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Sample records for heart injuries

  1. Iodide Protects Heart Tissue from Reperfusion Injury

    PubMed Central

    Iwata, Akiko; Morrison, Michael L.; Roth, Mark B.

    2014-01-01

    Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury. PMID:25379708

  2. [On the question of heart injuries].

    PubMed

    Korolev, M P; Urakcheev, Sh K; Pastukhova, N K; Sagatinov, R S; Starkov, G E

    2011-01-01

    The work is devoted to an analysis of hospitalized patients to the specialized department of injuries of the chest and abdomen of the Mariinskaja hospital at the period from 1993 through 2010. The diagnosis of injury of the pericardium and heart had 280 patients, during the operative treatment heart injuries were detected in 156 (55.71%) patients. Penetration to the heart chambers was found in 132 (84.61%) of them, with perforating and multiple injuries there were 24 (15.39%) patients. Operations were performed during 20 minutes after admission on 65 (28.9%), and during the following two hours on 160 (71.1%) patients. Expectant management and conservative treatment were used in treatment of 34 patients (12.14%), three patients were admitted in the state of apparent death and died during 15 minutes. The lethality of 41 patients was 26.28%. mainly it was those who were operated at the period from 80 to 100 minutes from the moment of injury. The success of treatment depends on the early hospitalization, correct diagnosis and emergent surgery.

  3. Radiation injury to the heart

    SciTech Connect

    Stewart, J.R.; Fajardo, L.F. Gillette, S. M.

    1995-03-30

    For the RTOG Consensus Conference on Late Effects of Cancer Treatment we summarize the clinical manifestations of cardiac complications appearing months to years following incidental irradiation of the heart during treatment of thoracic neoplasms. The most common effects present as pericardial disease, however, it is becoming more clear that precocious or accelerated coronary artery disease is an important late effect, especially in patients treated with radiation before the age of 21 years. To the extent it is known, the pathophysiology of the various syndromes is described and the extensive literature on dose, volume, and fractionation factors is reviewed. Based upon our current understanding of late cardiac effects, a clinical grading system has been developed and is published elsewhere in this issue. 49 refs., 1 tab.

  4. Penetrating Heart Injury due to Screwdriver Assault

    PubMed Central

    Dieng, P. A.; Diop, M. S.; Ciss, A. G.; Ba, P. S.; Diatta, S.; Gaye, M.; Fall, M. L.; Ndiaye, A.; Ndiaye, M.

    2015-01-01

    Penetrating heart injuries cause wounds in the cardiac chambers. Most of them are due to gunshot or stabbing by knives. Screwdriver is an uncommon weapon. Authors report a case of stab wound by screwdriver, treated at cardiovascular center in Dakar. This is a 16-year-old boy who experienced physical aggression. He was assaulted with a screwdriver and had stab wound on the anterior wall of the chest. Physical examination showed a screwdriver penetrating the sternum bone over a right angle. He had a mild pericardial blood effusion and a right ventricle wound 5 mm in diameter with transection of the right coronary vein. The screwdriver was removed without cardiopulmonary bypass (CPB) and the ventricle wound repaired by direct suture of stitches reinforced with Teflon pledgets. The right coronary artery was ligated. Postoperative period was free of events. Screwdriver is uncommonly used as a weapon. It is a dangerous device because of its rigid structure and narrow tip. PMID:25945263

  5. Targeting MMP-2 to treat ischemic heart injury.

    PubMed

    Hughes, Bryan G; Schulz, Richard

    2014-07-01

    Matrix metalloproteinase (MMPs) are long understood to be involved in remodeling of the extracellular matrix. However, over the past decade, it has become clear that one of the most ubiquitous MMPs, MMP-2, has numerous intracellular targets in cardiac myocytes. Notably, MMP-2 proteolyzes components of the sarcomere, and its intracellular activity contributes to ischemia-reperfusion injury of the heart. Together with the well documented role played by MMPs in the myocardial remodeling that occurs following myocardial infarction, this has led to great interest in targeting MMPs to treat cardiac ischemic injury. In this review we will describe the expanding understanding of intracellular MMP-2 biology, and how this knowledge may lead to improved treatments for ischemic heart injury. We also critically review the numerous preclinical studies investigating the effects of MMP inhibition in animal models of myocardial infarction and ischemia-reperfusion injury, as well as the recent clinical trials that are part of the effort to translate these results into clinical practice. Acknowledging the disappointing results of past clinical trials of MMP inhibitors for other diseases, we discuss the need for carefully designed preclinical and clinical studies to avoid mistakes that have been previously made. We conclude that inhibition of MMPs, and in particular MMP-2, shows promise as a therapy to prevent the progression from ischemic injury to heart failure. However, it is critical that the full breadth of MMP-2 biology be taken into account as such therapies are developed.

  6. Annular injuries following the insertion of heart valve prostheses 1

    PubMed Central

    Bowes, Vernon F.; Datta, Bhoopendra N.; Silver, Malcolm D.; Minielly, John A.

    1974-01-01

    Bowes, V. F., Datta, B. N., Silver, M. D. and Minielly, J. A. (1974).Thorax, 29, 530-533. Annular injuries following the insertion of heart valve prostheses. The clinical presentation and morphological findings in eight cases of annular injury associated with the insertion of prosthetic heart valves are discussed. The lesions presented as a separation of the left atrium and ventricle at the mitral annulus (one patient), a sinus or false aneurysm in the left posterior atrioventricular groove (two patients), or as a separation of the aortic root from the base of the heart (five patients). The pathogenesis of the lesions is similar. Annular tissue was weakened either by the removal of excess tissue or by an abnormal stress placed on normal tissue or by a slight stress placed on tissue altered by disease, and, as a result, it separated or tore. The resultant haemorrhage either caused the patient's death or, with time, produced the other morphological findings. Factors predisposing patients to the injuries are discussed and a differential diagnosis of annular pseudoaneurysms is provided. Images PMID:4279466

  7. Retrospective study of heart injuries occurred in Manaus - Amazon.

    PubMed

    Costa, Cleinaldo de Almeida; Birolini, Dario; de Araújo, Antônio Oliveira; Chaves, Altair Rodrigues; Cabral, Pedro Henrique Oliveira; Lages, Roberto Oliver; Padilha, Thiago Litaiff

    2012-01-01

    To evaluate the forms of treatment employed to heart injuries and the main aspects related to their morbidity and mortality. A retrospective study of 102 patients with cardiac injuries treated in the two emergency rooms in Manaus (Dr. John Lucio Pereira Machado Emergency Hospital and August 28 County Emergency Hospital) from January 1998 to June 2006. Of the 102 patients, 95.1% were men; mean age was 27 years; stab wounds accounted for 81.4% of cases and gunshot wounds for 18.6%; cardiorrhaphy was performed in 98.1% of cases. The heart chambers affected were: Right Ventricle (RV): 43.9% (36.2% isolated and 7.7% associated with other chambers); Left Ventricle (LV): 37.2%; Right Atrium (RA): 8.5%; and Left Atrium (LA): 10.4%; specific mortalities were of 21%, 23%, 22% and 45%, respectively. The mortality injuries to two associated chambers was 37.5%, 20% being for RA + RV, 100% for RV + LV, and zero for RV + LA. The lung accounted for 33.7% of the 89 associated lesions. Mean time of surgery and hospital stay were 121 minutes and 8.2 days, respectively. About 22.5% of patients displayed 41 complications. The mortality rate was 28.4%. Lesions grade IV and V corresponded to 55% and 41% of cases, with specific mortality of 26% and 15%, respectively. All patients with grade injuries VI died. Cardiac stab wounds were associated with lower mortality, cardiac lesions grade IV were associated with higher mortality and a shorter operative time was associated with greater severity and mortality.

  8. Cardiopulmonary Circuit Models for Predicting Injury to the Heart

    NASA Astrophysics Data System (ADS)

    Ward, Richard; Wing, Sarah; Bassingthwaighte, James; Neal, Maxwell

    2004-11-01

    Circuit models have been used extensively in physiology to describe cardiopulmonary function. Such models are being used in the DARPA Virtual Soldier (VS) Project* to predict the response to injury or physiological stress. The most complex model consists of systemic circulation, pulmonary circulation, and a four-chamber heart sub-model. This model also includes baroreceptor feedback, airway mechanics, gas exchange, and pleural pressure influence on the circulation. As part of the VS Project, Oak Ridge National Laboratory has been evaluating various cardiopulmonary circuit models for predicting the effects of injury to the heart. We describe, from a physicist's perspective, the concept of building circuit models, discuss both unstressed and stressed models, and show how the stressed models are used to predict effects of specific wounds. *This work was supported by a grant from the DARPA, executed by the U.S. Army Medical Research and Materiel Command/TATRC Cooperative Agreement, Contract # W81XWH-04-2-0012. The submitted manuscript has been authored by the U.S. Department of Energy, Office of Science of the Oak Ridge National Laboratory, managed for the U.S. DOE by UT-Battelle, LLC, under contract No. DE-AC05-00OR22725. Accordingly, the U.S. Government retains a non-exclusive, royalty-free license to publish or reproduce the published form of this contribution, or allow others to do so, for U.S. Government purpose.

  9. Burn-induced subepicardial injury in frog heart: a simple model mimicking ST segment changes in ischemic heart disease.

    PubMed

    Kazama, Itsuro

    2016-02-01

    To mimic ischemic heart disease in humans, several animal models have been created, mainly in rodents by surgically ligating their coronary arteries. In the present study, by simply inducing burn injuries on the bullfrog heart, we reproduced abnormal ST segment changes in the electrocardiogram (ECG), mimicking those observed in ischemic heart disease, such as acute myocardial infarction and angina pectoris. The "currents of injury" created by a voltage gradient between the intact and damaged areas of the myocardium, negatively deflected the ECG vector during the diastolic phase, making the ST segment appear elevated during the systolic phase. This frog model of heart injury would be suitable to explain the mechanisms of ST segment changes observed in ischemic heart disease.

  10. [The forensic medical diagnosis of closed injuries to the heart in blunt chest trauma].

    PubMed

    Kapustin, A V

    1997-01-01

    Describes the morphological changes of cardiomyocytes in contusions and concussions of the heart and reflective heart arrest resulting in rapid sudden death after blunt injury to the chest. Presents the principles and criteria of forensic medical diagnosis of death from heart concussions in such cases.

  11. [Results of the treatment of open heart injuries at a central regional hospital].

    PubMed

    Segida, V F; Efremov, N I; Chernov, A I

    1994-09-01

    In a period of 10 years seven patients with open injury to the heart were treated. Their ages ranged from 17 to 39 years. One patient had a gunshot injury, in six the injury was inflicted with a knife. In three patients the injuries were combined (concurrent injury to the lung in 2 and to the diaphragm in one) and in four isolated. Perforating injury of both ventricles and damage of the interventricular septum were found in one case. All patients underwent emergency closure of the heart wounds with an atraumatic synthetic thread and drainage of the pleural cavity. Complications developed in the postoperative period in six patients: suppuration of the operative wound in one and pericarditis in five. One patient died. Analysis of the obtained data testifies to the expediency of two-stage treatment with rehabilitation in cardiological departments. This shortens the period of rehabilitation of patients with open injuries to the heart treated in a central regional hospital.

  12. C/EBP Transcription Factors Mediate Epicardial Activation During Heart Development and Injury

    PubMed Central

    Huang, Guo N.; Thatcher, Jeffrey E.; McAnally, John; Kong, Yongli; Qi, Xiaoxia; Tan, Wei; DiMaio, J. Michael; Amatruda, James F.; Gerard, Robert D.; Hill, Joseph A.; Bassel-Duby, Rhonda; Olson, Eric N.

    2013-01-01

    The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration. PMID:23160954

  13. Effects of gender on heart injury after intracerebral hemorrhage in rats.

    PubMed

    Ye, Zi; Xie, Qing; Xi, Guohua; Keep, Richard F; Hua, Ya

    2011-01-01

    Intracerebral hemorrhage (ICH)-induced brain injury is less in female than in male rats, and estrogen can reduce such injury in males. Myocardial injury occurs after ischemic and hemorrhagic stroke, and the current study investigated the effects of gender on heart injury after ICH in rats. In the first part of the study, male and female rats had an intracerebral injection of 100 μL autologous blood, and sham-operated rats had a needle insertion. In the second part of the study, male rats were treated with 17β-estrodiol or vehicle 2 h after ICH. All rats were then killed after 3 days and heart samples collected for histology and Western blot analysis. ICH caused heart injury, including petechial hemorrhage in male and female rats. To quantify heart stress following ICH, heat shock proteins (HSP) 32 and 27 were measured by Western blot analysis. We found that heart HSP-32 levels were higher in female compared to male rats after ICH (p<0.01), but there was no effect of gender in sham-operated rats (p>0.05), nor were there gender differences in myocardial HSP27 levels. Treatment with 17β-estrodiol increased HSP-32 levels in male ICH rats (p<0.05). In conclusion, an ICH results in heart injury by an unknown mechanism. Gender and estrogen affect the heart response to ICH.

  14. GATA4 regulates Fgf16 to promote heart repair after injury.

    PubMed

    Yu, Wei; Huang, Xiuzhen; Tian, Xueying; Zhang, Hui; He, Lingjuan; Wang, Yue; Nie, Yu; Hu, Shengshou; Lin, Zhiqiang; Zhou, Bin; Pu, William; Lui, Kathy O; Zhou, Bin

    2016-03-15

    Although the mammalian heart can regenerate during the neonatal stage, this endogenous regenerative capacity is lost with age. Importantly, replication of cardiomyocytes has been found to be the key mechanism responsible for neonatal cardiac regeneration. Unraveling the transcriptional regulatory network for inducing cardiomyocyte replication will, therefore, be crucial for the development of novel therapies to drive cardiac repair after injury. Here, we investigated whether the key cardiac transcription factor GATA4 is required for neonatal mouse heart regeneration. Using the neonatal mouse heart cryoinjury and apical resection models with an inducible loss of GATA4 specifically in cardiomyocytes, we found severely depressed ventricular function in the Gata4-ablated mice (mutant) after injury. This was accompanied by reduced cardiomyocyte replication. In addition, the mutant hearts displayed impaired coronary angiogenesis and increased hypertrophy and fibrosis after injury. Mechanistically, we found that the paracrine factor FGF16 was significantly reduced in the mutant hearts after injury compared with littermate controls and was directly regulated by GATA4. Cardiac-specific overexpression of FGF16 via adeno-associated virus subtype 9 (AAV9) in the mutant hearts partially rescued the cryoinjury-induced cardiac hypertrophy, promoted cardiomyocyte replication and improved heart function after injury. Altogether, our data demonstrate that GATA4 is required for neonatal heart regeneration through regulation of Fgf16, suggesting that paracrine factors could be of potential use in promoting myocardial repair. © 2016. Published by The Company of Biologists Ltd.

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

    PubMed

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

    2016-02-15

    Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg(-1)·day(-1)) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated end-diastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. Copyright © 2016 the American Physiological Society.

  16. Reviparin-sodium prevents complement-mediated myocardial injury in the isolated rabbit heart.

    PubMed

    Park, J L; Tanhehco, E J; Kilgore, K S; Gralinski, M R; Lucchesi, B R

    1997-11-01

    The cytoprotective action of reviparin-sodium (LU-47311: Clivarin), a low-molecular-weight heparin, was examined in an ex vivo model of complement-mediated myocardial injury. The effective concentration of reviparin was determined by using an in vitro rabbit erythrocyte-lysis assay using 4% normal human plasma. Reviparin (0.01-2.73 mg/ml) reduced erythrocyte lysis in a concentration-dependent manner. Subsequently, 0.91 mg/ml of reviparin was evaluated in an ex vivo rabbit isolated-heart model of human complement-mediated injury. Hearts perfused in the presence of 0.91 mg/ml of reviparin (n = 10) demonstrated significant preservation of ventricular function compared with vehicle-treated hearts (n = 10), as evidenced by coronary artery perfusion pressure, left ventricular developed pressure, and left ventricular end-diastolic pressure. A reduction in myocyte creatine kinase release was observed in reviparin-treated hearts compared with controls. Myocardial injury in vehicle-treated hearts was associated with an increased assembly of the membrane-attack complex, as determined by immunohistochemical localization of C5b-9 neoantigen. Reviparin decreased fluid-phase Bb formation detected in the lymphatic drainage of plasma-perfused hearts. The results of this study demonstrate that reviparin inhibits complement-mediated myocardial injury as assessed in an ex vivo experimental model of complement activation.

  17. Fibronectin is deposited by injury-activated epicardial cells and is necessary for zebrafish heart regeneration

    PubMed Central

    Wang, Jinhu; Karra, Ravi; Dickson, Amy L.; Poss, Kenneth D.

    2013-01-01

    Unlike adult mammals, adult zebrafish vigorously regenerate lost heart muscle in response to injury. The epicardium, a mesothelial cell layer enveloping the myocardium, is activated to proliferate after cardiac injury and can contribute vascular support cells or provide mitogens to regenerating muscle. Here, we applied proteomics to identify secreted proteins that are associated with heart regeneration. We found that Fibronectin, a main component of the extracellular matrix, is induced and deposited after cardiac damage. In situ hybridization and transgenic reporter analyses indicated that expression of two fibronectin paralogues, fn1 and fn1b, are induced by injury in epicardial cells, while the itgb3 receptor is induced in cardiomyocytes near the injury site. fn1, the more dynamic of these paralogs, is induced chamber-wide within one day of injury before localizing epicardial Fn1 synthesis to the injury site. fn1 loss-of-function mutations disrupted zebrafish heart regeneration, as did induced expression of a dominant-negative Fibronectin cassette, defects that were not attributable to direct inhibition of cardiomyocyte proliferation. These findings reveal a new role for the epicardium in establishing an extracellular environment that supports heart regeneration. PMID:23988577

  18. High-mobility group box-1 in ischemia-reperfusion injury of the heart.

    PubMed

    Andrassy, Martin; Volz, Hans C; Igwe, John C; Funke, Benjamin; Eichberger, Sebastian N; Kaya, Ziya; Buss, Sebastian; Autschbach, Frank; Pleger, Sven T; Lukic, Ivan K; Bea, Florian; Hardt, Stefan E; Humpert, Per M; Bianchi, Marco E; Mairbäurl, Heimo; Nawroth, Peter P; Remppis, Andrew; Katus, Hugo A; Bierhaus, Angelika

    2008-06-24

    High-mobility group box-1 (HMGB1) is a nuclear factor released by necrotic cells and by activated immune cells. HMGB1 signals via members of the toll-like receptor family and the receptor for advanced glycation end products (RAGE). Although HMGB1 has been implicated in ischemia/reperfusion (I/R) injury of the liver and lung, its role in I/R injury of the heart remains unclear. Here, we demonstrate that HMGB1 acts as an early mediator of inflammation and organ damage in I/R injury of the heart. HMGB1 levels were already elevated 30 minutes after hypoxia in vitro and in ischemic injury of the heart in vivo. Treatment of mice with recombinant HMGB1 worsened I/R injury, whereas treatment with HMGB1 box A significantly reduced infarct size and markers of tissue damage. In addition, HMGB1 inhibition with recombinant HMGB1 box A suggested an involvement of the mitogen-activated protein kinases jun N-terminal kinase and extracellular signal-regulated kinase 1/2, as well as the nuclear transcription factor nuclear factor-kappaB in I/R injury. Interestingly, infarct size and markers of tissue damage were not affected by administration of recombinant HMGB1 or HMGB1 antagonists in RAGE(-/-) mice, which demonstrated significantly reduced damage in reperfused hearts compared with wild-type mice. Coincubation studies using recombinant HMGB1 in vitro induced an inflammatory response in isolated macrophages from wild-type mice but not in macrophages from RAGE(-/-) mice. HMGB1 plays a major role in the early event of I/R injury by binding to RAGE, resulting in the activation of proinflammatory pathways and enhanced myocardial injury. Therefore, blockage of HMGB1 might represent a novel therapeutic strategy in I/R injury.

  19. Oxygen surrounding the heart during ischemic conservation determines the myocardial injury during reperfusion.

    PubMed

    Feng, Yansheng; Bopassa, Jean Chrisostome

    2015-01-01

    There is discrepancy regarding the duration of reperfusion required using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining to assess myocardial infarction in an isolated, perfused heart model. Several investigators prefer long-term reperfusion (120 minutes) to determine myocardial injury, while others have used a shorter duration (30-40 minutes). We investigated whether oxygen surrounding the myocardium during ischemia plays a critical role in the installation of myocardial infarction during reperfusion. Mice hearts were perfused with a Langendorff apparatus using Krebs Henseleit (KH) buffer oxygenated with 95% O2 plus 5% CO2 at 37°C. Hearts were either immersed in KH or suspended in air during 18 minutes of global ischemia in a normothermic, water-jacketed chamber. Hearts then were reperfused for 40, 60, or 90 minutes. We found that hearts immersed in KH had decreased recovery of function and increased myocardial infarct size, reaching a steady-state level after 40 minutes of reperfusion. In contrast, hearts suspended in air approached steady-state after 90 minutes of reperfusion. Thus, mitochondrial reactive oxygen species (ROS) production was much lower in air-maintained hearts than in KH-immersed hearts. To investigate whether an increase in oxygen surrounding the myocardium during ischemia might cause further damage, we bubbled the KH solution with nitrogen (KH+N2) rather than oxygen (KH+O2). With this alteration, recovery of cardiac function was improved and myocardial infarct size and mitochondrial ROS production were reduced compared with hearts immersed in KH+O2. In conclusion, short-term (40 minutes) reperfusion is sufficient to reach steady-state myocardial infarct size when hearts are immersed in physiologic solution during ischemia; however, a longer duration of reperfusion (90 minutes) is required if hearts are suspended in air. Thus, oxygen surrounding the heart during ischemia determines the extent of myocardium injury during reperfusion.

  20. Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

    PubMed Central

    Li, Qing; Hwang, Yuying C; Ananthakrishnan, Radha; Oates, Peter J; Guberski, Dennis; Ramasamy, Ravichandran

    2008-01-01

    We investigated the role of polyol pathway enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH) in mediating injury due to ischemia-reperfusion (IR) in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a) changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b) ischemic injury and function after IR, (c) the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P) ratio (a measure of cytosolic NADH/NAD+), and lactate dehydrogenase (LDH) release (a marker of IR injury) were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients. PMID:18957123

  1. Pericardiocentesis followed by thoracotomy and repair of penetrating cardiac injury caused by nail gun injury to the heart

    PubMed Central

    Chirumamilla, Vasu; Prabhakaran, Kartik; Patrizio, Petrone; Savino, John A.; Marini, Corrado P.; Zoha, Zobair

    2016-01-01

    Introduction Work site injuries involving high projectile tools such as nail guns can lead to catastrophic injuries. Generally, penetrating cardiac injuries are associated with a high mortality rate. Presentation of case A construction worker was brought to the emergency room having sustained a nail gun injury to the chest. The patient was hypotensive, tachycardic with prominent jugular venous distention, and had a profound lactic acidosis. Bedside ultrasound confirmed the presence of pericardial fluid. Pericardiocentesis was performed twice using a central venous catheter inserted into the pericardial space, resulting in improvement in the patient’s hemodynamics. Thereafter he underwent left anterolateral thoracotomy and repair of a right atrial laceration. He recovered uneventfully. Discussion Penetrating cardiac injuries caused by nail guns, although rare, have been previously described. However, pericardiocentesis, while retaining a role in the management of medical causes of cardiac tamponade, has been reported only sporadically in the setting of trauma. We report a rare case of penetrating nail gun injury to the heart where pericardiocentesis was used as a temporizing measure to stabilize the patient in preparation for definitive but timely operative intervention. Conclusion We propose awareness that percardiocentesis can serve as a temporary life saving measure in the setting of trauma, particularly as a bridge to definitive therapy. To our knowledge, this represents the first reported case of catheter pericardiocentesis used to stabilize a patient until definitive repair of a penetrating cardiac injury caused by a nail gun. PMID:27107304

  2. Analysis of Heart Rate and Self-Injury with and without Restraint in an Individual with Autism

    ERIC Educational Resources Information Center

    Jennett, Heather; Hagopian, Louis P.; Beaulieu, Lauren

    2011-01-01

    The relation between self-injury and heart rate was analyzed for an individual who appeared anxious while engaging in self-injury. The analysis involved manipulating the presence or absence of restraint while simultaneously measuring heart rate. The following findings were obtained and replicated: (a) when some form of restraint was applied, heart…

  3. Analysis of Heart Rate and Self-Injury with and without Restraint in an Individual with Autism

    ERIC Educational Resources Information Center

    Jennett, Heather; Hagopian, Louis P.; Beaulieu, Lauren

    2011-01-01

    The relation between self-injury and heart rate was analyzed for an individual who appeared anxious while engaging in self-injury. The analysis involved manipulating the presence or absence of restraint while simultaneously measuring heart rate. The following findings were obtained and replicated: (a) when some form of restraint was applied, heart…

  4. Moderate exercise training attenuates aging-induced cardiac inflammation, hypertrophy and fibrosis injuries of rat hearts

    PubMed Central

    Liao, Po-Hsiang; Hsieh, Dennis Jine-Yuan; Kuo, Chia-Hua; Day, Cecilia-Hsuan; Shen, Chia-Yao; Lai, Chao-Hung; Chen, Ray-Jade; Padma, V. Vijaya

    2015-01-01

    Aging is the most important risk factor in cardiovascular disease (CVD), which is the leading causes of death worldwide and the second major cause of death in Taiwan. The major factor in heart failure during aging is heart remodeling, including long-term stress-induced cardiac hypertrophy and fibrosis. Exercise is good for aging heart health, but the impact of exercise training on aging is not defined. This study used 3-, 12- and 18-month-old rats and randomly divided each age group into no exercise training control groups (C3, A12 and A18) and moderate gentle swimming exercise training groups (E3, AE12 and AE18). The protocol of exercise training was swimming five times weekly with gradual increases from the first week from 20 to 60 min for 12 weeks. Analyses of protein from rat heart tissues and sections revealed cardiac inflammation, hypertrophy and fibrosis pathway increases in aged rat groups (A12 and A18), which were improved in exercise training groups (AE12 and AE18). There were no heart injuries in young rat hearts in exercise group E3. These data suggest that moderate swimming exercise training attenuated aging-induced cardiac inflammation, hypertrophy and fibrosis injuries of rat hearts. PMID:26496028

  5. Moderate exercise training attenuates aging-induced cardiac inflammation, hypertrophy and fibrosis injuries of rat hearts.

    PubMed

    Liao, Po-Hsiang; Hsieh, Dennis Jine-Yuan; Kuo, Chia-Hua; Day, Cecilia-Hsuan; Shen, Chia-Yao; Lai, Chao-Hung; Chen, Ray-Jade; Padma, V Vijaya; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-11-03

    Aging is the most important risk factor in cardiovascular disease (CVD), which is the leading causes of death worldwide and the second major cause of death in Taiwan. The major factor in heart failure during aging is heart remodeling, including long-term stress-induced cardiac hypertrophy and fibrosis. Exercise is good for aging heart health, but the impact of exercise training on aging is not defined. This study used 3-, 12- and 18-month-old rats and randomly divided each age group into no exercise training control groups (C3, A12 and A18) and moderate gentle swimming exercise training groups (E3, AE12 and AE18). The protocol of exercise training was swimming five times weekly with gradual increases from the first week from 20 to 60 min for 12 weeks. Analyses of protein from rat heart tissues and sections revealed cardiac inflammation, hypertrophy and fibrosis pathway increases in aged rat groups (A12 and A18), which were improved in exercise training groups (AE12 and AE18). There were no heart injuries in young rat hearts in exercise group E3. These data suggest that moderate swimming exercise training attenuated aging-induced cardiac inflammation, hypertrophy and fibrosis injuries of rat hearts.

  6. Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

    PubMed Central

    Brown, J M; Grosso, M A; Terada, L S; Whitman, G J; Banerjee, A; White, C W; Harken, A H; Repine, J E

    1989-01-01

    Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection. PMID:2648406

  7. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

    PubMed

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J J; Sawicki, Grzegorz

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  8. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart

    PubMed Central

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J. J.

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury. PMID:25961016

  9. Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury.

    PubMed

    Meng, Weixin; Xu, Ying; Li, Dandan; Zhu, Erjun; Deng, Li; Liu, Zonghong; Zhang, Guowei; Liu, Hongyu

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation.

  10. Clinically silent preoperative brain injuries do not worsen with surgery in neonates with congenital heart disease.

    PubMed

    Block, A J; McQuillen, P S; Chau, V; Glass, H; Poskitt, K J; Barkovich, A J; Esch, M; Soulikias, W; Azakie, A; Campbell, A; Miller, S P

    2010-09-01

    Preoperative brain injury, particularly stroke and white matter injury, is common in neonates with congenital heart disease. The objective of this study was to determine the risk of hemorrhage or extension of preoperative brain injury with cardiac surgery. This dual-center prospective cohort study recruited 92 term neonates, 62 with transposition of the great arteries and 30 with single ventricle physiology, from 2 tertiary referral centers. Neonates underwent brain magnetic resonance imaging scans before and after cardiac surgery. Brain injury was identified in 40 (43%) neonates on the preoperative magnetic resonance imaging scan (median 5 days after birth): stroke in 23, white matter injury in 21, and intraventricular hemorrhage in 7. None of the brain lesions presented clinically with overt signs or seizures. Preoperative brain injury was associated with balloon atrial septostomy (P = .003) and lowest arterial oxygen saturation (P = .007); in a multivariable model, only the effect of balloon atrial septostomy remained significant when adjusting for lowest arterial oxygen saturation. On postoperative magnetic resonance imaging in 78 neonates (median 21 days after birth), none of the preoperative lesions showed evidence of extension or hemorrhagic transformation (0/40 [95% confidence interval: 0%-7%]). The presence of preoperative brain injury was not a significant risk factor for acquiring new injury on postoperative magnetic resonance imaging (P = .8). Clinically silent brain injuries identified preoperatively in neonates with congenital heart disease, including stroke, have a low risk of progression with surgery and cardiopulmonary bypass and should therefore not delay clinically indicated cardiac surgery. In this multicenter cohort, balloon atrial septostomy remains an important risk factor for preoperative brain injury, particularly stroke. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  11. T-wave inversion after a severe head injury without ischemic heart disease.

    PubMed

    La Rocca, Roberto; Materia, Valeria; Pasquini, Annalisa; La Rosa, Felice Carmelo; Marte, Filippo; Patanè, Salvatore

    2011-09-01

    Electrocardiographic changes mimicking an acute coronary event with T-wave inversion have been reported in the resting electrocardiogram in patients without ischemic heart disease but with acute ischemic stroke, or subarachnoid hemorrhage, or intracerebral hemorrhage, or a severe head injury. We present a case of T-wave inversion in a 73-year-old Italian woman admitted to the Emergency Department following a severe head injury. Pericarditis, pericardial effusion, and acute coronary event were excluded. Ischemic stroke, subarachnoid hemorrhage, and intracerebral hemorrhage were also excluded. Also this case focuses attention on T-wave inversion after a severe head injury without ischemic heart disease. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Interplanetary travel and permanent injury to normal heart

    NASA Astrophysics Data System (ADS)

    Rowe, William J.

    1997-05-01

    This hypothesis is that some crewmen on prolonged space flights may develop permanent myocardial injury despite the absence of coronary atherosclerosis and even without the hazards of radiation beyond orbit. This may result from atrophy of skeletal muscle and bone resulting in magnesium ion deficiency predisposing to a vicious cycle with catecholamine elevations, with the latter aggravated by stress, dehydration-provoked angiotensin elevations, unremitting endurance exercise, and in turn a second vicious cycle with severe ischemia. Toxic free radicals can develop complicating ischemia and potential high radiation, with magnesium ion deficiency and high vascular catecholamines playing contributing roles. These free radicals may lead to inactivation of endothelium-derived relaxing factor (EDRF) causing coronary endothelial injury by a third vicious cycle, increased peripheral resistance and coronary vasospasm intensifying ischemia. Local and systemic thrombogenesis could contribute ultimately to focal fibrosis of the myocardium, if the ischemia is not recognized. Sufficient magnesium and time for repair are vital.

  13. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

    PubMed Central

    Seeley, Sarah L.; Stoops, Thorne S.; D’Souza, Manoranjan S.

    2017-01-01

    Background We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Methods Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Results Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Conclusions Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. PMID:28575091

  14. Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart.

    PubMed

    Rorabaugh, Boyd R; Seeley, Sarah L; Stoops, Thorne S; D'Souza, Manoranjan S

    2017-01-01

    We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.

  15. Tolerance to ischaemic injury in remodelled mouse hearts: less ischaemic glycogenolysis and preserved metabolic efficiency

    PubMed Central

    Masoud, Waleed G.T.; Abo Al-Rob, Osama; Yang, Yang; Lopaschuk, Gary D.; Clanachan, Alexander S.

    2015-01-01

    Aims Post-infarction remodelled failing hearts have reduced metabolic efficiency. Paradoxically, they have increased tolerance to further ischaemic injury. This study was designed to investigate the metabolic mechanisms that may contribute to this phenomenon and to examine the relationship between ischaemic tolerance and metabolic efficiency during post-ischaemic reperfusion. Methods and results Male C57BL/6 mice were subjected to coronary artery ligation (CAL) or SHAM surgery. After 4 weeks, in vivo mechanical function was assessed by echocardiography, and then isolated working hearts were perfused in this sequence: 45 min aerobic, 15 min global no-flow ischaemia, and 30 min aerobic reperfusion. Left ventricular (LV) function, metabolic rates, and metabolic efficiency were measured. Relative to SHAM, both in vivo and in vitro CAL hearts had depressed cardiac function under aerobic conditions (45 and 36%, respectively), but they had a greater recovery of LV function during post-ischaemic reperfusion (67 vs. 49%, P < 0.05). While metabolic efficiency (LV work per ATP produced) was 50% lower during reperfusion of SHAM hearts, metabolic efficiency in CAL hearts did not decrease. During ischaemia, glycogenolysis was 28% lower in CAL hearts, indicative of lower ischaemic proton production. There were no differences in mitochondrial abundance, calcium handling proteins, or key metabolic enzymes. Conclusion Compared with SHAM, remodelled CAL hearts are more tolerant to ischaemic injury and undergo no further deterioration of metabolic efficiency during reperfusion. Less glycogen utilization in CAL hearts during ischaemia may contribute to increased ischaemic tolerance by limiting ischaemic proton production that may improve ion homeostasis during early reperfusion. PMID:26150203

  16. Saffron (Crocus sativus) pretreatment confers cardioprotection against ischemia-reperfusion injuries in isolated rabbit heart.

    PubMed

    Nader, Moni; Chahine, Nathalie; Salem, Charelle; Chahine, Ramez

    2016-12-01

    Restoration of blood flow to the ischemic myocardium is imperative to avoid demise of cardiomyocytes, but is paradoxically associated with irreversible damage to cardiac tissues due to the excessive generation of reactive oxygen species (ROS). We have previously reported that saffron, a natural antioxidant, attenuated ischemia-reperfusion (IR) injuries in vitro; however, its role in a meaningful cardiac recovery remains unknown. Here, we show that saffron supplement (oral administration for 6 weeks) reduced myocardial damage and restored cardiac function in an IR model of rabbit hearts. This was evidenced by improved left ventricle pressure, heart rate and coronary flow, and left ventricle end diastolic pressure (LVEDP) in IR hearts (isolated from rabbits pre-exposed to saffron (S/IR)). Electrophysiological recordings revealed a significant decline in both premature ventricle contraction and ventricle tachycardia/fibrillation in S/IR compared to IR hearts. This was paralleled by increased expression of the contractile proteins α-actinin and Troponin C in the myocardium of S/IR hearts. Histological examination combined to biochemical analysis indicated that hearts pre-exposed to saffron exhibited reduced infarct size, lower lipid peroxidation, with increased glutathione peroxidase activity, and oxidation of nitro blue tetrazolium (by reactive oxygen species). Furthermore, in contrast with IR hearts, saffron pretreatment induced restoration of the phosphorylation level of the survival proteins Akt and 4EBP1 and reduced activity of p38. Collectively, our data demonstrate that the natural antioxidant saffron plays a pivotal role in halting IR-associated cardiac injuries and emerges as a novel preventive tool for ischemic heart disease.

  17. Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats

    PubMed Central

    Chen, Haibo; Liu, Si; Liu, Xuewen; Yang, Jinjing; Wang, Fang; Cong, Xiangfeng; Chen, Xi

    2017-01-01

    The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1–LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery. PMID:28377726

  18. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

    PubMed Central

    Fujisaki, Noritomo; Kohama, Keisuke; Nishimura, Takeshi; Yamashita, Hayato; Ishikawa, Michiko; Kanematsu, Akihiro; Yamada, Taihei; Lee, Sungsoo; Yumoto, Tetsuya; Tsukahara, Kohei; Kotani, Joji; Nakao, Atsunori

    2016-01-01

    Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects. Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors. PMID:27867479

  19. The vestigial enzyme D-dopachrome tautomerase protects the heart against ischemic injury.

    PubMed

    Qi, Dake; Atsina, Kwame; Qu, Lintao; Hu, Xiaoyue; Wu, Xiaohong; Xu, Bin; Piecychna, Marta; Leng, Lin; Fingerle-Rowson, Günter; Zhang, Jiasheng; Bucala, Richard; Young, Lawrence H

    2014-08-01

    The cellular response to stress involves the recruitment and coordination of molecular signaling pathways that prevent cell death. D-dopachrome tautomerase (DDT) is an enzyme that lacks physiologic substrates in mammalian cells, but shares partial sequence and structural homology with macrophage migration inhibitory factor (MIF). Here, we observed that DDT is highly expressed in murine cardiomyocytes and secreted by the heart after ischemic stress. Antibody-dependent neutralization of secreted DDT exacerbated both ischemia-induced cardiac contractile dysfunction and necrosis. We generated cardiomyocyte-specific DDT knockout mice (Myh6-Cre Ddtfl/fl), which demonstrated normal baseline cardiac size and function, but had an impaired physiologic response to ischemia-reperfusion. Hearts from Myh6-Cre Ddtfl/fl mice exhibited more necrosis and LV contractile dysfunction than control hearts after coronary artery ligation and reperfusion. Furthermore, treatment with DDT protected isolated hearts against injury and contractile dysfunction after ischemia-reperfusion. The protective effect of DDT required activation of the metabolic stress enzyme AMP-activated protein kinase (AMPK), which was mediated by a CD74/CaMKK2-dependent mechanism. Together, our data indicate that cardiomyocyte secretion of DDT has important autocrine/paracrine effects during ischemia-reperfusion that protect the heart against injury.

  20. Clinically Silent Preoperative Brain Injuries Do Not Worsen with Surgery in Newborns with Congenital Heart Disease

    PubMed Central

    Block, AJ; McQuillen, PS; Chau, V; Glass, H; Poskitt, KJ; Barkovich, AJ; Esch, M; Soulikias, W; Azakie, A; Campbell, A; Miller, SP

    2010-01-01

    Objective Preoperative brain injury, particularly stroke and white matter injury (WMI), is common in newborns with congenital heart disease (CHD). The objective of this study was to determine the risk of hemorrhage or extension of preoperative brain injury with cardiac surgery. Methods This dual-center prospective cohort study recruited 92 term newborns: 62 with transposition of the great arteries (TGA), and 30 with single ventricle physiology from two tertiary referral centers. Newborns underwent brain MRI scans before and after cardiac surgery. Results Brain injury was identified in 40 (43%) newborns on the preoperative MRI scan (median five days of life): stroke in 23, WMI in 21, and intraventricular hemorrhage in 7. None of the brain lesions presented clinically with overt signs or seizures. Preoperative brain injury was associated with balloon atrial septostomy (BAS) (P=0.003) and lowest SaO2 (P=0.007); in a multivariable model, only the effect of BAS remained significant when adjusting for lowest SaO2. On postoperative MRI in 78 newborns (median 21 days of life), none of the preoperative lesions showed evidence of extension or hemorrhagic transformation (0/40 [95% CI: 0-7%]). The presence of preoperative brain injury was not a significant risk factor for acquiring new injury on the postoperative MRI (P=0.8). Conclusion Clinically silent brain injuries identified preoperatively in newborns with CHD, including stroke, have a low risk of progression with surgery and cardiopulmonary bypass, and should therefore not delay clinically indicated cardiac surgery. In this multi-center cohort, BAS remains an important risk factor for preoperative brain injury, particularly stroke. PMID:20434174

  1. The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat

    PubMed Central

    Wang, Yunru; Xu, Peng; Wang, Yang; Liu, Haiyan; Zhou, Yuwen; Cao, Xuebin

    2013-01-01

    Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction. Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique. Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dt max under the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats. Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside. PMID:24454984

  2. The synthetic pentasaccharide fondaparinux prevents coronary microvascular injury and myocardial dysfunction in the ischemic heart.

    PubMed

    Montaigne, David; Marechal, Xavier; Lancel, Steve; Decoster, Brigitte; Asseman, Philippe; Neviere, Remi

    2008-11-01

    Fondaparinux is a synthetic pentasaccharide with powerful anticoagulant properties, which may also reduce ischemia-reperfusion (I/R) injury in vivo. However, the relative contributions of the anticoagulant and anti-inflammatory activities of fondaparinux to the observed protection are unknown. To address this issue, a crystalloid-perfused heart model was used to assess potential effects of fondaparinux on IR-induced heart injury in the absence of blood. Fondaparinux protects the ischemic myocardium independently of its haemostasis effects. Fondaparinux improved post ischemic myocardial contractile performance and tissue damage. These beneficial effects of fondaparinux may be related to the observed reduction in IR-induced oxidative stress and endothelial activation. In addition, fondaparinux altered NADPH oxidase activity and phosphorylated extracellular signal-regulated kinase (ERK) 1/2, suggesting activation of survival signaling pathways. The present study provides novel information by demonstrating that fondaparinux can attenuate inflammatory responses and oxidative stress in connection with IR heart injury. These findings could represent a potential therapeutic strategy for the prevention of myocardial dysfunction.

  3. Acute Kidney Injury and Fluid Overload in Neonates Following Surgery for Congenital Heart Disease.

    PubMed

    Piggott, Kurt D; Soni, Meshal; Decampli, William M; Ramirez, Jorge A; Holbein, Dianna; Fakioglu, Harun; Blanco, Carlos J; Pourmoghadam, Kamal K

    2015-07-01

    Acute kidney injury (AKI) and fluid overload have been shown to increase morbidity and mortality. The reported incidence of AKI in pediatric patients following surgery for congenital heart disease is between 15% and 59%. Limited data exist looking at risk factors and outcomes of AKI or fluid overload in neonates undergoing surgery for congenital heart disease. Neonates aged 6 to 29 days who underwent surgery for congenital heart disease and who were without preoperative kidney disease were included in the study. The AKI was determined utilizing the Acute Kidney Injury Network criteria. Ninety-five neonates were included in the study. The incidence of neonatal AKI was 45% (n = 43), of which 86% had stage 1 AKI. Risk factors for AKI included cardiopulmonary bypass time, selective cerebral perfusion, preoperative aminoglycoside use, small kidneys by renal ultrasound, and risk adjustment for congenital heart surgery category. There were eight mortalities (five from stage 1 AKI group, three from stage 2, and zero from stage 3). Fluid overload and AKI both increased hospital length of stay and postoperative ventilator days. To avoid increased risk of morbidity and possibly mortality, every attempt should be made to identify and intervene on those risk factors, which may be modifiable or identifiable preoperatively, such as small kidneys by renal ultrasound. © The Author(s) 2015.

  4. Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

    PubMed

    Yao, Kozo; Ina, Yasuhiro; Sonoda, Rie; Nagashima, Ken; Ohmori, Kenji; Ohno, Tetsuji

    2003-01-01

    We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

  5. Hydrogen sulfide post-conditioning preserves interfibrillar mitochondria of rat heart during ischemia reperfusion injury.

    PubMed

    Banu, Shakila A; Ravindran, Sriram; Kurian, Gino A

    2016-07-01

    Cardiac mitochondrial dysfunction is considered to be the main manifestation in the pathology of ischemia reperfusion injury, and by restoring its functional activity, hydrogen sulfide (H2S), a novel endogenous gaseotransmitter renders cardioprotection. Given that interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria are the two main types in the heart, the present study investigates the specific H2S-mediated action on IFM and SSM during ischemic reperfusion in the Langendorff rat heart model. Rats were randomly divided into five groups, namely normal, ischemic control, reperfusion control (I/R), ischemic post-conditioning (POC), and H2S post-conditioning (POC_H2S). In reperfusion control, cardiac contractility decreased, and lactate dehydrogenase, creatine kinase, and infracted size increased compared to both normal and ischemic group. In hearts post-conditioned with H2S and the classical method improved cardiac mechanical function and decreased cardiac markers in the perfusate and infarct size significantly. Both POC and POC_H2S exerts its cardioprotective effect of preserving the IFM, as evident by significant improvement in electron transport chain enzyme activities and mitochondrial respiration. The in vitro action of H2S on IFM and SSM from normal and I/R rat heart supports H2S and mediates cardioprotection via IFM preservation. Our study indicates that IFM play an important role in POC_H2S mediated cardioprotection from reperfusion injury.

  6. Effect of Laser Acupuncture on Heart Rate Variability of Nonpatients and Patients with Spinal Cord Injury.

    PubMed

    Wong, Yiu Ming

    2017-01-01

    Sensory loss in a complete spinal cord injury (SCI) can be described as an injury that removes the ability of the brain to receive electrical afferent signals generated below the site of the injury. The sensory nervous system appears to be the same as the meridians in the concept of Oriental medicine, thus, we assumed that a complete SCI would lead to discontinuation of the meridians in humans. In this case series report with a cross-sectional view, we observed quantitative changes in heart rate variability induced by laser acupuncture at bilateral GB34 and ST36 points for 15 minutes in eight patients with complete SCIs between the levels of T8 and T12, and eight healthy individuals as a control group. A comparison between pre- and post-treatment data demonstrated that the physiological effect on the heart rate variability was absent when the laser acupuncture was applied below the level of injury among the patients with complete SCI, while the healthy counterparts showed the opposite pattern. The preliminary data suggest that the purported meridian system may not be different from the known sensory nervous system, as the transected spinal cord leads to interrupted meridians. The findings in the present case series warranted further investigation.

  7. A Retained Bullet in Pericardial Sac: Penetrating Gunshot Injury of the Heart

    PubMed Central

    Kaya, Adnan; Caliskan, Emine; Tatlisu, Mustafa Adem; Hayiroglu, Mert Ilker; Tekessin, Ahmet Ilker; Cakilli, Yasin; Avsar, Sahin; Oz, Ahmet; Uzman, Osman

    2016-01-01

    Penetrating cardiac trauma is rarely seen but when present there is a short time lag to keep the patients alive. Cardiac gunshot injuries are exceptional and it occurs mostly during interpersonal disagreements casualties or a mistakenly fired gun nowadays. Here we present a case of cardiac gunshot injury from the war of Kobani, Syria. The patient was mistakenly diagnosed to have a sole bullet in the left shoulder while he had a penetrating cardiac trauma with a bullet in the heart and pericardial effusion possibly giving rise to pericardial tamponade. Luckily the cardiac gunshot injury was noticed one day later and the patient was referred to a tertiary hospital. Intrapericardial bullet was conservatively followed up. The patient was discharged one week later after resection of the bullet in the shoulder. PMID:26977324

  8. [Penetrating knife injury to the heart treated with emergency department thoracotomy--case report].

    PubMed

    Sigurðardóttir, Anna; Stefánsson, Sigurjón Örn; Jóhannesdóttir, Bergrós Kristín; Gudbjartsson, Tomas

    2015-12-01

    Penetrating cardiac injuries usually result in an excessive bleeding and a cardiac tamponade with a very high mortality. If patients reach hospital alive, or within 15 minutes after no signs of life are found, an emergency department thoracotomy (EDT) can be indicated. However, the indications and outcome of this procedure have been debated. We report a 40 year old male that sustained a cardiac stab injury, causing a cardiac tamponade and a circulatory arrest. By performing an EDT with a pericardiotomy and direct cardiac massage, his circulation could be restored and the perforation of the heart sutured. Twelve months later the patient is in good health. This case shows that an EDT can be life saving in patients with penetrating cardiac injuries.

  9. Early biomarkers of doxorubicin-induced heart injury in a mouse model

    SciTech Connect

    Desai, Varsha G.; Kwekel, Joshua C.; Vijay, Vikrant; Moland, Carrie L.; Herman, Eugene H.; Lee, Taewon; Han, Tao; Lewis, Sherry M.; Davis, Kelly J.; Muskhelishvili, Levan; Kerr, Susan; Fuscoe, James C.

    2014-12-01

    Cardiac troponins, which are used as myocardial injury markers, are released in plasma only after tissue damage has occurred. Therefore, there is a need for identification of biomarkers of earlier events in cardiac injury to limit the extent of damage. To accomplish this, expression profiling of 1179 unique microRNAs (miRNAs) was performed in a chronic cardiotoxicity mouse model developed in our laboratory. Male B6C3F{sub 1} mice were injected intravenously with 3 mg/kg doxorubicin (DOX; an anti-cancer drug), or saline once a week for 2, 3, 4, 6, and 8 weeks, resulting in cumulative DOX doses of 6, 9, 12, 18, and 24 mg/kg, respectively. Mice were euthanized a week after the last dose. Cardiac injury was evidenced in mice exposed to 18 mg/kg and higher cumulative DOX dose whereas examination of hearts by light microscopy revealed cardiac lesions at 24 mg/kg DOX. Also, 24 miRNAs were differentially expressed in mouse hearts, with the expression of 1, 1, 2, 8, and 21 miRNAs altered at 6, 9, 12, 18, and 24 mg/kg DOX, respectively. A pro-apoptotic miR-34a was the only miRNA that was up-regulated at all cumulative DOX doses and showed a significant dose-related response. Up-regulation of miR-34a at 6 mg/kg DOX may suggest apoptosis as an early molecular change in the hearts of DOX-treated mice. At 12 mg/kg DOX, up-regulation of miR-34a was associated with down-regulation of hypertrophy-related miR-150; changes observed before cardiac injury. These findings may lead to the development of biomarkers of earlier events in DOX-induced cardiotoxicity that occur before the release of cardiac troponins. - Highlights: • Upregulation of miR-34a before doxorubicin-induced cardiac tissue injury • Apoptosis might be an early event in mouse heart during doxorubicin treatment. • Expression of miR-150 declined before doxorubicin-induced cardiac tissue injury.

  10. The semisynthetic polysaccharide pentosan polysulfate prevents complement-mediated myocardial injury in the rabbit perfused heart.

    PubMed

    Kilgore, K S; Naylor, K B; Tanhehco, E J; Park, J L; Booth, E A; Washington, R A; Lucchesi, B R

    1998-06-01

    Pentosan polysulfate (PPS) is a highly sulfated semisynthetic polysaccharide possessing a higher negative charge density and degree of sulfation than heparin. Like other glycosaminoglycans, the structural and chemical properties of PPS promote binding of the drug to the endothelium. Glycosaminoglycans, including heparin, inhibit complement activation independent of an action on the coagulation system. This ability provides a compelling argument for the implementation of this class of compounds in experimental models of cellular injury mediated by complement. The objective of this study was to examine whether PPS could reduce myocardial injury resulting from activation of the complement system. We used the rabbit isolated heart perfused with 4% normal human plasma as a source of complement. Hemodynamic variables were obtained before addition of PPS (0.03 01 mg/ml) and every 10 min after the addition of human plasma. Compared with vehicle-treated hearts, left ventricular end-diastolic pressure was improved at the conclusion of the 60-min protocol in hearts treated with PPS (58.9 +/- 13.6 vs. 15. 2 +/- 4.8 mm Hg). Further evidence as to the protective effects of PPS was demonstrated by decreased creatine kinase release compared with vehicle (86.5 +/- 28.5 U/l vs. 631.0 +/- 124.8 U/l). An enzyme-linked immunosorbent assay for the presence of the membrane attack complex in lymph and tissue samples demonstrated decreased membrane attack complex formation in PPS-treated hearts, which suggests inhibition of complement activation. This conclusion was supported further by the ability of PPS to inhibit complement-mediated red blood cell lysis in vitro. The results of this study indicate that PPS can reduce tissue injury and preserve organ function that otherwise would be compromised during activation of the human complement cascade.

  11. The Brain in Congenital Heart Disease across the Lifespan: The Cumulative Burden of Injury

    PubMed Central

    Marelli, Ariane; Miller, Steven P.; Marino, Bradley Scott; Jefferson, Angela L.; Newburger, Jane W.

    2017-01-01

    The number of patients surviving with congenital heart disease (CHD) has soared over the last three decades. Adults constitute the fastest growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has largely been focused on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. In summary, against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions. PMID:27185022

  12. Brain in Congenital Heart Disease Across the Lifespan: The Cumulative Burden of Injury.

    PubMed

    Marelli, Ariane; Miller, Steven P; Marino, Bradley Scott; Jefferson, Angela L; Newburger, Jane W

    2016-05-17

    The number of patients surviving with congenital heart disease (CHD) has soared over the last 3 decades. Adults constitute the fastest-growing segment of the CHD population, now outnumbering children. Research to date on the heart-brain intersection in this population has been focused largely on neurodevelopmental outcomes in childhood and adolescence. Mutations in genes that are highly expressed in heart and brain may cause cerebral dysgenesis. Together with altered cerebral perfusion in utero, these factors are associated with abnormalities of brain structure and brain immaturity in a significant portion of neonates with critical CHD even before they undergo cardiac surgery. In infancy and childhood, the brain may be affected by risk factors related to heart disease itself or to its interventional treatments. As children with CHD become adults, they increasingly develop heart failure, atrial fibrillation, hypertension, diabetes mellitus, and coronary disease. These acquired cardiovascular comorbidities can be expected to have effects similar to those in the general population on cerebral blood flow, brain volumes, and dementia. In both children and adults, cardiovascular disease may have adverse effects on achievement, executive function, memory, language, social interactions, and quality of life. Against the backdrop of shifting demographics, risk factors for brain injury in the CHD population are cumulative and synergistic. As neurodevelopmental sequelae in children with CHD evolve to cognitive decline or dementia during adulthood, a growing population of CHD can be expected to require support services. We highlight evidence gaps and future research directions.

