardiac myocyte homeostasis makes the use of computer models necessary due to the unreliability of intuitive approaches. However the complexity of the model should not imply a cumbersome operation of the program. As with any tool, computer models have to be easy to operate or their strength will be diminished and potential users will not benefit fully from them. The contribution of the computer modeler to their respective biological fields will be more successful and enduring if modelers devote sufficient time to implement their equations into a model with user-friendly characteristics. PMID:15142742

  7. 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

  8. Mechanically induced orientation of adult rat cardiac myocytes in vitro

    NASA Technical Reports Server (NTRS)

    Samuel, J.-L.; Vandenburgh, H. H.

    1990-01-01

    The present study describes the spatial orientation of a population of freshly isolated adult rat cardiac myocytes using a computerized mechanical cell stimulator device for tissue cultured cells. A continuous unidirectional stretch of the substratum at 60 to 400 microns/min for 120 to 30 min, respectively, during the cell attachment period in a serum-free medium was found to induce a significant threefold increase in the number of rod-shaped myocytes oriented parallel to the direction of movement. The myocytes orient less well with unidirectional substratum stretching after their adhesion to the substratum. Adult myocytes plated onto a substratum undergoing continuous 10-percent stretch-relaxation cycling show no significant change in the myocyte orientation or cytoskeletal organization. In addition to the type of mechanical activity, orientation of rod-shaped myocytes is dependent on the speed of the substratum, the final stretch amplitude, and the timing between initiation of substratum stretching and adhesion of myocytes to the substratum.

  9. 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

  10. Isolated Tricuspid Regurgitation: Initial Manifestation of Cardiac Amyloidosis

    PubMed Central

    Yoon, Dong Woog; Park, Byung-Jo; Kim, In Sook; Jeong, Dong Seop

    2015-01-01

    Amyloid deposits in the heart are not exceptional in systemic amyloidosis. The clinical manifestations of cardiac amyloidosis may include restrictive cardiomyopathy, characterized by progressive diastolic and eventually systolic bi-ventricular dysfunction; arrhythmia; and conduction defects. To the best of our knowledge, no previous cases of isolated tricuspid regurgitation as the initial manifestation of cardiac amyloidosis have been reported. We describe a rare case of cardiac amyloidosis that initially presented with severe tricuspid regurgitation in a 42-year-old woman who was successfully treated with tricuspid valve replacement. Unusual surgical findings prompted additional evaluation that established a diagnosis of plasma cell myeloma. PMID:26665112

  11. Isolation, culture, purification and ultrastructural investigation of cardiac telocytes

    PubMed Central

    Li, Yan-Yan; Zhang, Song; Li, Yi-Gang; Wang, Yan

    2016-01-01

    Telocytes (TCs), a novel type of stromal cells, are crucial to cardiac renovation and regeneration. To dissect the pathophysiological effects of cardiac TCs in heart disease, it is essential to develop an effective method to isolate, culture, purify and characterize these cells. In the present study, cardiac TCs were isolated from the hearts of rats by enzymatic digestion. Histology and CD34/PDGFRα expression by flow cytometric assay were used to characterize the cultured cardiac TCs, which were purified by flow cytometric sorting and confirmed by immunofluorescence and electron microscopy. Typical TCs were observed in primary culture, with these exhibiting typical fusiform cell bodies with long moniliform telopodes. Based on flow cytometric sorting with antibodies to CD34 and PDGFRα, there was a substantial increase in the purity of cardiac TCs. Furthermore, immunofluorescence demonstrated that almost all the sorted TCs expressed vimentin, a marker of TCs. Moreover, electron micrographs showed typical TCs based on their ultrastructural features. Using this method, we developed a reproducible protocol for the isolation and purification of cardiac TCs from rat hearts, which yielded TCs with typical characteristics. PMID:27314536

  12. Isolation, culture, purification and ultrastructural investigation of cardiac telocytes.

    PubMed

    Li, Yan-Yan; Zhang, Song; Li, Yi-Gang; Wang, Yan

    2016-08-01

    Telocytes (TCs), a novel type of stromal cells, are crucial to cardiac renovation and regeneration. To dissect the pathophysiological effects of cardiac TCs in heart disease, it is essential to develop an effective method to isolate, culture, purify and characterize these cells. In the present study, cardiac TCs were isolated from the hearts of rats by enzymatic digestion. Histology and CD34/PDGFRα expression by flow cytometric assay were used to characterize the cultured cardiac TCs, which were purified by flow cytometric sorting and confirmed by immunofluorescence and electron microscopy. Typical TCs were observed in primary culture, with these exhibiting typical fusiform cell bodies with long moniliform telopodes. Based on flow cytometric sorting with antibodies to CD34 and PDGFRα, there was a substantial increase in the purity of cardiac TCs. Furthermore, immunofluorescence demonstrated that almost all the sorted TCs expressed vimentin, a marker of TCs. Moreover, electron micrographs showed typical TCs based on their ultrastructural features. Using this method, we developed a reproducible protocol for the isolation and purification of cardiac TCs from rat hearts, which yielded TCs with typical characteristics. PMID:27314536

  13. Case report: isolated cardiac amyloidosis: an enigma unravelled.

    PubMed

    Khalid, Umair; Awar, Omar; Verstovsek, Gordana; Cheong, Benjamin; Yellapragada, Sarvari Venkata; Jneid, Hani; Deswal, Anita; Virani, Salim S

    2015-01-01

    Amyloidosis is a rare, multisystem disease characterized by deposition of fibrils in extracellular tissue involving kidney, liver, heart, autonomic nervous system, and several other organs. This report discusses a 75-year-old male who presented with worsening dyspnea on exertion, orthopnea, and lower-extremity edema. On physical exam, he had elevated jugular venous pressure and lower-extremity edema. Electrocardiogram depicted low voltage in limb leads and a prolonged PR interval. Echocardiogram revealed left ventricular hypertrophy, severe biatrial dilatation, and restrictive filling physiology. Coronary angiography showed absence of significant epicardial coronary artery disease. On right heart catheterization, a "dip-and-plateau sign" was noted on right ventricular pressure tracings. A diagnosis of cardiac amyloidosis was considered, but a complete hematology work-up for systemic amyloidosis was negative. Cardiac magnetic resonance imaging was pursued, showing delayed gadolinium enhancement, and this ultimately led to the myocardial biopsy confirming the diagnosis of isolated cardiac amyloidosis. Further genetic analyses confirmed isolated cardiac amyloid caused by mutant transthyretin protein (Val-122-Ile). Isolated cardiac amyloidosis is an extremely rare entity, and diagnosis may be difficult despite the use of multimodality imaging. If the index of suspicion is high, then myocardial biopsy should be considered. PMID:25793032

  14. 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

  15. Venoarterial Extracorporeal Membrane Oxygenation in Adults With Cardiac Arrest.

    PubMed

    Patel, Jignesh K; Schoenfeld, Elinor; Parnia, Sam; Singer, Adam J; Edelman, Norman

    2016-07-01

    Cardiac arrest (CA) is a major cause of morbidity and mortality worldwide. Despite the use of conventional cardiopulmonary resuscitation (CPR), rates of return of spontaneous circulation and survival with minimal neurologic impairment remain low. Utilization of venoarterial extracorporeal membrane oxygenation (ECMO) for CA in adults is steadily increasing. Propensity-matched cohort studies have reported outcomes associated with ECMO use to be superior to that of conventional CPR alone in in-hospital patients with CA. In this review, we discuss the mechanism, indications, complications, and evidence for ECMO in CA in adults. PMID:25922385

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

    PubMed Central

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

    2006-01-01

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

  17. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells.

    PubMed

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; MacLellan, W Robb; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  18. Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

    PubMed Central

    Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

    2015-01-01

    It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

  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. Isolation Syndrome after Cardiac Arrest and Therapeutic Hypothermia

    PubMed Central

    Forgacs, Peter B.; Fridman, Esteban A.; Goldfine, Andrew M.; Schiff, Nicholas D.

    2016-01-01

    Here, we present the first description of an isolation syndrome in a patient who suffered prolonged cardiac arrest and underwent a standard therapeutic hypothermia protocol. Two years after the arrest, the patient demonstrated no motor responses to commands, communication capabilities, or visual tracking at the bedside. However, resting neuronal metabolism and electrical activity across the entire anterior forebrain was found to be normal despite severe structural injuries to primary motor, parietal, and occipital cortices. In addition, using quantitative electroencephalography, the patient showed evidence for willful modulation of brain activity in response to auditory commands revealing covert conscious awareness. A possible explanation for this striking dissociation in this patient is that altered neuronal recovery patterns following therapeutic hypothermia may lead to a disproportionate preservation of anterior forebrain cortico-thalamic circuits even in the setting of severe hypoxic injury to other brain areas. Compared to recent reports of other severely brain-injured subjects with such dissociation of clinically observable (overt) and covert behaviors, we propose that this case represents a potentially generalizable mechanism producing an isolation syndrome of blindness, motor paralysis, and retained cognition as a sequela of cardiac arrest and therapeutic hypothermia. Our findings further support that highly-preserved anterior cortico-thalamic integrity is associated with the presence of conscious awareness independent from the degree of injury to other brain areas. PMID:27375420

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

    PubMed Central

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

    2010-01-01

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

  2. 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

  3. Ketamine in adult cardiac surgery and the cardiac surgery Intensive Care Unit: An evidence-based clinical review

    PubMed Central

    Mazzeffi, Michael; Johnson, Kyle; Paciullo, Christopher

    2015-01-01

    Ketamine is a unique anesthetic drug that provides analgesia, hypnosis, and amnesia with minimal respiratory and cardiovascular depression. Because of its sympathomimetic properties it would seem to be an excellent choice for patients with depressed ventricular function in cardiac surgery. However, its use has not gained widespread acceptance in adult cardiac surgery patients, perhaps due to its perceived negative psychotropic effects. Despite this limitation, it is receiving renewed interest in the United States as a sedative and analgesic drug for critically ill-patients. In this manuscript, the authors provide an evidence-based clinical review of ketamine use in cardiac surgery patients for intensive care physicians, cardio-thoracic anesthesiologists, and cardio-thoracic surgeons. All MEDLINE indexed clinical trials performed during the last 20 years in adult cardiac surgery patients were included in the review. PMID:25849690

  4. Modelling diffusive O(2) supply to isolated preparations of mammalian skeletal and cardiac muscle.

    PubMed

    Barclay, C J

    2005-01-01

    The purpose of this study was to use A. V. Hill's equation describing diffusion of O(2) into cylindrical muscles to assess the adequacy of O(2) supply for commonly used isolated preparations of mammalian cardiac and skeletal muscles. The diffusion equation was solved numerically to give the maximum, steady state O(2) diffusion distances (i.e. the distance from the surface of the muscle to the radial location where P(O(2)) is 0) for both resting and contracting muscles and for a range of temperatures. Non-steady state solutions for the rest-to-work transition were also determined to estimate how long contractile activity could be continued before anoxia develops at the muscle centre. The influence on muscle oxygenation of myoglobin-facilitated O(2) diffusion was also assessed. The analysis was performed for typical sized, whole muscles from adult rats and mice, for frog sartorius muscle and for a range of temperatures. Muscle O(2) consumption rates were taken from the literature. The results indicated that (1) diffusive O(2) supply would be adequate to support resting metabolism of soleus and EDL muscles of rat and mouse but may not be adequate to support the transient high resting metabolic rate of papillary muscles shortly after dissection, (2) during steady contractile activity of soleus and EDL muscles, particularly those from the rat, over a reasonable range of duty cycles, adequate O(2) supply could only be ensured if the radii of preparations was substantially smaller than those of whole muscles and (3) for cardiac muscles, diffusive O(2) supply could only support steady-state metabolism at twitch frequencies <1 Hz for whole papillary muscles from rat and <3 Hz for those from mouse. Reducing experimental temperature markedly enhances O(2) supply to skeletal, but not cardiac, muscle. O(2) supply from myoglobin had only minimal effects on oxygenation under typical isolated muscle conditions. PMID:16322911

  5. Fetal-Adult Cardiac Transcriptome Analysis in Rats with Contrasting Left Ventricular Mass Reveals New Candidates for Cardiac Hypertrophy

    PubMed Central

    Grabowski, Katja; Riemenschneider, Mona; Schulte, Leonard; Witten, Anika; Schulz, Angela; Stoll, Monika; Kreutz, Reinhold

    2015-01-01

    Reactivation of fetal gene expression patterns has been implicated in common cardiac diseases in adult life including left ventricular (LV) hypertrophy (LVH) in arterial hypertension. Thus, increased wall stress and neurohumoral activation are discussed to induce the return to expression of fetal genes after birth in LVH. We therefore aimed to identify novel potential candidates for LVH by analyzing fetal-adult cardiac gene expression in a genetic rat model of hypertension, i.e. the stroke-prone spontaneously hypertensive rat (SHRSP). To this end we performed genome-wide transcriptome analysis in SHRSP to identify differences in expression patterns between day 20 of fetal development (E20) and adult animals in week 14 in comparison to a normotensive rat strain with contrasting low LV mass, i.e. Fischer (F344). 15232 probes were detected as expressed in LV tissue obtained from rats at E20 and week 14 (p < 0.05) and subsequently screened for differential expression. We identified 24 genes with SHRSP specific up-regulation and 21 genes with down-regulation as compared to F344. Further bioinformatic analysis presented Efcab6 as a new candidate for LVH that showed only in the hypertensive SHRSP rat differential expression during development (logFC = 2.41, p < 0.001) and was significantly higher expressed in adult SHRSP rats compared with adult F344 (+ 76%) and adult normotensive Wistar-Kyoto rats (+ 82%). Thus, it represents an interesting new target for further functional analyses and the elucidation of mechanisms leading to LVH. Here we report a new approach to identify candidate genes for cardiac hypertrophy by combining the analysis of gene expression differences between strains with a contrasting cardiac phenotype with a comparison of fetal-adult cardiac expression patterns. PMID:25646840

  6. The uptake of cardiac glycosides in relation to their actions in isolated cardiac muscle

    PubMed Central

    Godfraind, T.; Lesne, M.

    1972-01-01

    1. The uptake of 3H-digitoxin, 3H-ouabain and 3H-dihydro-ouabain by isolated guinea-pig atria has been studied and compared with the inhibition of the sodium pump and with the inotropic effect. 2. Analysis of the curve relating the uptake of digitoxin and ouabain at equilibrium to the bath concentration enabled a non-saturable and a saturable binding site to be distinguished. 3. The uptake of inactive doses of dihydro-ouabain was only by a non-saturable mechanism. 4. The uptake of labelled digitoxin and ouabain was reduced in the presence of another glycoside. The amount of bound glycoside was nearly equivalent to the estimated non-saturable uptake. 5. The uptake was reduced at 4° C to the clearance of the non-saturable site. 6. ED50 of digitoxin and of ouabain for inhibition of the sodium pump were measured and compared to the ED50 for inotropic effect and to the concentrations producing a half-saturation of the saturable binding site. 7. It is concluded that binding to the saturable site may be responsible for the cardiac actions of the glycosides. PMID:4656610

  7. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Outcomes and Quality.

    PubMed

    D'Agostino, Richard S; Jacobs, Jeffrey P; Badhwar, Vinay; Paone, Gaetano; Rankin, J Scott; Han, Jane M; McDonald, Donna; Shahian, David M

    2016-01-01

    The Society of Thoracic Surgeons Adult Cardiac Database is one of the longest-standing, largest, and most highly regarded clinical data registries in health care. It serves as the foundation for all quality measurement and improvement activities of The Society of Thoracic Surgeons. This report summarizes current aggregate national outcomes in adult cardiac surgery and reviews database-related activities in the areas of quality measurement and performance improvement. PMID:26616408

  8. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    PubMed Central

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  9. Down-Regulation of Replication Factor C-40 (RFC40) Causes Chromosomal Missegregation in Neonatal and Hypertrophic Adult Rat Cardiac Myocytes

    PubMed Central

    Oka, Masahiko; Ochi, Rikuo; Jong, Chian Ju; Gebb, Sarah; Benjamin, John; Schaffer, Stephen; Hobart, Holly H.; Downey, James; McMurtry, Ivan; Gupte, Rakhee

    2012-01-01

    Background Adult mammalian cardiac myocytes are generally assumed to be terminally differentiated; nonetheless, a small fraction of cardiac myocytes have been shown to replicate during ventricular remodeling. However, the expression of Replication Factor C (RFC; RFC140/40/38/37/36) and DNA polymerase δ (Pol δ) proteins, which are required for DNA synthesis and cell proliferation, in the adult normal and hypertrophied hearts has been rarely studied. Methods We performed qRT-PCR and Western blot analysis to determine the levels of RFC and Pol δ message and proteins in the adult normal cardiac myocytes and cardiac fibroblasts, as well as in adult normal and pulmonary arterial hypertension induced right ventricular hypertrophied hearts. Immunohistochemical analyses were performed to determine the localization of the re-expressed DNA replication and cell cycle proteins in adult normal (control) and hypertrophied right ventricle. We determined right ventricular cardiac myocyte polyploidy and chromosomal missegregation/aneuploidy using Fluorescent in situ hybridization (FISH) for rat chromosome 12. Results RFC40-mRNA and protein was undetectable, whereas Pol δ message was detectable in the cardiac myocytes isolated from control adult hearts. Although RFC40 and Pol δ message and protein significantly increased in hypertrophied hearts as compared to the control hearts; however, this increase was marginal as compared to the fetal hearts. Immunohistochemical analyses revealed that in addition to RFC40, proliferative and mitotic markers such as cyclin A, phospho-Aurora A/B/C kinase and phospho-histone 3 were also re-expressed/up-regulated simultaneously in the cardiac myocytes. Interestingly, FISH analyses demonstrated cardiac myocytes polyploidy and chromosomal missegregation/aneuploidy in these hearts. Knock-down of endogenous RFC40 caused chromosomal missegregation/aneuploidy and decrease in the rat neonatal cardiac myocyte numbers. Conclusion Our novel findings

  10. Older Adults in Cardiac Rehabilitation: A New Strategy for Enhancing Physical Function.

    ERIC Educational Resources Information Center

    Rejeski, W. Jack; Foy, Capri Gabrielle; Brawley, Lawrence R.; Brubaker, Peter H.; Focht, Brian C.; Norris, James L., III; Smith, Marci L.

    2002-01-01

    Contrasted the effect of a group-mediated cognitive- behavioral intervention (GMCB) versus traditional cardiac rehabilitation (CRP) upon changes in objective and self-reported physical function of older adults after 3 months of exercise therapy. Both groups improved significantly. Adults with lower function at the outset of the intervention…

  11. Alpha actin isoforms expression in human and rat adult cardiac conduction system.

    PubMed

    Orlandi, Augusto; Hao, Hiroyuki; Ferlosio, Amedeo; Clément, Sophie; Hirota, Seiichi; Spagnoli, Luigi Giusto; Gabbiani, Giulio; Chaponnier, Christine

    2009-04-01

    In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of alpha-skeletal (alpha-SKA), alpha-cardiac (alpha-CA), alpha-smooth muscle (alpha-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of alpha-SMA, alpha-CA, calponin and caldesmon, whereas alpha-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of alpha-SMA and alpha-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were alpha-SMA, calponin, caldesmon and vimentin negative, and alpha-CA and alpha-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial alpha-SMA positive cardiomyocytes co-expressing alpha-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. PMID:19281784

  12. Cardiac issues in adults with the mucopolysaccharidoses: current knowledge and emerging needs.

    PubMed

    Braunlin, Elizabeth; Wang, Raymond

    2016-08-15

    The growing availability of innovative treatments for rare genetic diseases with a cardiac component-such as the mucopolysaccharidoses (MPSs)-has changed these syndromes from 'back of the textbook' curiosities of childhood to chronic, but rare, adult cardiac conditions that require both centres of expertise and knowledgeable subspecialists. The MPSs are inherited progressive lysosomal storage diseases, occurring in about 1:25 000 births and resulting from absence of functional hydrolases responsible for the degradation of glycosaminoglycans, naturally occurring complex sugars ubiquitous throughout the body. In the heart, accumulation of glycosaminoglycans occurs within the cardiac valves, the epicardial coronary arteries, the myocytes and cardiac interstitium and the walls of the great vessels. As a consequence, cardiac valve regurgitation and stenosis, diffuse coronary artery stenosis, myocardial dysfunction and aortic root dilation often occur. Haematopoietic cell transplantation and enzyme replacement therapy have changed the previously lethal natural history of the MPSs to one of survival well into adulthood. Despite this improved lifespan, the left-sided cardiac valves continue to show progressive functional involvement and cardiac valve replacement is not uncommon, especially in adults. The risk of any intervention is increased in these patients because of the systemic effects of the disease on the respiratory system and cervical cord. Our current understanding of other cardiac issues in adults with the MPSs, especially with the coronary circulation and myocardium, is meagre and more needs to be known to effectively care for this emerging population of adults. Incorporation of the MPSs, as well as other now-treatable rare diseases, into the educational curriculum of current and future adult subspecialists is an important next step. PMID:27102649

  13. NH2-terminal truncations of cardiac troponin I and cardiac troponin T produce distinct effects on contractility and calcium homeostasis in adult cardiomyocytes

    PubMed Central

    Wei, Hongguang

    2014-01-01

    Cardiac troponin I (TnI) has an NH2-terminal extension that is an adult heart-specific regulatory structure. Restrictive proteolytic truncation of the NH2-terminal extension of cardiac TnI occurs in normal hearts and is upregulated in cardiac adaptation to hemodynamic stress or β-adrenergic deficiency. NH2-terminal truncated cardiac TnI (cTnI-ND) alters the conformation of the core structure of cardiac TnI similarly to that produced by PKA phosphorylation of Ser23/24 in the NH2-terminal extension. At organ level, cTnI-ND enhances ventricular diastolic function. The NH2-terminal region of cardiac troponin T (TnT) is another regulatory structure that can be selectively cleaved via restrictive proteolysis. Structural variations in the NH2-terminal region of TnT also alter the molecular conformation and function. Transgenic mouse hearts expressing NH2-terminal truncated cardiac TnT (cTnT-ND) showed slower contractile velocity to prolong ventricular rapid-ejection time, resulting in higher stroke volume. Our present study compared the effects of cTnI-ND and cTnT-ND in cardiomyocytes isolated from transgenic mice on cellular morphology, contractility, and calcium kinetics. Resting cTnI-ND, but not cTnT-ND, cardiomyocytes had shorter length than wild-type cells with no change in sarcomere length. cTnI-ND, but not cTnT-ND, cardiomyocytes produced higher contractile amplitude and faster shortening and relengthening velocities in the absence of external load than wild-type controls. Although the baseline and peak levels of cytosolic Ca2+ were not changed, Ca2+ resequestration was faster in both cTnI-ND and cTnT-ND cardiomyocytes than in wild-type control. The distinct effects of cTnI-ND and cTnT-ND demonstrate their roles in selectively modulating diastolic or systolic functions of the heart. PMID:25518962

  14. Isolated heart transplantation for familial transthyretin (TTR) V122I cardiac amyloidosis.

    PubMed

    Thenappan, Thenappan; Fedson, Savitri; Rich, Jonathan; Murks, Catherine; Husain, Aliya; Pogoriler, Jennifer; Anderson, Allen S

    2014-06-01

    Transthyretin (TTR) cardiac amyloidosis is characterized by deposition of either mutant or wild type TTR amyloid protein in the myocardium ultimately leading to progressive cardiomyopathy and heart failure. The most common TTR gene mutation that leads to TTR cardiac amyloidosis is the valine-to-isoleucine substitution at position 122 (V122I or Ile122). Currently, the only definitive treatment suggested for mutant TTR cardiac amyloidosis is the combined or sequential liver-heart transplantation in eligible patients, since liver is the source of TTR production. Here, we report a case of heterozygous Val122L mutated TTR-related cardiac amyloidosis treated with isolated heart transplantation with no recurrence of amyloid in the cardiac allograft and no systemic abnormalities 5 years after heart transplantation. Abbreviations MMF mycophenolate mofetil NYHA New York Heart Association TTR transthyretin VE minute ventilation. PMID:24818650

  15. Provision of Transition Education and Referral Patterns from Pediatric Cardiology to Adult Cardiac Care.

    PubMed

    Harbison, Anna L; Grady, Stafford; Chi, Kevin; Fernandes, Susan M

    2016-02-01

    ACC/AHA guidelines recommend a structured preparation for and transfer to adult-oriented cardiac care for adult survivors of pediatric onset heart disease (POHD). Given this, we sought to describe the transition and transfer practices for a cohort of young adults with POHD and to determine factors associated with successful transfer to adult-oriented cardiac care. We performed a single-center, retrospective chart review on patients ≥18 years of age, with POHD likely to require lifelong cardiac care, who were seen in outpatient pediatric cardiology (PC) between 2008 and 2011. Successful transfer was defined as the subsequent attendance at adult cardiology (AC) within 2 years of PC visit. We identified 118 patients who met study criteria. Mean age 22.4 ± 2.0 years, 59 % male, 64 % white and 40 % Hispanic. Mean transition education topics noted was 3.3 ± 1.8 out of 20 and covered the underlying cardiac disease (89 %), follow-up and current medications (56 %) and exercise limitations (34 %). Recommendations for follow-up were AC (57 %) and PC (33 %). Of those told to transfer to AC, 79 % successfully transferred. Characteristics of successful transfer included: prior cardiac surgery (p = 0.008), cardiac medication use (p = 0.006) and frequency of follow-up ≤1 year (p = 0.037). One-quarter of all subjects did not follow-up within at least 2 years. Despite published guidelines, transition education appears lacking and the approach to transfer to adult cardiac care is not consistent. Given the increased risk of morbidity and mortality in this patient population, standardization of transition education and transfer processes appear warranted. PMID:26385471

  16. Moderate Physical Activity in Healthy Adults Is Associated With Cardiac Remodeling

    PubMed Central

    Dawes, Timothy J.W.; Corden, Ben; Cotter, Sorcha; de Marvao, Antonio; Walsh, Roddy; Ware, James S.; Cook, Stuart A.

    2016-01-01

    Background— Cardiac mass and volumes are often elevated in athletes, but it is not known whether moderate physical activity is also associated with cardiac dilatation and hypertrophy in a healthy adult population. Methods and Results— In total, 1096 adults (54% female, median age 39 years) without cardiovascular disease or cardiomyopathy-associated genetic variants underwent cardiac magnetic resonance imaging to determine biventricular volumes and function. Physical activity was assessed using a validated activity questionnaire. The relationship between cardiac parameters and activity was assessed using multiple linear regression adjusting for age, sex, race, and systolic blood pressure. Logistic regression was performed to determine the effect of activity on the likelihood of subjects having cardiac dilatation or hypertrophy according to standard cardiac magnetic resonance normal ranges. Increasing physical activity was associated with greater left ventricular (LV) mass (β=0.23; P<0.0001) and elevated LV and right ventricular volumes (LV: β=0.26, P<0.0001; right ventricular: β=0.26, P<0.0001). Physical activity had a larger effect on cardiac parameters than systolic blood pressure (0.06≤β≤0.21) and a similar effect to age (−0.20≤β≤−0.31). Increasing physical activity was a risk factor for meeting imaging criteria for LV hypertrophy (adjusted odds ratio 2.1; P<0.0001), LV dilatation (adjusted odds ratio 2.2; P<0.0001), and right ventricular dilatation (adjusted odds ratio 2.2; P<0.0001). Conclusions— Exercise-related cardiac remodeling is not confined to athletes, and there is a risk of overdiagnosing cardiac dilatation or hypertrophy in a proportion of active, healthy adults. PMID:27502059

  17. Impact of hepatic cirrhosis on outcome in adult cardiac surgery.

    PubMed

    Dimarakis, Ioannis; Grant, Stuart; Corless, Rebecca; Velissaris, Theodore; Prince, Martin; Bridgewater, Ben; Asimakopoulos, George

    2015-02-01

    Increasing prevalence of hepatic disease is likely to translate in a growing number of patients with significant hepatic disease requiring cardiac surgery. Available cardiac risk stratification models do not address the risk associated with hepatic disease. However, weighted mean mortality rates based on previous studies of cardiac surgery in patients with hepatic disease demonstrate operative mortality rates that range from 9.88% (standard deviation [SD] 9.69) for patients in Child-Turcotte-Pugh (CTP) class A cirrhosis to 69.23% (SD 28.55) for patients with CTP class C cirrhosis. This review comprehensively appraises the pathophysiology of hepatic disease, reported clinical outcomes and considerations for risk stratification. PMID:25291160

  18. Use of del Nido Cardioplegia for Adult Cardiac Surgery at the Cleveland Clinic: Perfusion Implications

    PubMed Central

    Kim, Kuna; Ball, Clifford; Grady, Patrick; Mick, Stephanie

    2014-01-01

    Abstract: Cardiac arrest by cardioplegia provides a reproducible and safe method to induce and maintain electromechanical cardiac quiescence. Techniques of intraoperative myocardial protection are constantly evolving. For the past three decades, modified Buckberg cardioplegia solution has been used for adult cardiac surgery at the Cleveland Clinic. This formulation serves as the crystalloid component, which is delivered 4:1 with oxygenated patient’s blood to crystalloid. Meanwhile, our use of the del Nido cardioplegia solution in adult patients, heretofore primarily used in pediatric cardiac surgical centers, has been increasing over the past several years. Single-dose, cold blood del Nido cardioplegia can be delivered antegrade if the duration of the operation will be limited and if there is no significant coronary artery disease or aortic insufficiency that would limit the distribution of cardioplegia. The addition of del Nido cardioplegia to our cardioplegia armamentarium allows us to customize our myocardial protection strategies for different surgical needs. This article aims to provide information on technical aspects of del Nido cardioplegia in adult cardiac surgery and its use at the Cleveland Clinic in the adult surgical population. PMID:26357803

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

    PubMed Central

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

    2014-01-01

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

  20. Cardiac-Specific Disruption of GH Receptor Alters Glucose Homeostasis While Maintaining Normal Cardiac Performance in Adult Male Mice.

    PubMed

    Jara, Adam; Liu, Xingbo; Sim, Don; Benner, Chance M; Duran-Ortiz, Silvana; Qian, Yanrong; List, Edward O; Berryman, Darlene E; Kim, Jason K; Kopchick, John J

    2016-05-01

    GH is considered necessary for the proper development and maintenance of several tissues, including the heart. Studies conducted in both GH receptor null and bovine GH transgenic mice have demonstrated specific cardiac structural and functional changes. In each of these mouse lines, however, GH-induced signaling is altered systemically, being decreased in GH receptor null mice and increased in bovine GH transgenic mice. Therefore, to clarify the direct effects GH has on cardiac tissue, we developed a tamoxifen-inducible, cardiac-specific GHR disrupted (iC-GHRKO) mouse line. Cardiac GH receptor was disrupted in 4-month-old iC-GHRKO mice to avoid developmental effects due to perinatal GHR gene disruption. Surprisingly, iC-GHRKO mice showed no difference vs controls in baseline or postdobutamine stress test echocardiography measurements, nor did iC-GHRKO mice show differences in longitudinal systolic blood pressure measurements. Interestingly, iC-GHRKO mice had decreased fat mass and improved insulin sensitivity at 6.5 months of age. By 12.5 months of age, however, iC-GHRKO mice no longer had significant decreases in fat mass and had developed glucose intolerance and insulin resistance. Furthermore, investigation via immunoblot analysis demonstrated that iC-GHRKO mice had appreciably decreased insulin stimulated Akt phosphorylation, specifically in heart and liver, but not in epididymal white adipose tissue. These changes were accompanied by a decrease in circulating IGF-1 levels in 12.5-month-old iC-GHRKO mice. These data indicate that whereas the disruption of cardiomyocyte GH-induced signaling in adult mice does not affect cardiac function, it does play a role in systemic glucose homeostasis, in part through modulation of circulating IGF-1. PMID:27035649

  1. Gender comparison of contractile performance and beta-adrenergic response in isolated rat cardiac trabeculae.

    PubMed

    Monasky, Michelle M; Varian, Kenneth D; Janssen, Paul M L

    2008-03-01

    It is known that gender can affect susceptibility to development of various cardiomyopathies. However, it is unclear whether basic mechanical contractile function of the myocardium differs between genders, whether they respond differently to stressors, or both. To test for a possible gender factor, contractile parameters of healthy, isolated myocardium were investigated under near physiological conditions. Right ventricular ultra-thin trabeculae from young adult LBN-f1 rats were electrically stimulated to isometrically contract at 37 degrees C. No differences were found in developed force or kinetic parameters. In each muscle, the force-frequency relationship was measured at 4, 6, and 8 Hz, encompassing most of the in vivo range. Again, no differences were observed in force-frequency behavior; developed force rose from 21.6 +/- 4.0 at 4 Hz to 30.3 +/- 5.8 mN/mm(2) at 8 Hz in females and from 23.4 +/- 3.4 to 29.8 +/- 3.4 mN/mm(2 )in males. The response to beta-adrenergic stimulation was similar; at 1 microM isoproterenol, developed force increased to 34.5 +/- 6.2 mN/mm(2) in females and 32.3 +/- 3.2 mN/mm(2) in males (female vs. male, not significant). We conclude that basic mechanical performance of healthy isolated myocardium under physiological conditions is not different between males and females, and a different response to stress must underlie gender-based differences in cardiac performance. PMID:18030479

  2. Muscle-derived stem cells isolated as non-adherent population give rise to cardiac, skeletal muscle and neural lineages

    SciTech Connect

    Arsic, Nikola; Mamaeva, Daria; Lamb, Ned J.; Fernandez, Anne

    2008-04-01

    Stem cells with the ability to differentiate in specialized cell types can be extracted from a wide array of adult tissues including skeletal muscle. Here we have analyzed a population of cells isolated from skeletal muscle on the basis of their poor adherence on uncoated or collagen-coated dishes that show multi-lineage differentiation in vitro. When analysed under proliferative conditions, these cells express stem cell surface markers Sca-1 (65%) and Bcrp-1 (80%) but also MyoD (15%), Neuronal {beta} III-tubulin (25%), GFAP (30%) or Nkx2.5 (1%). Although capable of growing as non-attached spheres for months, when given an appropriate matrix, these cells adhere giving rise to skeletal muscle, neuronal and cardiac muscle cell lineages. A similar cell population could not be isolated from either bone marrow or cardiac tissue suggesting their specificity to skeletal muscle. When injected into damaged muscle, these non-adherent muscle-derived cells are retrieved expressing Pax7, in a sublaminar position characterizing satellite cells and participate in forming new myofibers. These data show that a non-adherent stem cell population can be specifically isolated and expanded from skeletal muscle and upon attachment to a matrix spontaneously differentiate into muscle, cardiac and neuronal lineages in vitro. Although competing with resident satellite cells, these cells are shown to significantly contribute to repair of injured muscle in vivo supporting that a similar muscle-derived non-adherent cell population from human muscle may be useful in treatment of neuromuscular disorders.