  13. Inhibition of HtrA2/Omi ameliorates heart dysfunction following ischemia/reperfusion injury in rat heart in vivo.

    PubMed

    Bhuiyan, Md Shenuarin; Fukunaga, Kohji

    2007-02-28

    High temperature requirement A2 (HtrA2)/Omi is a mitochondrial serine protease that is released into the cytosol from mitochondria and in turn promotes caspase activation by proteolyzing inhibitor of apoptosis proteins. Here we asked whether treatment with an HtrA2/Omi inhibitor, 5-[5-(2-nitrophenyl)furfuryliodine]-1,3-diphenyl-2-thiobarbituric acid (UCF-101), restores heart dysfunction following ischemia/reperfusion injury in vivo. Rats underwent a 30-min ischemia by occluding the left anterior descending artery, followed by 24 h reperfusion. UCF-101 (0.75 or 1.5 micromol/kg, i.p.) was administered 10 min before reperfusion. UCF-101 treatment significantly recovered the mean arterial blood pressure and ameliorated contractile dysfunction of the left ventricle 72 h after reperfusion with concomitant reduction of infarct size. Cardio-protection mediated by UCF-101 was correlated with reduced X-linked inhibitor of apoptosis protein (XIAP) degradation and inhibition of Caspase-9, Caspase-3, and Caspase-7 processing. Furthermore, UCF-101 prevented loss of membrane integrity by inhibiting fodrin breakdown in cardiomyocytes. UCF-101-induced cytoprotection was also correlated with reduced Fas ligand expression and inhibition of FLIP degradation following ischemia/reperfusion. These results suggest that UCF-101 rescues cardiomyocytes from ischemia/reperfusion injury by inhibiting XIAP degradation and Fas/Fas-ligand-induced apoptosis, thereby ameliorating ischemia/reperfusion-induced myocardial dysfunction.

  14. The mannose-binding lectin pathway is a significant contributor to reperfusion injury in the type 2 diabetic heart

    PubMed Central

    La Bonte, Laura R.; Dokken, Betsy; Davis-Gorman, Grace; Stahl, Gregory L.; McDonagh, Paul F.

    2010-01-01

    The severity of ischaemic heart disease is markedly enhanced in type 2 diabetes. We recently reported that complement activation exacerbates I/R injury in the type 2 diabetic heart. The purpose of this study was to isolate and examine MBL pathway activation following I/R injury in the diabetic heart. ZLC and ZDF rats underwent 30 minutes of left coronary artery occlusion followed by 120 minutes of reperfusion. Two different groups of ZDF rats were treated with either FUT-175, a broad complement inhibitor, or P2D5, a monoclonal antibody raised against rat MBL-A. ZDF rats treated with FUT175 and P2D5 had significantly decreased myocardial infarct size, C3 deposition and neutrophil accumulation compared with untreated ZDF controls. Taken together, these findings indicate that the MBL pathway plays a key role in the severity of complement-mediated I/R injury in the type 2 diabetic heart. PMID:20216929

  15. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

    PubMed Central

    Qu, Daoxu; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities. PMID:26788251

  16. Different Roles for Contracture and Calpain in Calcium Paradox-Induced Heart Injury

    PubMed Central

    Zhang, Jian-Ying; Bi, Sheng-Hui; Xu, Ming; Jin, Zhen-Xiao; Yang, Yang; Jiang, Xiao-Fan; Zhou, Jing-Jun

    2012-01-01

    The Ca2+ paradox represents a good model to study Ca2+ overload injury in ischemic heart diseases. We and others have demonstrated that contracture and calpain are involved in the Ca2+ paradox-induced injury. This study aimed to elucidate their roles in this model. The Ca2+ paradox was elicited by perfusing isolated rat hearts with Ca2+-free KH media for 3 min or 5 min followed by 30 min of Ca2+ repletion. The LVDP was measured to reflect contractile function, and the LVEDP was measured to indicate contracture. TTC staining and the quantification of LDH release were used to define cell death. Calpain activity and troponin I release were measured after Ca2+ repletion. Ca2+ repletion of the once 3-min Ca2+ depleted hearts resulted in almost no viable tissues and the disappearance of contractile function. Compared to the effects of the calpain inhibitor MDL28170, KB-R7943, an inhibitor of the Na+/Ca2+ exchanger, reduced the LVEDP level to a greater extent, which was well correlated with improved contractile function recovery and tissue survival. The depletion of Ca2+ for 5 min had the same effects on injury as the 3-min Ca2+ depletion, except that the LVEDP in the 5-min Ca2+ depletion group was lower than the level in the 3-min Ca2+ depletion group. KB-R7943 failed to reduce the level of LVEDP, with no improvement in the LVDP recovery in the hearts subjected to the 5-min Ca2+ depletion treatment; however, KB-R7943 preserved its protective effects in surviving tissue. Both KB-R7943 and MDL28170 attenuated the Ca2+ repletion-induced increase in calpain activity in 3 min or 5 min Ca2+ depleted hearts. However, only KB-R7943 reduced the release of troponin I from the Ca2+ paradoxic heart. These results provide evidence suggesting that contracture is the main cause for contractile dysfunction, while activation of calpain mediates cell death in the Ca2+ paradox. PMID:23284963

  17. [Protective effects of SMT on myocardial ultrastructure of ischemia reperfusion injury in heart of rat].

    PubMed

    Zheng, H Z; Cai, B; Feng, Y H; Sun, H; Cai, K R

    2000-11-01

    To Investigate the myocardial ultrastructure effects of SMT on the ischemia reperfusion injury (IRI) in the rat heart. Eighteen Spraqua-Dawley rats were randomly divided into three groups: ischemia reperfusion group (IR), subjected to 60 min of o-cclusion and 20 min of reperfusion of the anterior descending branch of left coronary artery; IR + SMT group (SMT), given the selective iNOS inhibitor S-methylisothiourea sulfate (SMT, 5 mg/kg, i.v.) before reperfusion; control group (C), didn't occlude coronary artery after exposing heart and observed 80 min. Electrocardiogram (ECG) was recorded. Nitrite and nitrate content were measured in myocardium and blood serum. The changes of myocardial ultrastructure were observed with electron microscope. Ischemia reperfusion induced ST segment elevation and T waves inversion or tallness in ECG, damaged myocardial ultrastructure, increased nitrite and nitrate content in myocardium and blood serum after IR compared with before IR(P < 0.01). Administration of SMT improved the changes of ECG and the injury of myocardial ultrastructure. Nitrite and nitrate content of myocardium were lower than IR group (P < 0.05). The change of nitrite and nitrate level of blood serum in SMT group was nearly in C group. SMT can prevent myocardium injury from reperfusion following ischemia.

  18. Effect of locally released catecholamines on lipolysis and injury of the hypoxic isolated rabbit heart.

    PubMed

    Karwatowska-Kryńska, E; Beresewicz, A

    1983-08-01

    The ability of endogenous myocardial catecholamines to stimulate lipolysis of endogenous triglycerides and the role of this process in the development of myocardial injury were studied in isolated, Langendorff-perfused rabbit heart preparations exposed to 3 h of hypoxic perfusion followed by 30 min of aerobic perfusion. Untreated hearts responded not only to hypoxia but also to reoxygenation with surges of noradrenaline outflow lasting 10 and 5 min, respectively. During hypoxia but not during reoxygenation a parallel surge of glycerol outflow was observed. Nicotinic acid (10(-5) M) prevented glycerol outflow during hypoxia but did not influence the outflow of noradrenaline during either hypoxia or reoxygenation. Neither noradrenaline nor glycerol were detected in the effluent from the hearts depleted of endogenous catecholamines by reserpine pretreatment. Those hearts also showed a smaller lactate dehydrogenase release during hypoxia (49% reduction) and no increase in lactate dehydrogenase release during reoxygenation. Similar reduction of lactate dehydrogenase release during hypoxia (52% reduction) was observed in the hearts treated with nicotinic acid. This drug, however, did not prevent the reoxygenation-induced lactate dehydrogenase release. The effects of reserpinization and nicotinic acid treatment on lactate dehydrogenase release were not additive. It is concluded that hypoxia is a stimulus for lipolysis in the isolated rabbit heart and most probably this process is catecholamine dependent. At least part of the deleterious effect of endogenous catecholamines on hypoxic myocardium might be attributed to catecholamine-stimulated lipolysis of endogenous triglycerides. The latter, however, does not seem to contribute to deleterious effects of endogenous catecholamines during reoxygenation.

  19. Long range correlations in the heart rate variability following the injury of cardiac arrest

    NASA Astrophysics Data System (ADS)

    Tong, Shanbao; Jiang, Dineng; Wang, Ziming; Zhu, Yisheng; Geocadin, Romeryko G.; Thakor, Nitish V.

    2007-07-01

    Cardiovascular and neurological recovery following cardiac arrest (CA) largely influence the morbidity and mortality of the patients. Monitoring the cardiovascular system has been an important clinical issue in intensive care unit (ICU). On the other hand, the rhythms of the heart rate variability following CA are still not fully understood, and there are limited number of literatures reporting the cardiovascular function recovery following CA. In this paper, we studied the scaling properties of heart rate variability (HRV) after CA by centered-moving-average-based detrended fluctuation analysis (DFA). Our results showed that the scaling factor of the baseline HRV is close to that of Brownian motion, and after a CA event it shifts to a 1/f noise-like rhythm. DFA could be a promising tool in evaluating the cardiovascular long term recovery following CA injury.

  20. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    NASA Astrophysics Data System (ADS)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  1. The effect of pericardial insulation on hypothermic phrenic nerve injury during open-heart surgery.

    PubMed

    Esposito, R A; Spencer, F C

    1987-03-01

    Phrenic nerve injury was evaluated prospectively in 133 patients undergoing open-heart surgery using iced saline slush for topical hypothermia. In the control group of 70 patients no attempt was made to shield the phrenic nerves from direct exposure to ice. Phrenic nerve damage occurred in 73% of these patients, as assessed by persistent diaphragm paralysis evident on inspiratory chest roentgenogram. In 2 patients the paralysis was bilateral. In the second group of 63 patients a pericardial insulation pad was used to prevent contact of the iced slush to the phrenic nerve. Diaphragm paralysis was observed in 17% of these patients. This difference was highly significant (p less than .001). Diaphragm paralysis in the control group was clinically significant; life-threatening respiratory complications developed in 7 patients (14%), frequently resulting in multiple reintubations, tracheostomy, and prolonged mechanical ventilation. In addition, 4 patients with phrenic nerve injury exhibited a clinical syndrome consistent with gastric ileus, which may possibly represent hypothermic injury to the thoracic vagi. The likelihood of phrenic nerve injury when iced saline slush is used for topical myocardial cooling and the possibility of developing serious respiratory disability would support the routine use of pericardial insulation when this method of hypothermia is used.

  2. Cannabinoid-2 receptor activation protects against infarct and ischemia-reperfusion heart injury.

    PubMed

    Wang, Peng-Fei; Jiang, Li-Sheng; Bu, Jun; Huang, Xiao-Jin; Song, Wei; Du, Yong-Ping; He, Ben

    2012-04-01

    Endocannabinoid system is reported to be activated during myocardial ischemia-reperfusion (IR) injury and protects against heart injury. We, therefore, observed changes in endocannabinoids levels during acute myocardial infarction (AMI) and myocardial IR injury and evaluated the role of cannabinoid-2 (CB2) receptor in infarct and IR heart injury. In contrast to 16 control patients with normal coronary artery angiogram, the endocannabinoid 2-arachidonoylglycerol level in the infarct-side coronary artery of 23 AMI patients increased significantly, with increased reactive oxygen species and tumor necrosis factor-α levels in both infarct-side coronary artery and radial artery. Then, 35 C57BL/6J mice were made into SHAM, AMI, or IR models. AMI and IR groups were treated with CB2-selective agonist HU308 ((+)-(1aH,3H,5aH)-4-[2,6-dimethoxy-4-(1,1-dimethylheptyl)phenyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carbinol), with or without CB2-selective antagonist AM630 [6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone through intraperitoneal injection. Compared with the SHAM, expressions of cannabinoid CB1/CB2 receptor proteins in AMI/IR animals were upregulated; production of 2-arachidonoylglycerol and anandamide and release of reactive oxygen species and tumor necrosis factor-α also increased. HU308 significantly decreased the infarct size and the levels of reactive oxygen species and tumor necrosis factor-α in AMI/IR animals. However, these effects were blocked by AM630. In conclusion, the endocannabinoid system was activated during AMI and IR, and CB2 receptor activation produces a protective role, thus offering a novel pharmaceutical target for treating these diseases.

  3. Penetrating Nail-Gun Injury of the Heart Managed by Adenosine-Induced Asystole in the Absence of a Heart-Lung Machine

    PubMed Central

    Rupprecht, Holger

    2014-01-01

    During his work, an 18-year-old carpenter-in-training overbalanced and shot himself in the left median thorax with a nail gun. The patient was delivered to our thoracic surgery unit with a tentative diagnosis of penetrating lung trauma. An emergent computed tomogram showed a heart-penetrating nail injury. The patient was taken to the operating room, where he underwent emergency surgery that included sternotomy, pericardiotomy, extraction of the nail, and trauma treatment of the heart injury. The surgery was performed in a unit without a heart-lung machine. For that reason, asystole was chemically induced by the intravenous administration of adenosine. The surgery was successful, and the patient was discharged from the hospital on the 10th postoperative day. In cases of penetrating injuries of the heart, especially those with a foreign body retained in situ, we believe that the intravenous administration of adenosine is an elegant solution for the rapid provocation of asystole. In contrast to other methods, adenosine-induced asystole enables relatively safe myocardial manipulation in the absence of a cardiac surgical unit and a heart-lung machine. PMID:25120400

  4. Penetrating nail-gun injury of the heart managed by adenosine-induced asystole in the absence of a heart-lung machine.

    PubMed

    Rupprecht, Holger; Ghidau, Marius

    2014-08-01

    During his work, an 18-year-old carpenter-in-training overbalanced and shot himself in the left median thorax with a nail gun. The patient was delivered to our thoracic surgery unit with a tentative diagnosis of penetrating lung trauma. An emergent computed tomogram showed a heart-penetrating nail injury. The patient was taken to the operating room, where he underwent emergency surgery that included sternotomy, pericardiotomy, extraction of the nail, and trauma treatment of the heart injury. The surgery was performed in a unit without a heart-lung machine. For that reason, asystole was chemically induced by the intravenous administration of adenosine. The surgery was successful, and the patient was discharged from the hospital on the 10th postoperative day. In cases of penetrating injuries of the heart, especially those with a foreign body retained in situ, we believe that the intravenous administration of adenosine is an elegant solution for the rapid provocation of asystole. In contrast to other methods, adenosine-induced asystole enables relatively safe myocardial manipulation in the absence of a cardiac surgical unit and a heart-lung machine.

  5. Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study.

    PubMed

    Wan, S; LeClerc, J L; Antoine, M; DeSmet, J M; Yim, A P; Vincent, J L

    1999-10-01

    The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.

  6. Reduced ischemia-reperfusion injury with isoproterenol in non-heart-beating donor lungs.

    PubMed

    Jones, D R; Hoffmann, S C; Sellars, M; Egan, T M

    1997-05-01

    Transplantation of lungs retrieved from non-heart-beating donors could expand the donor pool. Recent studies suggest that the ischemia-reperfusion injury (IRI) to the lung can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, as measured by Kfc, in lungs retrieved from non-heart-beating donors and reperfused with or without isoproterenol (iso). Using an in situ isolated perfused lung model, lungs were retrieved from non-heart-beating donor rats ventilated with O2 or not at varying intervals after death. The lungs were reperfused with or without iso (10 microM). Kfc, lung viability, and pulmonary hemodynamics were measured, and tissue levels of adenine nucleotides and cAMP were measured by HPLC. Iso-reperfusion decreased Kfc significantly (P < 0.05) compared to non-iso-reperfused groups at all postmortem ischemic times, irrespective of preharvest ventilation status. Pulmonary arterial pressures and resistances increased and venous resistances decreased with iso-reperfusion. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso-reperfused (r = 0.65) and iso-perfused (r = 0.84) lungs. cAMP levels increased significantly with iso-reperfusion. cAMP levels correlated with Kfc (r = 0.87) in iso-reperfused lungs. Iso-reperfusion of lungs retrieved from non-heart-beating donor rats results in decreased capillary permeability and increased lung tissue cAMP levels. Pharmacologic augmentation of tissue TAN and cAMP levels may further ameliorate the increased capillary permeability seen in lungs retrieved from non-heart-beating donors.

  7. Holes in the heart: an atlas of intracardiac injuries following penetrating trauma.

    PubMed

    Reddy, Darshan; Muckart, David J J

    2014-07-01

    The extraordinarily high rate of penetrating heart injuries in South Africa provides a substantial denominator from which we derive a subset of patients with intracardiac lesions as a result of these injuries. The surgical literature, which consists largely of case reports and case series, describing various patterns of injury is dated and a review of management in the era of modern imaging and surgical techniques is warranted. A retrospective observational chart review of all patients with intracardiac injuries following penetrating trauma who were referred to the Department of Cardiothoracic Surgery at Inkosi Albert Luthuli Central Hospital in Durban, South Africa, during the 10-year period between July 2003 and July 2013 was performed. The spectrum of pathology encountered included ventricular septal defects, valve apparatus lacerations, intracardiac fistulae, ventricular aneurysms and retained intracardiac missiles. Of the 17 patients, 10 required operative repair of the intracardiac lesions using cardiopulmonary bypass, with no early mortality noted. Seven patients were treated non-operatively, for reasons that varied from insignificant haemodynamic shunts to advanced human immunodeficiency virus (HIV) infection. The in-hospital mortality in this group consisted of 1 patient, who was moribund at presentation. The referral of patients for the repair of intracardiac injuries following penetrating cardiac trauma is often delayed. Symptoms of cardiac failure should be optimized medically prior to undertaking definitive surgical repair, thereby also allowing for detailed preoperative imaging to guide appropriate intervention. Utilizing standard principles of intracardiac shunt repair, as well as contemporary valve repair techniques, favourable surgical outcomes may be reproduced. Percutaneous catheter device techniques may prove useful in patients deemed unsuitable for surgical repair, such as patients with sternal wound sepsis. © The Author 2014. Published by

  8. Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor.

    PubMed

    Pantos, Constantinos; Mourouzis, Iordanis; Saranteas, Theodosios; Brozou, Vassiliki; Galanopoulos, Georgios; Kostopanagiotou, Georgia; Cokkinos, Dennis V

    2011-07-01

    We have previously shown that acute thyroid hormone treatment could limit reperfusion injury and increase post-ischemic recovery of function. In the present study, we further explore potential initiating mechanisms of this response. Thus, isolated rat hearts were subjected to 30 min zero-flow global ischemia (I) followed by 60-min reperfusion (R). Reperfusion injury was assessed by post-ischemic recovery of left ventricular developed pressure (LVDP%) and LDH release. T3 at a dose of 60 nM which had no effect on contractile function of non-ischemic myocardium, significantly increased LVDP% [48% (2.9) vs. 30.2% (3.3) for untreated group, P < 0.05] and reduced LDH release [8.3 (0.3) vs. 10 (0.42) for untreated group, P < 0.05] when administered at R. T4 (60 and 400 nM) had no effect on contractile function either in non-ischemic or ischemic myocardium. Administration of debutyl-dronedarone (DBD), a TRα1 antagonist abolished the T3-limiting effect on reperfusion injury: Thus, co-administration of T3 and DBD resulted in significantly lower LVDP%, [23% (4.7) vs. 48% (2.9) for T3 group, P < 0.05] and higher LDH release [9.9 (0.3) vs. 8.3 (0.3), for T3 group, P < 0.05]. In conclusion, acute T3 and not T4 treatment will be able to protect against reperfusion injury. T3 can exert this beneficial effect on ischemic myocardium at a dose that has no effects on non-ischemic myocardium. Acute T3-limiting effect on reperfusion injury is mediated, at least in part, via TRα1 receptor.

  9. [Effects of astragalus and its active ingredients on ischemia reperfusion injury in isolated guinea-pig heart].

    PubMed

    Zhang, Haining; Min, Dongyu; Fu, Mingyu; Tian, Jing; Wang, Qingwen; An, Xinjiang

    2014-09-01

    To explore the effects of astragalus (AST) , total flavone of astragalus (TFA), total saponins of astragalus (TSA) and astragalus polysaccharides (APS) on ischemia/reperfusion (40 min/60 min) injury in isolated guinea-pig heart. Isolated guinea-pig hearts underwent ischemia, then followed by K-H perfusion (I/R group), AST (60 mg/L),AST (60 mg/L), TFA (60 mg/L), TSA (60 mg/L) and APS (60 mg/L) perfusion (n = 6 each).Isolated hearts without ischemia serve as control group (n = 6). Activity of lactate dehydrogenas (LDH) and creatine kinase (CK) in effluent were measured.Infarct size, myocardial superoxide dismutase (SOD) activity and malondiadehyde (MDA) contents were also determined. Compared to control hearts, heart rate, coronary flow and myocardial superoxide dismutase (SOD) activity were significantly reduced, while LDH and CK in effluent as well as myocardial MDA were significantly increased in the I/R hearts during reperfusion (all P < 0.05), these changes could be partly reversed by AST and TFA perfusion.Infarct size was also significantly reduced in AST (11.9 ± 2.03) % and TFA (13.31 ± 1.17) % treated hearts compared to that in I/R group (18.9 ± 2.27) % (all P < 0.01). The findings indicate that AST and TFA could attenuate I/R injury in isolated guinea-pig heart possibly through enhancing the activity of SOD and reducing lipid peroxidation.

  10. Irisin Plays a Pivotal Role to Protect the Heart Against Ischemia and Reperfusion Injury.

    PubMed

    Wang, Hao; Zhao, Yu Tina; Zhang, Shouyan; Dubielecka, Patrycja M; Du, Jianfeng; Yano, Naohiro; Chin, Y Eugene; Zhuang, Shougang; Qin, Gangjian; Zhao, Ting C

    2017-02-09

    Irisin, a newly identified hormone, is critical to modulating body metabolism, thermogenesis and reducing oxidative stresses. However, whether irisin protects the heart against myocardial ischemia and reperfusion (I/R) injury remains unknown. In this study, we determine the effect of irisin on myocardial I/R injury in the Langendorff perfused heart and cultured myocytes. Adult C57/BL6 mice were treated with irisin (100mg/kg) or vehicle for 30 minutes to elicit preconditioning. The isolated hearts were subjected to 30 min ischemia followed by 30 min reperfusion. Left ventricular function was measured and infarction size were determined using by tetrazolium staining. Western blot was employed to determine myocardial SOD-1, active-caspase 3, annexin V, p38 and phospho-p38. H9c2 cardiomyoblasts were exposed to hypoxia and reoxygenation for assessment of the effects of irisin on mitochondrial respiration and mitochondrial permeability transition pore (mPTP). Irisin treatment produced remarkable improvements in ventricular functional recovery, as evident by the increase in RPP and attenuation in LVEDP. As compared to the vehicle treatment, irisin resulted in a marked reduction of myocardial infarct size. Notably, irisin treatment increased SOD-1 and p38 phosphorylation, but suppressed levels of active-caspase 3, cleaved PARP, and annexin V. In cardiomyoblasts exposed to hypoxia/reoxygenation, irisin treatment significantly attenuated hypoxia/reoxygenation (H/R), as indicated by the reduction of lactate dehydrogenase (LDH) leakage and apoptotic cardiomyocytes. Furthermore, irisin treatments suppressed the opening of mPTP, mitochondrial swelling, and protected mitochondria function. Our results indicate that irisin serves as a novel approach to eliciting cardioprotection, which is associated with the improvement of mitochondrial function. This article is protected by copyright. All rights reserved.

  11. Bcl-2–associated athanogene 3 protects the heart from ischemia/reperfusion injury

    PubMed Central

    Su, Feifei; Myers, Valerie D.; Knezevic, Tijana; Wang, JuFang; Gao, Erhe; Madesh, Muniswamy; Tahrir, Farzaneh G.; Gupta, Manish K.; Gordon, Jennifer; Rabinowitz, Joseph; Tilley, Douglas G.; Khalili, Kamel; Cheung, Joseph Y.

    2016-01-01

    Bcl-2–associated athanogene 3 (BAG3) is an evolutionarily conserved protein expressed at high levels in the heart and the vasculature and in many cancers. While altered BAG3 expression has been associated with cardiac dysfunction, its role in ischemia/reperfusion (I/R) is unknown. To test the hypothesis that BAG3 protects the heart from reperfusion injury, in vivo cardiac function was measured in hearts infected with either recombinant adeno-associated virus serotype 9–expressing (rAAV9-expressing) BAG3 or GFP and subjected to I/R. To elucidate molecular mechanisms by which BAG3 protects against I/R injury, neonatal mouse ventricular cardiomyocytes (NMVCs) in which BAG3 levels were modified by adenovirus expressing (Ad-expressing) BAG3 or siBAG3 were exposed to hypoxia/reoxygenation (H/R). H/R significantly reduced NMVC BAG3 levels, which were associated with enhanced expression of apoptosis markers, decreased expression of autophagy markers, and reduced autophagy flux. The deleterious effects of H/R on apoptosis and autophagy were recapitulated by knockdown of BAG3 with Ad-siBAG3 and were rescued by Ad-BAG3. In vivo, treatment of mice with rAAV9-BAG3 prior to I/R significantly decreased infarct size and improved left ventricular function when compared with mice receiving rAAV9-GFP and improved markers of autophagy and apoptosis. These findings suggest that BAG3 may provide a therapeutic target in patients undergoing reperfusion after myocardial infarction. PMID:27882354

  12. Lavandula Reduces Heart Injury via Attenuating Tumor Necrosis Factor-Alpha and Oxidative Stress in A Rat Model of Infarct-Like Myocardial Injury

    PubMed Central

    Vakili, Abedin; Sameni, Hamid Reza; Zahedi khorasani, Mahdi; Darabian, Mohsen

    2017-01-01

    Objective Lavender is used in herbal medicine for different therapeutic purposes. Nonetheless, potential therapeutic effects of this plant in ischemic heart disease and its possible mechanisms remain to be investigated. Materials and Methods In this experimental study, lavender oil at doses of 200, 400 or 800 mg/kg was administered through gastric gavage for 14 days before infarct-like myocardial injury (MI). The carotid artery and left ventricle were cannulated to record arterial blood pressure (BP) and cardiac function. At the end of experiment, the heart was removed and histopathological alteration, oxidative stress biomarkers as well as tumor necrosis factor-alpha (TNF-α) level were evaluated. Results Induction of M.I caused cardiac dysfunction, increased levels of lipid peroxidation, TNF-α and troponin I in heart tissue (P<0.001). Pretreatment with lavender oil at doses of 200 and 400 mg/kg significantly reduced myocardial injury, troponin I and TNF-α. In addition, it improved cardiac function and antioxidant enzyme activity (P<0.01). Conclusion Our finding showed that lavender oil has cardioprotective effect through inhibiting oxidative stress and inflammatory pathway in the rat model with infarct-like MI. We suggest that lavender oil may be helpful in prevention or attenuation of heart injury in patients with high risk of myocardial infarction and/or ischemic heart disease. PMID:28367419

  13. Could heart rate variability predict outcome in patients with severe head injury? A pilot study.

    PubMed

    Rapenne, T; Moreau, D; Lenfant, F; Vernet, M; Boggio, V; Cottin, Y; Freysz, M

    2001-07-01

    Despite major improvements in the resuscitation of patients with head injury, the outcome of patients with head trauma often remains poor and difficult to establish. Heart rate variability (HRV) analysis is a noninvasive tool used to measure autonomic nervous system (ANS) activity. The aim of this prospective study was to investigate whether HRV analysis might be a useful adjunct for predicting outcome in patients with severe head injury. Twenty patients with severe head trauma (Glasgow Coma Scale [GCS] Heart rate variability was assessed, in both time domain and spectral domain. The authors initially compared (on Day 1) HRV in patients who progressed to brain death to HRV in survivors; then during the awakening period compared HRV in surviving patients with good recovery (GCS >or= 10) to HRV in patients characterized by a worsened neurologic state (GCS < 10). Statistical analysis used the Kruskal-Wallis test, P < .05. To assess whether HRV could predict evolution to brain death, receiver operating characteristic (ROC) curves were generated the day after trauma for Total Power, natural logarithm of high-frequency component of spectral analysis (LnHF), natural logarithm of low-frequency component of spectral analysis (LnLF), and root mean square for successive interval differences (rMSSD). Seven patients died between Day 1 and Day 5 after trauma. Six of those had progressed to brain death. In these six patients, at Day 1, Global HRV and parasympathetic tone were significantly higher. Referring to the area under the rMSSD ROC curve, HRV might provide useful information in predicting early evolution of patients with severe head trauma. During the awakening period, global HRV and the parasympathetic tone were significantly lower in the worsened neurologic state group. In conclusion, HRV could be helpful as a predictor of imminent brain death

  14. Mitigation Effect of Proanthocyanidin on Secondary Heart Injury in Rats Caused by Mechanical Trauma

    PubMed Central

    Ma, Shuo; Chen, Chong; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Li, Xintao; Yu, Deqin; Li, Shuzhuang

    2017-01-01

    Multiple organ dysfunctional syndrome secondary to mechanical trauma (MT) has attracted considerable research attention. The heart is one of the most important organs of the body, and secondary cardiac insufficiency caused by MT seriously affects the quality of life. This study aims to investigate whether proanthocyanidin can alleviate myocardial injury and improve heart function in the process of MT leading to secondary cardiac insufficiency. Noble-Collip drum wasused to prepare MT model in rats. And myocardial apoptosis index was calculated after TUNEL staining. Ventricular intubation was employed to detect heart function. Changes in myocardial ultrastructure were observed using an electron microscope. ELISA was used to detect the content of TNF-α and reactive oxygen species generated from monocytes and cardiomyocytes. The changes in Ca2+ concentration in cardiomyocyte were observed by confocal microscope. Compared with trauma group, the administration group had a decreased apoptosis index of cardiomyocytes, and increased ±dp/dtmax. Meanwhile, proanthocyanidin can inhibit monocytes’ TNF-α production, and reduce plasma TNF-α concentration. Moreover, proanthocyanidin can attenuate the excessive oxidative stress reaction of cardiomyocyte, and inhibit calcium overload in cardiomyocytes. In conclusion, proanthocyanidin can effectively ease myocardial damage and improve cardiac function, through anti-inflammatory and antioxidant effects in secondary cardiac insufficiency caused by MT. PMID:28294148

  15. Brain Injury in Autonomic, Emotional, and Cognitive Regulatory Areas in Patients with Heart Failure

    PubMed Central

    Woo, Mary A.; Kumar, Rajesh; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.

    2009-01-01

    Background Heart failure (HF) is accompanied by autonomic, emotional, and cognitive deficits, indicating brain alterations. Reduced gray matter volume and isolated white matter infarcts occur in HF, but the extent of damage is unclear. Using magnetic resonance T2 relaxometry, we evaluated the extent of injury across the entire brain in HF. Methods and Results Proton-density and T2-weighted images were acquired from 13 HF (age 54.6 ± 8.3 years; 69% male, LVEF 0.28 ± 0.07) and 49 controls (50.6 ± 7.3 years, 59% male). Whole brain maps of T2 relaxation times were compared at each voxel between groups using analysis of covariance (covariates: age and gender). Higher T2 relaxation values, indicating injured brain areas (p < 0.005), emerged in sites that control autonomic, analgesic, emotional, and cognitive functions (hypothalamus, raphé magnus, cerebellar cortex, deep nuclei and vermis; temporal, parietal, prefrontal, occipital, insular, cingulate, and ventral frontal cortices; corpus callosum; anterior thalamus; caudate nuclei; anterior fornix and hippocampus). No brain areas showed higher T2 values in control vs. HF subjects. Conclusions Brain structural injury emerged in areas involved in autonomic, pain, mood, language, and cognitive function in HF patients. Comorbid conditions accompanying HF may result from neural injury associated with the syndrome. PMID:19327623

  16. [Injuries to blood vessels near the heart caused by central venous catheters].

    PubMed

    Abram, J; Klocker, J; Innerhofer-Pompernigg, N; Mittermayr, M; Freund, M C; Gravenstein, N; Wenzel, V

    2016-11-01

    Injuries to blood vessels near the heart can quickly become life-threatening and include arterial injuries during central venous puncture, which can lead to hemorrhagic shock. We report 6 patients in whom injury to the subclavian artery and vein led to life-threatening complications. Central venous catheters are associated with a multitude of risks, such as venous thrombosis, air embolism, systemic or local infections, paresthesia, hemothorax, pneumothorax, and cervical hematoma, which are not always immediately discernible. The subclavian catheter is at a somewhat lower risk of catheter-associated sepsis and symptomatic venous thrombosis than approaches via the internal jugular and femoral veins. Indeed, access via the subclavian vein carries a substantial risk of pneumo- and hemothorax. Damage to the subclavian vein or artery can also occur during deliberate and inadvertent punctures and result in life-threatening complications. Therefore, careful consideration of the access route is required in relation to the patient and the clinical situation, to keep the incidence of complications as low as possible. For catheterization of the subclavian vein, puncture of the axillary vein in the infraclavicular fossa is a good alternative, because ultrasound imaging of the target vessel is easier than in the subclavian vein and the puncture can be performed much further from the lung.

  17. Protecting the heart from ischemia/reperfusion injury: an update on remote ischemic preconditioning and postconditioning.

    PubMed

    Donato, Martín; Evelson, Pablo; Gelpi, Ricardo J

    2017-11-01

    The most effective strategy for reducing acute myocardial ischemic injury is timely and effective reperfusion. However, myocardial reperfusion can induce further cardiomyocyte death (reperfusion injury). Interventions that protect the heart from ischemia/reperfusion injury, reducing infarct size, can involve remote ischemic preconditioning and postconditioning. These interventions have a promising potential clinical application, and have been the focus of recent research. In this review, we provide an update of remote ischemic preconditioning and postconditioning mechanisms. Remote ischemic preconditioning cardioprotection can occur via a humoral pathway and/or a neural pathway. These two pathways have been described as mechanistically different, but it has been suggested that they could be interdependent. However, remote ischemic postconditioning mainly involves the humoral pathway. In this review, we will discuss the different pathways and mechanisms involved in remote ischemic preconditioning and postconditioning. Remote ischemic preconditioning and postconditioning is possible to perform in a clinical setting by intermittent ischemia of an upper or lower limb. Furthermore, clinical trials using this procedure in the context of predictable ischemia-reperfusion have produced promising results, and other studies to define the potential clinical use of these strategies are ongoing.

  18. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  19. Effects of selective phosphodiesterase-5-inhibition on myocardial contractility and reperfusion injury after heart transplantation.

    PubMed

    Loganathan, Sivakkanan; Radovits, Tamás; Hirschberg, Kristóf; Korkmaz, Sevil; Barnucz, Eniko; Karck, Matthias; Szabó, Gábor

    2008-11-27

    Recently, the infarct reducing and cardioprotective effects of phosphodiesterase-5-inhibitors were described. In this study, we investigated these effects on ischemia/reperfusion injury in a rat model of heart transplantation. Three groups were assigned for our study: a vardenafil preconditioning group, an ischemic control, and a nonischemic control. Hemodynamic parameters were significantly increased in the vardenafil group (Pmax: 82+/-4 vs. 110+/-12 vs. 127+/-13 mm Hg; dP/dtmax: 1740+/-116 vs. 3197+/-599 vs. 4397+/-602 mm Hg/sec; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Furthermore, we recorded increased ATP levels and significantly less apoptosis in the treatment group after terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (apoptosis index: 27.23%+/-1.54% vs. 16.77%+/-1.42% vs. 18.86%+/-1.07%; ischemic control vs. vardenafil vs. nonischemic control; P<0.05 vs. ischemic control). Our current results support the concept that the cGMP-PKG-pathway plays an important role in ischemia/reperfusion injury. We could show that up-regulating this pathway has a preconditioning-like effect and can effectively reduce ischemia/reperfusion injury.

  20. First-stage palliation strategy for univentricular heart disease may impact risk for acute kidney injury.

    PubMed

    Goldstein, Bryan H; Goldstein, Stuart L; Devarajan, Prasad; Zafar, Farhan; Kwiatkowski, David M; Marino, Bradley S; Morales, David L S; Krawczeski, Catherine D; Cooper, David S

    2017-09-11

    Norwood palliation for patients with single ventricle heart disease is associated with a significant risk for acute kidney injury, which portends a worse prognosis. We sought to investigate the impact of hybrid stage I palliation (Hybrid) on acute kidney injury risk. This study is a single-centre prospective case-control study of seven consecutive neonates with single ventricle undergoing Hybrid palliation. Levels of serum creatinine and four novel urinary biomarkers, namely neutrophil gelatinase-associated lipocalin, interleukin-18, liver fatty acid-binding protein, and kidney injury molecule-1, were obtained before and after palliation. Acute kidney injury was defined as a ⩾50% increase in serum creatinine within 48 hours after the procedure. Data were compared with a contemporary cohort of 12 neonates with single ventricle who underwent Norwood palliation. Patients who underwent Hybrid were more likely to be high-risk candidates (86 versus 25%, p=0.01) compared with those who underwent Norwood. Despite similar preoperative serum creatinine levels, there was a trend towards higher levels of postoperative peak serum creatinine (0.7 [0.63, 0.94] versus 0.56 [0.47, 0.74], p=0.06) and rate of acute kidney injury (67 versus 29%, p=0.17) in the Norwood cohort. Preoperative neutrophil gelatinase-associated lipocalin (58.4 [11, 86.3] versus 6.3 [5, 16.2], p=0.07) and interleukin-18 (30.6 [9.6, 167.2] versus 6.3 [6.3, 16.4], p=0.03) levels were higher in the Hybrid cohort. Nevertheless, longitudinal mixed-effect models demonstrated Hybrid palliation to be a protective factor against increased postoperative levels of neutrophil gelatinase-associated lipocalin (estimate -1.8 [-3.0, -9.0], p<0.001) and liver fatty acid-binding protein (-49.3 [-89.7, -8.8], p=0.018). In this single-centre case-control study, postoperative acute kidney injury risk did not differ significantly by single ventricle stage I treatment strategy; however, postoperative elevation in novel urinary

  1. [Effect of 2,3-butanedione monoxime on calcium paradox-induced heart injury in rats].

    PubMed

    Kong, Ling-Heng; Gu, Xiao-Ming; Su, Xing-Li; Sun, Na; Wei, Ming; Zhu, Juan-Xia; Chang, Pan; Zhou, Jing-Jun

    2016-05-01

    To investigate the Effect of 2,3-butanedione monoxime (BDM) on calcium paradox-induced heart injury and its underlying mechanisms. Thirty-two adult male SD rats were randomized into 4 groups, namely the control group, BDM treatment control group, calcium paradox group, and BDM treatment group. Isolated Sprague Dawley male rat hearts underwent Langendorff perfusion and the left ventricular pressure (LVP) and left ventricular end-diastolic pressure (LVEDP) were monitored. Left ventricular developed pressure (LVDP) was calculated to evaluate the myocardial performance. Lactate dehydrogenase (LDH) content in the coronary flow was determined. Triphenyltetrazolium chloride staining was used to measure the infarct size, and myocardial cell apoptosis was tested with TUNEL method. Western blotting was used to determine the expression of cleaved caspase-3 and cytochrome c. Compared with the control group, BDM at 20 mmol/L had no effect on cardiac performance, cell death, apoptotic index or the content of LDH, cleaved caspase-3 and cytochrome c at the end of perfusion under control conditions (P>0.05). Calcium paradox treatment significantly decreased the cardiac function and the level of LVDP and induced a larger infarct size (P<0.01), an increased myocardial apoptosis index (P<0.01), and up-regulated expressions of cleaved caspase-3 and cytochrome c (P<0.01). BDM (20 mmol/L) significantly attenuated these effects induced by calcium paradox, and markedly down-regulated the levels of LVEDP and LDH (P<0.01), lowered myocardial apoptosis index, decreased the content of cleaved caspase-3 and cytochrome c (P<0.01), increased LVDP, and reduced the infarct size (P<0.01). BDM suppresses cell apoptosis and contracture and improves heart function and cell survival in rat hearts exposed to calcium paradox, suggesting the value of BDM as an potential drug for myocardial ischemia reperfusion injur.

  2. Activated c-Kit receptor in the heart promotes cardiac repair and regeneration after injury

    PubMed Central

    Di Siena, S; Gimmelli, R; Nori, S L; Barbagallo, F; Campolo, F; Dolci, S; Rossi, P; Venneri, M A; Giannetta, E; Gianfrilli, D; Feigenbaum, L; Lenzi, A; Naro, F; Cianflone, E; Mancuso, T; Torella, D; Isidori, A M; Pellegrini, M

    2016-01-01

    The role of endogenous c-Kit receptor activation on cardiac cell homeostasis and repair remains largely unexplored. Transgenic mice carrying an activating point mutation (TgD814Y) in the kinase domain of the c-Kit gene were generated. c-KitTgD814Y receptor was expressed in the heart during embryonic development and postnatal life, in a similar timing and expression pattern to that of the endogenous gene, but not in the hematopoietic compartment allowing the study of a cardiac-specific phenotype. c-KitTgD814Y mutation produced a constitutive active c-Kit receptor in cardiac tissue and cells from transgenic mice as demonstrated by the increased phosphorylation of ERK1/2 and AKT, which are the main downstream molecular effectors of c-Kit receptor signaling. In adult transgenic hearts, cardiac morphology, size and total c-Kit+ cardiac cell number was not different compared with wt mice. However, when c-KitTgD814Y mice were subjected to transmural necrotic heart damage by cryoinjury (CI), all transgenic survived, compared with half of wt mice. In the sub-acute phase after CI, transgenic and wt mice showed similar heart damage. However, 9 days after CI, transgenic mice exhibited an increased number of c-Kit+CD31+ endothelial progenitor cells surrounding the necrotic area. At later follow-up, a consistent reduction of fibrotic area, increased capillary density and increased cardiomyocyte replenishment rate (as established by BrdU incorporation) were observed in transgenic compared with wt mice. Consistently, CD45−c-Kit+ cardiac stem cells isolated from transgenic c-KitTgD814Y mice showed an enhanced endothelial and cardiomyocyte differentiation potential compared with cells isolated from the wt. Constitutive activation of c-Kit receptor in mice is associated with an increased cardiac myogenic and vasculogenic reparative potential after injury, with a significant improvement of survival. PMID:27468693

  3. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

    PubMed Central

    Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.

    2013-01-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  4. Glutamate protects against Ca(2+) paradox-induced injury and inhibits calpain activity in isolated rat hearts.

    PubMed

    Zhang, Jian-Ying; Kong, Ling-Heng; Lai, Dong; Jin, Zhen-Xiao; Gu, Xiao-Ming; Zhou, Jing-Jun

    2016-10-01

    This study determined the effects of glutamate on the Ca(2+) paradoxical heart, which is a model for Ca(2+) overload-induced injury during myocardial ischaemia and reperfusion, and evaluated its effect on a known mediator of injury, calpain. An isolated rat heart was retrogradely perfused in a Langendorff apparatus. Ca(2+) paradox was elicited via perfusion with a Ca(2+) -free Krebs-Henseleit (KH) solution for 3 minutes followed by Ca(2+) -containing normal KH solution for 30 minutes. The Ca(2+) paradoxical heart exhibited almost no viable tissue on triphenyltetrazolium chloride staining and markedly increased LDH release, caspase-3 activity, cytosolic cytochrome c content, and apoptotic index. These hearts also displayed significantly increased LVEDP and a disappearance of LVDP. Glutamate (5 and 20 mmol/L) significantly alleviated Ca(2+) paradox-induced injury. In contrast, 20 mmol/L mannitol had no effect on Ca(2+) paradox. Ca(2+) paradox significantly increased the extent of the translocation of μ-calpain to the sarcolemmal membrane and the proteolysis of α-fodrin, which suggests calpain activation. Glutamate also blocked these effects. A non-selective inhibitor of glutamate transporters, dl-TBOA (10 μmol/L), had no effect on control hearts, but it reversed glutamate-induced cardioprotection and reduction in calpain activity. Glutamate treatment significantly increased intracellular glutamate content in the Ca(2+) paradoxical heart, which was also blocked by dl-TBOA. We conclude that glutamate protects the heart against Ca(2+) overload-induced injury via glutamate transporters, and the inhibition of calpain activity is involved in this process. © 2016 John Wiley & Sons Australia, Ltd.

  5. Akt protects the heart against ischaemia-reperfusion injury by modulating mitochondrial morphology.

    PubMed

    Ong, Sang-Bing; Hall, Andrew R; Dongworth, Rachel K; Kalkhoran, Siavash; Pyakurel, Aswin; Scorrano, Luca; Hausenloy, Derek J

    2015-03-01

    The mechanism through which the protein kinase Akt (also called PKB), protects the heart against acute ischaemia-reperfusion injury (IRI) is not clear. Here, we investigate whether Akt mediates its cardioprotective effect by modulating mitochondrial morphology. Transfection of HL-1 cardiac cells with constitutively active Akt (caAkt) changed mitochondrial morphology as evidenced by an increase in the proportion of cells displaying predominantly elongated mitochondria (73 ± 5.0 % caAkt vs 49 ± 5.8 % control: N=80 cells/group; p< 0.05). This effect was associated with delayed time taken to induce mitochondrial permeability transition pore (MPTP) opening (by 2.4 ± 0.5 fold; N=80 cells/group: p< 0.05); and reduced cell death following simulated IRI (32.8 ± 1.2 % caAkt vs 63.8 ± 5.6 % control: N=320 cells/group: p< 0.05). Similar effects on mitochondrial morphology, MPTP opening, and cell survival post-IRI, were demonstrated with pharmacological activation of Akt using the known cardioprotective cytokine, erythropoietin (EPO). The effect of Akt on inducing mitochondrial elongation was found to be dependent on the mitochondrial fusion protein, Mitofusin-1 (Mfn1), as ablation of Mfn1 in mouse embryonic fibroblasts (MEFs) abrogated Akt-mediated mitochondrial elongation. Finally, in vivo pre-treatment with EPO reduced myocardial infarct size (as a % of the area at risk) in adult mice subjected to IRI (26.2 ± 2.6 % with EPO vs 46.1 ± 6.5 % in control; N=7/group: p< 0.05), and reduced the proportion of cells displaying myofibrillar disarray and mitochondrial fragmentation observed by electron microscopy in adult murine hearts subjected to ischaemia from 5.8 ± 1.0 % to 2.2 ± 1.0 % (N=5 hearts/group; p< 0.05). In conclusion, we found that either genetic or pharmacological activation of Akt protected the heart against acute ischaemia-reperfusion injury by modulating mitochondrial morphology.

  6. Cyclic nucleotide phosphodiesterase 3A1 protects the heart against ischemia-reperfusion injury.

    PubMed

    Oikawa, Masayoshi; Wu, Meiping; Lim, Soyeon; Knight, Walter E; Miller, Clint L; Cai, Yujun; Lu, Yan; Blaxall, Burns C; Takeishi, Yasuchika; Abe, Jun-ichi; Yan, Chen

    2013-11-01

    Phosphodiesterase 3A (PDE3A) is a major regulator of cAMP in cardiomyocytes. PDE3 inhibitors are used for acute treatment of congestive heart failure, but are associated with increased incidence of arrhythmias and sudden death with long-term use. We previously reported that chronic PDE3A downregulation or inhibition induced myocyte apoptosis in vitro. However, the cardiac protective effect of PDE3A has not been demonstrated in vivo in disease models. In this study, we examined the role of PDE3A in regulating myocardial function and survival in vivo using genetically engineered transgenic mice with myocardial overexpression of the PDE3A1 isozyme (TG). TG mice have reduced cardiac function characterized by reduced heart rate and ejection fraction (52.5±7.8% vs. 83.9±4.7%) as well as compensatory expansion of left ventricular diameter (4.19±0.19mm vs. 3.10±0.18mm). However, there was no maladaptive increase of fibrosis and apoptosis in TG hearts compared to wild type (WT) hearts, and the survival rates also remained the same. The diminution of cardiac contractile function is very likely attributed to a decrease in beta-adrenergic receptor (β-AR) response in TG mice. Importantly, the myocardial infarct size (4.0±1.8% vs. 24.6±3.8%) and apoptotic cell number (1.3±1.0% vs. 5.6±1.5%) induced by ischemia/reperfusion (I/R) injury were significantly attenuated in TG mice. This was associated with decreased expression of inducible cAMP early repressor (ICER) and increased expression of anti-apoptotic protein BCL-2. To further verify the anti-apoptotic effects of PDE3A1, we performed in vitro apoptosis study in isolated adult TG and WT cardiomyocytes. We found that the apoptotic rates stimulated by hypoxia/reoxygenation or H2O2 were indeed significantly reduced in TG myocytes, and the differences between TG and WT myocytes were completely reversed in the presence of the PDE3 inhibitor milrinone. These together indicate that PDE3A1 negatively regulates β-AR signaling

  7. Heart Rate and the Role of the Active Receiver during Contingent Electric Shock for Severe Self-Injurious Behavior

    ERIC Educational Resources Information Center

    Duker, Pieter C.; Van den Munckhof, Marcia

    2007-01-01

    Five individuals, who were treated for severe self-injurious behaviors (SIB) with contingent electric shock, participated. Hereby, each occurrence of the target response was followed by a remotely administered aversive consequence. Participants' heart rates were compared at times when the active device of the equipment for the above procedure was…

  8. Heart Rate and the Role of the Active Receiver during Contingent Electric Shock for Severe Self-Injurious Behavior

    ERIC Educational Resources Information Center

    Duker, Pieter C.; Van den Munckhof, Marcia

    2007-01-01

    Five individuals, who were treated for severe self-injurious behaviors (SIB) with contingent electric shock, participated. Hereby, each occurrence of the target response was followed by a remotely administered aversive consequence. Participants' heart rates were compared at times when the active device of the equipment for the above procedure was…

  9. A unique nail gun injury to the heart with a delayed presentation.

    PubMed

    Jodati, Ahmadreza; Safaei, Naser; Toufan, Mehrnoush; Kazemi, Babak

    2011-09-01

    We describe a 24-year-old construction worker who was unaware that he had been shot by a pneumatic nail gun in the chest during work. After returning home, he felt some palpitations and mild shortness of breath, and in the mirror discovered a non-bleeding pinpoint skin wound in his upper chest. He admitted himself to the emergency department of a local hospital and, after a detailed history and a chest X-ray had been taken, he was surprisingly diagnosed with a penetrating nail injury to the heart and was referred to our center. Transthoracic echocardiography and chest computed tomography were done, and the patient was transported to the operating room. After the nail had been removed and the mitral valve repaired, the patient was discharged on the fifth postoperative day without any complications.

  10. Modulation of Mitochondrial Permeability Transition in Ischemia-Reperfusion Injury of the Heart. Advantages and Limitations.

    PubMed

    Di Lisa, Fabio; Bernardi, Paolo

    2015-01-01

    In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein that favors PTP opening. On the other hand, CyPD inhibition or deletion has been shown to worsen remodeling of the hypertrophic heart, an adverse outcome that must find an explanation within PTP modulation by CyPD. In this review, recent advancements in defining the molecular identity of the PTP are analyzed in relation to its pathophysiological functions and pharmacological modulation. In this respect, advantages and limitations of compounds targeting CyPD are discussed with the analysis of novel PTP inhibitors that do not interact with CyPD.

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

    PubMed Central

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

    2013-01-01

    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 was 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

  12. 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.

  13. Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

    PubMed Central

    Carvalho, Cristiano Marcelo Espinola; Silverio, Jaline Coutinho; da Silva, Andrea Alice; Pereira, Isabela Resende; Coelho, Janice Mery Chicarino; Britto, Constança Carvalho; Moreira, Otacílio Cruz; Marchevsky, Renato Sergio; Xavier, Sergio Salles; Gazzinelli, Ricardo Tostes; da Glória Bonecini-Almeida, Maria; Lannes-Vieira, Joseli

    2012-01-01

    Background The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2−/−) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Methodology Rhesus monkeys and C57BL/6 and Nos2−/− mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue. Results Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2−/− mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. Conclusion T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC

  14. Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury.

    PubMed

    Vilarinho, Karlos Alexandre Souza; de Oliveira, Pedro Paulo Martins; Saad, Mário José Abdalla; Eghtesady, Pirooz; Filho, Lindemberg Mota Silveira; Vieira, Reinaldo Wilson; Petrucci, Orlando

    2013-01-01

    The effect of erythropoietin (EPO) on neonatal hearts is not well understood. The current hypothesis is that EPO has protective effects against ischaemia-reperfusion when administered prior to ischaemia induction. Systolic and diastolic indices, as well as the Akt and extracellular-regulated kinase (Erk) signalling pathways, were studied in vivo using a neonatal pig heart model. Regional ischaemia was induced for 45 min by the ligation of the left anterior descending artery, followed by 90 min of reperfusion. The treatment groups consisted of: (i) untreated controls, (ii) treatment with EPO 3 min prior to ischaemia and (iii) treatment with EPO 24 h before ischaemia. Sophisticated myocardial contractility indices were assessed by pressure/volume loops of the left ventricle. The Akt and Erk pathways were evaluated via a western blot. Elastance was found to be higher in the group receiving EPO 3 min prior to ischaemia. In addition, preload recruitable stroke work was higher for both groups receiving EPO prior to ischaemia when compared with controls. The time constant of the isovolumic relaxation and end-diastolic pressure-volume relationship did not differ between the three groups after 90 min of reperfusion. Furthermore, EPO treatment enhanced phosphorylation of Akt, but not Erk, and EPO-treated animals showed lower levels of apoptosis-related proteins. EPO had a protective effect on neonatal systolic function after ischaemia/reperfusion injury, but no effect on diastolic function. This cardioprotective effect might be mediated by the activation of the Akt pathway.

  15. Lung capillary injury and repair in left heart disease: a new target for therapy?

    PubMed

    Azarbar, Sayena; Dupuis, Jocelyn

    2014-07-01

    The lungs are the primary organs affected in LHD (left heart disease). Increased left atrial pressure leads to pulmonary alveolar-capillary stress failure, resulting in cycles of alveolar wall injury and repair. The reparative process causes the proliferation of MYFs (myofibroblasts) with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. Although the resultant reduction in vascular permeability is initially protective against pulmonary oedema, the process becomes maladaptive causing a restrictive lung syndrome with impaired gas exchange. This pathological process may also contribute to PH (pulmonary hypertension) due to LHD. Few clinical trials have specifically evaluated lung structural remodelling and the effect of related therapies in LHD. Currently approved treatment for chronic HF (heart failure) may have direct beneficial effects on lung structural remodelling. In the future, novel therapies specifically targeting the remodelling processes may potentially be utilized. In the present review, we summarize data supporting the clinical importance and pathophysiological mechanisms of lung structural remodelling in LHD and propose that this pathophysiological process should be explored further in pre-clinical studies and future therapeutic trials.