  3. Calsequestrins in skeletal and cardiac muscle from adult Danio rerio.

    PubMed

    Furlan, Sandra; Mosole, Simone; Murgia, Marta; Nagaraj, Nagarjuna; Argenton, Francesco; Volpe, Pompeo; Nori, Alessandra

    2016-04-01

    Calsequestrin (Casq) is a high capacity, low affinity Ca(2+)-binding protein, critical for Ca(2+)-buffering in cardiac and skeletal muscle sarcoplasmic reticulum. All vertebrates have multiple genes encoding for different Casq isoforms. Increasing interest has been focused on mammalian and human Casq genes since mutations of both cardiac (Casq2) and skeletal muscle (Casq1) isoforms cause different, and sometime severe, human pathologies. Danio rerio (zebrafish) is a powerful model for studying function and mutations of human proteins. In this work, expression, biochemical properties cellular and sub-cellular localization of D. rerio native Casq isoforms are investigated. By quantitative PCR, three mRNAs were detected in skeletal muscle and heart with different abundances. Three zebrafish Casqs: Casq1a, Casq1b and Casq2 were identified by mass spectrometry (Data are available via ProteomeXchange with identifier PXD002455). Skeletal and cardiac zebrafish calsequestrins share properties with mammalian Casq1 and Casq2. Skeletal Casqs were found primarily, but not exclusively, at the sarcomere Z-line level where terminal cisternae of sarcoplasmic reticulum are located. PMID:26585961

  4. Undernutrition during pregnancy in mice leads to dysfunctional cardiac muscle respiration in adult offspring

    PubMed Central

    Beauchamp, Brittany; Thrush, A. Brianne; Quizi, Jessica; Antoun, Ghadi; McIntosh, Nathan; Al-Dirbashi, Osama Y.; Patti, Mary-Elizabeth; Harper, Mary-Ellen

    2015-01-01

    Intrauterine growth restriction (IUGR) is associated with an increased risk of developing obesity, insulin resistance and cardiovascular disease. However, its effect on energetics in heart remains unknown. In the present study, we examined respiration in cardiac muscle and liver from adult mice that were undernourished in utero. We report that in utero undernutrition is associated with impaired cardiac muscle energetics, including decreased fatty acid oxidative capacity, decreased maximum oxidative phosphorylation rate and decreased proton leak respiration. No differences in oxidative characteristics were detected in liver. We also measured plasma acylcarnitine levels and found that short-chain acylcarnitines are increased with in utero undernutrition. Results reveal the negative impact of suboptimal maternal nutrition on adult offspring cardiac energy metabolism, which may have life-long implications for cardiovascular function and disease risk. PMID:26182362

  5. Cardiac Autonomic Function during Submaximal Treadmill Exercise in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Mendonca, Goncalo V.; Pereira, Fernando D.; Fernhall, Bo

    2011-01-01

    This study determined whether the cardiac autonomic function of adults with Down syndrome (DS) differs from that of nondisabled persons during submaximal dynamic exercise. Thirteen participants with DS and 12 nondisabled individuals performed maximal and submaximal treadmill tests with metabolic and heart rate (HR) measurements. Spectral analysis…

  6. Determinants of HIV-related cardiac disease among adults in north central Nigeria

    PubMed Central

    Isiguzo, Godsent; Okeahialam, Basil; Danbauchi, Solomon; Odili, Augustin; Iroezindu, Michael

    2013-01-01

    Objective The aim of the present study was to evaluate the determinants of HIV-related cardiac disease (HRCD) among adults in north central Nigeria. This was a hospital-based cross-sectional study recruiting patients who were HIV positive attending the HIV clinic at Jos University teaching Hospital, Nigeria. Methods A total of 200 adults who were HIV positive and aged ≥18 years were consecutively recruited. All patients were administered a questionnaire and underwent clinical examination, laboratory investigation for haemoglobin estimation, CD4 cell count, viral load, serum lipid profile, hepatitis B surface antigen, anti-hepatitis C virus antibody, electrocardiogram and two-dimensional echocardiography Doppler studies. The outcome measure was echocardiography-defined cardiac disease, such as systolic dysfunction, diastolic dysfunction, isolated left ventricular dilatation, right ventricular dysfunction or pulmonary hypertension. Results The mean age of the study population was 38±9 years. The majority (71%) were women and were on average younger than the men (36±8 years vs 47±9 years, p<0.0002). Highly active anti-retroviral therapy (HAART) use was seen in 84.4% of subjects. The median CD4 cell count for the study population was 358 cells/µL; the count was 459 (95% CI 321 to 550) cells/µL for subjects without HRCD and 193 (95% CI 126 to 357) cells/µL for subjects with HRCD (p<0.001). HAART-naive subjects with HRCD had a mean CD4 cell count of 121 cells/µL vs 200 cells/µL for those on HAART (p<0.01). CD4 cell count (OR = 0.25, 95% CI 0.15 to 0.45) and duration of diagnosis (OR=3.88, 95% CI 1.20 to 13.71) were the significant determinants of HRCD on multivariate analysis. Conclusions Duration of HIV diagnosis and degree of immunosuppression were the significant determinants of HRCD. There is therefore a need to reduce cardiovascular morbidity in patients infected with HIV through early diagnosis/sustained use of HAART, early screening for HRCD

  7. Zebrafish Cardiac Muscle Thick Filaments: Isolation Technique and Three-Dimensional Structure

    PubMed Central

    González-Solá, Maryví; AL-Khayat, Hind A.; Behra, Martine; Kensler, Robert W.

    2014-01-01

    To understand how mutations in thick filament proteins such as cardiac myosin binding protein-C or titin, cause familial hypertrophic cardiomyopathies, it is important to determine the structure of the cardiac thick filament. Techniques for the genetic manipulation of the zebrafish are well established and it has become a major model for the study of the cardiovascular system. Our goal is to develop zebrafish as an alternative system to the mammalian heart model for the study of the structure of the cardiac thick filaments and the proteins that form it. We have successfully isolated thick filaments from zebrafish cardiac muscle, using a procedure similar to those for mammalian heart, and analyzed their structure by negative-staining and electron microscopy. The isolated filaments appear well ordered with the characteristic 42.9 nm quasi-helical repeat of the myosin heads expected from x-ray diffraction. We have performed single particle image analysis on the collected electron microscopy images for the C-zone region of these filaments and obtained a three-dimensional reconstruction at 3.5 nm resolution. This reconstruction reveals structure similar to the mammalian thick filament, and demonstrates that zebrafish may provide a useful model for the study of the changes in the cardiac thick filament associated with disease processes. PMID:24739166

  8. Perioperative Hemoglobin Trajectory in Adult Cardiac Surgical Patients

    PubMed Central

    Scott, David A.; Tung, Hon-Ming Andrew; Slater, Reuben

    2015-01-01

    Abstract: Preoperative anemia and nadir hemoglobin (Hb) during cardiopulmonary bypass (CPB) have been identified as significant risk factors for blood transfusion during cardiac surgery. The aim of this study was to confirm the association between preoperative anemia, perioperative fluid management, and blood transfusion. In addition, the proportion of elective cardiac surgery patients presenting for surgery with anemia was identified to examine whether the opportunity exists for timely diagnosis and intervention. Data from referral until hospital discharge were comprehensively reviewed over a 12-month period for all nonemergency cardiac surgical patients operated on in our institution. Of the 342 patients identified, elective cases were referred a median of 35 days before preoperative clinic and operated on a median of 14 days subsequently. Subacute cases had a median of 3 days from referral to surgery. As per the World Health Organization (WHO) criteria for anemia, 24.2% of elective and 29.6% of subacute patients were anemic. Blood transfusion was administered to 46.2% of patients during their admission. Transfusion was more likely in patients who were female (odds ratio [OR]: 2.45, 95%confidence interval [CI]: 1.28–4.70), had a low body mass index (BMI) (OR: .89, 95% CI: .84–.94), preoperative anemia (OR: 5.15, 95% CI: 2.59–10.24), or renal impairment (OR: 5.44, 95% CI: 2.42–12.22). Hemodilution minimization strategies reduced the Hb fall during CPB, but not transfusion rates. This study identifies a high prevalence of preoperative anemia with sufficient time for elective referrals to undergo appropriate diagnosis and interventions. It also confirms that low red cell mass (anemia and low BMI) and renal impairment are predictors of perioperative blood transfusion. Perfusion strategies to reduce hemodilution are effective at minimizing the intraoperative fall in Hb concentration but did not influence transfusion rate. PMID:26543251

  9. Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation.

    PubMed

    Epelman, Slava; Lavine, Kory J; Beaudin, Anna E; Sojka, Dorothy K; Carrero, Javier A; Calderon, Boris; Brija, Thaddeus; Gautier, Emmanuel L; Ivanov, Stoyan; Satpathy, Ansuman T; Schilling, Joel D; Schwendener, Reto; Sergin, Ismail; Razani, Babak; Forsberg, E Camilla; Yokoyama, Wayne M; Unanue, Emil R; Colonna, Marco; Randolph, Gwendalyn J; Mann, Douglas L

    2014-01-16

    Cardiac macrophages are crucial for tissue repair after cardiac injury but are not well characterized. Here we identify four populations of cardiac macrophages. At steady state, resident macrophages were primarily maintained through local proliferation. However, after macrophage depletion or during cardiac inflammation, Ly6c(hi) monocytes contributed to all four macrophage populations, whereas resident macrophages also expanded numerically through proliferation. Genetic fate mapping revealed that yolk-sac and fetal monocyte progenitors gave rise to the majority of cardiac macrophages, and the heart was among a minority of organs in which substantial numbers of yolk-sac macrophages persisted in adulthood. CCR2 expression and dependence distinguished cardiac macrophages of adult monocyte versus embryonic origin. Transcriptional and functional data revealed that monocyte-derived macrophages coordinate cardiac inflammation, while playing redundant but lesser roles in antigen sampling and efferocytosis. These data highlight the presence of multiple cardiac macrophage subsets, with different functions, origins, and strategies to regulate compartment size. PMID:24439267

  10. A mouse model for adult cardiac-specific gene deletion with CRISPR/Cas9.

    PubMed

    Carroll, Kelli J; Makarewich, Catherine A; McAnally, John; Anderson, Douglas M; Zentilin, Lorena; Liu, Ning; Giacca, Mauro; Bassel-Duby, Rhonda; Olson, Eric N

    2016-01-12

    Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)9 genomic editing has revolutionized the generation of mutant animals by simplifying the creation of null alleles in virtually any organism. However, most current approaches with this method require zygote injection, making it difficult to assess the adult, tissue-specific functions of genes that are widely expressed or which cause embryonic lethality when mutated. Here, we describe the generation of cardiac-specific Cas9 transgenic mice, which express high levels of Cas9 in the heart, but display no overt defects. In proof-of-concept experiments, we used Adeno-Associated Virus 9 (AAV9) to deliver single-guide RNA (sgRNA) that targets the Myh6 locus exclusively in cardiomyocytes. Intraperitoneal injection of postnatal cardiac-Cas9 transgenic mice with AAV9 encoding sgRNA against Myh6 resulted in robust editing of the Myh6 locus. These mice displayed severe cardiomyopathy and loss of cardiac function, with elevation of several markers of heart failure, confirming the effectiveness of this method of adult cardiac gene deletion. Mice with cardiac-specific expression of Cas9 provide a tool that will allow rapid and accurate deletion of genes following a single injection of AAV9-sgRNAs, thereby circumventing embryonic lethality. This method will be useful for disease modeling and provides a means of rapidly editing genes of interest in the heart. PMID:26719419

  11. Neurological symptoms and cerebrovascular accidents: manifestations of left-sided cardiac tumours in adults

    PubMed Central

    Said, S.A.M.; Droste, H.T.; Baart, J.C.; Klaver, M.M.; Sie, H.T.

    2004-01-01

    We present two adult patients with a left-sided cardiac tumour in whom the diagnosis was established by transthoracic and transoesophageal echocardiography. They both presented with a cerebrovascular accident. Cardiac surgery for tumour excision was offered but refused by one and successfully performed in the other. In one of the patients, right femoro-crural bypass was undertaken because of arterial insufficiency. The patient who refused surgical intervention died secondary to severe septic shock. In the other patient serial transthoracic and transoesophageal echocardiography showed no tumour recurrence at four years of follow-up post tumour extirpation. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:25696276

  12. Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function

    PubMed Central

    Sakabe, Noboru J.; Aneas, Ivy; Shen, Tao; Shokri, Leila; Park, Soo-Young; Bulyk, Martha L.; Evans, Sylvia M.; Nobrega, Marcelo A.

    2012-01-01

    The ongoing requirement in adult heart for transcription factors with key roles in cardiac development is not well understood. We recently demonstrated that TBX20, a transcriptional regulator required for cardiac development, has key roles in the maintenance of functional and structural phenotypes in adult mouse heart. Conditional ablation of Tbx20 in adult cardiomyocytes leads to a rapid onset and progression of heart failure, with prominent conduction and contractility phenotypes that lead to death. Here we describe a more comprehensive molecular characterization of the functions of TBX20 in adult mouse heart. Coupling genome-wide chromatin immunoprecipitation and transcriptome analyses (RNA-Seq), we identified a subset of genes that change expression in Tbx20 adult cardiomyocyte-specific knockout hearts which are direct downstream targets of TBX20. This analysis revealed a dual role for TBX20 as both a transcriptional activator and a repressor, and that each of these functions regulates genes with very specialized and distinct molecular roles. We also show how TBX20 binds to its targets genome-wide in a context-dependent manner, using various cohorts of co-factors to either promote or repress distinct genetic programs within adult heart. Our integrative approach has uncovered several novel aspects of TBX20 and T-box protein function within adult heart. Sequencing data accession number (http://www.ncbi.nlm.nih.gov/geo): GSE30943. PMID:22328084

  13. Fetal cardiac circulation in isolated aortic atresia assessed with ultrasound.

    PubMed

    Sayit, Aslı Tanrıvermiş; Ipek, Ali; Kurt, Aydın; Aghdasi, Bayan G; Arslan, Halil; Gümüş, Mehmet

    2012-01-01

    Congenital heart diseases are common, with an incidence of more than 8 in 1000 live births. Aortic atresia is a rare diagnosis and its prognosis is very poor. In this article, we present a case of isolated aortic atresia, a very rare cardiovascular anomaly, and its fetal ultrasound findings which include blood flow at foramen ovale from left to right, right deviation of the interventricular septum, dysfunction of the mitral valve and cardiomegaly. Aortic stenosis should be considered in the differential diagnosis of aortic atresia. However, in the case of severe aortic stenosis and/or accompanying ventricular septal defect, differential diagnosis may not be done. PMID:24592058

  14. Exosomes isolation protocols: facts and artifacts for cardiac regeneration.

    PubMed

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Pagano, Francesca; Chimenti, Isotta; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    In recent years, exosomes have attracted increasing scientific interest and are no longer considered just as containers for cell waste, but as important mediators of intercellular communication. Among many biomedical research topics, a possible direct role of exosomes in the regenerative medicine field has been underlined in recent studies, including those regarding the so called "paracrine hypothesis". In this perspective, a therapeutic role and/or use of exosomes for tissue regeneration seems to be plausible. However, the majority of the cells isolated and cultured in vitro are exposed to an exogenous exosomes source because of the wide use of foetal bovine serum as cell culture supplement. Bovine serum has been gradually considered as a major biological stimulus, but with still unknown outcome. In this review, we present the state of the art about the role of exosomes in regenerative medicine, particularly for the cardiovascular system. We also analyse the most commonly used exosome isolation techniques that, since their discovery, have undergone continuous development to reach the highest degree of scalability for future clinical translation. PMID:27100708

  15. Isolation, electron microscopic imaging, and 3-D visualization of native cardiac thin myofilaments.

    PubMed

    Spiess, M; Steinmetz, M O; Mandinova, A; Wolpensinger, B; Aebi, U; Atar, D

    1999-06-15

    An increasing number of cardiac diseases are currently pinpointed to reside at the level of the thin myofilaments (e.g., cardiomyopathies, reperfusion injury). Hence the aim of our study was to develop a new method for the isolation of mammalian thin myofilaments suitable for subsequent high-resolution electron microscopic imaging. Native cardiac thin myofilaments were extracted from glycerinated porcine myocardial tissue in the presence of protease inhibitors. Separation of thick and thin myofilaments was achieved by addition of ATP and several centrifugation steps. Negative staining and subsequent conventional and scanning transmission electron microscopy (STEM) of thin myofilaments permitted visualization of molecular details; unlike conventional preparations of thin myofilaments, our method reveals the F-actin moiety and allows direct recognition of thin myofilament-associated porcine cardiac troponin complexes. They appear as "bulges" at regular intervals of approximately 36 nm along the actin filaments. Protein analysis using SDS-polyacrylamide gel electrophoresis revealed that only approximately 20% troponin I was lost during the isolation procedure. In a further step, 3-D helical reconstructions were calculated using STEM dark-field images. These 3-D reconstructions will allow further characterization of molecular details, and they will be useful for directly visualizing molecular alterations related to diseased cardiac thin myofilaments (e.g., reperfusion injury, alterations of Ca2+-mediated tropomyosin switch). PMID:10388621

  16. Comparison of cardiac refractory periods in children and adults.

    PubMed

    DuBrow, W; Fisher, E A; Amaty-Leon, G; Denes, P; Wu, D; Rosen, K; Hastreiter, A R

    1975-03-01

    Atrial (A) and A-V nodal (AVN) effective and functional refractory periods (ERP & FRP) were determined by atrial extrastimulus technique in 40 children, aged 7 months to 16 years, with normal P-R intervals and QRS durations. These data were compared to adult data at longest cycle lengths (CL) assuring atrial capture. All values are listed in msec as means plus or minus standard errors of the means. CL was 566 plus or minus 15 in children and 699 plus or minus 29 in adults (P less than .001). Refractory periods (RP) in children and adults were, respectively: AERP 196 plus or minus 9 and 239 plus or minus 13 (P less than .01), AFRP 225 plus or minus 8 and 284 plus or minus 11 (P less than .001), AVNERP 239 plus or minus 11 and 293 plus or minus 7 (P smaller than .001), AVNFRP 360 plus or minus 13 and 403 plus or minus 7 (P smaller than .005). RP were then compared at three equivalent CL ranges: CL1, 850-600; CL2 599-460; CL3 459-280. The following RP were significantly shorter in children (P smaller than .05-.001): AERP, AFRP, AVENERP and AVNFRP at CL2 and CL3. RP of the bundle branches were compared and tended to be shorter in children. In conclusion, atrial and A-V nodal ERP and FRP are shorter in children than adults. This shortening is only partially related to the shorter CL in children. These data are germane to understanding the maturation of the conduction system in man. PMID:1139759

  17. Audio-visual relaxation training for anxiety, sleep, and relaxation among Chinese adults with cardiac disease.

    PubMed

    Tsai, Sing-Ling

    2004-12-01

    The long-term effect of an audio-visual relaxation training (RT) treatment involving deep breathing, exercise, muscle relaxation, guided imagery, and meditation was compared with routine nursing care for reducing anxiety, improving sleep, and promoting relaxation in Chinese adults with cardiac disease. This research was a quasi-experimental, two-group, pretest-posttest study. A convenience sample of 100 cardiology patients (41 treatment, 59 control) admitted to one large medical center hospital in the Republic of China (ROC) was studied for 1 year. The hypothesized relationships were supported. RT significantly (p <.05) improved anxiety, sleep, and relaxation in the treatment group as compared to the control group. It appears audio-visual RT might be a beneficial adjunctive therapy for adult cardiac patients. However, considerable further work using stronger research designs is needed to determine the most appropriate instructional methods and the factors that contribute to long-term consistent practice of RT with Chinese populations. PMID:15514963

  18. Physical Therapy Management for Adult Patients Undergoing Cardiac Surgery: A Canadian Practice Survey

    PubMed Central

    Anderson, Cathy M.; Jackson, Jennifer; Lucy, S. Deborah; Prendergast, Monique; Sinclair, Susanne

    2010-01-01

    ABSTRACT Purpose: To determine current Canadian physical therapy practice for adult patients requiring routine care following cardiac surgery. Methods: A telephone survey was conducted of a selected sample (n=18) of Canadian hospitals performing cardiac surgery to determine cardiorespiratory care, mobility, exercises, and education provided to patients undergoing cardiac surgery. Results: An average of 21 cardiac surgeries per week (range: 6–42) were performed, with an average length of stay of 6.4 days (range: 4.0–10.6). Patients were seen preoperatively at 7 of 18 sites and on postoperative day 1 (POD-1) at 16 of 18 sites. On POD-1, 16 sites performed deep breathing and coughing, 7 used incentive spirometers, 13 did upper-extremity exercises, and 12 did lower-extremity exercises. Nine sites provided cardiorespiratory treatment on POD-3. On POD-1, patients were dangled at 17 sites and mobilized out of bed at 13. By POD-3, patients ambulated 50–120 m per session 2–5 times per day. Sternal precautions were variable, but the lifting limit was reported as ranging between 5 lb and 10 lb. Conclusions: Canadian physical therapists reported the provision of cardiorespiratory treatment after POD-1. According to current available evidence, this level of care may be unnecessary for uncomplicated patients following cardiac surgery. In addition, some sites provide cardiorespiratory treatment techniques that are not supported by evidence in the literature. Further research is required. PMID:21629599

  19. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  20. Isolated rat cardiac myocytes as an experimental model to study calcium overload: the effect of calcium-entry blockers.

    PubMed

    Donck, L V; Pauwels, P J; Vandeplassche, G; Borgers, M

    1986-03-01

    Calcium overload and the effect of a series of calcium-entry blockers were studied in isolated adult cardiac myocytes from the rat challenged with veratrine. The isolation procedure resulted in a high yield of individual rod shaped, calcium tolerant myocytes. After incubation with veratrine, an alkaloid which induces both sodium and calcium influx, 93% of the myocytes became calcium intolerant: the quiescent rod shaped cells vigorously contracted after 30 sec of contact with veratrine and contracture (round cells) ensued within 1 min. Exposure for 30 min to various doses of calcium-entry blockers prior to veratrine addition resulted in the prevention of contracture, the degree of protection depending on the type and the concentration of calcium-entry blocker. Among the different calcium-entry blockers tested, the diarylalkylpiperazines lidoflazine, cinnarizine and flunarizine were protective from the 10(-7) M concentration onwards. Nicardipine was protective at the 10(-6) M and 10(-5) M concentrations, verapamil at 10(-5)M only while other blockers of the "slow channel" type (diltiazem and nifedipine) were not protective in the concentration range tested. This study shows that isolated myocytes represent a valid model for pharmacological investigations. The results with the calcium-entry blockers stress the heterogeneity of the different series of calcium-entry blockers. PMID:3951332

  1. Tai Chi as an adjunct physical activity for adults aged 45 years and older enrolled in phase III cardiac rehabilitation

    PubMed Central

    Taylor-Piliae, Ruth E; Silva, Edna; Sheremeta, Sharon Peachey

    2015-01-01

    Background Cardiac rehabilitation improves physical, cognitive and psychosocial functioning, yet services are greatly underutilized with increasing patterns of attrition over time. Tai Chi has been suggested as a possible adjunct to cardiac rehabilitation exercise training. Aim To describe differences in physical, cognitive and psychosocial functioning among adults ≥ 45 years old attending phase III cardiac rehabilitation, who have or have not self-selected Tai Chi exercise as an adjunct physical activity. Methods A cross-sectional design compared subjects attending group-based Wu style Tai Chi classes plus cardiac rehabilitation, with cardiac rehabilitation only. Subjects had a battery of physical and cognitive functioning tests administered to examine aerobic endurance, balance, strength, and flexibility, verbal retrieval/recall, attention, concentration and tracking. Subjects completed a health survey to ascertain cardiac event information, medical history, and psychosocial functioning (i.e. health-related quality of life, stress, depressive symptoms, social support, and Tai Chi self-efficacy). Results A total of 51 subjects (75% married, 84% college-educated, 96% White/European-American) participated. Subjects were on average 70 (± 8) years old and had attended cardiac rehabilitation for 45 (± 37) months. Approximately 45% (n = 23) attended Tai Chi classes plus cardiac rehabilitation, while 55% (n = 28) attended cardiac rehabilitation only. Subjects attending Tai Chi plus cardiac rehabilitation had better balance, perceived physical health, and Tai Chi self-efficacy compared to those attending cardiac rehabilitation only (p ≤ 0.03). Conclusion Tai Chi can be easily implemented in any community/cardiac rehabilitation facility, and may offer adults additional options after a cardiac event. PMID:21095159

  2. Bile acids are toxic for isolated cardiac mitochondria: a possible cause for hepatic-derived cardiomyopathies?

    PubMed

    Ferreira, Manuela; Coxito, Pedro M; Sardão, Vilma A; Palmeira, Carlos M; Oliveira, Paulo J

    2005-01-01

    Cholestasis and other liver diseases may affect the heart through the toxic effects of the retained bile acids on cardiac mitochondria, which could explain the origin of hepatic-derived cardiomyopathies. The objective of this work was to test the hypothesis that bile acids are toxic to heart mitochondria for concentrations that are relevant for cholestasis. Heart mitochondria were isolated from rat and subjected to incubation with selected bile acids (litocholic acid [LCA], deoxycholic acid [DCA], chenodeoxycholic acid [CDCA], glycochenodeoxycholic acid [GCDC], taurodeoxycholic acid [TDCA], and glycoursodeoxycholic acid [GUDC]). We observed that the most toxic bile acids were also the most lipophilic ones (LCA, DCA, and CDCA), inducing a decrease on state 3 respiration, respiratory control ratio, and membrane potential and causing the induction of the mitochondrial permeability transition. GUDC was the bile acid with lower indexes of toxicity on isolated heart mitochondria. The results of this research indicate that at toxicologically relevant concentrations, most bile acids (mainly the most lipophilic) alter mitochondrial bioenergetics. The impairment of cardiac mitochondrial function may be an important cause for the observed cardiac alterations during cholestasis. PMID:15738586

  3. Isolation and culture of neurospheres from the adult newt brain.

    PubMed

    Hameed, Liyakath Ali Shahul; Simon, András

    2015-01-01

    Neural stem cells (NSCs) give rise to neurons in the adult brain and are possible targets in regenerative therapies. In vitro cultures of NSCs as neurospheres have been established from cells isolated from diverse species. Newts are exceptional regenerators among vertebrates. These animals are able to efficiently replace neurons following ablation of those by activation and subsequent differentiation of NSCs. Here we describe the method for isolating and culturing of NSCs from the newt brain both during self-renewing and differentiating conditions. Newt NSC culture provides a useful tool for functional studies of NSC fate with the potential of resulting in novel regenerative strategies. PMID:25740488

  4. 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

  5. Spectrum of cardiac lesions associated with Isolated Cleft Mitral Valve and their impact on therapeutic choices

    PubMed Central

    El hammiri, Ayoub; Drighil, Abdenasser; Benhaourech, Sanaa

    2016-01-01

    Background Isolated cleft mitral valve (ICMV) may occur alone or in association with other congenital heart lesions. The aim of this study was to describe the profile of cardiac lesions associated with ICMV and their potential impact on therapeutic management. Methods We conducted a descriptive study with data retrieved from the Congenital Heart Disease (CHD) single-center registry of our institution, including patients with ICMV registered between December 2008 and November 2014. Results Among 2177 patients retrieved from the CHD registry, 22 (1%) had ICMV. Median age at diagnosis was 5 years (6 days to 36 years). Nine patients (40.9%) had Down syndrome. Seventeen patients (77.3%) had associated lesions, including 11 (64.7%) with accessory chordae in the left ventricular outflow tract (LVOT) with no obstruction, 15 (88.2%) had ventricular septal defect (VSD), three had secundum atrial septal defect, and four had patent ductus arteriosus. Thirteen patients (59.1%) required surgical repair. The decision to proceed with surgery was mainly based on the severity of the associated lesion in eight patients (61.5%) and on the severity of the mitral regurgitation in four patients (30.8%). In one patient, surgery was decided based on the severity of both the associated lesion and mitral regurgitation. Conclusion Our study shows that ICMV is rare and strongly associated with Down syndrome. The most common associated cardiac abnormalities were VSD and accessory chordae in the LVOT. We conclude that cardiac lesions associated with ICMV are of major interest, since in this study patients with cardiac lesions were diagnosed earlier. The decision to operate on these patients must take into account the severity of both mitral regurgitation and associated cardiac lesions. PMID:27096525

  6. 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

  7. IP(3)R-mediated Ca(2+) release is modulated by anandamide in isolated cardiac nuclei.

    PubMed

    Currie, Susan; Rainbow, Richard D; Ewart, Marie-Ann; Kitson, Susan; Pliego, Esperanza Herradon; Kane, Kathleen A; McCarron, John G

    2008-12-01

    Cannabinoids (CBs) are known to alter coronary vascular tone and cardiac performance. They also exhibit cardioprotective properties, particularly in their ability to limit the damage produced by ischaemia reperfusion injury. The mechanisms underlying these effects are unknown. Here we investigate the intracellular localisation of CB receptors in the heart and examine whether they may modulate localised nuclear Ca(2+) release. In isolated cardiac nuclear preparations, expression of both the inositol 1,4,5-trisphosphate receptor type 2 (IP(3)R) and CB receptors (CB(1)R and CB(2)R) was demonstrated by immunoblotting. Both receptors localised to the nucleus and purity of the nuclear preparations was confirmed by co-expression of the nuclear marker protein nucleolin but absence of cytoplasmic actin. To measure effects of IP(3)R and CBR agonists on nuclear Ca(2+) release, isolated nuclei were loaded with Fluo5N-AM. This dye accumulates in the nuclear envelope. Isolated nuclei responded to IP(3) with rapid and transient Ca(2+) release from the nuclear envelope. Anandamide inhibited this IP(3)-mediated release. Preincubation of nuclear preparations with either the CB(1)R antagonist (AM251) or the CB(2)R antagonist (AM630) reversed anandamide-mediated inhibition to 80% and 60% of control values respectively. When nuclei were pre-treated with both CBR antagonists, anandamide-mediated inhibition of IP(3)-induced Ca(2+) release was completely reversed. These results are the first to demonstrate the existence of cardiac nuclear CB receptors. They are also the first to show that anandamide can negatively modulate IP(3)-mediated nuclear Ca(2+) release. As such, this provides evidence for a novel key mechanism underlying the action of CBs and CBRs in the heart. PMID:18692061

  8. 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

  9. 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

  10. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Research.

    PubMed

    Badhwar, Vinay; Rankin, J Scott; Jacobs, Jeffrey P; Shahian, David M; Habib, Robert H; D'Agostino, Richard S; Thourani, Vinod H; Suri, Rakesh M; Prager, Richard L; Edwards, Fred H

    2016-07-01

    The Society of Thoracic Surgeons Adult Cardiac Database (ACSD) is an international voluntary effort that is the foundation of our specialty's efforts in clinical performance assessment and quality improvement. Containing nearly 6,000,000 patient records, the ACSD is a robust resource for clinical research. Seven major original publications and four review articles were generated from the ACSD in 2015. The risk-adjusted outcome analyses and quality measures reported in these studies have made substantial contributions to inform daily clinical practice. This report summarizes the ACSD-based research efforts published in 2015. PMID:27262913

  11. The first Caucasian patient with p.Val122Ile mutated-transthyretin cardiac amyloidosis treated with isolated heart transplantation.

    PubMed

    Ammirati, Enrico; Marziliano, Nicola; Vittori, Claudia; Pedrotti, Patrizia; Bramerio, Manuela A; Motta, Valentina; Orsini, Francesco; Veronese, Silvio; Merlini, Piera A; Martinelli, Luigi; Frigerio, Maria

    2012-06-01

    Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p.Val122Ile mutated TTR-related cardiac amyloidosis treated with heart transplantation due to this gene mutation frequent in Afro-Americans with a prevalent isolated heart involvement. The choice of isolated heart transplantation instead of combined heart and liver transplantations was based on (1) severe and progressive cardiac disease, (2) evidence of a gene mutation generally associated with isolated cardiac disease and (3) absence of relevant extra-cardiac involvement (with the possible exception of mild peripheral neuropathy). In any case, the very short post-transplant observation period of 10 months does not allow any conclusions on the long-term course of the presented strategy. Finally, it is the first European Caucasian family with the p.Val122Ile TTR mutation that has been described. Till now, very few Caucasian cases of p.Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p.Val122Ile. PMID:22449240

  12. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  13. Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery

    PubMed Central

    Eifert, Sandra; Guethoff, Sonja; Kaczmarek, Ingo; Beiras-Fernandez, Andres; Seeland, Ute; Gulbins, Helmut; Seeburger, Jörg; Deutsch, Oliver; Jungwirth, Bettina; Katsari, Elpiniki; Dohmen, Pascal; Pfannmueller, Bettina; Hultgren, Rebecka; Schade, Ina; Kublickiene, Karolina; Mohr, Friedrich W.; Gansera, Brigitte

    2014-01-01

    Summary Background Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. Methods We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. Results The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. Conclusions Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females. PMID:26288584

  14. Impact of adiposity on cardiac structure in adult life: the childhood determinants of adult health (CDAH) study

    PubMed Central

    2014-01-01

    Background We have examined the association between adiposity and cardiac structure in adulthood, using a life course approach that takes account of the contribution of adiposity in both childhood and adulthood. Methods The Childhood Determinants of Adult Health study (CDAH) is a follow-up study of 8,498 children who participated in the 1985 Australian Schools Health and Fitness Survey (ASHFS). The CDAH follow-up study included 2,410 participants who attended a clinic examination. Of these, 181 underwent cardiac imaging and provided complete data. The measures were taken once when the children were aged 9 to 15 years, and once in adult life, aged 26 to 36 years. Results There was a positive association between adult left ventricular mass (LVM) and childhood body mass index (BMI) in males (regression coefficient (β) 0.41; 95% confidence interval (CI): 0.14 to 0.67; p = 0.003), and females (β = 0.53; 95% CI: 0.34 to 0.72; p < 0.001), and with change in BMI from childhood to adulthood (males: β = 0.27; 95% CI: 0.04 to 0.51; p < 0.001, females: β = 0.39; 95% CI: 0.20 to 0.58; p < 0.001), after adjustment for confounding factors (age, fitness, triglyceride levels and total cholesterol in adulthood). After further adjustment for known potential mediating factors (systolic BP and fasting plasma glucose in adulthood) the relationship of LVM with childhood BMI (males: β = 0.45; 95% CI: 0.19 to 0.71; p = 0.001, females: β = 0.49; 95% CI: 0.29 to 0.68; p < 0.001) and change in BMI (males: β = 0.26; 95% CI: 0.04 to 0.49; p = 0.02, females: β = 0.40; 95% CI: 0.20 to 0.59; p < 0.001) did not change markedly. Conclusions Adiposity and increased adiposity from childhood to adulthood appear to have a detrimental effect on cardiac structure. PMID:24980215

  15. Adult stem cells and biocompatible scaffolds as smart drug delivery tools for cardiac tissue repair.

    PubMed

    Pagliari, Stefania; Romanazzo, Sara; Mosqueira, Diogo; Pinto-do-Ó, Perpetua; Aoyagi, Takao; Forte, Giancarlo

    2013-01-01

    The contribution of adult stem cells to cardiac repair is mostly ascribed to an indirect paracrine effect, rather than to their actual engraftment and differentiation into new contractile and vascular cells. This effect consists in a direct reduction of host cell death, promotion of neovascularization, and in a "bystander effect" on local inflammation. A number of cytokines secreted by adult stem/progenitor cells has been proposed to be responsible for the consistent beneficial effect reported in the early attempts to deliver different stem cell subsets to the injured myocardium. Aiming to maximize their beneficial activity on the diseased myocardium, the genetic modification of adult stem cells to enhance and/or control the secretion of specific cytokines would turn them into active drug delivery vectors. On the other hand, engineering biocompatible scaffolds as to release paracrine factors could result in multiple advantages: (1) achieve a local controlled release of the drug of interest, thus minimizing off-target effects, (2) enhance stem cell retention in the injured area and (3) boost the beneficial paracrine effects exerted by adult stem cells on the host tissue. In the present review, a critical overview of the state-of-the-art in the modification of stem cells and the functionalization of biocompatible scaffolds to deliver beneficial soluble factors to the injured myocardium is offered. Besides the number of concerns to be addressed before a clinical application can be foreseen for such concepts, this path could translate into the generation of active scaffolds as smart cell and drug delivery systems for cardiac repair. PMID:23745554

  16. [Transfer of cardiac catheterisation from a paediatric to an adult cardiological centre: results at 3 years].

    PubMed

    Agnoletti, G; Boudjemline, Y; Ladouceur, M; Iserin, L

    2007-05-01

    The advances of surgical and interventional treatment of congenital heart diseases have allowed a large number of patients with congenital heart disease to reach adult age. This population involves almost 0.3/1000 of total population in West Europe and North America and can be estimated around 200000 patients in France. Patients with operated Tetralogy of Fallot, benign forms of pulmonary atresia with ventricular septal defect, simple or complex transposition of the great arteries usually survive beyond childhood. These patients can need repeated interventions to treat lesions of native or reconstructed pulmonary arteries and/or aortic arch, to occlude residual shunts, to treat pulmonary incompetence. More complex heart diseases such as single ventricle, rarely allow survival until the adult age. The majority of these patients undergo heart transplant, often made difficult by multiple cardiac surgeries, anomalies of pulmonary arteries, chronic cyanosis, aorto-pulmonary shunts. Patients with relatively simple or complex congenital heart diseases need to be followed-up in specialized units, like those created more than twenty years ago in the United States, Canada, and United Kingdom. Interventional cardiac catheterisation play a major role in the management of this population. The results of 3 years of activity in a new centre treating GUCH patients are illustrated. PMID:17646764

  17. 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

  18. Cardiac and vascular responses of isolated rat tissues treated with diterpenes from Sinularia flexibilis (coelenterata: octocorallia).

    PubMed

    Aceret, T L; Brown, L; Miller, J; Coll, J C; Sammarco, P W

    1996-10-01

    The marine environment is a rich source of compounds with cardiovascular activity. This study characterizes the cardiac and vascular responses in isolated rat tissues of flexibilide, dihydroflexibilide and sinulariolide, three diterpenes isolated from the soft coral Sinularia flexibilis. On rat left ventricular papillary muscles, dihydroflexibilide and flexibilide showed similar potencies (-log EC50 = 4.69 +/- 0.05 and 4.66 +/- 0.06, respectively); the maximal response to dihydroflexibilide of 1.4 +/- 0.2 mN was 35 +/- 7% that of calcium chloride in the same muscles. All diterpenes relaxed rat thoracic aortic rings precontracted with KC1 (100 mM) with similar potencies (flexibilide, -log EC50 = 4.17 +/- 0.06). Flexibilide was further characterized and shown to increase force in isolated rat left atria by 0.8 +/- 0.5 mN at 1 x 10(-4) M, to increase rate of contraction in isolated rat right atria by 18 +/- 5 beta/min at 3 x 10(-5) M and to completely relax endothelium-denuded rat thoracic aortic rings (-log EC50 = 4.14 +/- 0.05). Toxicity as indicated by the occurrence of ectopic beats was not observed with the diterpenes at concentrations which produced complete relaxation of blood vessels, maximal positive inotropic activity and minor positive chronotropic responses. Thus, these compounds may be useful lead compounds in the search for improved treatment of cardiovascular disease, especially heart failure. PMID:8931257

  19. Possible mechanism of cardiac depressant activity of Berberis orthobotrys roots in isolated rabbit heart.

    PubMed

    Alamgeer; Akhtar, Muhammad Shoaib; Jabeen, Qaiser; Bashir, Sajid; Malik, Muhammad Nasir Hayat; Karim, Sabeha; Mushtaq, Muhammad Naveed; Rasool, Shahid; Latif, Fozia; Tabbasum, Nazia; Khan, Abdul Qayyum; Ahsan, Haseeb; Khan, Wasim; Javed, Ibrahim

    2014-01-01

    Berberis orhob, otrvs Bien. ex Aitch. (B.o.) has been reported to have antihypertensive effect in different experimental models. The aim of present study was to evaluate the possible antihypertensive mechanism. Aqueous methanolic extract of B.o. roots and its various fractions namely (ethyl acetate, n-butanol or aqueous) in different concentrations (10 ng/mL, 100 ng/mL, I pg/mL, 10 pg/mL, 100 pg/mL ) were evaluated in isolated perfused rabbit heart to assess their effect on force of contraction, HR and perfusion pressure. The crude extract of B.o. and its fractions exhibited a significant decrease in heart rate, contractility and perfusion pressure of isolated rabbit heart, however, butanolic fraction produced more prominent effect and was selected for further study. The effects of butanol fraction were not blocked by atropine (10' M) in isolated perfused heart. However, butanol fraction significantly blocked the effects of adrenaline (10' M). It is therefore conceivable that cardiac depressant activity of B.o. butanol fraction might be due to the presence of certain 3-blocking agents which might be responsible for antihypertensive effect However, further experiments are required to isolate the active compound(s) and elucidate exact mechanism of action. PMID:25272893

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  2. PRKAR1A in the development of cardiac myxoma: a study of 110 cases including isolated and syndromic tumors.

    PubMed

    Maleszewski, Joseph J; Larsen, Brandon T; Kip, Nefize Sertac; Castonguay, Mathieu C; Edwards, William D; Carney, J Aidan; Kipp, Benjamin R

    2014-08-01

    Cardiac myxoma usually occurs as a solitary mass, but occasionally develops as part of a familial syndrome, the Carney complex (CNC). Two thirds of CNC-associated cardiac myxomas exhibit mutations in PRKAR1A. PRKAR1A mutations occur in both familial and sporadic forms of CNC but have not been described in isolated (nonsyndromic) cardiac myxomas. A total of 127 consecutive cardiac myxomas surgically resected at Mayo Clinic (1993 to 2011) from 110 individuals were studied. Clinical, radiologic, and pathologic findings were reviewed. Of these, 103 patients had isolated cardiac myxomas, and 7 patients had the tumor as a component of CNC. Age and sex distributions were different for CNC (mean 26 y, range 14 to 44 y, 71% female) and non-CNC (mean 62 y, range 18 to 92 y, 63% female) patients. PRKAR1A immunohistochemical analysis (IHC) was performed, and myxoma cell reactivity was graded semiquantitatively. Bidirectional Sanger sequencing was performed in 3 CNC patients and 29 non-CNC patients, to test for the presence of mutations in all coding regions and intron/exon boundaries of the PRKAR1A gene. IHC staining showed that all 7 CNC cases lacked PRKAR1A antigenicity and that 33 (32%) isolated cardiac myxomas were similarly nonreactive. Of tumors subjected to sequencing analysis, 2 (67%) CNC myxomas and 9 (31%) non-CNC myxomas had pathogenic PRKAR1A mutations. No germline mutations were found in 4 non-CNC cases tested. PRKAR1A appears to play a role in the development of both syndromic and nonsyndromic cardiac myxomas. Routine IHC evaluation of cardiac myxomas for PRKAR1A expression may be useful in excluding a diagnosis of CNC. PMID:24618615

  3. Mitochondrial membrane potential in single living adult rat cardiac myocytes exposed to anoxia or metabolic inhibition.

    PubMed Central

    Di Lisa, F; Blank, P S; Colonna, R; Gambassi, G; Silverman, H S; Stern, M D; Hansford, R G

    1995-01-01

    1. The relation between mitochondrial membrane potential (delta psi m) and cell function was investigated in single adult rat cardiac myocytes during anoxia and reoxygenation. delta psi m was studied by loading myocytes with JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'- tetra-ethylbenzimidazolylcarbocyanine iodide), a fluorescent probe characterized by two emission peaks (539 and 597 nm with excitation at 490 nm) corresponding to monomer and aggregate forms of the dye. 2. De-energizing conditions applied to mitochondria, cell suspensions or single cells decreased the aggregate emission and increased the monomer emission. This latter result cannot be explained by changes of JC-1 concentration in the aqueous mitochondrial matrix phase indicating that hydrophobic interaction of the probe with membranes has to be taken into account to explain JC-1 fluorescence properties in isolated mitochondria or intact cells. 3. A different sensitivity of the two JC-1 forms to delta psi m changes was shown in isolated mitochondria by the effects of ADP and FCCP and the calibration with K+ diffusion potentials. The monomer emission was responsive to values of delta psi m below 140 mV, which hardly modified the aggregate emission. Thus JC-1 represents a unique double sensor which can provide semi-quantitative information in both low and high potential ranges. 4. At the onset of glucose-free anoxia the epifluorescence of individual myocytes studied in the single excitation (490 nm)-double emission (530 and 590 nm) mode showed a gradual decline of the aggregate emission, which reached a plateau while electrically stimulated (0.2 Hz) contraction was still retained. The subsequent failure of contraction was followed by the rise of the emission at 530 nm, corresponding to the monomer form of the dye, concomitantly with the development of rigor contracture. 5. The onset of the rigor was preceded by the increase in intracellular Mg2+ concentration ([Mg2+]i) monitored by mag-indo-1 epifluorescence

  4. An improved isolation procedure for adult mouse cardiomyocytes.

    PubMed

    Pinz, Ilka; Zhu, Ming; Mende, Ulrike; Ingwall, Joanne S

    2011-09-01

    Isolated adult mouse cardiomyocytes are an important tool in cardiovascular research, but are challenging to prepare. Because the energy supply determines cell function and viability, we compared total creatine ([Cr]) and [ATP] in isolated cardiomyocytes with the intact mouse heart. Isolated myocytes suffered severe losses of Cr (-70%) and ATP (-53%). Myocytes were not able to replete [Cr] during a 5 h incubation period in medium supplemented with 1 mM Cr. In contrast, adding 20 mM Cr to the digestion buffers was sufficient to maintain normal [Cr]. Supplementing buffers with 5 mM of inosine (Ino) and adenosine (Ado) to prevent loss of cellular nucleosides partially protected against loss of ATP. To test whether maintaining [ATP] and [Cr] improves contractile function, myocytes were challenged by varying pacing rate from 0.5 to 10 Hz and by adding isoproterenol (Iso) at 5 and 10 Hz. All groups performed well up to 5 Hz, showing a positive cell shortening-frequency relationship; however, only 16% of myocytes isolated under standard conditions were able to sustain pacing with Iso challenge at 10 Hz. In contrast, 30-50% of the myocytes with normal Cr levels were able to contract and maintain low diastolic [Ca(2+)]. Cell yield also improved in Cr and the Cr/Ino/Ado-treated groups (85-90% vs. 70-75% rod shaped in untreated myocytes). These data suggest that viability and performance of isolated myocytes are improved when they are protected from the severe loss of Cr and ATP during the isolation, making them an even better research tool. PMID:21327944

  5. Gene Transfer into Cardiac Myocytes

    PubMed Central

    Lang, Sarah E.; Westfall, Margaret V.

    2016-01-01

    Traditional methods for DNA transfection are often inefficient and toxic for terminally differentiated cells, such as cardiac myocytes. Vector-based gene transfer is an efficient approach for introducing exogenous cDNA into these types of primary cell cultures. In this chapter, separate protocols for adult rat cardiac myocyte isolation and gene transfer with recombinant adenovirus are provided and are routinely utilized for studying the effects of sarcomeric proteins on myofilament function. PMID:25836585

  6. An uncommon case of isolated parachute-like asymmetric mitral valve in an adult.

    PubMed

    Mochizuki, Yasuhide; Tanaka, Hidekazu; Fukuda, Yuko; Hirata, Ken-Ichi

    2014-09-01

    A 31-year-old asymptomatic male was referred to hospital for an examination of right bundle brunch block. Both, transthoracic and transesophageal echocardiography revealed normal left ventricular function, and two different-sized papillary muscles; the anterolateral muscle was more pronounced, with almost major chordae tendineae inserted into this dominant muscle, whereas the immature, flat posteromedial papillary muscle had very short chordae tendineae and was located higher in the left ventricle, inserted directly into the mitral annulus. The mitral valve orifice was eccentrically located at the lateral side, but no significant mitral stenosis or regurgitation was observed. No other congenital heart anomalies were identified. Thus, the final diagnosis was isolated parachute-like asymmetric mitral valve (PLAMV), without any other congenital heart anomalies. The patient was followed up closely with periodic echocardiographic examinations. Parachute mitral valve is a rare congenital cardiac defect characterized by focalized attachment of the chordae tendineae of both leaflets to a single papillary muscle. In contrast to true parachute mitral valve, PLAMV has two separate papillary muscles, one of which is more pronounced and into which all chordae are inserted. PLAMV was highly associated with other congenital heart anomalies, and the involved dominant muscle was most frequently a posteromedial papillary muscle. Isolated PLAMV in an adult is even more rare, while the presence of an immature posteromedial papillary muscle--as in the present case--is extremely rare. PMID:25799716

  7. 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

  8. Dynamic Measurement of Hemodynamic Parameters and Cardiac Preload in Adults with Dengue: A Prospective Observational Study

    PubMed Central

    Thanachartwet, Vipa; Wattanathum, Anan; Sahassananda, Duangjai; Wacharasint, Petch; Chamnanchanunt, Supat; Khine Kyaw, Ei; Jittmittraphap, Akanitt; Naksomphun, Mali; Surabotsophon, Manoon; Desakorn, Varunee

    2016-01-01

    Few previous studies have monitored hemodynamic parameters to determine the physiological process of dengue or examined inferior vena cava (IVC) parameters to assess cardiac preload during the clinical phase of dengue. From January 2013 to July 2015, we prospectively studied 162 hospitalized adults with confirmed dengue viral infection using non-invasive cardiac output monitoring and bedside ultrasonography to determine changes in hemodynamic and IVC parameters and identify the types of circulatory shock that occur in patients with dengue. Of 162 patients with dengue, 17 (10.5%) experienced dengue shock and 145 (89.5%) did not. In patients with shock, the mean arterial pressure was significantly lower on day 6 after fever onset (P = 0.045) and the pulse pressure was significantly lower between days 4 and 7 (P<0.05). The stroke volume index and cardiac index were significantly decreased between days 4 and 15 and between days 5 and 8 after fever onset (P<0.05), respectively. A significant proportion of patients with dengue shock had an IVC diameter <1.5 cm and IVC collapsibility index >50% between days 4 and 5 (P<0.05). Hypovolemic shock was observed in 9 (52.9%) patients and cardiogenic shock in 8 (47.1%), with a median (interquartile range) time to shock onset of 6.0 (5.0–6.5) days after fever onset, which was the median day of defervescence. Intravascular hypovolemia occurred before defervescence, whereas myocardial dysfunction occurred on the day of defervescence until 2 weeks after fever onset. Hypovolemic shock and cardiogenic shock each occurred in approximately half of the patients with dengue shock. Therefore, dynamic measures to estimate changes in hemodynamic parameters and preload should be monitored to ensure adequate fluid therapy among patients with dengue, particularly patients with dengue shock. PMID:27196051

  9. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

    PubMed Central

    Soliman, Rabie; Fouad, Eman; Belghith, Makhlouf; Abdelmageed, Tarek

    2016-01-01

    Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138), hemofiltration was done during CPB. Control group (n = 145), patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05), and the PH showed metabolic acidosis in group H (P < 0.05). The mixed venous oxygen saturation decreased in group H than group C (P < 0.05). The number of transfused packed red blood cells was lower in group H than group C (P < 0.05). The hematocrit was higher in group H than group C (P < 0.05). The urine output was lower in group H than group C (P < 0.05). Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass. PMID:26750673

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

    PubMed

    Haddad, Rami; Kasneci, Amanda; Mepham, Kathryn; Sebag, Igal A; Chalifour, Lorraine E

    2013-01-01

    Pregnant women, and thus their fetuses, are exposed to many endocrine disruptor compounds (EDCs). Fetal cardiomyocytes express sex hormone receptors making them potentially susceptible to re-programming by estrogenizing EDCs. Diethylstilbestrol (DES) is a proto-typical, non-steroidal estrogen. We hypothesized that changes in adult cardiac structure/function after gestational exposure to the test compound DES would be a proof in principle for the possibility of estrogenizing environmental EDCs to also alter the fetal heart. Vehicle (peanut oil) or DES (0.1, 1.0 and 10.0μg/kg/da.) was orally delivered to pregnant C57bl/6n dams on gestation days 11.5-14.5. At 3months, male progeny were left sedentary or were swim trained for 4weeks. Echocardiography of isoflurane anesthetized mice revealed similar cardiac structure/function in all sedentary mice, but evidence of systolic dysfunction and increased diastolic relaxation after swim training at higher DES doses. The calcium homeostasis proteins, SERCA2a, phospholamban, phospho-serine 16 phospholamban and calsequestrin 2, are important for cardiac contraction and relaxation. Immunoblot analyses of ventricle homogenates showed increased expression of SERCA2a and calsequestrin 2 in DES mice and greater molecular remodeling of these proteins and phospho-serine 16 phospholamban in swim trained DES mice. DES increased cardiac DNA methyltransferase 3a expression and DNA methylation in the CpG island within the calsequestrin 2 promoter in heart. Thus, gestational DES epigenetically altered ventricular DNA, altered cardiac function and expression, and reduced the ability of adult progeny to cardiac remodel when physically challenged. We conclude that gestational exposure to estrogenizing EDCs may impact cardiac structure/function in adult males. PMID:23142472

  11. Plasma Fatty Acid Binding Protein 4 and Risk of Sudden Cardiac Death in Older Adults

    PubMed Central

    Djoussé, Luc; Maziarz, Marlena; Biggs, Mary L.; Ix, Joachim H.; Zieman, Susan J.; Kizer, Jorge R.; Lemaitre, Rozenn N.; Mozaffarian, Dariush; Tracy, Russell P.; Mukamal, Kenneth J.; Siscovick, David S.; Sotoodehnia, Nona

    2013-01-01

    Although fatty acid binding protein 4 (FABP4) may increase risk of diabetes and exert negative cardiac inotropy, it is unknown whether plasma concentrations of FABP4 are associated with incidence of sudden cardiac death (SCD). We prospectively analyzed data on 4,560 participants of the Cardiovascular Health Study. FABP4 was measured at baseline using ELISA, and SCD events were adjudicated through review of medical records. We used Cox proportional hazards to estimate effect measures. During a median followup of 11.8 years, 146 SCD cases occurred. In a multivariable model adjusting for demographic, lifestyle, and metabolic factors, relative risk of SCD associated with each higher standard deviation (SD) of plasma FABP4 was 1.15 (95% CI: 0.95–1.38), P = 0.15. In a secondary analysis stratified by prevalent diabetes status, FABP4 was associated with higher risk of SCD in nondiabetic participants, (RR per SD higher FABP4: 1.33 (95% CI: 1.07–1.65), P = 0.009) but not in diabetic participants (RR per SD higher FABP4: 0.88 (95% CI: 0.62–1.27), P = 0.50), P for diabetes-FABP4 interaction 0.049. In summary, a single measure of plasma FABP4 obtained later in life was not associated with the risk of SCD in older adults overall. Confirmation of our post-hoc results in nondiabetic people in other studies is warranted. PMID:24455402

  12. Adult stem cells for cardiac repair: a choice between skeletal myoblasts and bone marrow stem cells.

    PubMed

    Ye, Lei; Haider, Husnain Kh; Sim, Eugene K W

    2006-01-01

    The real promise of a stem cell-based approach for cardiac regeneration and repair lies in the promotion of myogenesis and angiogenesis at the site of the cell graft to achieve both structural and functional benefits. Despite all of the progress and promise in this field, many unanswered questions remain; the answers to these questions will provide the much-needed breakthrough to harness the real benefits of cell therapy for the heart in the clinical perspective. One of the major issues is the choice of donor cell type for transplantation. Multiple cell types with varying potentials have been assessed for their ability to repopulate the infarcted myocardium; however, only the adult stem cells, that is, skeletal myoblasts (SkM) and bone marrow-derived stem cells (BMC), have been translated from the laboratory bench to clinical use. Which of these two cell types will provide the best option for clinical application in heart cell therapy remains arguable. With results pouring in from the long-term follow-ups of previously conducted phase I clinical studies, and with the onset of phase II clinical trials involving larger population of patients, transplantation of stem cells as a sole therapy without an adjunct conventional revascularization procedure will provide a deeper insight into the effectiveness of this approach. The present article discusses the pros and cons of using SkM and BMC individually or in combination for cardiac repair, and critically analyzes the progress made with each cell type. PMID:16380640

  13. The Importance of Emotional and Social Isolation to Loneliness among Very Old Rural Adults.

    ERIC Educational Resources Information Center

    Dugan, Elizabeth; Kivett, Vira R.

    1994-01-01

    Examined relative importance of emotional and social isolation to loneliness among very old rural adults (n=119). Found that emotional isolation, specifically loss of spouse, accounted for more loneliness than did social isolation. Hearing acuity and visits with siblings (social isolation variables) also were significant predictors of loneliness.…

  14. Review of isolated systolic hypertension in older adults.

    PubMed

    Kamath, Neetha; Cappuzzo, Kimberly A

    2010-06-01

    A 75-year-old patient comes to a community pharmacy to refill her blood pressure (BP) medications. She approached the pharmacist complaining of a headache and an unusually high BP reading that she had gotten from the automated machine. The patient was unaware of her usual BP, but knew that the reading was unusually high for her. Following evaluation of the patient and after obtaining several high systolic BP readings, the pharmacist appropriately calls for an ambulance. At the hospital, the patient is told she is in need of triple-bypass surgery. After her hospital stay, the patient is now diligent about refilling her BP medications on time and consistently monitors and records her BP at home. Isolated systolic hypertension is a growing concern in older adults, and a large percentage of adults are not appropriately managed. Pharmacists play an active role in educating patients on the importance of high BP monitoring and adherence to minimize the risk of cardiovascular events. PMID:20534408

  15. Isolated adult Tillaux fracture: a report of two cases.

    PubMed

    Oak, Nikhil R; Sabb, Brian J; Kadakia, Anish R; Irwin, Todd A

    2014-01-01

    A fracture of the lateral margin of the distal tibia has commonly been called a Tillaux fracture, which is an avulsion-type fracture that can result from the pull of the anterior inferior tibiofibular ligament. The common mechanism of injury described and observed has been one of external rotation of the foot relative to the tibia. Historically, this fracture pattern has been noted in the pediatric and adolescent populations and classified as a Salter-Harris III fracture through the epiphysis. It has typically occurred in children aged 12 to 14 years and is not commonly seen in adults. We discuss 2 cases of isolated Tillaux fractures in skeletally mature adults, aged 47 and 37 years, a population in which this fracture pattern to our knowledge and after review of the published data has not been described. It is important to recognize these distinct injuries and appropriately treat the pathologic features to prevent further instability and arthritis. PMID:24795204

  16. Proteomic profiling of cardiac tissue by isolation of nuclei tagged in specific cell types (INTACT)

    PubMed Central

    Amin, Nirav M.; Greco, Todd M.; Kuchenbrod, Lauren M.; Rigney, Maggie M.; Chung, Mei-I; Wallingford, John B.; Cristea, Ileana M.; Conlon, Frank L.

    2014-01-01

    The proper dissection of the molecular mechanisms governing the specification and differentiation of specific cell types requires isolation of pure cell populations from heterogeneous tissues and whole organisms. Here, we describe a method for purification of nuclei from defined cell or tissue types in vertebrate embryos using INTACT (isolation of nuclei tagged in specific cell types). This method, previously developed in plants, flies and worms, utilizes in vivo tagging of the nuclear envelope with biotin and the subsequent affinity purification of the labeled nuclei. In this study we successfully purified nuclei of cardiac and skeletal muscle from Xenopus using this strategy. We went on to demonstrate the utility of this approach by coupling the INTACT approach with liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic methodologies to profile proteins expressed in the nuclei of developing hearts. From these studies we have identified the Xenopus orthologs of 12 human proteins encoded by genes, which when mutated in human lead to congenital heart disease. Thus, by combining these technologies we are able to identify tissue-specific proteins that are expressed and required for normal vertebrate organ development. PMID:24496632

  17. Isolating the segment of the mitochondrial electron transport chain responsible for mitochondrial damage during cardiac ischemia

    SciTech Connect

    Chen, Qun; Yin, Guotian; Stewart, Sarah; Hu, Ying; Lesnefsky, Edward J.

    2010-07-09

    Ischemia damages the mitochondrial electron transport chain (ETC), mediated in part by damage generated by the mitochondria themselves. Mitochondrial damage resulting from ischemia, in turn, leads to cardiac injury during reperfusion. The goal of the present study was to localize the segment of the ETC that produces the ischemic mitochondrial damage. We tested if blockade of the proximal ETC at complex I differed from blockade distal in the chain at cytochrome oxidase. Isolated rabbit hearts were perfused for 15 min followed by 30 min stop-flow ischemia at 37 {sup o}C. Amobarbital (2.5 mM) or azide (5 mM) was used to block proximal (complex I) or distal (cytochrome oxidase) sites in the ETC. Time control hearts were buffer-perfused for 45 min. Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated. Ischemia decreased cytochrome c content in SSM but not in IFM compared to time control. Blockade of electron transport at complex I preserved the cytochrome c content in SSM. In contrast, blockade of electron transport at cytochrome oxidase with azide did not retain cytochrome c in SSM during ischemia. Since blockade of electron transport at complex III also prevented cytochrome c loss during ischemia, the specific site that elicits mitochondrial damage during ischemia is likely located in the segment between complex III and cytochrome oxidase.

  18. Calcium and magnesium levels in isolated mitochondria from human cardiac biopsies.

    PubMed

    Saetersdal, T; Engedal, H; Røli, J; Myklebust, R

    1980-01-01

    A non-enzymatic method is presented for isolating mitochondria from small-sized human cardiac samples, including ventricular needle biopsies of 15-25 mg of wet weight. Electron microscopy demonstrates that these fractions are rich in structurally well preserved mitochondria. Calcium and magnesium levels of fractions are determined by atomic absorption flame spectroscopy. Comparative analyses are made in similar fractions of the mouse ventricle. Calcium concentrations of mitocondria isolated in the presence of ruthenium red do not differ significantly between the human auricle and ventricle, averaging 61 nmol Ca/mg protein and 68 nmol Ca/mg protein, respectively. Mitochondrial calcium level is lower in the mouse ventricular fractions, averaging 7 nmol Ca/mg protein. Mitochondrial magnesium amounts to slightly less than 60% of the calcium levels in the human heart, while it exceeds the calcium level by more than 100 per cent in the mouse heart. There is no significant difference of mitochondrial calcium between normal auricles, and, auricles of patients with increased right atrial mean pressure and/or volume overload. PMID:7410123

  19. Isolation and characterization of embryonic stem cell-derived cardiac Purkinje cells.

    PubMed

    Maass, Karen; Shekhar, Akshay; Lu, Jia; Kang, Guoxin; See, Fiona; Kim, Eugene E; Delgado, Camila; Shen, Steven; Cohen, Lisa; Fishman, Glenn I

    2015-04-01

    The cardiac Purkinje fiber network is composed of highly specialized cardiomyocytes responsible for the synchronous excitation and contraction of the ventricles. Computational modeling, experimental animal studies, and intracardiac electrical recordings from patients with heritable and acquired forms of heart disease suggest that Purkinje cells (PCs) may also serve as critical triggers of life-threatening arrhythmias. Nonetheless, owing to the difficulty in isolating and studying this rare population of cells, the precise role of PC in arrhythmogenesis and the underlying molecular mechanisms responsible for their proarrhythmic behavior are not fully characterized. Conceptually, a stem cell-based model system might facilitate studies of PC-dependent arrhythmia mechanisms and serve as a platform to test novel therapeutics. Here, we describe the generation of murine embryonic stem cells (ESC) harboring pan-cardiomyocyte and PC-specific reporter genes. We demonstrate that the dual reporter gene strategy may be used to identify and isolate the rare ESC-derived PC (ESC-PC) from a mixed population of cardiogenic cells. ESC-PC display transcriptional signatures and functional properties, including action potentials, intracellular calcium cycling, and chronotropic behavior comparable to endogenous PC. Our results suggest that stem-cell derived PC are a feasible new platform for studies of developmental biology, disease pathogenesis, and screening for novel antiarrhythmic therapies. PMID:25524238

  20. Isolation and purification of islet cells from adult pigs.

    PubMed

    Qiao, A-Y; Zhang, W-H; Chen, X-J; Zhang, J; Xiao, G-H; Hu, Y-X; Tang, D-C

    2010-06-01

    We used in situ perfusion and a multiple-organ harvesting technique to collect islets from adult pig pancreata. The tissues were digested with collagenase P followed by purification in a lympholyte discontinuous gradient using a COBE2991 cell separator. The yield and purity of isolated islets were evaluated with a light microscope after dithizone (DTZ) staining. Islet function was assessed using an in vitro insulin release assay. The results showed that before purification 275,000 +/- 20,895 islet equivalents (IEQ) were obtained from 1 digested pancreas. After purification with gradient centrifugation, the islet yield was 230,350 +/- 26,679 IEQ/pancreas. Each gram of the purified pancreatic tissues yielded 2710 +/- 229 IEQ with an average purity of 50.2 +/- 2.0%. The purified islet cells responded to stimulation with high glucose concentrations (16.7 mmol/L), namely, 4.74-fold greater than the insulin secretion with exposure to the basal level of glucose (3.3 mmol/L; P < .001). These results suggested that the established isolation method can be applied to large-scale purification of fully functional islets from pig pancreata. PMID:20620533

  1. Metabolism of cardiac glycosides studied in the isolated perfused guinea-pig liver

    PubMed Central

    Kolenda, K.-D.; Lüllmann, H.; Peters, T.

    1971-01-01

    1. Metabolic degradation of tritiated ouabain, digoxin, and digitoxin has been investigated quantitatively using the isolated perfused guinea-pig liver. The cardiac glycosides and their metabolites have been extracted from the plasma, liver, and bile by different solvents and identified as far as possible by radio-chromatographic analysis. 2. The total metabolic activity in the experimental system was localized in the liver. 3. The hydrophilic glycoside ouabain could not penetrate into the metabolically active compartment of the liver and was, therefore, not degraded. The more lipophilic compound digitoxin, however, was completely degraded due to its high affinity for the metabolically active sites. The unchanged digitoxin cannot enter the aqueous bile fluid in contrast to its more hydrophilic metabolites. 4. The only detectable metabolic degradation of digoxin was a conjugation with glucuronic and/or sulphuric acid, but a cleavage of sugar molecules seemed not to occur. 5. In the case of digitoxin the metabolic processes are more complicated: sugar cleavage, conjugation, and C-12 hydroxylation take place simultaneously. An immediate hydroxylation of digitoxin leading to digoxin was not observed. After administration of digitoxin conjugation products as well as digoxigenin-bis-and digoxigenin-mono-digitoxosides were present in each of the compartments investigated, but the digitoxosides of digitoxigenin were intermediates in concentrations too low to be determined indicating a very high rate of conjugation and/or C-12 hydroxylation as compared with the cleavage of the digitoxoses. 6. A scheme for the metabolic pathways of the cardiac glycosides based on experimental results is presented. The metabolic behaviour of each of the three compounds involved is closely related to their physicochemical properties, especially the lipid solubility. PMID:5579464

  2. Hypoxia in early pregnancy induces cardiac dysfunction in adult offspring of Rattus norvegicus, a non-hypoxia-adapted species.