  16. Prenatal head growth and white matter injury in hypoplastic left heart syndrome.

    PubMed

    Hinton, Robert B; Andelfinger, Gregor; Sekar, Priya; Hinton, Andrea C; Gendron, Roxanne L; Michelfelder, Erik C; Robitaille, Yves; Benson, D Woodrow

    2008-10-01

    Children with hypoplastic left heart syndrome (HLHS) have an increased prevalence of central nervous system (CNS) abnormalities. The extent to which this problem is due to CNS maldevelopment, prenatal ischemia, postnatal chronic cyanosis and/or multiple exposures to cardiopulmonary bypass is unknown. To better understand the etiology of CNS abnormalities in HLHS, we evaluated 68 neonates with HLHS; in 28 cases, both fetal ultrasound and echocardiogram data were available to assess head size, head growth and aortic valve anatomy (atresia or stenosis). In addition, we evaluated neuropathology in 11 electively aborted HLHS fetuses. The mean head circumference percentile in HLHS neonates was significantly smaller than HLHS fetuses (22 +/- 2% versus 40 +/- 4%, p < 0.001). A significant decrease in head growth, defined as a 50% reduction in head circumference percentile, was observed in half (14/28) of HLHS fetuses and nearly a quarter (6/28) were already growth restricted (injury of varying severity. These patterns of prenatal head growth and brain histopathology identify a spectrum of abnormal CNS development and/or injury in HLHS fetuses.

  17. Attenuation of Ca paradox injury in guinea pig heart by K+ channel blocker, d-sotalol.

    PubMed

    Tribulova, N; Sosner, I; Varon, D; Manoach, M

    1999-01-01

    D-sotalol was shown to prevent Ca overload and intermyocyte uncoupling. The aim of this study was to investigate the effect of d-sotalol in Ca paradox conditions. Guinea pig hearts were perfused at 37 degrees C and constant pressure with oxygenated Tyrode solution. Ca paradox was induced by 10 min Ca free perfusion followed by 10 min Ca repletion. 10(-6) M d-sotalol was administered either during Ca depletion or during Ca repletion period. Electrical activity and ventricular contraction were simultaneously recorded and subcellular alterations were analysed. The contraction terminated in 5 min of Ca free perfusion and electrical activity disappeared within 5 min of Ca repletion. Nonuniform injury of myocardial tissue was observed. The majority of cardiomyocytes were irreversibly injured and profound dissociation of intercellular junctions was detected. Administration of d-sotalol during Ca free period preserved electrical activity and restored ventricular contraction accompanied by apparent protection of the ultrastructure, including intercellular connections. Uniform patterns of sarcomeres reflected synchronous contraction and protection of junctional couplings. In conclusion, d-sotalol attenuates Ca paradox injury. It seems that the protective effect of d-sotalol is most likely related to inhibition of potassium efflux antagonizing Na loading during Ca depletion period, as well as to attenuation of excess of [Ca2+]i via acceleration of sarcoplasmic Ca exchange during Ca repletion.

  18. [Association between fluid overload and acute renal injury after congenital heart disease surgery in infants].

    PubMed

    Luo, De-Qiang; Chen, Zi-Li; Dai, Wei; Chen, Feng

    2017-04-01

    To study the association between fluid overload and acute kidney injury (AKI) after congenital heart disease surgery in infants. A retrospective analysis was performed on 88 infants aged less than 6 months who underwent a radical surgery for congenital heart disease. The treatment outcomes were compared between the infants with AKI after surgery and those without. The effect of cumulative fluid overload on treatment outcomes 2 days after surgery was analyzed. The risk factors for the development of AKI after surgery were assessed by logistic regression analysis. Compared with those without AKI after surgery, the patients with AKI had younger age, lower body weights, higher serum creatinine levels and higher vasoactive-inotropic score, as well as longer durations of intraoperative extracorporeal circulation and aortic occlusion (P<0.05). Compared with those without AKI after surgery, the patients with AKI had a higher transfusion volume, a higher incidence rate of low cardiac output syndrome, a longer duration of mechanical ventilation, a longer length of stay in the intensive care unit (ICU), a longer length of hospital stay, a higher application rate of extracorporeal membrane oxygenation, a higher 30-day mortality rate, and higher levels of cumulative fluid overload 2 and 3 days after surgery (P<0.05). The logistic regression analysis showed that fluid overload and low cardiac output syndrome were major risk factors for the development of AKI after surgery. The children with cumulative fluid overload >5% at 2 days after surgery had a higher incidence rate of low cardiac output syndrome, a longer duration of mechanical ventilation, a longer length of stay in the ICU, a longer length of hospital stay, and a higher mortality rate (P<0.05). Infants with fluid overload after surgery for congenital heart disease tend to develop AKI, and fluid overload may be associated with poor outcomes after surgery.

  19. Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase.

    PubMed

    Hull, Travis D; Bolisetty, Subhashini; DeAlmeida, Angela C; Litovsky, Silvio H; Prabhu, Sumanth D; Agarwal, Anupam; George, James F

    2013-08-01

    The protective effect of heme oxygenase-1 (HO-1) expression in cardiovascular disease has been previously demonstrated using transgenic animal models in which HO-1 is constitutively overexpressed in the heart. However, the temporal requirements for protection by HO-1 induction relative to injury have not been investigated, but are essential to employ HO-1 as a therapeutic strategy in human cardiovascular disease states. Therefore, we generated mice with cardiac-specific, tamoxifen (TAM)-inducible overexpression of a human HO-1 (hHO-1) transgene (myosin heavy chain (MHC)-HO-1 mice) by breeding mice with cardiac-specific expression of a TAM-inducible Cre recombinase (MHC-Cre mice), with mice containing an hHO-1 transgene preceded by a floxed-stop signal. MHC-HO-1 mice overexpress HO-1 mRNA and the enzymatically active protein following TAM administration (40 mg/kg body weight on 2 consecutive days). In MHC-Cre controls, TAM administration leads to severe, acute cardiac toxicity, cardiomyocyte necrosis, and 80% mortality by day 3. This cardiac toxicity is accompanied by a significant increase in inflammatory cells in the heart that are predominantly neutrophils. In MHC-HO-1 mice, HO-1 overexpression ameliorates the depression of cardiac function and high mortality rate observed in MHC-Cre mice following TAM administration and attenuates cardiomyocyte necrosis and neutrophil infiltration. These results highlight that HO-1 induction is sufficient to prevent the depression of cardiac function observed in mice with TAM-inducible Cre recombinase expression by protecting the heart from necrosis and neutrophil infiltration. These findings are important because MHC-Cre mice are widely used in cardiovascular research despite the limitations imposed by Cre-induced cardiac toxicity, and also because inflammation is an important pathological component of many human cardiovascular diseases.

  20. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    PubMed Central

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  1. The association between cardiac physiology, acquired brain injury, and postnatal brain growth in critical congenital heart disease.

    PubMed

    Peyvandi, Shabnam; Kim, Hosung; Lau, Joanne; Barkovich, A James; Campbell, Andrew; Miller, Steven; Xu, Duan; McQuillen, Patrick

    2017-08-24

    To assess the trajectory of perioperative brain growth in relationship to cardiac diagnosis and acquired brain injuries. This was a cohort study of term neonates with hypoplastic left heart syndrome (HLHS) and transposition of the great arteries (TGA). Subjects underwent magnetic resonance imaging of the brain pre- and postoperatively to determine the severity of brain injury and total and regional brain volumes by the use of automated morphometry. Comparisons were made by cardiac lesion and injury status. A total of 79 subjects were included (49, TGA; 30, HLHS). Subjects with HLHS had more postoperative brain injury (55.6% vs 30.4%, P = .03) and more severe brain injury (moderate-to-severe white matter [WM] injury, P = .01). Total and regional perioperative brain growth was not different by brain injury status (either pre- or postoperative). However, subjects with moderate-to-severe WM injury had a slower rate of brain growth in WM and gray matter compared with those with no injury. Subjects with HLHS had a slower rate of growth globally and in WM and deep gray matter as compared with TGA (total brain volume: 12 cm(3)/wk vs 7 cm(3); WM: 2.1 cm(3)/wk vs 0.6 cm(3); deep gray matter: 1.5 cm(3)/wk vs 0.7 cm(3); P < .001), after we adjusted for gestational age at scan and the presence of brain injury. This difference remained after excluding subjects with moderate-to-severe WM injury. Neonates with HLHS have a slower rate of global and regional brain growth compared with TGA, likely related to inherent physiologic differences postoperatively. These findings demonstrate the complex interplay between cardiac lesion, brain injury, and brain growth. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death

    PubMed Central

    Aurora, Arin B.; Mahmoud, Ahmed I.; Luo, Xiang; Johnson, Brett A.; van Rooij, Eva; Matsuzaki, Satoshi; Humphries, Kenneth M.; Hill, Joseph A.; Bassel-Duby, Rhonda; Sadek, Hesham A.; Olson, Eric N.

    2012-01-01

    Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca2+ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca2+ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca2+ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca2+ influx; and to repression of several downstream effectors of Ca2+ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca2+ homeostasis and survival during cardiac injury. PMID:22426211

  3. Modification of caffeine-induced injury in Ca2+-free perfused rat hearts. Relationship to the calcium paradox.

    PubMed Central

    Vander Heide, R. S.; Altschuld, R. A.; Lamka, K. G.; Ganote, C. E.

    1986-01-01

    The pathogenesis of the calcium paradox has not been established. In calcium-free perfused hearts, caffeine, which releases calcium from the sarcoplasmic reticulum, causes severe myocardial injury, with creatine kinase (CK) release and contraction band necrosis similar in many respects to the calcium paradox. It has been postulated that contracture, initiated by a small rise in intracellular calcium, may cause sarcolemmal injury in both the calcium paradox and caffeine-induced myocardial injury. The present study was initiated to determine whether interventions which modulate caffeine-induced contracture will also correspondingly alter cellular injury. The effects of caffeine dose, procaine, extended calcium-free perfusion, elevated potassium, temperature, and increasing intracellular sodium on caffeine-induced contracture were examined in Langendorff-perfused adult rat hearts. Caffeine-induced contracture at 22 C increased over a dose range of 5-40 mM caffeine. Procaine, which inhibits caffeine-induced calcium release at doses between 5 and 20 mM, progressively reduced contracture caused by addition of 20 mM caffeine at 22 C. Hearts perfused with calcium-free solution containing 16 mM K+ showed a reduction in caffeine-induced contracture. Extended calcium-free perfusion (20 minutes) at temperatures from 18 to 37 C resulted in a progressive reduction of caffeine-induced contracture. Each of these interventions was also found to inhibit caffeine-induced injury at 37 C. Low temperature was found to have complex effects. Hypothermia enhanced caffeine contractures but also protected hearts from cell separations and CK release. Increasing intracellular sodium was found to enhance caffeine-induced contracture at 37 C. There was a direct correlation between measured intracellular sodium levels and the magnitude and duration of caffeine-induced contracture. These results demonstrate a direct correlation between the magnitude of contracture and myocardial injury in calcium

  4. Heart rate' based training intensity and its impact on injury incidence amongst elite level professional soccer players.

    PubMed

    Owen, Adam L; Forsyth, Jacky J; Wong, Del P; Dellal, Alexandre; Connelly, Sean; Chamari, Karim

    2014-12-24

    Elite level professional soccer players are suggested to have increased physical, technical, tactical and psychological capabilities when compared to their sub-elite counterparts. Ensuring these players remain at the elite level generally involves training many different bodily systems to a high intensity or level within a short duration. This study aimed to examine whether an increase in training volume at high intensity levels were related to injury incidence, or increased the odds of sustaining an injury. Training intensity was monitored through time spent in high- (T-HI) and very high- (T-VHI) intensity zones of 85-<90% and ≥90% of maximal heart rate (HRmax), and all injuries were recorded over two consecutive seasons. Twenty-three elite professional male soccer players (mean±SD age 25.6±4.6 years, stature 181.8±6.8 cm, and body mass of 79.3±8.1 kg) were studied throughout the 2-yrs span of the investigation. The results showed a mean total injury incidence of 18.8 (95% CI 14.7 to 22.9) injuries per 1000 h of exposure. Significant correlations were found between training volume at T-HI and injury incidence (r=0.57, p=0.005). Further analysis revealed how players achieving more time in the T-VHI zone during training increased the odds of sustaining a match injury (odds ratio=1.87, 95% CI 1.12 to 3.12, p=0.02), but did not increase the odds of sustaining a training injury. Reducing the number of competitive match injuries amongst elite professional level players may be possible if greater focus is placed on the training intensity and volume over a period of time ensuring the potential reduction of fatigue or overuse injuries. In addition, it is important to understand the optimal training load at which adaptation occurs without raising the risk of injury.

  5. [Protective effect of total glycosides of Ranunculus japonicus on myocardial ischemic-reperfusion injury in isolated rat hearts].

    PubMed

    Gao, Xiao-Wei; Liu, Yuan; Yang, Zhi-Cheng; Tan, Yu-Zhi

    2014-08-01

    To study the protective effect of total glycosides of Ranunculus japonicus (TGRJ) on myocardial ischemic-reperfusion injury in isolated rat hearts. The SD rats were randomly divided into normal control group, ischemia-reperfusion group, and TGRJ in 0.05, 0.10 and 0.20 mg/mL groups. The ischemia-reperfusion injury model was built using Langendroff isolated rats hearts perfusion system. The indexes of heart function such as heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular systolic pressure maximum rate of rise (+ dp/dt(max)), left ventricular diastolic pressure maximum rate of descent (-dp/dt(max)) and coronary flow (CF) before ischemia and later at 1, 5, 10, 20, 30 and 40 min after reperfusion were recorded. The activity of Lactate dehydrogenase (LDH) and creatine kinase (CK) at 20 and 40 min after reperfusion were determined. The myocardial tissues were stained with Triphenyltetrazolium chloride (TTC) and the percentage of myocardial infarction area was calculated. HR, LVDP, +dp/dt(max) and CF of the I/R group were significantly decreased after reperfusion, LDH and CK levels were increased and the area of myocardial infraction was 58.78%. TGRJ had improving effect on all above indexes. TGRJ has protective effet on the myo- cardial ischemic-reperfusion injury.

  6. Estrogen Regulates Angiotensin II Receptor Expression Patterns and Protects the Heart from Ischemic Injury in Female Rats1

    PubMed Central

    Xue, Qin; Xiao, Daliao; Zhang, Lubo

    2015-01-01

    Previous studies have shown that female offspring are resistant to fetal stress-induced programming of ischemic-sensitive phenotype in the heart; however, the mechanisms responsible remain unclear. The present study tested the hypothesis that estrogen plays a role in protecting females in fetal programming of increased heart vulnerability. Pregnant rats were divided into normoxic and hypoxic (10.5% O2 from Day 15 to 21 of gestation) groups. Ovariectomy (OVX) and estrogen (E2) replacement were performed in 8-wk-old female offspring. Hearts of 4-mo-old females were subjected to ischemia and reperfusion injury in a Langendorff preparation. OVX significantly decreased postischemic recovery of left ventricular function and increased myocardial infarction, and no difference was observed between normoxic and hypoxic groups. The effect of OVX was rescued by E2 replacement. OVX decreased the binding of glucocorticoid receptor (GR) to glucocorticoid response elements at angiotensin II type 1 (Agtr1) and type 2 (Agtr2) receptor promoters, resulting in a decrease in Agtr1 and an increase in Agtr2 in the heart. Additionally, OVX decreased estrogen receptor (ER) expression in the heart and inhibited ER/GR interaction in binding to glucocorticoid response elements at the promoters. Consistent with the changes in Agtrs, OVX significantly decreased Prkce abundance in the heart. These OVX-induced changes were abrogated by E2 replacement. The results indicate that estrogen is not directly responsible for the sex dimorphism in fetal programming of heart ischemic vulnerability but suggest a novel mechanism of estrogen in regulating cardiac Agtr1/Agtr2 expression patterns and protecting female hearts against ischemia and reperfusion injury. PMID:25972014

  7. [Mechanism of heart and lung injury induced by cerebral ischemia/reperfusion in both young and old mice].

    PubMed

    Lyu, Yanni; Fu, Longsheng; Qian, Yisong; Jiang, Mingjin; He, Libiao; Ouyang, Aijun; Zheng, Yu

    2017-06-01

    Objective To study the mechanism of heart and lung injury after cerebral ischemia/reperfusion in mice. Methods C57BL/6J mice were divided into young and old groups according to their ages, the former being 5-6 months old and the latter being 20-21 months old. Each group was divided into five subgroups subjected to sham operation, middle cerebral artery occlusion for 1-hour ischemia followed by 1-, 12-, 24-, 48-hour reperfusion. At different reperfusion time, HE and TUNEL staining were used to observe the morphological changes of heart and lung tissues; meanwhile, chemical colorimetry was performed to determine the changes of cardiac Na(+)-K(+)-ATPase and Ca(2+)-ATPase; the lung indexes were evaluated; the levels of nuclear factor (NF)-κBp65, p-NF-κBp65, IκBα, p-IκBα were detected by Western blotting; the levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) were determined by ELISA; and the release of NO was examined by colorimetry. Results We observed inflammatory responses in the lung tissues of young and old mice at 24-hour reperfusion and 1-hour reperfusion, respectively, and hemorrhage in the heart tissues of young and old mice at 24-hour reperfusion and 12-hour reperfusion, respectively.Lung tissues showed earlier response to the stimulation of cerebral ischemia/reperfusion than heart tissues did. Meanwhile, the results of Na(+)-K(+)-ATPase, Ca(2+)-ATPase, lung index, NF-κB signaling pathway and inflammatory cytokines in young and old mice were consistent with histological changes of heart and lung tissues. Conclusion Cerebral ischemia/reperfusion can cause heart and lung tissue injury in the old mice, and energy metabolism and inflammation cascade are the main mechanisms of the injury.

  8. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart.

    PubMed

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia.

  9. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart

    PubMed Central

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Objective: Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. Materials and Methods: The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. Results: The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). Conclusion: It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia. PMID:26693414

  10. The ethanolic extract of Kaempferia parviflora reduces ischaemic injury in rat isolated hearts.

    PubMed

    Malakul, Wachirawadee; Ingkaninan, Kornkanok; Sawasdee, Pattara; Woodman, Owen L

    2011-09-01

    The ethanolic extract of Kaempferia parviflora (KPE) has been reported to contain a range of flavonoids and to enhance endothelial synthesis of NO. We investigated the vascular relaxant, antioxidant and cardioprotective activities of KPE. Vascular function was assessed in rat aortic rings and superoxide generation determined using lucigenin enhanced chemiluminescence. Ischaemia and reperfusion were induced in rat isolated, perfused hearts. KPE caused vasorelaxation (R(max) 102 ± 2%), which was partly inhibited by removal of the endothelium (R(max) 91 ± 1%) or by N(G)-nitro-l-arginine (L-NNA, R(max) 83 ± 3%) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, R(max) 80 ± 2%). In addition KPE caused concentration-dependent inhibition of the contractile response to exogenous Ca(2+). KPE (10(-3)M) also significantly inhibited superoxide radical generation induced by of xanthine/xanthine oxidase (2.3 ± 0.4% of control) to a similar extent to the xanthine oxidase inhibitor allopurinol (10(-4)M, 1.6 ± 0.5%) or by rat isolated aorta in the presence of NADPH (30.0 ± 6.3% of control) similarly to the NADPH oxidase inhibitor diphenyliodonium (5 × 10(-6)M, 23.1 ± 5.6%). In the presence of oxidant stress generated by pyrogallol endothelium-dependent relaxation of rat aortic rings was impaired (ACh R(max) control 99 ± 1%; pyrogallol 44 ± 5%), an effect that was significantly reduced by KPE (10(-4)M, ACh R(max) 82 ± 4%). In addition, KPE was found to attenuate the ventricular dysfunction caused by 20 min global ischaemia and 30 min reperfusion (I/R) in rat isolated hearts (dP/dt IR 1016 ± 242, IR+KPE 2238±233 mm Hg/s). KPE is an effective vasodilator and antioxidant that is able to prevent myocardial ischaemia-reperfusion injury. We suggest that KPE may be useful as an adjunct to thrombolytic therapy in the management of reperfusion injury. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  11. Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts.

    PubMed

    Argaud, Laurent; Gateau-Roesch, Odile; Augeul, Lionel; Couture-Lepetit, Elisabeth; Loufouat, Joseph; Gomez, Ludovic; Robert, Dominique; Ovize, Michel

    2008-01-01

    Ca(2+) is the main trigger for mitochondrial permeability transition pore opening, which plays a key role in cardiomyocyte death after ischemia-reperfusion. We investigated whether a reduced accumulation of mitochondrial Ca(2+) might explain the attenuation of lethal reperfusion injury by postconditioning. Anesthetized New Zealand White rabbits underwent 30 min of ischemia, followed by either 240 (infarct size protocol) or 60 (mitochondria protocol) min of reperfusion. They received either no intervention (control), preconditioning by 5-min ischemia and 5-min reperfusion, postconditioning by four cycles of 1-min reperfusion and 1-min ischemia at the onset of reflow, or pharmacological inhibition of the transition pore opening by N-methyl-4-isoleucine-cyclosporin (NIM811; 5 mg/kg iv) given at reperfusion. Area at risk and infarct size were assessed by blue dye injection and triphenyltetrazolium chloride staining. Mitochondria were isolated from the risk region for measurement of 1) Ca(2+) retention capacity (CRC), and 2) mitochondrial content of total (atomic absorption spectrometry) and ionized (potentiometric technique) calcium concentration. CRC averaged 0.73 +/- 0.16 in control vs. 4.23 +/- 0.17 mug Ca(2+)/mg proteins in shams (P < 0.05). Postconditioning, preconditioning, or NIM811 significantly increased CRC (P < 0.05 vs. control). In the control group, total and free mitochondrial calcium significantly increased to 2.39 +/- 0.43 and 0.61 +/- 0.10, respectively, vs. 1.42 +/- 0.09 and 0.16 +/- 0.01 mug Ca(2+)/mg in sham (P < 0.05). Surprisingly, whereas total and ionized mitochondrial Ca(2+) decreased in preconditioning, it significantly increased in postconditioning and NIM811 groups. These data suggest that retention of calcium within mitochondria may explain the decreased reperfusion injury in postconditioned (but not preconditioned) hearts.

  12. The effects of Melissa officinalis (lemon balm) pretreatment on the resistance of the heart to myocardial injury.

    PubMed

    Joukar, Siyavash; Asadipour, Haleh; Sheibani, Mohammad; Najafipour, Hamid; Dabiri, Shahriar

    2016-01-01

    The antihyperlipidemic, antiarrhythmic, neuroprotective and hepatoprotective effects of Melissa officinalis L. (Lamiaceae) have been reported. However, no study has examined its effects on the resistance of the heart to stressful conditions. The objective of this study is to evaluate the effects of aqueous extract of M. officinalis aerial parts on Wistar rat heart with/without cardiac injury. Animals were grouped as control, isoproterenol (ISO), M. officinalis without (M50, M100, and M200) and with isoproterenol (M50 + ISO, M100 + ISO, and M200 + ISO). The aqueous extract of M. officinalis was orally administered at dosages of 50, 100, and 200 mg/kg/d, respectively, for 7 consecutive days. On the 6th and 7th day, ISO, M50 + ISO, M100 + ISO, and M200 + ISO groups received 85 mg/kg of isoproterenol for myocardial injury induction. On day 8, hemodynamic parameters were recorded and samplings were done. The extract (50, 100, and 200 mg/kg) significantly reduced the heart rate (264 ± 5, 259 ± 5 and 281 ± 3 versus 377 ± 13 in control group, p < 0.01). Blood pressure was significantly decreased in M50 + ISO (75 ± 5) versus M50 (110 ± 6) and M100 + ISO (72 ± 6) versus M100 (105 ± 5 mmHg, p < 0.01). The malondialdehyde levels of the injured hearts were lower in M50 + ISO and M100 + ISO groups than in the ISO group (p < 0.05). Serum cardiac troponin I was higher in the M200 + ISO group (5.1 ± 1.7) than in the ISO group (2.7 ± 0.7 ng/ml, p < 0.05). The lower dose of extract, by improving the balance of the redox system and by reducing the heart rate, may increase the heart resistance to injury. However, the higher doses of extract may intensify the injury of ischemic heart.

  13. Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury

    PubMed Central

    Kaludercic, Nina; Carpi, Andrea; Menabò, Roberta; Lisa, Fabio Di; Paolocci, Nazareno

    2010-01-01

    Recent evidence highlights monoamine oxidases (MAO) as another prominent source of oxidative stress. MAO are a class of enzymes located in the outer mitochondrial membrane, deputed to the oxidative breakdown of key neurotransmitters such as norepinephrine, epinephrine and dopamine, and in the process generate H2O2. All these monoamines are endowed with potent modulatory effects on myocardial function. Thus, when the heart is subjected to chronic neuro-hormonal and/or peripheral hemodynamic stress, the abundance of circulating/tissue monoamines can make MAO-derived H2O2 production particularly prominent. This is the case of acute cardiac damage due to ischemia/reperfusion injury or, on a more chronic stand, of the transition from compensated hypertrophy to overt ventricular dilation/pump failure. Here, we will first briefly discuss mitochondrial status and contribution to acute and chronic cardiac disorders. We will illustrate possible mechanisms by which MAO activity affects cardiac biology and function, along with a discussion as to their role as a prominent source of reactive oxygen species. Finally, we will speculate on why MAO inhibition might have therapeutic value for treating cardiac affections of ischemic and non-ischemic origin. PMID:20869994

  14. Propofol Protects the Immature Rabbit Heart against Ischemia and Reperfusion Injury: Impact on Functional Recovery and Histopathological Changes

    PubMed Central

    Shirakawa, Makoto; Imura, Hajime; Nitta, Takashi

    2014-01-01

    The general anesthetic propofol protects the adult heart against ischemia and reperfusion injury; however, its efficacy has not been investigated in the immature heart. This work, for the first time, investigates the cardioprotective efficacy of propofol at clinically relevant concentrations in the immature heart. Langendorff perfused rabbit hearts (7–12 days old) were exposed to 30 minutes' global normothermic ischemia followed by 40 minutes' reperfusion. Left ventricular developed pressure (LVDP) and coronary flow were monitored throughout. Lactate release into coronary effluent was measured during reperfusion. Microscopic examinations of the myocardium were monitored at the end of reperfusion. Hearts were perfused with different propofol concentrations (1, 2, 4, and 10 μg/mL) or with cyclosporine A, prior to ischemic arrest and for 20 minutes during reperfusion. Propofol at 4 and 10 μg/mL caused a significant depression in LVDP prior to ischemia. Propofol at 2 μg/mL conferred significant and maximal protection with no protection at 10 μg/mL. This protection was associated with improved recovery in coronary flow, reduced lactate release, and preservation of cardiomyocyte ultrastructure. The efficacy of propofol at 2 μg/mL was similar to the effect of cyclosporine A. In conclusion, propofol at a clinically relevant concentration is cardioprotective in the immature heart. PMID:25243155

  15. Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

    PubMed Central

    Wu, Yang; Leng, Yan; Meng, Qingtao; Xue, Rui; Zhao, Bo; Zhan, Liying

    2017-01-01

    Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim. PMID:28191472

  16. BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase.

    PubMed

    Szabados, E; Literati-Nagy, P; Farkas, B; Sumegi, B

    2000-04-15

    The protective effect of O-(3-piperidino-2-hydroxy-1-propyl)nicotinic amidoxime (BGP-15) against ischemia-reperfusion-induced injury was studied in the Langendorff heart perfusion system. To understand the molecular mechanism of the cardioprotection, the effect of BGP-15 on ischemic-reperfusion-induced reactive oxygen species (ROS) formation, lipid peroxidation single-strand DNA break formation, NAD(+) catabolism, and endogenous ADP-ribosylation reactions were investigated. These studies showed that BGP-15 significantly decreased leakage of lactate dehydrogenase, creatine kinase, and aspartate aminotransferase in reperfused hearts, and reduced the rate of NAD(+) catabolism. In addition, BGP-15 dramatically decreased the ischemia-reperfusion-induced self-ADP-ribosylation of nuclear poly(ADP-ribose) polymerase(PARP) and the mono-ADP-ribosylation of an endoplasmic reticulum chaperone GRP78. These data raise the possibility that BGP-15 may have a direct inhibitory effect on PARP. This hypothesis was tested on isolated enzyme, and kinetic analysis showed a mixed-type (noncompetitive) inhibition with a K(i) = 57 +/- 6 microM. Furthermore, BGP-15 decreased levels of ROS, lipid peroxidation, and single-strand DNA breaks in reperfused hearts. These data suggest that PARP may be an important molecular target of BGP-15 and that BGP-15 decreases ROS levels and cell injury during ischemia-reperfusion in the heart by inhibiting PARP activity.

  17. The incidence and economic costs of cancer, motor vehicle injuries, coronary heart disease, and stroke: a comparative analysis.

    PubMed Central

    Hartunian, N S; Smart, C N; Thompson, M S

    1980-01-01

    The economic impact of disease and injury has most often been calculated by examining the costs associated with the prevalence of the impairments in the reference year. An alternative accounting approach is to assign all disease costs to the year of incidence, an approach which entails present-valuing to the year of incidence both health care expenditures and lost productivity. The incidence approach is the more appropriate for gauging the economic gains achievable through prevention, immediate rehabilitation, and arresting progression. Incidence-based costs have been estimated for the United States in 1975 for cancer, coronary heart disease, motor vehicle injuries, and stroke. A noteworthy finding is the relative economic importance of motor vehicle injuries, which frequently have been overlooked in the ordering of public health expenditure priorities. After cancer, which generated approximately $23.1 billion in present-valued costs in 1975 (discounted at 6 per cent), motor vehicle injuries and coronary heart disease constitute the next most expensive conditions--having generated estimated annual costs of $14.4 billion and $13.7 billion, respectively. Stroke, at $6.5 billion, follows in economic importance. PMID:7435742

  18. Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney.

    PubMed

    Gobe, Glenda C; Morais, Christudas; Vesey, David A; Johnson, David W

    2013-07-01

    There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure. A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.

  19. The second member of transient receptor potential-melastatin channel family protects hearts from ischemia-reperfusion injury

    PubMed Central

    Miller, Barbara A.; Wang, JuFang; Hirschler-Laszkiewicz, Iwona; Gao, Erhe; Song, Jianliang; Zhang, Xue-Qian; Koch, Walter J.; Madesh, Muniswamy; Mallilankaraman, Karthik; Gu, Tongda; Chen, Shu-jen; Keefer, Kerry; Conrad, Kathleen; Feldman, Arthur M.

    2013-01-01

    The second member of the transient receptor potential-melastatin channel family (TRPM2) is expressed in the heart and vasculature. TRPM2 channels were expressed in the sarcolemma and transverse tubules of adult left ventricular (LV) myocytes. Cardiac TRPM2 channels were functional since activation with H2O2 resulted in Ca2+ influx that was dependent on extracellular Ca2+, was significantly higher in wild-type (WT) myocytes compared with TRPM2 knockout (KO) myocytes, and inhibited by clotrimazole in WT myocytes. At rest, there were no differences in LV mass, heart rate, fractional shortening, and +dP/dt between WT and KO hearts. At 2–3 days after ischemia-reperfusion (I/R), despite similar areas at risk and infarct sizes, KO hearts had lower fractional shortening and +dP/dt compared with WT hearts. Compared with WT I/R myocytes, expression of the Na+/Ca2+ exchanger (NCX1) and NCX1 current were increased, expression of the α1-subunit of Na+-K+-ATPase and Na+ pump current were decreased, and action potential duration was prolonged in KO I/R myocytes. Post-I/R, intracellular Ca2+ concentration transients and contraction amplitudes were equally depressed in WT and KO myocytes. After 2 h of hypoxia followed by 30 min of reoxygenation, levels of ROS were significantly higher in KO compared with WT LV myocytes. Compared with WT I/R hearts, oxygen radical scavenging enzymes (SODs) and their upstream regulators (forkhead box transcription factors and hypoxia-inducible factor) were lower, whereas NADPH oxidase was higher, in KO I/R hearts. We conclude that TRPM2 channels protected hearts from I/R injury by decreasing generation and enhancing scavenging of ROS, thereby reducing I/R-induced oxidative stress. PMID:23376831

  20. Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass.

    PubMed

    Cheng, Chi; Xu, Jun-Mei; Yu, Tian

    2017-06-01

    To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits. Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected. In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis. CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus. Copyright © 2017. Published by Elsevier Inc.

  1. Cardiac Micro-Injury Measured by Troponin T Predicts Collagen Metabolism in Adults Aged ≥ 65 Years with Heart Failure

    PubMed Central

    Kop, Willem J.; Gottdiener, John S.; deFilippi, Christopher R.; Barasch, Eddy; Seliger, Stephen L.; Jenny, Nancy S.; Christenson, Robert H.

    2014-01-01

    Background Repeated myocardial micro-injuries lead to collagen deposition and fibrosis, thereby increasing the risk of clinical heart failure. Little is known about the longitudinal association between increases in myocardial injury and the biology of collagen synthesis and deposition. Methods and Results Repeated measures of highly sensitive cardiac troponin T (cTnT) were obtained in participants of the Cardiovascular Health Study (N-353; mean age=74±6 years, 52% women) at baseline and at three years follow-up. Biomarkers of collagen metabolism were obtained at follow-up and included carboxyterminal propeptide of procollagen type I (PIP), carboxyterminal telopeptide of type I collagen (CITP); and aminoterminal propeptide of procollagen III (PIIINP). Multivariable linear regression analyses were used to examine the association between baseline cTnT and changes in cTnT with collagen metabolism markers at follow-up, adjusting for demographics, heart failure status, and cardiovascular risk factors. Results indicated that cTnT increases over 3-years were significantly associated with higher levels of CITP (β=0.22, p<0.001) and PIIINP (β=0.12, p=0.035) at follow-up when adjusting for demographic, clinical and biochemical covariates including baseline cTnT. These associations were stronger in heart failure patients than in controls. Conclusions Increases in myocardial micro-injury measured by changes in cTnT adversely affect markers of collagen metabolism. These findings are important to the biology of myocardial fibrosis and tissue repair. Serial evaluation of cTnT combined with collagen metabolism markers may further elucidate the pathophysiology of heart failure. PMID:22685114

  2. Histone Deacetylases Exert Class-Specific Roles in Conditioning the Brain and Heart Against Acute Ischemic Injury

    PubMed Central

    Aune, Sverre E.; Herr, Daniel J.; Kutz, Craig J.; Menick, Donald R.

    2015-01-01

    Ischemia-reperfusion (IR) injury comprises a significant portion of morbidity and mortality from heart and brain diseases worldwide. This enduring clinical problem has inspired myriad reports in the scientific literature of experimental interventions seeking to elucidate the pathology of IR injury. Elective cardiac surgery presents perhaps the most viable scenario for protecting the heart and brain from IR injury due to the opportunity to condition the organs prior to insult. The physiological parameters for the preconditioning of vital organs prior to insult through mechanical and pharmacological maneuvers have been heavily examined. These investigations have revealed new insights into how preconditioning alters cellular responses to IR injury. However, the promise of preconditioning remains unfulfilled at the clinical level, and research seeking to implicate cell signals essential to this protection continues. Recent discoveries in molecular biology have revealed that gene expression can be controlled through posttranslational modifications, without altering the chemical structure of the genetic code. In this scenario, gene expression is repressed by enzymes that cause chromatin compaction through catalytic removal of acetyl moieties from lysine residues on histones. These enzymes, called histone deacetylases (HDACs), can be inhibited pharmacologically, leading to the de-repression of protective genes. The discovery that HDACs can also alter the function of non-histone proteins through posttranslational deacetylation has expanded the potential impact of HDAC inhibitors for the treatment of human disease. HDAC inhibitors have been applied in a very small number of experimental models of IR. However, the scientific literature contains an increasing number of reports demonstrating that HDACs converge on preconditioning signals in the cell. This review will describe the influence of HDACs on major preconditioning signaling pathways in the heart and brain. PMID

  3. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury.

    PubMed

    Ray, P S; Maulik, G; Cordis, G A; Bertelli, A A; Bertelli, A; Das, D K

    1999-07-01

    The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 microM for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09+/-4.88 mm Hg vs. 58.47+/-3.88 mm Hg, 68.87+/-5.07 mm Hg vs. 49.74+/-2.65 mm Hg and 51.67+/-3.95 mm Hg vs. 30.50+/-4.80 mm Hg at reperfusion timepoints R-15, R-60, and R-120, respectively). From R-30 onwards, aortic flow was markedly higher in the RVT treated group as compared with the control group, the differences being most significant at R-90 (32.45+/-2.19 ml/min vs. 19.83+/-1.62 ml/min) and R-120 (27.15+/-2.27 ml/min vs. 14.10+/-1.69 ml/min). In contrast to the KHB treated group, the RVT-treated group displayed significant reduction in MDA formation

  4. Prostaglandin E Receptor Subtype 4 Signaling in the Heart: Role in Ischemia/Reperfusion Injury and Cardiac Hypertrophy

    PubMed Central

    Cai, Yin; Tang, Eva Hoi Ching; Ma, Haichun

    2016-01-01

    Prostaglandin E2 (PGE2) is an endogenous lipid mediator, produced from the metabolism of arachidonic acids, upon the sequential actions of phospholipase A2, cyclooxygenases, and prostaglandin E synthases. The various biological functions governed by PGE2 are mediated through its four distinct prostaglandin E receptors (EPs), designated as EP1, EP2, EP3, and EP4, among which the EP4 receptor is the one most widely distributed in the heart. The availability of global or cardiac-specific EP4 knockout mice and the development of selective EP4 agonists/antagonists have provided substantial evidence to support the role of EP4 receptor in the heart. However, like any good drama, activation of PGE2-EP4 signaling exerts both protective and detrimental effects in the ischemic heart disease. Thus, the primary object of this review is to provide a comprehensive overview of the current progress of the PGE2-EP4 signaling in ischemic heart diseases, including cardiac hypertrophy and myocardial ischemia/reperfusion injury. A better understanding of PGE2-EP4 signaling should promote the development of more effective therapeutic approaches to treat the ischemic heart diseases without triggering unwanted side effects. PMID:27190998

  5. Nitrative Thioredoxin Inactivation as a Cause of Enhanced Myocardial Ischemia/Reperfusion Injury in the Aging Heart

    PubMed Central

    Zhang, Hangxiang; Tao, Ling; Jiao, Xiangying; Gao, Erhe; Lopez, Bernard L.; Christopher, Theodore A.; Koch, Walter; Ma, Xin L.

    2007-01-01

    Objective Several recent studies have demonstrated that thioredoxin (Trx) is an important anti-apoptotic/cytoprotective molecule. The present study was designed to determine whether Trx activity is altered in the aging heart in a way that may contribute to increased susceptibility to myocardial ischemia/reperfusion (MI/R). Methods and Results Compared to young animals, MI/R-induced cardiomyocyte apoptosis and infarct size were increased in aging animals (P<0.01). Trx activity was decreased in the aging heart before MI/R, and this difference was further amplified after MI/R. Trx expression was moderately increased and Trx nitration, a post-translational modification that inhibits Trx activity, was increased in the aging heart. Moreover, Trx-ASK1 complex formation was reduced and activity of p38 MAPK was increased. Treatment with FP15 (a peroxynitrite decomposition catalyst) reduced Trx nitration, increased Trx activity, restored Trx-ASK1 interaction, reduced P38 MAPK activity, attenuated caspase 3 activation and reduced infarct size in aging animals (p<0.01). Conclusions Our results demonstrated that Trx activity is decreased in the aging heart by post-translational nitrative modification. Interventions that restore Trx activity in the aging heart may be novel therapies to attenuate MI/R injury in aging patients. PMID:17561092

  6. Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart.

    PubMed Central

    Montrucchio, G.; Alloatti, G.; Mariano, F.; de Paulis, R.; Comino, A.; Emanuelli, G.; Camussi, G.

    1990-01-01

    This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion. Images Figure 8 PMID:2372044

  7. Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition.

    PubMed

    Javadov, S A; Lim, K H; Kerr, P M; Suleiman, M S; Angelini, G D; Halestrap, A P

    2000-01-14

    Diminishing oxidative stress may protect the heart against ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest. Isolated perfused Wistar rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working heart mode) in the presence or absence of propofol. MPT pore opening was determined using [3H]-2-deoxyglucose-6-phosphate ([3H]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress. Propofol (2 micrograms/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4 +/- 6.2 to 53.3 +/- 7.3 mmHg and left ventricular end diastolic pressure from 52.9 +/- 4.3 to 37.5 +/- 3.9 mmHg). Recovery was also improved in propofol (4 micrograms/ml) treated working hearts following cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42 +/- 0.05 to 0.60 +/- 0.03 J/s, representing 45-64% of baseline values, when compared to controls (P < 0.05). Propofol inhibited MPT pore opening during reperfusion, [3H]-DOG-6P entrapment being 16.7 vs. 22.5 ratio units in controls (P < 0.05). Mitochondria isolated from non-ischaemic, propofol-treated hearts exhibited increased respiratory chain activity and were less sensitive to calcium-induced MPT pore opening. Propofol confers significant protection against global normothermic ischaemia and during cold cardioplegic arrest. This effect is associated with less opening of mitochondrial MPT pores, probably as a result of diminished oxidative stress. Propofol may be a useful adjunct to cardioplegic solutions in heart surgery.

  8. Heart rate-based training intensity and its impact on injury incidence among elite-level professional soccer players.

    PubMed

    Owen, Adam L; Forsyth, Jacky J; Wong, Del P; Dellal, Alexandre; Connelly, Sean P; Chamari, Karim

    2015-06-01

    Elite-level professional soccer players are suggested to have increased physical, technical, tactical, and psychological capabilities when compared with their subelite counterparts. Ensuring these players remain at the elite level generally involves training many different bodily systems to a high intensity or level within a short duration. This study aimed to examine whether an increase in training volume at high-intensity levels was related to injury incidence, or increased the odds of sustaining an injury. Training intensity was monitored through time spent in high-intensity (T-HI) and very high-intensity (T-VHI) zones of 85-<90% and ≥90% of maximal heart rate (HRmax), and all injuries were recorded over 2 consecutive seasons. Twenty-three, elite professional male soccer players (mean ± SD age, 25.6 ± 4.6 years; stature, 181.8 ± 6.8 cm; and body mass, 79.3 ± 8.1 kg) were studied throughout the 2-years span of the investigation. The results showed a mean total injury incidence of 18.8 (95% confidence interval [CI], 14.7-22.9) injuries per 1,000 hours of exposure. Significant correlations were found between training volume at T-HI and injury incidence (r = 0.57, p = 0.005). Further analysis revealed how players achieving more time in the T-VHI zone during training increased the odds of sustaining a match injury (odds ratio = 1.87; 95% CI, 1.12-3.12, p = 0.02) but did not increase the odds of sustaining a training injury. Reducing the number of competitive match injuries among elite-level professional players may be possible if greater focus is placed on the training intensity and volume over a period of time ensuring the potential reduction of fatigue or overuse injuries. In addition, it is important to understand the optimal training load at which adaptation occurs without raising the risk of injury.

  9. Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury

    PubMed Central

    Zhang, Weilin; Ren, He; Xu, Chunling; Zhu, Chongzhuo; Wu, Hao; Liu, Dong; Wang, Jun; Liu, Lei; Li, Wei; Ma, Qi; Du, Lei; Zheng, Ming; Zhang, Chuanmao; Liu, Junling; Chen, Quan

    2016-01-01

    Mitochondrial dysfunction underlies many prevalent diseases including heart disease arising from acute ischemia/reperfusion (I/R) injury. Here, we demonstrate that mitophagy, which selectively removes damaged or unwanted mitochondria, regulated mitochondrial quality and quantity in vivo. Hypoxia induced extensive mitochondrial degradation in a FUNDC1-dependent manner in platelets, and this was blocked by in vivo administration of a cell-penetrating peptide encompassing the LIR motif of FUNDC1 only in wild-type mice. Genetic ablation of Fundc1 impaired mitochondrial quality and increased mitochondrial mass in platelets and rendered the platelets insensitive to hypoxia and the peptide. Moreover, hypoxic mitophagy in platelets protected the heart from worsening of I/R injury. This represents a new mechanism of the hypoxic preconditioning effect which reduces I/R injury. Our results demonstrate a critical role of mitophagy in mitochondrial quality control and platelet activation, and suggest that manipulation of mitophagy by hypoxia or pharmacological approaches may be a novel strategy for cardioprotection. DOI: http://dx.doi.org/10.7554/eLife.21407.001 PMID:27995894

  10. Targeted myocardial delivery of GDF11 gene rejuvenates the aged mouse heart and enhances myocardial regeneration after ischemia-reperfusion injury.

    PubMed

    Du, Guo-Qing; Shao, Zheng-Bo; Wu, Jie; Yin, Wen-Juan; Li, Shu-Hong; Wu, Jun; Weisel, Richard D; Tian, Jia-Wei; Li, Ren-Ke

    2017-01-01

    Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16(+) cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1(+)) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

  11. Organ dysfunction, injury and failure in acute heart failure: from pathophysiology to diagnosis and management. A review on behalf of the Acute Heart Failure Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

    PubMed

    Harjola, Veli-Pekka; Mullens, Wilfried; Banaszewski, Marek; Bauersachs, Johann; Brunner-La Rocca, Hans-Peter; Chioncel, Ovidiu; Collins, Sean P; Doehner, Wolfram; Filippatos, Gerasimos S; Flammer, Andreas J; Fuhrmann, Valentin; Lainscak, Mitja; Lassus, Johan; Legrand, Matthieu; Masip, Josep; Mueller, Christian; Papp, Zoltán; Parissis, John; Platz, Elke; Rudiger, Alain; Ruschitzka, Frank; Schäfer, Andreas; Seferovic, Petar M; Skouri, Hadi; Yilmaz, Mehmet Birhan; Mebazaa, Alexandre

    2017-07-01

    Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

  12. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

    PubMed Central

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines. PMID:24632844

  13. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis.

    PubMed

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-05-01

    To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to (1)H-NMR-based metabolomic analysis. Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.

  14. Acute kidney injury in octogenarians after heart valve replacement surgery: a study of two periods over the last decade.

    PubMed

    Thongprayoon, Charat; Cheungpasitporn, Wisit; Lin, Jing; Mao, Michael A; Qian, Qi

    2017-10-01

    Data on postoperative acute kidney injury (AKI) in octogenarians are limited. This study examines the AKI occurrence and clinical impact in octogenarians following open-heart valve replacement surgery in two periods over the last 15 years. A total of 452 consecutive octogenarians (non-kidney transplant and non-dialysis) who underwent heart valve replacement at the Mayo Clinic during the years 2011-13 (contemporary cohort) were examined. The results were compared with a comparable 209 consecutive octogenarians in 2002-03 (past cohort). Pre-existing chronic kidney disease (CKD) was defined based on estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula). Outcomes included postoperative AKI defined by the Acute Kidney Injury Network (AKIN) criteria, length of hospital stay (LOS), discharge disposition and patient survival (hospital and 1 year). AKI occurrence in the contemporary cohort was lower than the past cohort (35% versus 47%, respectively, P < 0.003). Compared with the past cohort, the contemporary cohort had fewer known perioperative AKI risk factors (pre-existing CKD, comorbidity, heart failure, surgical duration, cross-clamp time, blood transfusion and large-volume intravenous fluids). In both periods, AKI adversely impacts mortality, LOS and discharge to a care facility. Postoperative AKI in octogenarians following heart valve replacement surgery has declined over the last decade. As a result, the AKI-attributable percentage mortality has accordingly decreased. However, AKI continues to exert a heavy morbidity and mortality burden. These results are highly pertinent to practice since the octogenarian population is growing.

  15. Effect of Transient and Sustained Acute Kidney Injury on Readmissions in Acute Decompensated Heart Failure.

    PubMed

    Freda, Benjamin J; Knee, Alexander B; Braden, Gregory L; Visintainer, Paul F; Thakar, Charuhas V

    2017-06-01

    Although acute kidney injury (AKI) is common in heart failure, yet the impact of the onset, timing, and duration of AKI on short-term outcomes is not well studied. AKI was defined as an increase in serum creatinine SCr of ≥0.3 mg/dl or 1.5 times relative to the admission and further categorized as transient AKI (T-AKI: SCr returning to within 10% of baseline); sustained AKI (S-AKI: those with at least 72 hours of hospital stay and did not meet T-AKI); and unknown duration AKI (U-AKI: those with less than 72 hours stay and did not meet T-AKI). Reference category was no AKI (stable or <0.3 mg/dl change in SCr). The main outcome was 30-day all-cause hospital readmission. Unadjusted and adjusted association between AKI category of interest and main outcome was represented as percent and relative risks with 95% CIs. Statistical significance was set at an alpha of 0.05. From the Cerner Health Facts sample, 14,017 of 22,059 available subjects met the eligibility criteria. Approximately, 19.2% of our sample met the primary outcome. Compared with no AKI (readmission rate of 17.7%; 95% CI 16.4% to 18.9%), the adjusted rate of readmission was highest in patients with S-AKI (22.8%, 95% CI 20.8% to 24.8%; p <0.001), followed by 20.2% (95% CI 17.5% to 22.8%; p = 0.05) in T-AKI patients. Compared with no AKI, the adjusted relative risk of 30-day readmission was 1.29 (95% CI 1.17 to 1.42), 1.14 (95% CI 1.00 to 1.31), and 1.12 (95% CI, 1.01 to 1.26) in S-AKI, T-AKI, and U-AKI, respectively. In conclusion, both sustained AKI and patients with transient elevation still remain at a higher risk of readmission within 30 days. Future studies should focus on examining process-of-care after discharge in patients with different patterns of AKI. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Bone marrow mesenchymal stem cell transplantation improves radiation-induced heart injury through DNA damage repair in rat model.

    PubMed

    Gao, Song; Zhao, Zhiying; Wu, Rong; Zeng, Yuecan; Zhang, Zhenyong; Miao, Jianing; Yuan, Zhengwei

    2017-03-01

    Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points. After irradiation, BMSC transplantation significantly enhanced the cardiac function in rats. By analyzing the expression of PPAR-α, PPAR-γ, TGF-β, IL-6, and IL-8, we found that BMSC transplantation alleviated radiation-induced myocardial fibrosis and decreased the inflammatory reaction. Furthermore, we found that expression of γ-H2AX, XRCC4, DNA ligase4, and TP53BP1, which are associated with DNA repair, was up-regulated, along with increased secretion of growth factors SDF-1, CXCR4, VEGF, and IGF in rat myocardium in the IRR + BMSCs transplantation groups compared with the IRR group. Thus, BMSC transplantation has the potential to improve RIHI via DNA repair and be a new therapeutic approach for patients with myocardial injury.

  17. Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce ischaemia-reperfusion injury in heart

    PubMed Central

    Nederlof, Rianne; Eerbeek, Otto; Hollmann, Markus W; Southworth, Richard; Zuurbier, Coert J

    2014-01-01

    Mitochondrially bound hexokinase II (mtHKII) has long been known to confer cancer cells with their resilience against cell death. More recently, mtHKII has emerged as a powerful protector against cardiac cell death. mtHKII protects against ischaemia-reperfusion (IR) injury in skeletal muscle and heart, attenuates cardiac hypertrophy and remodelling, and is one of the major end-effectors through which ischaemic preconditioning protects against myocardial IR injury. Mechanisms of mtHKII cardioprotection against reperfusion injury entail the maintenance of regulated outer mitochondrial membrane (OMM) permeability during ischaemia and reperfusion resulting in stabilization of mitochondrial membrane potential, the prevention of OMM breakage and cytochrome C release, and reduced reactive oxygen species production. Increasing mtHK may also have important metabolic consequences, such as improvement of glucose-induced insulin release, prevention of acidosis through enhanced coupling of glycolysis and glucose oxidation, and inhibition of fatty acid oxidation. Deficiencies in expression and distorted cellular signalling of HKII may contribute to the altered sensitivity of diabetes to cardiac ischaemic diseases. The interaction of HKII with the mitochondrion constitutes a powerful endogenous molecular mechanism to protect against cell death in almost all cell types examined (neurons, tumours, kidney, lung, skeletal muscle, heart). The challenge now is to harness mtHKII in the treatment of infarction, stroke, elective surgery and transplantation. Remote ischaemic preconditioning, metformin administration and miR-155/miR-144 manipulations are potential means of doing just that. LINKED ARTICLES This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24032601

  18. Apigenin attenuates heart injury in lipopolysaccharide-induced endotoxemic model by suppressing sphingosine kinase 1/sphingosine 1-phosphate signaling pathway.

    PubMed

    Zhang, Tianzhu; Yan, Tianhua; Du, Juan; Wang, Shumin; Yang, Huilin

    2015-05-25

    Sepsis is a cluster of heterogeneous syndromes associated with progressive endotoxemic developments, ultimately leading to damage of multiple organs, including the heart. This study is to investigate the effects of apigenin on heart injury in lipopolysaccharide-induced endotoxemic rat model. Normal Wistar rats were randomly divided into four groups: control group, LPS group (15 mg/kg), LPS plus apigenin groups with different apigenin doses (50 mg/kg, 100 mg/kg). Serum levels of creatine kinase (CK), lactate dehydrogenase (LDH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) were measured after the rats were sacrificed. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax and Bcl-2 in heart were measured by Western blot. In vitro, we evaluated the protective effect of apigenin on rat embryonic heart-derived myogenic cell line H9c2 induced by LPS. Apigenin decreased serum levels of CK-MB, LDH, TNF-α, IL-6, IL-1β. SphK1/S1P signaling pathway proteins, cleaved caspase-3, cleaved caspase-9, Bax in heart were found inhibited and Bcl-2 increased in the apigenin groups in vivo. In addition, apigenin inhibited intracellular calcium, the MAPK pathway and SphK1/S1P signaling pathway in vitro. Apigenin exerts pronounced cardioprotection in rats subjected to LPS likely through suppressing myocardial apoptosis and inflammation by inhibiting the SphK1/S1P signaling pathway.

  19. Peri-operative heart-type fatty acid binding protein is associated with acute kidney injury after cardiac surgery

    PubMed Central

    Schaub, Jennifer A.; Garg, Amit X.; Coca, Steven G.; Testani, Jeffrey M.; Shlipak, Michael G.; Eikelboom, John; Kavsak, Peter; McArthur, Eric; Shortt, Colleen; Whitlock, Richard; Parikh, Chirag R.

    2015-01-01

    Acute Kidney Injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. Since heart fatty acid binding protein (H-FABP) is a myocardial protein that detects cardiac injury, we sought to determine if plasma H-FABP was associated with AKI in the TRIBE-AKI cohort; a multi-center cohort of 1219 patients at high risk for AKI who underwent cardiac surgery. The primary outcomes of interest were any AKI (Acute Kidney Injury Network (AKIN) stage 1 or higher) and severe AKI (AKIN stage 2 or higher). The secondary outcome was long-term mortality after discharge. Patients who developed AKI had higher levels of H-FABP pre- and post-operatively than patients who did not have AKI. In analyses adjusted for known AKI risk factors, first post-operative log(H-FABP) was associated with severe AKI (adjusted OR 5.39 [95% CI, 2.87-10.11] per unit increase), while pre-operative log(H-FABP) was associated with any AKI (2.07 [1.48-2.89]) and mortality (1.67 [1.17-2.37]). These relationships persisted after adjustment for change in serum creatinine (for first postoperative log(H-FABP)) and biomarkers of cardiac and kidney injury, including brain natriuretic peptide, cardiac troponin-I, interleukin-18, liver fatty acid binding protein, kidney injury molecule-1, and neutrophil gelatinase associated lipocalin. Thus, peri-operative plasma H-FABP levels may be used for risk-stratification of AKI and mortality following cardiac surgery. PMID:25830762

  20. An investigation on cardioprotective potential of Marrubium vulgare aqueous fraction against ischemia-reperfusion injury in isolated rat heart.

    PubMed

    Garjani, Alireza; Tila, Dena; Hamedeyazdan, Sanaz; Vaez, Haleh; Rameshrad, Maryam; Pashaii, Mahdiyeh; Fathiazad, Fatemeh

    2017-02-15

    The aim of this study was to evaluate the cardioprotective effects of aqueous fraction of M. vulgare hydroalcoholic extract on cardiac parameters in ischemic-reperfused isolated rat hearts. The aerial parts of the plant were extracted with methanol 70% by maceration. The water-soluble portion of the total hydroalcoholic extract was prepared with liquid-liquid extraction (LLE). Afterwards, the antioxidant activity, total phenolic and flavonoids content of the aqueous fraction were determined. In order to evaluate the effects of the aqueous fraction on cardiac parameters and I/R injury, the Langendroff method was used on Male Wistar rats. Harvested hearts were cannulated immediately to the langendroff apparatus and subjected into 30 min regional ischemia and 2 hrs reperfusion, either by a modified Krebs-Henseleit Buffer Solution (KHBS) or enriched KHBS with plant extract (10, 20, 40 µg/mL). The aqueous fraction was found to be a scavenger of DPPH radical with RC50 value of 47µg/mL. The total phenolic and flavonoids content of the fraction was 6.05g gallic acid equivalent and 36.13mg quercetin equivalent per 100g of dry plant material. In addition, 40 µg/mL of M. vulgare aqueous fraction significantly decreased infarct size in comparison to control group. All doses considerably reduced the total ventricular ectopic beats (VEBs) during 30 min of ischemia. The extract at dose of 40 µg/mL noticeably decreased the arrhythmias during the first 30 min of reperfusion. The results of the study indicated aqueous fraction of M. vulgare possesses a protective effect against I/R injuries in isolated rat hearts.

  1. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury

    PubMed Central

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-01-01

    Background Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. Methods and Results We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Conclusions Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a

  2. Cardioprotective effects of 44Bu, a newly synthesized compound, in rat heart subjected to ischemia/reperfusion injury.

    PubMed

    Basgut, Bilgen; Kayki, Gizem; Bartosova, Ladislava; Ozakca, Isil; Seymen, Aytac; Kandilci, H Burak; Ugur, Mehmet; Turan, Belma; Ozcelikay, A Tanju

    2010-08-25

    Excessive intracellular Na+ accumulation followed by Ca2+ overload in cardiac tissue is one of the important mechanisms leading to ischemia/reperfusion injury. In the present study, the cardioprotective effects of 44Bu, 2-hydroxy-3-(butylamino) propyl-4-{(butoxycarbonyl)amino}benzoate hydrochloride, a novel Na+ channel blocker, on ischemia/reperfusion injury were investigated and compared to lidocaine. Isolated rat hearts perfused at the constant flow were exposed to global ischemia for 60 min followed by 30 min of reperfusion. In control hearts, ischemia/reperfusion markedly decreased left ventricular developed pressure and increased left ventricular end-diastolic pressure, and caused lactate dehydrogenase release and infarction. 44Bu (0.1, 0.3 and 1 microM) or lidocaine (1 and 200 microM) was administrated during the last 10 min before ischemia and the first 5 min of the reperfusion period. A significant post-ischemic functional recovery in the same degree was elicited by 0.3 and 1 microM 44Bu or 200 microM lidocaine. These effects of 44Bu and lidocaine closely correlated with the reduction in the infarct size and lactate dehydrogenase release. In contrast, 44Bu (0.1 microM) or lidocaine (1 microM) treatment did not result in a significant recovery in any of the examined parameters. In accordance with functional results, our electrophysiological data demonstrated that 44Bu was a more potent agent than lidocaine in terms of transient Na+ current inhibition. On the other hand, 44Bu did not cause any change in Ca2+ currents and on Na+/H+ exchange activity. These results show that 44Bu, as a novel Na+ channel blocker, has cardioprotective effects against ischemia/reperfusion injury. Crown Copyright (c) 2010. Published by Elsevier B.V. All rights reserved.

  3. Role of Opioid Receptors Signaling in Remote Electrostimulation - Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts

    PubMed Central

    Tsai, Hsin-Ju; Huang, Shiang-Suo; Tsou, Meng-Ting; Wang, Hsiao-Ting; Chiu, Jen-Hwey

    2015-01-01

    Aims Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart. Methods & Results Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively. Conclusion The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling. PMID:26430750

  4. miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury.

    PubMed

    Wang, K; Liu, C-Y; Zhang, X-J; Feng, C; Zhou, L-Y; Zhao, Y; Li, P-F

    2015-06-01

    Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Emerging evidences suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction (MI) and heart failure. However, the molecular components regulating mitochondrial network in the heart remain largely unidentified. Here we report that miR-361 and prohibitin 1 (PHB1) constitute an axis that regulates mitochondrial fission and apoptosis. The results show that PHB1 attenuates mitochondrial fission and apoptosis in response to hydrogen peroxide treatment in cardiomyocytes. Cardiac-specific PHB1 transgenic mice show reduced mitochondrial fission and myocardial infarction sizes after myocardial infarction surgery. MiR-361 is responsible for the dysfunction of PHB1 and suppresses the translation of PHB1. Knockdown of miR-361 reduces mitochondrial fission and apoptosis in vivo and in vitro. MiR-361 cardiac-specific transgenic mice represent elevated mitochondrial fission and myocardial infarction sizes upon myocardial ischemia injury. This study identifies a novel signaling pathway composed of miR-361 and PHB1 that regulates mitochondrial fission program and apoptosis. This discovery will shed new light on the therapy of myocardial infarction and heart failure.

  5. miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury

    PubMed Central

    Wang, K; Liu, C-Y; Zhang, X-J; Feng, C; Zhou, L-Y; Zhao, Y; Li, P-F

    2015-01-01

    Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Emerging evidences suggest that the abnormal mitochondrial fission participates in pathogenesis of cardiac diseases, including myocardial infarction (MI) and heart failure. However, the molecular components regulating mitochondrial network in the heart remain largely unidentified. Here we report that miR-361 and prohibitin 1 (PHB1) constitute an axis that regulates mitochondrial fission and apoptosis. The results show that PHB1 attenuates mitochondrial fission and apoptosis in response to hydrogen peroxide treatment in cardiomyocytes. Cardiac-specific PHB1 transgenic mice show reduced mitochondrial fission and myocardial infarction sizes after myocardial infarction surgery. MiR-361 is responsible for the dysfunction of PHB1 and suppresses the translation of PHB1. Knockdown of miR-361 reduces mitochondrial fission and apoptosis in vivo and in vitro. MiR-361 cardiac-specific transgenic mice represent elevated mitochondrial fission and myocardial infarction sizes upon myocardial ischemia injury. This study identifies a novel signaling pathway composed of miR-361 and PHB1 that regulates mitochondrial fission program and apoptosis. This discovery will shed new light on the therapy of myocardial infarction and heart failure. PMID:25501599

  6. Voluntary physical activity protects from susceptibility to skeletal muscle contraction-induced injury but worsens heart function in mdx mice.

    PubMed

    Hourdé, Christophe; Joanne, Pierre; Medja, Fadia; Mougenot, Nathalie; Jacquet, Adeline; Mouisel, Etienne; Pannerec, Alice; Hatem, Stéphane; Butler-Browne, Gillian; Agbulut, Onnik; Ferry, Arnaud

    2013-05-01

    It is well known that inactivity/activity influences skeletal muscle physiological characteristics. However, the effects of inactivity/activity on muscle weakness and increased susceptibility to muscle contraction-induced injury have not been extensively studied in mdx mice, a murine model of Duchenne muscular dystrophy with dystrophin deficiency. In the present study, we demonstrate that inactivity (ie, leg immobilization) worsened the muscle weakness and the susceptibility to contraction-induced injury in mdx mice. Inactivity also mimicked these two dystrophic features in wild-type mice. In contrast, we demonstrate that these parameters can be improved by activity (ie, voluntary wheel running) in mdx mice. Biochemical analyses indicate that the changes induced by inactivity/activity were not related to fiber-type transition but were associated with altered expression of different genes involved in fiber growth (GDF8), structure (Actg1), and calcium homeostasis (Stim1 and Jph1). However, activity reduced left ventricular function (ie, ejection and shortening fractions) in mdx, but not C57, mice. Altogether, our study suggests that muscle weakness and susceptibility to contraction-induced injury in dystrophic muscle could be attributable, at least in part, to inactivity. It also suggests that activity exerts a beneficial effect on dystrophic skeletal muscle but not on the heart.

  7. Pulmonary Instillation of Multi-Walled Carbon Nanotubes Promotes Coronary Vasoconstriction and Exacerbates Injury in Isolated Hearts

    PubMed Central

    Thompson, Leslie C.; Frasier, Chad R.; Sloan, Ruben C.; Mann, Erin E.; Harrison, Benjamin S.; Brown, Jared M.; Brown, David A.; Wingard, Christopher J.

    2014-01-01

    The growing use of multi-walled carbon nanotubes (MWCNTs) across industry has increased human exposures. We tested the hypothesis that pulmonary instillation of MWCNT would exacerbate cardiac ischemia/reperfusion (I/R) injury. One day following intratracheal instillation of 1, 10, or 100 μg MWCNT in Sprague-Dawley rats, we used a Langendorff isolated heart model to examine cardiac I/R injury. In the 100 μg MWCNT group we report increased premature ventricular contractions at baseline and increased myocardial infarction. This was associated with increased endothelin-1 (ET-1) release and depression of coronary flow during early reperfusion. We also tested if isolated coronary vascular responses were affected by MWCNT instillation and found trends for enhanced coronary tone, which were dependent on ET-1, cyclooxygenase, thromboxane, and Rho-kinase. We conclude that instillation of MWCNT promoted cardiac injury by depressing coronary flow, invoking vasoconstrictive mechanisms involving ET-1, cyclooxygenase, thromboxane, and Rho-kinase. PMID:23102262

  8. Promotion of CHIP-mediated p53 degradation protects the heart from ischemic injury.

    PubMed

    Naito, Atsuhiko T; Okada, Sho; Minamino, Tohru; Iwanaga, Koji; Liu, Mei-Lan; Sumida, Tomokazu; Nomura, Seitaro; Sahara, Naruhiko; Mizoroki, Tatsuya; Takashima, Akihiko; Akazawa, Hiroshi; Nagai, Toshio; Shiojima, Ichiro; Komuro, Issei

    2010-06-11

    The number of patients with coronary heart disease, including myocardial infarction, is increasing and novel therapeutic strategy is awaited. Tumor suppressor protein p53 accumulates in the myocardium after myocardial infarction, causes apoptosis of cardiomyocytes, and plays an important role in the progression into heart failure. We investigated the molecular mechanisms of p53 accumulation in the heart after myocardial infarction and tested whether anti-p53 approach would be effective against myocardial infarction. Through expression screening, we found that CHIP (carboxyl terminus of Hsp70-interacting protein) is an endogenous p53 antagonist in the heart. CHIP suppressed p53 level by ubiquitinating and inducing proteasomal degradation. CHIP transcription was downregulated after hypoxic stress and restoration of CHIP protein level prevented p53 accumulation after hypoxic stress. CHIP overexpression in vivo prevented p53 accumulation and cardiomyocyte apoptosis after myocardial infarction. Promotion of CHIP function by heat shock protein (Hsp)90 inhibitor, 17-allylamino-17-demethoxy geldanamycin (17-AAG), also prevented p53 accumulation and cardiomyocyte apoptosis both in vitro and in vivo. CHIP-mediated p53 degradation was at least one of the cardioprotective effects of 17-AAG. We found that downregulation of CHIP level by hypoxia was responsible for p53 accumulation in the heart after myocardial infarction. Decreasing the amount of p53 prevented myocardial apoptosis and ameliorated ventricular remodeling after myocardial infarction. We conclude that anti-p53 approach would be effective to treat myocardial infarction.

  9. Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart.

    PubMed

    Boerma, Marjan; Wang, Junru; Sridharan, Vijayalakshmi; Herbert, Jean-Marc; Hauer-Jensen, Martin

    2013-01-01

    Radiation therapy in the treatment of cancer is dose limited by radiation injury in normal tissues such as the intestine and the heart. To identify the mechanistic involvement of transforming growth factor-beta 1 (TGF-β1) in intestinal and cardiac radiation injury, we studied the influence of pharmacological induction of TGF-β1 with xaliproden (SR 57746A) in rat models of radiation enteropathy and radiation-induced heart disease (RIHD). Because it was uncertain to what extent TGF-β induction may enhance radiation injury in heart and intestine, animals were exposed to irradiation schedules that cause mild to moderate (acute) radiation injury. In the radiation enteropathy model, male Sprague-Dawley rats received local irradiation of a 4-cm loop of rat ileum with 7 once-daily fractions of 5.6 Gy, and intestinal injury was assessed at 2 weeks and 12 weeks after irradiation. In the RIHD model, male Sprague-Dawley rats received local heart irradiation with a single dose of 18 Gy and were followed for 6 months after irradiation. Rats were treated orally with xaliproden starting 3 days before irradiation until the end of the experiments. Treatment with xaliproden increased circulating TGF-β1 levels by 300% and significantly induced expression of TGF-β1 and TGF-β1 target genes in the irradiated intestine and heart. Various radiation-induced structural changes in the intestine at 2 and 12 weeks were significantly enhanced with TGF-β1 induction. Similarly, in the RIHD model induction of TGF-β1 augmented radiation-induced changes in cardiac function and myocardial fibrosis. These results lend further support for the direct involvement of TGF-β1 in biological mechanisms of radiation-induced adverse remodeling in the intestine and the heart.

  10. Inhibition of the activity of poly (ADP-ribose) polymerase reduces heart ischaemia/reperfusion injury via suppressing JNK-mediated AIF translocation

    PubMed Central

    Song, Zhao-Feng; Ji, Xiao-Ping; Li, Xiao-Xing; Wang, Sheng-Jun; Wang, Shu-Hua; Yun-Zhang

    2008-01-01

    Poly (ADP-ribose) polymerase (PARP) has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion (I/R) injury. However, the mechanisms of PARP-mediated heart I/R injury in vivo are still not thoroughly understood. Therefore, in this study, we investigate the effect of PARP inhibition on heart I/R injury and try to elucidate the underlying mechanisms. Studies were performed with I/R rats' hearts in vivo. Ischaemia followed by reperfusion caused a significant increase in Poly (ADP-ribose) (PAR), c-Jun NH2-terminal kinase (JNK) and apoptosis-inducing factor (AIF) activity. Administration of 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), an inhibitor of PARP, decreased myocardial infarction size from 61.11±7.46%[0] to 38.83±5.67% (P<0.05) and cells apoptosis from 35±5.3% to 20±4.1% (P<0.05) and simultaneously improved the cardiac function. Western blot analysis showed that administration of DPQ reduced the activation of JNK and attenuated mitochondrial-nuclear translocation of AIF. Additionally, administration of SP600125, an inhibitor of JNK, attenuated mitochondrial-nuclear translocation of AIF. The results of the present study demonstrated that the inhibition of PARP was able to reduce heart I/R injury in vivo. Our results also suggested that JNK may be downstream of PARP activation and be required for PARP-mediated AIF translocation. Inhibition of the activity of PARP may reduce heart I/R injury via suppressing AIF translocation mediated by JNK. PMID:18782186

  11. Ischemic Postconditioning Does Not Provide Cardioprotection from Long Term Ischemic Injury in Isolated Male or Female Rat Hearts

    PubMed Central

    Lee, Daniel S.; Steinbaugh, Gregory E.; Quarrie, Ricardo; Yang, Fuchun; Talukder, Hassan; Zweier, Jay L.; Crestanello, Juan A.

    2010-01-01

    Background Ischemic postconditioning(PoC) is a cardio-protective strategy in which initial reperfusion is interrupted by episodes of ischemia. It is unclear whether PoC can be achieved in the Langendorff perfused rat heart model. We investigated 1) whether postconditioning occurs in Langendorff perfused rat heart and 2) whether there is a gender specific response to PoC. Materials and methods Male/female rat hearts(n=8/group) were subjected to 30 minutes of equilibration, 30 minutes of ischemia, and 120 minutes of reperfusion (CONTROL). PoC was induced by 6 cycles(PoC 6c10s), 3 cycles(PoC 3c10s), or 2 cycles(PoC 2c10s) of 10 second reperfusion/10 second ischemia. Rate pressure product(RPP) and infarct size were measured. Male rats(n=7/group) were subjected in vivo to 30 minute left coronary ligation followed by 24 hours of reperfusion(CONTROL) or PoC 6c10s and 24 hours of reperfusion. Results Recovery of RPP was 18±4% in male CONTROL vs. 17±2% for 6c10s, 16±1% for 3c10s, and 15±3% for 2c10s. Female CONTROL hearts recovered 25±3% of their RPP vs. 21±2% for 6c10s. Infarct size was 25±3% for male CONTROL vs. 26±3% for 6c10s, 30±2% for 3c10s, 28±1% for 2c10s; and 30±2% for female CONTROL vs. 29±2% in 6c10s. In vivo Infarct size for CONTROL and PoC 6c10s was 44±3% and 28±5%, respectively (p<0.05). Conclusions In the Langendorff perfused rat hearts, none of the PoC protocols improved myocardial tolerance to ischemia reperfusion injury nor decreased infarct size; however, in vivo postconditioning did confer protection. The lack of protection in the isolated hearts was not gender specific. PMID:20934717

  12. Chronic Losartan Treatment Up-Regulates AT1R and Increases the Heart Vulnerability to Acute Onset of Ischemia and Reperfusion Injury in Male Rats.

    PubMed

    Song, Minwoo A; Dasgupta, Chiranjib; Zhang, Lubo

    2015-01-01

    Inhibition of angiotensin II type 1 receptor (AT1R) is an important therapy in the management of hypertension, particularly in the immediate post-myocardial infarction period. Yet, the role of AT1R in the acute onset of myocardial ischemia and reperfusion injury still remains controversial. Thus, the present study determined the effects of chronic losartan treatment on heart ischemia and reperfusion injury in rats. Losartan (10 mg/kg/day) was administered to six-month-old male rats via an osmotic pump for 14 days and hearts were then isolated and were subjected to ischemia and reperfusion injury in a Langendorff preparation. Losartan significantly decreased mean arterial blood pressure. However, heart weight, left ventricle to body weight ratio and baseline cardiac function were not significantly altered by the losartan treatment. Of interest, chronic in vivo losartan treatment significantly increased ischemia-induced myocardial injury and decreased post-ischemic recovery of left ventricular function. This was associated with significant increases in AT1R and PKCδ expression in the left ventricle. In contrast, AT2R and PKCε were not altered. Furthermore, losartan treatment significantly increased microRNA (miR)-1, -15b, -92a, -133a, -133b, -210, and -499 expression but decreased miR-21 in the left ventricle. Of importance, addition of losartan to isolated heart preparations blocked the effect of increased ischemic-injury induced by in vivo chronic losartan treatment. The results demonstrate that chronic losartan treatment up-regulates AT1R/PKCδ and alters miR expression patterns in the heart, leading to increased cardiac vulnerability to ischemia and reperfusion injury.

  13. The lightning heart: a case report and brief review of the cardiovascular complications of lightning injury.

    PubMed

    McIntyre, William F; Simpson, Christopher S; Redfearn, Damian P; Abdollah, Hoshiar; Baranchuk, Adrian

    2010-09-05

    Lightning strike is a rare natural phenomenon, which carries a risk of dramatic medical complications to multiple organ systems and a high risk of fatality. The known complications include but are not limited to: myocardial infarction, arrhythmia, cardiac contusion, stroke, cutaneous burns, respiratory disorders, neurological disorders, acute kidney injury and death. We report a case of a healthy young man who suffered a lightning injury and discuss the cardiovascular complications of lightning injury, ranging from ECG changes to death. The patient in our case, a 27-year old previously healthy male, developed a syndrome of rhabdomyolysis and symptomatic cardiogenic pulmonary edema. Electrocardiographic findings included transient T-wave inversions, late transition shift and long QT. His clinical condition improved with supportive measures.Early recognition of lightning injury syndromes and anticipation of complications may help us improve outcomes for these patients. Evaluation of patients having experienced a lightning injury should include a minimum of a detailed history and physical examination, 12-lead ECG and drawing of baseline troponins. Prolonged electrocardiographical monitoring (for monitoring of ventricular arrhythmias) and assessment for signs and symptoms of hemodynamic compromise may be warranted.

  14. [Unique mechanism in heart-shaped balloon burst resulting in blunt ocular injury].

    PubMed

    Brosh, Koby; Bekenstein, Yehonadav; Strassman, Israel

    2014-05-01

    We have previously shown that heart-shaped balloons have a different explosion mechanism than spherical balloons in which the former splits into two rubber parts still attached to the balloon base with a backward whiplash motion. This backward whiplash motion may cause significant blunt ocular trauma if the balloon is inflated by mouth. In this article, the energy of the blunt ocular trauma is estimated by the high speed camera photos analysis of the balloon burst. Furthermore, we describe the followup of eight patients with ocular trauma following inflation of heart-shaped balloons.

  15. Intralipid, a Clinically Safe Compound, Protects the Heart Against Ischemia-Reperfusion Injury More Efficiently Than Cyclosporine-A

    PubMed Central

    Li, Jingyuan; Iorga, Andrea; Sharma, Salil; Youn, Ji-Youn; Partow-Navid, Rod; Umar, Soban; Cai, Hua; Rahman, Siamak; Eghbali, Mansoureh

    2013-01-01

    Background We have recently shown that post-ischemic administration of intralipid protects the heart against ischemia/reperfusion injury. Here we compared the cardioprotective effects of intralipid with cyclosporine-A, a potent inhibitor of the mitochondrial permeability transition pore opening. Methods In-vivo rat hearts or isolated Langendorff-perfused mouse hearts were subjected to ischemia followed by reperfusion with Intralipid (0.5%, 1% and 2% ex-vivo and 20% in-vivo), cyclosporine-A (0.2μM, 0.8μM and 1.5μM ex-vivo and 10mg/kg in-vivo) or vehicle. The hemodynamic function, infarct size, calcium retention capacity, mitochodrial superoxide production and phosphorylation levels of Akt/GSK-3β were measured. The values are mean±SEM. Results Administration of intralipid at reperfusion significantly reduced myocardial infarct size compared with cyclosporine-A in-vivo ((infarct size/area at risk)%: 22.9±2.5% vs. 35.2±3.5%; p=0.030, n=7/group). Postischemic administration of intralipid at its optimal dose (1%) was more effective than cyclosporine-A (0.8μM) in protecting the ex-vivo heart against ischemia/reperfusion injury as the rate pressure product at the end of reperfusion was significantly higher (mmHg*beats/min:12740±675(n=7) vs. 9203±10781(n=5), p=0.024), and the infarct size was markedly smaller (17.3±2.9(n=7) vs. 29.2±2.7(n=5), p=0.014). Intralipid was as efficient as cyclosporine-A in inhibiting the mPTP opening (calcium retention capacity=280±8.2 vs. 260.3±2.9nmol/mg-mitochondria-protein in cyclosporine-A, p=0.454, n=6) and in reducing cardiac mitochondrial superoxide production. Unlike intralipid, which increased phosphorlyation of Akt (6-fold) and GSK-3β (5-fold), cyclosporine-A had no effect on the activation of these pro-survival kinases. Conclusions Although intralipid inhibits the opening of the mitochondrial permeability transition pore as efficiently as cyclosporine-A, intralipid is more effective in reducing the infarct size and

  16. Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury

    PubMed Central

    Peyvandi, Shabnam; De Santiago, Veronica; Chakkarapani, Elavazhagan; Chau, Vann; Campbell, Andrew; Poskitt, Kenneth J.; Xu, Duan; Barkovich, A. James; Miller, Steven; McQuillen, Patrick

    2016-01-01

    IMPORTANCE The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits. OBJECTIVE To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD. DESIGN, SETTING, AND PARTICIPANTS Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis. MAIN OUTCOMES AND MEASURES The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development. RESULTS Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95%CI, 0.1%-1.2%; P = .02

  17. Association of Prenatal Diagnosis of Critical Congenital Heart Disease With Postnatal Brain Development and the Risk of Brain Injury.

    PubMed

    Peyvandi, Shabnam; De Santiago, Veronica; Chakkarapani, Elavazhagan; Chau, Vann; Campbell, Andrew; Poskitt, Kenneth J; Xu, Duan; Barkovich, A James; Miller, Steven; McQuillen, Patrick

    2016-04-01

    The relationship of prenatal diagnosis of critical congenital heart disease (CHD) with brain injury and brain development is unknown. Given limited improvement of CHD outcomes with prenatal diagnosis, the effect of prenatal diagnosis on brain health may reveal additional benefits. To compare the prevalence of preoperative and postoperative brain injury and the trajectory of brain development in neonates with prenatal vs postnatal diagnosis of CHD. Cohort study of term newborns with critical CHD recruited consecutively from 2001 to 2013 at the University of California, San Francisco and the University of British Columbia. Term newborns with critical CHD were studied with brain magnetic resonance imaging preoperatively and postoperatively to determine brain injury severity and microstructural brain development with diffusion tensor imaging by measuring fractional anisotropy and the apparent diffusion coefficient. Comparisons of magnetic resonance imaging findings and clinical variables were made between prenatal and postnatal diagnosis of critical CHD. A total of 153 patients with transposition of the great arteries and single ventricle physiology were included in this analysis. The presence of brain injury on the preoperative brain magnetic resonance imaging and the trajectory of postnatal brain microstructural development. Among 153 patients (67% male), 96 had transposition of the great arteries and 57 had single ventricle physiology. The presence of brain injury was significantly higher in patients with postnatal diagnosis of critical CHD (41 of 86 [48%]) than in those with prenatal diagnosis (16 of 67 [24%]) (P = .003). Patients with prenatal diagnosis demonstrated faster brain development in white matter fractional anisotropy (rate of increase, 2.2%; 95% CI, 0.1%-4.2%; P = .04) and gray matter apparent diffusion coefficient (rate of decrease, 0.6%; 95% CI, 0.1%-1.2%; P = .02). Patients with prenatal diagnosis had lower birth weight (mean, 3184.5 g; 95% CI, 3050

  18. beta2 adrenergic agonists in acute lung injury? The heart of the matter.

    PubMed

    Lee, Jae W

    2009-01-01

    Despite extensive research into its pathophysiology, acute lung injury/acute respiratory distress syndrome (ALI/ARDS) remains a devastating syndrome with mortality approaching 40%. Pharmacologic therapies that reduce the severity of lung injury in vivo and in vitro have not yet been translated to effective clinical treatment options, and innovative therapies are needed. Recently, the use of beta2 adrenergic agonists as potential therapy has gained considerable interest due to their ability to increase the resolution of pulmonary edema. However, the results of clinical trials of beta agonist therapy for ALI/ARDS have been conflicting in terms of benefit. In the previous issue of Critical Care, Briot and colleagues present evidence that may help clarify the inconsistent results. The authors demonstrate that, in oleic acid lung injury in dogs, the inotropic effect of beta agonists may recruit damaged pulmonary capillaries, leading to increased lung endothelial permeability.

  19. Potential markers and metabolic processes involved in the mechanism of radiation-induced heart injury.

    PubMed

    Slezak, Jan; Kura, Branislav; Babal, Pavel; Barancik, Miroslav; Ferko, Miroslav; Frimmel, Karel; Kalocayova, Barbora; Kukreja, Rakesh C; Lazou, Antigone; Mezesova, Lucia; Okruhlicova, Ludmila; Ravingerova, Tanya; Singal, Pawan K; Szeiffova Bacova, Barbara; Viczenczova, Csilla; Vrbjar, Norbert; Tribulova, Narcis

    2017-10-01

    Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity - "radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage.

  20. Cardioprotective effects of salidroside on myocardial ischemia-reperfusion injury in coronary artery occlusion-induced rats and Langendorff-perfused rat hearts.

    PubMed

    Chang, Xiayun; Zhang, Kai; Zhou, Rui; Luo, Fen; Zhu, Lingpeng; Gao, Jin; He, He; Wei, Tingting; Yan, Tianhua; Ma, Chunhua

    2016-07-15

    The current study was designed to investigate the protective role of salisroside on rats through the study of energy metabolism homeostasis and inflammation both in ex vivo and in vivo. Energy metabolism homeostasis and inflammation injury were respectively assessed in global ischemia of isolated hearts and coronary artery ligated rats. Excessive release of cardiac enzymes and pro-inflammatory cytokines was inhibited by salidroside in coronary artery occlusion-induced rats. ST segment was also restored with the treatment of salidroside. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis showed that salidroside could significantly alleviate myocardial injury in vivo. Accumulated data in ex vivo indicated that salidroside improved heart function recovery, which was reflected by enhanced myocardial contractility and coronary flow in isolated hearts. The contents of ATP and glycogen both in ex vivo and in vivo were restored by salidroside compared with those in the model group. Besides, the expressions of p-AMPK, PPAR-α and PGC-1α in rats and isolated hearts subjected to salidroside were significantly elevated, while the levels of p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were dramatically reduced by salidroside. The present study comprehensively elaborated the protective effects of salidroside on myocardial injury and demonstrated that AMPK/PGC-1α and AMPK/NF-κB signaling cascades were implicated in the myocardial ischemia-reperfusion injury (I/R) model. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Comparison of Heart Rate Response to Tennis Activity between Persons with and without Spinal Cord Injuries: Implications for a Training Threshold

    ERIC Educational Resources Information Center

    Barfield, J. P.; Malone, Laurie A.; Coleman, Tristica A.

    2009-01-01

    The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT).…

  2. Comparison of Heart Rate Response to Tennis Activity between Persons with and without Spinal Cord Injuries: Implications for a Training Threshold

    ERIC Educational Resources Information Center

    Barfield, J. P.; Malone, Laurie A.; Coleman, Tristica A.

    2009-01-01

    The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT).…

  3. Human recombinant relaxin reduces heart injury and improves ventricular performance in a swine model of acute myocardial infarction.

    PubMed

    Perna, Avio-Maria; Masini, Emanuela; Nistri, Silvia; Bani Sacchi, Tatiana; Bigazzi, Mario; Bani, Daniele

    2005-05-01

    This study shows that relaxin can be effective in the treatment of acute myocardial infarction. In a swine model of heart ischemia-reperfusion currently used to test cardiotropic drugs because of its similarities with human myocardial infarction, human recombinant relaxin (2.5 and 5 microg/kg body weight), given at reperfusion after a 30-min ischemia, markedly reduced the main serum markers of myocardial damage (myoglobin, CK-MB, and troponin T) and the metabolic and histopathologic parameters of myocardial inflammation and cardiomyocyte injury, resulting in overall improvement of ventricular performance (increased cardiac index) compared to the controls. These results provide a background for future clinical trials with human relaxin as adjunctive therapy to catheter-based coronary angioplasty in patients with acute myocardial infarction.

  4. Biomarkers of renal injury and function: diagnostic, prognostic and therapeutic implications in heart failure.

    PubMed

    van Veldhuisen, Dirk J; Ruilope, Luis M; Maisel, Alan S; Damman, Kevin

    2016-09-01

    Heart failure guidelines suggest evaluating renal function as a routine work-up in every patient with heart failure. Specifically, it is advised to calculate glomerular filtration rate and determine blood urea nitrogen. The reason for this is that renal impairment and worsening renal function (WRF) are common in heart failure, and strongly associate with poor outcome. Renal function, however, consists of more than glomerular filtration alone, and includes tubulointerstitial damage and albuminuria. For each of these renal entities, different biomarkers exist that have been investigated in heart failure. Hypothetically, and in parallel to data in nephrology, these markers may aid in the diagnosis of renal dysfunction, or for risk stratification, or could help in therapeutic decision-making. However, as reviewed in the present manuscript, while these markers may carry prognostic information (although not always additive to established markers of renal function), their role in predicting WRF is limited at best. More importantly, none of these markers have been evaluated as a therapeutic target nor have their serial values been used to guide therapy. The evidence is most compelling for the oldest-serum creatinine (in combination with glomerular filtration rate)-but even for this biomarker, evidence to guide therapy to improve outcome is circumstantial at best. Although many new renal biomarkers have emerged at the horizon, they have only limited usefulness in clinical practice until thoroughly and prospectively studied. For now, routine measurement of (novel) renal biomarkers can help to determine cardiovascular risk, but there is no role for these biomarkers to change therapy to improve clinical outcome in heart failure.

  5. C1q/TNF-Related Protein 9 Protects Diabetic Rat Heart against Ischemia Reperfusion Injury: Role of Endoplasmic Reticulum Stress

    PubMed Central

    Bai, Sanxing; Cheng, Liang; Yang, Yang; Fan, Chongxi; Zhao, Dajun; Qin, Zhigang; Feng, Xiao; Zhao, Lin; Ma, Jipeng; Wang, Xiaowu; Yang, Jian; Xu, Xuezeng

    2016-01-01

    As a newly identified adiponectin paralog, C1q/TNF-related protein 9 (CTRP9) reduces myocardial ischemia reperfusion (IR) injury through partially understood mechanisms. In the present study, we sought to identify the role of endoplasmic reticulum stress (ERS) in CTRP9 induced cardioprotection in diabetic heart. Isolated hearts from high-fat-diet (HFD) induced type 2 diabetic Sprague-Dawley rats were subjected to ex vivo IR protocol via a Langendorff apparatus at the presence of globular CTRP9. CTRP9 significantly improved post-IR heart function and reduced cardiac infarction, cardiomyocytes apoptosis, Caspase-3, Caspase-9, Caspase-12, TNF-α expression, and lactate dehydrogenase activity. The cardioprotective effect of CTRP9 was associated with reduced ERS and increased expression of disulfide-bond A oxidoreductase-like protein (DsbA-L) in diabetic heart. CTRP9 reduced ERS in thapsigargin (TG) treated cardiomyocytes and protected endoplasmic reticulum (ER) stressed H9c2 cells against simulated ischemia reperfusion (SIR) injury, concurrent with increased expression of DsbA-L. Knockdown of DsbA-L increased ERS and attenuated CTRP9 induced protection against SIR injury in H9c2 cells. Our findings demonstrated for the first time that CTRP9 exerts cardioprotection by reducing ERS in diabetic heart through increasing DsbA-L. PMID:27795806

  6. Oral pretreatment with a green tea polyphenol for cardioprotection against ischemia-reperfusion injury in an isolated rat heart model.

    PubMed

    Yanagi, Shigeki; Matsumura, Kazuaki; Marui, Akira; Morishima, Manabu; Hyon, Suong-Hyu; Ikeda, Tadashi; Sakata, Ryuzo

    2011-02-01

    Ischemia-reperfusion injury is among the most serious problems in cardiac surgery. Epigallocatechin-3-gallate, a major polyphenolic component of green tea, is thought to be cardioprotective through its antioxidant activities. We investigated cardioprotective effects of oral epigallocatechin-3-gallate pretreatment against ischemia-reperfusion injury in isolated rat hearts and considered possible underlying mechanisms. Rats were given epigallocatechin-3-gallate solution orally at 0.1, 1, or 10 mmol/L (n=12 per group) for 2 weeks; controls (n=12) received tap water alone for 2 weeks. Subsequently, Langendorff-perfused hearts were subjected to global ischemia for 30 minutes, followed by 60 minutes of reperfusion. Recoveries at 60 minutes after reperfusion of left ventricular developed pressure and maximum positive and minimum negative first derivatives of left ventricular pressure were significantly higher in 1-mmol/L group than in 0.1-mmol/L (P<.0001), 10-mmol/L (P<.05), and control (P<.0001) groups. Oxidative stress after reperfusion, as reflected by 8-hydroxy-2'-deoxyguanosine index, was lower in 1-mmol/L group than in control (P<.01) and 0.1-mmol/L (P<.05) groups. Western blot analysis after reperfusion showed p38 activation and active caspase-3 expression to be lower in 1-mmol/L group than in control group (P<.05). Oral pretreatment with epigallocatechin-3-gallate preserved cardiac function after ischemia-reperfusion, an effect that may involve its antioxidative, antiapoptotic properties, although a high dose did not lead to dramatic improvement in cardiac function. Oral epigallocatechin-3-gallate pretreatment may be a novel and simple cardioprotective method for preventing perioperative cardiac dysfunction in cardiac surgery. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  7. In Nonagenarians, Acute Kidney Injury Predicts In-Hospital Mortality, while Heart Failure Predicts Hospital Length of Stay

    PubMed Central

    Chao, Chia-Ter; Lin, Yu-Feng; Tsai, Hung-Bin; Hsu, Nin-Chieh; Tseng, Chia-Lin; Ko, Wen-Je

    2013-01-01

    Background/Aims The elderly constitute an increasing proportion of admitted patients worldwide. We investigate the determinants of hospital length of stay and outcomes in patients aged 90 years and older. Methods We retrospectively analyzed all admitted patients aged >90 years from the general medical wards in a tertiary referral medical center between August 31, 2009 and August 31, 2012. Patients’ clinical characteristics, admission diagnosis, concomitant illnesses at admission, and discharge diagnosis were collected. Each patient was followed until discharge or death. Multivariate logistic regression analysis was utilized to study factors associated with longer hospital length of stay (>7 days) and in-hospital mortality. Results A total of 283 nonagenarian in-patients were recruited, with 118 (41.7%) hospitalized longer than one week. Nonagenarians admitted with pneumonia (p = 0.04) and those with lower Barthel Index (p = 0.012) were more likely to be hospitalized longer than one week. Multivariate logistic regression analysis revealed that patients with lower Barthel Index (odds ratio [OR] 0.98; p = 0.021) and those with heart failure (OR 3.05; p = 0.046) had hospital stays >7 days, while patients with lower Barthel Index (OR 0.93; p = 0.005), main admission nephrologic diagnosis (OR 4.83; p = 0.016) or acute kidney injury (OR 30.7; p = 0.007) had higher in-hospital mortality. Conclusion In nonagenarians, presence of heart failure at admission was associated with longer hospital length of stay, while acute kidney injury at admission predicted higher hospitalization mortality. Poorer functional status was associated with both prolonged admission and higher in-hospital mortality. PMID:24223127

  8. Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury.

    PubMed Central

    Mestril, R; Chi, S H; Sayen, M R; O'Reilly, K; Dillmann, W H

    1994-01-01

    Myocardial ischemia markedly increases the expression of several members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms. Increased expression of HSP70 has been shown to exert a protective effect against a lethal heat shock. We have examined the possibility of using this resistance to a lethal heat shock as a protective effect against an ischemic-like stress in vitro using a rat embryonic heart-derived cell line H9c2 (2-1). Myogenic cells in which the heat shock proteins have been induced by a previous heat shock are found to become resistant to a subsequent simulated ischemic stress. In addition, to address the question of how much does the presence of the HSP70 contribute to this protective effect, we have generated stably transfected cell lines overexpressing the human-inducible HSP70. Embryonal rat heart-derived H9c2(2-1) cells were used for this purpose. This stably transfected cell line was found to be significantly more resistant to an ischemic-like stress than control myogenic cells only expressing the selectable marker (neomycin) or the parental cell line H9c2(2-1). This finding implicates the inducible HSP70 protein as playing a major role in protecting cardiac cells against ischemic injury. Images PMID:8113409

  9. A PET/MR Imaging Approach for the Integrated Assessment of Chemotherapy-induced Brain, Heart, and Bone Injuries in Pediatric Cancer Survivors: A Pilot Study.

    PubMed

    Theruvath, Ashok J; Ilivitzki, Anat; Muehe, Anne; Theruvath, Johanna; Gulaka, Praveen; Kim, Christine; Luna-Fineman, Sandra; Sakamoto, Kathleen M; Yeom, Kristen W; Yang, Phillip; Moseley, Michael; Chan, Frandics; Daldrup-Link, Heike E

    2017-08-04

    Purpose To develop a positron emission tomography (PET)/magnetic resonance (MR) imaging protocol for evaluation of the brain, heart, and joints of pediatric cancer survivors for chemotherapy-induced injuries in one session. Materials and Methods Three teams of experts in neuroimaging, cardiac imaging, and bone imaging were tasked to develop a 20-30-minute PET/MR imaging protocol for detection of chemotherapy-induced tissue injuries of the brain, heart, and bone. In an institutional review board-approved, HIPAA-compliant, prospective study from April to July 2016, 10 pediatric cancer survivors who completed chemotherapy underwent imaging of the brain, heart, and bone with a 3-T PET/MR imager. Cumulative chemotherapy doses and clinical symptoms were correlated with the severity of MR imaging abnormalities by using linear regression analyses. MR imaging measures of brain perfusion and metabolism were compared among eight patients who were treated with methotrexate and eight untreated age-matched control subjects by using Wilcoxon rank-sum tests. Results Combined brain, heart, and bone examinations were completed within 90 minutes. Eight of 10 cancer survivors had abnormal findings on brain, heart, and bone images, including six patients with and two patients without clinical symptoms. Cumulative chemotherapy doses correlated significantly with MR imaging measures of left ventricular ejection fraction and end-systolic volume, but not with the severity of brain or bone abnormalities. Methotrexate-treated cancer survivors had significantly lower cerebral blood flow and metabolic activity in key brain areas compared with control subjects. Conclusion The feasibility of a single examination for assessment of chemotherapy-induced injuries of the brain, heart, and joints was shown. Earlier detection of tissue injuries may enable initiation of timely interventions and help to preserve long-term health of pediatric cancer survivors. (©) RSNA, 2017 Online supplemental material

  10. Prevention and Treatment of Functional and Structural Radiation Injury in the Rat Heart by Pentoxifylline and Alpha-Tocopherol

    SciTech Connect

    Boerma, Marjan Roberto, Kerrey A.; Hauer-Jensen, Martin

    2008-09-01

    Purpose: Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX) and {alpha}-tocopherol on cardiac injury in a rat model of RIHD. Methods and Materials: Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for 6 months after irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and {alpha}-tocopherol (20 IU/kg/day) and received these compounds either from 1 week before until 6 months after irradiation or starting 3 months after irradiation, a time point at which histopathologic changes become apparent in our model of RIHD. Results: Radiation-induced increases in left ventricular diastolic pressure (in mm Hg: 35 {+-} 6 after sham-irradiation, 82 {+-} 11 after irradiation) were significantly reduced by PTX and {alpha}-tocopherol (early treatment: 48 {+-} 7; late treatment: 53 {+-} 6). PTX and {alpha}-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 {+-} 0.2 {mu}m{sup 2} per 100 {mu}m{sup 2}; early treatment: 2.7 {+-} 0.8; late treatment: 2.2 {+-} 0.2) and III (radiation only: 13.9 {+-} 0.8; early treatment: 11.0 {+-} 1.2; late treatment: 10.6 {+-} 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and {alpha}-tocopherol. Conclusions: Treatment with PTX and {alpha}-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and left ventricular function, both when started before irradiation and when started later during the process of RIHD.

  11. The assessment of neural injury following open heart surgery by physiological tremor analysis.

    PubMed

    Németh, Adám; Hejjel, László; Ajtay, Zénó; Kellényi, Lóránd; Solymos, Andor; Bártfai, Imre; Kovács, Norbert; Lenkey, Zsófia; Cziráki, Attila; Szabados, Sándor

    2013-02-21

    The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3(rd) to 5(th) post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450). The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.

  12. Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

    PubMed

    Dong, Boming; Stewart, Paul W; Egan, Thomas M

    2013-08-01

    We sought to determine whether ventilation of lungs after death in non-heart-beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function. One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% oxygen (control group) or 500 ppm carbon monoxide in 60% oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, flushed with cold Perfadex and stored cold for 2 hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60% oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay. Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1β messenger RNA. Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function. Copyright © 2013 The American Association for

  13. CD38 Deficiency Protects the Heart from Ischemia/Reperfusion Injury through Activating SIRT1/FOXOs-Mediated Antioxidative Stress Pathway

    PubMed Central

    Guan, Xiao-Hui; Liu, Xiao-Hong; Hong, Xuan; Zhao, Ning; Xiao, Yun-Fei; Wang, Ling-Fang; Qian, Yi-Song; Deng, Ke-Yu; Ji, Guangju; Fu, Mingui

    2016-01-01

    Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac muscle. We previously observed that CD38 deficiency remarkably protects mouse embryonic fibroblasts (MEFs) from oxidative stress-induced injury. However, whether CD38 deficiency protects from I/R injury in the heart is not explored. Here, we showed that the hearts of CD38 deficient mice or wild type mice supplied with exogenous NAD were significantly protected from ischemia/reperfusion injury, seen as reduction of the myocardial infarct sizes when the mice were subjected to 30 min ischemia followed by 24 hours of reperfusion. Consistently, the protection of CD38 deficiency on hypoxia/reoxygenation (H/R) injury was confirmed with a CD38 knockdown H9c2 stable cell line. Furthermore, we observed that knockdown of CD38 remarkably inhibited ROS generation and intracellular Ca2+ overloading induced by H/R in H9c2 cells. The FOXO1 and FOXO3 expressions were significantly elevated by H/R injury in CD38 knockdown cells compared with normal H9c2 cells. The cell immunofluorescence assay showed that FOXO1 nuclear translocation was significantly increased in CD38 knockdown H9c2 cells. In addition, we demonstrated that the increase of FOXO1 nuclear translocation was associated with the increased expressions of antioxidant catalase and SOD2 and the attenuated expression of the ROS generation enzyme NOX4. In conclusion, our results provide new evidence that CD38 deficiency protects the heart from I/R injury through activating SIRT1/FOXOs-mediated antioxidative stress pathway. PMID:27547294

  14. Remote ischemic preconditioning with--but not without--metabolic support protects the neonatal porcine heart against ischemia-reperfusion injury.

    PubMed

    Schmidt, Michael R; Støttrup, Nicolaj B; Contractor, Hussain; Hyldebrandt, Janus A; Johannsen, Mogens; Pedersen, Christian M; Birkler, Rune; Ashrafian, Houman; Sørensen, Keld E; Kharbanda, Rajesh K; Redington, Andrew N; Bøtker, Hans E

    2014-01-01

    While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo. 32 newborn piglets were randomized into 4 groups: control, GI, GI+rIPC and rIPC. GI and GI+rIPC groups received GI infusion continuously from 40 min prior to ischemia. rIPC and GI+rIPC groups underwent four cycles of 5 min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the left anterior descending artery followed by 2 h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dt(max) as % of baseline) after 2 h reperfusion was 68.5±13.8% in control, 53.7±11.2% in rIPC (p<0.05), and improved in GI (83.6±18.8%, p<0.05) and GI+rIPC (87.0±15.7%, p<0.01). rIPC+GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Mesenchymal stem cells preconditioned with trimetazidine promote neovascularization of hearts under hypoxia/reoxygenation injury

    PubMed Central

    Hu, Xiaowu; Yang, Junjie; Wang, Ying; Zhang, You; Ii, Masaaki; Shen, Zhenya; Hui, Jie

    2015-01-01

    Background: Cell-based angiogenesis is a promising treatment for ischemic diseases; however, survival of implanted cells is impaired by the ischemic microenvironment. In this study, mesenchymal stem cells (MSCs) for cell transplantation were preconditioned with trimetazidine (TMZ). We hypothesized that TMZ enhances the survival rate of MSCs under hypoxic stimuli through up-regulation of HIF1-α. Methods and results: Bone marrow-derived rat mesenchymal stem cells were preconditioned with 10 μM TMZ for 6 h. TMZ preconditioning of MSCs remarkably increased cell viability and the expression of HIF1-α and Bcl-2, when cells were under hypoxia/reoxygenation (H/R) stimuli. But the protective effects of TMZ were abolished after knocking down of HIF-1α. Three days after implantation of the cells into the peri-ischemic zone of rat myocardial ischemia-reperfusion (I/R) injury model, survival of the TMZ-preconditioned MSCs was high. Furthermore, capillary density and cardiac function were significantly better in the rats implanted with TMZ-preconditioned MSCs 28 days after cell injection. Conclusions: TMZ preconditioning increased the survival rate of MSCs, through up-regulation of HIF1-α, thus contributing to neovascularization and improved cardiac function of rats subjected to myocardial I/R injury. PMID:26629255

  16. Preoperative heart rate and myocardial injury after non-cardiac surgery: results of a predefined secondary analysis of the VISION study

    PubMed Central

    Abbott, T. E. F.; Ackland, G. L.; Archbold, R. A.; Wragg, A.; Kam, E.; Ahmad, T.; Khan, A. W.; Niebrzegowska, E.; Rodseth, R. N.; Devereaux, P. J.; Pearse, R. M.

    2016-01-01

    Background Increased baseline heart rate is associated with cardiovascular risk and all-cause mortality in the general population. We hypothesized that elevated preoperative heart rate increases the risk of myocardial injury after non-cardiac surgery (MINS). Methods We performed a secondary analysis of a prospective international cohort study of patients aged ≥45 yr undergoing non-cardiac surgery. Preoperative heart rate was defined as the last measurement before induction of anaesthesia. The sample was divided into deciles by heart rate. Multivariable logistic regression models were used to determine relationships between preoperative heart rate and MINS (determined by serum troponin concentration), myocardial infarction (MI), and death within 30 days of surgery. Separate models were used to test the relationship between these outcomes and predefined binary heart rate thresholds. Results Patients with missing outcomes or heart rate data were excluded from respective analyses. Of 15 087 patients, 1197 (7.9%) sustained MINS, 454 of 16 007 patients (2.8%) sustained MI, and 315 of 16 037 patients (2.0%) died. The highest heart rate decile (>96 beats min−1) was independently associated with MINS {odds ratio (OR) 1.48 [1.23–1.77]; P<0.01}, MI (OR 1.71 [1.34–2.18]; P<0.01), and mortality (OR 3.16 [2.45–4.07]; P<0.01). The lowest decile (<60 beats min−1) was independently associated with reduced mortality (OR 0.50 [0.29–0.88]; P=0.02), but not MINS or MI. The predefined binary thresholds were also associated with MINS, but more weakly than the highest heart rate decile. Conclusions Preoperative heart rate >96 beats min−1 is associated with MINS, MI, and mortality after non-cardiac surgery. This association persists after accounting for potential confounding factors. Clinical trial registration NCT00512109. PMID:27440628

  17. CD8+ T-Cells Expressing Interferon Gamma or Perforin Play Antagonistic Roles in Heart Injury in Experimental Trypanosoma Cruzi-Elicited Cardiomyopathy

    PubMed Central

    Cipitelli, Márcio da Costa; Vinagre, Nathália Ferreira; Rodrigues, Maurício Martins; Gazzinelli, Ricardo Tostes; Lannes-Vieira, Joseli

    2012-01-01

    In Chagas disease, CD8+ T-cells are critical for the control of Trypanosoma cruzi during acute infection. Conversely, CD8+ T-cell accumulation in the myocardium during chronic infection may cause tissue injury leading to chronic chagasic cardiomyopathy (CCC). Here we explored the role of CD8+ T-cells in T. cruzi-elicited heart injury in C57BL/6 mice infected with the Colombian strain. Cardiomyocyte lesion evaluated by creatine kinase-MB isoenzyme activity levels in the serum and electrical abnormalities revealed by electrocardiogram were not associated with the intensity of heart parasitism and myocarditis in the chronic infection. Further, there was no association between heart injury and systemic anti-T. cruzi CD8+ T-cell capacity to produce interferon-gamma (IFNγ) and to perform specific cytotoxicity. Heart injury, however, paralleled accumulation of anti-T. cruzi cells in the cardiac tissue. In T. cruzi infection, most of the CD8+ T-cells segregated into IFNγ+ perforin (Pfn)neg or IFNγnegPfn+ cell populations. Colonization of the cardiac tissue by anti-T. cruzi CD8+Pfn+ cells paralleled the worsening of CCC. The adoptive cell transfer to T. cruzi-infected cd8−/− recipients showed that the CD8+ cells from infected ifnγ−/−pfn+/+ donors migrate towards the cardiac tissue to a greater extent and caused a more severe cardiomyocyte lesion than CD8+ cells from ifnγ+/+pfn−/− donors. Moreover, the reconstitution of naïve cd8−/− mice with CD8+ cells from naïve ifnγ+/+pfn−/− donors ameliorated T. cruzi-elicited heart injury paralleled IFNγ+ cells accumulation, whereas reconstitution with CD8+ cells from naïve ifnγ−/−pfn+/+ donors led to an aggravation of the cardiomyocyte lesion, which was associated with the accumulation of Pfn+ cells in the cardiac tissue. Our data support a possible antagonist effect of CD8+Pfn+ and CD8+IFNγ+ cells during CCC. CD8+IFNγ+ cells may exert a beneficial role, whereas CD8+Pfn+ may play a detrimental role

  18. Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.

    PubMed

    Hou, Xuejiao; Han, Jichun; Yuan, Changsheng; Ren, Huanhuan; Zhang, Ya; Zhang, Tao; Xu, Lixia; Zheng, Qiusheng; Chen, Wen

    2016-01-01

    This study evaluated the antioxidative and cardioprotective effects of total flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion (I/R) injury using an isolated Langendorff rat heart model. The possible mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was also studied. XSRTF (5, 10, and 20 µg/mL) dissolved in Krebs-Henseleit buffer was administered to isolated rat heart. The XSRTF showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP, and decreased CK and LDH levels in coronary flow. This pretreatment also increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-α, and CRP levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the hearts from the XSRTF-treated group were lower than those in the hearts from the I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

  19. Sevoflurane Postconditioning Protects Rat Hearts against Ischemia-Reperfusion Injury via the Activation of PI3K/AKT/mTOR Signaling

    PubMed Central

    Zhang, Jing; Wang, Chen; Yu, Shuchun; Luo, Zhenzhong; Chen, Yong; Liu, Qin; Hua, Fuzhou; Xu, Guohai; Yu, Peng

    2014-01-01

    Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway plays a key role in myocardial ischemia-reperfusion (I/R) injury. Mammalian target of rapamycin (mTOR), a downstream target of PI3K/AKT signaling, is necessary and sufficient to protect the heart from I/R injury. Inhaled anesthetic sevoflurane is widely used in cardiac surgeries because its induction and recovery are faster and smoother than other inhaled anesthetics. Sevoflurane proved capable of inducing postconditioning effects in the myocardium. However, the underlying molecular mechanisms for sevoflurane-induced postconditioning (SPC) were largely unclear. In the present study, we demonstrated that SPC protects myocardium from I/R injury with narrowed cardiac infarct focus, increased ATP content, and decreased cardiomyocyte apoptosis, which are mainly due to the activation of PI3K/AKT/mTOR signaling and the protection of mitochondrial energy metabolism. Application of dactolisib (BEZ235), a PI3K/mTOR dual inhibitor, abolishes the up-regulation of pho-AKT, pho-GSK, pho-mTOR, and pho-p70s6k induced by SPC, hence abrogating the anti-apoptotic effect of sevoflurane and reducing SPC-mediated protection of heart from I/R injury. As such, this study proved that PI3K/AKT/mTOR pathway plays an important role in SPC induced cardiac protection against I/R injury. PMID:25471136

  20. Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration.