    PubMed

    Hauton, David

    2012-11-01

    Environmental stresses such as hypoxia can alter the development of the fetus that are manifested later in life, but the impact of early maternal hypoxia (MH) on cardiac performance, coronary flow and catecholamine responsiveness in adult offspring is less clear. The effects of exposure to chronic hypoxia (FIO(2)=0.12) in early intrauterine development (days E1-10) on cardiac performance of the adult offspring were estimated using the Langendorff-perfused rat heart. Cardiac dysfunction is presented as increased end-diastolic volume, with decreased ventricular stiffness in both male and female adult offspring (P<0.01 for both). While developed pressures were preserved in female MH rats, males demonstrated a decrease in systolic function, estimated as peak developed pressure (P<0.01). Challenge with dobutamine (300 nM), an adrenergic positive inotrope, increased cardiac work for control rats (P<0.01 for male and female rats) but not in MH-male rats. Coronary flow was reduced (P<0.01) and SERCA2 protein expression increased (2-fold, P<0.05) in female offspring, while eNOS protein levels were increased (2.5-fold, P<0.05) in females. This suggests gender-specific differences in compensatory responses to early MH, with female rats increasing calcium turnover to improve contractility and increasing coronary flow through increased expression of eNOS protein, partially restoring coronary perfusion while male rats show little compensation. PMID:22892476

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

    SciTech Connect

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

    2013-01-01

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

  4. Hospital Resource Utilization for Common Noncardiac Diagnoses in Adult Survivors of Single Cardiac Ventricle.

    PubMed

    Seckeler, Michael D; Moe, Tabitha G; Thomas, Ian D; Meziab, Omar; Andrews, Jennifer; Heller, Elissa; Klewer, Scott E

    2015-12-01

    Single ventricle congenital heart disease (SV CHD) has transformed from a nearly universally fatal condition to a chronic illness. As the number of adults living with SV CHD continues to increase, there needs to be an understanding of health care resource utilization (HCRU), particularly for noncardiac conditions, for this patient population. We performed a retrospective database review of the University HealthSystem Consortium Clinical Database/Resource Manager for adult patients with SV CHD hospitalized for noncardiac conditions from January 2011 to November 2014. Patients with SV CHD were identified using International Classification of Disease (ICD)-9 codes associated with SV CHD (hypoplastic left heart, tricuspid atresia, and SV) and stratified into 2 groups by age (18 to 29 years and 30 to 40 years). Direct cost, length of stay (LOS), intensive care unit (ICU) admission rate and mortality data were compared with age-matched patients without CHD. There were 2,083,651 non-CHD and 590 SV CHD admissions in Group 1 and 2,131,046 non-CHD and 297 SV CHD admissions in Group 2. There was no difference in LOS in Group 1, but there were higher costs for several diagnoses. LOS and costs were higher for several diagnoses in Group 2. ICU admission rate and in-hospital mortality were higher for several diagnoses for patients with SV CHD in both groups. In conclusion, adults with SV CHD admitted for noncardiac diagnoses have higher HCRU (longer LOS and higher ICU admission rates) compared with similarly aged patients without CHD. These findings stress the importance of good primary care in this population with complex, chronic cardiac disease to prevent hospitalizations and higher HCRU. PMID:26455384

  5. Sudden cardiac death in adults with congenitally corrected transposition of the great arteries

    PubMed Central

    McCombe, A; Touma, F; Jackson, D; Canniffe, C; Choudhary, P; Pressley, L; Tanous, D; Robinson, Peter J; Celermajer, D

    2016-01-01

    Background Congenitally corrected transposition of the great arteries (ccTGA) is a rare congenital heart disease. There have been only few reports of sudden cardiac death (SCD) in patients with ccTGA and reasonable ventricular function. Methods A retrospective review of the medical records of all patients attending our adult congenital heart centre, with known ccTGA. Results From a database of over 3500 adult patients with congenital heart disease, we identified 39 (∼1%) with ccTGA and ‘two-ventricle’ circulations. 65% were male. The mean age at diagnosis was 12.4±11.4 years and the mean age at last time of review was 34.3±11.3 years. 24 patients (56%) had a history of surgical intervention. 8 (19%) had had pacemaker implantation and 2 had had a defibrillator implanted for non-sustained ventricular tachycardia (NSVT). In 544 years of patient follow-up, there had been five cases of SCD in our population; 1 death per 109 patient-years. Two of these patients had had previously documented supraventricular or NSVT. However, they were all classified as New York Heart Association (NYHA) class I or II, and systemic (right) ventricular function had been recorded as normal, mildly or mildly–moderately impaired, at most recent follow-up. Conclusions Our experience suggests the need for improved risk stratification and/or surveillance for malignant arrhythmia in adults with ccTGA, even in those with reasonable functional class on ventricular function. PMID:27493760

  6. Wild isolates of murine cytomegalovirus induce myocarditis and antibodies that cross-react with virus and cardiac myosin.

    PubMed Central

    Fairweather, D; Lawson, C M; Chapman, A J; Brown, C M; Booth, T W; Papadimitriou, J M; Shellam, G R

    1998-01-01

    The laboratory-adapted K181 strain of murine cytomegalovirus (MCMV) induces both acute and chronic myocarditis, associated with autoantibodies to cardiac myosin, in susceptible BALB/c mice. However, the K181 MCMV strain has been maintained in the laboratory for many years and may not resemble naturally occurring strains of MCMV in its ability to induce myocarditis. Accordingly, six different isolates of MCMV from wild Mus domesticus were compared with K181 MCMV for their ability to induce myocarditis and autoantibodies to cardiac myosin in BALB/c mice. These isolates were shown to induce acute myocarditis similar to K181 MCMV, with associated focal and diffuse myocardial inflammation. However, the levels of myocarditis induced by the wild isolates during the chronic phase of the disease (days 32-56 post-infection) were low in contrast to the K181 strain. Interestingly, 30% of wild-trapped mice showed histological evidence of myocarditis and all were sero-positive to MCMV. Sera from BALB/c mice infected with wild MCMV isolates and from wild-trapped mice contained antibodies that cross-reacted with MCMV and cardiac myosin (S2 region). The cross-reactive region of MCMV was found to be a 50,000-55,000 MW viral polypeptide. These findings suggest that molecular mimicry may be involved in the pathogenesis of autoimmune myocarditis following infection with both laboratory and wild MCMV strains. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:9741351

  7. Met signaling in cardiomyocytes is required for normal cardiac function in adult mice.

    PubMed

    Arechederra, María; Carmona, Rita; González-Nuñez, María; Gutiérrez-Uzquiza, Alvaro; Bragado, Paloma; Cruz-González, Ignacio; Cano, Elena; Guerrero, Carmen; Sánchez, Aránzazu; López-Novoa, José Miguel; Schneider, Michael D; Maina, Flavio; Muñoz-Chápuli, Ramón; Porras, Almudena

    2013-12-01

    Hepatocyte growth factor (HGF) and its receptor, Met, are key determinants of distinct developmental processes. Although HGF exerts cardio-protective effects in a number of cardiac pathologies, it remains unknown whether HGF/Met signaling is essential for myocardial development and/or physiological function in adulthood. We therefore investigated the requirement of HGF/Met signaling in cardiomyocyte for embryonic and postnatal heart development and function by conditional inactivation of the Met receptor in cardiomyocytes using the Cre-α-MHC mouse line (referred to as α-MHCMet-KO). Although α-MHCMet-KO mice showed normal heart development and were viable and fertile, by 6 months of age, males developed cardiomyocyte hypertrophy, associated with interstitial fibrosis. A significant upregulation in markers of myocardial damage, such as β-MHC and ANF, was also observed. By the age of 9 months, α-MHCMet-KO males displayed systolic cardiac dysfunction. Mechanistically, we provide evidence of a severe imbalance in the antioxidant defenses in α-MHCMet-KO hearts involving a reduced expression and activity of catalase and superoxide dismutase, with consequent reactive oxygen species accumulation. Similar anomalies were observed in females, although with a slower kinetics. We also found that Met signaling down-regulation leads to an increase in TGF-β production and a decrease in p38MAPK activation, which may contribute to phenotypic alterations displayed in α-MHCMet-KO mice. Consistently, we show that HGF acts through p38α to upregulate antioxidant enzymes in cardiomyocytes. Our results highlight that HGF/Met signaling in cardiomyocytes plays a physiological cardio-protective role in adult mice by acting as an endogenous regulator of heart function through oxidative stress control. PMID:23994610

  8. Beating and insulting children as a risk for adult cancer, cardiac disease and asthma.

    PubMed

    Hyland, Michael E; Alkhalaf, Ahmed M; Whalley, Ben

    2013-12-01

    The use of physical punishment for children is associated with poor psychological and behavioral outcomes, but the causal pathway is controversial, and the effects on later physical health unknown. We conducted a cross-sectional survey of asthma, cancer, and cardiac patients (150 in each category, 75 male) recruited from outpatient clinics and 250 healthy controls (125 male). All participants were 40-60 years old and citizens of Saudi Arabia, where the use of beating and insults is an acceptable parenting style. Demographic data and recalled frequency of beatings and insults as a child were assessed on an 8-point scale. Beating and insults were highly correlated (ρ = 0.846). Propensity score matching was used to control for demographic differences between the disease and healthy groups. After controlling for differences, more frequent beating (once or more per month) and insults were associated with a significantly increased risk for cancer (RR = 1.7), cardiac disease (RR = 1.3) and asthma (RR = 1.6), with evidence of increased risk for cancer and asthma with beating frequency of once every 6 months or more. Our results show that a threatening parenting style of beating and insults is associated with increased risk for somatic disease, possibly because this form of parenting induces stress. Our findings are consistent with previous research showing that child abuse and other early life stressors adversely affect adult somatic health, but provide evidence that the pathogenic effects occur also with chronic minor stress. A stress-inducing parenting style, even when normative, has long term adverse health consequences. PMID:23054177

  9. Putative population of adipose-derived stem cells isolated from mediastinal tissue during cardiac surgery.

    PubMed

    Patel, Amit N; Yockman, James; Vargas, Vanessa; Bull, David A

    2013-01-01

    Mesenchymal stem cells have been isolated from various adult human tissues and are valuable for not only therapeutic applications but for the study of tissue homeostasis and disease progression. Subcutaneous adipose depots have been shown to contain large amounts of stem cells. There is little information that has been reported to date describing the isolation and characterization of mesenchymal stem cells from visceral adipose tissue. In this study, we describe a mesenchymal stem cell population isolated from mediastinal adipose depots. The cells express CD44, CD105, CD166, and CD90 and are negative for hematopoietic markers CD34, CD45, and HLA-DR. In addition, the cells have a multilineage potential, with the ability to differentiate into adipogenic, osteogenic, and chondrogenic cell types. The biological function of visceral adipose tissue remains largely unknown and uncharacterized. However, the proximity of adipose tissue to the heart suggests a potential role in the pathogenesis of cardiovascular disease in obesity. In addition, with the ability of fat to regulate metabolic activity in humans, this novel stem cell source may be useful to further study the mechanisms involved in metabolic disorders. PMID:22490339

  10. Modeling the Calcium Sequestration System in Isolated Guinea Pig Cardiac Mitochondria*

    PubMed Central

    Bazil, Jason N.; Blomeyer, Christoph A.; Pradhan, Ranjan K.; Camara, Amadou K.S.; Dash, Ranjan K.

    2012-01-01

    Under high Ca2+ load conditions, Ca2+ concentrations in the extra-mitochondrial and mitochondrial compartments do not display reciprocal dynamics. This is due to a paradoxical increase in the mitochondrial Ca2+ buffering power as the Ca2+ load increases. Here we develop and characterize a mechanism of the mitochondrial Ca2+ sequestration system using an experimental data set from isolated guinea pig cardiac mitochondria. The proposed mechanism elucidates this phenomenon and others in a mathematical framework and is integrated into a previously corroborated model of oxidative phosphorylation including the Na+/Ca2+ cycle. The integrated model reproduces the Ca2+ dynamics observed in both compartments of the isolated mitochondria respiring on pyruvate after a bolus of CaCl2 followed by ruthenium red and a bolus of NaCl. The model reveals why changes in mitochondrial Ca2+ concentration of Ca2+ loaded mitochondria appear significantly mitigated relative to the corresponding extra-mitochondrial Ca2+ concentration changes after Ca2+ efflux is initiated. The integrated model was corroborated by simulating the set-point phenomenon. The computational results support the conclusion that the Ca2+ sequestration system is composed of at least two classes of Ca2+ buffers. The first class represents prototypical Ca2+ buffering, and the second class encompasses the complex binding events associated with the formation of amorphous calcium phosphate. With the Ca2+ sequestration system in mitochondria more precisely defined, computer simulations can aid in the development of innovative therapeutics aimed at addressing the myriad of complications that arise due to mitochondrial Ca2+ overload. PMID:23180139

  11. Does Parsonnet scoring model predict mortality following adult cardiac surgery in India?

    PubMed Central

    Srilata, Moningi; Padhy, Narmada; Padmaja, Durga; Gopinath, Ramachandran

    2015-01-01

    Aims and Objectives: To validate the Parsonnet scoring model to predict mortality following adult cardiac surgery in Indian scenario. Materials and Methods: A total of 889 consecutive patients undergoing adult cardiac surgery between January 2010 and April 2011 were included in the study. The Parsonnet score was determined for each patient and its predictive ability for in-hospital mortality was evaluated. The validation of Parsonnet score was performed for the total data and separately for the sub-groups coronary artery bypass grafting (CABG), valve surgery and combined procedures (CABG with valve surgery). The model calibration was performed using Hosmer–Lemeshow goodness of fit test and receiver operating characteristics (ROC) analysis for discrimination. Independent predictors of mortality were assessed from the variables used in the Parsonnet score by multivariate regression analysis. Results: The overall mortality was 6.3% (56 patients), 7.1% (34 patients) for CABG, 4.3% (16 patients) for valve surgery and 16.2% (6 patients) for combined procedures. The Hosmer–Lemeshow statistic was <0.05 for the total data and also within the sub-groups suggesting that the predicted outcome using Parsonnet score did not match the observed outcome. The area under the ROC curve for the total data was 0.699 (95% confidence interval 0.62–0.77) and when tested separately, it was 0.73 (0.64–0.81) for CABG, 0.79 (0.63–0.92) for valve surgery (good discriminatory ability) and only 0.55 (0.26–0.83) for combined procedures. The independent predictors of mortality determined for the total data were low ejection fraction (odds ratio [OR] - 1.7), preoperative intra-aortic balloon pump (OR - 10.7), combined procedures (OR - 5.1), dialysis dependency (OR - 23.4), and re-operation (OR - 9.4). Conclusions: The Parsonnet score yielded a good predictive value for valve surgeries, moderate predictive value for the total data and for CABG and poor predictive value for combined

  12. [Study of pantothenic acid derivatives as cardiac protectors in a model of experimental ischemia and reperfusion of the isolated heart].

    PubMed

    Kumerova, A O; Utno, L Ia; Lipsberga, Z E; Shkestere, I Ia

    1992-04-01

    An isolated heart model with experimental ischemia and reperfusion was used to show effective decrease in lactate, increase in ATP content and prevention of conjugated dienes accumulation in the myocardium by derivatives of pantothenic acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones applied simultaneously as ingredients of perfusate (25 microM) in postischemic period. In that way derivatives of pantothenic acid should be regarded as cardiac protectors. PMID:1391892

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

    PubMed Central

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

    2015-01-01

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

  14. Adrenergic responsiveness is reduced, while baseline cardiac function is preserved in old adult conscious monkeys

    NASA Technical Reports Server (NTRS)

    Sato, N.; Kiuchi, K.; Shen, Y. T.; Vatner, S. F.; Vatner, D. E.

    1995-01-01

    To examine the physiological deficit to adrenergic stimulation with aging, five younger adult (3 +/- 1 yr old) and nine older adult (17 +/- 1 yr old) healthy monkeys were studied after instrumentation with a left ventricular (LV) pressure gauge, aortic and left atrial catheters, and aortic flow probes to measure cardiac output directly. There were no significant changes in baseline hemodynamics in conscious older monkeys. For example, an index of contractility, the first derivative of LV pressure (LV dP/dt) was similar (3,191 +/- 240, young vs. 3,225 +/- 71 mmHg/s, old) as well as in isovolumic relaxation, tau (24.3 +/- 1.7 ms, young vs. 23.0 +/- 1.0 ms, old) was similar. However, inotropic, lusitropic, and chronotropic responses to isoproterenol (Iso; 0.1 micrograms/kg), norepinephrine (NE; 0.4 micrograms/kg), and forskolin (For; 75 nmol/kg) were significantly (P < 0.05) depressed in older monkeys. For example. Iso increased LV dP/dt by by 146 +/- 14% in younger monkeys and by only 70 +/- 5% in older monkeys. Iso also reduced tau more in younger monkeys (-28 +/- 7%) compared with older monkeys (-13 +/- 3%). Furthermore, peripheral vascular responsiveness to Iso, NE, For, and phenylephrine (PE; 5 micrograms/kg) was significantly (P < 0.05) reduced in older monkeys. For example, phenylephrine (5 micrograms/kg) increased total peripheral resistence by 69 +/- 4% in younger monkeys and by only 45 +/- 3% in older monkeys. Thus in older monkeys without associated cardiovascular disease, baseline hemodynamics are preserved, but adrenergic receptor responsiveness is reduced systemically, not just in the heart.

  15. Bioreactance Is Not Interchangeable with Thermodilution for Measuring Cardiac Output during Adult Liver Transplantation

    PubMed Central

    Han, Sangbin; Lee, Jong Hwan; Kim, Gaabsoo; Ko, Justin Sangwook; Choi, Soo Joo; Kwon, Ji Hae; Heo, Burn Young; Gwak, Mi Sook

    2015-01-01

    Background Thermodilution technique using a pulmonary artery catheter is widely used for the assessment of cardiac output (CO) in patients undergoing liver transplantation. However, the unclearness of the risk-benefit ratio of this method has led to an interest in less invasive modalities. Thus, we evaluated whether noninvasive bioreactance CO monitoring is interchangeable with thermodilution technique. Methods Nineteen recipients undergoing adult-to-adult living donor liver transplantation were enrolled in this prospective observational study. COs were recorded automatically by the two devices and compared simultaneously at 3-minute intervals. The Bland–Altman plot was used to evaluate the agreement between bioreactance and thermodilution. Clinically acceptable agreement was defined as a percentage error of limits of agreement <30%. The four quadrant plot was used to evaluate concordance between bioreactance and thermodilution. Clinically acceptable concordance was defined as a concordance rate >92%. Results A total of 2640 datasets were collected. The mean CO difference between the two techniques was 0.9 l/min, and the 95% limits of agreement were -3.5 l/min and 5.4 l/min with a percentage error of 53.9%. The percentage errors in the dissection, anhepatic, and reperfusion phase were 50.6%, 56.1%, and 53.5%, respectively. The concordance rate between the two techniques was 54.8%. Conclusion Bioreactance and thermodilution failed to show acceptable interchangeability in terms of both estimating CO and tracking CO changes in patients undergoing liver transplantation. Thus, the use of bioreactance as an alternative CO monitoring to thermodilution, in spite of its noninvasiveness, would be hard to recommend in these surgical patients. PMID:26017364

  16. The cardiac stem cell compartment is indispensable for myocardial cell homeostasis, repair and regeneration in the adult.

    PubMed

    Nadal-Ginard, Bernardo; Ellison, Georgina M; Torella, Daniele

    2014-11-01

    Resident cardiac stem cells in embryonic, neonatal and adult mammalian heart have been identified by different membrane markers and transcription factors. However, despite a flurry of publications no consensus has been reached on the identity and actual regenerative effects of the adult cardiac stem cells. Intensive research on the adult mammalian heart's capacity for self-renewal of its muscle cell mass has led to a consensus that new cardiomyocytes (CMs) are indeed formed throughout adult mammalian life albeit at a disputed frequency. The physiological significance of this renewal, the origin of the new CMs, and the rate of adult CM turnover are still highly debated. Myocyte replacement, particularly after injury, was originally attributed to differentiation of a stem cell compartment. More recently, it has been reported that CMs are mainly replaced by the division of pre-existing post-mitotic CMs. These latter results, if confirmed, would shift the target of regenerative therapy toward boosting mature CM cell-cycle re-entry. Despite this controversy, it is documented that the adult endogenous c-kit(pos) cardiac stem cells (c-kit(pos) eCSCs) participate in adaptations to myocardial stress, and, when transplanted into the myocardium, regenerate most cardiomyocytes and microvasculature lost in an infarct. Nevertheless, the in situ myogenic potential of adult c-kit(pos) cardiac cells has been questioned. To revisit the regenerative potential of c-kit(pos) eCSCs, we have recently employed experimental protocols of severe diffuse myocardial damage in combination with several genetic murine models and cell transplantation approaches showing that eCSCs are necessary and sufficient for CM regeneration, leading to complete cellular, anatomical, and functional myocardial recovery. Here we will review the available data on adult eCSC biology and their regenerative potential placing it in the context of the different claimed mechanisms of CM replacement. These data are in

  17. 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

  18. In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Effects on fetal and adult cardiac gene expression and adult cardiac and renal morphology

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mouse heart is a target of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during fetal development, and microarray analysis demonstrates significant changes in expression of cardiac genes involved in extracellular matrix (ECM) remodeling. We tested the hypothesis that developmental TCDD exposure wo...

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

    PubMed

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

    2012-08-01

    Centrifugal pump (CP) and roller pump (RP) designs are the dominant main arterial pumps used in cardiopulmonary bypass (CPB). Trials reporting clinical outcome measures comparing CP and RP are controversial. Therefore, a meta-analysis was undertaken to evaluate clinical variables from randomized controlled trials (RCTs). Keyword searches were performed on Medline (1966-2011), EmBase (1980-2011), and CINAHL (1981-2011) for studies comparing RP and CP as the main arterial pump in adult CPB. Pooled fixed-effects estimates for dichotomous and continuous data were calculated as an odds ratio and weighted-mean difference, respectively. The P value was utilized to assess statistical significance (P < 0.05) between CP and RP groups. Eighteen RCTs met inclusion criteria, which represented 1868 patients (CP = 961, RP = 907). The prevailing operation was isolated coronary artery bypass graft surgery (CP = 88%, RP = 87%). Fixed-effects pooled estimates were performed for end-of-CPB (ECP) and postoperative day one (PDO) for platelet count (ECP: P = 0.51, PDO: P = 0.16), plasma free hemoglobin (ECP: P = 0.36, PDO: P = 0.24), white blood cell count (ECP: P = 0.21, PDO: P = 0.66), and hematocrit (ECP: P = 0.06, PDO: P = 0.51). No difference was demonstrated for postoperative blood loss (P = 0.65) or red blood cell transfusion (P = 0.71). Intensive care unit length of stay (P = 0.30), hospital length of stay (P = 0.33), and mortality (P = 0.91) were similar between the CP and RP groups. Neurologic outcomes were not amenable to pooled analysis; nevertheless, the results were inconclusive. There was no reported pump-related malfunction or mishap. The meta-analysis of RCTs comparing CP and RP in adult cardiac surgery suggests no significant difference for hematological variables, postoperative blood loss, transfusions, neurological outcomes, or mortality. PMID:22804106

  20. Drosophila Models of Cardiac Disease

    PubMed Central

    Piazza, Nicole; Wessells, R.J.

    2013-01-01

    The fruit fly Drosophila melanogaster has emerged as a useful model for cardiac diseases, both developmental abnormalities and adult functional impairment. Using the tools of both classical and molecular genetics, the study of the developing fly heart has been instrumental in identifying the major signaling events of cardiac field formation, cardiomyocyte specification, and the formation of the functioning heart tube. The larval stage of fly cardiac development has become an important model system for testing isolated preparations of living hearts for the effects of biological and pharmacological compounds on cardiac activity. Meanwhile, the recent development of effective techniques to study adult cardiac performance in the fly has opened new uses for the Drosophila model system. The fly system is now being used to study long-term alterations in adult performance caused by factors such as diet, exercise, and normal aging. The fly is a unique and valuable system for the study of such complex, long-term interactions, as it is the only invertebrate genetic model system with a working heart developmentally homologous to the vertebrate heart. Thus, the fly model combines the advantages of invertebrate genetics (such as large populations, facile molecular genetic techniques, and short lifespan) with physiological measurement techniques that allow meaningful comparisons with data from vertebrate model systems. As such, the fly model is well situated to make important contributions to the understanding of complicated interactions between environmental factors and genetics in the long-term regulation of cardiac performance. PMID:21377627

  1. Geophysical variables and behavior: CIII. Days with sudden infant deaths and cardiac arrhythmias in adults share a factor with PC1 geomagnetic pulsations: implications for pursuing mechanism.

    PubMed

    Persinger, M A; O'Connor, R P

    2001-06-01

    If geomagnetic-mediated stimuli trigger many sudden infant deaths, then the days in which they and hospital admissions for cardiac arrhythmias for adults occur should share a similar source of variance. Factor analyses of the days in which a sudden infant death occurred in Ontario or adults were admitted for one of eight categories of cardiac crisis in the Sudbury (Ontario) Region for the year 1984 supported the hypothesis. This factor, with which infant deaths and adult cardiac arrhythmias each shared about 40% of their variance, also shared about 40% of the variance with a factor with which about 35% of the variance in daily occurrence of geomagnetic pulsations (0.2 Hz to 5 Hz) was associated. These results are consistent with the important role of geomagnetic variables in the occurrence of transient electrical anomalies in brain function rather than cardiac blood flow. PMID:11453188

  2. Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes

    PubMed Central

    Agarwal, Shailesh R.; MacDougall, David A.; Tyser, Richard; Pugh, Sara D.; Calaghan, Sarah C.; Harvey, Robert D.

    2011-01-01

    β1-Adrenergic receptors (β1ARs) and E-type prostaglandin receptors (EPRs) both produce compartmentalized cAMP responses in cardiac myocytes. The role of cholesterol-dependent lipid rafts in producing these compartmentalized responses was investigated in adult rat ventricular myocytes. β1ARs were found in lipid raft and non-lipid raft containing membrane fractions, while EPRs were only found in non-lipid raft fractions. Furthermore, β1AR activation enhanced the L-type Ca2+ current, intracellular Ca2+ transient, and myocyte shortening, while EPR activation had no effect, consistent with the idea that these functional responses are regulated by cAMP produced by receptors found in lipid raft domains. Using methyl-β-cyclodextrin to disrupt lipid rafts by depleting membrane cholesterol did not eliminate compartmentalized behavior, but it did selectively alter specific receptor-mediated responses. Cholesterol depletion enhanced the sensitivity of functional responses produced by β1ARs without having any effect on EPR activation. Changes in cAMP activity were also measured in intact cells using two different FRET-based biosensors: a type II PKA-based probe to monitor cAMP in subcellular compartments that include microdomains associated with caveolar lipid rafts and a freely diffusible Epac2-based probe to monitor total cytosolic cAMP. β1AR and EPR activation elicited responses detected by both FRET probes. However, cholesterol depletion only affected β1AR responses detected by the PKA probe. These results indicate that lipid rafts alone are not sufficient to explain the difference between β1AR and EPR responses. They also suggest that β1AR regulation of myocyte contraction involves the local production of cAMP by a subpopulation of receptors associated with caveolar lipid rafts. PMID:21115018

  3. Isolation of cardiac myosin light-chain isotypes by chromatofocusing. Comparison of human cardiac atrial light-chain 1 and foetal ventricular light-chain 1.

    PubMed

    Vincent, N D; Cummins, P

    1985-04-01

    Cardiac myosin light chain isotypes have been resolved using chromatofocusing, a new preparative column chromatographic technique. The method relies on production of narrow-range, shallow and stable pH gradients using ion-exchange resins and buffers with even buffering capacity over the required pH range. Light chains were resolved in order of decreasing isoelectric point in the pH range 5.2-4.5. Gradients of delta pH = 0.004-0.006/ml elution volume were achieved which were capable of resolving light chains with isoelectric point differences of only 0.03. Analytical isoelectric focusing of light chains in polyacrylamide gels could be used to predict the results of preparative chromatofocusing for method development. Chromatofocusing was capable of resolving human and bovine cardiac light chain 1 and 2 subunits, atrial (ALC) and ventricular (VLC) light chain isotypes and homologous VLC-2 and VLC-2* light chains. The technique was used to purify and resolve the human foetal ventricular light chain 1 (FLC-1) from adult ventricular light chain 1 (VLC-1) present in foetal ventricles and the atrial light chain 1 (ALC-1) in adult atria. Comparative peptide mapping studies and amino acid analyses were carried out on FLC-1 and ALC-1. No differences were detected between FLC-1 and ALC-1 using three different proteases and amino acid compositions were similar with the exception of glycine content. The studies indicate that FLC-1 and ALC-1 are homologous, and possibly identical, light chains. Comparison of human FLC-1/ALC-1 with VLC-1 suggested marked structural and chemical differences in these light chain isotypes, in particular in the contents of methionine, proline, lysine and alanine residues. Differences in the contents of these residues were also apparent in the corresponding bovine atrial and ventricular light chains [Wikman-Coffelt, J. & Srivastava, S. (1979) FEBS Lett. 106, 207-212]. The latter three residues are known to be rich in the N-termini of cardiac and

  4. Can the direct cardiac effects of the electric pulses generated by the TASER X26 cause immediate or delayed sudden cardiac arrest in normal adults?

    PubMed

    Ideker, Raymond E; Dosdall, Derek J

    2007-09-01

    There is only a small amount of experimental data about whether the TASER X26, a nonlethal weapon that delivers a series of brief electrical pulses to cause involuntary muscular contraction to temporarily incapacitate an individual, can initiate ventricular fibrillation to cause sudden cardiac arrest either immediately or sometime after its use. Therefore, this paper uses the fundamental law of electrostimulation and experimental data from the literature to estimate the likelihood of such events. Because of the short duration of the TASER pulses, the large duration of the cardiac cell membrane time constant, the small fraction of current from electrodes on the body surface that passes through the heart, and the resultant high pacing threshold from the body surface, the fundamental law of electrostimulation predicts that the TASER pulses will not stimulate an ectopic beat in the large majority of normal adults. Since the immediate initiation of ventricular fibrillation in a normal heart requires a very premature stimulated ectopic beat and the threshold for such premature beats is higher than less premature beats, it is unlikely that TASER pulses can immediately initiate ventricular fibrillation in such individuals through the direct effect of the electric field generated through the heart by the TASER. In the absence of preexisting heart disease, the delayed development of ventricular fibrillation requires the electrical stimuli to cause electroporation or myocardial necrosis. However, the electrical thresholds for electroporation and necrosis are many times higher than that required to stimulate an ectopic beat. Therefore, it is highly unlikely that the TASER X26 can cause ventricular fibrillation minutes to hours after its use through direct cardiac effects of the electric field generated by the TASER. PMID:17721165

  5. Does short preoperative statin therapy prevent infectious complications in adults undergoing cardiac or non-cardiac surgery?

    PubMed Central

    Li, Hua; Lin, Yuan-Long; Diao, Shu-Ling; Ma, Bao-Xin; Liu, Xian-Liang

    2016-01-01

    Objectives: To evaluate the effect of preoperative statin therapy on the incidence of postoperative infection. Methods: This systematic review of the literature was carried out in August 2015. Studies were retrieved via PubMed, Embase, and the Cochrane Library (1980 to 2015), and the reference files were limited to English-language articles. We used a standardized protocol, and a meta-analysis was performed for data abstraction. Results: Five studies comprising 1,362 patients qualified for the analysis. The incidence of postoperative infections in the statin group (1.1%) was not significantly lower than that in the placebo group (2.4%), with a risk ratio (RR) of 0.56 (95% confidence interval [CI] 0.24-1.33, p=0.19). Patients of 3 studies underwent cardiac surgery. The aggregated results of these studies failed to show significant differences in postoperative infection when a fixed effects model was used (RR: 0.39; 95% CI: 0.08-1.97, p=0.26]. Conclusions: We failed to find sufficient evidence to support the association between statin use and postoperative infectious complications. The absence of any evidence for a beneficial effect in available randomized trials reduces the likelihood of a causal effect as reported in observational studies. PMID:27146610

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

    PubMed

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

    2015-09-01

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

  7. Three-Dimensional Adult Cardiac Extracellular Matrix Promotes Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    PubMed

    Fong, Ashley H; Romero-López, Mónica; Heylman, Christopher M; Keating, Mark; Tran, David; Sobrino, Agua; Tran, Anh Q; Pham, Hiep H; Fimbres, Cristhian; Gershon, Paul D; Botvinick, Elliot L; George, Steven C; Hughes, Christopher C W

    2016-08-01

    Pluripotent stem cell-derived cardiomyocytes (CMs) have great potential in the development of new therapies for cardiovascular disease. In particular, human induced pluripotent stem cells (iPSCs) may prove especially advantageous due to their pluripotency, their self-renewal potential, and their ability to create patient-specific cell lines. Unfortunately, pluripotent stem cell-derived CMs are immature, with characteristics more closely resembling fetal CMs than adult CMs, and this immaturity has limited their use in drug screening and cell-based therapies. Extracellular matrix (ECM) influences cellular behavior and maturation, as does the geometry of the environment-two-dimensional (2D) versus three-dimensional (3D). We therefore tested the hypothesis that native cardiac ECM and 3D cultures might enhance the maturation of iPSC-derived CMs in vitro. We demonstrate that maturation of iPSC-derived CMs was enhanced when cells were seeded into a 3D cardiac ECM scaffold, compared with 2D culture. 3D cardiac ECM promoted increased expression of calcium-handling genes, Junctin, CaV1.2, NCX1, HCN4, SERCA2a, Triadin, and CASQ2. Consistent with this, we find that iPSC-derived CMs in 3D adult cardiac ECM show increased calcium signaling (amplitude) and kinetics (maximum upstroke and downstroke) compared with cells in 2D. Cells in 3D culture were also more responsive to caffeine, likely reflecting an increased availability of calcium in the sarcoplasmic reticulum. Taken together, these studies provide novel strategies for maturing iPSC-derived CMs that may have applications in drug screening and transplantation therapies to treat heart disease. PMID:27392582

  8. [Cardiac MRI in the follow-up of adult congenital cardiomyopathy patients].