    PubMed

    Solskov, Lasse; Løfgren, Bo; Kristiansen, Steen B; Jessen, Niels; Pold, Rasmus; Nielsen, Torsten T; Bøtker, Hans Erik; Schmitz, Ole; Lund, Sten

    2008-07-01

    The UK Prospective Diabetes Study demonstrated that the hypoglycaemic drug metformin is associated with a reduction in cardiovascular events in a group of obese type 2 diabetes patients. The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 +/- 3.9%versus 36.7 +/- 3.6%, P < 0.01, n = 8-14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-alpha2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin.

  1. Inhibition of inflammation and oxidative stress by an imidazopyridine derivative X22 prevents heart injury from obesity.

    PubMed

    Qian, Yuanyuan; Zhang, Yali; Zhong, Peng; Peng, Kesong; Xu, Zheng; Chen, Xuemei; Lu, Kongqin; Chen, Gaozhi; Li, Xiaokun; Liang, Guang

    2016-08-01

    Inflammation and oxidative stress plays an important role in the development of obesity-related complications and cardiovascular disease. Benzimidazole and imidazopyridine compounds are a class of compounds with a variety of activities, including anti-inflammatory, antioxidant and anti-cancer. X22 is an imidazopyridine derivative we synthesized and evaluated previously for anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. However, its ability to alleviate obesity-induced heart injury via its anti-inflammatory actions was unclear. This study was designed to evaluate the cardioprotective effects of X22 using cell culture studies and a high-fat diet rat model. We observed that palmitic acid treatment in cardiac-derived H9c2 cells induced a significant increase in reactive oxygen species, inflammation, apoptosis, fibrosis and hypertrophy. All of these changes were inhibited by treatment with X22. Furthermore, oral administration of X22 suppressed high-fat diet-induced oxidative stress, inflammation, apoptosis, hypertrophy and fibrosis in rat heart tissues and decreased serum lipid concentration. We also found that the anti-inflammatory and anti-oxidative actions of X22 were associated with Nrf2 activation and nuclear factor-kappaB (NF-κB) inhibition, respectively, both in vitro and in vivo. The results of this study indicate that X22 may be a promising cardioprotective agent and that Nrf2 and NF-κB may be important therapeutic targets for obesity-related complications. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Effects of Respiratory Training on Heart Rate Variability and Baroreflex Sensitivity in Individuals with Chronic Spinal Cord Injury.

    PubMed

    Legg Ditterline, Bonnie E; Aslan, Sevda C; Randall, David C; Harkema, Susan J; Castillo, Camilo; Ovechkin, Alexander V

    2017-08-09

    To evaluate the effects of pressure threshold respiratory training (RT) on heart rate variability and baroreflex sensitivity in persons with chronic spinal cord injury (SCI). Before-after intervention case-controlled clinical study. SCI research center and outpatient rehabilitation unit. Persons with chronic SCI ranging from C2 to T11 that participated in RT (n=24) and untrained chronic SCI controls ranging from C2 to T9 (n=20). A total of 21 ± 2 of RT sessions performed 5 days a week during a four-week period using a combination of pressure threshold inspiratory and expiratory devices. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and beat-to-beat arterial blood pressure (BP) and heart rate (HR) changes during 5-second long maximum expiratory pressure maneuver (5s MEP) and sit-up orthostatic stress test acquired before and after the RT program. In contrast to the untrained controls, individuals in RT group experienced significantly increased FVC and FEV1 (both p < .01) in association with improved quality of sleep, cough, and speech. Sympathetically (phase II) and parasympathetically (phase IV) mediated baroreflex sensitivity both significantly (p < .05) increased during 5s MEP. During orthostatic stress test, improved autonomic control over HR was associated with significantly increased sympathetic and parasympathetic modulation (low- and high-frequency change, p < .01 and p < .05, respectively). The results indicate that inspiratory-expiratory pressure threshold RT is a promising technique to positively impact both respiratory and cardiovascular dysregulation observed in persons with chronic SCI. Copyright © 2017. Published by Elsevier Inc.

  3. [Resuscitation for myocardial infarction and head injury: first the heart or first the head?].

    PubMed

    van Noord, Peter T; Gosselink, A T Marcel; Haringman, Jasper J

    2014-01-01

    Loss of circulation in a patient results in collapse and therefore possible head injury. After percutaneous coronary intervention (PCI) including anticoagulation, comatose patients are sedated for mild therapeutic hypothermia. Recognised or unrecognised head trauma may have dramatic clinical consequences. A 42-year-old male with unrecognised head trauma died due to a massive intracranial haemorrhage (ICH) during the hypothermia phase after being treated with PCI. A 76-year-old female, on anticoagulation for atrial fibrillation, with recognised ICH which resulted in an adjusted PCI, died after five days due to a lethal re-bleed. In a 55-year-old male with neurological abnormalities after mild head trauma, the PCI was postponed for a (negative) head CT which might have increased cardiac muscle damage. Nowadays more patients reach hospital after being resuscitated for cardiac arrest and possible head trauma should be considered in all these patients. This could lead to adjustments being made in the treatment protocol.

  4. How Does the Ca(2+)-paradox Injury Induce Contracture in the Heart?-A Combined Study of the Intracellular Ca(2+) Dynamics and Cell Structures in Perfused Rat Hearts.

    PubMed

    Mani, Hiroki; Tanaka, Hideo; Adachi, Tetsuya; Ikegawa, Masaya; Dai, Ping; Fujita, Naohisa; Takamatsu, Tetsuro

    2015-01-01

    The calcium (Ca(2+))-paradox injury of the heart, induced by restoration of extracellular Ca(2+) after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca(2+)-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca(2+) dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca(2+) paradox. Under rapid-scanning confocal microscopy, repletion of Ca(2+) following its depletion produced high-frequency Ca(2+) waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca(2+) influx in the injury. However, saponin-induced membrane permeabilization of Ca(2+) showed no apparent contracture despite the emergence of high-frequency Ca(2+) waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca(2+) paradox. In immunohistochemistry Ca(2+) depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca(2+) influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca(2+)-paradox injury.

  5. Molecular Evidence of Stress-Induced Acute Heart Injury in a Mouse Model Simulating Posttraumatic Stress Disorder

    DTIC Science & Technology

    2014-02-25

    exposures lead directly to irreversible changes in the heart, which is reflected by heart pain, cardiac arrhythmias , and heart failure. In addition, our...pro- cess (Fig. 2). The miR-29 family members have been implicated in arrhythmias , myocardial fibrosis, and other heart conditions (22–24). In addition

  6. Role of 12-week resistance training in preserving the heart against ischemia-reperfusion-induced injury.

    PubMed

    Soufi, Farhad Ghadiri; Saber, Mohaddeseh Mahmoudi; Ghiassie, Rafigheh; Alipour, Mohsen

    2011-01-01

    Discovering an effective approach to provide cardioprotection against coronary artery disease has long been sought. We studied the cardioprotective effect of resistance training against ischemia-reperfusion-induced injury. Twenty male rats were divided into trained and sedentary groups (n = 10 in each). The rats were exercised in squat-training apparatus (12 repetitions/set, four sets/day and five days/week for 12 weeks). After the last training session, transient regional ischemia of left anterior descending coronary artery (40 min) was followed by 80 min of reperfusion. Coronary flow, left ventricular developed pressure, diastolic pressure and infarct size were measured. After 35 min of ischemia, coronary flow and developed pressure were higher in trained than untrained groups (10.37 ± 0.96 vs 7.54 ± 0.89 mL/min × g, p < 0.01 for coronary flow and 67.74 ± 3.31 vs 52.39 ± 4.28 mm Hg, p < 0.01 for developed pressure) and this difference persisted until 50 min of reperfusion (10.59 ± 0.88 vs 7.71 ± 0.73 mL/ /min × g, p < 0.01 for coronary flow and 58.12 ± 4.07 vs 39.56 ± 3.79 mm Hg, p < 0.01 for developed pressure). Diastolic pressure was significantly lower from 35 min of ischemia (11.51 ± 5.37 vs 24.53 ± 5.44 mm Hg, p < 0.05) through 35 min of reperfusion in trained rather than sedentary rats (30.62 ± 3.19 vs 43 ± 7.11 mm Hg, p < 0.01). Resistance exercise training reduced the infarct size statistically in trained rats as compared with sedentary animals (39.32 ± 4.09 vs 29.36 ± 4.17 percentage of zone at risk, p < 0.05). These results show that chronic resistance exercise provides cardioprotection against myocardial injuries.

  7. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

    PubMed Central

    Khandelwal, Vinoth Kumar Megraj; Balaraman, R.; Pancza, Dezider; Ravingerová, Táňa

    2011-01-01

    Hemidesmus indicus (L.) R. Br. (HI) and Hibiscus rosa-sinensis L. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions. PMID:20953394

  8. Argonaute proteins in cardiac tissue contribute to the heart injury during viral myocarditis.

    PubMed

    Sun, Shougang; Ma, Jialiang; Zhang, Quan; Wang, Qiongying; Zhou, Lei; Bai, Feng; Hu, Hao; Chang, Peng; Yu, Jing; Gao, Bingren

    2016-01-01

    MicroRNAs (miRNAs) are a group of short, noncoding, regulatory RNA molecules the dysregulation of which contributes to the pathogenesis of myocarditis. Argonaute proteins are essential components of miRNA-induced silencing complex and play important roles during miRNA biogenesis and function. However, the expression pattern of four AGO family members has not yet been detected in the coxsackievirus B3 (CVB3)-induced myocarditis tissue samples. In this study, we detected the expression of four AGOs in the CVB3-infected mouse heart tissues and found that AGO1 and AGO3 up-regulated significantly at 4 and 8h after CVB3 infection. Further in vitro research indicated that up-regulated AGO1 and AGO3 are related to the down-regulated TNFAIP3, which is a negative regulator of NF-κB pathway. Subsequently, we confirmed that TNFAIP3 is a direct target of miR-19a/b, and during CVB3 infection, the expression of miR-19a/b and miR-125a/b is not significantly changed. TNFAIP3 level is mainly reduced by up-regulated AGO1 and AGO3. This research sheds light on the relationship between overexpressed AGO proteins and CVB3-induced myocarditis, and this provides potential therapeutic target for viral myocarditis.

  9. Maintenance of cAMP in non-heart-beating donor lungs reduces ischemia-reperfusion injury.

    PubMed

    Hoffmann, S C; Bleiweis, M S; Jones, D R; Paik, H C; Ciriaco, P; Egan, T M

    2001-06-01

    Studies suggest that pulmonary vascular ischemia-reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the beta(2)-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O(2) or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 microM) and roli (2 microM). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p < 0.05) compared with non-iso/roli-reperfused groups after 2 h of postmortem ischemia. Total adenine nucleotide (TAN) levels correlated with Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.

  10. Non-suicidal Self-Injury in Eating Disordered Patients: Associations with Heart Rate Variability and State-Trait Anxiety.

    PubMed

    Giner-Bartolome, Cristina; Mallorquí-Bagué, Núria; Tolosa-Sola, Iris; Steward, Trevor; Jimenez-Murcia, Susana; Granero, Roser; Fernandez-Aranda, Fernando

    2017-01-01

    Background: Non-suicidal self-injury (NSSI) is commonly present in individuals with eating disorders (EDs) and is often employed as a maladaptive emotion regulation strategy to avoid or abate negative emotions. One of the most prevalent negative emotions experienced by self-injurers is anxiety; however, this emotion has not been extensively studied in this population. Thus, the aim of our study was to investigate the influence of anxiety on NSSI in patients with ED from two different dimensions: state anxiety and trait anxiety. Methods: The study comprised a total of 66 females: 12 ED patients with NSSI, 32 ED patients without a history of NSSI, and 22 healthy controls. State and trait anxiety were assessed by means of State-Trait Anxiety Inventory (STAI-S-T) and physiological data [i.e., heart rate variability (HRV)] were collected. Results: STAI-trait scores were significantly higher in ED patients with NSSI than ED patients without NSSI. Furthermore, when conducting logistic regression analyses higher STAI-trait scores were associated with NSSI in ED patients. However, no differences in STAI-state scores and HRV were found between ED patients with and without NSSI. Discussion: The present findings suggest that anxiety as a trait is associated with the use of maladaptive strategies (i.e., NSSI) in ED patients. These results uphold the need to target trait anxiety in ED treatment in order to prevent possible NSSI behaviors.

  11. Non-suicidal Self-Injury in Eating Disordered Patients: Associations with Heart Rate Variability and State-Trait Anxiety

    PubMed Central

    Giner-Bartolome, Cristina; Mallorquí-Bagué, Núria; Tolosa-Sola, Iris; Steward, Trevor; Jimenez-Murcia, Susana; Granero, Roser; Fernandez-Aranda, Fernando

    2017-01-01

    Background: Non-suicidal self-injury (NSSI) is commonly present in individuals with eating disorders (EDs) and is often employed as a maladaptive emotion regulation strategy to avoid or abate negative emotions. One of the most prevalent negative emotions experienced by self-injurers is anxiety; however, this emotion has not been extensively studied in this population. Thus, the aim of our study was to investigate the influence of anxiety on NSSI in patients with ED from two different dimensions: state anxiety and trait anxiety. Methods: The study comprised a total of 66 females: 12 ED patients with NSSI, 32 ED patients without a history of NSSI, and 22 healthy controls. State and trait anxiety were assessed by means of State-Trait Anxiety Inventory (STAI-S-T) and physiological data [i.e., heart rate variability (HRV)] were collected. Results: STAI-trait scores were significantly higher in ED patients with NSSI than ED patients without NSSI. Furthermore, when conducting logistic regression analyses higher STAI-trait scores were associated with NSSI in ED patients. However, no differences in STAI-state scores and HRV were found between ED patients with and without NSSI. Discussion: The present findings suggest that anxiety as a trait is associated with the use of maladaptive strategies (i.e., NSSI) in ED patients. These results uphold the need to target trait anxiety in ED treatment in order to prevent possible NSSI behaviors. PMID:28736544

  12. ROS-Mediated NLRP3 Inflammasome Activation in Brain, Heart, Kidney, and Testis Ischemia/Reperfusion Injury

    PubMed Central

    Minutoli, Letteria; Puzzolo, Domenico; Rinaldi, Mariagrazia; Irrera, Natasha; Marini, Herbert; Arcoraci, Vincenzo; Bitto, Alessandra; Crea, Giovanni; Pisani, Antonina; Squadrito, Francesco; Trichilo, Vincenzo; Bruschetta, Daniele; Micali, Antonio; Altavilla, Domenica

    2016-01-01

    Ischemia and reperfusion (I/R) causes a reduction in arterial blood supply to tissues, followed by the restoration of perfusion and consequent reoxygenation. The reestablishment of blood flow triggers further damage to the ischemic tissue through reactive oxygen species (ROS) accumulation, interference with cellular ion homeostasis, and inflammatory responses to cell death. In normal conditions, ROS mediate important beneficial responses. When their production is prolonged or elevated, harmful events are observed with peculiar cellular changes. In particular, during I/R, ROS stimulate tissue inflammation and induce NLRP3 inflammasome activation. The mechanisms underlying the activation of NLRP3 are several and not completely elucidated. It was recently shown that NLRP3 might sense directly the presence of ROS produced by normal or malfunctioning mitochondria or indirectly by other activators of NLRP3. Aim of the present review is to describe the current knowledge on the role of NLRP3 in some organs (brain, heart, kidney, and testis) after I/R injury, with particular regard to the role played by ROS in its activation. Furthermore, as no specific therapy for the prevention or treatment of the high mortality and morbidity associated with I/R is available, the state of the art of the development of novel therapeutic approaches is illustrated. PMID:27127546

  13. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity.

    PubMed

    Nduhirabandi, Frederic; Du Toit, Eugene F; Blackhurst, Dee; Marais, David; Lochner, Amanda

    2011-03-01

    Obesity, a major risk factor for ischemic heart disease, is associated with increased oxidative stress and reduced antioxidant status. Melatonin, a potent free radical scavenger and antioxidant, has powerful cardioprotective effects in lean animals but its efficacy in obesity is unknown. We investigated the effects of chronic melatonin administration on the development of the metabolic syndrome as well as ischemia-reperfusion injury in a rat model of diet-induced obesity (DIO). Male Wistar rats received a control diet, a control diet with melatonin, a high-calorie diet, or a high-calorie diet with melatonin (DM). Melatonin (4 mg/kg/day) was administered in the drinking water. After 16 wk, biometric and blood metabolic parameters were measured. Hearts were perfused ex vivo for the evaluation of myocardial function, infarct size (IFS) and biochemical changes [activation of PKB/Akt, ERK, p38 MAPK, AMPK, and glucose transporter (GLUT)-4 expression). The high-calorie diet caused increases in body weight (BW), visceral adiposity, serum insulin and triglycerides (TRIG), with no change in glucose levels. Melatonin treatment reduced the BW gain, visceral adiposity, blood TRIG, serum insulin, homeostatic model assessment index and thiobarbituric acid reactive substances in the DIO group. Melatonin reduced IFS in DIO and control groups and increased percentage recovery of functional performance of DIO hearts. During reperfusion, hearts from melatonin-treated rats had increased activation of PKB/Akt, ERK42/44 and reduced p38 MAPK activation. Chronic melatonin treatment prevented the metabolic abnormalities induced by DIO and protected the heart against ischemia-reperfusion injury. These beneficial effects were associated with activation of the reperfusion injury salvage kinases pathway.

  14. Estrogen protects the heart from ischemia-reperfusion injury via COX-2-derived PGI2.

    PubMed

    Booth, Erin Anne; Flint, RaShonda Renee; Lucas, Kathryn Louise; Knittel, Andrea Kathleen; Lucchesi, Benedict R

    2008-09-01

    There is an accumulating body of data to suggest that estrogen mediates its cardioprotective effects via cyclooxygenase activation and synthesis of prostaglandins (PG), specifically PGI2. We hypothesized that inhibition of COX-2 would prevent estrogen's cardioprotective effects after myocardial ischemia-reperfusion. Acute treatment with 17beta-estradiol (E2; 20 microg/rabbit) increased COX-2 protein expression and activity in the myocardium. To determine the effects of COX-2 inhibition on infarct size after E2 treatment, New Zealand white rabbits were anesthetized and administered the COX-2 inhibitor nimesulide (5 mg/kg) or vehicle intravenously 30 minutes before an intravenous injection of E2. Thirty minutes after estrogen treatment, the coronary artery was occluded for 30 minutes followed by 4 hours of reperfusion. E2 significantly decreased infarct size as a percent of area at risk when compared to vehicle (18.9 +/- 3.1 versus 47.0 +/- 4.1; P < 0.001). Pretreatment with nimesulide nullified the infarct size sparing effect of E2 (55.8 +/- 5.6). Treatment with the PGI2 receptor antagonist RO3244794 also abolished the protective effects of E2 (45.3 +/- 4.5). The results indicate that estrogen protects the myocardium from ischemia-reperfusion injury through increased production of COX-2-derived PGI2. The data indicate that selective COX-2 inhibitors might counteract the potential cytoprotective effects of estrogen in premenopausal or postmenopausal women.

  15. Time-to-Surgery and Pre-operative Cerebral Hemodynamics Predict Post-operative White Matter Injury in Neonates with Hypoplastic Left Heart Syndrome

    PubMed Central

    Lynch, Jennifer M.; Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Xiao, Rui; Goff, Donna A.; Nicolson, Susan C.; Montenegro, Lisa M.; Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.; Yodh, Arjun G.; Naim, Maryam Y.; Licht, Daniel J.

    2014-01-01

    Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury. PMID:25109755

  16. Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury.

    PubMed

    Wu, Shi-Zheng; Li, Ying-Lan; Huang, Wei; Cai, Wen-Feng; Liang, Jialiang; Paul, Christian; Jiang, Lin; Wu, Zhi-Chao; Xu, Meifeng; Zhu, Ping; Wang, Yigang

    2017-03-01

    It has been reported that CXCR4-overexpressing mesenchymal stem cells (MSC(CX4) ) can repair heart tissue post myocardial infarction. This study aims to investigate the MSCCX4-derived paracrine cardio-protective signaling in the presence of myocardial infarction. Mesenchymal stem cells (MSCs) were divided into 3 groups: MSC only, MSC(CX4) , and CXCR4 gene-specific siRNA-transduced MSC. Mesenchymal stem cells were exposed to hypoxia, and then MSCs-conditioned culture medium was incubated with neonatal and adult cardiomyocytes, respectively. Cell proliferation-regulating genes were assessed by real-time polymerase chain reaction (RT-PCR). In vitro: The number of cardiomyocytes undergoing DNA synthesis, cytokinesis, and mitosis was increased to a greater extent in MSC(CX4) medium-treated group than control group, while this proproliferative effect was reduced in CXCR4 gene-specific siRNA-transduced MSC-treated cells. Accordingly, the maximal enhancement of vascular endothelial growth factor, cyclin 2, and transforming growth factor-β2 was observed in hypoxia-exposed MSC(CX4) . In vivo: MSCs were labeled with enhanced green fluorescent protein (EGFP) and engrafted into injured myocardium in rats. The number of EGFP and CD31 positive cells in the MSC(CX4) group was significantly increased than other 2 groups, associated with the reduced left ventricular (LV) fibrosis, the increased LV free wall thickness, the enhanced angiogenesis, and the improved contractile function. CXCR4 overexpression can mobilize MSCs into ischemic area, whereby these cells can promoted angiogenesis and alleviate LV remodeling via paracrine signaling mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Evaluation of Chronic Physical and Psychological Stress Induction on Cardiac Ischemia / Reperfusion Injuries in Isolated Male Rat Heart: The Role of Sympathetic Nervous System.

    PubMed

    Rakhshan, Kamran; Imani, Alireza; Faghihi, Mahdieh; Nabavizadeh, Fatemeh; Golnazari, Masoumeh; Karimian, SeyedMorteza

    2015-08-01

    Exposure to stress leads to physiological changes called "stress response" which are the result of the changes in the adrenomedullary hormone system, hypothalamus-pituitary-adrenal (HPA) and sympathetic nervous system (SNS) activity. In the present study, the effects of chronic physical and psychological stress and also the role of sympathetic system effects in stress on ischemia/reperfusion (I/R) injuries have been studied in isolated rat heart. Rat heart was isolated and subjected to 30 min regional ischemia and 120 min reperfusion. The daily stress was induced for one week prior to I/R induction. Sympathectomy was done chemically by injection of hydroxyl-dopamine prior to stress induction. There were no significant changes in heart rate and Coronary Flow between groups. Left ventricular developed pressure (LVDP) and rate product pressure (RPP) in both physical and psychological stress groups decreased significantly compared to those in control group (P<0.05), but there was no significant difference between physical and psychological stress groups. Infarct size significantly increased in both physical and psychological stress groups and control group(P<0.05. Sympathectomy before induction of stress led to the elimination of the deleterious effects of stress as compared with stress groups (P<0.05). These results show that induction of chronic physical and psychological stress prior to ischemia/reperfusion causes enhancement of myocardial injuries and it seems that increased sympathetic activity in response to stress is responsible for these adverse effects of stress on ischemic/reperfused heart.

  18. Is oxidative stress primarily involved in reperfusion injury of the ischemic heart

    SciTech Connect

    Nohl, H.; Stolze, K.; Napetschnig, S.; Ishikawa, T. )

    1991-01-01

    Reperfusion injury of ischemic organs is suggested to result from metabolic derangements initiating an imbalanced formation of free oxygen radicals. Most investigators in this field have used the spin-trap 5,5'-dimethyl-N-pyrroline-N-oxide (DMPO) to stabilize these short-lived radicals and make them visible by means of the electron spin resonance (ESR) technique. ESR signals obtained from intravascular DMPO were reported to indicate the formation of free OH. radicals and, in some cases, also carbon-centered radicals. We were unable to confirm these findings. Carbon-centered radicals were not obtained irrespectively of conditions studied, while oxygen-centered DMPO-adducts could only be detected in minor amounts. Instead, we observed an ascorbyl-related ESR signal. The addition of ethylenediaminetetraacetic acid (EDTA), which was used by many investigators in this field, was found to greatly influence ESR-spectra of the reperfusion fluid. The ascorbyl radical concentration was clearly reduced and the DMPO-OH. adduct became more prominent. The addition of iron further stimulated this change eliciting a Fenton-type reaction responsible for DMPO-OH.-related ESR spectra in the perfusate after ischemia. Accordingly, we observed the release of iron and ascorbic acid into the perfusate as a consequence of ischemia. We could demonstrate that iron in the presence of ascorbate and EDTA causes both types of radicals detected in the perfusate. DMPO-OH. generation in the presence of EDTA was found to result from free OH. radicals that were not generated in the absence of EDTA.

  19. Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs.

    PubMed

    Guo, Hui-Cai; Zhang, Zhe; Zhang, Li-Nan; Xiong, Chen; Feng, Chen; Liu, Qian; Liu, Xu; Shi, Xiao-Lu; Wang, Yong-Li

    2009-07-01

    To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts. Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (p(B)=404 mmHg, p(O2)=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence. After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H(2)O(2)) were attenuated by CIHH and CAT. These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig.Acta Pharmacologica Sinica (2009) 30: 947-955; doi: 10.1038/aps.2009.57; published online 22 June 2009.

  20. Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs

    PubMed Central

    Guo, Hui-cai; Zhang, Zhe; Zhang, Li-nan; Xiong, Chen; Feng, Chen; Liu, Qian; Liu, Xu; Shi, Xiao-lu; Wang, Yong-li

    2009-01-01

    Aim: To investigate the protection and the anti-oxidative mechanism afforded by chronic intermittent hypobaric hypoxia (CIHH) against ischemia/reperfusion (I/R) injury in guinea pig hearts. Methods: Adult male guinea pigs were exposed to CIHH by mimicking a 5000 m high altitude (pB=404 mmHg, pO2=84 mmHg) in a hypobaric chamber for 6 h/day for 28 days. Langendorff-perfused isolated guinea pig hearts were used to measure variables of left ventricular function during baseline perfusion, ischemia and the reperfusion period. The activity and protein expression of antioxidant enzymes in the left myocardium were evaluated using biochemical methods and Western blotting, respectively. Intracellular reactive oxygen species (ROS) were assessed using ROS-sensitive fluorescence. Results: After 30 min of global no-flow ischemia followed by 60 min of reperfusion, myocardial function had better recovery rates in CIHH guinea pig hearts than in control hearts. The activity and protein expression of superoxide dismutase (SOD) and catalase (CAT) were significantly increased in the myocardium of CIHH guinea pigs. Pretreatment of control hearts with an antioxidant mixture containing SOD and CAT exerted cardioprotective effects similar to CIHH. The irreversible CAT inhibitor aminotriazole (ATZ) abolished the cardioprotection of CIHH. Cardiac contractile dysfunction and oxidative stress induced by exogenous hydrogen peroxide (H2O2) were attenuated by CIHH and CAT. Conclusions: These data suggest that CIHH protects the heart against I/R injury through upregulation of antioxidant enzymes in guinea pig. PMID:19543301

  1. Effect of the myosin light chain kinase inhibitor ML-7 on the proteome of hearts subjected to ischemia-reperfusion injury.

    PubMed

    Lin, Han-bin; Cadete, Virgilio J J; Sawicka, Jolanta; Wozniak, Mieczyslaw; Sawicki, Grzegorz

    2012-09-18

    In the development of ischemia/reperfusion (I/R) injury, the role of the myosin light chain (MLC) phosphorylation has been given increased consideration. ML-7, a MLC kinase inhibitor, has been shown to protect cardiac function from I/R, however the exact mechanism remains unclear. Isolated rat hearts were perfused under aerobic conditions (controls) or subjected to I/R in the presence or absence of ML-7. Continuous administration of ML-7 (5 μM) from 10 min before onset of ischemia to the first 10 min of reperfusion resulted in significant recovery of heart contractility. Analysis of gels from two-dimensional electrophoresis revealed eight proteins with decreased levels in I/R hearts. Six proteins are involved in energy metabolism:ATP synthase beta subunit, cytochrome b-c1 complex subunit 1, 24-kDa mitochondrial NADH dehydrogenase, NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, cytochrome c oxidase subunit, and succinyl-CoA ligase subunit. The other two proteins with decreased levels in I/R hearts are: peroxiredoxin-2 and tubulin. Administration of ML-7 increased level of succinyl-CoA ligase, key enzyme involved in the citric acid cycle. The increased level of succinyl-CoA ligase in I/R hearts perfused with ML-7 suggests that the cardioprotective effect of ML-7, at least partially, also may involve increase of energy production. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure.

    PubMed

    Breidthardt, Tobias; Socrates, Thenral; Drexler, Beatrice; Noveanu, Markus; Heinisch, Corinna; Arenja, Nisha; Klima, Theresia; Züsli, Christina; Reichlin, Tobias; Potocki, Mihael; Twerenbold, Raphael; Steiger, Jürg; Mueller, Christian

    2012-01-07

    The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P<0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P<0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P=0.04) in multivariable regression analysis. Plasma NGAL levels do not adequately predict AKI in patients with AHF.

  3. Plasma neutrophil gelatinase-associated lipocalin for the prediction of acute kidney injury in acute heart failure

    PubMed Central

    2012-01-01

    Introduction The accurate prediction of acute kidney injury (AKI) in patients with acute heart failure (AHF) is an unmet clinical need. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel sensitive and specific marker of AKI. Methods A total of 207 consecutive patients presenting to the emergency department with AHF were enrolled. Plasma NGAL was measured in a blinded fashion at presentation and serially thereafter. The potential of plasma NGAL levels to predict AKI was assessed as the primary endpoint. We defined AKI according to the AKI Network classification. Results Overall 60 patients (29%) experienced AKI. These patients were more likely to suffer from pre-existing chronic cardiac or kidney disease. At presentation, creatinine (median 140 (interquartile range (IQR), 91 to 203) umol/L versus 97 (76 to 132) umol/L, P < 0.01) and NGAL (114.5 (IQR, 67.1 to 201.5) ng/ml versus 74.5 (60 to 113.9) ng/ml, P < 0.01) levels were significantly higher in AKI compared to non-AKI patients. The prognostic accuracy for measurements obtained at presentation, as quantified by the area under the receiver operating characteristic curve was mediocre and comparable for the two markers (creatinine 0.69; 95%CI 0.59 to 0.79 versus NGAL 0.67; 95%CI 0.57 to 0.77). Serial measurements of NGAL did not further increase the prognostic accuracy for AKI. Creatinine, but not NGAL, remained an independent predictor of AKI (hazard ratio (HR) 1.12; 95%CI 1.00 to 1.25; P = 0.04) in multivariable regression analysis. Conclusions Plasma NGAL levels do not adequately predict AKI in patients with AHF. PMID:22226205

  4. Axillofemoral Bypass Markedly Improved Acute Decompensated Heart Failure and Kidney Injury in a Patient with Severely Calcified Stenosis of Thoracoabdominal Aorta (Atypical Aortic Coarctation).

    PubMed

    Ishizuka, Masato; Yamada, Shintaro; Maemura, Sonoko; Yamamoto, Keisuke; Takizawa, Masataka; Uozumi, Hiroki; Minegishi, Sachito; Kobayashi, Jotaro; Ikenouchi, Hiroshi

    2017-09-30

    Atypical aortic coarctation (AAC) has been reported to occur anywhere along the aorta, except for the ascending aorta. The associated symptoms include hypotension in the lower half of the body, secondary hypertension in the upper half of the body, and heart failure. Here we present an 80-year-old Asian woman complaining of progressive exertional dyspnea. She was diagnosed with acute decompensated heart failure and kidney injury due to severely calcified stenosis of the thoracoabdominal aorta, the so called AAC. She received hemodiafiltration, and pulmonary congestion improved in part. Generally, surgical treatments are quite invasive in elderly patients. Endovascular stent graft placement is less invasive, however, fracture and rupture should be considered at severely calcified lesions like this case. Therefore, we selected extra-anatomical axillofemoral bypass. Her recovery after the surgery was remarkable. In a few days, she became free from hemodiafiltration, intravenous diuretics, and oxygen administration. We thought the contributive factors are the increase in kidney blood flow and the correction of afterload mismatch. The decrease in pulse pressure may reflect the reduction in systemic arterial compliance by axillofemoral bypass. The operative mortality of axillofemoral bypass was reported to be acceptable, although the patency of the axillofemoral bypass graft was not high enough. In conclusion, axillofemoral bypass is effective and feasible for elderly patients with acute decompensated heart failure and kidney injury due to AAC.

  5. Comparison of changes in heart rate variability and sacral skin perfusion in response to postural changes in people with spinal cord injury

    PubMed Central

    Jan, Yih-Kuen; Anderson, Mark; Soltani, Jeanine; Burns, Stephanie; Foreman, Robert D.

    2012-01-01

    The current clinical practice has established guidelines to assess influences of severity of autonomic injury on the control of heart and blood pressure following spinal cord injury (SCI). However, the influences of SCI-induced autonomic impairment on microvascular dysfunction have not yet been established. Heart rate variability (HRV) has been shown to be a potential tool for quantifying residual sympathovagal regulation of the cardiovascular system following SCI, and may be used to assess the effect of autonomic injury on skin microvascular dysfunction. A total of 26 people were recruited into the study, including 12 people with SCI and 14 healthy controls. R-R intervals and sacral skin perfusion were continually recorded during 10-min upright and 10-min prone postures. The sympathovagal balance was defined as the ratio of the power of the low frequency to the high frequency of HRV. The results showed that postural changes of healthy people produced significant changes in the sympathovagal balance; lower sympathovagal balance was associated with higher skin perfusion (p<0.05). People with SCI did not show a significant change of HRV and skin perfusion in response to postural changes. In this study, we have demonstrated that the sympathovagal balance assessed by HRV was associated with the skin vasoconstrictive response to postural changes. PMID:23761001

  6. Electrical injury

    MedlinePlus

    ... damage, especially to the heart, muscles, or brain. Electric current can cause injury in three ways: Cardiac arrest ... How long you were in contact with the electricity How the electricity moved through your body Your ...

  7. KR-31762, a novel KATP channel opener, exerts cardioprotective effects by opening SarcKATP channels in rat models of ischemia/reperfusion-induced heart injury.

    PubMed

    Lee, Sung-Hun; Yang, Min-Kyu; Lim, Jong-Hyun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Won, Hyung-Sik; Lee, Chang-Soo; Choi, Wahn-Soo; Shin, Hwa-Sup

    2008-04-01

    The cardioprotective effects of KR-31762, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, KR-31762 (3 and 10 microM) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate x LVDP) after 30-min reperfusion in a concentration-dependent manner, while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31762 also significantly increased the time to contracture (TTC) during ischemic period (20.0, 22.4 and 26.4 min for control, 3 and 10 microM, respectively), while decreasing the release of lactate dehydrogenase (LDH) from the heart during 30 min reperfusion (30.4, 14.3 and 19.7 U/g heart weight, respectively). All these parameters except LDH release were reversed by glyburide (1 microM), a nonselective blocker of K+(ATP) channel, but not by 5-hydroxydecanoate, a selective blocker of mitoK+(ATP) channel. In anesthetized rats subjected to 45-min occlusion of left anterior descending coronary artery followed by 90-min reperfusion, KR-31762 significantly decreased the infarct size (60.8, 40.5 and 37.8% for control, 0.3 and 1.0 mg/kg, iv, respectively). KR-31762 slightly relaxed the isolated rat aorta precontracted with methoxamine (IC(50): 23.5 microM). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal K(ATP) channel in rat hearts with the minimal vasorelaxant effects.

  8. Ranolazine reduces Ca2+ overload and oxidative stress and improves mitochondrial integrity to protect against ischemia reperfusion injury in isolated hearts.

    PubMed

    Aldakkak, Mohammed; Camara, Amadou K S; Heisner, James S; Yang, Meiying; Stowe, David F

    2011-10-01

    Ranolazine is a clinically approved drug for treating cardiac ventricular dysrhythmias and angina. Its mechanism(s) of protection is not clearly understood but evidence points to blocking the late Na+ current that arises during ischemia, blocking mitochondrial complex I activity, or modulating mitochondrial metabolism. Here we tested the effect of ranolazine treatment before ischemia at the mitochondrial level in intact isolated hearts and in mitochondria isolated from hearts at different times of reperfusion. Left ventricular (LV) pressure (LVP), coronary flow (CF), and O2 metabolism were measured in guinea pig isolated hearts perfused with Krebs-Ringer's solution; mitochondrial (m) superoxide (O2·-), Ca2+, NADH/FAD (redox state), and cytosolic (c) Ca2+ were assessed on-line in the LV free wall by fluorescence spectrophotometry. Ranolazine (5 μM), infused for 1 min just before 30 min of global ischemia, itself did not change O2·-, cCa2+, mCa2+ or redox state. During late ischemia and reperfusion (IR) O2·- emission and m[Ca2+] increased less in the ranolazine group vs. the control group. Ranolazine decreased c[Ca2+] only during ischemia while NADH and FAD were not different during IR in the ranolazine vs. control groups. Throughout reperfusion LVP and CF were higher, and ventricular fibrillation was less frequent. Infarct size was smaller in the ranolazine group than in the control group. Mitochondria isolated from ranolazine-treated hearts had mild resistance to permeability transition pore (mPTP) opening and less cytochrome c release than control hearts. Ranolazine may provide functional protection of the heart during IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block the late Na+ current. Subsequently it indirectly reduces O2·- emission, preserves bioenergetics, delays mPTP opening, and restricts loss of cytochrome c, thereby reducing necrosis and apoptosis.

  9. Cardiac surgery in patients with congenital heart disease is associated with acute kidney injury and the risk of chronic kidney disease.

    PubMed

    Madsen, Nicolas L; Goldstein, Stuart L; Frøslev, Trine; Christiansen, Christian F; Olsen, Morten

    2017-09-01

    Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort study included patients with congenital heart disease born between 1990-2010 with first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in- and out-patient laboratory serum creatinine data, we identified individuals fulfilling KDIGO stages of AKI within 5 days of cardiac surgery. A unique personal identifier enabled unambiguous data linkage and virtually complete follow-up. The cumulative incidences of CKD stages 2-5 according to presence of CS-AKI were computed utilizing serum creatinine values and Pottel's formula. Using Cox regression, the corresponding hazard ratios were computed, adjusting for sex, age at first cardiac surgery, calendar period of surgery, and congenital heart disease severity. Of 382 patients with congenital heart disease undergoing cardiac surgery, 127 experienced CS-AKI within 5 days of surgery. Median follow-up was 4.9 years. The five-year cumulative incidence of CKD for patients with CS-AKI was 12% (95% confidence interval 7%-20%), significantly higher than the 3% (1%-5%) for those without CS-AKI with a significant adjusted hazard ratio of 3.8 (1.4-10.4). Thus, CS-AKI in patients with congenital heart disease is common and is associated with an increased risk for CKD. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  10. Cardiomyocyte-specific overexpression of an active form of Rac predisposes the heart to increased myocardial stunning and ischemia-reperfusion injury

    PubMed Central

    Talukder, M. A. Hassan; Elnakish, Mohammad T.; Yang, Fuchun; Nishijima, Yoshinori; Alhaj, Mazin A.; Velayutham, Murugesan; Hassanain, Hamdy H.

    2013-01-01

    The GTP-binding protein Rac regulates diverse cellular functions including activation of NADPH oxidase, a major source of superoxide production (O2·−). Rac1-mediated NADPH oxidase activation is increased after myocardial infarction (MI) and heart failure both in animals and humans; however, the impact of increased myocardial Rac on impending ischemia-reperfusion (I/R) is unknown. A novel transgenic mouse model with cardiac-specific overexpression of constitutively active mutant form of Zea maize Rac D (ZmRacD) gene has been reported with increased myocardial Rac-GTPase activity and O2·− generation. The goal of the present study was to determine signaling pathways related to increased myocardial ZmRacD and to what extent hearts with increased ZmRacD proteins are susceptible to I/R injury. The effect of myocardial I/R was examined in young adult wild-type (WT) and ZmRacD transgenic (TG) mice. In vitro reversible myocardial I/R for postischemic cardiac function and in vivo regional myocardial I/R for MI were performed. Following 20-min global ischemia and 45-min reperfusion, postischemic cardiac contractile function and heart rate were significantly reduced in TG hearts compared with WT hearts. Importantly, acute regional myocardial I/R (30-min ischemia and 24-h reperfusion) caused significantly larger MI in TG mice compared with WT mice. Western blot analysis of cardiac homogenates revealed that increased myocardial ZmRacD gene expression is associated with concomitant increased levels of NADPH oxidase subunit gp91phox, O2·−, and P21-activated kinase. Thus these findings provide direct evidence that increased levels of active myocardial Rac renders the heart susceptible to increased postischemic contractile dysfunction and MI following acute I/R. PMID:23161879

  11. Cardioprotective Effects of Red Blood Cells on Ischemia and Reperfusion Injury in Isolated Rat Heart: Release of Nitric Oxide as a Potential Mechanism.

    PubMed

    Yang; Nichols; Mehta

    1996-10-01

    BACKGROUND: Circulating cells influence myocardial function during ischemia and reperfusion, (eg, neutrophils exacerbate, and platelets protect the myocardium from deterioration). This study was designed to determine the role of red blood cells on myocardial function following ischemia and reperfusion in isolated rat hearts. METHODS AND RESULTS: Exposure of buffer-perfused hearts to 40 minutes of total ischemia followed by 30 minutes of reperfusion resulted in myocardial dysfunction and injury, indicated by decrease in the force of cardiac contraction (FCC, -25 +/- 4%), increase in the coronary perfusion pressure (CPP, +20 +/- 3%) and decrease in myocardial superoxide dismutase (SOD, 2.5 +/- 0.2 vs 3.5 +/- 0.4 U/mg protein in sham ischemic hearts, P <.05). Perfusion of the hearts with washed rat red blood cells showed significant protective effects against ischemia and reperfusion, indicated by minimal change in FCC (-10 +/- 4%) and CPP (+3 +/- 3%) (both P <.01 vs buffer alone perfused hearts) and preservation of myocardial SOD activity (2.8 +/- 0.4 U/mg protein, P <.05 vs buffer alone perfused hearts). The cardioprotective effects of red blood cells were attenuated when the red blood cells were preincubated with the nitric oxide blood cells were attenuated when the red blood cells were preincubated with the nitric oxide blood cells were attenuated when the red blood cells were preincubated with the nitric oxide synthase inhibitors N(omicron)-nitro-l-arginine (l-NNA, 5 x 10(-4)M) or N(omicron)-nitro-l-arginine methyl ester (l-NAME, 5 x 10(-4)M) at 37 degrees C for 60 minutes before perfusion of the heart. Perfusion of hearts with the nitric oxide precursor l-arginine (2 x 10(-4)M) also exerted significant protective effects on FCC ( - 14 +/- 4%), CPP (+12 +/- 3%) and myocardial SOD activity (2.9 +/- 0.2 U/mg protein) following ischemia and reperfusion. In other studies, washed rat red blood cells expressed nitric oxide synthetase activity which was inhibited by

  12. Ginseng protects rodent hearts from acute myocardial ischemia-reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism.

    PubMed

    Zhou, Hua; Hou, Shao Zhen; Luo, Pei; Zeng, Bao; Wang, Jing Rong; Wong, Yuen Fan; Jiang, Zhi Hong; Liu, Liang

    2011-05-17

    Ginseng (Panax ginseng C.A. Meyer) is widely used in Asian communities for treating cardiovascular diseases. However, the mechanism by which it protects the myocardium in ischemia-reperfusion (I/R) injury remains unclear. In this study, we aim to investigate whether a standardized ginseng extract (RSE) protects rodent hearts against I/R injury and if glucocorticoid and/or estrogen receptor-mediated activation of Akt and Erk1/2 (the reperfusion injury salvage kinase pathway, RISK) and subsequent nitric oxide (NO) synthesis signaling are involved in this effect. Rats or gene-deleted mice were subjected to 30 min ischemia by occluding the left anterior descending coronary artery and 90 min reperfusion. Infarct size, serum level of creatine kinase (CK), lactate dehydrogenase (LDH), and NO, expression and phosphorylation of glucocorticoid receptor (GR), estrogen receptor (ER), phosphatidylinositol-3 kinase (PI3K), Akt, NO synthase (NOS), extracellular signal-regulated kinase (Erk) 1/2, p38, and c-Jun NH2 terminal kinases (JNK) were examined in rat or mice treated with or without RSE in the absence or presence of pharmacological inhibitors. RSE significantly reduced infarct size in a dose-dependent manner and reduced the incidence of arrhythmia, increased serum NO production, reduced serum activities of creatine kinase and lactate dehydrogenase. The infarct size reduction effect of RSE was abolished by RU468 (an inhibitor of GR), tamoxifen (an inhibitor of ER), LY294002 (an inhibitor of PI3K), Akt inhibitor IV (an inhibitor of Akt protein kinase), U0126 (an inhibitor of Erk1/2) and NG-nitro-l-arginine methyl ester hydrochloride (an inhibitor of NOS), but not actinomycin D (an inhibitor of transcription process). RSE also significantly increased the activation of GR/ER, PI3K-Akt-eNOS cascades and Erk1/2 signaling in rat heart. However, RSE did not markedly reduce infarct size in endothelium NOS(-/-) mice. This differs from its effect in inducible NOS(-/-) and wild type

  13. Short-term consumption of Ilex paraguariensis extracts protects isolated hearts from ischemia/reperfusion injury and contradicts exercise-mediated cardioprotection.

    PubMed

    Cahuê, Fábio; Souza, Simone; Dos Santos, Camilli Fernanda Martins; Machado, Victor; Nascimento, José H M; Barcellos, Luciane; Salerno, Verônica P

    2017-07-06

    Perfusion of hearts with extracts of Ilex paraguariensis (IP/mate) appears to reduce ischemia/reperfusion (I/R) injury. To determine if oral consumption of IP/mate can provide similar cardioprotection, short-term consumption was investigated alone or in association with exercise in rats. Animals were grouped into control (C), IP/mate consumption (M), exercise (E), and exercise with mate (E+M). M and E+M groups consumed IP/mate (1 g·kg(-1) body weight in 1 mL water) by gavage. E and E+M groups swam 7× per week for 30 min carrying an additional 5% of body weight. After 1 week, hearts were tested ex vivo to measure left ventricle developed pressure (LVDP), systolic and end diastolic pressure (LVSP/LVEDP), maximum velocity of contraction and relaxation (dP/dt+ and dP/dt-) during I/R and infarction size. In addition, cardiac tissue was analyzed for oxidative stress by lipid peroxidation and protein carbonyl levels along with activity of catalase and superoxide dismutase (SOD). LVDP was higher in hearts from M and E groups as well as decreased infarction sizes than others. At the end of reperfusion, dP/dt+ was increased in E and M and dP/dt- was higher in M. LVSP was higher in M and E compared with C. Protein carbonyl and thiobarbituric acid reactive substances levels were higher in M while SOD activity was increased in E. No differences were observed in other activities. The results suggest that short-term consumption of IP/mate has protective effects on heart I/R injury similar to exercise, but the combination of these interventions appears to contradict the beneficial adaptations from exercise.

  14. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    PubMed

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P < 0.05), decreased the duration of ventricular tachycardia and suppressed ventricular fibrillation. Likewise, the extent of lethal injury (infarct size) determined by tetrazolium staining and expressed in percentage of risk area, was significantly lower in both treated groups, moreover, the effect of P was more pronounced (27 +/- 2 % and 10 +/- 2 % in S and P groups, respectively, vs. 42 +/- 1 % in C; P < 0.05). In contrast, only S, but not P, was able to improve postischemic recovery of left ventricular developed pressure (LVDP; 48 +/- 12 % of preischemic values vs. 25 +/- 4 % in C and 21 +/ -7 % in P groups; P < 0.05). Our results suggest that differences in water solubility of statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  15. Inhibition of the Cardiomyocyte-Specific Kinase TNNI3K Limits Oxidative Stress, Injury, and Adverse Remodeling in the Ischemic Heart

    PubMed Central

    Vagnozzi, Ronald J.; Gatto, Gregory J.; Kallander, Lara S.; Hoffman, Nicholas E.; Mallilankaraman, Karthik; Ballard, Victoria L. T.; Lawhorn, Brian G.; Stoy, Patrick; Philp, Joanne; Graves, Alan P.; Naito, Yoshiro; Lepore, John J.; Gao, Erhe; Madesh, Muniswamy; Force, Thomas

    2015-01-01

    Percutaneous coronary intervention is first-line therapy for acute coronary syndromes (ACS) but can promote cardiomyocyte death and cardiac dysfunction via reperfusion injury, a phenomenon driven in large part by oxidative stress. Therapies to limit this progression have proven elusive, with no major classes of new agents since the development of anti-platelets/anti-thrombotics. We report that cardiac troponin I–interacting kinase (TNNI3K), a cardiomyocyte-specific kinase, promotes ischemia/reperfusion injury, oxidative stress, and myocyte death. TNNI3K-mediated injury occurs through increased mitochondrial superoxide production and impaired mitochondrial function and is largely dependent on p38 mitogen-activated protein kinase (MAPK) activation. We developed a series of small-molecule TNNI3K inhibitors that reduce mitochondrial-derived superoxide generation, p38 activation, and infarct size when delivered at reperfusion to mimic clinical intervention. TNNI3K inhibition also preserves cardiac function and limits chronic adverse remodeling. Our findings demonstrate that TNNI3K modulates reperfusion injury in the ischemic heart and is a tractable therapeutic target for ACS. Pharmacologic TNNI3K inhibition would be cardiac-selective, preventing potential adverse effects of systemic kinase inhibition. PMID:24132636

  16. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart

    PubMed Central

    Edin, Matthew L.; Wang, ZhongJing; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; DeGraff, Laura M.; Foley, Julie F.; Torphy, Robert; Ronnekleiv, Oline K.; Tomer, Kenneth B.; Lee, Craig R.; Zeldin, Darryl C.

    2011-01-01

    Cytochrome P450 (CYP) epoxygenases CYP2C8 and CYP2J2 generate epoxyeicosatrienoic acids (EETs) from arachidonic acid. Mice with expression of CYP2J2 in cardiomyocytes (αMHC-CYP2J2 Tr) or treated with synthetic EETs have increased functional recovery after ischemia/reperfusion (I/R); however, no studies have examined the role of cardiomyocyte- vs. endothelial-derived EETs or compared the effects of different CYP epoxygenase isoforms in the ischemic heart. We generated transgenic mice with increased endothelial EET biosynthesis (Tie2-CYP2C8 Tr and Tie2-CYP2J2 Tr) or EET hydrolysis (Tie2-sEH Tr). Compared to wild-type (WT), αMHC-CYP2J2 Tr hearts showed increased recovery of left ventricular developed pressure (LVDP) and decreased infarct size after I/R. In contrast, LVDP recovery and infarct size were unchanged in Tie2-CYP2J2 Tr and Tie2-sEH Tr hearts. Surprisingly, compared to WT, Tie2-CYP2C8 Tr hearts had significantly reduced LVDP recovery (from 21 to 14%) and increased infarct size after I/R (from 51 to 61%). Tie2-CYP2C8 Tr hearts also exhibited increased reactive oxygen species (ROS) generation, dihydroxyoctadecenoic acid (DiHOME) formation, and coronary resistance after I/R. ROS scavengers and CYP2C8 inhibition reversed the detrimental effects of CYP2C8 expression in Tie2-CYP2C8 Tr hearts. Treatment of WT hearts with 250 nM 9,10-DiHOME decreased LVDP recovery compared to vehicle (16 vs. 31%, respectively) and increased coronary resistance after I/R. These data demonstrate that increased ROS generation and enhanced DiHOME synthesis by endothelial CYP2C8 impair functional recovery and mask the beneficial effects of increased EET production following I/R.—Edin, M. L., Wang, Z. J., Bradbury, J. A., Graves, J. P., Lih, F. B., DeGraff, L. M., Foley, J. F., Torphy, R., Ronnekleiv, O. K., Tomer, K. B., Lee, C. R., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse

  17. On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury

    PubMed Central

    Cole, Mark A.; Abd Jamil, Amira H.; Heather, Lisa C.; Murray, Andrew J.; Sutton, Elizabeth R.; Slingo, Mary; Sebag-Montefiore, Liam; Tan, Suat Cheng; Aksentijević, Dunja; Gildea, Ottilie S.; Stuckey, Daniel J.; Yeoh, Kar Kheng; Carr, Carolyn A.; Evans, Rhys D.; Aasum, Ellen; Schofield, Christopher J.; Ratcliffe, Peter J.; Neubauer, Stefan; Robbins, Peter A.; Clarke, Kieran

    2016-01-01

    The role of peroxisome proliferator-activated receptor α (PPARα)-mediated metabolic remodeling in cardiac adaptation to hypoxia has yet to be defined. Here, mice were housed in hypoxia for 3 wk before in vivo contractile function was measured using cine MRI. In isolated, perfused hearts, energetics were measured using 31P magnetic resonance spectroscopy (MRS), and glycolysis and fatty acid oxidation were measured using [3H] labeling. Compared with a normoxic, chow-fed control mouse heart, hypoxia decreased PPARα expression, fatty acid oxidation, and mitochondrial uncoupling protein 3 (UCP3) levels, while increasing glycolysis, all of which served to maintain normal ATP concentrations ([ATP]) and thereby, ejection fractions. A high-fat diet increased cardiac PPARα expression, fatty acid oxidation, and UCP3 levels with decreased glycolysis. Hypoxia was unable to alter the high PPARα expression or reverse the metabolic changes caused by the high-fat diet, with the result that [ATP] and contractile function decreased significantly. The adaptive metabolic changes caused by hypoxia in control mouse hearts were found to have occurred already in PPARα-deficient (PPARα−/−) mouse hearts and sustained function in hypoxia despite an inability for further metabolic remodeling. We conclude that decreased cardiac PPARα expression is essential for adaptive metabolic remodeling in hypoxia, but is prevented by dietary fat.—Cole, M. A., Abd Jamil, A. H., Heather, L. C., Murray, A. J., Sutton, E. R., Slingo, M., Sebag-Montefiore, L., Tan, S. C., Aksentijević, D., Gildea, O. S., Stuckey, D. J., Yeoh, K. K., Carr, C. A., Evans, R. D., Aasum, E., Schofield, C. J., Ratcliffe, P. J., Neubauer, S., Robbins, P. A., Clarke, K. On the pivotal role of PPARα in adaptation of the heart to hypoxia and why fat in the diet increases hypoxic injury. PMID:27103577

  18. Acute kidney injury following first-stage palliation in hypoplastic left heart syndrome: hybrid versus Norwood palliation.