    PubMed

    Monney, P; Stalder, N; Clair, M; Vogt, P; Schwitter, J; Meijboom, E J; Bouchardy, J

    2011-06-01

    Magnetic resonance imaging is a rapidly developing modality in cardiology. It offers an excellent image definition and a large field of view, allowing a more accurate morphological assessment of cardiac malformations. Due to its unique versatility and its ability to provide myocardial tissue characterization, cardiac magnetic resonance (CMR) is now recognized as a central imaging modality for a wide range of congenital heart diseases, including assessment of post-surgical cardiac anatomy, quantification of valvular disease and detection of myocardial ischemia. CMR provides useful diagnostic information without any radiation exposure, and improves the global management of patients with congenital heart disease. PMID:21717692

  9. Plasma High Sensitivity Troponin T Levels in Adult Survivors of Childhood Leukaemias: Determinants and Associations with Cardiac Function

    PubMed Central

    Cheung, Yiu-fai; Yu, Wei; Cheuk, Daniel Ka-leung; Cheng, Frankie Wai-tsoi; Yang, Janet Yee-kwan; Yau, Jeffrey Ping-wa; Ho, Karin Ka-huen; Li, Chi-kong; Li, Rever Chak-ho; Yuen, Hui-leung; Ling, Alvin Siu-cheung; Li, Vivian Wing-yi; Wong, Wai-keung; Tsang, Kwong-cheong; Chan, Godfrey Chi-fung

    2013-01-01

    Background We sought to quantify plasma high sensitivity cardiac troponin (hs-cTnT) levels, their determinants, and their associations with left ventricular (LV) myocardial deformation in adult survivors of childhood acute leukaemias. Methods and Results One hundred adult survivors (57 males) of childhood acute leukaemias, aged 24.1±4.2 years, and 42 age-matched controls (26 males) were studied. Plasma cTnT was determined using a highly sensitive assay. Genotyping of NAD(P)H oxidase and multidrug resistance protein polymorphisms was performed. Left ventricular function was assessed by conventional, three-dimensional, and speckle tracking echocardiography. The medians (interquartile range) of hs-cTnT in male and female survivors were 4.9 (4.2 to 7.2) ng/L and 1.0 (1.0 to 3.5) ng/L, respectively. Nineteen survivors (13 males, 6 females) (19%) had elevated hs-cTnT (>95th centile of controls). Compared to those without elevated hs-TnT levels, these subjects had received larger cumulative anthracycline dose and were more likely to have leukaemic relapse, stem cell transplant, and cardiac irradiation. Their LV systolic and early diastolic myocardial velocities, isovolumic acceleration, and systolic longitudinal strain rate were significantly lower. Survivors having CT/TT at CYBA rs4673 had higher hs-cTnT levels than those with CC genotype. Functionally, increased hs-cTnT levels were associated with worse LV longitudinal systolic strain and systolic and diastolic strain rates. Conclusions Increased hs-cTnT levels occur in a significant proportion of adult survivors of childhood acute leukaemias and are associated with larger cumulative anthracycline dose received, history of leukaemic relapse, stem cell transplant, and cardiac irradiation, genetic variants in free radical metabolism, and worse LV myocardial deformation. PMID:24204736

  10. In-hospital resuscitation: recognising and responding to adults in cardiac arrest.

    PubMed

    Simpson, Elizabeth

    2016-08-17

    Survival rates following in-hospital cardiac arrest remain low. The majority of patients who survive a cardiac arrest will be in a monitored environment, have a witnessed cardiac arrest and present with a shockable rhythm, usually ventricular fibrillation. Nurses have a responsibility to preserve safety, which requires the ability to accurately assess patients for signs of deterioration in physical health, and to provide assistance when an emergency arises in practice. Nurses must work within the limits of their competence and be able to establish the urgency of a situation. Nurses in all areas of practice must be able to recognise the signs of cardiac arrest and know the prompt response sequence required to improve the patient's chances of survival. This article focuses on inpatient resuscitation in acute healthcare environments and is aimed at staff who may be the first to respond to an in-hospital cardiac arrest. This does not include specialist units such as neurosurgery, intensive therapy units and cardiac catheterisation laboratories, where medical experts are available and clinical priorities may differ. PMID:27533415

  11. Sufficient myocardial protection of del Nido cardioplegia regardless of ventricular mass and myocardial ischemic time in adult cardiac surgical patients

    PubMed Central

    Kim, Ji Seong; Jeong, Jin Hee; Moon, Sin Ju; Ahn, Hyuk

    2016-01-01

    Background Del Nido (DN) cardioplegic solution (CPS) has been widely used during pediatric cardiac surgery. However, its use in the field of adult cardiac surgery is not popular yet. We evaluated efficacy of DN cardioplegia in adult cardiac surgical patients. Methods Fifty-three adult patients (mean age, 54±16 years) who underwent cardiovascular surgery using DN cardioplegia were enrolled. Myocardial troponin I (TnI) level up to three days after surgery and early clinical outcomes were evaluated. Propensity score matching was performed to compare these results with those after surgery using blood cardioplegia (BC). Results DN cardioplegia was infused with an initial dose of 1,126±221 mL, and an additional 500 mL was reinfused in 15 patients 91 minutes after initial infusion. After release of aortic cross clamp (ACC), spontaneous defibrillation was achieved in 94.3% (50/53). The peak TnI level after surgery was 9.8 ng/mL (range, 2.0–90.2 ng/mL). Linear regression models demonstrated that neither left ventricular mass (LVM) nor ACC time was associated with increased level of peak TnI (P=0.928 and 0.595, respectively). Early mortality occurred in one patient (1.9%). Postoperative complications included atrial fibrillation (n=18, 34.0%), acute kidney injury (n=4, 7.5%), low cardiac output syndrome (n=1, 1.9%), and respiratory complications (n=1, 1.9%). Propensity score matching extracted 39 pairs. Spontaneous defibrillation was achieved more frequently in the DN than BC groups (37/39 vs. 12/39, P<0.001). Peak level and serial changes of TnI were not statistically different between the two groups (P=0.085 and 0.959, respectively). There were also no significant differences in early mortality and postoperative complication rates between the two groups. Conclusions DN cardioplegia is as effective as BC for adult patients in terms of myocardial protection and early clinical outcomes.

  12. Spectrally resolved time-correlated single photon counting: a novel approach for characterization of endogenous fluorescence in isolated cardiac myocytes.

    PubMed

    Chorvat, D; Chorvatova, A

    2006-12-01

    A new setup for time-resolved fluorescence micro-spectroscopy of cells, based on multi-dimensional time-correlated single photon counting, was designed and tested. Here we demonstrate that the spectrometer allows fast and reproducible measurements of endogenous flavin fluorescence measured directly in living cardiac cells after excitation with visible picosecond laser diodes. Two complementary approaches for the analysis of spectrally- and time-resolved autofluorescence data are presented, comprising the fluorescence decay fitting by exponential series and the time-resolved emission spectroscopy analysis. In isolated cardiac myocytes, we observed three distinct lifetime pools with characteristic lifetime values spanning from picosecond to nanosecond range and the time-dependent red shift of the autofluorescence emission spectra. We compared obtained results to in vitro recordings of free flavin adenine dinucleotide (FAD) and FAD in lipoamide dehydrogenase (LipDH). The developed setup combines the strength of both spectral and fluorescence lifetime analysis and provides a solid base for the study of complex systems with intrinsic fluorescence, such as identification of the individual flavinoprotein components in living cardiac cells. This approach therefore constitutes an important instrumental advancement towards redox fluorimetry of living cardiomyocytes, with the perspective of its applications in the investigation of oxidative metabolic state under pathophysiological conditions, such as ischemia and/or metabolic disorders. PMID:17033778

  13. Isolated congenital cardiac diverticulum originating from the left ventricular apex: Report of a pediatric case.

    PubMed

    Uysal, Fahrettin; Bostan, Ozlem Mehtap; Toprak, Muhammed Hamza Halil; Signak, Isik Senkaya; Cil, Ergun

    2016-01-01

    Congenital ventricular diverticulum is a rare cardiac anomaly defined as a localized protrusion of the ventricular free wall. Although, it is usually asymptomatic, complications such as embolism, infective endocarditis, and arrhythmias can occur. The diagnosis can be made by echocardiography, cardiac magnetic resonance imaging, or catheter angiography. Surgical resection is the treatment of choice in symptomatic patients, whereas the management of asymptomatic patients often represents a therapeutic dilemma. We report here, a 9-month-old patient with asymptomatic congenital left ventricular (LV) diverticulum associated with epigastric hernia. PMID:27212863

  14. Isolated congenital cardiac diverticulum originating from the left ventricular apex: Report of a pediatric case

    PubMed Central

    Uysal, Fahrettin; Bostan, Ozlem Mehtap; Toprak, Muhammed Hamza Halil; Signak, Isik Senkaya; Cil, Ergun

    2016-01-01

    Congenital ventricular diverticulum is a rare cardiac anomaly defined as a localized protrusion of the ventricular free wall. Although, it is usually asymptomatic, complications such as embolism, infective endocarditis, and arrhythmias can occur. The diagnosis can be made by echocardiography, cardiac magnetic resonance imaging, or catheter angiography. Surgical resection is the treatment of choice in symptomatic patients, whereas the management of asymptomatic patients often represents a therapeutic dilemma. We report here, a 9-month-old patient with asymptomatic congenital left ventricular (LV) diverticulum associated with epigastric hernia. PMID:27212863

  15. Mammalian Fetal Cardiac Regeneration Following Myocardial Infarction is Associated with Differential Gene Expression Compared to the Adult

    PubMed Central

    Zgheib, Carlos; Allukian, Myron W.; Xu, Junwang; Morris, Michael W.; Caskey, Robert C.; Herdrich, Benjamin J.; Hu, Junyi; Gorman, Joseph H.; Gorman, Robert C.; Liechty, Kenneth W.

    2014-01-01

    Background In adults, MI results in a brisk inflammatory response, myocardium loss and scar formation. We have recently reported the first mammalian large animal model of cardiac regeneration following MI in fetal sheep. We hypothesize that the fetus ability to regenerate functional myocardium following MI is due to differential gene expression regulating the response to MI in the fetus compared to the adult. Methods MI was created in adult (n=4) or early gestation fetal (n=4) sheep. Tissue harvested after 3 or 30 days, RNA extracted for microarray, followed by PCA and global gene expression analysis for the gene ontology (GO) terms: “response to wounding”, “inflammatory response”, “extracellular matrix”, “cell cycle”, “cell migration”, “cell proliferation” and “apoptosis”. Results PCA demonstrated that the global gene expression pattern in adult infarcts was distinctly different from uninfarcted region at 3 days and remained different 30 days post-MI. In contrast, gene expression in the fetal infarct was different from the uninfarcted region at 3 days, but by 30 days it returned to a baseline expression pattern similar to the uninfarcted region. 3 days post-MI there was an increase in the expression of genes related to all GO terms in fetal and adult infarcts, but this increase was much more pronounced in adults. By 30 days, the fetal gene expression returned to baseline, whereas in the adult remained significantly elevated. Conclusions These data demonstrate that the global gene expression pattern is dramatically different in the fetal regenerative response to MI compared to the adult response and may partly be responsible for the regeneration. PMID:24792251

  16. Cardiac cell proliferation assessed by EdU, a novel analysis of cardiac regeneration.

    PubMed

    Zeng, Bin; Tong, Suiyang; Ren, Xiaofeng; Xia, Hao

    2016-08-01

    Emerging evidence suggests that mammalian hearts maintain the capacity for cardiac regeneration. Rapid and sensitive identification of cardiac cellular proliferation is prerequisite for understanding the underlying mechanisms and strategies of cardiac regeneration. The following immunologically related markers of cardiac cells were analyzed: cardiac transcription factors Nkx2.5 and Gata 4; specific marker of cardiomyocytes TnT; endothelial cell marker CD31; vascular smooth muscle marker smooth muscle myosin IgG; cardiac resident stem cells markers IsL1, Tbx18, and Wt1. Markers were co-localized in cardiac tissues of embryonic, neonatal, adult, and pathological samples by 5-ethynyl-2'-deoxyuridine (EdU) staining. EdU was also used to label isolated neonatal cardiomyocytes in vitro. EdU robustly labeled proliferating cells in vitro and in vivo, co-immunostaining with different cardiac cells markers. EdU can rapidly and sensitively label proliferating cardiac cells in developmental and pathological states. Cardiac cell proliferation assessed by EdU is a novel analytical tool for investigating the mechanism and strategies of cardiac regeneration in response to injury. PMID:25480318

  17. Cardiac and pulmonary anaphylaxis in guinea pigs and rabbits induced by glycoprotein isolated from tobacco leaves and cigarette smoke condensate

    SciTech Connect

    Levi, R.; Zavecz, J.H.; Burke, J.A.; Becker, C.G.

    1982-03-01

    Cigarette smoking is a major risk factor for heart attack. The pathologic mechanisms responsible for this association are obscure. It has been reported that approximately one-third of human volunteers, smokers and nonsmokers, exhibit immediate cutaneous hypersensitivity to a glycoprotein antigen (TGP) purified from cured tobacco leaves and present in cigarette smoke. It is also known that the heart is a primary target organ for anaphylactic reaction in many animals, including primates. In experiments described herein anaphylaxis was induced in the isolated hearts and lungs of rabbits and guinea pigs previously sensitized by immunization with TGP and challenged with TGP isolated from either tobacco leaf or cigarette smoke condensate. Cardiac anaphylaxis was characterized by sinus tachycardia, decreased contractility, decreased coronary perfusion accompanied by hypoxic electrocardiographic changes, and a variety of rhythm disturbances, including idioventricular tachyarrhythmias. These observations suggest that allergic reactions to tobacco constituents may initiate cardiac arrhythmia and sudden death in some smokers and may, in part, underly the association between cigarette smoking and heart attack.

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

    PubMed

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

    2016-07-01

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

  19. C-type natriuretic peptide activates a non-selective cation current in acutely isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated signalling.

    PubMed

    Rose, R A; Hatano, N; Ohya, S; Imaizumi, Y; Giles, W R

    2007-04-01

    In the heart, fibroblasts play an essential role in the deposition of the extracellular matrix and they also secrete a number of hormonal factors. Although natriuretic peptides, including C-type natriuretic peptide (CNP) and brain natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the effects of CNP on fibroblast electrophysiology have not been examined. In this study, acutely isolated ventricular fibroblasts from the adult rat were used to measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non-selective cation current (NSCC). This current has a reversal potential near 0 mV. Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts revealed the expression of several transient receptor potential (TRP) channel transcripts. Additional electrophysiological analysis showed that U73122, a phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are defining characteristics of specific TRPC channels. More detailed molecular analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5 transcripts. These data indicate that CNP, acting via the NPR-C receptor, activates a NSCC that is at least partially carried by TRPC channels in cardiac fibroblasts. PMID:17204501

  20. Pro: early extubation in the operating room following cardiac surgery in adults.

    PubMed

    Singh, Karen E; Baum, Victor C

    2012-12-01

    There is growing evidence that the general current approach in many centers of continued mechanical ventilation following cardiac surgery has evolved through historical experience rather than having a strong physiological basis in current practice. There is evidence going back several decades supporting very early (in the operating room [OR]) extubation in pediatric cardiac anesthesia. The authors provide evidence from numerous sources showing that extubation in the OR or shortly after arrival in the ICU is safe and cost-effective and is not prevented by the type of cardiac surgery or the use of cardiopulmonary bypass. They query if the paradigm should not be reversed and very early extubation be the routine unless contraindicated. Like any anesthetic technique, appropriate patient selection is called for, but this technique is widely appropriate. PMID:22798230

  1. Isolation, culture and analysis of adult subependymal neural stem cells.

    PubMed

    Belenguer, Germán; Domingo-Muelas, Ana; Ferrón, Sacri R; Morante-Redolat, José Manuel; Fariñas, Isabel

    2016-01-01

    Individual cells dissected from the subependymal neurogenic niche of the adult mouse brain proliferate in medium containing basic fibroblast growth factor (bFGF) and/or epidermal growth factor (EGF) as mitogens, to produce multipotent clonal aggregates called neurospheres. These cultures constitute a powerful tool for the study of neural stem cells (NSCs) provided that they allow the analysis of their features and potential capacity in a controlled environment that can be modulated and monitored more accurately than in vivo. Clonogenic and population analyses under mitogen addition or withdrawal allow the quantification of the self-renewing and multilineage potency of these cells and the identification of the mechanisms involved in these properties. Here, we describe a set of procedures developed and/or modified by our group including several experimental options that can be used either independently or in combination for the ex vivo assessment of cell properties of NSCs obtained from the adult subependymal niche. PMID:27016251

  2. Ethics in Evaluating a Sociotechnical Intervention With Socially Isolated Older Adults.

    PubMed

    Waycott, Jenny; Morgans, Amee; Pedell, Sonja; Ozanne, Elizabeth; Vetere, Frank; Kulik, Lars; Davis, Hilary

    2015-11-01

    The purpose of this article is to consider how ethical principles can inform the effective design and implementation of technology-based interventions that aim to promote the well-being of socially isolated older adults. We evaluated a new iPad application with small groups of older adults. In this article, we reflect on the ethical issues encountered at each stage of the research process. Drawing on the ethical principles of beneficence, research merit and integrity, justice, and respect, we identify key issues to consider in the future design and implementation of social isolation interventions that use new technologies. Key issues include (a) providing sufficient support to facilitate ongoing social interactions, (b) managing older adults' expectations, (c) providing encouragement without coercion, and (d) responding to individual needs. We conclude that it is important to report on ethical challenges incurred when evaluating social isolation interventions to inform future research in this important area. PMID:25646003

  3. Lay Referral Patterns Involved in Cardiac Treatment Decision Making among Middle-Aged and Older Adults

    ERIC Educational Resources Information Center

    Schoenberg, Nancy E.; Amey, Cheryl H.; Stoller, Eleanor Palo; Muldoon, Susan B.

    2003-01-01

    Purpose: This study examined age and contextually related factors that are influential in lay referral patterns during cardiac treatment decision making. Design and Methods: A complementary design was used. The Myocardial Infarction (MI) Onset Study identified demographic correlates of who sought medical care for 1,388 MI (heart attack) survivors.…

  4. Depression, Social Isolation, and the Lived Experience of Dancing in Disadvantaged Adults.

    PubMed

    Murrock, Carolyn J; Graor, Christine Heifner

    2016-02-01

    This qualitative study described the lived experience of dancing as it related to depression and social isolation in 16 disadvantaged adults who completed a 12-week dance intervention. It is the first qualitative study to explore the experience of dance as an adjunct therapy, depression, and social isolation. A descriptive phenomenological framework consisted of two focus groups using semi-structured interviews. A Giorgian approach guided thematic analysis. Four themes emerged: (1) dance for myself and health, (2) social acceptance, (3) connection with others: a group, and (4) not wanting to stop: unexpected benefits from dancing. As the participants continued to dance, they developed a sense of belonging and group identity, which may have maintained group involvement and contributed to reducing depression and social isolation. Thus, dancing is a complementary therapy that should be considered when working with adults with depression and social isolation. PMID:26804498

  5. Adult abdominal Burkitt lymphoma with isolated peritoneal involvement

    PubMed Central

    Oliveira, Catarina; Matos, Hugo; Serra, Paula; Catarino, Rui; Estevão, Amélia

    2014-01-01

    Burkitt lymphoma is a fast-growing high grade B-cell neoplasm that rarely affects adults. Three clinical variants are described in the World Health Organization classification: endemic, sporadic, and immunodeficiency-associated. The non-endemic form typically presents as an abdominal mass in children. Symptoms usually occur due to mass effect or direct intestinal involvement. We describe a very unusual presentation of a sporadic Burkitt lymphoma case in a 61-year-old male with diffuse peritoneal and omental involvement, without lymphadenopathies, mimicking peritoneal carcinomatosis. PMID:24967011

  6. Effects of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults.

    PubMed

    Chang, Xiao-Rong; Yan, Jie; Shen, Jing; Liu, Mi; Wang, Xiao-Juan

    2010-09-01

    The effect of acupuncture at the acupoints of 12 meridians on gastrointestinal and cardiac electricity in healthy adults was studied. Specific regulation between meridian points and viscera was also investigated. An electrogastrogram (EGG), electrointestinogram (EIG), carotid pulse graph, phonocardiogram and electrocardiogram were obtained in 30 healthy adults before and after acupuncture at various acupoints of 12 meridians. The effects of acupuncture on the amplitude and frequency of the EGG, EIG, pre-ejection period and the left ventricular ejection time were then analyzed. Acupuncture revealed that LR3 decreased the amplitude of the EGG while LI11 (Quchi), SJ5 (Waiguan), ST36 (Zusanli), SP9 (Yinlingquan) and SI6 (Yanglao) increased the amplitude. Multiple comparisons among the latter five acupoints indicated that there were significant differences between SP9, LI11, SJ5 and ST36 (p < 0.01, p < 0.01, p < 0.05) and SI6, LI11 and SJ5 (p < 0.01, p < 0.05). SP9 effected EGG amplitude the most, followed by SI6, ST36, SJ5 and LI11. Four acupoints increased the amplitude of the EIG (p < 0.05), including HT5 (Tongli), GB34 (Yanglingquan), SP9 and SI6. No significant differences were observed between these acupoints, but SI6 showed the most obvious effect on EIG amplitude, followed by GB34, SP9 and HT5. No significant effects on the frequency of the gastrointestinal slow wave or on cardiac function indexes were observed. Effects were observed, however, on pre-ejection period and left ventricular ejection time. Routine acupuncture had no detrimental effects on the stomach, intestine and heart in healthy adults, but instead regulated physiological function within a normal range. These findings demonstrate the existence of specific connections between the meridian points and the viscera. The results suggest that multiple meridians control the same viscus, and the same meridian can regulate the functions of multiple viscera. PMID:20869017

  7. Adult Vampire Bats Produce Contact Calls When Isolated: Acoustic Variation by Species, Population, Colony, and Individual

    PubMed Central

    Carter, Gerald G.; Logsdon, Ryane; Arnold, Bryan D.; Menchaca, Angelica; Medellin, Rodrigo A.

    2012-01-01

    Background Bat pups produce individually distinct isolation calls to facilitate maternal recognition. Increasing evidence suggests that, in group-living bat species, adults often use similar calls to maintain contact. We investigated if isolated adults from all three species of the highly cooperative vampire bats (Phyllostomidae: Desmodontinae) would produce vocally distinct contact calls when physically isolated. Methods/Principal Findings We assessed variation in contact calls recorded from isolated captive and wild-caught adult common vampire bats (Desmodus rotundus), white-winged vampire bats (Diaemus youngi) and hairy-legged vampire bats (Diphylla ecaudata). We compared species-typical contact call structure, and used information theory and permuted discriminate function analyses to examine call structure variation, and to determine if the individuality of contact calls is encoded by different call features across species and populations. We found that isolated adult vampire bats produce contact calls that vary by species, population, colony, and individual. However, much variation occurred within a single context and individual. We estimated signature information for captive Diaemus (same colony), captive Desmodus (same colony), and wild Desmodus (different colonies) at 3.21, 3.26, and 3.88 bits, respectively. Contact calls from a captive colony of Desmodus were less individually distinct than calls from wild-caught Desmodus from different colonies. Both the degree of individuality and parameters encoding individuality differed between the bats from a single captive colony and the wild-caught individuals from different groups. This result is consistent with, but not sufficient evidence of, vocal convergence in groups. Conclusion Our results show that adult vampire bats of all three species produce highly variable contact calls when isolated. Contact calls contain sufficient information for vocal discrimination, but also possess more intra-individual variation

  8. Care for the adult family members of victims of unexpected cardiac death.

    PubMed

    Zalenski, Robert; Gillum, Richard F; Quest, Tammie E; Griffith, James L

    2006-12-01

    More than 300,000 sudden coronary deaths occur annually in the United States, despite declining cardiovascular death rates. In 2000, deaths from heart disease left an estimated 190,156 new widows and 68,493 new widowers. A major unanswered question for emergency providers is whether the immediate care of the loved ones left behind by the deceased should be a therapeutic task for the staff of the emergency department in the aftermath of a fatal cardiac arrest. Based on a review of the literature, the authors suggest that more research is needed to answer this question, to assess the current immediate needs and care of survivors, and to find ways to improve care of the surviving family of unexpected cardiac death victims. This would include improving quality of death disclosure, improving care for relatives during cardiopulmonary resuscitation of their family member, and improved methods of referral for services for prevention of psychological and cardiovascular morbidity during bereavement. PMID:16946285

  9. O-GlcNAcylation Negatively Regulates Cardiomyogenic Fate in Adult Mouse Cardiac Mesenchymal Stromal Cells.

    PubMed

    Zafir, Ayesha; Bradley, James A; Long, Bethany W; Muthusamy, Senthilkumar; Li, Qianhong; Hill, Bradford G; Wysoczynski, Marcin; Prabhu, Sumanth D; Bhatnagar, Aruni; Bolli, Roberto; Jones, Steven P

    2015-01-01

    In both preclinical and clinical studies, cell transplantation of several cell types is used to promote repair of damaged organs and tissues. Nevertheless, despite the widespread use of such strategies, there remains little understanding of how the efficacy of cell therapy is regulated. We showed previously that augmentation of a unique, metabolically derived stress signal (i.e., O-GlcNAc) improves survival of cardiac mesenchymal stromal cells; however, it is not known whether enhancing O-GlcNAcylation affects lineage commitment or other aspects of cell competency. In this study, we assessed the role of O-GlcNAc in differentiation of cardiac mesenchymal stromal cells. Exposure of these cells to routine differentiation protocols in culture increased markers of the cardiomyogenic lineage such as Nkx2.5 and connexin 40, and augmented the abundance of transcripts associated with endothelial and fibroblast cell fates. Differentiation significantly decreased the abundance of O-GlcNAcylated proteins. To determine if O-GlcNAc is involved in stromal cell differentiation, O-GlcNAcylation was increased pharmacologically during the differentiation protocol. Although elevated O-GlcNAc levels did not significantly affect fibroblast and endothelial marker expression, acquisition of cardiomyocyte markers was limited. In addition, increasing O-GlcNAcylation further elevated smooth muscle actin expression. In addition to lineage commitment, we also evaluated proliferation and migration, and found that increasing O-GlcNAcylation did not significantly affect either; however, we found that O-GlcNAc transferase--the protein responsible for adding O-GlcNAc to proteins--is at least partially required for maintaining cellular proliferative and migratory capacities. We conclude that O-GlcNAcylation contributes significantly to cardiac mesenchymal stromal cell lineage and function. O-GlcNAcylation and pathological conditions that may affect O-GlcNAc levels (such as diabetes) should be

  10. mTOR Complexes Repress Hypertrophic Agonist-Stimulated Expression of Connective Tissue Growth Factor in Adult Cardiac Muscle Cells.

    PubMed

    Sundararaj, Kamala; Pleasant, Dorea L; Moschella, Phillip C; Panneerselvam, Kavin; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

    2016-02-01

    Connective tissue growth factor (CTGF) is a fibrogenic cytokine that promotes fibrosis in various organs. In the heart, both cardiomyocytes (CM) and cardiac fibroblasts have been reported as a source of CTGF expression, aiding cardiac fibrosis. Although the mammalian target of rapamycin (mTOR) forms 2 distinct complexes, mTORC1 and mTORC2, and plays a central role in integrating biochemical signals for protein synthesis and cellular homeostasis, we explored its role in CTGF expression in adult feline CM. CM were stimulated with 10 μM phenylephrine (PE), 200 nM angiotensin (Ang), or 100 nM insulin for 24 hours. PE and Ang, but not insulin, caused an increase in CTGF mRNA expression with the highest expression observed with PE. Inhibition of mTOR with torin1 but not rapamycin significantly enhanced PE-stimulated CTGF expression. Furthermore, silencing of raptor and rictor using shRNA adenoviral vectors to suppress mTORC1 and mTORC2, respectively, or blocking phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 (LY) or Akt signaling by dominant-negative Akt expression caused a substantial increase in PE-stimulated CTGF expression as measured by both mRNA and secreted protein levels. However, studies with dominant-negative delta isoform of protein kinase C demonstrate that delta isoform of protein kinase C is required for both agonist-induced CTGF expression and mTORC2/Akt-mediated CTGF suppression. Finally, PE-stimulated CTGF expression was accompanied with a corresponding increase in Smad3 phosphorylation and pretreatment of cells with SIS3, a Smad3 specific inhibitor, partially blocked the PE-stimulated CTGF expression. Therefore, a PI3K/mTOR/Akt axis plays a suppressive role on agonist-stimulated CTGF expression where the loss of this mechanism could be a contributing factor for the onset of cardiac fibrosis in the hypertrophying myocardium. PMID:26371948

  11. Association between hemoglobin levels and clinical outcomes in adult patients after in-hospital cardiac arrest: a retrospective cohort study.

    PubMed

    Wang, Chih-Hung; Huang, Chien-Hua; Chang, Wei-Tien; Tsai, Min-Shan; Yu, Ping-Hsun; Wang, An-Yi; Chen, Nai-Chuan; Chen, Wen-Jone

    2016-08-01

    In addition to cardiac output, oxygen delivery is determined by the amount of oxygen carried by hemoglobin, which is estimated by the product of hemoglobin level and peripheral hemoglobin oxygen saturation (SpO2). Optimal hemoglobin concentration for post-cardiac arrest syndrome (PCAS) has not yet been investigated thoroughly. We conducted a retrospective observational study in a single medical center. We included adult patients between 2006 and 2012 who experienced in-hospital cardiac arrest, and achieved sustained return of spontaneous circulation (ROSC). We used multivariable logistic regression analysis to identify factors associated with favorable neurological status at hospital discharge, defined as a score of 1 or 2 on the Cerebral Performance Category scale. Minimum hemoglobin concentration and SpO2 during the initial 24 h after ROSC were used for analysis. Anemia was defined by the World Health Organization criteria as a hemoglobin concentration <12 g/dL in women and <13 g/dL in men. Of the 426 patients included in our analysis, 387 patients (90.8 %) met the criteria for anemia. The mean minimum hemoglobin concentration among all the patients was 9.2 g/dL. The product of hemoglobin × SpO2 was correlated with a favorable neurological outcome (odds ratio 1.003, 95 % confidence interval 1.002-1.004). According to recommended SpO2 by resuscitation guidelines (94-98 %), we calculated the corresponding range of minimum required hemoglobin concentration to be 8.6-9.0 g/dL for a favorable neurological outcome. Anemia common among PCAS patients. Neurological outcome in PCAS might be correlated with hemoglobin concentration following resuscitation. PMID:26758060

  12. TESTOSTERONE AND SOCIAL ISOLATION INFLUENCE ADULT NEUROGENESIS IN THE DENTATE GYRUS OF MALE RATS

    PubMed Central

    Spritzer, Mark D.; Ibler, Erin; Inglis, William; Curtis, Molly G.

    2011-01-01

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): 1) sham/pair-housed, 2) sham/isolated, 3) castrate/pair-housed, and 4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n =8/group): 1) oil/pair-housed, 2) oil/isolated, 3) testosterone/pair-housed, and 4) testosterone/isolated. All rats were injected with 5-Bromo-2’-deoxyuridine (BrdU, 200 mg/kg body mass) and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and sub-granular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating levels of

  13. Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats.

    PubMed

    Spritzer, M D; Ibler, E; Inglis, W; Curtis, M G

    2011-11-10

    Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2) sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated, and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed, and (4) testosterone/isolated. All rats were injected with 5-bromo-2'-deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating

  14. The Impact of Team-Based Learning's Readiness Assurance Process on Virtually Isolated Adults

    ERIC Educational Resources Information Center

    Barclay, Matthew W.

    2011-01-01

    The purpose of this study was to test the effectiveness of the readiness assurance process of team-based learning (TBL) in virtually isolated settings. Many Internet sites offer courses for adults to use on their own without access to mentors or other learners. However, educational theory suggests that people learn better with others than by…

  15. Connecting Socially Isolated Older Rural Adults with Older Volunteers through Expressive Arts.

    PubMed

    MacLeod, Ann; Skinner, Mark W; Wilkinson, Fay; Reid, Heather

    2016-03-01

    Employing a participatory arts-based research approach, we examined an innovative program from rural Ontario, Canada, designed to address social isolation among older people. Older socially isolated adults were matched to trained volunteers, where in dyads, the eight pairs created expressive art in their home setting over the course of 10 home visits. With thematic and narrative inquiry, we analysed the experiences and perceptions of the program leader, older participants, and older volunteers via their artistic creations, weekly logs, evaluations, and field notes. The findings reveal a successful intervention that positively influenced the well-being of older adult participants and older volunteers, especially in regards to relationships, personal development, and creating meaning as well as extending the intervention's impact beyond the program's duration. We also discuss opportunities for similar programs to inform policy and enable positive community-based health and social service responses to rural social isolation. PMID:26934547

  16. Novel biomarkers for early diagnosis of acute kidney injury after cardiac surgery in adults

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is a common and serious complication and it is associated with increased morbidity and mortality. Diagnosis of acute kidney injury is based on the serum creatinine levels which rise several hours to days after the initial injury. Thus, novel biomarkers that will enable faster diagnosis are needed in clinical practice. There are numerous urine and serum proteins that indicate kidney injury and are under extensive research. Despite promising basic research results and assembled data, which indicate superiority of some biomarkers to creatinine, we are still awaiting clinical application. PMID:27212976

  17. Molecular characterization and LD(50) identify virulent isolates of Staphylococcus epidermidis from adult sepsis.

    PubMed

    Herndona, B L; Bialkowska-Hobrzanska, H; Dall, L

    2000-02-01

    Staphylococcus epidermidis plays an important role in infections of patients with implanted prosthetic devices. The exact clinical significance of recovered S. epidermidis from clinical specimens is difficult to assess, as they are inhabitants of the normal skin. In this study, 11 adults with clinical sepsis and blood cultures that grew only S. epidermidis were the host population. Bacterial virulence in vivo was determined by using the mouse LD(50) assay where the intravenous lethality was determined for each patient isolate. Bacterial dose (CFU x 10(9)) that produced lethality in 50% of the animals at 12 h was the value used for comparison. Restriction fragment length polymorphism (RFLP) analysis of chromosomal DNA by pulsed-field gel electrophoresis (PFGE) was used for identification of individual strains and their clonal organization. Confirmation of species assignment was done by RFLP analysis of 16S + 23S rRNA gene regions (ribotyping). Plasmid profile analysis was also conducted. Four of 11 blood isolates from adults with S. epidermidis sepsis had indistinguishable or closely related DNA patterns and were considered clone A. The same clone was previously seen to account for the majority of sepsis in a neonatal intensive care unit. There were significant differences in virulence characteristics of the S. epidermidis isolates. Clone A isolates produced lethality by LD(50) in mice at a dose averaging 2.35; clone B isolate at a dose of 2.54, and the remaining isolates, representing six distinct clones, were lethal to mice at significantly larger doses (3.51-5.17, average 4.16). These data suggest that individual clones of S. epidermidis isolated from septic adults have detectable differences in virulence as defined by an animal bioassay, and the more virulent clone is widespread. PMID:10705046

  18. Bispyridinium non-oximes: An evaluation of cardiac effects in isolated hearts and smooth muscle relaxing effects in jejunum.

    PubMed

    Neumaier, Katharina; Worek, Franz; Thiermann, Horst; Wille, Timo

    2016-09-01

    Bispyridinium non-oximes seem to be promising candidates for the generic treatment of nerve agent poisoning as they interact with nicotinic and muscarinic acetylcholine receptors. The lead compound MB327 showed therapeutic effectiveness in vitro and in vivo but was toxic at higher doses. In the present study, the effect of various bispyridinium non-oximes on isolated heart and small intestine function was investigated. Bispyridinium non-oximes and oximes were tested in at least seven different concentrations in rat jejunum preparations pre-treated with carbachol. All bispyridinium non-oximes showed classical dose response curves with MB327 being the most effective (EC50=6.6μM) and MB782 being slightly less effective (EC50=10.4μM). Neither the bispyridinium non-oximes nor the oximes showed cardiotoxic effects in the isolated Langendorff heart. The tested bispyridinum compounds showed no direct cardiac effect but had variable smooth muscle relaxing effects. Further in vivo studies are required to get more insight into potential toxic mechanisms of these promising nerve agent antidotes. PMID:27184650

  19. Cancer survivorship: cardiotoxic therapy in the adult cancer patient; cardiac outcomes with recommendations for patient management.