    PubMed

    Garcia, Richard U; Natarajan, Girija; Walters, Henry L; Delius, Ralph E; Aggarwal, Sanjeev

    2017-09-11

    The aim of this study was to evaluate the prevalence of acute kidney injury after first-stage surgical palliation in patients with a single ventricle and to explore associated risk factors and outcomes. Design and patients This single-centre retrospective study included neonates who underwent either Norwood or Hybrid procedure from 2008 to 2015 for a single ventricle. Postoperative acute kidney injury was defined using the paediatric risk, injury, failure, loss, end-stage renal disease (pRIFLE), criteria within 72 hours of the procedure. Main results Our cohort (n=48) underwent surgical palliation at a mean (SD) age of 12 (11) days. Postoperative acute kidney injury was diagnosed in 14 (29%) patients. The prevalence of acute kidney injury in the Hybrid group was 16% and 53% in the Norwood group. Infants who developed acute kidney injury underwent surgery at younger ages [6 (5-10) versus 10 (8-16) days, p=0.016], and had a higher peak lactate level in the initial 24 hours [5.9 (4.2-9.1) versus 3.4 (2.4-6.7), p=0.007]. Norwood procedure was significantly associated with acute kidney injury [odds ratio 11.7 (95% confidence interval 1.3-101.9), p=0.03]. ICU stay [38 (21-84) versus 16 (6-45) days, p=0.038] and time to extubation [204 (120-606) versus 72 (26-234) hours, p=0.014] were longer in those with acute kidney injury. The two patients who developed early postoperative renal failure as per pRIFLE died before discharge from associated comorbidities. Acute kidney injury occurs in a third of the patients with single ventricle after surgical palliation but is mostly transient. Norwood, compared with Hybrid procedure, is a risk factor for postoperative acute kidney injury, which, in turn, is associated with longer ICU stay and time to extubation.

  19. A case of marked diuresis by combined dopamine and atrial natriuretic peptide administration without renal injury in acute decompensated heart failure.

    PubMed

    Kamiya, Masataka; Sato, Naoki; Akiya, Mai; Okazaki, Hirotake; Takahashi, Yasuhiro; Mizuno, Kyoichi

    2013-01-01

    Renal injury is an important factor for worsening outcome in acute decompensated heart failure (ADHF). An 81-year-old woman was admitted due to ADHF with dyspnea and mild peripheral edema. The patient was managed with intravenous administration of atrial natriuretic peptide (ANP) at a dose of 0.0125 μg/kg/minute, which did not control volume overload even at an increased dose of 0.025 μg/kg/minute. After a low dose of dopamine (DA) of 1.0 μg/kg/ minute was added, urine output increased markedly to 120 from 30 mL/hour. Furthermore, her heart rate decreased to 80-100 from 120 bpm and the congestion improved with a reduced brain natriuretic peptide level. Interestingly, the combination of ANP and DA therapy reduced serum creatinine as well as the levels of urinary liver-type fatty acid binding protein, a novel reno-tubular stress marker, by 98.9%, and an oxidative stress marker, urinary 8-hydroxydeoxyguanosine, by 88.2% from baseline levels. Thus, this ADHF patient, a nonresponder to ANP alone, improved without renal injury when administered combination therapy consisting of low doses of ANP and DA, suggesting that this combined therapy might be useful for better management of ADHF in patients without diuretic responses with ANP alone. Further prospective studies are warranted.

  20. Altered expression of P2Y2 and P2X7 purinergic receptors in the isolated rat heart mediates ischemia-reperfusion injury.

    PubMed

    Granado, Miriam; Amor, Sara; Montoya, Juan José; Monge, Luis; Fernández, Nuria; García-Villalón, Ángel Luis

    2015-10-01

    The aim of this study is to analyze the expression of purinergic receptors in the heart after ischemia-reperfusion, and their possible role in ischemia-reperfusion injury. Rat hearts were perfused according to the Langendorff technique and subjected to 30 min ischemia followed by 15 min reperfusion. Ischemia-reperfusion reduced the gene expression and protein content of purinergic receptors of the P2Y2 subtype, and increased the gene expression and protein content of the P2X7 subtype. Treatment with the agonist of the P2Y2 subtype 2-thio-UTP and with the antagonist of the P2X7 subtype Brilliant Blue improved myocardial function parameters, reduced cell death and increased the myocardial expression of antiapoptotic markers after ischemia-reperfusion. These results suggest that the myocardial expression of the protective P2Y2 subtype of purinergic receptors is reduced, whereas that of the harmful subtype P2X7 subtype is increased during coronary ischemia-reperfusion. This may contribute to myocardial injury in this condition. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury.

    PubMed

    Khalaf, Aseel; Babiker, Fawzi

    2016-09-01

    We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I

  2. Hydrogen sulfide preconditions the db/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner

    PubMed Central

    Peake, Bridgette F.; Nicholson, Chad K.; Lambert, Jonathan P.; Hood, Rebecca L.; Amin, Hena; Amin, Sana

    2013-01-01

    Hydrogen sulfide (H2S) therapy protects nondiabetic animals in various models of myocardial injury, including acute myocardial infarction and heart failure. Here, we sought to examine whether H2S therapy provides cardioprotection in the setting of type 2 diabetes. H2S therapy in the form of sodium sulfide (Na2S) beginning 24 h or 7 days before myocardial ischemia significantly decreased myocardial injury in db/db diabetic mice (12 wk of age). In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, we focused on the role of nuclear factor E2-related factor (Nrf2) signaling. Our results indicate that diabetes does not alter the ability of H2S to increase the nuclear localization of Nrf2, but does impair aspects of Nrf2 signaling. Specifically, the expression of NADPH quinine oxidoreductase 1 was increased after the acute treatment, whereas the expression of heme-oxygenase-1 (HO-1) was only increased after 7 days of treatment. This discrepancy was found to be the result of an increased nuclear expression of Bach1, a known repressor of HO-1 transcription, which blocked the binding of Nrf2 to the HO-1 promoter. Further analysis revealed that 7 days of Na2S treatment overcame this impairment by removing Bach1 from the nucleus in an Erk1/2-dependent manner. Our findings demonstrate for the first time that exogenous administration of Na2S attenuates myocardial ischemia-reperfusion injury in db/db mice, suggesting the potential therapeutic effects of H2S in treating a heart attack in the setting of type 2 diabetes. PMID:23479260

  3. Hydrogen sulfide preconditions the db/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner.

    PubMed

    Peake, Bridgette F; Nicholson, Chad K; Lambert, Jonathan P; Hood, Rebecca L; Amin, Hena; Amin, Sana; Calvert, John W

    2013-05-01

    Hydrogen sulfide (H2S) therapy protects nondiabetic animals in various models of myocardial injury, including acute myocardial infarction and heart failure. Here, we sought to examine whether H2S therapy provides cardioprotection in the setting of type 2 diabetes. H2S therapy in the form of sodium sulfide (Na2S) beginning 24 h or 7 days before myocardial ischemia significantly decreased myocardial injury in db/db diabetic mice (12 wk of age). In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, we focused on the role of nuclear factor E2-related factor (Nrf2) signaling. Our results indicate that diabetes does not alter the ability of H2S to increase the nuclear localization of Nrf2, but does impair aspects of Nrf2 signaling. Specifically, the expression of NADPH quinine oxidoreductase 1 was increased after the acute treatment, whereas the expression of heme-oxygenase-1 (HO-1) was only increased after 7 days of treatment. This discrepancy was found to be the result of an increased nuclear expression of Bach1, a known repressor of HO-1 transcription, which blocked the binding of Nrf2 to the HO-1 promoter. Further analysis revealed that 7 days of Na2S treatment overcame this impairment by removing Bach1 from the nucleus in an Erk1/2-dependent manner. Our findings demonstrate for the first time that exogenous administration of Na2S attenuates myocardial ischemia-reperfusion injury in db/db mice, suggesting the potential therapeutic effects of H2S in treating a heart attack in the setting of type 2 diabetes.

  4. Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury.

    PubMed Central

    Marber, M S; Mestril, R; Chi, S H; Sayen, M R; Yellon, D M; Dillmann, W H

    1995-01-01

    Myocardial protection and changes in gene expression follow whole body heat stress. Circumstantial evidence suggests that an inducible 70-kD heat shock protein (hsp70i), increased markedly by whole body heat stress, contributes to the protection. Transgenic mouse lines were constructed with a cytomegalovirus enhancer and beta-actin promoter driving rat hsp70i expression in heterozygote animals. Unstressed, transgene positive mice expressed higher levels of myocardial hsp70i than transgene negative mice after whole body heat stress. This high level of expression occurred without apparent detrimental effect. The hearts harvested from transgene positive mice and transgene negative littermates were Langendorff perfused and subjected to 20 min of warm (37 degrees C) zero-flow ischemia and up to 120 min of reflow while contractile recovery and creatine kinase efflux were measured. Myocardial infarction was demarcated by triphenyltetrazolium. In transgene positive compared with transgene negative hearts, the zone of infarction was reduced by 40%, contractile function at 30 min of reflow was doubled, and efflux of creatine kinase was reduced by approximately 50%. Our findings suggest for the first time that increased myocardial hsp70i expression results in protection of the heart against ischemic injury and that the antiischemic properties of hsp70i have possible therapeutic relevance. Images PMID:7706448

  5. Young Bone-Marrow Sca-1+ Stem Cells Rejuvenate the Aged Heart and Improve Function after Injury through PDGFRβ-Akt pathway

    PubMed Central

    Li, Shu-Hong; Sun, Lu; Yang, Lei; Li, Jiao; Shao, Zhengbo; Du, Guo-Qing; Wu, Jun; Weisel, Richard D.; Li, Ren-Ke

    2017-01-01

    Bone marrow (BM) reconstitution with young BM cells in aged recipients restores the functionality of cardiac resident BM-derived progenitors. This study investigated the cell type primarily responsible for this effect. We reconstituted old mice with BM cells from young or old mice and found that the number of stem cell antigen 1 (Sca-1) cells homing to the heart was significantly greater in young than old chimeras. We then reconstituted old mice with young BM Sca-1+ or Sca-1− cells. We found that Sca-1 cells repopulated the recipient BM and homed to the heart. The number of BM-derived cells in the aged myocardium co-expressing PDGFRβ was 3 times greater in Sca-1+ than Sca-1− chimeric mice. Sca-1+ chimeras had more active cell proliferation in the infarcted heart and improved ventricular function after MI. The improved regeneration involved activation of the PDGFRβ/Akt/p27Kip1 pathway. Sca-1+ stem cells rejuvenated cardiac tissue in aged mice. Restoration of the Sca-1+ subset of stem cells by BM reconstitution improved cardiac tissue regeneration after injury in aged mice. PMID:28139736

  6. Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes.

    PubMed

    Korkmaz-Icöz, Sevil; Atmanli, Ayhan; Radovits, Tamás; Li, Shiliang; Hegedüs, Peter; Ruppert, Mihály; Brlecic, Paige; Yoshikawa, Yutaka; Yasui, Hiroyuki; Karck, Matthias; Szabó, Gábor

    2016-03-01

    We recently demonstrated that the pre-treatment of rats with zinc and acetylsalicylic acid complex in the form of bis(aspirinato)zinc(II) [Zn(ASA)2] is superior to acetylsalicylic acid in protecting the heart from acute myocardial ischemia. Herein, we hypothesized that Zn(ASA)2 treatment after the onset of an acute myocardial injury could protect the heart. The rats were treated with a vehicle or Zn(ASA)2 after an isoproterenol injection. Isoproterenol-induced cardiac damage [inflammatory infiltration into myocardial tissue, DNA-strand breakage evidenced by TUNEL-assay, increased 11-dehydro thromboxane (TX)B2-levels, elevated ST-segment, widened QRS complex and prolonged QT-interval] was prevented by the Zn(ASA)2 treatment. In isoproterenol-treated rats, load-independent left ventricular contractility parameters were significantly improved after Zn(ASA)2. Furthermore, Zn(ASA)2 significantly increased the myocardial mRNA-expression of superoxide dismutase-1, glutathione peroxidase-4 and decreased the level of Na(+)/K(+)/ATPase. Postconditioning with Zn(ASA)2 protects the heart from acute myocardial ischemia. Its mechanisms of action might involve inhibition of pro-inflammatory prostanoids and upregulation of antioxidant enzymes.

  7. Chest Injuries and Disorders

    MedlinePlus

    ... inside of the chest cavity. Chest injuries and disorders include Heart diseases Lung diseases and collapsed lung Pleural disorders Esophagus disorders Broken ribs Thoracic aortic aneurysms Disorders ...

  8. The effects of age and resveratrol on the hypoxic preconditioning protection against hypoxia-reperfusion injury: studies in rat hearts and human cardiomyocytes.

    PubMed

    Zheng, Hong; Guo, Hai; Hong, Yi; Zheng, Fen; Wang, Jiang

    2015-09-01

    The loss of effectiveness of ischaemic preconditioning in protecting old hearts from ischaemia/reperfusion damage is thought to be due to low sirtuin 1 levels in old hearts. We sought to determine whether resveratrol (RES), an activator of sirtuin 1, would restore this protection to that seen with ischaemic preconditioning in young hearts. A Langendorff heart perfusion model was established in 80 old and 80 adult rats to test the effects of hypoxic preconditioning (HPC) and/or RES on preventing hypoxia-reperfusion (H/R) injury. The effects were further tested by comparing the effects of HPC and RES on cell survival rate and lactate dehydrogenase (LDH) in cardiomyocytes from 15 old and 15 young humans. The HPC + RES group performed better in both adult and old groups than the corresponding H/R, HPC and RES groups, causing ∼50% in the adult and 40% in the old group restoration of left ventricular developed pressure and ∼90% in the adult and 80% in the old group restoration of dp/dtmax. HPC and RES each reduced apoptosis in both groups. The HPC + RES treatment showed an additive benefit in reducing apoptosis in the adult group but not in the old group. In H/R-treated young and old human cardiomyocytes, cell survival and LDH level were significantly improved in the RES + HPC group compared with the HPC group. This study showed that RES lessened the ageing effect and enhanced the cardioprotective effect of HPC in older individuals. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  9. FTY720 prevents ischemia/reperfusion injury-associated arrhythmias in an ex vivo rat heart model via activation of Pak1/Akt signaling.

    PubMed

    Egom, E Eroume A; Ke, Yunbo; Musa, Hanny; Mohamed, Tamer M A; Wang, Tao; Cartwright, Elizabeth; Solaro, R John; Lei, Ming

    2010-02-01

    Recent studies demonstrated a role of sphingosine-1-phosphate (S1P) in the protection against the stress of ischemia/reperfusion (I/R) injury. In experiments reported here, we have investigated the signaling through the S1P cascade by FTY720, a sphingolipid drug candidate displaying structural similarity to S1P, underlying the S1P cardioprotective effect. In ex vivo rat heart and isolated sinoatrial node models, FTY720 significantly prevented arrhythmic events associated with I/R injury including premature ventricular beats, VT, and sinus bradycardia as well as A-V conduction block. Real-time PCR and Western blot analysis demonstrated the expression of the S1P receptor transcript pools and corresponding proteins including S1P1, S1P2, and S1P3 in tissues dissected from sinoatrial node, atrium and ventricle. FTY720 (25 nM) significantly blunted the depression of the levels of phospho-Pak1 and phospho-Akt with ischemia and with reperfusion. There was a significant increase in phospho-Pak1 levels by 35%, 199%, and 205% after 5, 10, and 15 min of treatment with 25 nM FTY720 compared with control nontreated myocytes. However, there was no significant difference in the levels of total Pak1 expression between nontreated and FTY720 treated. Phospho-Akt levels were increased by 44%, 63%, and 61% after 5, 10, and 15 min of treatment with 25 nM FTY720, respectively. Our data provide the first evidence that FTY720 prevents I/R injury-associated arrhythmias and indicate its potential significance as an important and new agent protecting against I/R injury. Our data also indicate, for the first time, that the cardioprotective effect of FTY720 is likely to involve activation of signaling through the Pak1.

  10. Assessing Cardiac Injury in Mice With Dual Energy-MicroCT, 4D-MicroCT, and MicroSPECT Imaging After Partial Heart Irradiation

    SciTech Connect

    Lee, Chang-Lung; Min, Hooney; Befera, Nicholas; Clark, Darin; Qi, Yi; Das, Shiva; Johnson, G. Allan; Badea, Cristian T.; Kirsch, David G.

    2014-03-01

    Purpose: To develop a mouse model of cardiac injury after partial heart irradiation (PHI) and to test whether dual energy (DE)-microCT and 4-dimensional (4D)-microCT can be used to assess cardiac injury after PHI to complement myocardial perfusion imaging using micro-single photon emission computed tomography (SPECT). Methods and Materials: To study cardiac injury from tangent field irradiation in mice, we used a small-field biological irradiator to deliver a single dose of 12 Gy x-rays to approximately one-third of the left ventricle (LV) of Tie2Cre; p53{sup FL/+} and Tie2Cre; p53{sup FL/−} mice, where 1 or both alleles of p53 are deleted in endothelial cells. Four and 8 weeks after irradiation, mice were injected with gold and iodinated nanoparticle-based contrast agents, and imaged with DE-microCT and 4D-microCT to evaluate myocardial vascular permeability and cardiac function, respectively. Additionally, the same mice were imaged with microSPECT to assess myocardial perfusion. Results: After PHI with tangent fields, DE-microCT scans showed a time-dependent increase in accumulation of gold nanoparticles (AuNp) in the myocardium of Tie2Cre; p53{sup FL/−} mice. In Tie2Cre; p53{sup FL/−} mice, extravasation of AuNp was observed within the irradiated LV, whereas in the myocardium of Tie2Cre; p53{sup FL/+} mice, AuNp were restricted to blood vessels. In addition, data from DE-microCT and microSPECT showed a linear correlation (R{sup 2} = 0.97) between the fraction of the LV that accumulated AuNp and the fraction of LV with a perfusion defect. Furthermore, 4D-microCT scans demonstrated that PHI caused a markedly decreased ejection fraction, and higher end-diastolic and end-systolic volumes, to develop in Tie2Cre; p53{sup FL/−} mice, which were associated with compensatory cardiac hypertrophy of the heart that was not irradiated. Conclusions: Our results show that DE-microCT and 4D-microCT with nanoparticle-based contrast agents are novel imaging approaches

  11. Urinary kidney injury molecule 1 (KIM-1) and interleukin 18 (IL-18) as risk markers for heart failure in older adults: the Health, Aging, and Body Composition (Health ABC) Study.

    PubMed

    Driver, Todd H; Katz, Ronit; Ix, Joachim H; Magnani, Jared W; Peralta, Carmen A; Parikh, Chirag R; Fried, Linda; Newman, Anne B; Kritchevsky, Stephen B; Sarnak, Mark J; Shlipak, Michael G

    2014-07-01

    Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure. Retrospective cohort study. 2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort. Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively). Incident heart failure over a median follow-up of 12 years. Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51). Generalizability to other populations is uncertain. Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude. Published by Elsevier Inc.

  12. Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury

    USDA-ARS?s Scientific Manuscript database

    Acute pharmacological inhibition of cardiac malonyl coenzyme A decarboxylase (MCD) protects the heart from ischemic damage by inhibiting fatty acid oxidation and stimulating glucose oxidation. However, it is unknown whether chronic inhibition of MCD results in altered cardiac function, energy metabo...

  13. Pharmacological postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of mitochondrial permeability transition pore.

    PubMed

    Duan, Xin; Ji, Bingyang; Yu, Kun; Liu, Jinping; Hei, Feilong; Long, Cun

    2011-01-01

    Postconditioning has been verified to provide cardioprotection and is associated with the state of mitochondrial permeability transition pore. However, there are a few limitations with clinical use of classic postconditioning; therefore, the purpose of this investigation was to study whether inhibition of mitochondrial permeability transition pore opening with cyclosporine A also provided cardioprotection. Langendorff-perfused Sprague-Dawley rat hearts were perfused for 20 minutes with Krebs-Henseleit buffer followed by 30 minutes of crystalloid cardioplegia and 60 minutes of reperfusion. Control hearts (Con group) were reperfused with Krebs-Henseleit buffer. Postconditioning hearts (Ipo group) were with six cycles of 10 seconds reocclusion separated by 10 seconds perfusion before reperfusion. Cyclosporine A postconditioning hearts (CsA group) were reperfused with Krebs-Henseleit buffer containing 0.8 μmol/L cyclosporine A at first 5 minutes of reperfusion. Compared with Con group, myocardial performance was better preserved in CsA group. Mitochondrial outer membrane integrity was preserved, with less cytosolic diffusion of cytochrome C (p < 0.05) and less frequency of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling-positive myocytes in Ipo and CsA group (p < 0.05). Postconditioning prevented apoptosis-related mitochondrial permeabilization and dysfunction after cardioplegic arrest. Cyclosporine A postconditioning had a better effect than classic postconditioning in myocardial performance.

  14. Na/H exchange inhibition protects newborn heart from ischemia/reperfusion injury by limiting Na+-dependent Ca2+ overload.

    PubMed

    Liu, Hong; Cala, Peter M; Anderson, Steve E

    2010-03-01

    The results of the Guardian/Expedition trials demonstrate the need for more precisely controlled studies to inhibit Na/H exchange (NHE1) during ischemia/reperfusion. This is because overwhelming evidence is consistent with the hypothesis that myocardial ischemic injury results in part from increases in intracellular Na (Nai) mediated by NHE1 that in turn promote Na/Ca exchanger-mediated increases in intracellular Ca ([Ca]i) and Ca-dependent cell damage. We used a more potent and specific NHE1 inhibitor HOE 694 (HOE) to test whether inhibition of NHE1 during ischemia limits increases in Nai and [Ca]i in newborns. NMR was used to measure pHi, Nai, [Ca]i, and ATP in isolated newborn rabbit hearts. Perfusion pressure, left ventricular developed pressure, and creatine kinase were measured. HOE was added before global ischemia. Results are reported as mean +/- SE. Nai (mEq/kg dry weight) rose from 11.6 +/- 0.9 before ischemia to 114.0 +/- 16.1 at the end of ischemia and recovered to 55.2 +/- 11.8 in the control group. During ischemia and reperfusion, the corresponding values for Nai in the HOE group (63.1 +/- 8.4 and 15.9 +/- 2.5, respectively, P < 0.05) were lower than control. In the control group [Ca]i (nM/L) rose from 331 +/- 41 to 1069 +/- 71 and recovered to 814 +/- 51, whereas in the HOE group [Ca]i rose less (P < 0.05): 359 +/- 50, 607 +/- 85, and 413 +/- 40, respectively. Total creatine kinase release was significantly reduced in the HOE group. Perfusion pressure and left ventricular developed pressure also recovered significantly better in the HOE group than in the control. In conclusion, NHE1 inhibition diminishes ischemia-induced increases in Nai and therefore [Ca], and thus diminishes myocardial injury in neonatal hearts.

  15. Endothelial insulin resistance protects the heart against prolonged ischemia-reperfusion injury but does not prevent insulin transport across the endothelium in a mouse Langendorff model.

    PubMed

    Sharma, Vikram; Kearney, Mark T; Davidson, Sean M; Yellon, Derek M

    2014-11-01

    The endothelium plays an important role in the maintenance of cardiovascular homeostasis in healthy individuals. Insulin resistance can lead to the development of endothelial dysfunction, which is an important step in the pathogenesis of atherosclerosis. We investigated specifically whether the presence of vascular insulin resistance and endothelial dysfunction has any influence on the myocardial tolerance to ischemia-reperfusion (IR) injury, using Endothelial Specific Mutant Insulin Receptor Over-expressing (ESMIRO) mice, which exhibit vascular insulin resistance and vascular dysfunction. ESMIRO or wild-type (WT) littermate mouse hearts were isolated and perfused on a Langendorff apparatus. These were subjected to either 35-minute or 45-minute ischemia followed by reperfusion, after which infarct size was determined. The ability of insulin to activate its target kinase pathway, that is, phosphoinositide 3 (PI3) kinase/protein kinase B (AKT) in ESMIRO hearts was also assessed by Western blot analysis. Compared to 35-minute ischemia, the extended 45-minute ischemic protocol significantly exacerbated myocardial infarction in WT mice, (56% ± 4%, n = 6 vs 32% ± 4%, n = 9; P < .01) but not in ESMIRO littermates (34% ± 7%, n = 6 vs 32% ± 3%, n = 9; not significant), suggesting some form of protective phenotype. Insulin treatment was associated with a significant increase in AKT phosphorylation in the myocardium in both the ESMIRO mice and WT littermates, and this was attenuated in both by inhibition of PI3 kinase using LY294002. Thus, insulin was able to directly activate PI3 kinase/AKT in the myocardium despite the absence of functional endothelial insulin receptors in the ESMIRO mice. (1) Insulin at pharmacologic concentrations can be transported across the endothelium independent of vascular insulin receptors and (2) vascular insulin resistance and/or endothelial dysfunction are protective against prolonged IR injury in the Langendorff model. © The Author(s) 2014.

  16. CDK9 and its repressor LARP7 modulate cardiomyocyte proliferation and response to injury in the zebrafish heart

    PubMed Central

    Matrone, Gianfranco; Wilson, Kathryn S.; Maqsood, Sana; Mullins, John J.; Tucker, Carl S.; Denvir, Martin A.

    2015-01-01

    ABSTRACT Cyclin dependent kinase (Cdk)9 acts through the positive transcription elongation factor-b (P-TEFb) complex to activate and expand transcription through RNA polymerase II. It has also been shown to regulate cardiomyocyte hypertrophy, with recent evidence linking it to cardiomyocyte proliferation. We hypothesised that modification of CDK9 activity could both impair and enhance the cardiac response to injury by modifying cardiomyocyte proliferation. Cdk9 expression and activity were inhibited in the zebrafish (Danio rerio) embryo. We show that dephosphorylation of residue Ser2 on the C-terminal domain of RNA polymerase II is associated with impaired cardiac structure and function, and cardiomyocyte proliferation and also results in impaired functional recovery following cardiac laser injury. In contrast, de-repression of Cdk9 activity, through knockdown of La-related protein (Larp7) increases phosphorylation of Ser2 in RNA polymerase II and increases cardiomyocyte proliferation. Larp7 knockdown rescued the structural and functional phenotype associated with knockdown of Cdk9. The balance of Cdk9 and Larp7 plays a key role in cardiomyocyte proliferation and response to injury. Larp7 represents a potentially novel therapeutic target to promote cardiomyocyte proliferation and recovery from injury. PMID:26542022

  17. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart.

    PubMed

    Jiang, Jiangtao; Yuan, Xuan; Wang, Ting; Chen, Hongmei; Zhao, Hong; Yan, Xinyan; Wang, Zhiping; Sun, Xiling; Zheng, Qiusheng

    2014-03-01

    This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated by the use of improved Langendorff retrograde perfusion technology, the total flavonoids (5 μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P < 0.01) in total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  18. Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury.

    PubMed

    Liu, Youbin; Li, Guangnan; Lu, Huimin; Li, Wei; Li, Xianglu; Liu, Huimin; Li, Xingda; Li, Tianyu; Yu, Bo

    2014-06-10

    Long noncoding RNAs (lncRNAs) play important regulatory roles in cellular physiology. The contributions of lncRNAs to ischemic heart disease remain largely unknown. The aim of this study was to investigate the profile of myocardial lncRNAs and their potential roles at early stage of reperfusion. lncRNAs and mRNAs were profiled by microarray and the expression of some highly-dysregulated lncRNAs was further validated using polymerase chain reaction. Our results revealed that 64 lncRNAs were up-regulated and 87 down-regulated, while 50 mRNAs were up-regulated and 60 down-regulated in infarct region at all reperfusion sampled. Gene ontology analysis indicated that dysregulated transcripts were associated with immune response, spermine catabolic process, taxis, chemotaxis, polyamine catabolic process, spermine metabolic process, chemokine activity and chemokine receptor binding. Target gene-related pathway analysis showed significant changes in cytokine-cytokine receptor interaction, the chemokine signaling pathway and nucleotide oligomerization domain (NOD)-like receptor signaling pathway which have a close relationship with myocardial ischemia/reperfusion injury (MI/RI). Besides, a gene co-expression network was constructed to identify correlated targets of 10 highly-dysregulated lncRNAs. These lncRNAs may play their roles by this network in post-ischemic heart. Such results provide a foundation for understanding the roles and mechanisms of myocardial lncRNAs at early stage of reperfusion.

  19. Mild Type 2 Diabetes Mellitus Reduces the Susceptibility of the Heart to Ischemia/Reperfusion Injury: Identification of Underlying Gene Expression Changes.

    PubMed

    Korkmaz-Icöz, Sevil; Lehner, Alice; Li, Shiliang; Vater, Adrian; Radovits, Tamás; Hegedűs, Péter; Ruppert, Mihály; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor

    2015-01-01

    Despite clinical studies indicating that diabetic hearts are more sensitive to ischemia/reperfusion injury, experimental data is contradictory. Although mild diabetes prior to ischemia/reperfusion may induce a myocardial adaptation, further research is still needed. Nondiabetic Wistar (W) and type 2 diabetic Goto-Kakizaki (GK) rats (16-week-old) underwent 45 min occlusion of the left anterior descending coronary artery and 24 h reperfusion. The plasma glucose level was significantly higher in diabetic rats compared to the nondiabetics. Diabetes mellitus was associated with ventricular hypertrophy and increased interstitial fibrosis. Inducing myocardial infarction increased the glucose levels in diabetic compared to nondiabetic rats. Furthermore, the infarct size was smaller in GK rats than in the control group. Systolic and diastolic functions were impaired in W + MI and did not reach statistical significance in GK + MI animals compared to the corresponding controls. Among the 125 genes surveyed, 35 genes showed a significant change in expression in GK + MI compared to W + MI rats. Short-term diabetes promotes compensatory mechanisms that may provide cardioprotection against ischemia/reperfusion injury, at least in part, by increased antioxidants and the upregulation of the prosurvival PI3K/Akt pathway, by the downregulation of apoptotic genes, proinflammatory cytokine TNF-α, profibrogenic TGF-β, and hypertrophic marker α-actin-1.

  20. Reduced heart rate variability in chronic severe traumatic brain injury: Association with impaired emotional and social functioning, and potential for treatment using biofeedback.

    PubMed

    Francis, Heather M; Fisher, Alana; Rushby, Jacqueline A; McDonald, Skye

    2016-01-01

    Heart rate variability (HRV) may provide an index of capacity for social functioning and may be remediated by HRV biofeedback. Given reductions in HRV are found following traumatic brain injury (TBI), the present study aimed to determine whether lower HRV in TBI is associated with social function, and whether HRV biofeedback might be a useful remediation technique in this population. Resting state HRV and measures of social and emotional processing were collected in 30 individuals with severe TBI (3-34 years post-injury) and 30 controls. This was followed by a single session of HRV biofeedback. HRV was positively associated with social cognition and empathy, and negatively associated with alexithymia for the TBI group. Both TBI and control groups showed significantly increased HRV on both time-domain (i.e., SDNN, rMSSD) and frequency-domain measures (LF, HF, LF:HF ratio) during biofeedback compared to baseline. These results suggest that decreased HRV is linked to social and emotional function following severe TBI, and may be a novel target for therapy using HRV biofeedback techniques.

  1. Glutamine-induced protection of isolated rat heart from ischemia/reperfusion injury is mediated via the hexosamine biosynthesis pathway and increased protein O-GlcNAc levels

    PubMed Central

    Liu, Jia; Marchase, Richard B.; Chatham, John C.

    2007-01-01

    It has been shown that glutamine protects the heart from ischemia/reperfusion (I/R) injury; however, the mechanisms underlying this protection have not been identfied. Glutamine: fructose-6-phosphate amidotransferase (GFAT) regulates the entry of glucose into the hexosamine biosynthesis pathway (HBP) and activation of this pathway has been shown to be cardioprotective. Glutamine is required for metabolism of glucose via GFAT; therefore, the goal of this study was to determine whether glutamine cardioprotection could be attributed to increased flux through the HBP and elevated levels of O-linked N-acetyl-glucosamine (O-GlcNAc) on proteins. Hearts from male rats were isolated and perfused with Krebs-Henseliet buffer containing 5mM glucose, and global, no-flow ischemia was induced for 20 minutes followed by 60 minutes of reperfusion. 30 minute pre-treatment with 2.5 mM glutamine significantly improved functional recovery (RPP: 15.6±5.7% Vs. 59.4±6.1%; p<0.05) and decreased cardiac Troponin I release (25.4±3.0 Vs. 4.7±1.9; p<0.05) during reperfusion. This protection was associated with a significant increase in the levels of protein O-GlcNAc and ATP. Pre-treatment with 80 μM azaserine, an inhibitor of GFAT, completely reversed the protection seen with glutamine and prevented the increase in protein O-GlcNAc. O-GlcNAc transferase (OGT) catalyzes the formation of O-GlcNAc, and inhibition of OGT with 5mM alloxan also reversed the protection associated with glutamine. These data support the hypothesis that in the ex vivo perfused heart glutamine cardioprotection is due, at least in part, to enhanced flux through the HBP and increased protein O-GlcNAc levels. PMID:17069847

  2. Findings of Vascular Brain Injury and Structural Loss from Cranial Magnetic Resonance Imaging in Elderly American Indians: The Strong Heart Study.

    PubMed

    Suchy-Dicey, Astrid M; Shibata, Dean K; Madhyastha, Tara M; Grabowski, Thomas J; Longstreth, W T; Buchwald, Dedra S

    2017-01-01

    The Cerebrovascular Disease and its Consequences in American Indians study conducted cranial MRI examination of surviving participants of the Strong Heart Study, a longitudinal cohort of elderly American Indians. Of the 1,033 recruited participants, some were unable to complete the MRI (n = 22), some scans were unusable due to participant motion or technical errors (n = 13), and one community withdrew consent after data collection (n = 209), leaving 789 interpretable MRI scan images. Six image sequences were obtained in contiguous slices on 1.5T scanners. Neuroradiologists graded white matter hyperintensities (WMH), sulci, and ventricles on a 0- to 9-point scale, and recorded the presence of infarcts and hemorrhages. Intracranial, brain, hippocampal, and WMH volumes were estimated by automated image processing. The median scores for graded measures were 2 (WMH) and 3 (sulci, ventricles). About one-third of participants had lacunar (20%) or other infarcts (13%); few had hemorrhages (5.7%). Findings of cortical atrophy were also prevalent. Statistical analyses indicated significant associations between older age and findings of vascular injury and atrophy; male gender was associated with findings of cortical atrophy. Vascular brain injury is the likely explanation in this elderly American Indian population for brain infarcts, hemorrhages, WMH grade, and WMH volume. Although vascular brain injury may play a role in other findings, independent degenerative other disease processes may underlie abnormal sulcal widening, ventricular enlargement, hippocampal volume, and total brain volume. Further examination of risk factors and outcomes with these findings may expand the understanding of neurological conditions in this understudied population. © 2017 S. Karger AG, Basel.

  3. Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106

    PubMed Central

    Luo, Tao; Liu, Han; Kim, Jin Kyung

    2016-01-01

    A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β. PMID:27930699

  4. The Long-Term Consumption of Ginseng Extract Reduces the Susceptibility of Intermediate-Aged Hearts to Acute Ischemia Reperfusion Injury.

    PubMed

    Luo, Pei; Dong, Gengting; Liu, Liang; Zhou, Hua

    2015-01-01

    A large number of experimental studies using young adult subjects have shown that ginseng (Panax ginseng C.A. Meyer) protects against ischemia heart disease. However, ginseng has not been explored for its anti-I/R effect and mechanism of action in the aged myocardium. The present study was designed to evaluate the effects of the long-term consumption of ginseng extract on myocardial I/R in an in vivo rat model and explore the potential underlying mechanism. Young (6-mo-old) and intermediate-aged (18-mo-old) rats were gavaged with either standardized ginseng extract (RSE) at 80 mg/kg or vehicle for 90 days. The rats were sacrificed after LAD coronary artery ligation was performed to induce 30 min of ischemia, followed by 90 min of reperfusion. The myocardial infarct size was measured. Left ventricular function was evaluated using pressure-volume loops. The levels of survival, apoptotic and longevity protein expression were assessed through Western blot analysis. Myocardial pathology was detected through H&E or Masson's trichrome staining. We observed higher infarct expansion with impairment in the LV functional parameters, such as LVSP and LVEDP, in aged rats compared with young rats. Enhanced Akt phosphorylation and eNOS expression in RSE-treated aged hearts were accompanied with reduced infarct size, improved cardiac performance, and inducted survival signals. In contrast, p-Erk and caspase 7 were significantly downregulated in aged rats, suggesting that cardiomyocyte apoptosis was suppressed after RSE treatment. RSE also inhibited caspase-3/7 activation and decreased Bax/Bcl-2 ratio. Consistent with the results of apoptosis, Sirt1 and Sirt3 were significantly increased in the RSE-treated aged heart compared with vehicle-treated I/R, suggesting that the anti-aging effect was correlated with the anti-apoptotic activity of RSE. These findings suggest that the long-term consumption of ginseng extract reduced the susceptibility of intermediate-aged hearts to acute

  5. The Long-Term Consumption of Ginseng Extract Reduces the Susceptibility of Intermediate-Aged Hearts to Acute Ischemia Reperfusion Injury

    PubMed Central

    Luo, Pei; Dong, Gengting; Liu, Liang; Zhou, Hua

    2015-01-01

    susceptibility of intermediate-aged hearts to acute ischemia reperfusion injury in rats. These effects might be mediated through the activation of Akt/eNOS, suppression of Erk/caspase 7 and upregulation of Sirt1 and Sirt3 in intermediate-aged rats. PMID:26650753

  6. Low-Dose Gamma Irradiation of Decellularized Heart Valves Results in Tissue Injury in Vitro and in Vivo

    PubMed Central

    Helder, Meghana R. K.; Hennessy, Ryan S.; Spoon, Daniel B.; Tefft, Brandon J.; Witt, Tyra A.; Marler, Ronald J.; Pislaru, Sorin V.; Simari, Robert D.; Stulak, John M.; Lerman, Amir

    2017-01-01

    Background Decellularized heart valves are emerging as a potential alternative to current bioprostheses for valve replacement. While techniques of decellularization have been thoroughly examined, terminal sterilization techniques have not received the same scrutiny. Methods This study evaluated low dose gamma irradiation as a sterilization method for decellularized heart valves. Incubation of valves and transmission electron microscopy evaluation after different doses of gamma irradiation were used to determine the optimal dose of gamma irradiation. Quantitative evaluation of mechanical properties was done by tensile mechanical testing of isolated cusps. Sterilize decellularized heart valves were tested in a sheep model (n=3, 1 1,500 Gy and 2 3,000 Gy) of pulmonary valve replacement. Results Valves sterilized with gamma radiation between 1,000 Gy and 3,000 Gy were found to be optimal with in-vitro testing. However, with in-vivo showed deteriorating valve function within 2 months. On explant the valve with 1,500 Gy gamma irradiation showed signs of endocarditis with neutrophils on hematoxylin and eosin staining, positive gram stain resembling streptococcus infection. The 3,000 Gy valves had no evidence of infection, but the hematoxylin and eosin staining showed evidence of wound remodeling with macrophages and fibroblasts. Tensile strength testing showed decreased strength (0 Gy-2.53±0.98 MPa, 1,500 Gy-2.03±1.23 MPa, 3,000 Gy-1.26±0.90 MPa) with increasing levels of irradiation. Conclusions Low dose gamma irradiation does not maintain the mechanical integrity of valves and the balance between sterilization and damage may not be able to be achieved with gamma irradiation. Other methods of terminal sterilization must be pursued and evaluated. PMID:26453425

  7. Acute Ethanol Exposure Increases the Susceptibility of the Donor Hearts to Ischemia/Reperfusion Injury after Transplantation in Rats

    PubMed Central

    Loganathan, Sivakkanan; Weymann, Alexander; Radovits, Tamás; Barnucz, Enikő; Hirschberg, Kristóf; Hegedüs, Peter; Zhou, Yan; Tao, Liang; Páli, Szabolcs; Veres, Gábor; Karck, Matthias; Szabó, Gábor

    2012-01-01

    Background Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. Methods Rats received saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. Results Ethanol administration resulted in decreased load-dependent (−34±9%) and load-independent (−33±12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47±10%), elongated QT-interval (+38±4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial contractility and relaxation

  8. Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats.

    PubMed

    Li, Shiliang; Korkmaz, Sevil; Loganathan, Sivakkanan; Weymann, Alexander; Radovits, Tamás; Barnucz, Enikő; Hirschberg, Kristóf; Hegedüs, Peter; Zhou, Yan; Tao, Liang; Páli, Szabolcs; Veres, Gábor; Karck, Matthias; Szabó, Gábor

    2012-01-01

    Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation. Rats received saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively. Ethanol administration resulted in decreased load-dependent (-34 ± 9%) and load-independent (-33 ± 12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47 ± 10%), elongated QT-interval (+38 ± 4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial contractility and relaxation, oxidative stress and

  9. Frequency and influencing factors of cardiopulmonary resuscitation-related injuries during implementation of the American Heart Association 2010 Guidelines: a retrospective study based on autopsy and postmortem computed tomography.

    PubMed

    Yamaguchi, Rutsuko; Makino, Yohsuke; Chiba, Fumiko; Torimitsu, Suguru; Yajima, Daisuke; Inokuchi, Go; Motomura, Ayumi; Hashimoto, Mari; Hoshioka, Yumi; Shinozaki, Tomohiro; Iwase, Hirotaro

    2017-09-13

    To determine the frequency of cardiopulmonary resuscitation (CPR)-related injuries and factors involved in their occurrence, data based on forensic autopsy and postmortem computed tomography (PMCT) during implementation of the 2010 American Heart Association Guidelines for CPR were studied. We retrospectively evaluated data on adult patients with non-traumatic deaths who had undergone manual CPR and autopsy from January 2012 to December 2014. CPR-related injuries were analyzed on autopsy records and PMCT images and compared with results of previous studies. In total, 180 consecutive cases were analyzed. Rib fractures and sternal fractures were most frequent (overall frequency, 66.1 and 52.8%, respectively), followed by heart injuries (12.8%) and abdominal visceral injuries (2.2%). Urgently life-threatening injuries were rare (2.8%). Older age was an independent risk factor for rib fracture [adjusted odds ratio (AOR), 1.06; 95% confidence interval (CI), 1.04-1.08; p < 0.001], ≥ 3 rib fractures (AOR, 1.06; 95% CI, 1.02-1.09; p = 0.002), and sternal fracture (AOR, 1.03; 95% CI, 1.01-1.05; p < 0.001). Female sex was significantly associated with sternal fracture (AOR, 2.08; 95% CI, 1.02-4.25; p = 0.04). Chest compression only by laypersons was inversely associated with rib and sternal fractures. Body mass index and in-hospital cardiac arrest were not significantly associated with any complications. The frequency of thoracic skeletal injuries was similar to that in recent autopsy-based studies. Implementation of the 2010 Guidelines had little impact on the frequency of CPR-related thoracic skeletal injuries or urgently life-threatening complications. Older age was the only independent factor related to thoracic skeletal injuries.

  10. Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability.

    PubMed

    Maffei Facinó, R; Carini, M; Aldini, G; Berti, F; Rossoni, G; Bombardelli, E; Morazzoni, P

    1996-12-01

    An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 micrograms/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF1 alpha into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 micrograms/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/ min). The cardioprotective agent allopurinol infused at 20 micrograms/ml had effects on the contractility and on the release of 6-keto-PGF1 alpha comparable to those of 200 micrograms/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 microM: rate constant K = 7.55 x 10(5) M-1 s-1, determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 microM; rate constant K = 1.2 x 10(12) M-1 s-1, determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 microM and 0.35 microM, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximately 9.

  11. Myocardial injury in coronary artery bypass grafting: On-pump versus off-pump comparison by measuring heart-type fatty-acid-binding protein release.

    PubMed

    Malik, Vishwas; Kale, Shailaja C; Chowdhury, Ujjwal K; Ramakrishnan, Lakshmy; Chauhan, Sandeep; Kiran, Usha

    2006-01-01

    This prospective study uses heart-type fatty-acid-binding protein (hFABP) and creatine kinase-MB (CK-MB) release to compare myocardial injury in on-pump versus off-pump coronary artery bypass grafting (CABG). Fifty patients were randomly assigned to on-pump or off-pump CABG. The hFABP and CK-MB concentrations were measured in serial venous blood samples drawn before heparinization in both groups and after aortic unclamping at 1, 2, 4, 8, 24, 48, and 72 hours in the on-pump group. In the off-pump group, samples were taken after the last distal anastomosis at the same time intervals as in the on-pump group. The total amount of hFABP and CK-MB released was significantly higher in the on-pump than in the off-pump group (hFABP = 100.43 +/- 77.63 vs 3.94 +/- 0.36 ng/mL, P < 0.0001; CK-MB = 33.33 +/- 3.81 vs 28.65 +/- 3.91 log units, P < 0.001). In all patients, hFABP levels peaked as early as 1 hour after declamping (on-pump group) or 2 hours after the last distal anastomosis (off-pump group), whereas CK-MB peaked only at 4 hours after declamping (on-pump group) or 24 hours after the last distal anastomosis (off-pump group). The lower release of hFABP and CK-MB in the off-pump CABG group indicates that on-pump CABG with cardioplegic arrest causes more myocardial damage than does off-pump CABG. Heart-type fatty-acid-binding protein is a more rapid marker of perioperative myocardial damage, peaks earlier than CK-MB, and may predict the requirement for intensive monitoring for postoperative myocardial infarction.

  12. Heart Health - Brave Heart

    MedlinePlus

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

  13. The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits

    PubMed Central

    WANG, YAN; LI, YIGANG; SONG, LEI; LI, YANYAN; JIANG, SHAN; ZHANG, SONG

    2016-01-01

    Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine-threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia-reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt-AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt-AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B-cell lymphoma 2 (Bcl-2) and a decrease in caspase-3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt-AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function. PMID:27151366

  14. Angiotensin II type 2 receptor ligand PD123319 attenuates hyperoxia-induced lung and heart injury at a low dose in newborn rats

    PubMed Central

    Sengers, Rozemarijn M. A.; Laghmani, El Houari; Chen, Xueyu; Lindeboom, Melissa P. H. A.; Roks, Anton J. M.; Folkerts, Gert; Walther, Frans J.

    2014-01-01

    Intervening in angiotensin (Ang)-II type 2 receptor (AT2) signaling may have therapeutic potential for bronchopulmonary dysplasia (BPD) by attenuating lung inflammation and preventing arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We first investigated the role of AT2 inhibition with PD123319 (0.5 and 2 mg·kg−1·day−1) on the beneficial effect of AT2 agonist LP2–3 (5 μg/kg twice a day) on RVH in newborn rats with hyperoxia-induced BPD. Next we determined the cardiopulmonary effects of PD123319 (0.1 mg·kg−1·day−1) in two models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression. Ten days of coadministration of LP2–3 and PD123319 abolished the beneficial effects of LP2–3 on RVH in experimental BPD. In the early treatment model PD123319 attenuated cardiopulmonary injury by reducing alveolar septal thickness, pulmonary influx of inflammatory cells, including macrophages and neutrophils, medial wall thickness of small arterioles, and extravascular collagen III deposition, and by preventing RVH. In the late treatment model PD123319 diminished PAH and RVH, demonstrating that PAH is reversible in the neonatal period. At high concentrations PD123319 blocks the beneficial effects of the AT2-agonist LP2–3 on RVH. At low concentrations PD123319 attenuates cardiopulmonary injury by reducing pulmonary inflammation and fibrosis and preventing PAH-induced RVH but does not affect alveolar and vascular development in newborn rats with experimental BPD. PMID:24951776

  15. Angiotensin II type 2 receptor ligand PD123319 attenuates hyperoxia-induced lung and heart injury at a low dose in newborn rats.

    PubMed

    Wagenaar, Gerry T M; Sengers, Rozemarijn M A; Laghmani, El Houari; Chen, Xueyu; Lindeboom, Melissa P H A; Roks, Anton J M; Folkerts, Gert; Walther, Frans J

    2014-08-01

    Intervening in angiotensin (Ang)-II type 2 receptor (AT2) signaling may have therapeutic potential for bronchopulmonary dysplasia (BPD) by attenuating lung inflammation and preventing arterial hypertension (PAH)-induced right ventricular hypertrophy (RVH). We first investigated the role of AT2 inhibition with PD123319 (0.5 and 2 mg·kg(-1)·day(-1)) on the beneficial effect of AT2 agonist LP2-3 (5 μg/kg twice a day) on RVH in newborn rats with hyperoxia-induced BPD. Next we determined the cardiopulmonary effects of PD123319 (0.1 mg·kg(-1)·day(-1)) in two models: early treatment during continuous exposure to hyperoxia for 10 days and late treatment starting on day 6 in rat pups exposed postnatally to hyperoxia for 9 days, followed by a 9-day recovery period in room air. Parameters investigated included lung and heart histopathology, fibrin deposition, vascular leakage, and differential mRNA expression. Ten days of coadministration of LP2-3 and PD123319 abolished the beneficial effects of LP2-3 on RVH in experimental BPD. In the early treatment model PD123319 attenuated cardiopulmonary injury by reducing alveolar septal thickness, pulmonary influx of inflammatory cells, including macrophages and neutrophils, medial wall thickness of small arterioles, and extravascular collagen III deposition, and by preventing RVH. In the late treatment model PD123319 diminished PAH and RVH, demonstrating that PAH is reversible in the neonatal period. At high concentrations PD123319 blocks the beneficial effects of the AT2-agonist LP2-3 on RVH. At low concentrations PD123319 attenuates cardiopulmonary injury by reducing pulmonary inflammation and fibrosis and preventing PAH-induced RVH but does not affect alveolar and vascular development in newborn rats with experimental BPD.

  16. The transplantation of Akt-overexpressing amniotic fluid-derived mesenchymal stem cells protects the heart against ischemia-reperfusion injury in rabbits.

    PubMed

    Wang, Yan; Li, Yigang; Song, Lei; Li, Yanyan; Jiang, Shan; Zhang, Song

    2016-07-01

    Amniotic fluid-derived mesenchymal stem cells (AFMSCs) are an attractive cell source for applications in regenerative medicine, due to characteristics such as proliferative capacity and multipotency. In addition, Akt, a serine‑threonine kinase, maintains stem cells by promoting viability and proliferation. Whether the transplantation of Akt-overexpressing AFMSCs protects the heart against ischemia‑reperfusion (I/R) injury has yet to be elucidated. Accordingly, the Akt gene was overexpressed in AFMSCs using lentiviral transduction, and Akt‑AFMSCs were transplanted into the ischemic myocardium of rabbits prior to reperfusion. Any protective effects resulting from this procedure were subsequently sought after three weeks later. A histological examination revealed that there was a decrease in intramyocardial inflammation and ultrastructural damage, and an increase in capillary density and in the levels of GATA binding protein 4, connexin 43 and cardiac troponin T in the Akt‑AFMSC group compared with the control group. A significant decrease in cardiomyocyte apoptosis, accompanying an increase in phosphorylated Akt and B‑cell lymphoma 2 (Bcl-2) and a decrease in caspase‑3, was also observed. Furthermore, the left ventricular function was markedly augmented in the Akt‑AFMSC group compared with the control group. These observations suggested that the protective effect of AFMSCs may be due to the delivery of secreted cytokines, promotion of neoangiogenesis, prevention of cardiomyocyte apoptosis, transdifferentiation into cardiomyocytes and promotion of the viability of AFMSCs, which are assisted by Akt gene modification. Taken together, the results of the present study have indicated that transplantation of Akt-AFMSCs is able to alleviate myocardial I/R injury and improve cardiac function.

  17. Heart-fatty acid-binding and tau proteins relate to brain injury severity and long-term outcome in subarachnoid haemorrhage patients.

    PubMed

    Zanier, E R; Zoerle, T; Fiorini, M; Longhi, L; Cracco, L; Bersano, A; Branca, V; Benedetti, M D; De Simoni, M G; Monaco, S; Stocchetti, N

    2013-09-01

    Vasospasm and other secondary neurological insults may follow subarachnoid haemorrhage (SAH). Biomarkers have the potential to stratify patient risk and perhaps serve as an early warning sign of delayed ischaemic injury. Serial cerebrospinal fluid (CSF) samples were collected from 38 consecutive patients with aneurysmal SAH admitted to the neurosurgical intensive care unit. We measured heart-fatty acid-binding protein (H-FABP) and tau protein (τ) levels in the CSF to evaluate their association with brain damage, and their potential as predictors of the long-term outcome. H-FABP and τ were analysed in relation to acute clinical status, assessed by the World Federation of Neurological Surgeons (WFNS) scale, radiological findings, clinical vasospasm, and 6-month outcome. H-FABP and τ increased after SAH. H-FABP and τ were higher in patients in poor clinical status on admission (WFNS 4-5) compared with milder patients (WFNS 1-3). Elevated H-FABP and τ levels were also observed in patients with early cerebral ischaemia, defined as a CT scan hypodense lesion visible within the first 3 days after SAH. After the acute phase, H-FABP, and τ showed a delayed increase with the occurrence of clinical vasospasm. Finally, patients with the unfavourable outcome (death, vegetative state, or severe disability) had higher peak levels of both proteins compared with patients with good recovery or moderate disability. H-FABP and τ show promise as biomarkers of brain injury after SAH. They may help to identify the occurrence of vasospasm and predict the long-term outcome.

  18. Acute Effects of Implantable Cardioverter-Defibrillator Shocks on Biomarkers of Myocardial Injury, Apoptosis, Heart Failure, and Systemic Inflammation.

    PubMed

    Brewster, Jordan; Sexton, Travis; Dhaliwal, Gary; Charnigo, Richard; Morales, Gustavo; Parrott, Kevin; Darrat, Yousef; Gurley, John; Smyth, Susan; Elayi, Claude S

    2017-04-01

    Implantable cardioverter-defibrillator (ICD) shocks are potentially associated with myocardial injury, altered hemodynamics, apoptosis, and inflammatory signaling. Their precise cellular impact can be explored after defibrillation testing (DFT) via biomarkers. We evaluated changes in biomarkers after ICD shocks during DFT. We prospectively enrolled outpatients presenting for first implantation of a cardiac device. Biomarkers indicative of myocardial injury, inflammation, and apoptosis were measured before and after implantation, and compared between patients receiving DFT (DFT+) to those not (DFT-). Sixty-three patients were enrolled, 40 in the DFT+ group and 23 in the DFT- group. Average levels of troponin I, hsCRP, Calprotectin, N-terminal pro B-type natriuretic peptide (NTproBNP), and sFas increased by >50% after cardiac device implantation compared to baseline. Increase in troponin never exceeded the 50-fold upper limit of normal (2 ng/mL). Troponin trended higher in the DFT+ group at 8 hours (median 0.18 ng/mL, interquartile range [IQR] 0.11-0.48) versus the DFT- group (0.10 ng/mL, IQR 0.06-0.28, P = 0.0501); NTproBNP had a similar trend (P = 0.0581). sFas significantly increased in the DFT+ group from baseline (median 4663 pg/mL, IQR 2908-5679) to 24 hours (5039 pg/mL, IQR 3274-6261; P = 0.0338) but not in the DFT- group (P = 0.4705). DFT testing is associated with acutely increased plasma levels of troponin and sFas, a biomarker of apoptosis, along with a trend toward higher NTproBNP. © 2017 Wiley Periodicals, Inc.