    PubMed

    Steingart, Richard M; Yadav, Nandini; Manrique, Carlos; Carver, Joseph R; Liu, Jennifer

    2013-12-01

    Many types of cancer are now curable or, if not cured, becoming a chronic illness. In 2012, it was estimated that there were more than 13,500,000 cancer survivors in the United States. Late outcomes of these survivors are increasingly related to cardiovascular disease, either as a consequence of the direct effects of cancer therapy or its adverse effects on traditional cardiac risk factors (eg, obesity, hypertension, dyslipidemia, and diabetes mellitus). This article describes the therapies that have led to advances in cancer survival and the acute and chronic cardiovascular toxicities associated with these therapies. Recommendations are made for the surveillance and management of cancer survivors. Published guidelines on the subject of cardio-oncology are reviewed in light of clinical experience caring for these patients. To supplement this cancer-related knowledge base, appropriateness criteria and guidelines for cardiac care in the general population were extrapolated to cancer survivors. The result is a series of recommendations for surveillance and management of cardiovascular disease in cancer survivors. PMID:24331191

  20. A multistep procedure to prepare pre-vascularized cardiac tissue constructs using adult stem sells, dynamic cell cultures, and porous scaffolds

    PubMed Central

    Pagliari, Stefania; Tirella, Annalisa; Ahluwalia, Arti; Duim, Sjoerd; Goumans, Marie-Josè; Aoyagi, Takao; Forte, Giancarlo

    2014-01-01

    The vascularization of tissue engineered products represents a key issue in regenerative medicine which needs to be addressed before the translation of these protocols to the bedside can be foreseen. Here we propose a multistep procedure to prepare pre-vascularized three-dimensional (3D) cardiac bio-substitutes using dynamic cell cultures and highly porous biocompatible gelatin scaffolds. The strategy adopted exploits the peculiar differentiation potential of two distinct subsets of adult stem cells to obtain human vascularized 3D cardiac tissues. In the first step of the procedure, human mesenchymal stem cells (hMSCs) are seeded onto gelatin scaffolds to provide interconnected vessel-like structures, while human cardiomyocyte progenitor cells (hCMPCs) are stimulated in vitro to obtain their commitment toward the cardiac phenotype. The use of a modular bioreactor allows the perfusion of the whole scaffold, providing superior performance in terms of cardiac tissue maturation and cell survival. Both the cell culture on natural-derived polymers and the continuous medium perfusion of the scaffold led to the formation of a densely packaged proto-tissue composed of vascular-like and cardiac-like cells, which might complete maturation process and interconnect with native tissue upon in vivo implantation. In conclusion, the data obtained through the approach here proposed highlight the importance to provide stem cells with complementary signals in vitro able to resemble the complexity of cardiac microenvironment. PMID:24917827

  1. Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression

    PubMed Central

    Moulay, Gilles; Ohtani, Tomohito; Ogut, Ozgur; Guenzel, Adam; Behfar, Atta; Zakeri, Rosita; Haines, Philip; Storlie, Jimmy; Bowen, Lorna; Pham, Linh; Kaye, David; Sandhu, Gurpreet; O'Connor, Michael; Russell, Stephen; Redfield, Margaret

    2015-01-01

    Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy. PMID:25915925

  2. Cardiac AAV9 Gene Delivery Strategies in Adult Canines: Assessment by Long-term Serial SPECT Imaging of Sodium Iodide Symporter Expression.

    PubMed

    Moulay, Gilles; Ohtani, Tomohito; Ogut, Ozgur; Guenzel, Adam; Behfar, Atta; Zakeri, Rosita; Haines, Philip; Storlie, Jimmy; Bowen, Lorna; Pham, Linh; Kaye, David; Sandhu, Gurpreet; O'Connor, Michael; Russell, Stephen; Redfield, Margaret

    2015-07-01

    Heart failure is a leading cause of morbidity and mortality, and cardiac gene delivery has the potential to provide novel therapeutic approaches. Adeno-associated virus serotype 9 (AAV9) transduces the rodent heart efficiently, but cardiotropism, immune tolerance, and optimal delivery strategies in large animals are unclear. In this study, an AAV9 vector encoding canine sodium iodide symporter (NIS) was administered to adult immunocompetent dogs via epicardial injection, coronary infusion without and with cardiac recirculation, or endocardial injection via a novel catheter with curved needle and both end- and side-holes. As NIS mediates cellular uptake of clinical radioisotopes, expression was tracked by single-photon emission computerized tomography (SPECT) imaging in addition to Western blot and immunohistochemistry. Direct epicardial or endocardial injection resulted in strong cardiac expression, whereas expression after intracoronary infusion or cardiac recirculation was undetectable. A threshold myocardial injection dose that provides robust nonimmunogenic expression was identified. The extent of transmural myocardial expression was greater with the novel catheter versus straight end-hole needle delivery. Furthermore, the authors demonstrate that cardiac NIS reporter gene expression and duration can be quantified using serial noninvasive SPECT imaging up to 1 year after vector administration. These data are relevant to efforts to develop cardiac gene delivery as heart failure therapy. PMID:25915925

  3. Long-term hypothermic preservation of cardiac myocytes isolated from the neonatal rat ventricle: a comparison of various crystalloid solutions.

    PubMed

    Orita, H; Fukasawa, M; Uchino, H; Uchida, T; Shiono, S; Washio, M

    1995-01-01

    In this study, the functional and biochemical effects of crystalloid solutions on immature cardiac myocytes incubated under hypothermic conditions were evaluated. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days, following which 12.5 x 10(5) myocytes per flask were incubated at 4 degrees C for 3, 6, 12, and 18 h in five types of crystalloid solutions: lactated Ringer's (LR), St. Thomas' Hospital (ST), University of Wisconsin (UW), 5% glucose-based potassium (GK), and normal saline (NS). The levels of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) in the solutions were measured after each hypothermic incubation, following which the myocytes were cultured for an additional 24 h at 37 degrees C to evaluate the recovery of the myocyte beating rate. In the LR, UW, and NS groups, the recovery ratios of the myocyte beating rate were over 95% of the control (the beating rate prior to hypothermic incubation) at 3 h, but decreased to 20.3, 15.1, and 0%, respectively, at 18 h. The ST and GK groups had significantly lower recovery ratios than the other three groups (72.9% and 63.4%, respectively) at 3 h. The release of CPK and LDH in the LR, UW, and NS groups was significantly suppressed compared to the ST and GK groups, with the greatest suppression observed in the LR group. Moreover, the ST and GK groups had the highest CPK and LDH levels, respectively. Thus, LR solution had the least cytotoxic effects, indicating that it could be the most suitable basic solution of the various cardioplegic or preservation solutions during the neonatal period. PMID:7640455

  4. Genetic dissection of cardiac growth control pathways

    NASA Technical Reports Server (NTRS)

    MacLellan, W. R.; Schneider, M. D.

    2000-01-01

    Cardiac muscle cells exhibit two related but distinct modes of growth that are highly regulated during development and disease. Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle irreversibly soon after birth, following which the predominant form of growth shifts from hyperplastic to hypertrophic. Much research has focused on identifying the candidate mitogens, hypertrophic agonists, and signaling pathways that mediate these processes in isolated cells. What drives the proliferative growth of embryonic myocardium in vivo and the mechanisms by which adult cardiac myocytes hypertrophy in vivo are less clear. Efforts to answer these questions have benefited from rapid progress made in techniques to manipulate the murine genome. Complementary technologies for gain- and loss-of-function now permit a mutational analysis of these growth control pathways in vivo in the intact heart. These studies have confirmed the importance of suspected pathways, have implicated unexpected pathways as well, and have led to new paradigms for the control of cardiac growth.

  5. Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: patterns and differences

    PubMed Central

    Cavalca, Viviana; Tremoli, Elena; Porro, Benedetta; Veglia, Fabrizio; Myasoedova, Veronika; Squellerio, Isabella; Manzone, Daniela; Zanobini, Marco; Trezzi, Matteo; Di Minno, Matteo Nicola Dario; Werba, José Pablo; Tedesco, Calogero; Alamanni, Francesco; Parolari, Alessandro

    2013-01-01

    OBJECTIVES We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency. METHODS In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis. RESULTS Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis. CONCLUSIONS Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve

  6. Primary Prevention of Sudden Cardiac Death in Adults with Transposition of the Great Arteries: A Review of Implantable Cardioverter-Defibrillator Placement

    PubMed Central

    Cedars, Ari M.

    2015-01-01

    Transposition of the great arteries encompasses a set of structural congenital cardiac lesions that has in common ventriculoarterial discordance. Primarily because of advances in medical and surgical care, an increasing number of children born with this anomaly are surviving into adulthood. Depending upon the subtype of lesion or the particular corrective surgery that the patient might have undergone, this group of adult congenital heart disease patients constitutes a relatively new population with unique medical sequelae. Among the more common and difficult to manage are cardiac arrhythmias and other sequelae that can lead to sudden cardiac death. To date, the question of whether implantable cardioverter-defibrillators should be placed in this cohort as a preventive measure to abort sudden death has largely gone unanswered. Therefore, we review the available literature surrounding this issue. PMID:26413012

  7. Prevalence and Prognosis of Unrecognized Myocardial Infarction Determined by Cardiac Magnetic Resonance in Older Adults

    PubMed Central

    Schelbert, Erik B.; Cao, Jie J.; Sigurdsson, Sigurdur; Aspelund, Thor; Kellman, Peter; Aletras, Anthony H.; Dyke, Christopher K.; Thorgeirsson, Gudmundur; Eiriksdottir, Gudny; Launer, Lenore J.; Gudnason, Vilmundur; Harris, Tamara B.; Arai, Andrew E.

    2013-01-01

    Context Unrecognized myocardial infarction (MI) is prognostically important but electrocardiography (ECG), the main epidemiology tool for detection, is insensitive to MI. Objective Determine prevalence and mortality risk for unrecognized MI (UMI) detected by cardiac magnetic resonance (CMR) or ECG. Design ICELAND MI is a cohort substudy of the Age, Gene/Environment Susceptibility-Reykjavik Study (enrollment January 2004–January 2007) using ECG or CMR to detect UMI. Setting Community dwelling participants in Iceland over age 67. Participants 936 participants (ages 67–93 years) including 670 who were randomly selected and 266 with diabetes. Main Outcome Measures MI prevalence and mortality through September 1, 2011. Results reported with 95% confidence limits and net reclassification improvement (NRI). Results Of 936 participants, 91 had recognized MI (RMI; 9.7% CI 8–12%), and 157 had UMI by CMR (17%; CI 14–19%) which was more prevalent than the 46 UMI by ECG (5%; CI 4–6%, p<0.001). Diabetic participants had more UMI by CMR than UMI by ECG (n=72; 21%; CI 17–26% vs. n=15; 4%; CI 2–7%, p<0.001). UMI by CMR was associated with atherosclerosis risk factors, coronary calcium, coronary revascularization, and peripheral vascular disease. Over a median of 6.4 years, 33% (CI 23–43%) of individuals with RMI died (30 of 91) and 28% (CI 21–35%) with UMI died (44 of 157), both higher rates than the 17% (CI 15–20%) with no MI that died (119 of 688). UMI by CMR improved risk stratification for mortality over RMI (NRI: 0.34; CI 0.16–0.53). Adjusting for age, sex, diabetes, and RMI, UMI by CMR remained associated with mortality (HR 1.45 CI 1.02–2.06, absolute risk increase (ARI) 8%) and significantly improved risk stratification for mortality, NRI 0.16 (CI 0.01–0.31)) but UMI by ECG did not (HR 0.88, CI 0.45–1.73 ARI −2%; NRI: −0.05; CI −0.17–0.05). Compared to those with RMI, participants with UMI by CMR used cardiac medications such as statins

  8. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. 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:26801961

  9. 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

  10. When, where and how to initiate hypothermia after adult cardiac arrest.

    PubMed

    Taccone, F S; Donadello, K; Beumier, M; Scolletta, S

    2011-09-01

    Therapeutich hypothermia (TH) has been shown to improve neurological outcome and survival after witnessed cardiac arrest (CA) that is due to ventricular fibrillation. Although TH is widely used following witnessed CA as well as all forms of initial rhythm, the mortality rate after CA remains unacceptably high, and additional study is needed to understand when and how to implement hypothermia in the post-resuscitation phase. Experimental studies have emphasized the importance of initiating cooling soon after the return of spontaneous circulation (ROSC) or even during cardiopulmonary resuscitation (CPR). Clinical studies have shown that pre-hospital induction of hypothermia is feasible and has no major adverse events-even when used intra-arrest-and may provide some additional benefits compared to delayed in-hospital cooling. Thus, hypothermia use should not be limited to the Intensive Care Unit but can be initiated in the field/ambulance or in the Emergency Department, then continued after hospital admission- even during specific procedures such as coronary angiography-as part of the global management of CA patients. Various methods (both non-invasive and invasive) are available to achieve and maintain the target temperature; however, only some of these methods-which include cold fluids, ice packs, iced pads and helmet and trans-nasal cooling- are easily deployed in the pre-hospital setting. PMID:21878875

  11. Isolation and characterization of a Streptococcus pyogenes protein that binds to basal laminae of human cardiac muscle.

    PubMed Central

    Winters, B D; Ramasubbu, N; Stinson, M W

    1993-01-01

    A 9-kDa glycosaminoglycan-binding protein (GAG-BP) was isolated from Streptococcus pyogenes and purified to homogeneity by affinity chromatography on heparin-agarose. The protein selectively bound to the basal laminae of human cardiac muscle and had an apparent dissociation constant of 2.5 x 10(-7) M. Chemical analyses indicated that the GAG-BP was rich in alanine, lysine, and arginine (pI 9.5) and devoid of tyrosine, methionine, histidine, and half-cystine. There were no detectable carbohydrate or phosphate substituents. The amino acid sequence of the N terminus of GAG-BP showed homology with those of histone-like DNA-binding proteins of several other bacteria. Circular dichroism spectroscopy indicated that the protein was made up of 50% beta-sheet and 50% beta-turn and random coil in aqueous solution; however, when the protein complexed with heparin, it adopted a more ordered structure containing 25% alpha-helix, 50% beta-sheet, and 25% beta-turn and random coil. The GAG-BP cross-reacted serologically with a component of similar size in extracts of other group A streptococci and was present in the culture medium during late logarithmic growth. Images PMID:8335359

  12. Pancreatic Islets: Methods for Isolation and Purification of Juvenile and Adult Pig Islets.

    PubMed

    Brandhorst, Heide; Johnson, Paul R V; Brandhorst, Daniel

    2016-01-01

    The current situation of organ transplantation is mainly determined by the disbalance between the number of available organs and the number of patients on the waiting list. This obvious dilemma might be solved by the transplantation of porcine organs into human patients. The metabolic similarities which exist between both species made pancreatic islets of Langerhans to that donor tissue which will be most likely transplanted in human recipients. Nevertheless, the successful isolation of significant yields of viable porcine islets is extremely difficult and requires extensive experiences in the field. This review is focussing on the technical challenges, pitfalls and particularities that are associated with the isolation of islets from juvenile and adult pigs considering donor variables that can affect porcine islet isolation outcome. PMID:27586421

  13. Naïve adult stem cells isolation from primary human fibroblast cultures.

    PubMed

    Wenzel, Vera; Roedl, Daniela; Ring, Johannes; Djabali, Karima

    2013-01-01

    Over the last decade, several adult stem cell populations have been identified in human skin (1-4). The isolation of multipotent adult dermal precursors was first reported by Miller F. D laboratory (5, 6). These early studies described a multipotent precursor cell population from adult mammalian dermis (5). These cells--termed SKPs, for skin-derived precursors-- were isolated and expanded from rodent and human skin and differentiated into both neural and mesodermal progeny, including cell types never found in skin, such as neurons (5). Immunocytochemical studies on cultured SKPs revealed that cells expressed vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors, in addition to fibronectin and multipotent stem cell markers (6). Until now, the adult stem cells population SKPs have been isolated from freshly collected mammalian skin biopsies. Recently, we have established and reported that a population of skin derived precursor cells could remain present in primary fibroblast cultures established from skin biopsies (7). The assumption that a few somatic stem cells might reside in primary fibroblast cultures at early population doublings was based upon the following observations: (1) SKPs and primary fibroblast cultures are derived from the dermis, and therefore a small number of SKP cells could remain present in primary dermal fibroblast cultures and (2) primary fibroblast cultures grown from frozen aliquots that have been subjected to unfavorable temperature during storage or transfer contained a small number of cells that remained viable (7). These rare cells were able to expand and could be passaged several times. This observation suggested that a small number of cells with high proliferation potency and resistance to stress were present in human fibroblast cultures (7). We took advantage of these findings to establish a protocol for rapid isolation of adult stem cells from primary fibroblast cultures that are

  14. Omega 3 polyunsaturated fatty acid modulates dihydropyridine effects on L-type Ca2+ channels, cytosolic Ca2+, and contraction in adult rat cardiac myocytes.

    PubMed Central

    Pepe, S; Bogdanov, K; Hallaq, H; Spurgeon, H; Leaf, A; Lakatta, E

    1994-01-01

    The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (ICa), cytosolic Ca2+ (Cai), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca(2+)-channel blocker nitrendipine (10 nM) reduced peak ICa (measured by whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+ transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the twitch amplitude (measured via photodiode array) during steady-state electrical stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM) significantly increased ICa, the amplitude of the Cai transient, and contraction. When cells were exposed to DHA (5 microM) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 microM did not block the inhibitory effects of nitrendipine nor did it prevent the potentiating effects of BAY K 8644. DHA modulation of DHP action could be reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml. Neither DHA nor arachidonic acid alone (5 microM) had any apparent effect on the parameters measured. DHA (5 microM) had no influence over beta-adrenergic receptor stimulation (isoproterenol, 0.01-1 microM)-induced increases in ICa, Cai, or contraction. The findings that DHA inhibits the effect of DHP agonists and antagonists on Ca(2+)-channel current but has no effect alone or on beta-adrenergic-induced increases in ICa suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with ICa modulation. Images PMID:7522322

  15. Cardiac mechanics are impaired during fatiguing exercise and cold pressor test in healthy older adults

    PubMed Central

    Muller, Matthew D.; Mast, Jessica L.; Patel, Hardikkumar

    2013-01-01

    We sought to determine how the aging left ventricle (LV) responds to sympathetic nervous system (SNS) activation. Three separate echocardiographic experiments were conducted in 11 healthy young (26 ± 1 yr) and 11 healthy older (64 ± 1 yr) adults. Tissue Doppler imaging was used to measure systolic myocardial velocity (Sm), early diastolic myocardial velocity (Em), and late diastolic myocardial velocity (Am) during isometric fatiguing handgrip (IFHG), a 2-min cold pressor test (CPT), and 5 min of normobaric hypoxia. Heart rate (HR) and mean arterial pressure (MAP) were also monitored on a beat-by-beat basis; rate pressure product (RPP) was used as an index of myocardial oxygen demand. At peak IFHG, the groups had similar increases in RPP, but the ΔSm was significantly greater (i.e., larger impairment) in the older subjects (−0.82 ± 0.13 cm/s) compared with the young subjects (0.37 ± 0.30 cm/s). At peak IFHG, the ΔEm was similar between older (−1.59 ± 0.68 cm/s) and young subjects (−1.06 ± 0.76 cm/s). In response to the CPT, both Sm and Em were reduced in the older adults but did not change relative to baseline in the young subjects. Normobaric hypoxia elevated HR and RPP in both groups but did not alter Tissue Doppler parameters. These data indicate that Sm and Em are reduced in healthy older adults during IFHG and CPT. We speculate that suboptimal LV adaptations to SNS stress may partly explain why acute heavy exertion can trigger myocardial ischemia. PMID:23154996

  16. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors

    PubMed Central

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-01-01

    Abstract Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed. PMID:26886643

  17. A Cyclin D2-Rb Pathway Regulates Cardiac Myocyte Size and RNA Polymerase III After Biomechanical Stress in Adult Myocardium

    PubMed Central

    Angelis, Ekaterini; Garcia, Alejandro; Chan, Shing S.; Schenke-Layland, Katja; Ren, Shuxen; Goodfellow, Sarah J.; Jordan, Maria C.; Roos, Kenneth P.; White, Robert J.; MacLellan, W. Robb

    2008-01-01

    Normally, cell cycle progression is tightly coupled to the accumulation of cell mass; however, the mechanisms whereby proliferation and cell growth are linked are poorly understood. We have identified Cyclin D2 (CycD2), a G1 cyclin implicated in mediating S phase entry, as a potential regulator of hypertrophic growth in adult post mitotic myocardium. To examine the role of CycD2 and its downstream targets, we subjected CycD2-null mice to mechanical stress. Hypertrophic growth in response to transverse aortic constriction (TAC) was attenuated in CycD2 null compared to wildtype mice. Blocking the increase in CycD2 in response to hypertrophic agonists prevented phosphorylation of CycD2-target Rb in vitro and mice deficient for Rb had potentiated hypertrophic growth. Hypertrophic growth requires new protein synthesis and transcription of tRNA genes by RNA pol III, which increases with hypertrophic signals. This load-induced increase in RNA pol III activity is augmented in Rb-deficient hearts. Rb binds and represses Brf-1 and TBP, subunits of RNA pol III-specific transcription factor B, in adult myocardium under basal conditions. However this association is disrupted in response to TAC. RNA pol III activity is unchanged in CycD2-/- myocardium after TAC, and there is no dissociation of TBP from Rb. These investigations identify an essential role for the CycD2-Rb pathway as a governor of cardiac myocyte enlargement in response to biomechanical stress and, more fundamentally, as a regulator of the load-induced activation of RNA pol III. PMID:18420946

  18. 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

  19. Use and Utility of Hemostatic Screening in Adults Undergoing Elective, Non-Cardiac Surgery

    PubMed Central

    Weil, Isabel A.; Seicean, Sinziana; Neuhauser, Duncan; Schiltz, Nicholas K.; Seicean, Andreea

    2015-01-01

    Introduction One view of value in medicine is outcome relative to cost of care provided. With respect to operative care, increased attention has been placed on evaluation and optimization of patients prior to undergoing an elective surgery. We examined more than 2 million patients having elective, non-cardiac surgery to assess the incidence and utility of pre-operative hemostatic screening, compared with a composite of history variables that may indicate a propensity for bleeding, to assess several important outcomes of surgery. Materials & Methods We queried the NSQIP database to identify 2,020,533 patients and compared hemostatic tests (PT, aPTT, platelet count) and history covariables indicative of potential for abnormal hemostasis. We compared outcomes across predictor values; used Person’s chi-square tests to compare differences, and logistic regression to model outcomes. Results Approximately 36% of patients had all three tests pre-operatively while 16% had none of them; 11.2% had a history predictive of potential abnormal bleeding. Outcomes of interest across the cohort included death in 0.7%, unplanned return to the operating room or re-admission within 30 days in 3.8% and 6.2% of patients; 5.3% received a transfusion during or after surgery. Sub-analyses in each of the nine surgical specialties’ most common procedures yielded similar results. Conclusion The limited predictive value of each hemostatic screening test, as well as excess costs associated with them, across a broad spectrum of elective surgeries, suggests that limiting pre-operative testing to a more select group of patients may be reasonable, equally efficacious, efficient, and cost-effective. PMID:26623648

  20. 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

  1. Effects of trimebutine maleate on electrical activities of isolated mammalian cardiac preparations.

    PubMed

    Igawa, O; Kotake, H; Hirai, S; Hisatome, I; Hasegawa, J; Mashiba, H

    1989-05-01

    The effects of trimebutine maleate on electrical activity in guinea-pig isolated papillary muscles and rabbit sino-atrial nodes have been studied by means of a standard microelectrode method. In papillary muscles, trimebutine (above 10 microM) decreased the maximum rate of rise (Vmax) and the action potential duration at 90% repolarization (APD90), whereas the resting potential was not significantly altered. As to a decrease in Vmax, trimebutine produced a negative shift of the curve relating Vmax to the resting potential along the voltage axis. Trimebutine also depressed the slow action potentials of papillary muscles produced by 27 mM K and 0.2 mM Ba. In spontaneously beating sino-atrial node preparations, trimebutine (above 10 microM) decreased the heart rate, Vmax and the rate of diastolic depolarization. These results indicate that trimebutine maleate possesses a depressant action on the electrical activities of the fast- and slow-response fibres of the heart mainly due to inhibitions of both fast Na+ and slow Ca2+ channels. PMID:2569517

  2. Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference.

    PubMed

    Pavón, Natalia; Martínez-Abundis, Eduardo; Hernández, Luz; Gallardo-Pérez, Juan Carlos; Alvarez-Delgado, Carolina; Cerbón, Marco; Pérez-Torres, Israel; Aranda, Alberto; Chávez, Edmundo

    2012-10-01

    In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined. At the mitochondrial level respiratory control, transmembranal potential and calcium management were determined; Western blot of some mitochondrial components was also performed. Alterations in cardiac function were worst in intact males and castrated females as compared with those found in intact females and castrated males, cytokine levels were modulated also by hormonal status. Regarding mitochondria, in those obtained from hearts from castrated females without ischemia-reperfusion, all evaluated parameters were similar to those observed in mitochondria after ischemia-reperfusion. The results show hormonal influences on the heart at functional and mitochondrial levels. PMID:22609314

  3. The influence of patient size on dose conversion coefficients: a hybrid phantom study for adult cardiac catheterization

    NASA Astrophysics Data System (ADS)

    Johnson, Perry; Lee, Choonsik; Johnson, Kevin; Siragusa, Daniel; Bolch, Wesley E.

    2009-06-01

    In this study, the influence of patient size on organ and effective dose conversion coefficients (DCCs) was investigated for a representative interventional fluoroscopic procedure—cardiac catheterization. The study was performed using hybrid phantoms representing an underweight, average and overweight American adult male. Reference body sizes were determined using the NHANES III database and parameterized based on standing height and total body mass. Organ and effective dose conversion coefficients were calculated for anterior-posterior, posterior-anterior, left anterior oblique and right anterior oblique projections using the Monte Carlo code MCNPX 2.5.0 with the metric dose area product being used as the normalization factor. Results show body size to have a clear influence on DCCs which increased noticeably when body size decreased. It was also shown that if patient size is neglected when choosing a DCC, the organ and effective dose will be underestimated to an underweight patient and will be overestimated to an underweight patient, with errors as large as 113% for certain projections. Results were further compared with those published for a KTMAN-2 Korean patient-specific tomographic phantom. The published DCCs aligned best with the hybrid phantom which most closely matched in overall body size. These results highlighted the need for and the advantages of phantom-patient matching, and it is recommended that hybrid phantoms be used to create a more diverse library of patient-dependent anthropomorphic phantoms for medical dose reconstruction.

  4. Prospective Surveillance for Cardiac Adverse Events in Healthy Adults Receiving Modified Vaccinia Ankara Vaccines: A Systematic Review

    PubMed Central

    Elizaga, Marnie L.; Vasan, Sandhya; Marovich, Mary A.; Sato, Alicia H.; Lawrence, Dale N.; Chaitman, Bernard R.; Frey, Sharon E.; Keefer, Michael C.

    2013-01-01

    Background Vaccinia-associated myo/pericarditis was observed during the US smallpox vaccination (DryVax) campaign initiated in 2002. A highly-attenuated vaccinia strain, modified vaccinia Ankara (MVA) has been evaluated in clinical trials as a safer alternative to DryVax and as a vector for recombinant vaccines. Due to the lack of prospectively collected cardiac safety data, the US Food and Drug Administration required cardiac screening and surveillance in all clinical trials of MVA since 2004. Here, we report cardiac safety surveillance from 6 phase I trials of MVA vaccines. Methods Four clinical research organizations contributed cardiac safety data using common surveillance methods in trials administering MVA or recombinant MVA vaccines to healthy participants. ‘Routine cardiac investigations’ (ECGs and cardiac enzymes obtained 2 weeks after injections of MVA or MVA-HIV recombinants, or placebo-controls), and ‘Symptom-driven cardiac investigations’ are reported. The outcome measure is the number of participants who met the CDC-case definition for vaccinia-related myo/pericarditis or who experienced cardiac adverse events from an MVA vaccine. Results Four hundred twenty-five study participants had post-vaccination safety data analyzed, 382 received at least one MVA-containing vaccine and 43 received placebo; 717 routine ECGs and 930 cardiac troponin assays were performed. Forty-five MVA recipients (12%) had additional cardiac testing performed; 22 for cardiac symptoms, 19 for ECG/laboratory changes, and 4 for cardiac symptoms with an ECG/laboratory change. No participant had evidence of symptomatic or asymptomatic myo/pericarditis meeting the CDC-case definition and judged to be related to an MVA vaccine. Conclusions Prospective surveillance of MVA recipients for myo/pericarditis did not detect cardiac adverse reactions in 382 study participants. Trial Registration ClinicalTrials.gov NCT00082446 NCT003766090 NCT00252148 NCT00083603 NCT00301184

  5. Non-coding small (micro) RNAs of Pseudomonas aeruginosa isolated from clinical isolates from adult patients with cystic fibrosis.

    PubMed

    Rao, J R; Nelson, D; Moore, J E; Millar, B C; Goldsmith, C E; Rendall, J; Elborn, J S

    2010-01-01

    MicroRNAs are a class of small non-coding RNAs widely reported in eukaryotic multicellular organisms. In this study, a number of small non-coding micro (mi)RNA species in clinical isolates of prokaryote Pseudomonas aeruginosa were obtained from the sputum of adult patients with cystic fibrosis (CF) utilising a DynaExpress miRNA cloning kit, and five miRNAs of 16-47 nucleotides that were smaller than those encountered or described (80-100 nucleotides) previously in bacterial systems were described. This report presents data on these unknown cellular miRNAs cloned from P. aeruginosa isolates from CF patients. Adapting a computational miRNA prediction model that takes advantage of the highly conserved known miRNA hair pin stems regions, the results revealed that the fold structure of the microRNAs had a high homology to the recently reported human bacterial infection response (BiR)-related microRNA, mi-146, associated with the Toll-like receptor (TLR) family, which is the primary evolutionarily conserved sensors of pathogen-associated molecular patterns (PAMPs), and known to trigger host inflammatory and immune responses. PMID:20973407

  6. Magnetic resonance-compatible model of isolated working heart from large animal for multimodal assessment of cardiac function, electrophysiology, and metabolism.

    PubMed

    Vaillant, Fanny; Magat, Julie; Bour, Pierre; Naulin, Jérôme; Benoist, David; Loyer, Virginie; Vieillot, Delphine; Labrousse, Louis; Ritter, Philippe; Bernus, Olivier; Dos Santos, Pierre; Quesson, Bruno

    2016-05-15

    To provide a model close to the human heart, and to study intrinsic cardiac function at the same time as electromechanical coupling, we developed a magnetic resonance (MR)-compatible setup of isolated working perfused pig hearts. Hearts from pigs (40 kg, n = 20) and sheep (n = 1) were blood perfused ex vivo in the working mode with and without loaded right ventricle (RV), for 80 min. Cardiac function was assessed by measuring left intraventricular pressure and left ventricular (LV) ejection fraction (LVEF), aortic and mitral valve dynamics, and native T1 mapping with MR imaging (1.5 Tesla). Potential myocardial alterations were assessed at the end of ex vivo perfusion from late-Gadolinium enhancement T1 mapping. The ex vivo cardiac function was stable across the 80 min of perfusion. Aortic flow and LV-dP/dtmin were significantly higher (P < 0.05) in hearts perfused with loaded RV, without differences for heart rate, maximal and minimal LV pressure, LV-dP/dtmax, LVEF, and kinetics of aortic and mitral valves. T1 mapping analysis showed a spatially homogeneous distribution over the LV. Simultaneous recording of hemodynamics, LVEF, and local cardiac electrophysiological signals were then successfully performed at baseline and during electrical pacing protocols without inducing alteration of MR images. Finally, (31)P nuclear MR spectroscopy (9.4 T) was also performed in two pig hearts, showing phosphocreatine-to-ATP ratio in accordance with data previously reported in vivo. We demonstrate the feasibility to perfuse isolated pig hearts in the working mode, inside an MR environment, allowing simultaneous assessment of cardiac structure, mechanics, and electrophysiology, illustrating examples of potential applications. PMID:26968545

  7. An Examination of the Social Networks and Social Isolation in Older and Younger Adults Living with HIV/AIDS

    ERIC Educational Resources Information Center

    Emlet, Charles A.

    2006-01-01

    This study examined social networks and social isolation in older (50 years or more) and younger (ages 20 to 39) adults with HIV/AIDS. The author conducted interviews with 88 individuals living with HIV/AIDS in the Pacific Northwest. Both groups' social networks had similar patterns; however, older adults were more likely to live alone. More than…

  8. High-efficiency immunomagnetic isolation of solid tissue-originated integrin-expressing adult stem cells.

    PubMed

    Palmon, Aaron; David, Ran; Neumann, Yoav; Stiubea-Cohen, Raluca; Krief, Guy; Aframian, Doron J

    2012-02-01

    Isolation of highly pure specific cell types is crucial for successful adult stem cell-based therapy. As the number of such cells in adult tissue is low, an extremely efficient method is needed for their isolation. Here, we describe cell-separation methodologies based on magnetic-affinity cell sorting (MACS) MicroBeads with monoclonal antibodies against specific membrane proteins conjugated to superparamagnetic particles. Cells labeled with MACS MicroBeads are retained in a magnetic field within a MACS column placed in a MACS separator, allowing fast and efficient separation. Both positively labeled and non-labeled fractions can be used directly for downstream applications as the separated cell fractions remain viable with no functional impairment. As immunomagnetic separation depends on the interaction between a cell's membrane and the magnetically labeled antibody, separation of specific cells originating from solid tissues is more complex and demands a cell-dissociating pretreatment. In this paper, we detail the use of immunomagnetic separation for the purpose of regenerating damaged salivary gland (SG) function in animal and human models of irradiated head and neck cancer. Each year 500,000 new cases of head and neck cancer occur worldwide. Most of these patients lose SG function following irradiation therapy. SGs contain integrin α6β1-expressing epithelial stem cells. We hypothesized that these cells can be isolated, multiplied in culture and auto-implanted into the irradiated SGs to regenerate damaged SG function. PMID:22019721

  9. Detection and characterization of colonization factor of enterotoxigenic Escherichia coli isolated from adults with diarrhea.