  19. [Evaluation of postoperative myocardial injury by heart-type fatty acid-binding protein in off-pump coronary artery bypass grafting surgery].

    PubMed

    Carmona, P; Mateo, E; Montoro, A; Alós, L; Coret, M; Errando, C L; Llagunes, J; De Andrés, J

    2015-01-01

    Postoperative myocardial infarction is a serious and frequent complication of cardiac surgery. Nonetheless, diagnosis in this context it is occasionally challenging. We sought to evaluate the kinetics and diagnostic accuracy of the new biomarker « heart-type fatty acid-binding protein » (h-FABP) in the early detection of myocardial injury in patients undergoing off-pump coronary artery bypass grafting, compared with classical biomarkers. A prospective study was conducted on 17 consecutive patients who underwent off-pump coronary artery bypass grafting during a 2 month period. Blood samples were drawn for measurement of myocardial ischemic injury biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1), immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic complications, defined according to electrocardiographic, echocardiographic and hemodynamic criteria, were recorded. Earlier biomarkers peak plasma values occurred at T4 with troponin (2.9 ± 5.2 ng/mL), and at T5 with h-FABP (37.9 ± 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6 (741 ± 779 and 37 ± 51 U/L, respectively). The optimized cut-off obtained for h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%, respectively, for diagnosis of perioperative ischemic injury, with an area under the ROC curve for h-FABP of 0.83 (95% CI 0.6-1.0) vs. 0.63 (95% CI 0.33-0.83) for troponin. This cut-off value for h-FABP is reached on average at T2 (mean value of h-FABP at T2: 18.9 ± 21.5 ng/mL). This is the first study evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary artery bypass grafting, and the cut-off value established could help to extend earlier detection of myocardial ischemia in this context. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S

  20. Proton magnetic resonance spectroscopy in the evaluation of children with congenital heart disease and acute central nervous system injury.

    PubMed

    Ashwal, S; Holshouser, B A; Hinshaw, D B; Schell, R M; Bailey, L

    1996-08-01

    We studied nine infants and children, aged 1 week to 42 months, with severe acute central nervous system injuries associated with cardiac disease or corrective operations by means of single-voxel proton magnetic resonance spectroscopy to determine whether this technique would be useful in predicting neurologic outcome. Proton magnetic resonance spectroscopic data were acquired from the occipital gray and parietal white matter (8 cm3 volume, stimulated echo-acquisition mode sequence with echo time of 20 msec and repetition time of 3.0 seconds) a median of 9 days after operation (range 3 to 42 days). Data were expressed as ratios of areas under metabolite peaks, including N-acetyl compounds, choline-containing compounds, creatine and phosphocreatine, and lactate. Four patients had cerebral insults before operation, one had both a preoperative and a perioperative insult, three had perioperative insults, and one had a prolonged cardiac arrest 2 days after operation. Outcomes (Glasgow Outcome Scale scores) were assigned at discharge and 6 to 12 months after injury. Six patients were in a vegetative state or had severe impairment at discharge, and two still had severe impairment at 6- to 12-month follow-up. Proton magnetic resonance spectroscopy showed lactate in these two patients, along with markedly reduced ratios of N-acetyl compounds to creatine compounds. The other four patients with severe impairment recovered to a level of mild disability at follow-up. Proton magnetic resonance spectroscopy showed no lactate in these four patients; however, one patient showed moderately reduced ratio of N-acetyl compounds to creatine compounds. The three patients who had mild or moderate impairment at discharge showed no lactate and mild or no changes in metabolite ratios; follow-up revealed normal or mild outcomes. Overall, we found that the presence of lactate and markedly reduced ratios of N-acetyl compounds to creatine compounds were predictive of severe outcomes at discharge

  1. Histopathological evaluation of melatonin as a protective agent in heart injury induced by radiation in a rat model.

    PubMed

    Gürses, Iclal; Özeren, Murat; Serin, Meltem; Yücel, Neslihan; Erkal, Haldun Şükrü

    2014-12-01

    Melatonin is a hormone which is known to be a powerful cardioprotective agent due to its free radical-scavenging properties. This study was carried out to evaluate whether melatonin administration prior to irradiation would have a protective effect on cardiac histopathological changes in an experimental rat model. Rats were divided into four groups. Single dose of 18 Gy radiation and sham radiation exposure were used in related groups. 50mg/kg dose of melatonin were injected intraperitonally 15 min prior to radiation exposure. Analyses and assessments were performed 6 months after radiation exposure. Severe myocardial fibrosis was observed prominently in three regions: the apex, tips of papillary muscles and adjacent to the atrioventricular valves. Inflammation was found to be more in irradiated groups. Increased inflammation and fibrosis were in concordance. The number of mast cells was found to be decreased in irradiated groups. Myocyte necrosis and fibrosis were diminished with melatonin while vasculitis was prevented. Elementary pathological lesions of radiation-induced heart disease (RIHD) are fibrosis, vascular damage, vasculitis and myocyte necrosis. Development of vasculitis was prevented by the use of melatonin. Fibrosis and necrosis were prominently decreased. Prevention of RIHD with the use of melatonin at the long term is encouraging according to the histopathological results. Copyright © 2014 Elsevier GmbH. All rights reserved.

  2. Heart Failure

    MedlinePlus

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

  3. Comparison of heart rate response to tennis activity between persons with and without spinal cord injuries: implications for a training threshold.

    PubMed

    Barfield, J P; Malone, Laurie A; Coleman, Tristica A

    2009-03-01

    The purpose of this study was to evaluate the ability of individuals with spinal cord injury (SCI) to reach a training threshold during on-court sport activity. Monitors collected heart rate (HR) data every 5 s for 11 wheelchair tennis players (WCT) with low paraplegia and 11 able-bodied controls matched on experience and skill level (ABT). Average HR was determined for time spent in practice (e.g, drills) and game (i.e., a competitive set), and the ability to surpass 50% peak HR (HRpeak) and 64% HRpeak in each condition was evaluated. Average exercise intensity (%HRpeak) was not significantly different between the groups during practice (M WCT = 68.18, SD = 7.53%, M ABT = 68.78, SD = 5.44%; t = .22, p = .83) or game (M WCT = 68.17, SD = .17%, M ABT = 71.55, SD = 4.75%; t = 1.12, p =.28). Allparticipants averaged an intensity > or = 50% HR-peak during practice and game, and the difference between group participants averaging an intensity > or = 64% HRpeak was not significant during practice (chi2 = .92, p = .34) or game (chi2 = 3.85, p = .05). In terms of reaching a health and fitness training threshold during tennis, individuals with low-level SCI are similar to matched controls.

  4. A lipophilic nitric oxide donor and a lipophilic antioxidant compound protect rat heart against ischemia-reperfusion injury if given as hybrid molecule but not as a mixture.

    PubMed

    Rastaldo, Raffaella; Raffaella, Rastaldo; Cappello, Sandra; Sandra, Cappello; Di Stilo, Antonella; Antonella, Di Stilo; Folino, Anna; Anna, Folino; Losano, Gianni; Gianni, Losano; Pagliaro, Pasquale; Pasquale, Pagliaro

    2012-03-01

    Low concentrations of a hydrophilic nitric oxide donor (NOD) are reported to reduce myocardial reperfusion injury only when combined with a lipophilic antioxidant (AOX) to form a hybrid molecule (HYB). Here we tested whether liposoluble NOD requires to be combined with AOX to be protective. Isolated rat hearts underwent 30 minutes of ischemia and 120 minutes of reperfusion. To induce postconditioning, 1 μM solutions of the following liposoluble compounds were given during the first 20 minutes of reperfusion: NOD with weak (w-NOD) or strong NO-releasing potency (s-NOD); weak HYB built up with w-NOD and a per se ineffective AOX lead; strong HYB built up with s-NOD and the same AOX; mixtures of w-NOD plus AOX or s-NOD plus AOX. A significant reduction of infarct size with improved recovery of cardiac function was obtained only with weak HYB. We suggest that w-NOD requires the synergy with a per se ineffective AOX to protect. The synergy is possible only if the 2 moieties enter the cell simultaneously as a hybrid, but not as a mixture. It seems that strong HYB was ineffective because an excessive intracellular NO release produces a large amount of reactive species, as shown from the increased nitrotyrosine production.

  5. Hemodynamic effects of left atrial or left ventricular cannulation for acute circulatory support in a bovine model of left heart injury.

    PubMed

    Kapur, Navin K; Paruchuri, Vikram; Pham, Duc Thinh; Reyelt, Lara; Murphy, Barbara; Beale, Corinna; Bogins, Courtney; Wiener, Daniel; Nilson, James; Esposito, Michele; Perkins, Scott; Perides, George; Karas, Richard H

    2015-01-01

    Our objective was to examine the hemodynamic effects of a trans-aortic axial flow catheter (Impella CP) in the left ventricle (LV) versus left atrial (LA) to femoral artery bypass using a centrifugal pump (TandemHeart: TH) in a bovine model of acute LV injury. In three male calves, we performed sequential activation of a CP then TH device in each animal. After 60 minutes of left anterior descending artery ligation, a CP was activated at maximal power. The CP was then removed and the TH activated at 5,500 then a maximum of 7,500 rotations per minute (RPM). The CP generated a maximum 3.1 ± 0.2 L/minute (LPM) of flow, whereas the TH at 5,500 and 7,500 RPM generated 3.1 ± 0.4 and 4.4 ± 0.3 LPM. At 3.1 LPM, the CP and TH reduced LV stroke work (LVSW) similarly. The TH reduced stroke volume, whereas the CP did not. The CP reduced end-systolic pressure, whereas the TH did not. At a maximum flow of 4.4 LPM, the TH provided a greater reduction in LVSW than maximal CP activation. This is the first report to compare the hemodynamic effects of trans-aortic LV unloading versus LA-to-femoral artery (FA) bypass.

  6. Drp1 loss-of-function reduces cardiomyocyte oxygen dependence protecting the heart from ischemia-reperfusion injury.

    PubMed

    Zepeda, Ramiro; Kuzmicic, Jovan; Parra, Valentina; Troncoso, Rodrigo; Pennanen, Christian; Riquelme, Jaime A; Pedrozo, Zully; Chiong, Mario; Sánchez, Gina; Lavandero, Sergio

    2014-06-01

    Mitochondria are key organelles for ATP production in cardiomyocytes, which is regulated by processes of fission and fusion. We hypothesized that the mitochondria fusion protein dynamin-related protein 1 (Drp1) inhibition, attenuates ischemia-reperfusion (I/R) injury through modifications in mitochondrial metabolism. Rats were subjected to I/R through coronary artery ligation, and isolated cardiomyocytes were treated with an ischemia-mimicking solution. In vivo, cardiac function, myocardial infarction area, and mitochondrial morphology were determined, whereas in vitro, viability, mitochondrial membrane potential, intracellular ATP levels, and oxygen consumption rate (OCR) were assessed. In both models, an adenovirus expressing Drp1 dominant-negative K38A (Drp1K38A) was used to induce Drp1 loss-of-function. Our results showed that I/R stimulated mitochondrial fission. Myocardial infarction size and cell death induced by I/R were significantly reduced, whereas cardiac function after I/R was improved in Drp1K38A-treated rats compared with controls. Drp1K38A-transduced cardiomyocytes showed lower OCR with no decrease in intracellular ATP levels, and on I/R, a larger decrease in OCR with a smaller reduction in intracellular ATP level was observed. However, proton leak-associated oxygen consumption was comparatively higher in Drp1K38A-treated cardiomyocytes, suggesting a protective mitochondrial uncoupling effect against I/R. Collectively, our results show that Drp1 inhibition triggers cardioprotection by reducing mitochondrial metabolism during I/R.

  7. How Does the Ca2+-paradox Injury Induce Contracture in the Heart?—A Combined Study of the Intracellular Ca2+ Dynamics and Cell Structures in Perfused Rat Hearts—

    PubMed Central

    Mani, Hiroki; Tanaka, Hideo; Adachi, Tetsuya; Ikegawa, Masaya; Dai, Ping; Fujita, Naohisa; Takamatsu, Tetsuro

    2015-01-01

    The calcium (Ca2+)-paradox injury of the heart, induced by restoration of extracellular Ca2+ after its short-term depletion, is known to provoke cardiomyocyte contracture. However, undetermined is how the Ca2+-paradox provokes such a distinctive presentation of myocytes in the heart. To address this, we imaged sequential intracellular Ca2+ dynamics and concomitant structures of the subepicardial ventricular myocytes in fluo3-loaded, Langendorff-perfused rat hearts produced by the Ca2+ paradox. Under rapid-scanning confocal microscopy, repletion of Ca2+ following its depletion produced high-frequency Ca2+ waves in individual myocytes with asynchronous localized contractions, resulting in contracture within 10 min. Such alterations of myocytes were attenuated by 5-mM NiCl2, but not by verapamil, SEA0400, or combination of ryanodine and thapsigargin, indicating a contribution of non-specific transmembrane Ca2+ influx in the injury. However, saponin-induced membrane permeabilization of Ca2+ showed no apparent contracture despite the emergence of high-frequency Ca2+ waves, indicating an essential role of myocyte-myocyte and myocyte-extracellular matrix (ECM) mechanical connections in the Ca2+ paradox. In immunohistochemistry Ca2+ depletion produced separation of the intercalated disc that expresses cadherin and dissipation of β-dystroglycan located along the sarcolemma. Taken together, along with the trans-sarcolemmal Ca2+ influx, disruption of cell-cell and cell-ECM connections is essential for contracture in the Ca2+-paradox injury. PMID:25861132

  8. Heart MRI

    MedlinePlus

    Magnetic resonance imaging - cardiac; Magnetic resonance imaging - heart; Nuclear magnetic resonance - cardiac; NMR - cardiac; MRI of the heart; Cardiomyopathy - MRI; Heart failure - MRI; Congenital heart disease - MRI

  9. Towards defining heart failure in adults with congenital heart disease.

    PubMed

    Bolger, Aidan P; Gatzoulis, Michael A

    2004-12-01

    Injury to the myocardium disrupts geometric integrity and results in changes to intracardiac pressure, wall stress and tension, and the pattern of blood flow through the heart. Significant disruption to pump function results in heart failure which is defined in terms of symptoms: breathlessness and fatigue, signs of salt and water retention, and neurohormonal activation. This syndrome most commonly occurs in the context of injury due to ischaemic heart disease and dilated cardiomyopathy but because patients with congenital heart disease (CHD) are born with sometimes gross distortions of cardiac anatomy they too are subject to the forces that drive heart failure. This paper explores the available data relating to the clinical and neurohormonal manifestations of heart failure in patients with congenital heart disease and describes how, by additionally exploring events at a cellular level, we may be able to arrive at a definition of heart failure relevant to this population.

  10. The Protective Effects of Salidroside from Exhaustive Exercise-Induced Heart Injury by Enhancing the PGC-1 α–NRF1/NRF2 Pathway and Mitochondrial Respiratory Function in Rats

    PubMed Central

    Zhang, Long-fei; Cui, Yu-juan; Chang, Yu-mei; Jiang, Cai-wu; Meng, Zhen-zhi; Xu, Peng; Liu, Hai-yan; Wang, Dong-ying; Cao, Xue-bin

    2015-01-01

    Objective. To test the hypothesis that salidroside (SAL) can protect heart from exhaustive exercise-induced injury by enhancing mitochondrial respiratory function and mitochondrial biogenesis key signaling pathway PGC-1α–NRF1/NRF2 in rats. Methods. Male Sprague-Dawley rats were divided into 4 groups: sedentary (C), exhaustive exercise (EE), low-dose SAL (LS), and high-dose SAL (HS). After one-time exhaustive swimming exercise, we measured the changes in cardiomyocyte ultrastructure and cardiac marker enzymes and mitochondrial electron transport system (ETS) complexes activities in situ. We also measured mitochondrial biogenesis master regulator PGC-1α and its downstream transcription factors, NRF1 and NRF2, expression at gene and protein levels. Results. Compared to C group, the EE group showed marked myocardium ultrastructure injury and decrease of mitochondrial respiratory function (P < 0.05) and protein levels of PGC-1α, NRF1, and NRF2 (P < 0.05) but a significant increase of PGC-1α, NRF1, and NRF2 genes levels (P < 0.05); compared to EE group, SAL ameliorated myocardium injury, increased mitochondrial respiratory function (P < 0.05), and elevated both gene and protein levels of PGC-1α, NRF-1, and NRF-2. Conclusion. Salidroside can protect the heart from exhaustive exercise-induced injury. It might act by improving myocardial mitochondrial respiratory function by stimulating the expression of PGC-1α–NRF1/NRF2 pathway. PMID:26167242

  11. Snowstorms May Bring Blizzard of Heart Troubles

    MedlinePlus

    ... admissions for heart trouble two days after these weather events. Hospital admissions for heart attacks, chest pain ... to cardiac events, the research team studied cold weather-related conditions such as frostbite, falls and injuries ...

  12. Hearts from Mice Fed a Non-Obesogenic High-Fat Diet Exhibit Changes in Their Oxidative State, Calcium and Mitochondria in Parallel with Increased Susceptibility to Reperfusion Injury

    PubMed Central

    Littlejohns, Ben; Pasdois, Philippe; Duggan, Simon; Bond, Andrew R.; Heesom, Kate; Jackson, Christopher L.; Angelini, Gianni D.; Halestrap, Andrew P.; Suleiman, M.-Saadeh

    2014-01-01

    Rationale High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown. Objectives To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury. Methods and Results Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet. Conclusions This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults. PMID:24950187

  13. Hearts from mice fed a non-obesogenic high-fat diet exhibit changes in their oxidative state, calcium and mitochondria in parallel with increased susceptibility to reperfusion injury.

    PubMed

    Littlejohns, Ben; Pasdois, Philippe; Duggan, Simon; Bond, Andrew R; Heesom, Kate; Jackson, Christopher L; Angelini, Gianni D; Halestrap, Andrew P; Suleiman, M-Saadeh

    2014-01-01

    High-fat diet with obesity-associated co-morbidities triggers cardiac remodeling and renders the heart more vulnerable to ischemia/reperfusion injury. However, the effect of high-fat diet without obesity and associated co-morbidities is presently unknown. To characterize a non-obese mouse model of high-fat diet, assess the vulnerability of hearts to reperfusion injury and to investigate cardiac cellular remodeling in relation to the mechanism(s) underlying reperfusion injury. Feeding C57BL/6J male mice high-fat diet for 20 weeks did not induce obesity, diabetes, cardiac hypertrophy, cardiac dysfunction, atherosclerosis or cardiac apoptosis. However, isolated perfused hearts from mice fed high-fat diet were more vulnerable to reperfusion injury than those from mice fed normal diet. In isolated cardiomyocytes, high-fat diet was associated with higher diastolic intracellular Ca2+ concentration and greater damage to isolated cardiomyocytes following simulated ischemia/reperfusion. High-fat diet was also associated with changes in mitochondrial morphology and expression of some related proteins but not mitochondrial respiration or reactive oxygen species turnover rates. Proteomics, western blot and high-performance liquid chromatography techniques revealed that high-fat diet led to less cardiac oxidative stress, higher catalase expression and significant changes in expression of putative components of the mitochondrial permeability transition pore (mPTP). Inhibition of the mPTP conferred relatively more cardio-protection in the high-fat fed mice compared to normal diet. This study shows for the first time that high-fat diet, independent of obesity-induced co-morbidities, triggers changes in cardiac oxidative state, calcium handling and mitochondria which are likely to be responsible for increased vulnerability to cardiac insults.

  14. Comparing Early Liver Graft Function From Heart Beating and Living-Donors: A Pilot Study Aiming to Identify New Biomarkers of Liver Injury.

    PubMed

    Yang, Qi Joy; Kluger, Michael; Goryński, Krzysztof; Pawliszyn, Janusz; Bojko, Barbara; Yu, Ai-Ming; Noh, Keumhan; Selzner, Markus; Jerath, Angela; McCluskey, Stuart; Sandy Pang, K; Wąsowicz, Marcin

    2017-01-19

    Liver and kidney functions among recipients of liver transplantation (LT) surgery with heart beating (HBD, n = 13) or living donors (LD, n = 9) with different cold ischemic times were examined during the neohepatic phase for clearing rocuronium bromide (ROC, cleared by liver and kidney) and tranexamic acid (TXA, cleared by kidney). Solid phase micro-extraction and LC-MS/MS was applied to determine the plasma concentrations of ROC and TXA, and creatinine was determined by standard laboratory methods. Metabolomics and the relative expressions of miRNA122, miRNA148a, and γ-glutamyltranspeptidase (GGT), liver injury biomarkers, were also measured. ROC clearance for HBD was significantly lower than that for LD (0.147 ± 0.052 vs. 0.265 ± 0.148 mL · min(-1)  · g(-1) liver) after intravenous injection (0.6 mg · kg(-1) ). Clearance of TXA, a compound cleared by glomerular filtration, given as a 1 g bolus followed by infusion (10 mg · kg(-1)  · h(-1) ), was similar between HBD and LD (~1 mL · min(-1)  · kg(-1) ). Metabolomics data revealed higher bile acids, phospholipids, and lipid ω-oxidation metabolite clusters for HBD. miR122 and miR148a expressions were similar for HBD and LD whereas GGT expression was significantly increased for HBD. TXA clearance in both groups was lower than GFR, showing a small extent of hepatorenal coupling.

  15. A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children following Congenital Heart Surgery with Cardiopulmonary Bypass

    PubMed Central

    Axelrod, David M.; Sutherland, Scott M.; Anglemyer, Andrew; Grimm, Paul C.; Roth, Stephen J.

    2015-01-01

    Objective Acute kidney injury (AKI) occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass (CPB) and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of AKI in certain populations. This study sought to determine if post-operative administration of aminophylline attenuates AKI in children undergoing congenital cardiac surgery with CPB. Design Single-center, double-blinded, placebo-controlled, randomized clinical trial (RCT). Setting Tertiary center, pediatric cardiovascular intensive care unit. Patients 144 children after congenital heart surgery with CPB. Interventions Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every six hours for 72 hours. Measurements and Main Results The primary outcome variable was development of any AKI, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included the development of severe AKI, time between CVICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin (NGAL). The unadjusted rate and severity of AKI were not different between groups; 43/72 (60%) of the treatment group and 36/72 (50%) of the placebo group developed AKI (p=0.32). Stage 2/3 AKI occurred in 23/72 (32%) of the treatment group and 15/72 (21%) of the placebo group (p=0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group versus 18% in the placebo group, p =0.30). Conclusions In this placebo-controlled RCT, we found no effect of

  16. Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.

    PubMed

    Takaya, Yoichi; Yoshihara, Fumiki; Yokoyama, Hiroyuki; Kanzaki, Hideaki; Kitakaze, Masafumi; Goto, Yoichi; Anzai, Toshihisa; Yasuda, Satoshi; Ogawa, Hisao; Kawano, Yuhei; Kangawa, Kenji

    2017-02-07

    Although hypoalbuminemia at admission is a risk for acute kidney injury (AKI) and mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of decreased serum albumin levels (DAL) during ADHF therapy has not been elucidated. This study aimed to evaluate whether DAL was associated with AKI, and whether intravenous atrial natriuretic peptide (ANP) administration, which provides an effective treatment for ADHF but promotes albumin extravasation, was associated with DAL and AKI. A total of 231 consecutive patients with ADHF were enrolled. AKI was defined as ≥0.3 mg/dl absolute or 1.5-fold increase in serum creatinine levels within 48 h. AKI occurred in 73 (32%) of the 231 patients during ADHF therapy. The median value of decreases in serum albumin levels was 0.3 g/dl at 7 days after admission. When DAL was defined as ≥0.3 g/dl decrease in serum albumin levels, DAL occurred in 113 patients, and was independently associated with AKI. Of the 231 patients, 73 (32%) were treated with intravenous ANP. DAL occurred more frequently in patients receiving ANP than in those not receiving ANP (77 vs. 36%, p < 0.001), and ANP was independently associated with DAL. The incidence of AKI was higher in patients receiving ANP than in those not receiving ANP (48 vs. 24%, p < 0.001). ANP was independently associated with AKI. In conclusion, DAL is associated with AKI. Intravenous ANP administration may be one of the promoting factors of DAL, which leads to AKI, indicating a possible novel mechanism of AKI.

  17. Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart.

    PubMed

    Sonne, David P; Engstrøm, Thomas; Treiman, Marek

    2008-02-07

    Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.03-3.0 nM), for their protective effects against ischemia-reperfusion injury (IRI) in an isolated rat heart preparation. When administered, the agents were only present for the first 15 min of a 120 min reperfusion period (postconditioning protocol). Exe-4, but not GLP-1(9-36) amide, showed a strong infarct-limiting action (from 33.2% +/-2.7% to 14.5% +/-2.2% of the ischemic area, p<0.05). This infarct size-limiting effect of Exe-4 was abolished by exendin(9-39) (Exe(9-39)), a GLP-1 receptor antagonist. In contrast, both Exe-4 and GLP-1(9-36) amide were able to augment left ventricular performance (left ventricular developed pressure and rate-pressure product) during the last 60 min of reperfusion. These effects were only partially antagonized by Exe(9-39). We suggest that Exe-4, in addition to being currently exploited in treatment of diabetes, may present a suitable candidate for postconditioning trials in clinical settings of IRI. The divergent agonist effects of Exe-4 and GLP-1(9-36), along with correspondingly divergent antagonistic efficacy of Exe(9-39), seem consistent with the presence of more than one type of GLP-1 receptor in this system.

  18. A Comparison of Traditional and Novel Definitions (RIFLE, AKIN, and KDIGO) of Acute Kidney Injury for the Prediction of Outcomes in Acute Decompensated Heart Failure

    PubMed Central

    Roy, Andrew K.; Mc Gorrian, Catherine; Treacy, Cecelia; Kavanaugh, Edel; Brennan, Alice; Mahon, Niall G.; Murray, Patrick T.

    2013-01-01

    Aims To determine if newer criteria for diagnosing and staging acute kidney injury (AKI) during heart failure (HF) admission are more predictive of clinical outcomes at 30 days and 1 year than the traditional worsening renal function (WRF) definition. Methods We analyzed prospectively collected clinical data on 637 HF admissions with 30-day and 1-year follow-up. The incidence, stages, and outcomes of AKI were determined using the following four definitions: KDIGO, RIFLE, AKIN, and WRF (serum creatinine rise ≥0.3 mg/dl). Receiver operating curves were used to compare the predictive ability of each AKI definition for the occurrence of adverse outcomes (death, rehospitalization, dialysis). Results AKI by any definition occurred in 38.3% (244/637) of cases and was associated with an increased incidence of 30-day (32.3 vs. 6.9%, χ2 = 70.1; p < 0.001) and 1-year adverse outcomes (67.5 vs. 31.0%, χ2 = 81.4; p < 0.001). Most importantly, there was a stepwise increase in primary outcome with increasing stages of AKI severity using RIFLE, KDIGO, or AKIN (p < 0.001). In direct comparison, there were only small differences in predictive abilities between RIFLE and KDIGO and WRF concerning clinical outcomes at 30 days (AUC 0.76 and 0.74 vs. 0.72, χ2 = 5.6; p = 0.02) as well as for KDIGO and WRF at 1 year (AUC 0.67 vs. 0.65, χ2 = 4.8; p = 0.03). Conclusion During admission for HF, the benefits of using newer AKI classification systems (RIFLE, AKIN, KDIGO) lie with the ability to identify those patients with more severe degrees of AKI who will go on to experience adverse events at 30 days and 1 year. The differences in terms of predictive abilities were only marginal. PMID:23801998

  19. Heart murmurs

    MedlinePlus

    Chest sounds - murmurs; Heart sounds - abnormal; Murmur - innocent; Innocent murmur; Systolic heart murmur; Diastolic heart murmur ... The heart has 4 chambers: Two upper chambers (atria) Two lower chambers (ventricles) The heart has valves that close ...

  20. Cordycepin, 3'-deoxyadenosine, prevents rat hearts from ischemia/reperfusion injury via activation of Akt/GSK-3β/p70S6K signaling pathway and HO-1 expression.

    PubMed

    Park, Eun-Seok; Kang, Do-Hyun; Yang, Min-Kyu; Kang, Jun Chul; Jang, Yong Chang; Park, Jong Seok; Kim, Si-Kwan; Shin, Hwa-Sup

    2014-03-01

    Cordycepin (3'-deoxyadenosine) isolated from Cordyceps militaris, a species of the fungal genus Cordyceps, has been shown to exhibit many pharmacological functions, such as anticancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the preventive role of cordycepin in ischemic/reperfusion (I/R) injury of isolated rat hearts and anesthetized rats. After Sprague-Dawley rats received cordycepin (3, 10, and 30 mg/kg) or control (0.5 % carboxyl methylcellulose) orally once a day for a week, hearts were isolated and mounted on Langendorff heart perfusion system. Isolated hearts were perfused with Krebs-Henseleit buffer for 15-min pre-ischemic stabilization period and subjected to 30-min global ischemia and 30-min reperfusion. Cordycepin administration (10 mg/kg, p.o.) significantly increased left ventricular developed pressure during the reperfusion period compared to that in the control group, but without any effect on coronary flow. Cordycepin (10 mg/kg, p.o.) significantly increased the phosphorylation of Akt/GSK-3β/p70S6K pathways, which are known to modulate multiple survival pathways. In addition, cordycepin decreased Bax and cleaved caspase-3 expression while increasing Bcl-2 expression, Bcl-2/Bax ratio, and heme oxygenase (HO-1) expression in isolated rat hearts. In anesthetized rats subjected to 30 min occlusion of left anterior descending coronary artery/2.5-h reperfusion, cordycepin (1, 3, and 10 mg/kg, i.v.) administered 15 min before the onset of ischemia dose-dependently decreased the infarct size in left ventricle. In conclusion, cordycepin could be an attractive therapeutic candidate with oral activity against I/R-associated heart diseases such as myocardial infarction.

  1. The epicardium signals the way towards heart regeneration

    PubMed Central

    Masters, Megan; Riley, Paul R.

    2014-01-01

    From historical studies of developing chick hearts to recent advances in regenerative injury models, the epicardium has arisen as a key player in heart genesis and repair. The epicardium provides paracrine signals to nurture growth of the developing heart from mid-gestation, and epicardium-derived cells act as progenitors of numerous cardiac cell types. Interference with either process is terminal for heart development and embryogenesis. In adulthood, the dormant epicardium reinstates an embryonic gene programme in response to injury. Furthermore, injury-induced epicardial signalling is essential for heart regeneration in zebrafish. Given these critical roles in development, injury response and heart regeneration, the application of epicardial signals following adult heart injury could offer therapeutic strategies for the treatment of ischaemic heart disease and heart failure. PMID:24933704

  2. Heart Disease

    MedlinePlus

    ... type of heart disease you have. Symptoms of heart disease in your blood vessels (atherosclerotic disease) Cardiovascular disease ... can sometimes be found early with regular evaluations. Heart disease symptoms caused by abnormal heartbeats (heart arrhythmias) A ...

  3. Failure of remote ischemic preconditioning to reduce the risk of postoperative acute kidney injury in children undergoing operation for complex congenital heart disease: a randomized single-center study.

    PubMed

    Pedersen, Kirsten Rønholt; Ravn, Hanne Berg; Povlsen, Johan Vestergaard; Schmidt, Michael Rahbek; Erlandsen, Erland Jørn; Hjortdal, Vibeke Elisabeth

    2012-03-01

    The objective of this study was to evaluate whether remote ischemic preconditioning can protect kidney function in children undergoing operation for complex congenital heart disease. Children (n = 113) aged 0 to 15 years admitted for complex congenital heart disease were randomly allocated according to age to remote ischemic preconditioning and control groups. After exclusion of 8 patients, we conducted the analysis on 105 patients (remote ischemic preconditioning group, n = 54; control group, n = 51). Before surgery, remote ischemic preconditioning was performed as 4 cycles of 5 minutes of ischemia by inflating a cuff around a leg to 40 mm Hg above the systolic pressure. End points were development of acute kidney injury, initiation of dialysis, plasma creatinine, estimated glomerular filtration rate, plasma cystatin C, plasma and urinary neutrophil gelatinase-associated lipocalin, and urinary output. Secondary end points included postoperative blood pressure, inotropic score, and mortality, as well as morbidity reflected by reoperation and stays in the intensive care unit and hospital. Overall, 57 of the children (54%) had acute kidney injury develop, with 27 (50%) in the remote ischemic preconditioning group and 30 (59%) in the control group (P > .2). Remote ischemic preconditioning was not associated with improvement in either any of the renal biomarkers or any of the secondary end points. We found no evidence that remote ischemic preconditioning provided protection of kidney function in children undergoing operation for complex congenital heart disease. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  4. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    PubMed

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  5. Heart Failure

    MedlinePlus

    Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped ... Tiredness and shortness of breath Common causes of heart failure are coronary artery disease, high blood pressure and ...

  6. Urotensin-ⅡReceptor Antagonist SB-710411 Protects Rat Heart against Ischemia-Reperfusion Injury via RhoA/ROCK Pathway

    PubMed Central

    Luo, Sheng-Yong; Chen, Shuo; Qin, Yi-De; Chen, Zhi-Wu

    2016-01-01

    Aim SB-710411 is a rat selective urotensin-II (U-II) receptor antagonist, which can block U-II-induced contraction of the aorta and inhibit U-II-induced myocardial fibrosis in rats. However, the effect of SB-710411 on myocardial ischemia-reperfusion (I/R) injury is unclear. The present study was designed to investigate whether SB-710411 has a protective effect on myocardial I/R injury in rats and the possible mechanisms. Methods and Results Myocardial I/R injury was induced by occluding the left anterior descending coronary artery in adult male Sprague-Dawley rats. Hemodynamic parameters, electrocardiogram (ECG), infarct size, histological alteration, lactate dehydrogenase (LDH), creatine phosphokinase-MB (CK-MB), cardiac troponin I (cTnI), RhoA, and the protein expressions of U-II receptor (UTR), ROCK1 and ROCK2 were evaluated. Cardiac I/R injury significantly up-regulated the expressions of UTR, ROCK1 and ROCK2 proteins in rat myocardium. SB-710411 1.0 and 2.0 μg/kg significantly reduced cardiac I/R-induced the infarct size and histological damage in rat myocardium, markedly inhibited the changes of hemodynamic parameters and the increases of ST-segment in ECG, the serum LDH and CK-MB activities and cTnI level in rats subjected to myocardial I/R injury. Furthermore, SB-710411 obviously prevented myocardial I/R-increased RhoA activity and UTR, ROCK1 and ROCK2 protein expressions. Conclusions Our results indicate that cardiac I/R injury increases myocardial UTR expression, and SB-710411 has a potent protective effect on myocardial I/R injury in rats. The cardioprotection may be associated with the inhibition of UTR-RhoA/ROCK pathway. PMID:26771557

  7. Heart Attack Recovery FAQs

    MedlinePlus

    ... a Heart Attack Treatment of a Heart Attack Life After a Heart Attack Heart Failure About Heart Failure ... a Heart Attack • Treatment of a Heart Attack • Life After a Heart Attack Lifestyle Changes Recovery FAQs • Heart ...

  8. About Heart Attacks

    MedlinePlus

    ... a Heart Attack Treatment of a Heart Attack Life After a Heart Attack Heart Failure About Heart Failure ... a Heart Attack • Treatment of a Heart Attack • Life After a Heart Attack Lifestyle Changes Recovery FAQs • Heart ...

  9. Menopause and Heart Disease

    MedlinePlus

    ... a Heart Attack Treatment of a Heart Attack Life After a Heart Attack Heart Failure About Heart Failure ... a Heart Attack • Treatment of a Heart Attack • Life After a Heart Attack Lifestyle Changes Recovery FAQs • Heart ...

  10. Enhanced glucose uptake via GLUT4 fuels recovery from calcium overload after ischaemia-reperfusion injury in sevoflurane- but not propofol-treated hearts.

    PubMed

    Lucchinetti, E; Wang, L; Ko, K W S; Troxler, H; Hersberger, M; Zhang, L; Omar, M A; Lopaschuk, G D; Clanachan, A S; Zaugg, M

    2011-06-01

    So far, no study has explored the effects of sevoflurane, propofol, and Intralipid on metabolic flux rates of fatty acid oxidation (FOX) and glucose oxidation (GOX) in hearts exposed to ischaemia-reperfusion. Isolated paced working rat hearts were exposed to 20 min of ischaemia and 30 min of reperfusion. Peri-ischaemic sevoflurane (2 vol%) and propofol (100 µM) in the formulation of 1% Diprivan(®) were assessed for their effects on oxidative energy metabolism and intracellular diastolic and systolic Ca(2+) concentrations. Substrate flux was measured using [(3)H]palmitate and [(14)C]glucose and [Ca(2+)] using indo-1AM. Western blotting was used to determine the expression of the sarcolemmal glucose transporter GLUT4 in lipid rafts. Biochemical analyses of nucleotides, ceramides, and 32 acylcarnitines were also performed. Sevoflurane, but not propofol, improved the recovery of left ventricular work (P=0.008) and myocardial efficiency (P=0.008) compared with untreated ischaemic hearts. This functional improvement was accompanied by reduced increases in post-ischaemic diastolic and systolic intracellular Ca(2+) concentrations (P=0.008). Sevoflurane, but not propofol, increased GOX (P=0.009) and decreased FOX (P=0.019) in hearts exposed to ischaemia-reperfusion. GLUT4 expression was markedly increased in lipid rafts of sevoflurane-treated hearts (P=0.016). Increased GOX closely correlated with reduced Ca(2+) overload. Intralipid alone decreased energy charge and increased long-chain and hydroxyacylcarnitine tissue levels, whereas sevoflurane decreased toxic ceramide formation. Enhanced glucose uptake via GLUT4 fuels recovery from Ca(2+) overload after ischaemia-reperfusion in sevoflurane- but not propofol-treated hearts. The use of a high propofol concentration (100 µM) did not result in similar protection.

  11. Heart attack

    MedlinePlus

    ... infarction; Non-ST - elevation myocardial infarction; NSTEMI; CAD - heart attack; Coronary artery disease - heart attack ... made up of cholesterol and other cells. A heart attack may occur when: A tear in the ...

  12. β-Sitosterol enhances cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration: protection against oxidant injury in H9c2 cells and rat hearts.

    PubMed

    Wong, Hoi Shan; Chen, Na; Leong, Pou Kuan; Ko, Kam Ming

    2014-07-01

    Herba Cistanches (Cistanche deserticola Y. C. Ma) is a 'Yang-invigorating' tonic herb in Chinese medicine. Preliminary chemical analysis indicated that β-sitosterol (BS) is one of the chemical constituents in an active fraction of Herba Cistanches. To investigate whether BS is an active ingredient of Herba Cistanches, the effects of BS on H9c2 cells and rat hearts were examined. The results indicated that BS stimulated the mitochondrial ATP generation capacity in H9c2 cells, which was associated with the increased production of mitochondrial reactive oxygen species. BS also stimulated mitochondrial state 3 and state 4 respiration, with the resultant decrease in coupling efficiency. BS produced an up-regulation of cellular glutathione redox cycling and protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cells. However, the protective effect of BS against myocardial ischemia/reperfusion injury was seen in female but not male rats ex vivo. The cardioprotection afforded by BS was likely mediated by an up-regulation of mitochondrial glutathione redox cycling in female rat hearts. In conclusion, the ensemble of results suggests that BS is an active ingredient of Herba Cistanches. The gender-dependent effect of BS on myocardial protection will further be investigated. Copyright © 2013 John Wiley & Sons, Ltd.

  13. Heart Diseases

    MedlinePlus

    ... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...

  14. Heart Transplantation

    MedlinePlus

    A heart transplant removes a damaged or diseased heart and replaces it with a healthy one. The healthy heart comes from a donor who has died. It is the last resort for people with heart failure when all other treatments have failed. The ...

  15. Optimized Heart Sampling and Systematic Evaluation of Cardiac Therapies in Mouse Models of Ischemic Injury: Assessment of Cardiac Remodeling and Semi-Automated Quantification of Myocardial Infarct Size.

    PubMed

    Valente, Mariana; Araújo, Ana; Esteves, Tiago; Laundos, Tiago L; Freire, Ana G; Quelhas, Pedro; Pinto-do-Ó, Perpétua; Nascimento, Diana S

    2015-12-02

    Cardiac therapies are commonly tested preclinically in small-animal models of myocardial infarction. Following functional evaluation, post-mortem histological analysis is essential to assess morphological and molecular alterations underlying the effectiveness of treatment. However, non-methodical and inadequate sampling of the left ventricle often leads to misinterpretations and variability, making direct study comparisons unreliable. Protocols are provided for representative sampling of the ischemic mouse heart followed by morphometric analysis of the left ventricle. Extending the use of this sampling to other types of in situ analysis is also illustrated through the assessment of neovascularization and cellular engraftment in a cell-based therapy setting. This is of interest to the general cardiovascular research community as it details methods for standardization and simplification of histo-morphometric evaluation of emergent heart therapies. © 2015 by John Wiley & Sons, Inc. Copyright © 2015 John Wiley & Sons, Inc.

  16. Biomarkers in acute heart failure.

    PubMed

    Mallick, Aditi; Januzzi, James L

    2015-06-01

    The care of patients with acutely decompensated heart failure is being reshaped by the availability and understanding of several novel and emerging heart failure biomarkers. The gold standard biomarkers in heart failure are B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide, which play an important role in the diagnosis, prognosis, and management of acute decompensated heart failure. Novel biomarkers that are increasingly involved in the processes of myocardial injury, neurohormonal activation, and ventricular remodeling are showing promise in improving diagnosis and prognosis among patients with acute decompensated heart failure. These include midregional proatrial natriuretic peptide, soluble ST2, galectin-3, highly-sensitive troponin, and midregional proadrenomedullin. There has also been an emergence of biomarkers for evaluation of acute decompensated heart failure that assist in the differential diagnosis of dyspnea, such as procalcitonin (for identification of acute pneumonia), as well as markers that predict complications of acute decompensated heart failure, such as renal injury markers. In this article, we will review the pathophysiology and usefulness of established and emerging biomarkers for the clinical diagnosis, prognosis, and management of acute decompensated heart failure. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  17. KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.

    PubMed

    Yang, Min-Kyu; Lee, Sung-Hun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Chung, Hun-Jong; Won, Hyung-Sik; Lee, Chang-Soo; Kwon, Suk-Hyung; Choi, Wahn-Soo; Shin, Hwa-Sup

    2009-02-01

    The cardioprotective effects of KR-31761, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 microM, 3 microM, and 10 microM, respectively) and double product (DP: heart rate x LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 microM, 3 microM, and 10 microM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 microM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 microM) and glyburide (1 microM), selective and nonselective blockers of the mitochondrial K+(ATP) (mitoK+(ATP)) channel and K+(ATP) channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+(ATP) (sarcK+(ATP)) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: > 30.0 microM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+(ATP) and sarcK+(ATP) channels in rat hearts with a minimal vasorelaxant effect.

  18. Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats

    PubMed Central

    Lai, Chao-Hung; Tsai, Cheng-Chih; Kuo, Wei-Wen; Ho, Tsung-Jung; Day, Cecilia-Hsuan; Pai, Pei-ying; Chung, Li-Chin; Huang, Chun-Chih; Wang, Hsueh-Fang; Liao, Po-Hsiang; Huang, Chih-Yang

    2016-01-01

    High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats. PMID:27076784

  19. Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats.

    PubMed

    Lai, Chao-Hung; Tsai, Cheng-Chih; Kuo, Wei-Wen; Ho, Tsung-Jung; Day, Cecilia-Hsuan; Pai, Pei-ying; Chung, Li-Chin; Huang, Chun-Chih; Wang, Hsueh-Fang; Liao, Po-Hsiang; Huang, Chih-Yang

    2016-01-01

    High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats.

  20. Sex-Specific Association of Sleep Apnea Severity with Subclinical Myocardial Injury, Ventricular Hypertrophy, and Heart Failure Risk in a Community Dwelling Cohort: The Atherosclerosis Risk in Communities-Sleep Heart Health Study

    PubMed Central

    Roca, Gabriela Querejeta; Redline, Susan; Claggett, Brian; Bello, Natalie; Ballantyne, Christie M.; Solomon, Scott D.; Shah, Amil M.

    2015-01-01

    Background Risk factors for obstructive sleep apnea (OSA) and development of subsequent cardiovascular (CV) complications differ by sex. We hypothesize that the relationship between OSA and high sensitivity troponin T (hs-TnT), cardiac structure, and CV outcomes differs by sex. Methods and Results 752 men and 893 women free of CV disease participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies were included. All participants (mean age 62.5±5.5 years) underwent polysomnography and measurement of hs-TnT. OSA severity was defined using established clinical categories. Subjects were followed for 13.6±3.2 years for incident coronary disease, heart failure, and CV and all-cause mortality. Surviving subjects underwent an echocardiography after 15.2±0.8 years. OSA was independently associated with hs-TnT among women (p=0.03) but not in men (p=0.94). Similarly, OSA was associated with incident HF or death in women (p=0.01) but not men (p=0.10). This association was no longer significant after adjusting for hs-TnT (p=0.09). Among surviving participants without an incident CV event, OSA assessed in mid-life was independently associated with higher left ventricle mass index only among women (p=0.001). Conclusions Sex-specific differences exist in the relationship between OSA and CV disease. OSA, assessed in mid-life, is independently associated with higher levels of concomitantly measured hs-TnT among women but not men, in whom other comorbidities associated with OSA may play a more important role. During 13-year follow-up, OSA was associated with incident HF or death only among women, and among those without an incident event, was independently associated with LV hypertrophy only in women. PMID:26316620

  1. Role of licochalcone C in cardioprotection against ischemia/reperfusion injury of isolated rat heart via antioxidant, anti-inflammatory, and anti-apoptotic activities.

    PubMed

    Zhou, Mingjie; Liu, Liqun; Wang, Wenjuan; Han, Jichun; Ren, Huanhuan; Zheng, Qiusheng; Wang, Dong

    2015-07-01

    This study aimed to evaluate the protective effect of licochalcone C against myocardial ischemia/reperfusion injury in rats. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined by using enzyme-linked immunosorbent assay. Cell morphology was observed and mitochondrial damage was assessed by HE coloration and transmission electron microscopy, respectively. Cardiomyocyte apoptosis was determined by using terminal deoxynucleotidyl transferased UTP nick-end labeling (TUNEL). Pretreatment with licochalcone C significantly improved the recovery of LVDP and ±dp/dtmax, and increased the levels of SOD and GSH/GSSG ratio. However, pretreatment with licochalcone C not only decreased the TUNEL-positive cell ratio and morphological changes, but also weaken the mitochondrial injury and the levels of CK, LDH, MDA, and TNF-α. These results suggested an important function of licochalcone C extracted from traditional Chinese medicine in the cardioprotection via antioxidant, anti-inflammatory, and anti-apoptotic activities. Copyright © 2015. Published by Elsevier Inc.

  2. Heart Attack

    MedlinePlus

    ... it as instructed while awaiting emergency help. Take aspirin, if recommended . Taking aspirin during a heart attack could reduce heart damage by helping to keep your blood from clotting. Aspirin can interact with other medications, however, so don' ...

  3. Heart pacemaker

    MedlinePlus

    ... 28 grams). Most pacemakers have 2 parts: The generator contains the battery and the information to control ... are wires that connect the heart to the generator and carry the electrical messages to the heart. ...

  4. Heart Failure

    MedlinePlus

    ... your body. An ejection fraction is an important measurement of how well your heart is pumping and ... catheterization and cardiac MRI. This is an important measurement of how well your heart is pumping and ...

  5. Heart Block

    MedlinePlus

    ... refers to the number of times your heart beats per minute. "Rhythm" refers to the pattern of regular or irregular pulses produced as the heart beats.) With each heartbeat, an electrical signal spreads across ...

  6. Heart Disease

    MedlinePlus

    ... wear to record a continuous ECG, usually for 24 to 72 hours. Holter monitoring is used to detect heart rhythm ... your doctor to make sure you're properly managing your heart condition. ... making the same lifestyle changes that can improve your heart disease, such ...

  7. Heart Attack

    MedlinePlus

    ... a million people in the U.S. have a heart attack. About half of them die. Many people have permanent heart damage or die because they don't get ... It's important to know the symptoms of a heart attack and call 9-1-1 if someone ...

  8. Cardiac Per2 Functions as Novel Link between Fatty Acid Metabolism and Myocardial Inflammation during Ischemia and Reperfusion Injury of the Heart

    PubMed Central

    Bonney, Stephanie; Kominsky, Doug; Brodsky, Kelley; Eltzschig, Holger; Walker, Lori; Eckle, Tobias

    2013-01-01

    Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In contrast to Clock−/−, Per2−/− mice have larger infarct sizes with deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we measured lactate during reperfusion in Per1−/−, Per2−/− or wildtype mice. As lactate measurements in whole blood indicated an exclusive role of Per2 in controlling lactate production during myocardial ischemia, we next performed gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2−/− mice. Surprisingly, high-throughput gene array analysis revealed dominantly lipid metabolism as the differentially regulated pathway in wildtype mice when compared to Per2−/−. In all ischemia-reperfusion protocols used, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2−/− mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated ‘Per2-genes’. Subsequent studies on inflammatory markers showed increasing IL-6 or TNFα levels during reperfusion in Per2−/− mice. In summary, these studies reveal an important role of cardiac Per2 for fatty acid metabolism and inflammation during myocardial ischemia and reperfusion, respectively. PMID:23977055

  9. Comparison of coronary artery calcification scores and National Cholesterol Education program guidelines for coronary heart disease risk assessment and treatment paradigms in individuals with chronic traumatic spinal cord injury.

    PubMed

    Lieberman, Jesse A; Hammond, Flora M; Barringer, Thomas A; Norton, H J; Goff, David C; Bockenek, William L; Scelza, William M

    2011-01-01

    To investigate the risk of coronary heart disease (CHD) in individuals with spinal cord injury (SCI) according to the National Cholesterol Educational Program (NCEP) guidelines and CT coronary artery calcium scores (CCS). Cross-sectional study of consecutive sample of males with SCI presenting to a single site for CHD risk assessment. Males age 45-70 with traumatic SCI (American Spinal Injury Association (ASIA) A, B, and C) injured for at least 10 years with no prior history of clinical CHD. Medical history, blood-pressure, and fasting lipid panel were used to calculate risk for CHD with the use of the Framingham risk score (FRS). Risk and treatment eligibility status was assessed based on NCEP/FRS recommendations and by presence and amount of CCS. Percent agreement (PA) and kappa were calculated between the two algorithms. Spearman correlations were calculated between CCS and FRS and individual risk factors. A total of 38 men were assessed; 18 (47.4%) had CCS > 0. The PA between NCEP/FRS assessment and CCS was 18% with a kappa of -0.03. 11 (28.9%) had CCS > 100 or >75th percentile for their age, sex, and race, which might qualify them for lipid-lowering treatment. Only 26 were placed into the same treatment category by NCEP/FRS and CCS, for a PA of 68% with a kappa of 0.35. In all, 20 (52.6%) were eligible for lipid-lowering treatment by either NCEP/FRS (n=9) or CCS (n = 11). Seven subjects were above the treatment threshold based on CCS, but not NCEP/FRS and five subjects were above the NCEP/FRS threshold, but not CCS. Just four subjects were eligible by both algorithms. CCS only correlated with FRS (r = 0.508, P = 0.001) and age (r = 0.679, P < 0.001).

  10. Preventing Musculoskeletal Sports Injuries in Youth: A Guide for Parents

    MedlinePlus

    ... of heart and lungs), warm-up exercises, proper coaching, use of safety equipment. Track and Field Common ... males, sunscreen, water. Injury prevention: Proper conditioning and coaching. Football Common injuries and locations: Bruises, sprains, strains, ...

  11. Head Injuries

    MedlinePlus

    ... before. Often, the injury is minor because your skull is hard and it protects your brain. But ... injuries can be more severe, such as a skull fracture, concussion, or traumatic brain injury. Head injuries ...

  12. Back Injuries

    MedlinePlus

    ... extending from your neck to your pelvis. Back injuries can result from sports injuries, work around the house or in the garden, ... back is the most common site of back injuries and back pain. Common back injuries include Sprains ...

  13. Heart-to-Heart

    NASA Image and Video Library

    2017-06-26

    NASA didn’t miss a (heart)beat when the opportunity arose to study the cardiovascular systems of identical twin astronauts, one aboard the International Space Station and the other on Earth. Results from the Cardio Ox investigation, part of the research of the One Year Mission of astronaut Scott Kelly, may provide a better understanding of cardiovascular disease risk that astronauts encounter during and after long-duration spaceflight. Stuart Lee, the lead scientist for the Cardiovascular and Vision Laboratory at NASA’s Johnson Space Center, explains the importance of spaceflight weightlessness research on the cardiovascular system and how results could be used to create countermeasures, preventing potential health consequences for future space travelers as well as those of us on Earth. For more on ISS science, follow us on Twitter: @ISS_research or at https://twitter.com/ISS_Research or at: https://www.nasa.gov/mission_pages/station/research/index.html

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

    PubMed

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

    2013-08-01

    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.

  15. Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

    PubMed Central

    Zhou, Mingjie; Ren, Huanhuan; Han, Jichun; Wang, Wenjuan; Zheng, Qiusheng; Wang, Dong

    2015-01-01

    Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats. Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β (GSK-3β), phospho-GSK-3β (P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis. Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and ±dp/dtmax, as well as increased the levels of SOD and P-GSK-3β and GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α. Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3β activity in rats with I/R. PMID:26265983

  16. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome.

    PubMed

    Ishiguro, Hisaaki; Horiba, Mitsuru; Takenaka, Hiroharu; Sumida, Arihiro; Opthof, Tobias; Ishiguro, Yuko S; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo

    2011-01-01

    Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  17. Quality of cardiopulmonary resuscitation affects cardioprotection by induced hypothermia at 34 °C against ischemia/reperfusion injury in a rat isolated heart model.