    PubMed Central

    Evans, D G; Evans, D J; Tjoa, W S; DuPont, H L

    1978-01-01

    The fimbriate colonization factor antigen (CEA) of Escherichia coli strain H-1047 was isolated and used to prepare anti-CFA antiserum. Enterotoxigenic E. coli (ETEC) isolated from 29 adults with diarrhea acquired in Mexico were examined for CFA by using this serum. Retrospectively, it was found that ETEC possessing the H-10407-type CFA were isolated from 25 (86%) of these diarrhea cases as compared with 2 of 11 (18%) from asymptomatic controls from whom ETEC had been isolated. CFA was found onE. coli of various serotypes, as demonstrated by bacterial agglutination by the anti-CFA serum. Heat treating the cells at 65 degress C for 1 h prevented the agglutination. CFA-positive strains did not react with anti-CFA serum when the cultures were grown at a low incubation temperature (18 degrees C). E. coli isolates identified serologically as CFA positive were shown to adhere to the intestinal villous surfaces of infant rabbits. By the indirect immunofluorescence technique, it was found that adhesion occurred preferentially in the upper 20 cm of the small intestine. Also, the ability or inability of various isolates to adhere to intestinal mucosa in vivo correlated with the presence or absence of fimbriae on the cells when grown in vitro. Agglutinability with anti-CFA serum, fimbriae, and adhesiveness were spontaneously lost by many isolates after laboratory passage in a manner previously described with E. coli H-10407. These observations suggest that the H-10407-type CFA plays a role in the virulence of ETEC possessing this antigen. Images PMID:344221

  10. 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

  11. Hormone responsiveness of cultured Sertoli cells obtained from adult rats after their rapid isolation under less harsh conditions.

    PubMed

    Gautam, M; Bhattacharya, I; Devi, Y S; Arya, S P; Majumdar, S S

    2016-05-01

    During adulthood, testicular Sertoli cells (Sc) coordinate all stages of germ cell (Gc) development involved in sperm production. However, our understanding about the functions of adult Sc is limited because of the difficulties involved in the process of isolating these cells from the adult testis, mainly because of the presence of large number of advanced Gc which interfere with Sc isolation at this age. Most of our knowledge about Sc function are derived from studies which used pre-pubertal rat Sc (18 ± 2-day old) as it is easy to isolate and culture Sc at this age. To this end, we established a less time consuming and less harsh procedure of isolating Sc from adult (60 days of age) rat testis for facilitating research on Sc-mediated regulation of spermatogenesis during adulthood. The cells were isolated using collagenase digestion at higher temperature, reducing the exposure time of cells to the enzyme. Step-wise digestion with intermittent removal of small clusters of tissue helped in increasing the yield of Sc. Isolated Sc were cultured and treated with FSH and testosterone (T) to evaluate their hormone responsiveness in terms of lactate, E2 , cAMP production. Adult Sc were found to be active and produced high amounts of lactate in a FSH-independent manner. FSH-mediated augmentation of cAMP and E2 production by adult Sc was less as compared with that by pre-pubertal Sc obtained from 18-day-old rats. Androgen-binding ability of adult Sc was significantly higher than pre-pubertal Sc. Although T treatment remarkably augmented expression of Claudin 11, it failed to augment lactate production by adult Sc. This efficient and rapid procedure for isolation and culture of functionally viable adult rat Sertoli cells may pave the way for determining their role in regulation and maintenance of spermatogenesis. PMID:26991307

  12. Left Atrial Passive Emptying Function Determined by Cardiac Magnetic Resonance Predicts Atrial Fibrillation Recurrence after Pulmonary Vein Isolation

    PubMed Central

    Dodson, John A.; Neilan, Tomas G.; Shah, Ravi V.; Farhad, Hoshang; Blankstein, Ron; Steigner, Michael; Michaud, Gregory F.; John, Roy; Abbasi, Siddique A.; Jerosch-Herold, Michael; Kwong, Raymond Y.

    2014-01-01

    Background While pulmonary vein isolation (PVI) has become a mainstream therapy for selected patients with atrial fibrillation (AF), late recurrent AF is common and its risk factors remain poorly defined. The purpose of our study was to test the hypothesis that reduced left atrial passive emptying function (LAPEF) as determined by cardiac magnetic resonance (CMR) has a strong association with late recurrent AF following PVI. Methods and Results 346 AF patients referred for CMR PV mapping prior to PVI were included. Maximum LA volumes (VOLmax) and volumes before atrial contraction (VOLbac) were measured; LAPEF was calculated as (VOLmax − VOLbac)/VOLmax × 100. Kaplan-Meier curves were constructed to determine late recurrent AF stratified by LAPEF quintile. Cox proportional hazards regression was used to adjust for known markers of recurrence. Over a median follow-up of 27 months, 124 patients (35.8%) experienced late recurrent AF. Patients with recurrence were more likely to have non-paroxysmal AF (75.8% vs. 51.4%, P<0.01), higher mean VOLmax (60.2 ml/m2 vs. 52.8 ml/m2, P<0.01), and lower mean LAPEF (19.1% vs. 26.0%, P<0.01). Patients in the lowest LAPEF quintile were at highest risk of developing recurrent AF (two-year recurrence lowest vs. highest: 60.5% vs. 17.3%, P<0.01). After adjusting for known predictors of recurrence, patients with low LAPEF remained significantly more likely to recur (HR lowest vs. highest quintile = 3.92, 95% CI 2.01–7.65). Conclusion We found a strong association between LAPEF and recurrent AF after PVI that persisted after multivariable adjustment. PMID:24902586

  13. Comparative study of the effect of verapamil and vitamin D on iron overload-induced oxidative stress and cardiac structural changes in adult male rats.

    PubMed

    Abd Allah, Eman S H; Ahmed, Marwa A; Abdel Mola, Asmaa Fathi

    2014-11-01

    The present study was designed to compare the effect of verapamil and vitamin D on the expression of the voltage-dependent LTCC alpha 1c subunit (Cav1.2) and thereby on iron overload-induced cardiac dysfunction in adult male rat. Forty rats were randomly divided into four groups. Control group received the vehicle, iron overload group received ferrous sulfate intraperitoneally (IP) for 4 weeks, iron overload+verapamil received ferrous sulfate and verapamil IP concurrently for 4 weeks and iron overload+vitamin D group received ferrous sulfate IP and vitamin D3 orally concurrently for 4 weeks. Serum ferritin, total antioxidant capacity (TAC), total peroxide (TP) and cardiac iron and calcium were determined. Oxidative stress index (OSI) was calculated. Histopathological studies using H&E, Masson trichrome and Prussian blue stains and immunohistochemical studies using Cav1.2 antibody were also carried out. Administration of ferrous sulfate induced a significant increase in serum ferritin, OSI, cardiac iron and calcium contents. Moreover, cardiomyocytes were degenerated and the expression of Cav1.2 protein was increased in iron overload group as compared to control. Verapamil decreased ferrous sulfate-induced increase in serum ferritin, OSI and cardiac iron deposition. In addition, verapamil improved myocardial degeneration and decreased the expression of Cav1.2 protein. In contrast, vitamin D produced insignificant changes in ferrous sulfate-induced increase in cardiac iron content, myocardial degeneration and the expression of Cav1.2 protein. These results indicate that verapamil has a protective effect against iron overload-induced cardiac dysfunction, oxidative stress and structural changes, while vitamin D has an insignificant effect on these parameters. PMID:25092628

  14. Isolation of intact astrocytes from the optic nerve head of adult mice

    PubMed Central

    Choi, Hee Joo; Sun, Daniel; Jakobs, Tatjana C.

    2015-01-01

    The astrocytes of the optic nerve head are a specialized subtype of white matter astrocytes that form the direct cellular environment of the unmyelinated ganglion cell axons. Due to their potential involvement in glaucoma, these astrocytes have become a target of research. Due to the heterogeneity of the optic nerve tissue, which also contains other cell types, in some cases it may be desirable to conduct gene expression studies on small numbers of well-characterized astrocytes or even individual cells. Here, we describe a simple method to isolate individual astrocytes. This method permits obtaining astrocytes with intact morphology from the adult mouse optic nerve and reduces contamination of the isolated astrocytes by other cell types. Individual astrocytes can be recognized by their morphology and collected under microscopic control. The whole procedure can be completed in 2-3 hours. We also discuss downstream applications like multiplex single-cell PCR and quantitative PCR (qPCR). PMID:26093274

  15. Prevalence of isolated diastolic hypertension and associated risk factors among adults in Kanpur, India

    PubMed Central

    Midha, Tanu; Lalchandani, Arati; Nath, Bhola; Kumari, Ranjeeta; Pandey, Umeshwar

    2012-01-01

    Background Isolated diastolic hypertension (IDH) is a largely unrecognized subtype of hypertension, more commonly seen in the younger age group. Aims (1) To determine the prevalence of IDH in the adult population of Kanpur district. (2) To study the associated risk factors of IDH. Methods A community-based cross-sectional study was conducted in 801 subjects, aged 20 years and above, using multistage stratified random sampling technique. Results The prevalence of IDH was 4.5%, which was 6.2% in men and 3.1% in women. A significant proportion of IDH was seen in the 40–49 years age group. Multivariate logistic regression analysis of the associated risk factors showed that gender, physical activity and BMI were significantly associated with IDH. Conclusion Isolated diastolic hypertension is an emerging problem in developing countries. IDH is more common among men, sedentary individuals and those with a higher BMI. PMID:22929820

  16. Comprehensive Echocardiographic Detection of Treatment-related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results from the St. Jude Lifetime Cohort Study

    PubMed Central

    Armstrong, Gregory T.; Joshi, Vijaya M.; Ness, Kirsten K.; Marwick, Thomas H.; Zhang, Nan; Srivastava, DeoKumar; Griffin, Brian P.; Grimm, Richard A.; Thomas, James; Phelan, Dermot; Collier, Patrick; Krull, Kevin R.; Mulrooney, Daniel A.; Green, Daniel M.; Hudson, Melissa M.; Robison, Leslie L.; Plana, Juan Carlos

    2015-01-01

    Background Treatment-related cardiac death is the primary non-cancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction using modern echocardiographic techniques may identify a high risk subset of survivors for early intervention. Objective To determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies using state of the art echocardiographic evaluation of cardiac function including strain imaging Methods Echocardiographic assessment included three dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain and diastolic function, graded per American Society of Echocardiography (ASE) guidelines on 1,820 adult (median age 31 [range 18-65] years) survivors of childhood cancer (median time from diagnosis 23 years [range10-48] years) exposed to either anthracycline chemotherapy (N=1,050), chest-directed radiotherapy (RT, N=306), or both therapies (N=464). Results Only 5.8% of survivors had an abnormal 3D LVEF (<50%). However, 32.1% of survivors with a normal 3D LVEF had evidence for cardiac dysfunction by either global longitudinal strain (28.0%), ASE graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed RT (1-19.9 Gy, Rate Ratio (RR) 1.38, 95% Confidence Interval (CI) 1.14-1.66; 20-29.9 Gy, RR 1.65, 95% CI 1.31-2.08; >30 Gy, RR 2.39, 95% CI 1.79-3.18) and anthracycline dose >300 mg/m2 (RR 1.72, 95% CI 1.31-2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (Rate Ratio [RR] 1.94, 95% CI 1.66-2.28) as well as abnormal diastolic function (RR 1.68, 95% CI 1.39-2.03), but not abnormal 3D LVEF (RR 1.07, 95% CI 0.74-1.53). Conclusions and Relevance Abnormal global longitudinal strain and abnormal diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a

  17. Metabolic Effects of Social Isolation in Adult C57BL/6 Mice

    PubMed Central

    Sun, Meng; Choi, Eugene Y.; Magee, Daniel J.; Stets, Colin W.; During, Matthew J.; Lin, En-Ju D.

    2014-01-01

    Obesity and metabolic dysfunction are risk factors for a number of chronic diseases, such as type 2 diabetes, hypertension, heart disease, stroke, and certain forms of cancers. Both animal studies and human population-based and clinical studies have suggested that chronic stress is a risk factor for metabolic disorders. A good social support system is known to exert positive effects on the mental and physical well-being of an individual. On the other hand, long-term deprivation of social contacts may represent a stressful condition that has negative effects on health. In the present study, we investigated the effects of chronic social isolation on metabolic parameters in adult C57BL/6 mice. We found that individually housed mice had increased adipose mass compared to group-housed mice, despite comparable body weight. The mechanism for the expansion of white adipose tissue mass was depot-specific. Notably, food intake was reduced in the social isolated animals, which occurred around the light-dark phase transition periods. Similarly, reductions in heat generated and the respiratory exchange ratio were observed during the light-dark transitions. These phase-specific changes due to long-term social isolation have not been reported previously. Our study shows social isolation contributes to increased adiposity and altered metabolic functions.

  18. 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

  19. A new method of using gas exchange measurements for the noninvasive determination of cardiac output: clinical experiences in adults following cardiac surgery.

    PubMed

    Osterlund, B; Gedeon, A; Krill, P; Johansson, G; Reiz, S

    1995-08-01

    New mathematical algorithms have been applied to a computer controlled closed breathing circuit system for non-invasive measurement of cardiac output (COniv). This system has been described in an animal study. Forty patients were studied 5 and 18 hours after cardiac surgery using the thermodilution technique as the reference (COtd). The variables entered into the algorithms for COniv were oxygen uptake, carbon dioxide elimination, end-tidal carbon dioxide partial pressure, tidal volume and arterial oxygen saturation. Mixed venous carbon dioxide partial pressure was obtained from an automatically implemented short rebreathing manoeuvre. Pulmonary perfusion was calculated by a modified Fick equation for carbon dioxide and the shunt flow added to obtain COniv. During mechanical ventilation, there was a good agreement between COtd and COniv (r = 0.8). The bias was -0.14 l/min and the precision was 0.77 l/min. The reproducibility of COniv was 0.03 l/min and for COtd -0.03 l/min with a standard deviation of the difference being 0.35 l/min for COniv and 0.31 l/min for COtd. In awake, but sedated extubated patients, the method proved unsatisfactory on account for uneven tidal volumes and difficulties with leakage around the mouth piece. We conclude that this new technique provides reliable and reproducible measures of cardiac output in sedated, ventilated patients. PMID:7484024

  20. Preoperative evaluation of the adult patient undergoing non-cardiac surgery: guidelines from the European Society of Anaesthesiology.

    PubMed

    De Hert, Stefan; Imberger, Georgina; Carlisle, John; Diemunsch, Pierre; Fritsch, Gerhard; Moppett, Iain; Solca, Maurizio; Staender, Sven; Wappler, Frank; Smith, Andrew

    2011-10-01

    The purpose of these guidelines on the preoperative evaluation of the adult non-cardiac surgery patient is to present recommendations based on available relevant clinical evidence. The ultimate aims of preoperative evaluation are two-fold. First, we aim to identify those patients for whom the perioperative period may constitute an increased risk of morbidity and mortality, aside from the risks associated with the underlying disease. Second, this should help us to design perioperative strategies that aim to reduce additional perioperative risks. Very few well performed randomised studies on the topic are available and many recommendations rely heavily on expert opinion and are adapted specifically to the healthcare systems in individual countries. This report aims to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists all over Europe to integrate - wherever possible - this knowledge into daily patient care. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of subcommittees of scientific subcommittees and individual members of the ESA. Electronic databases were searched from the year 2000 until July 2010 without language restrictions. These searches produced 15 425 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. The Scottish Intercollegiate Guidelines Network grading system was used to assess the level of evidence and to grade recommendations. The final draft guideline was posted on the ESA website for 4 weeks and the link was sent to all ESA members, individual or national (thus including most European national anaesthesia societies). Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines. PMID

  1. Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults

    PubMed Central

    Wilson, Carole L.; Gough, Peter J.; Chang, Cindy A.; Chan, Christina K.; Frey, Jeremy M.; Liu, Yonggang; Braun, Kathleen R.; Chin, Michael T.; Wight, Thomas N.; Raines, Elaine W.

    2013-01-01

    Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf−/− valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis. PMID:23354118

  2. Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.

    PubMed

    Zhang, William R; Garg, Amit X; Coca, Steven G; Devereaux, Philip J; Eikelboom, John; Kavsak, Peter; McArthur, Eric; Thiessen-Philbrook, Heather; Shortt, Colleen; Shlipak, Michael; Whitlock, Richard; Parikh, Chirag R

    2015-12-01

    Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ≥ 50% or ≥ 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. PMID:25855775

  3. Human progenitor cells derived from cardiac adipose tissue ameliorate myocardial infarction in rodents.

    PubMed

    Bayes-Genis, Antoni; Soler-Botija, Carolina; Farré, Jordi; Sepúlveda, Pilar; Raya, Angel; Roura, Santiago; Prat-Vidal, Cristina; Gálvez-Montón, Carolina; Montero, José Anastasio; Büscher, Dirk; Izpisúa Belmonte, Juan Carlos

    2010-11-01

    Myocardial infarction caused by vascular occlusion results in the formation of nonfunctional fibrous tissue. Cumulative evidence indicates that cell therapy modestly improves cardiac function; thus, novel cell sources with the potential to repair injured tissue are actively sought. Here, we identify and characterize a cell population of cardiac adipose tissue-derived progenitor cells (ATDPCs) from biopsies of human adult cardiac adipose tissue. Cardiac ATDPCs express a mesenchymal stem cell-like marker profile (strongly positive for CD105, CD44, CD166, CD29 and CD90) and have immunosuppressive capacity. Moreover, cardiac ATDPCs have an inherent cardiac-like phenotype and were able to express de novo myocardial and endothelial markers in vitro but not to differentiate into adipocytes. In addition, when cardiac ATDPCs were transplanted into injured myocardium in mouse and rat models of myocardial infarction, the engrafted cells expressed cardiac (troponin I, sarcomeric α-actinin) and endothelial (CD31) markers, vascularization increased, and infarct size was reduced in mice and rats. Moreover, significant differences between control and cell-treated groups were found in fractional shortening and ejection fraction, and the anterior wall remained significantly thicker 30days after cardiac delivery of ATDPCs. Finally, cardiac ATDPCs secreted proangiogenic factors under in vitro hypoxic conditions, suggesting a paracrine effect to promote local vascularization. Our results indicate that the population of progenitor cells isolated from human cardiac adipose tissue (cardiac ATDPCs) may be valid candidates for future use in cell therapy to regenerate injured myocardium. PMID:20713059

  4. Numerically simulated cardiac exposure to electric current densities induced by TASER X-26 pulses in adult men

    NASA Astrophysics Data System (ADS)

    Leitgeb, N.; Niedermayr, F.; Neubauer, R.; Loos, G.

    2010-10-01

    There is still an ongoing debate whether or not electronic stun devices (ESDs) induce cardiac fibrillation. To assess the ventricular fibrillation risk of law enforcing electronic control devices, quantitative estimates of cardiac electric current densities induced by delivered electric pulses are essential. Numerical simulations were performed with the finite integration technique and the anatomical model of a standardized European man (NORMAN) segmented into 2 mm voxels and 35 different tissues. The load-dependent delivery of TASER X-26 pulses has been taken into account. Cardiac exposure to electric current densities of vertically and horizontally aligned dart electrodes was quantified and different hit scenarios compared. Since fibrillation thresholds critically depend on exposed volume, the provided quantitative data are essential for risk assessment. The maximum cardiac rms current densities amounted to 7730 A m-2. Such high current densities and exposed cardiac volumes do not exclude ventricular fibrillation.

  5. Streptococcus pyogenes Pneumonia in Adults: Clinical Presentation and Molecular Characterization of Isolates 2006-2015

    PubMed Central

    Tamayo, Esther; Montes, Milagrosa; Vicente, Diego; Pérez-Trallero, Emilio

    2016-01-01

    Introduction In the preantibiotic era Streptococcus pyogenes was a common cause of severe pneumonia but currently, except for postinfluenza complications, it is not considered a common cause of community-acquired pneumonia in adults. Aim and Material and Methods This study aimed to identify current clinical episodes of S. pyogenes pneumonia, its relationship with influenza virus circulation and the genotypes of the involved isolates during a decade in a Southern European region (Gipuzkoa, northern Spain). Molecular analysis of isolates included emm, multilocus-sequence typing, and superantigen profile determination. Results Forty episodes were detected (annual incidence 1.1 x 100,000 inhabitants, range 0.29–2.29). Thirty-seven episodes were community-acquired, 21 involved an invasive infection and 10 developed STSS. The associated mortality rate was 20%, with half of the patients dying within 24 hours after admission. Influenza coinfection was confirmed in four patients and suspected in another. The 52.5% of episodes occurred outside the influenza seasonal epidemic. The 67.5% of affected persons were elderly individuals and adults with severe comorbidities, although 13 patients had no comorbidities, 2 of them had a fatal outcome. Eleven clones were identified, the most prevalent being emm1/ST28 (43.6%) causing the most severe cases. Conclusions S. pyogenes pneumonia had a continuous presence frequently unrelated to influenza infection, being rapidly fatal even in previously healthy individuals. PMID:27027618

  6. Isolation of neural crest derived chromaffin progenitors from adult adrenal medulla.

    PubMed

    Chung, Kuei-Fang; Sicard, Flavie; Vukicevic, Vladimir; Hermann, Andreas; Storch, Alexander; Huttner, Wieland B; Bornstein, Stefan R; Ehrhart-Bornstein, Monika

    2009-10-01

    Chromaffin cells of the adrenal medulla are neural crest-derived cells of the sympathoadrenal lineage. Unlike the closely-related sympathetic neurons, a subpopulation of proliferation-competent cells exists even in the adult. Here, we describe the isolation, expansion, and in vitro characterization of proliferation-competent progenitor cells from the bovine adrenal medulla. Similar to neurospheres, these cells, when prevented from adherence to the culture dish, grew in spheres, which we named chromospheres. These chromospheres were devoid of mRNA specific for smooth muscle cells (MYH11) or endothelial cells (PECAM1). During sphere formation, markers for differentiated chromaffin cells, such as phenylethanolamine-N-methyl transferase, were downregulated while neural progenitor markers nestin, vimentin, musashi 1, and nerve growth factor receptor, as well as markers of neural crest progenitor cells such as Sox1 and Sox9, were upregulated. Clonal analysis and bromo-2'-deoxyuridine-incorporation analysis demonstrated the self-renewing capacity of chromosphere cells. Differentiation protocols using NGF and BMP4 or dexamethasone induced neuronal or endocrine differentiation, respectively. Electrophysiological analyses of neural cells derived from chromospheres revealed functional properties of mature nerve cells, such as tetrodotoxin-sensitive sodium channels and action potentials. Our study provides evidence that proliferation and differentiation competent chromaffin progenitor cells can be isolated from adult adrenal medulla and that these cells might harbor the potential for the treatment of neurodegenerative diseases, such as Parkinson's disease. PMID:19609938

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

    PubMed Central

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

    1994-01-01

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

  8. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  9. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  10. Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

    PubMed

    Thornton, Christina S; Grinwis, Margot E; Sibley, Christopher D; Parkins, Michael D; Rabin, Harvey R; Surette, Michael G

    2015-11-01

    The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates. In this study, we assessed antibiotic resistance in 413 streptococcal isolates from adult CF patients against nine antibiotics relevant in CF treatment. We observed very low rates of cephalosporin resistance [cefepime and ceftriaxone ( < 2%)], and higher rates of resistance to tetracycline (∼34%) and sulfamethoxazole/trimethoprim (∼45%). The highest rate of antibiotic resistance was to the macrolides [azithromycin (56.4%) and erythromycin (51.6%)]. We also investigated the molecular mechanisms of macrolide resistance and found that only half of our macrolide-resistant streptococci isolates contained the mef (efflux pump) or erm (methylation of 23S ribosomal target site) genes. The majority of isolates were, however, found to have point mutations at position 2058 or 2059 of the 23S ribosomal subunit - a molecular mechanism of resistance not commonly reported in the non-pyogenic and non-pneumococcal streptococci, and unique in comparison with previous studies. The high rates of resistance observed here may result in poor outcomes where specific streptococci are contributing to CF airway disease and serve as a reservoir of resistance genes within the CF airway microbiome. PMID:26408040

  11. Cardiac action potential imaging

    NASA Astrophysics Data System (ADS)

    Tian, Qinghai; Lipp, Peter; Kaestner, Lars

    2013-06-01

    Action potentials in cardiac myocytes have durations in the order of magnitude of 100 milliseconds. In biomedical investigations the documentation of the occurrence of action potentials is often not sufficient, but a recording of the shape of an action potential allows a functional estimation of several molecular players. Therefore a temporal resolution of around 500 images per second is compulsory. In the past such measurements have been performed with photometric approaches limiting the measurement to one cell at a time. In contrast, imaging allows reading out several cells at a time with additional spatial information. Recent developments in camera technologies allow the acquisition with the required speed and sensitivity. We performed action potential imaging on isolated adult cardiomyocytes of guinea pigs utilizing the fluorescent membrane potential sensor di-8-ANEPPS and latest electron-multiplication CCD as well as scientific CMOS cameras of several manufacturers. Furthermore, we characterized the signal to noise ratio of action potential signals of varying sets of cameras, dye concentrations and objective lenses. We ensured that di-8-ANEPPS itself did not alter action potentials by avoiding concentrations above 5 μM. Based on these results we can conclude that imaging is a reliable method to read out action potentials. Compared to conventional current-clamp experiments, this optical approach allows a much higher throughput and due to its contact free concept leaving the cell to a much higher degree undisturbed. Action potential imaging based on isolated adult cardiomyocytes can be utilized in pharmacological cardiac safety screens bearing numerous advantages over approaches based on heterologous expression of hERG channels in cell lines.

  12. Characterization and isolation of immature neurons of the adult mouse piriform cortex.

    PubMed

    Rubio, A; Belles, M; Belenguer, G; Vidueira, S; Fariñas, I; Nacher, J

    2016-07-01

    Physiological studies indicate that the piriform or primary olfactory cortex of adult mammals exhibits a high degree of synaptic plasticity. Interestingly, a subpopulation of cells in the layer II of the adult piriform cortex expresses neurodevelopmental markers, such as the polysialylated form of neural cell adhesion molecule (PSA-NCAM) or doublecortin (DCX). This study analyzes the nature, origin, and potential function of these poorly understood cells in mice. As previously described in rats, most of the PSA-NCAM expressing cells in layer II could be morphologically classified as tangled cells and only a small proportion of larger cells could be considered semilunar-pyramidal transitional neurons. Most were also immunoreactive for DCX, confirming their immature nature. In agreement with this, detection of PSA-NCAM combined with that of different cell lineage-specific antigens revealed that most PSA-NCAM positive cells did not co-express markers of glial cells or mature neurons. Their time of origin was evaluated by birthdating experiments with halogenated nucleosides performed at different developmental stages and in adulthood. We found that virtually all cells in this paleocortical region, including PSA-NCAM-positive cells, are born during fetal development. In addition, proliferation analyses in adult mice revealed that very few cells were cycling in layer II of the piriform cortex and that none of them was PSA-NCAM-positive. Moreover, we have established conditions to isolate and culture these immature neurons in the adult piriform cortex layer II. We find that although they can survive under certain conditions, they do not proliferate in vitro either. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 748-763, 2016. PMID:26487449

  13. Is rate–pressure product of any use in the isolated rat heart? Assessing cardiac ‘effort’ and oxygen consumption in the Langendorff‐perfused heart

    PubMed Central

    Aksentijević, Dunja; Lewis, Hannah R.

    2016-01-01

    New Findings What is the central question of this study? Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species‐independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff‐perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β‐adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate–pressure product (RPP); a rather ill‐defined index of ‘work’ or, more correctly, ‘effort’. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV˙O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV˙O2 in Langendorff‐perfused rat hearts. Paced hearts (300–750 beats min−1) were perfused either with Krebs–Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV˙O2) was recorded. Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux

  14. CD13 and ROR2 Permit Isolation of Highly Enriched Cardiac Mesoderm from Differentiating Human Embryonic Stem Cells

    PubMed Central

    Skelton, Rhys J.P.; Brady, Bevin; Khoja, Suhail; Sahoo, Debashis; Engel, James; Arasaratnam, Deevina; Saleh, Kholoud K.; Abilez, Oscar J.; Zhao, Peng; Stanley, Edouard G.; Elefanty, Andrew G.; Kwon, Murray; Elliott, David A.; Ardehali, Reza

    2016-01-01

    Summary The generation of tissue-specific cell types from human embryonic stem cells (hESCs) is critical for the development of future stem cell-based regenerative therapies. Here, we identify CD13 and ROR2 as cell-surface markers capable of selecting early cardiac mesoderm emerging during hESC differentiation. We demonstrate that the CD13+/ROR2+ population encompasses pre-cardiac mesoderm, which efficiently differentiates to all major cardiovascular lineages. We determined the engraftment potential of CD13+/ROR2+ in small (murine) and large (porcine) animal models, and demonstrated that CD13+/ROR2+ progenitors have the capacity to differentiate toward cardiomyocytes, fibroblasts, smooth muscle, and endothelial cells in vivo. Collectively, our data show that CD13 and ROR2 identify a cardiac lineage precursor pool that is capable of successful engraftment into the porcine heart. These markers represent valuable tools for further dissection of early human cardiac differentiation, and will enable a detailed assessment of human pluripotent stem cell-derived cardiac lineage cells for potential clinical applications. PMID:26771355

  15. Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

    PubMed

    Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

    2016-09-01

    Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

  16. Differences in the Molecular Epidemiology and Antibiotic Susceptibility of Clostridium difficile Isolates in Pediatric and Adult Patients.

    PubMed

    Kociolek, Larry K; Gerding, Dale N; Osmolski, James R; Patel, Sameer J; Snydman, David R; McDermott, Laura A; Hecht, David W

    2016-08-01

    The rising incidence of Clostridium difficile infections (CDIs) in adults is partly related to the global spread of fluoroquinolone-resistant strains, namely, BI/NAP1/027. Although CDIs are also increasingly diagnosed in children, BI/NAP1/027 is relatively uncommon in children. Little is known about the antibiotic susceptibility of pediatric CDI isolates. C. difficile was cultured from tcdB-positive stools collected from children diagnosed with CDI between December 2012 and December 2013 at an academic children's hospital. CDI isolates were grouped by restriction endonuclease analysis (REA). MICs were measured by agar dilution method for 7 antibiotics. Susceptibility breakpoints were based on guidelines from CLSI and/or the European Committee on Antimicrobial Susceptibility Testing (EUCAST). MICs and REA groupings of C. difficile isolates from 74 adult patients (29 isolates underwent REA) from a temporally and geographically similar adult cohort were compared to those of pediatric isolates. Among 122 pediatric and 74 adult isolates, respectively, the rates of resistance were as follows: metronidazole, 0% and 0%; vancomycin, 0% and 8% (P = 0.003); rifaximin, 1.6% and 6.7% (P = 0.11); clindamycin, 18.9% and 25.3% (P = 0.29); and moxifloxacin, 2.5% and 36% (P = <0.0001). Only 1 of 122 (0.8%) BI/NAP1/027 isolates was identified among the children, compared to 9 of 29 (31%) isolates identified among the adults (P = <0.0001). The 3 moxifloxacin-resistant pediatric isolates were of REA groups BI and CF and a nonspecific group. The 2 rifaximin-resistant pediatric isolates were of REA groups DH and Y. The 21 clindamycin-resistant pediatric isolates were distributed among 9 REA groups (groups A, CF, DH, G, L, M, and Y and 2 unique nonspecific REA groups). These data suggest that a diverse array of relatively antibiotic-susceptible C. difficile strains predominate in a cohort of children with CDI compared to adults. PMID:27270275

  17. Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate

    PubMed Central

    Hauser, Stefan; Widera, Darius; Qunneis, Firas; Müller, Janine; Zander, Christin; Greiner, Johannes; Strauss, Christina; Lüningschrör, Patrick; Heimann, Peter; Schwarze, Hartmut; Ebmeyer, Jörg; Sudhoff, Holger; Araúzo-Bravo, Marcos J.; Greber, Boris; Zaehres, Holm; Schöler, Hans; Kaltschmidt, Christian

    2012-01-01

    Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75NTR, and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75NTR positive ITSCs that formed larger neurospheres and proliferated faster than p75NTR negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy. PMID:22128806

  18. Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers.

    PubMed

    He, Z P; Tan, W Q; Tang, Y F; Zhang, H J; Feng, M F

    2004-04-01

    Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem-like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV-6, cytokeratin-19 (CK-19) and albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis displayed that the freshly isolated cells co-expressed albumin, cytokeratin-7 (CK-7) and CK-19 mRNA, indicating that they were essentially bipotential hepatic stem-like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK-7 and CK-19 in the cells derived from the expanding colonies at day 95 were confirmed by RT-PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential

  19. Cardiac Rehabilitation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Rehabilitation? Cardiac rehabilitation (rehab) is a medically supervised program ... be designed to meet your needs. The Cardiac Rehabilitation Team Cardiac rehab involves a long-term commitment ...

  20. Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats.

    PubMed

    Carnevali, L; Mastorci, F; Graiani, G; Razzoli, M; Trombini, M; Pico-Alfonso, M A; Arban, R; Grippo, A J; Quaini, F; Sgoifo, A

    2012-05-15

    Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic-pituitary-adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression-cardiovascular comorbidity. PMID:22330326

  1. Respiratory neuron characterization reveals intrinsic bursting properties in isolated adult turtle brainstems (Trachemys scripta).

    PubMed

    Johnson, Stephen M; Hedrick, Michael S; Krause, Bryan M; Nilles, Jacob P; Chapman, Mark A

    2016-04-01

    It is not known whether respiratory neurons with intrinsic bursting properties exist within ectothermic vertebrate respiratory control systems. Thus, isolated adult turtle brainstems spontaneously producing respiratory motor output were used to identify and classify respiratory neurons based on their firing pattern relative to hypoglossal (XII) nerve activity. Most respiratory neurons (183/212) had peak activity during the expiratory phase, while inspiratory, post-inspiratory, and novel pre-expiratory neurons were less common. During synaptic blockade conditions, ∼10% of respiratory neurons fired bursts of action potentials, with post-inspiratory cells (6/9) having the highest percentage of intrinsic burst properties. Most intrinsically bursting respiratory neurons were clustered at the level of the vagus (X) nerve root. Synaptic inhibition blockade caused seizure-like activity throughout the turtle brainstem, which shows that the turtle respiratory control system is not transformed into a network driven by intrinsically bursting respiratory neurons. We hypothesize that intrinsically bursting respiratory neurons are evolutionarily conserved and represent a potential rhythmogenic mechanism contributing to respiration in adult turtles. PMID:25462012

  2. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012

    PubMed Central

    Song, Jin-Su; Kim, Eui-Chong

    2016-01-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period. PMID:27134492

  3. Serotype Distribution and Antimicrobial Susceptibilities of Invasive Streptococcus pneumoniae Isolates from Adults in Korea from 1997 to 2012.

    PubMed

    Kim, Chung Jong; Song, Jin-Su; Choi, Su-Jin; Song, Kyoung Ho; Choe, Pyeong Gyun; Park, Wan Beom; Bang, Ji Hwan; Kim, Eu Suk; Park, Sang Won; Kim, Hong Bin; Kim, Nam-Joong; Kim, Eui-Chong; Oh, Myoung-Don

    2016-05-01

    In Republic of Korea, a 7-valent pneumococcal conjugated vaccine (PCV7) was licensed for use in infants in 2003, and 13-valent PCV (PCV13) replaced it since 2010. We investigated trends in serotype distribution and antibiotic susceptibility of pneumococcal isolates from adult patients with invasive pneumococcal diseases (IPD). Invasive pneumococcal isolates from adult patients of ≥ 16 years of age were collected from 1997 to 2012. Serotypes of the isolates were determined by the Quellung reaction. Distribution of serotypes was analyzed according to the vaccine types. Antibiotic susceptibility was tested by using E-test strips. A total of 272 invasive pneumococcal isolates were included. The most common serotypes were serotype 19F (8.5%, 23/272), and serotype 3 (8.1%, 22/272), and 24.6% (67/272) of the isolates were of non-vaccine serotypes. Of the 272 isolates, 2.6% (7/272) were penicillin MICs of ≥ 4 µg/mL. The proportion of the PCV13 serotypes decreased from 63.3% (50/79) in 1997-2003 to 48.6% (17/35) in 2011-2012, whereas that of non-vaccine serotypes was 26.6% (21/79) and 25.7% (9/35), respectively, for the same periods. The proportion of the PCV13 serotypes showed a decreasing trend among adult patients with IPD over the study period. PMID:27134492

  4. Cardiac Outcomes in Adult Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy: A Cross-Sectional Study from the St. Jude Lifetime Cohort

    PubMed Central

    Mulrooney, Daniel A.; Armstrong, Gregory T.; Huang, Sujuan; Ness, Kirsten K.; Ehrhardt, Matthew J.; Joshi, Vijaya M.; Plana, Juan Carlos; Soliman, Elsayed Z.; Green, Daniel M.; Srivastava, Deokumar; Santucci, Aimee; Krasin, Matthew J.; Robison, Leslie L.; Hudson, Melissa M.

    2016-01-01

    Background Studies of cardiac disease among adult survivors of childhood cancer have generally relied upon self-reported or registry-based data. Objective Systematically assess cardiac outcomes among childhood cancer survivors Design Cross-sectional Setting St. Jude Children's Research Hospital Patients 1,853 adult survivors of childhood cancer, ≥18 years old, and ≥10 years from treatment with cardiotoxic therapy for childhood cancer. Measurements History/physical examination, fasting metabolic and lipid panels, echocardiogram, electrocardiogram (ECG), 6-minute walk test (6MWT) all collected at baseline evaluation. Results Half (52.3%) of the survivors were male, median age 8.0 years (range: 0-24) at cancer diagnosis, 31.0 years (18-60) at evaluation. Cardiomyopathy was present in 7.4% (newly identified at the time of evaluation in 4.7%), coronary artery disease (CAD) in 3.8% (newly identified in 2.2%), valvular regurgitation/stenosis in 28.0% (newly identified in 24.8%), and conduction/rhythm abnormalities in 4.6% (newly identified in 1.4%). Nearly all (99.7%) were asymptomatic. The prevalences of cardiac conditions increased with age at evaluation, ranging from 3-24% among those 30-39 years to 10-37% among those ≥40 years. On multivariable analysis, anthracycline exposure ≥250 mg/m2 increased the odds of cardiomyopathy (odds ratio [OR] 2.7, 95% CI 1.1-6.9) compared to anthracycline unexposed survivors. Radiation to the heart increased the odds of cardiomyopathy (OR 1.9 95% CI 1.1-3.7) compared to radiation unexposed survivors. Radiation >1500 cGy with any anthracycline exposure conferred the greatest odds for valve findings. Limitations 61% participation rate of survivors exposed to cardiotoxic therapies, which were limited to anthracyclines and cardiac-directed radiation. A comparison group and longitudinal assessments are not available. Conclusions Cardiovascular screening identified considerable subclinical disease among adult survivors of childhood

  5. Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament.

    PubMed

    Athanassiou-Papaefthymiou, M; Papagerakis, P; Papagerakis, S

    2015-11-01

    We report a novel method for the isolation of adult human epithelial stem cells (hEpiSCs) from the epithelial component of the periodontal ligament-the human epithelial cell rests of Malassez (hERM). hEpiSC-rich integrin-α6(+ve) hERM cells derived by fluorometry can be clonally expanded, can grow organoids, and express the markers of pluripotency (OCT4, NANOG, SOX2), polycomb protein RING1B, and the hEpiSC supermarker LGR5. They maintain the growth profile of their originating hERM in vitro. Subcutaneous cotransplantation with mesenchymal stem cells from the dental pulp on poly-l-lactic acid scaffolds in nude mice gave rise to perfect heterotopic ossicles in vivo with ultrastructure of dentin, enamel, cementum, and bone. These remarkable fully mineralized ossicles underscore the importance of epithelial-mesenchymal crosstalk in tissue regeneration using human progenitor stem cells, which may have already committed to lineage despite maintaining hallmarks of pluripotency. In addition, we report the clonal expansion and isolation of human LGR5(+ve) cells from the hERM in xeno-free culture conditions. The genetic profile of LGR5(+ve) cells includes both markers of pluripotency and genes important for secretory epithelial and dental epithelial cell differentiation, giving us a first insight into periodontal ligament-derived hEpiSCs. PMID:26392003

  6. Isolation of high-purity myenteric plexus from adult human and mouse gastrointestinal tract

    PubMed Central

    Grundmann, David; Klotz, Markus; Rabe, Holger; Glanemann, Matthias; Schäfer, Karl-Herbert

    2015-01-01

    The enteric nervous system (ENS) orchestrates a broad range of important gastrointestinal functions such as intestinal motility and gastric secretion. The ENS can be affected by environmental factors, diet and disease. Changes due to these alterations are often hard to evaluate in detail when whole gut samples are used. Analyses based on pure ENS tissue can more effectively reflect the ongoing changes during pathological processes. Here, we present an optimized approach for the isolation of pure myenteric plexus (MP) from adult mouse and human. To do so, muscle tissue was individually digested with a purified collagenase. After incubation and a gentle mechanical disruption step, MP networks could be collected with anatomical integrity. These tissues could be stored and used either for immediate genomic, proteomic or in vitro approaches, and enteric neurospheres could be generated and differentiated. In a pilot experiment, the influence of bacterial lipopolysaccharide on human MP was analyzed using 2-dimensional gel electrophoresis. The method also allows investigation of factors that are secreted by myenteric tissue in vitro. The isolation of pure MP in large amounts allows new analytical approaches that can provide a new perspective in evaluating changes of the ENS in experimental models, human disease and aging. PMID:25791532

  7. Trophic effect of human pericardial fluid on adult cardiac myocytes. Differential role of fibroblast growth factor-2 and factors related to ventricular hypertrophy.

    PubMed

    Corda, S; Mebazaa, A; Gandolfini, M P; Fitting, C; Marotte, F; Peynet, J; Charlemagne, D; Cavaillon, J M; Payen, D; Rappaport, L; Samuel, J L

    1997-11-01

    Pericardial fluid (PF) may contain myocardial growth factors that exert paracrine actions on cardiac myocytes. The aims of this study were (1) to investigate the effects of human PF and serum, collected from patients undergoing cardiac surgery, on the growth of cultured adult rat cardiac myocytes and (2) to relate the growth activity of both fluids to the adaptive changes in overloaded human hearts. Both PF and serum increased the rate of protein synthesis, measured by [14C]phenylalanine incorporation in adult rat cardiomyocytes (PF, +71.9 +/- 8.2% [n = 17]; serum, +14.9 +/- 6.5% [n = 13]; both P < .01 versus control medium). The effects of both PF and serum on cardiomyocyte growth correlated positively with the respective left ventricular (LV) mass. However, the magnitude of change with PF was 3-fold greater than with serum (P < .01). These trophic effects of PF were mimicked by exogenous basic fibroblast growth factor (FGF2) and inhibited by anti-FGF2 antibodies and transforming growth factor-beta (TGF-beta), suggesting a relationship to FGF2. In addition, FGF2 concentration in PF was 20 times greater than in serum. On the other hand, the LV mass-dependent trophic effect, present in both fluids, was independent of FGF2 concentration or other factors, such as angiotensin II, atrial natriuretic factor, and TGF-beta. These data suggest that FGF2 in human PF is a major determining factor in normal myocyte growth, whereas unidentified LV mass-dependent factor(s), present in both PF and serum, participates in the development of ventricular hypertrophy. PMID:9351441

  8. Primary culture of purified Leydig cells isolated from adult rat testes.

    PubMed

    Browning, J Y; Heindel, J J; Grotjan, H E

    1983-02-01

    Methods for isolating highly purified Leydig cells permit the study of acute responses and biochemical properties of Leydig cells independent of other testicular cell types. The present study describes the development of a primary culture system for purified Leydig cells from adult rats in which the cells retain their ability to secrete testosterone for at least 72 h in culture. When Leydig cells were cultured in tissue culture medium 199--0.1% BSA (M199-BSA), basal testosterone secretion declined by 72 h, whereas hCGB-stimulated testosterone secretion was reduced by 48 h. Changing the culture medium twice daily or adding 0.5% fetal calf serum (fcs) enhanced basal and gonadotropin-stimulated testosterone secretion at 72 h in culture, although responsiveness to hCG was reduced to 57% of that in freshly isolated cells. Incubation of Leydig cells in the defined culture medium Dulbecco's Modified Eagles-Ham's F-12 (1:1, vol/vol) supplemented with 15 mM Hepes buffer, transferrin, insulin, and epidermal growth factor (DHG:F12 + Hepes + TIE) in either the presence or absence of 0.5% fcs yielded functional Leydig cells for longer intervals in culture. Furthermore, testosterone secretion was greater in DHG:F12 + Hepes + TIE than in M199-BSA at all time intervals tested. In DHG:F12 + Hepes + TIE, basal and gonadotropin-stimulated testosterone production by Leydig cells were maintained for 72 h in culture. Degenerative changes in morphology were apparent in some cells at 72 h, but not at earlier times in culture. This primary culture system for isolated Leydig cells provides a valuable tool to examine the temporally regulated events in Leydig cell function. PMID:6848362

  9. Neuroprotective properties of marrow-isolated adult multilineage-inducible cells in rat hippocampus following global cerebral ischemia are enhanced when complexed to biomimetic microcarriers.

    PubMed

    Garbayo, Elisa; Raval, Ami P; Curtis, Kevin M; Della-Morte, David; Gomez, Lourdes A; D'Ippolito, Gianluca; Reiner, Teresita; Perez-Stable, Carlos; Howard, Guy A; Perez-Pinzon, Miguel A; Montero-Menei, Claudia N; Schiller, Paul C

    2011-12-01

    Cell-based therapies for global cerebral ischemia represent promising approaches for neuronal damage prevention and tissue repair promotion. We examined the potential of marrow-isolated adult multilineage-inducible (MIAMI) cells, a homogeneous subpopulation of immature human mesenchymal stromal cell, injected into the hippocampus to prevent neuronal damage induced by global ischemia using rat organotypic hippocampal slices exposed to oxygen-glucose deprivation and rats subjected to asphyxial cardiac arrest. We next examined the value of combining fibronectin-coated biomimetic microcarriers (FN-BMMs) with epidermal growth factor (EGF)/basic fibroblast growth factor (bFGF) pre-treated MIAMI compared to EGF/bFGF pre-treated MIAMI cells alone, for their in vitro and in vivo neuroprotective capacity. Naïve and EGF/bFGF pre-treated MIAMI cells significantly protected the Cornu Ammonis layer 1 (CA1) against ischemic death in hippocampal slices and increased CA1 survival in rats. MIAMI cells therapeutic value was significantly increased when delivering the cells complexed with FN-BMMs, probably by increasing stem cell survival and paracrine secretion of pro-survival and/or anti-inflammatory molecules as concluded from survival, differentiation and gene expression analysis. Four days after oxygen and glucose deprivation and asphyxial cardiac arrest, few transplanted cells administered alone survived in the brain whereas stem cell survival improved when injected complexed with FN-BMMs. Interestingly, a large fraction of the transplanted cells administered alone or in complexes expressed βIII-tubulin suggesting that partial neuronal transdifferentiation may be a contributing factor to the neuroprotective mechanism of MIAMI cells. PMID:21496021

  10. The Effects of Radiofrequency or Cryothermal Ablation on Biomechanical Properties of Isolated Human or Swine Cardiac Tissues

    PubMed Central

    Quallich, Stephen G.; Kriege, Kevin E.

    2016-01-01

    Changes in cardiac tissue properties following the application of various ablation modalities may lead to the development of an array of associated complications. The application of either radio frequency (RF) or cryothermal ablations will alter the biomechanical properties of various cardiac tissues in a differential manner; in some cases, this may be attributable to increased incidences of cardiac tamponade, pulmonary vein stenosis, and/or atrial-esophageal fistula. Thus, a greater understanding of the underlying changes in tissue properties induced by ablative therapies will ultimately promote safer and more efficacious procedures. The effects of applied RF or cryothermal energies on the biomechanical properties of the pulmonary vein, left atrial, or right atrial samples (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\text {n}=369$ \\end{document}) were examined from fresh excised porcine (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\text {n}=35$ \\end{document}) and donated human tissue (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$\\text {n}=11$ \\end{document}). RF ablations were found to reduce the tensile strength of the porcine cardiac specimens (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt

  11. Isolated intestinal transplants vs. liver-intestinal transplants in adult patients in the United States: 22 yr of OPTN data.

    PubMed

    Desai, Chirag S; Gruessner, Angelika C; Khan, Khalid M; Fishbein, Thomas M; Jie, Tun; Rodriguez Rilo, Horacio L; Gruessner, Rainer W G

    2012-01-01

    We examined the outcomes of adult intestinal transplants (ITx); isolated ITx vs. liver-intestinal transplants (L-ITx) were compared using the UNOS database (1987-2009). Of 759 ITx transplants in 687 patients, 463 (61%) were isolated and 296 (39%) were L-ITx. Patient survival for primary isolated ITx at one, three, and five yr was 84%, 66.7%, and 54.2%; and primary L-ITx was, 67%, 53.3%, and 46% (p = 0.0005). Primary isolated ITx graft survival at one, three, and five yr was 80.7%, 57.6%, 42.8%; primary L-ITx was 64.1%, 51%, 44.1% (p = 0.0003 at one, three yr, Wilcoxon test). For retransplants (n = 72), patient and graft survival for isolated ITx (n = 41) at five yr was 40% in era 1 (1987-2000) and 16% in era 2 (p = 0.47); for retransplanted L-ITx (n = 31), it improved from 14% to 64% in era 2 (p = 0.01). Cox regression: creatinine >1.3 mg/dL and pre-transplant hospitalization were negative predictors for outcome of both; bilirubin >1.3 mg/dL was a negative predictor for isolated ITx and donor age >40 yr for L-ITx. Isolated ITx should be considered prior to liver disease for adults with intestinal failure; L-ITx is preferable for retransplantation. PMID:22192061

  12. Properties of ionic currents from isolated adult rat carotid body chemoreceptor cells: effect of hypoxia.

    PubMed Central

    López-López, J R; González, C; Pérez-García, M T

    1997-01-01

    1. The electrical properties of chemoreceptor cells from neonatal rat and adult rabbit carotid bodies (CBs) are strikingly different. These differences have been suggested to be developmental and/or species related. To distinguish between the two possibilities, the whole-cell configuration of the patch-clamp technique was used to characterize the ionic currents present in isolated chemoreceptor cells from adult rat CBs. Since hypoxia-induced inhibition of O2-sensitive K+ currents is considered a crucial step in O2 chemoreception, the effect of hypoxia on the adult rat chemoreceptor cell currents was also studied. 2. Outward currents were carried mainly by K+, and two different components could be distinguished: a Ca(2+)-dependent K+ current (IK(Ca)) sensitive to Cd2+ and charybdotoxin (CTX), and a Ca(2+)-insensitive, voltage-dependent K+ current (IK(V)). IK(V) showed a slow voltage-dependent activation (time constant (tau) of 87.4 ms at -20 mV and 8.8 ms at +60 mV) and a very slow inactivation, described by the sum of two exponentials (tau 1 = 684 +/- 150 ms and tau 2 = 4.96 +/- 0.76 s at + 30 mV), that was almost voltage insensitive. The kinetic and pharmacological properties of IK(V) are typical of a delayed rectifier K+ channel. 3. Voltage-dependent Ca2+ currents (ICa) were present in nineteen of twenty-seven cells. TTX-sensitive Na+ currents were also observed in about 10% of the cells. 4. Low PO2 (< 10 mmHg) reduced the whole outward current amplitude by 22.17 +/- 1.96% (n = 27) at +20 mV. This effect was absent in the presence of Cd2+. Since low PO2 did not affect ICa, we conclude that hypoxia selectively blocks IK(Ca). 5. The properties of the currents recorded in adult rat chemoreceptor cells, including the specific inhibition of IK(Ca) by hypoxia, are similar to those reported in neonatal rat CB cells, implying that the differences between rat and rabbit chemoreceptor cells are species related. PMID:9080372

  13. Protocol to Isolate a Large Amount of Functional Oligodendrocyte Precursor Cells from the Cerebral Cortex of Adult Mice and Humans

    PubMed Central

    Medina-Rodríguez, Eva María; Arenzana, Francisco Javier; Bribián, Ana; de Castro, Fernando

    2013-01-01

    During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs), a cell type that is a significant proportion of the total cells (3-8%) in the adult central nervous system (CNS) of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS) and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair. PMID:24303061

  14. Protection against cardiac anoxia--role and limitations of increased glycogen reserves in the isolated rat right ventricular strip.

    PubMed

    Towart, R; Schlossmann, K; Kazda, S

    1981-01-01

    The effects of drugs on rat cardiac glycogen reserves in vivo, and on the subsequent in vitro sensitivity of the right ventricular strip preparation to anoxia have been investigated. Isoproterenol (0.2 mg/kg i.p.) causes immediate cardiac stimulation and reduction of glycogen reserves, coupled with an increased susceptibility to anoxia. Several hours after administration, glycogen levels are found to be greatly (100-200%) increased, by a "supercompensation" mechanism, and a marked tolerance to anoxia can be simultaneously demonstrated. In contrast, large doses of corticosteroids (dexamethasone, 8 mg/kg i.m.) increase glycogen levels without initial stimulation and glycogen depletion; increased myocardial tolerance to anoxia parallels the increase in glycogen reserves in vivo. We conclude that the myocardial tolerance to anoxia in this model is related to increased glycogen reserves, which increase the rate and/or duration of anaerobic glycolysis during anoxia. PMID:7332516

  15. Conus artery occlusion causing isolated right ventricular outflow tract infarction: novel application of cardiac magnetic resonance in anterior STEMI

    PubMed Central

    Lyle, Melissa; Tweet, Marysia; Young, Phillip M.; Best, Patricia J. M.

    2016-01-01

    Acute ST elevation in the anterior precordial leads typically suggests an anteroseptal infarction due to left anterior descending coronary artery obstruction, but the differential can be broad. Conus branch artery occlusion is a potentially overlooked cause of anteroseptal ST elevation myocardial infraction. Cardiac magnetic resonance (CMR) imaging is an emerging technology which can differentiate the etiology of anterior ST elevation in patients with no apparent coronary abnormalities on coronary angiography and normal echocardiography. PMID:27280090

  16. Clinical practice in perioperative monitoring in adult cardiac surgery: is there a standard of care? Results from an national survey.

    PubMed

    Bignami, Elena; Belletti, Alessandro; Moliterni, Paola; Frati, Elena; Guarnieri, Marcello; Tritapepe, Luigi

    2016-06-01

    This study was to investigate and define what is considered as a current clinical practice in hemodynamic monitoring and vasoactive medication use after cardiac surgery in Italy. A 33-item questionnaire was sent to all intensive care units (ICUs) admitting patients after cardiac surgery. 71 out of 92 identified centers (77.2 %) returned a completed questionnaire. Electrocardiogram, invasive blood pressure, central venous pressure, pulse oximetry, diuresis, body temperature and blood gas analysis were identified as routinely used hemodynamic monitoring, whereas advanced monitoring was performed with pulmonary artery catheter or echocardiography. Crystalloids were the fluids of choice for volume replacement (86.8 % of Centers). To guide volume management, central venous pressure (26.7 %) and invasive blood pressure (19.7 %) were the most frequently used parameters. Dobutamine was the first choice for treatment of left heart dysfunction (40 %) and epinephrine was the first choice for right heart dysfunction (26.8 %). Half of the Centers had an internal protocol for vasoactive drugs administration. Intra-aortic balloon pump and extra-corporeal membrane oxygenation were widely available among Cardiothoracic ICUs. Angiotensin-converting enzyme inhibitors were suspended in 28 % of the Centers. The survey shows what is considered as standard monitoring in Italian Cardiac ICUs. Standard, routinely used monitoring consists of ECG, SpO2, etCO2, invasive BP, CVP, diuresis, body temperature, and BGA. It also shows that there is large variability among the various Centers regarding hemodynamic monitoring of fluid therapy and inotropes administration. Further research is required to better standardize and define the indicators to improve the standards of intensive care after cardiac surgery among Italian cardiac ICUs. PMID:26089166

  17. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  18. Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats.

    PubMed

    Segura, Bertha; Melo, Angel I; Fleming, Alison S; Mendoza-Garrido, Maria Eugenia; González del Pliego, Margarita; Aguirre-Benitez, Elsa L; Hernández-Falcón, Jesús; Jiménez-Estrada, Ismael

    2014-12-01

    Sensory and social deprivation from the mother and littermates during early life disturbs the development of the central nervous system, but little is known about its effect on the development of the peripheral nervous system. To assess peripheral effects of early isolation, male rat pups were reared artificially in complete social isolation (AR); reared artificially with two same-age conspecifics (AR-Social); or reared by their mothers and with littermates (MR). As adults, the electrophysiological properties of the sensory sural (SU) nerve were recorded. We found that the amplitude and normalized area (with respect to body weight) of the compound action potential (CAP) response provoked by single electrical pulses of graded intensity in the SU nerves of AR animals were shorter than the CAP recorded in SU nerves from MR and AR-Social animals. The slope of the stimulus-response curve of AR SU nerves was smaller than that of the other nerves. The histological characterization of axons in the SU nerves was made and showed that the myelin thickness of axons in AR SU nerves was significant lower (2-7µm) than that of the axons in the other nerves. Furthermore, the area and axon diameter of SU nerves of both AR and AR-Social animals were significant lower than in MR animals. This is the first report to show that maternal and littermate deprivation by AR disturbs the development of the myelination and electrophysiological properties of axons in the SU nerve; the replacement of social cues prevents most of the effects. PMID:24897933

  19. Airway strategies for lung isolation in a patient with high-velocity nail gun injuries to the right cardiac ventricle and floor of the mouth: a case report

    PubMed Central

    2013-01-01

    Introduction We report a case of deliberate self-harm in which three three-inch nails were fired from a nail gun resulting in mandibular fixation and two penetrating injuries to the right cardiac ventricle. This combination of high-velocity penetrating injury has not been previously described. Case presentation A 69-year-old Caucasian man with a medical history of chronic depression was brought to hospital after a failed suicide attempt. The attempt consisted of self-asphyxiation with car exhaust fumes and shooting himself thrice with a three-inch nail gun. He sustained a penetrating nail injury to the floor of his mouth, effectively pinning his mouth closed, and penetrating injuries to the right ventricular free wall and at the junction of the right atrioventricular septum. The patient required emergency surgery with requirements for thoracotomy and sternotomy, lung isolation and cardiopulmonary bypass. Conclusions This is the first reported case of a combination high-velocity penetrating nail gun injury to the face and the right cardiac ventricle. This rare case offers airway strategies to accommodate the surgical requirement for lung separation for penetrating chest trauma in a patient with iatrogenically limited mouth opening. PMID:23714118

  20. Isolation and Culture of Dental Epithelial Stem Cells from the Adult Mouse Incisor

    PubMed Central

    Chavez, Miquella G.; Hu, Jimmy; Seidel, Kerstin; Li, Chunying; Jheon, Andrew; Naveau, Adrien; Horst, Orapin; Klein, Ophir D.

    2014-01-01

    Understanding the cellular and molecular mechanisms that underlie tooth regeneration and renewal has become a topic of great interest1-4, and the mouse incisor provides a model for these processes. This remarkable organ grows continuously throughout the animal's life and generates all the necessary cell types from active pools of adult stem cells housed in the labial (toward the lip) and lingual (toward the tongue) cervical loop (CL) regions. Only the dental stem cells from the labial CL give rise to ameloblasts that generate enamel, the outer covering of teeth, on the labial surface. This asymmetric enamel formation allows abrasion at the incisor tip, and progenitors and stem cells in the proximal incisor ensure that the dental tissues are constantly replenished. The ability to isolate and grow these progenitor or stem cells in vitro allows their expansion and opens doors to numerous experiments not achievable in vivo, such as high throughput testing of potential stem cell regulatory factors. Here, we describe and demonstrate a reliable and consistent method to culture cells from the labial CL of the mouse incisor. PMID:24834972

  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. 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

  3. Social Isolation Stress Induces Anxious-Depressive-Like Behavior and Alterations of Neuroplasticity-Related Genes in Adult Male Mice

    PubMed Central

    Ieraci, Alessandro; Mallei, Alessandra; Popoli, Maurizio

    2016-01-01

    Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice. PMID:26881124

  4. Cardiac Catheterization

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Catheterization? Cardiac catheterization (KATH-eh-ter-ih-ZA-shun) is a ... disease. Doctors also can use ultrasound during cardiac catheterization to see blockages in the coronary arteries. Ultrasound ...

  5. Localization of chemosensitive structures in the isolated brainstem of adult guinea-pig.

    PubMed Central

    Morin-Surun, M P; Boudinot, E; Schäfer, T; Denavit-Saubié, M

    1995-01-01

    1. Central respiratory chemosensitivity has been intensively examined but some questions remain unsolved; namely, what is the nature of the stimulus (fixed acid and/or CO2) and where is the site of brainstem chemosensitivity (near the ventral medullary surface or structures deeper within the brainstem)? To examine these questions, we used the in vitro isolated brainstem of adult guinea-pig perfused independently through the basilar artery and the bath. 2. Respiratory motor output was recorded with a suction electrode from cranial hypoglossal (XII) roots. Changes in pH and CO2 in the Krebs perfusate were made by changing either the bicarbonate concentration or the PCO2 saturating the Krebs solution. 3. Changes in basilar artery perfusate consisting of (i) an acidifying increase in PCO2 (hypercapnic acidic Krebs solution), (ii) an increase in PCO2 with no change in pH (hypercapnic Krebs solution), or (iii) a decrease in pH with no change in PCO2 (acidic Krebs solution) evoked increases in respiratory frequency and a concomitant decrease in inspiratory burst amplitude. 4. Bath superfusion with hypercapnic acidic Krebs solution increased the inspiratory burst amplitude with no effect on respiratory burst frequency. 5. Bath superfusion with hypercapnic non-acidic Krebs solution increased the inspiratory burst amplitude and decreased the respiratory frequency, while normocapnic acidic Krebs solution increased the respiratory frequency with no change in burst amplitude. 6. These results show that respiratory responses to changes in CO2 and pH depend upon the sites of action. While a CO2 increase or a pH decrease affected the respiratory frequency in the deep brainstem structures (perfused through the basilar artery), CO2 respiratory chemosensitivity at the ventral surface could be differentiated from the hydrogen ion chemosensitivity. This suggests that different mechanisms mediated respiratory responses when deep versus superficial brainstem structures were stimulated

  6. Ionic mechanism underlying recovery of rhythmic activity in adult isolated neurons

    PubMed Central

    Haedo, Rodolfo J.; Golowasch, Jorge

    2013-01-01

    Neurons exhibit long-term excitability changes necessary for maintaining proper cell and network activity in response to various inputs and perturbations. For instance, the adult crustacean pyloric network can spontaneously recover rhythmic activity after complete shutdown resulting from permanent removal of neuromodulatory inputs. Dissociated lobster stomatogastric ganglion (STG) neurons have been shown to spontaneously develop oscillatory activity via excitability changes. Rhythmic electrical stimulation can eliminate these oscillatory patterns in some cells. The ionic mechanisms underlying these changes are only partially understood. We used dissociated crab STG neurons to study the ionic mechanisms underlying spontaneous recovery of rhythmic activity and stimulation-induced activity changes. Similar to lobster neurons, rhythmic activity spontaneously develops in crab STG neurons. Rhythmic hyperpolarizing stimulation can eliminate, but more commonly accelerate the emergence of stable oscillatory activity depending on Ca++ influx at hyperpolarized voltages. Our main finding is that up-regulation of a Ca++-current and down-regulation of a high-threshold K+-current underlies the spontaneous homeostatic development of oscillatory activity. However, because of a non-linear dependence on stimulus frequency, hyperpolarization-induced oscillations appear to be inconsistent with a homeostatic regulation of activity. We find no difference in the activity patterns or the underlying ionic currents involved between neurons of the fast pyloric and the slow gastric mill networks during the first ten days in isolation. Dynamic-clamp experiments confirm that these conductance modifications can explain the observed activity changes. We conclude that spontaneous and stimulation-induced excitability changes in STG neurons can both result in intrinsic oscillatory activity via regulation of the same two conductances. PMID:16807346

  7. Fluid absorption in the isolated midgut of adult female yellow fever mosquitoes (Aedes aegypti)

    PubMed Central

    Onken, Horst; Moffett, David F.

    2015-01-01

    ABSTRACT The transepithelial voltage (Vte) and the volume of isolated posterior midguts of adult female yellow fever mosquitoes (Aedes aegypti) were monitored. In all experiments, the initial Vte after filling the midgut was lumen negative, but subsequently became lumen positive at a rate of approximately 1 mV min−1. Simultaneously, the midgut volume decreased, indicating spontaneous fluid absorption. When the midguts were filled and bathed with mosquito saline, the average rate of fluid absorption was 36.5±3.0 nl min−1 (N=4, ±s.e.m.). In the presence of theophylline (10 mmol l−1), Vte reached significantly higher lumen-positive values, but the rate of fluid absorption was not affected (N=6). In the presence of NaCN (5 mmol l−1), Vte remained close to 0 mV (N=4) and fluid absorption was reduced (14.4±1.3 nl min−1, N=3, ±s.e.m.). When midguts were filled with buffered NaCl (154 mmol l−1 plus 1 mmol l−1 HEPES) and bathed in mosquito saline with theophylline, fluid absorption was augmented (50.0±5.8 nl min−1, N=12, ±s.e.m.). Concanamycin A (10 µmol l−1), ouabain (1 mmol l−1), and acetazolamide (1 mmol l−1) affected Vte in different ways, but all reduced fluid absorption by 60–70% of the value before addition of the drugs. PMID:25944920

  8. Fulminant isolated cardiac sarcoidosis with pericardial effusion and acute heart failure: Challenging aspects of diagnosis and treatment

    PubMed Central

    Fluschnik, Nina; Lund, Gunnar; Becher, Peter Moritz; Blankenberg, Stefan; Muellerleile, Kai

    2016-01-01

    This case report illustrates challenging aspects of diagnosis and treatment of isolated sarcoid heart disease (SHD) and the role of cardiovascular magnetic resonance (CMR) imaging. Here, we present a previously healthy 45-year-old man, who was admitted with pericardial effusion and symptoms of acute heart failure. CMR followed by targeted left ventricular endomyocardial biopsy (EMB) revealed the diagnosis of isolated SHD. The combined use of CMR and EMB was crucial in diagnosing SHD. Furthermore, this case report demonstrates the value of CMR for monitoring response to therapy and lesion healing. PMID:26989672

  9. A comprehensive gene expression analysis at sequential stages of in vitro cardiac differentiation from isolated MESP1-expressing-mesoderm progenitors.

    PubMed

    den Hartogh, Sabine C; Wolstencroft, Katherine; Mummery, Christine L; Passier, Robert

    2016-01-01

    In vitro cardiac differentiation of human pluripotent stem cells (hPSCs) closely recapitulates in vivo embryonic heart development, and therefore, provides an excellent model to study human cardiac development. We recently generated the dual cardiac fluorescent reporter MESP1(mCherry/w)NKX2-5(eGFP/w) line in human embryonic stem cells (hESCs), allowing the visualization of pre-cardiac MESP1+ mesoderm and their further commitment towards the cardiac lineage, marked by activation of the cardiac transcription factor NKX2-5. Here, we performed a comprehensive whole genome based transcriptome analysis of MESP1-mCherry derived cardiac-committed cells. In addition to previously described cardiac-inducing signalling pathways, we identified novel transcriptional and signalling networks indicated by transient activation and interactive network analysis. Furthermore, we found a highly dynamic regulation of extracellular matrix components, suggesting the importance to create a versatile niche, adjusting to various stages of cardiac differentiation. Finally, we identified cell surface markers for cardiac progenitors, such as the Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), belonging to the same subfamily of LGR5, and LGR6, established tissue/cancer stem cells markers. We provide a comprehensive gene expression analysis of cardiac derivatives from pre-cardiac MESP1-progenitors that will contribute to a better understanding of the key regulators, pathways and markers involved in human cardiac differentiation and development. PMID:26783251

  10. A comprehensive gene expression analysis at sequential stages of in vitro cardiac differentiation from isolated MESP1-expressing-mesoderm progenitors

    PubMed Central

    den Hartogh, Sabine C.; Wolstencroft, Katherine; Mummery, Christine L.; Passier, Robert

    2016-01-01

    In vitro cardiac differentiation of human pluripotent stem cells (hPSCs) closely recapitulates in vivo embryonic heart development, and therefore, provides an excellent model to study human cardiac development. We recently generated the dual cardiac fluorescent reporter MESP1mCherry/wNKX2-5eGFP/w line in human embryonic stem cells (hESCs), allowing the visualization of pre-cardiac MESP1+ mesoderm and their further commitment towards the cardiac lineage, marked by activation of the cardiac transcription factor NKX2-5. Here, we performed a comprehensive whole genome based transcriptome analysis of MESP1-mCherry derived cardiac-committed cells. In addition to previously described cardiac-inducing signalling pathways, we identified novel transcriptional and signalling networks indicated by transient activation and interactive network analysis. Furthermore, we found a highly dynamic regulation of extracellular matrix components, suggesting the importance to create a versatile niche, adjusting to various stages of cardiac differentiation. Finally, we identified cell surface markers for cardiac progenitors, such as the Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), belonging to the same subfamily of LGR5, and LGR6, established tissue/cancer stem cells markers. We provide a comprehensive gene expression analysis of cardiac derivatives from pre-cardiac MESP1-progenitors that will contribute to a better understanding of the key regulators, pathways and markers involved in human cardiac differentiation and development. PMID:26783251