    PubMed

    Mochizuki, Toshiaki; Jiang, Qiliang; Katoh, Takasumi; Aoki, Katsunori; Sato, Shigehito

    2013-06-01

    In this study, we aimed to compare the effects of low- and high-quality cardiopulmonary resuscitation (CPR) on cardioprotection by induced hypothermia (IH) at 34 °C and examine whether extracellular signal-regulated kinase or endothelial nitric oxide synthase mediates this cardioprotection. Left ventricle infarct sizes were evaluated in six groups of rat hearts (n = 6) following Langendorff perfusion and triphenyltetrazolium chloride staining. Controls underwent 30 min of global ischemia at 37 °C, followed by 10 min of simulated low- or high-quality CPR reperfusion and 90 min of reperfusion at 75 mmHg. The IH groups underwent IH at 34 °C during reperfusion. The U0126 group received U0126 (60 μM)-an extracellular signal-regulated kinase inhibitor-during reperfusion at 34 °C. The L-NIO (N-(1-iminoethyl)-L-ornithine dihydrochloride) group received L-NIO (2 μM)-an endothelial nitric oxide synthase inhibitor-5 min before global ischemia at 37 °C to the end of reperfusion at 34 °C. Infarct size did not significantly differ between the control and IH groups receiving low-quality CPR. However, IH with high-quality CPR reduced the infarct size from 47.2% ± 10.2% to 26.0% ± 9.4% (P = 0.005). U0126 reversed the IH-induced cardioprotection (45.9% ± 9.4%, P = 0.010), whereas L-NIO had no significant effect. Cardiopulmonary resuscitation quality affects IH-induced cardioprotection. Extracellular signal-regulated kinase may mediate IH-induced cardioprotection.

  18. Cilostazol protects the heart against ischaemia reperfusion injury in a rabbit model of myocardial infarction: focus on adenosine, nitric oxide and mitochondrial ATP-sensitive potassium channels.

    PubMed

    Bai, Yushan; Muqier; Murakami, Hiroya; Iwasa, Masamitsu; Sumi, Shohei; Yamada, Yoshihisa; Ushikoshi, Hiroaki; Aoyama, Takuma; Nishigaki, Kazuhiko; Takemura, Genzou; Uno, Bunji; Minatoguchi, Shinya

    2011-10-01

    1. The present study examined whether or not cilostazol reduces the myocardial infarct size, and investigated its mechanism in a rabbit model of myocardial infarction. 2. Japanese white rabbits underwent 30 min of coronary occlusion, followed by 48 h of reperfusion. Cilostazol (1 and 5 mg/kg) or vehicle was given intravenously 5 min before ischaemia. 8-p-sulfophenyl theophylline (8SPT; an adenosine receptor blocker, 7.5 mg/kg), Nω-nitro-L-arginine methylester (l-NAME; an NOS inhibitor, 10 mg/kg) or 5-hydroxydecanoic acid sodium salt (5-HD; a mitochondrial ATP-sensitive potassium (KATP) channel blocker, 5 mg/kg) was given intravenously 5 min before cilostazol injection. Infarct size was determined as a percentage of the risk area. 3. The myocardial interstitial levels of adenosine and nitrogen oxide (NOx) during ischaemia and reperfusion, and the intensity of myocardial dihydroethidium staining were determined. 4. Infarct size was significantly reduced in the cilostazol 1 mg/kg (38.4% (2.9%)) and cilostazol 5 mg/kg (30.7% (4.7%)) groups compared with that in the control group (46.5% (4.2%)). The infarct size-reducing effect of cilostazol was completely abolished by 8SPT (46.6% (3.5%)), L-NAME (49.0% (5.5%)), or 5HD (48.5% (5.1%)). 8SPT, L-NAME or 5HD alone did not affect the infarct size. Cilostazol treatment significantly increased myocardial levels of adenosine and NOx during ischaemia, and attenuated the intensity of dihydroethidium staining during reperfusion. 5. These findings show that cilostazol reduces the myocardial infarct size by increasing adenosine and NOx levels, attenuating superoxide production and opening the mitochondrial KATP channels. Cilostazol might provide a new strategy for the treatment of coronary heart disease.

  19. Heart regeneration.

    PubMed

    Breckwoldt, Kaja; Weinberger, Florian; Eschenhagen, Thomas

    2016-07-01

    Regenerating an injured heart holds great promise for millions of patients suffering from heart diseases. Since the human heart has very limited regenerative capacity, this is a challenging task. Numerous strategies aiming to improve heart function have been developed. In this review we focus on approaches intending to replace damaged heart muscle by new cardiomyocytes. Different strategies for the production of cardiomyocytes from human embryonic stem cells or human induced pluripotent stem cells, by direct reprogramming and induction of cardiomyocyte proliferation are discussed regarding their therapeutic potential and respective advantages and disadvantages. Furthermore, different methods for the transplantation of pluripotent stem cell-derived cardiomyocytes are described and their clinical perspectives are discussed. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  20. Hypoplastic left heart syndrome

    MedlinePlus

    HLHS; Congenital heart - hypoplastic left heart; Cyanotic heart disease - hypoplastic left heart ... Hypoplastic left heart is a rare type of congenital heart disease. It is more common in males than in females. As ...

  1. Heart palpitations

    MedlinePlus

    ... or longer Echocardiogram Electrophysiology study (EPS) Coronary angiography ... E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2015:chap ...

  2. Heart Attack Symptoms in Women

    MedlinePlus

    ... a Heart Attack Treatment of a Heart Attack Life After a Heart Attack Heart Failure About Heart Failure ... a Heart Attack • Treatment of a Heart Attack • Life After a Heart Attack Lifestyle Changes Recovery FAQs • Heart ...

  3. Heart Truth

    MedlinePlus

    ... overall health and will allow you to enjoy quality time with your loved ones. Make a commitment to yourself and share it with a loved one for support. Learn more about The Heart Truth program, the risk factors for heart disease, and the stories of other ...

  4. Heart Attack

    MedlinePlus

    ... test your blood several times during the first 24 hours to 48 hours after yours symptoms start.Other ... do to help prevent heart attack?A healthy lifestyle can help prevent heart attack. This ... your stress.Controlling your blood pressure.Managing your ...

  5. Heart Anatomy

    MedlinePlus

    ... español An Incredible Machine Bonus poster (PDF) The Human Heart Anatomy Blood The Conduction System The Coronary Arteries The Heart Valves The Heartbeat Vasculature of the Arm Vasculature of the Head Vasculature of the Leg Vasculature of the Torso ...

  6. Stingray barb injury: a cause of late coronary occlusion and stent failure.

    PubMed

    Saunders, Craig R; Saro, Enrique; Patel, Parag; Swidryk, John; Bacani, Victor O; Russo, Mark J; Stone, Jay H

    2013-11-01

    Stingray injuries to the heart are rare, and survivors of this injury are even rarer. To date, there are only three reported survivors of this mode of penetrating cardiac injury, all inflicted by the living animal itself. The following is a report of a stingray injury, inflicted by a human, causing coronary complications 17 years after the injury was sustained.

  7. Sports Injuries

    MedlinePlus

    ... sometimes you can injure yourself when you play sports or exercise. Accidents, poor training practices, or improper ... can also lead to injuries. The most common sports injuries are Sprains and strains Knee injuries Swollen ...

  8. Eye Injuries

    MedlinePlus

    The structure of your face helps protect your eyes from injury. Still, injuries can damage your eye, sometimes severely enough that you could lose your vision. Most eye injuries are preventable. If you play sports or ...

  9. Acupuncture therapy related cardiac injury.

    PubMed

    Li, Xue-feng; Wang, Xian

    2013-12-01

    Cardiac injury is the most serious adverse event in acupuncture therapy. The causes include needling chest points near the heart, the cardiac enlargement and pericardial effusion that will enlarge the projected area on the body surface and make the proper depth of needling shorter, and the incorrect needling method of the points. Therefore, acupuncture practitioners must be familiar with the points of the heart projected area on the chest and the correct needling methods in order to reduce the risk of acupuncture therapy related cardiac injury.

  10. Hamstring injuries.

    PubMed

    Ropiak, Christopher R; Bosco, Joseph A

    2012-01-01

    Hamstring injuries are a frequent injury in athletes. Proximal injuries are common, ranging from strain to complete tear. Strains are managed nonoperatively, with rest followed by progressive stretching and strengthening. Reinjury is a concern. High grade complete tears are better managed surgically, with reattachment to the injured tendon or ischial tuberosity. Distal hamstring injury is usually associated with other knee injuries, and isolated injury is rare.

  11. INO-4885 [5,10,15,20-Tetra[N-(benzyl-4′-carboxylate)-2-pyridinium]-21H,23H-porphine Iron(III) Chloride], a Peroxynitrite Decomposition Catalyst, Protects the Heart against Reperfusion Injury in Mice

    PubMed Central

    Jiao, Xiang-Ying; Gao, Erhe; Yuan, Yuexin; Wang, Yajing; Lau, Wayne Bond; Koch, Walter; Ma, Xin-Liang; Tao, Ling

    2009-01-01

    Oxidative/nitrative stress caused by peroxynitrite, the reaction product of superoxide (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document}) and nitric oxide (NO), is the primary cause of myocardial ischemia/reperfusion injury. The present study determined whether INO-4885 [5,10,15,20-tetra[N-(benzyl-4′-carboxylate)-2-pyridinium]-21H,23H-porphine iron(III) chloride], a new peroxynitrite decomposition catalyst, may provide cellular protection and protect heart from myocardial ischemia/reperfusion injury. Adult male mice were subjected to 30 min of ischemia and 3 or 24 h of reperfusion. Mice were randomized to receive vehicle, INO-4885 without catalytic moiety, or INO-4885 (3-300 μg/kg i.p.) 10 min before reperfusion. Infarct size, apoptosis, nitrotyrosine content, NO/\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document} production, and inducible nitric-oxide synthase (iNOS)/NADPH oxidase expression were determined. INO-4885 treatment reduced ischemia/reperfusion-induced protein nitration and caspase 3 activation in a dose-dependent fashion in the range of 3 to 100 μg/kg. However, doses exceeding 100 μg/kg produced nonspecific effects and attenuated its protective ability. At the optimal dose (30 μg/kg), INO-4885 significantly reduced infarct size (p < 0.01), decreased apoptosis (p < 0.01), and reduced tissue nitrotyrosine content (p < 0.01). As expected, INO-4885 had no

  12. Rugby injuries.

    PubMed

    McIntosh, Andrew S

    2005-01-01

    The purpose of this chapter is to review critically the existing studies on the epidemiology of pediatric rugby injuries and discuss suggestions for injury prevention and further research. Data were sourced from the sports medicine and science literature mainly since 1990, and from a prospective injury surveillance project in rugby undertaken by the University of New South Wales (UNSW) in Sydney during 2002. Literature searches were performed using Medline and SportsDiscus. Reported injury rates were between 7 and 18 injuries per 1,000 hours played, with the rate of injuries resulting in loss of playing or training time measured at 6.5-10.6 per 1,000 hours played. Injury rates increased with age and level of qualification. Head injury and concussion accounted for 10-40% of all injuries. In the UNSW study, concussion accounted for 25% of injuries resulting in loss of playing or training time in the under 13 year age group. Upper and lower extremity injuries were equally apportioned, with musculoskeletal injuries being the main type of injury. Fractures were observed in the upper extremity and ankle, and joint/ligament injuries affected the shoulder, knee and ankle. The tackle was associated with around 50% of all injuries. The scrum produced fewer injuries, but is historically associated with spinal cord injury. Rugby is a contact sport with injury risks related to physical contact, primarily in the tackle. Most injuries affect the musculoskeletal system, with the exception of concussion. Spinal cord injury is rare, but catastrophic. Research is required to understand better injury risks and to reduce the incidence of shoulder, knee and ankle joint injuries, concussion and spinal injury.

  13. Wine and heart health

    MedlinePlus

    Health and wine; Wine and heart disease; Preventing heart disease - wine; Preventing heart disease - alcohol ... more often just to lower your risk of heart disease. Heavier drinking can harm the heart and ...

  14. What Is Heart Failure?

    MedlinePlus

    ... page from the NHLBI on Twitter. What Is Heart Failure? Heart failure is a condition in which the heart can' ... force. Some people have both problems. The term "heart failure" doesn't mean that your heart has stopped ...

  15. Heart Attack

    MedlinePlus

    ... yourself MedlinePlus for More Information National Institute on Aging Related Topics Heart Failure High Blood Cholesterol High ... us | Customer Support | site map National Institute on Aging | U.S. National Library of Medicine | National Institutes of ...

  16. Hearts Wish.

    ERIC Educational Resources Information Center

    Jones, Lethonee A.

    1989-01-01

    Investigates characteristics and themes in 102 drawings by sexually abused children. Themes of the drawings included genitalia, the absence of specific body parts, phallic symbols, inappropriate smiles, distorted body images, kinetic activity, prominent hands and fingers, and hearts. (RJC)

  17. Heart Transplant

    MedlinePlus

    ... of this information Order our Heart Transplant brochure Video: Preparing For Your Surgery Find helpful tips from ... how to plan and prepare for your surgery. Video: Recovering From Your Surgery Find helpful tips from ...

  18. What Is a Heart Murmur?

    MedlinePlus

    ... Heart Murmur Related Topics Anemia Congenital Heart Defects Heart Valve Disease Holes in the Heart How the Heart Works ... heart defect that is present since birth or heart valve disease. Depending on the heart problem causing the abnormal ...

  19. Heart failure

    PubMed Central

    2011-01-01

    Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of multidisciplinary interventions for heart failure? What are the effects of exercise in people with heart failure? What are the effects of drug treatments for heart failure? What are the effects of devices for treatment of heart failure? What are the effects of coronary revascularisation for treatment of heart failure? What are the effects of drug treatments in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 80 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium

  20. [Artificial heart and heart transplantation].

    PubMed

    Moosdorf, R

    2012-12-01

    The advances in the treatment of many different heart diseases have on the one side led to a significant prolongation of life expectancy but have also contributed to an increase of patients with heart failure. This tendency is supported even more so by the demographic development of our population. The replacement of insufficient organs has always been in the focus of medical research. In the 1960's Shumway and Lower developed the technique of cardiac transplantation and also worked intensively on the treatment and diagnosis of rejection. However, it was Barnard who, in 1967 performed the first human cardiac transplantation. Other centers followed worldwide but the mortality was high and the new therapy was controversially discussed in many journals. By the introduction of cyclosporin as a new immunosuppressive agent in 1978, results improved rapidly and cardiac transplantation became an accepted therapeutic option for patients with end stage heart failure and also for children and newborns with congenital heart defects. Today, with newer immunosuppressive regimens and improved techniques, cardiac transplantation offers excellent results with a long-term survival of nearly 50% of patients after 15 years and among the pediatric population even after 20 years. However, the donor organ shortage as well as the increasing number of elderly patients with end stage heart failure has necessitated work on other alternatives. Neither stem cell transplantation nor xenotransplantation of animal organs are yet an option and there are still some obstacles to be overcome. In contrast, the development of so-called artificial hearts has made significant progress. While the first implants of totally artificial hearts were associated with many comorbidities and patients were seriously debilitated, new devices today offer a reasonable quality of life and long-term survival. Most of these systems are no longer replacing but mainly assisting the heart, which remains in place. These

  1. Association of N-terminal pro-brain natriuretic peptide with contrast-induced acute kidney injury and long-term mortality in patients with heart failure and mid-range ejection fraction

    PubMed Central

    Wang, Kun; Li, Hua-long; Chen, Li-ling; Bei, Wei-jie; Lin, Kai-yang; Smyth, Brendan; Chen, Shi-qun; Guo, Xiao-sheng; Guo, Wei; Liu, Yuan-hui; Chen, Peng-yuan; Chen, Ji-yan; Chen, Kai-hong; Liu, Yong; Tan, Ning

    2017-01-01

    Abstract The potential value of N-terminal pro-brain natriuretic peptide (NT-proBNP) for contrast-induced acute kidney injury (CI-AKI) in patients with heart failure and mid-range ejection fraction (HFmrEF) is unclear. We investigated whether NT-proBNP is associated with CI-AKI and long-term mortality following elective cardiac catheterization in patients with HFmrEF. A total of 174 consecutive patients with HFmrEF undergoing elective coronary angiography or intervention were enrolled. The primary endpoint was the development of CI-AKI, defined as an absolute increase of ≥0.3 mg/dL or ≥ 50% from baseline serum creatinine with 48 hours after contrast medium exposure. Receiver-operating characteristic curve analysis was conducted, and Youden index was used to determine the best cutoff NT-proBNP value. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the independent risk factors for CI-AKI and long-term mortality, respectively. The incidence of CI-AKI was 12.1%. Patients with CI-AKI had higher NT-proBNP values than those without (4373[1561.9–7470.5] vs 1303[625.2–2482.3], P = 0.003). Receiver-operating characteristic curve revealed that NT-proBNP was not significantly different from the Mehran risk score in predicting CI-AKI (area under the curve [AUC] = 0.723 vs 0.767, P = 0.516). The best cutoff NT-proBNP value for CI-AKI was 3299 pg/mL, with 70.6% sensitivity and 83.1% specificity. Multivariable analysis demonstrated that NT-proBNP ≥3299 pg/mL is significantly related to CI-AKI (odds ratio = 12.79; 95% confidence interval, 3.18–51.49; P < 0.001). Cox regression analysis showed that NT-proBNP ≥3299 pg/mL is associated with long-term mortality (adjusted hazard ratio = 11.91; 95%CI, 2.16–65.70; P = 0.004) during follow-up. In patients with HFmrEF, NT-proBNP ≥3299 pg/mL is associated with CI-AKI and long-term mortality following elective coronary

  2. Association of N-terminal pro-brain natriuretic peptide with contrast-induced acute kidney injury and long-term mortality in patients with heart failure and mid-range ejection fraction: An observation study.

    PubMed

    Wang, Kun; Li, Hua-Long; Chen, Li-Ling; Bei, Wei-Jie; Lin, Kai-Yang; Smyth, Brendan; Chen, Shi-Qun; Guo, Xiao-Sheng; Guo, Wei; Liu, Yuan-Hui; Chen, Peng-Yuan; Chen, Ji-Yan; Chen, Kai-Hong; Liu, Yong; Tan, Ning

    2017-03-01

    The potential value of N-terminal pro-brain natriuretic peptide (NT-proBNP) for contrast-induced acute kidney injury (CI-AKI) in patients with heart failure and mid-range ejection fraction (HFmrEF) is unclear. We investigated whether NT-proBNP is associated with CI-AKI and long-term mortality following elective cardiac catheterization in patients with HFmrEF.A total of 174 consecutive patients with HFmrEF undergoing elective coronary angiography or intervention were enrolled. The primary endpoint was the development of CI-AKI, defined as an absolute increase of ≥0.3 mg/dL or ≥ 50% from baseline serum creatinine with 48 hours after contrast medium exposure. Receiver-operating characteristic curve analysis was conducted, and Youden index was used to determine the best cutoff NT-proBNP value. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify the independent risk factors for CI-AKI and long-term mortality, respectively.The incidence of CI-AKI was 12.1%. Patients with CI-AKI had higher NT-proBNP values than those without (4373[1561.9-7470.5] vs 1303[625.2-2482.3], P = 0.003). Receiver-operating characteristic curve revealed that NT-proBNP was not significantly different from the Mehran risk score in predicting CI-AKI (area under the curve [AUC] = 0.723 vs 0.767, P = 0.516). The best cutoff NT-proBNP value for CI-AKI was 3299 pg/mL, with 70.6% sensitivity and 83.1% specificity. Multivariable analysis demonstrated that NT-proBNP ≥3299 pg/mL is significantly related to CI-AKI (odds ratio = 12.79; 95% confidence interval, 3.18-51.49; P < 0.001). Cox regression analysis showed that NT-proBNP ≥3299 pg/mL is associated with long-term mortality (adjusted hazard ratio = 11.91; 95%CI, 2.16-65.70; P = 0.004) during follow-up.In patients with HFmrEF, NT-proBNP ≥3299 pg/mL is associated with CI-AKI and long-term mortality following elective coronary angiography or

  3. Heart failure

    PubMed Central

    2010-01-01

    Introduction Heart failure occurs in 3% to 4% of adults aged over 65 years, usually as a consequence of coronary artery disease or hypertension, and causes breathlessness, effort intolerance, fluid retention, and increased mortality. The 5-year mortality in people with systolic heart failure ranges from 25% to 75%, often owing to sudden death following ventricular arrhythmia. Risks of cardiovascular events are increased in people with left ventricular systolic dysfunction (LVSD) or heart failure. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments, and of drug and invasive treatments, for heart failure? What are the effects of angiotensin-converting enzyme inhibitors in people at high risk of heart failure? What are the effects of treatments for diastolic heart failure? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 85 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: aldosterone receptor antagonists, amiodarone, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation, antiplatelet agents, beta-blockers, calcium channel blockers, cardiac resynchronisation therapy, digoxin (in people already receiving diuretics and angiotensin-converting enzyme inhibitors), exercise, hydralazine plus isosorbide dinitrate, implantable cardiac

  4. Snowboard injuries.

    PubMed

    Pino, E C; Colville, M R

    1989-01-01

    A retrospective survey of 267 snowboarders was undertaken to determine the population at risk and types and mechanisms of injuries sustained in this sport. Snowboarders are young (average age, 21 years), male (greater than 90%), view themselves in average or above average physical condition (96%), and have varied sports interests. One hundred ten injuries that resulted in a physician visit were reported. Ligament sprains, fractures, and contusions were the most frequent types of injury. Fifty percent of all injuries occurred in the lower extremities, with ankle injuries being the most common. Snowboard riders using equipment with increased ankle support seem to be more protected from lower extremity injuries. The lower extremity injuries were concentrated in the forward limb of the snowboarder, where the rider's weight is disproportionately distributed. Differences in the mechanism and spectrum of injury between snowboarding and skiing injuries were noted, including: impact rather than torsion as the major mechanism of injury, a significant lack of thumb injuries, comparative increase in ankle injuries, a decrease in knee injuries, and a higher percentage of upper extremity injuries.

  5. Healthy Heart Quizzes

    MedlinePlus

    ... Cholesterol Tools & Resources Congenital Defects Children & Adults About Congenital Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & ...

  6. Inhaled matters of the heart

    PubMed Central

    Zaky, Ahmed; Ahmad, Aftab; Dell’Italia, Louis J; Jahromi, Leila; Reisenberg, Lee Ann; Matalon, Sadis; Ahmad, Shama

    2015-01-01

    Inhalations of atmospheric pollutants, especially particulate matters, are known to cause severe cardiac effects and to exacerbate preexisting heart disease. Heart failure is an important sequellae of gaseous inhalation such as that of carbon monoxide. Similarly, other gases such as sulphur dioxide are known to cause detrimental cardiovascular events. However, mechanisms of these cardiac toxicities are so far unknown. Increased susceptibility of the heart to oxidative stress may play a role. Low levels of antioxidants in the heart as compared to other organs and high levels of reactive oxygen species produced due to the high energetic demand and metabolic rate in cardiac muscle are important in rendering this susceptibility. Acute inhalation of high concentrations of halogen gases is often fatal. Severe respiratory injury and distress occurs upon inhalation of halogens gases, such as chlorine and bromine; however, studies on their cardiac effects are scant. We have demonstrated that inhalation of high concentrations of halogen gases cause significant cardiac injury, dysfunction, and failure that can be critical in causing mortalities following exposures. Our studies also demonstrated that cardiac dysfunction occurs as a result of a direct insult independent of coexisting hypoxia, since it is not fully reversed by oxygen supplementation. Therefore, studies on offsite organ effects of inhaled toxic gases can impact development of treatment strategies upon accidental or deliberate exposures to these agents. Here we summarize the knowledge of cardiovascular effects of common inhaled toxic gases with the intent to highlight the importance of consideration of cardiac symptoms while treating the victims. PMID:26665179

  7. Snowboarding injuries.

    PubMed

    Sachtleben, Thomas R

    2011-01-01

    Snowboarding has gained immense popularity during the past 30 years and continues to appeal to many young participants. Injury patterns and characteristics of injuries seen commonly in snowboarders have rapidly evolved during this time. Risk factors have emerged, and various methods of reducing injuries to snowboarders have been investigated. It is important that medical providers are knowledgeable about this growing sport and are prepared to adequately evaluate and treat snowboarding injuries. This article will review the issues and discuss diagnostic and treatment principles regarding injuries seen commonly in snowboarders. Injury prevention should be emphasized, particularly with young riders and beginners.

  8. Skateboard injuries.

    PubMed

    Cass, D T; Ross, F

    1990-08-06

    The recent increase in skateboard injuries is causing concern. Over a 30-month period there were 80 admissions (69 children) to Westmead Hospital because of skateboard injuries. Among children most injuries were minor, involving fractures to the upper limbs (47) or minor head injuries (8). The only serious injuries were a ruptured urethra and a closed head injury. Over the same time period skateboard riding caused five deaths in New South Wales. These all involved head injuries and in four instances collisions with cars. The data strongly support other studies that show skateboard riding is particularly dangerous near traffic and should be proscribed. However, in parkland and around the home the skateboard is an enjoyable toy with an acceptable risk of minor injury. Helmets should be worn and would have prevented all the head injury admissions in this series. Children under 10 have a higher risk of fractures and head injuries due to insufficient motor development to control the boards and the resultant falls. Skateboard injuries are an example of injuries caused by a "fad epidemic". To cope with these types of periodic events up-to-date data collection is needed, followed rapidly by an intervention programme so that serious injuries can be kept to a minimum.

  9. Women's Heart Disease: Heart Attack Symptoms

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Attack Symptoms Past Issues / Winter 2014 Table ... NHLBI has uncovered some of the causes of heart diseases and conditions, as well as ways to prevent ...

  10. Women's Heart Disease: Heart Disease Risk Factors

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

  11. Heart Health: The Heart Truth Campaign 2009

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health The Heart Truth Campaign 2009 Past Issues / Winter 2009 Table ... one of the celebrities supporting this year's The Heart Truth campaign. Both R&B singer Ashanti (center) ...

  12. Heart Health - Heart Disease: Symptoms, Diagnosis, Treatment

    MedlinePlus

    ... Bar Home Current Issue Past Issues Cover Story Heart Health Heart Disease: Symptoms, Diagnosis, Treatment Past Issues / Winter 2009 ... of this page please turn Javascript on. Most heart attacks happen when a clot in the coronary ...

  13. Heart failure in children - overview

    MedlinePlus

    Congestive heart failure - children; Cor pulmonale - children; Cardiomyopathy - children; CHF - children; Congenital heart defect - heart failure in children; Cyanotic heart disease - heart failure in children; Birth defect of the heart - heart ...

  14. Knee Injuries

    MedlinePlus

    ... your knee, like keeping it from bending outward. anterior cruciate ligament (ACL): The ACL connects your femur to your ... Injuries Sports and Exercise Safety Osgood-Schlatter Disease Anterior Cruciate Ligament (ACL) Injuries Bones, Muscles, and Joints Meniscus Tears ...

  15. Birth Injury

    MedlinePlus

    ... Are Up to Date Additional Content Medical News Birth Injury By Arthur E. Kopelman, MD, Professor of ... Problems in Newborns Overview of Problems in Newborns Birth Injury Prematurity Postmaturity Small for Gestational Age (SGA) ...

  16. Inhalation Injuries

    MedlinePlus

    ... you can inhale that can cause acute internal injuries. Particles in the air from fires and toxic ... and lung diseases worse. Symptoms of acute inhalation injuries may include Coughing and phlegm A scratchy throat ...

  17. Corneal injury

    MedlinePlus

    ... as sand or dust Ultraviolet injuries: Caused by sunlight, sun lamps, snow or water reflections, or arc- ... a corneal injury if you: Are exposed to sunlight or artificial ultraviolet light for long periods of ...

  18. Urethral Injuries

    MedlinePlus

    ... and Related Injuries (Video) Rotator Cuff Injury (News) Violent Video Games May Not 'Desensitize' Players, Brain Scans ... Comfort Am I Correct? More Videos News HealthDay Violent Video Games May Not 'Desensitize' Players, Brain Scans ...

  19. Regenerating new heart with stem cells

    PubMed Central

    Anversa, Piero; Kajstura, Jan; Rota, Marcello; Leri, Annarosa

    2013-01-01

    This article discusses current understanding of myocardial biology, emphasizing the regeneration potential of the adult human heart and the mechanisms involved. In the last decade, a novel conceptual view has emerged. The heart is no longer considered a postmitotic organ, but is viewed as a self-renewing organ characterized by a resident stem cell compartment responsible for tissue homeostasis and cardiac repair following injury. Additionally, HSCs possess the ability to transdifferentiate and acquire the cardiomyocyte, vascular endothelial, and smooth muscle cell lineages. Both cardiac and hematopoietic stem cells may be used therapeutically in an attempt to reverse the devastating consequences of chronic heart failure of ischemic and nonischemic origin. PMID:23281411

  20. Getting a New Heart

    MedlinePlus

    ... 22, 2002 December 2006 March 2012 Getting A New Heart Facts About Heart Transplants American Society of ... represent the views of the Society. ________________________________________________________ Getting a New Heart Facts About Heart Transplants When you have ...

  1. Who Needs Heart Surgery?

    MedlinePlus

    ... signs of a previous or current heart attack. Stress Test Some heart problems are easier to diagnose when your heart is working hard and beating fast. During stress testing , you exercise to make your heart work ...

  2. American Heart Association

    MedlinePlus

    ... Heart.org Media for Heart.org American Heart Association An office pop-in from a coworker came ... employers for help. Why does the American Heart Association name a top college football coach? For Bear ...

  3. What Is Heart Surgery?

    MedlinePlus

    ... Another type of heart surgery is called off-pump, or beating heart, surgery. It's like traditional open- ... heart-lung bypass machine isn't used. Off-pump heart surgery is limited to CABG. Surgeons can ...

  4. Anatomy of the Heart

    MedlinePlus

    ... picture of the outside of a normal, healthy, human heart. Heart Exterior Figure A shows the location of ... picture of the inside of a normal, healthy, human heart. Heart Interior Figure A shows the location of ...

  5. Heart disease - resources

    MedlinePlus

    Resources - heart disease ... The following organizations are good resources for information on heart disease: American Heart Association -- www.heart.org Centers for Disease Control and Prevention -- www.cdc.gov/heartdisease

  6. Diabetic Heart Disease

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Diabetic Heart Disease? The term "diabetic heart disease" (DHD) refers to ... Kidney Diseases' Introduction to Diabetes Web page. What Heart Diseases Are Involved in Diabetic Heart Disease? DHD may ...

  7. Heart Diseases and Disorders

    MedlinePlus

    ... Resources Heart Diseases & Disorders Back to Patient Resources Heart Diseases & Disorders Millions of people experience irregular heartbeats, called ... harmless and happen in healthy people free of heart disease. However, some abnormal heart rhythms can be serious ...

  8. Heart attack first aid

    MedlinePlus

    First aid - heart attack; First aid - cardiopulmonary arrest; First aid - cardiac arrest ... A heart attack occurs when the blood flow that carries oxygen to the heart is blocked. The heart muscle ...

  9. Coronary heart disease

    MedlinePlus

    Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...

  10. Diabetic Heart Disease

    MedlinePlus

    ... be coronary heart disease (CHD), heart failure, and diabetic cardiomyopathy. Diabetes by itself puts you at risk for heart disease. Other risk factors include Family history of heart disease Carrying extra ...

  11. Cycling injuries.

    PubMed Central

    Cohen, G. C.

    1993-01-01

    Bicycle-related injuries have increased as cycling has become more popular. Most injuries to recreational riders are associated with overuse or improper fit of the bicycle. Injuries to racers often result from high speeds, which predispose riders to muscle strains, collisions, and falls. Cyclists contact bicycles at the pedals, seat, and handlebars. Each is associated with particular cycling injuries. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:8471908

  12. Skateboard injuries

    PubMed Central

    Christian, M. Sheila; Khan, O.

    1980-01-01

    One hundred and nineteen cases of injuries sustained by skateboard users are reviewed. A significant proportion of the injuries sustained were fractures. The absence of adequate protective measures was noted. A decrease in the popularity of the sport, as judged by the annual incidence of skateboard injuries, is apparent in this series. Imagesp102-ap102-b PMID:7407446

  13. Orienteering injuries

    PubMed Central

    Folan, Jean M.

    1982-01-01

    At the Irish National Orienteering Championships in 1981 a survey of the injuries occurring over the two days of competition was carried out. Of 285 individual competitors there was a percentage injury rate of 5.26%. The article discusses the injuries and aspects of safety in orienteering. Imagesp236-ap237-ap237-bp238-ap239-ap240-a PMID:7159815

  14. Pediatric heart surgery

    MedlinePlus

    Heart surgery - pediatric; Heart surgery for children; Acquired heart disease; Heart valve surgery - children ... There are many kinds of heart defects. Some are minor, and others are more serious. Defects can occur inside the heart or in the large blood vessels ...

  15. Targeted Laser Ablation of the Zebrafish Larval Heart Induces Models of Heart Block, Valvular Regurgitation, and Outflow Tract Obstruction

    PubMed Central

    Matrone, Gianfranco; Maqsood, Sana; Taylor, Jonathan; Mullins, John J.; Tucker, Carl S.

    2014-01-01

    Abstract Mammalian models of cardiac disease have provided unique and important insights into human disease but have become increasingly challenging to produce. The zebrafish could provide inexpensive high-throughput models of cardiac injury and repair. We used a highly targeted laser, synchronized to fire at specific phases of the cardiac cycle, to induce regional injury to the ventricle, atrioventricular (AV) cushion, and bulbus arteriosus (BA). We assessed the impact of laser injury on hearts of zebrafish early larvae at 72 h postfertilization, to different regions, recording the effects on ejection fraction (EF), heart rate (HR), and blood flow at 2 and 24 h postinjury (hpi). Laser injury to the apex, midzone, and outflow regions of the ventricle resulted in reductions of the ventricle EF at 2 hpi with full recovery of function by 24 hpi. Laser injury to the ventricle, close to the AV cushion, was more likely to cause bradycardia and atrial–ventricular dysfunction, suggestive of an electrical conduction block. At 2 hpi, direct injury to the AV cushion resulted in marked regurgitation of blood from the ventricle to the atrium. Laser injury to the BA caused temporary outflow tract obstruction with cessation of ventricle contraction and circulation. Despite such damage, 80% of embryos showed complete recovery of the HR and function within 24 h of laser injury. Precision laser injury to key structures in the zebrafish developing heart provides a range of potentially useful models of hemodynamic overload, injury, and repair. PMID:25272304

  16. Hypoxia and Fetal Heart Development

    PubMed Central

    Patterson, A.J.; Zhang, L

    2010-01-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although “normal” hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart’s development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation. PMID:20712587

  17. Twelve-hour reanimation of a human heart following donation after circulatory death.

    PubMed

    Rosenfeldt, Franklin; Ou, Ruchong; Woodard, John; Esmore, Donald; Marasco, Silvana

    2014-01-01

    Despite increasing use of donation after cardiac death (DCD) and encouraging results for non-cardiac transplants, DCD cardiac transplantation has not been widely adopted because, (1) the DCD heart sustains warm ischaemic injury during the death process and (2) conventional static cold storage significantly adds to the ischaemic injury. We have developed a simple system for perfusion of the DCD heart with cold crystalloid solution using gravity-feed that can reduce ischaemic injury and potentially render the heart suitable for transplantation. This report describes the first application of this technique to a human DCD heart with good functional metabolic recovery over 12h on an ex vivo rig.

  18. Waterbike injuries.

    PubMed Central

    Jeffery, R S; Caiach, S

    1991-01-01

    Jet skiing is a rapidly growing sport. The craft incorporate safety features and the manufacturers issue detailed safety instructions. Racing is conducted with adequate attention to clothing, safety and insurance. However, casual use is widespread and is sometimes irresponsible. Serious injuries to riders are uncommon: dental and knee injuries are described. A case of renal contusion and a head injury were caused by other riders and two potentially fatal injuries illustrate the risk for other water users. The number of injuries associated with the use of personal watercraft is likely to increase and may be influenced by appropriate organization or regulation. Images Figure 2 Figure 3 Figure 4 PMID:1810620

  19. [Evaluation and treatment of cardiac injuries].

    PubMed

    Echevarría, J R; San Román, A

    2000-05-01

    Cardiac injuries caused by a heart traumatism are not frequent but, of great importance given their high morbidity. Two different groups in terms of etiology, clinical picture, application of diagnostic techniques, treatment and prognosis can be considered. On one hand, there are cardiac injuries caused by a thoracal contusion, which provokes a contused lesion can affect the free wall, the interventricular septum, the valves, the subvalvular apparatus, the conduction system and the coronary vessels and, on the other hand, cardiac injuries caused by penetrating objects. Cardiac injury can lead to a life-threatening hemodynamic instability which mandates prompt and clear diagnostic and therapeutic approaches.

  20. Heart Research

    NASA Technical Reports Server (NTRS)

    1991-01-01

    James Antaki and a group of researchers from the University of Pittsburgh School of Medicine used many elements of the Technology Utilization Program while looking for a way to visualize and track material points within the heart muscle. What they needed were tiny artificial "eggs" containing copper sulfate solution, small enough (about 2 mm in diameter) that they would not injure the heart, and large enough to be seen in Magnetic Resonance Imaging (MRI) images; they also had to be biocompatible and tough enough to withstand the beating of the muscle. The group could not make nor buy sufficient containers. After reading an article on microspheres in NASA Tech Briefs, and a complete set of reports on microencapsulation from the Jet Propulsion Laboratory (JPL), JPL put Antaki in touch with Dr.Taylor Wang of Vanderbilt University who helped construct the myocardial markers. The research is expected to lead to improved understanding of how the heart works and what takes place when it fails.

  1. Bicycling injuries.

    PubMed

    Silberman, Marc R

    2013-01-01

    Bicycling injuries can be classified into bicycle contact, traumatic, and overuse injuries. Despite the popularity of cycling, there are few scientific studies regarding injuries. Epidemiological studies are difficult to compare due to different methodologies and the diverse population of cyclists studied. There are only three studies conducted on top level professionals. Ninety-four percent of professionals in 1 year have experienced at least one overuse injury. Most overuse injuries are mild with limited time off the bike. The most common site of overuse injury is the knee, and the most common site of traumatic injury is the shoulder, with the clavicle having the most common fracture. Many overuse and bicycle contact ailments are relieved with simple bike adjustments.

  2. Crosstalk between the heart and peripheral organs in heart failure.

    PubMed

    Jahng, James Won Suk; Song, Erfei; Sweeney, Gary

    2016-03-11

    Mediators from peripheral tissues can influence the development and progression of heart failure (HF). For example, in obesity, an altered profile of adipokines secreted from adipose tissue increases the incidence of myocardial infarction (MI). Less appreciated is that heart remodeling releases cardiokines, which can strongly impact various peripheral tissues. Inflammation, and, in particular, activation of the nucleotide-binding oligomerization domain-like receptors with pyrin domain (NLRP3) inflammasome are likely to have a central role in cardiac remodeling and mediating crosstalk with other organs. Activation of the NLRP3 inflammasome in response to cardiac injury induces the production and secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition to having local effects in the myocardium, these pro-inflammatory cytokines are released into circulation and cause remodeling in the spleen, kidney, skeletal muscle and adipose tissue. The collective effects of various cardiokines on peripheral organs depend on the degree and duration of myocardial injury, with systematic inflammation and peripheral tissue damage observed as HF progresses. In this article, we review mechanisms regulating myocardial inflammation in HF and the role of factors secreted by the heart in communication with peripheral tissues.

  3. Reduced Heart Rate Volatility

    PubMed Central

    Grogan, Eric L.; Morris, John A.; Norris, Patrick R.; France, Daniel J.; Ozdas, Asli; Stiles, Renée A.; Harris, Paul A.; Dawant, Benoit M.; Speroff, Theodore

    2004-01-01

    Objective: To determine if using dense data capture to measure heart rate volatility (standard deviation) measured in 5-minute intervals predicts death. Background: Fundamental approaches to assessing vital signs in the critically ill have changed little since the early 1900s. Our prior work in this area has demonstrated the utility of densely sampled data and, in particular, heart rate volatility over the entire patient stay, for predicting death and prolonged ventilation. Methods: Approximately 120 million heart rate data points were prospectively collected and archived from 1316 trauma ICU patients over 30 months. Data were sampled every 1 to 4 seconds, stored in a relational database, linked to outcome data, and de-identified. HR standard deviation was continuously computed over 5-minute intervals (CVRD, cardiac volatility–related dysfunction). Logistic regression models incorporating age and injury severity score were developed on a test set of patients (N = 923), and prospectively analyzed in a distinct validation set (N = 393) for the first 24 hours of ICU data. Results: Distribution of CVRD varied by survival in the test set. Prospective evaluation of the model in the validation set gave an area in the receiver operating curve of 0.81 with a sensitivity and specificity of 70.1 and 80.0, respectively. CVRD predict death as early as 24 hours in the validation set. Conclusions: CVRD identifies a subgroup of patients with a high probability of dying. Death is predicted within first 24 hours of stay. We hypothesize CVRD is a surrogate for autonomic nervous system dysfunction. PMID:15319726

  4. Heart Rate Variability Analysis in General Medicine

    PubMed Central

    Gang, Yi; Malik, Marek

    2003-01-01

    Autonomic nervous system plays an integral role in homeostasis. Autonomic modulation can frequently be altered in patients with cardiac disorders as well as in patients with other critical illnesses or injuries. Assessment of heart rate variability is based on analysis of consecutive normal R-R intervals and may provide quantitative information on the modulation of cardiac vagal and sympathetic nerve input. The hypothesis that depressed heart rate variability may occur over a broad range of illness and injury, and may inversely correlated with disease severity and outcome has been tested in various clinical settings over the last decade. This article reviews recent literature concerning the potential clinical implications and limitations of heart rate variability assessment in general medicine. PMID:16943988

  5. Cardiorenal syndrome in children with heart failure.

    PubMed

    Price, Jack F; Goldstein, Stuart L

    2009-09-01

    Concomitant cardiac and renal dysfunction has been termed the cardiorenal syndrome (CRS). This clinical condition usually manifests as heart failure with worsening renal function and occurs frequently in the acute care setting. A consistent definition of CRS has not been universally agreed upon, although a recent classification of CRS describes several subtypes depending on the primary organ injured and the chronicity of the injury. CRS may develop in adults and children and is a strong predictor of morbidity and mortality in hospitalized and ambulatory patients. The underlying physiology of CRS is not well understood, creating a significant challenge for clinicians when treating heart failure patients with renal insufficiency. This review summarizes recent data characterizing the incidence, physiology, and management of children who have heart failure and acute kidney injury.

  6. Congenital Heart Defects (For Parents)

    MedlinePlus

    ... heart, lungs, and blood vessels make up the circulatory system . The heart is the central pump of this ... Heart Defects Getting an EKG (Video) Your Heart & Circulatory System Heart Murmurs Mitral Valve Prolapse Movie: Heart & Circulatory ...

  7. Congenital Heart Defects (For Parents)

    MedlinePlus

    ... heart, lungs, and blood vessels make up the circulatory system . The heart is the central pump of this ... Heart Defects Getting an EKG (Video) Your Heart & Circulatory System Heart Murmurs Mitral Valve Prolapse Movie: Heart & Circulatory ...

  8. Unusual attempted suicide by shooting through heart.

    PubMed

    Kadis, P; Pogorevc, L; Sipek, M; Vidovic, D

    2005-01-17

    Gunshot wounds in the heart are frequent suicidal injuries, especially in men. Most of them are lethal, but some cases of survival due to immediate and proper surgical treatment are reported. However, survival without specific treatment is extremely rare. In our case, a 44-year man attempted suicide by home-made shooting device. A special 12 cm long and 2.5 mm wide needle-like missile entered his body at the left anterior part of his chest, passed through the heart and lower lobe of right lung and exited at the right side of his back. The patient was able to move normally and he also looked for medical help immediately after attempting suicide. We found large atypical-shaped entrance wound on the anterior part of the chest, which was surgically treated, and tiny pointed exit wound under the right scapula. The patient was stable from cardio-circulatory and respiratory aspects from the time of admission to discharge from the hospital. We found only minimal pericardial bleeding (up to 10 mm thick) and there was no need for surgical intervention. In the next 2 weeks the haematoma absorbed spontaneously. The gunshot injury healed without any complication. Paranoid psychosis was diagnosed by psychiatrist and this probably had been the cause of attempting suicide. We think that the favorable outcome of the proved heart gunshot injury in our patient was due to the needle-shaped low-energy missile, which caused only tiny gunshot (stab) hole in the heart. Such a heart injury caused only minimal bleeding into the pericardial sac without heart tamponade.

  9. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  10. Migration of cardiomyocytes is essential for heart regeneration in zebrafish.

    PubMed

    Itou, Junji; Oishi, Isao; Kawakami, Hiroko; Glass, Tiffany J; Richter, Jenna; Johnson, Austin; Lund, Troy C; Kawakami, Yasuhiko

    2012-11-01

    Adult zebrafish possess a significant ability to regenerate injured heart tissue through proliferation of pre-existing cardiomyocytes, which contrasts with the inability of mammals to do so after the immediate postnatal period. Zebrafish therefore provide a model system in which to study how an injured heart can be repaired. However, it remains unknown what important processes cardiomyocytes are involved in other than partial de-differentiation and proliferation. Here we show that migration of cardiomyocytes to the injury site is essential for heart regeneration. Ventricular amputation induced expression of cxcl12a and cxcr4b, genes encoding a chemokine ligand and its receptor. We found that cxcl12a was expressed in the epicardial tissue and that Cxcr4 was expressed in cardiomyocytes. We show that pharmacological blocking of Cxcr4 function as well as genetic loss of cxcr4b function causes failure to regenerate the heart after ventricular resection. Cardiomyocyte proliferation was not affected but a large portion of proliferating cardiomyocytes remained localized outside the injury site. A photoconvertible fluorescent reporter-based cardiomyocyte-tracing assay demonstrates that cardiomyocytes migrated into the injury site in control hearts but that migration was inhibited in the Cxcr4-blocked hearts. By contrast, the epicardial cells and vascular endothelial cells were not affected by blocking Cxcr4 function. Our data show that the migration of cardiomyocytes into the injury site is regulated independently of proliferation, and that coordination of both processes is necessary for heart regeneration.

  11. Skiing Injuries

    PubMed Central

    Bartlett, L. H.

    1975-01-01

    In the broad spectrum of orthopedic skiing injuries, ‘second aid’ on the mountain and at the base by the physician is very important. All skiing physicians should carry minimal medical supplies, including narcotic medication. Diagnosis and treatment of injuries at the hospital are outlined. Most ski fractures of the tibia can be treated by conservative methods. A more aggressive approach to diagnosis and treatment of ligamentous injuries of the knee is recommended. PMID:20469236

  12. Environmental injuries.

    PubMed

    Leikin, J B; Aks, S E; Andrews, S; Auerbach, P S; Cooper, M A; Jacobsen, T D; Krenzelok, E P; Shicker, L; Weiner, S L

    1997-12-01

    Environmental injuries and illnesses can happen in home, work, or recreational settings. The variety and severity of these injuries might require the clinician to call on skills from internal medicine, emergency medicine, and toxicology. Diseases of thermoregulation are hypothermia and hyperthermia. In each instance, treatment is based on the need to restore the patient's core temperature to normal and on monitoring for complications. The victim of a fire might suffer inhalation injury in addition to burns, and it is more likely that the inhalation injury will be fatal. Oxygen deprivation and inhalation of irritant or asphyxiant chemicals contribute to injury. Toxic plants can be the source of poisoning emergencies, especially in children. Misinformation and myths that surround common plants can create diagnostic problems (i.e., which plants really are toxic and require emergency measures). Venomous marine organisms can cause a wide range of injury, from cutaneous eruption to fatal envenomation. Most are encountered in a recreational setting, such as water sports, but keepers of home aquariums are subject to stings from venomous fish. Lightning injury can present many diagnostic and treatment dilemmas. An important point in this regard is that lightning injury and high-voltage electrical injury are different in pathology and require different approaches for treatment. A discussion of electrical, chemical, and thermal burns makes such differences apparent.

  13. Paragliding injuries.

    PubMed Central

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-01-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries. Images p99-a p100-a p100-b p100-c PMID:1751899

  14. Paragliding injuries.

    PubMed

    Krüger-Franke, M; Siebert, C H; Pförringer, W

    1991-06-01

    Regulations controlling the sport of paragliding were issued in April 1987 by the German Department of Transportation. The growing popularity of this sport has led to a steady increase in the number of associated injuries. This study presents the incidence, localization and degree of injuries associated with paragliding documented in Germany, Austria and Switzerland. The 283 injuries suffered by 218 paragliders were documented in the period 1987-1989: 181 occurred during landing, 28 during starting procedures and nine during flight. The mean patient age was 29.6 years. There were 34.9% spinal injuries, 13.4% upper extremity injuries and 41.3% lower limb injuries. Over half of these injuries were treated surgically and in 54 instances permanent disability remained. In paragliding the lower extremities are at greatest risk of injury during landing. Proper equipment, especially sturdy footwear, exact training in landing techniques as well as improved instruction in procedures during aborted or crash landings is required to reduce the frequency of these injuries.

  15. Heart failure - surgeries and devices

    MedlinePlus

    CHF - surgery; Congestive heart failure - surgery; Cardiomyopathy - surgery; HF - surgery; Intra-aortic balloon pumps - heart failure; IABP - heart failure; Catheter based assist devices - heart failure

  16. Injury prevention: the time has come.

    PubMed Central

    Cushman, R

    1995-01-01

    Although cancer, heart disease and stroke occupy much of society's attention to health matters, injuries account for more potential years of life lost before age 65 than all these diseases combined. The time has come to set the record straight and to give injury its rightful place on the health policy agenda. Contrary to popular belief, most injuries are no accident. More than 90% of injuries are both predictable and preventable. Injury prevention, a multidisciplinary effort, is coming of age in Canada. Education alone is not enough. New technology, innovative approaches to safety education and the mobilization of community resources can help to change behaviour and legislation to decrease the risk of injury. Physicians have an important role to play in this process. PMID:7804918

  17. Can You Recognize a Heart Attack? Quiz

    MedlinePlus

    ... a Heart Attack Treatment of a Heart Attack Life After a Heart Attack Heart Failure About Heart Failure ... a Heart Attack • Treatment of a Heart Attack • Life After a Heart Attack Lifestyle Changes Recovery FAQs • Heart ...

  18. Rowing injuries.

    PubMed

    Rumball, Jane S; Lebrun, Constance M; Di Ciacca, Stephen R; Orlando, Karen

    2005-01-01

    Participation in the sport of rowing has been steadily increasing in recent decades, yet few studies address the specific injuries incurred. This article reviews the most common injuries described in the literature, including musculoskeletal problems in the lower back, ribs, shoulder, wrist and knee. A review of basic rowing physiology and equipment is included, along with a description of the mechanics of the rowing stroke. This information is necessary in order to make an accurate diagnosis and treatment protocol for these injuries, which are mainly chronic in nature. The most frequently injured region is the low back, mainly due to excessive hyperflexion and twisting, and can include specific injuries such as spondylolysis, sacroiliac joint dysfunction and disc herniation. Rib stress fractures account for the most time lost from on-water training and competition. Although theories abound for the mechanism of injury, the exact aetiology of rib stress fractures remains unknown. Other injuries discussed within, which are specific to ribs, include costochondritis, costovertebral joint subluxation and intercostal muscle strains. Shoulder pain is quite common in rowers and can be the result of overuse, poor technique, or tension in the upper body. Injuries concerning the forearm and wrist are also common, and can include exertional compartment syndrome, lateral epicondylitis, deQuervain's and intersection syndrome, and tenosynovitis of the wrist extensors. In the lower body, the major injuries reported include generalised patellofemoral pain due to abnormal patellar tracking, and iliotibial band friction syndrome. Lastly, dermatological issues, such as blisters and abrasions, and miscellaneous issues, such as environmental concerns and the female athlete triad, are also included in this article.Pathophysiology, mechanism of injury, assessment and management strategies are outlined in the text for each injury, with special attention given to ways to correct

  19. Prometheus's heart: what lies beneath.

    PubMed

    Barile, Lucio; Lionetti, Vincenzo

    2012-02-01

    A heart attack kills off many cells in the heart. Parts of the heart become thin and fail to contract properly following the replacement of lost cells by scar tissue. However, the notion that the same adult cardiomyocytes beat throughout the lifespan of the organ and organism, without the need for a minimum turnover, gives way to a fascinating investigations. Since the late 1800s, scientists and cardiologists wanted to demonstrate that the cardiomyocytes cannot be generated after the perinatal period in human beings. This curiosity has been passed down in subsequent years and has motivated more and more accurate studies in an attempt to exclude the presence of renewed cardiomyocytes in the tissue bordering the ischaemic area, and then to confirm the dogma of the heart as terminally differentiated organ. Conversely, peri-lesional mitosis of cardiomyocytes were discovered initially by light microscopy and subsequently confirmed by more sophisticated technologies. Controversial evidence of mechanisms underlying myocardial regeneration has shown that adult cardiomyocytes are renewed through a slow turnover, even in the absence of damage. This turnover is ensured by the activation of rare clusters of progenitor cells interspersed among the cardiac cells functionally mature. Cardiac progenitor cells continuously interact with each other, with the cells circulating in the vessels of the coronary microcirculation and myocardial cells in auto-/paracrine manner. Much remains to be understood; however, the limited functional recovery in human beings after myocardial injury clearly demonstrates weak regenerative potential of cardiomyocytes and encourages the development of new approaches to stimulate this process.

  20. Alleviating Autonomic Dysreflexia after Spinal Cord Injury

    DTIC Science & Technology

    2015-10-01

    SPN innervation. We have previously shown that we are able to promote robust functional axonal regeneration using a combination of transplantation and...spinal cord injury, transplantation , axon regeneration   2   ACCOMPLISHMENTS Through 9-30-2014 through 9-30-2015, we focused our efforts on...pressure and heart rate in conscious animals. At least one week later, we assay blood pressure and heart rate in these animals at rest and after

  1. ACL Injuries

    MedlinePlus

    ... is an ACL injury? ACL refers to the anterior cruciate ligament. It is 1 of 4 ligaments in your ... best results. After surgery, you will need intense physical therapy to ... allow the ligament to heal naturally. Living with an ACL injury ...

  2. Whiplash injuries.

    PubMed

    Malanga, Gerard; Peter, Jason

    2005-10-01

    Whiplash injuries are very common and usually are associated with rear-end collisions. However, a whiplash injury can be caused by any event that results in hyperextension and flexion of the cervical spine. These injuries are of serious concern to all consumers due to escalating cost of diagnosis, treatment, insurance, and litigation. Most acute whiplash injury cases respond well to conservative treatments, which result in resolution of symptoms usually within weeks to a few months after the injury occurred. Chronic whiplash injuries often are harder to diagnose and treat and often result in poor outcomes. Current research shows that various structures in the cervical spine receive nociceptive innervation and potentially may be the cause of chronic pain symptoms. One potential pain generator showing promise is the facet or zygapophyseal joints. Various researchers have proven that these joints are injured during whiplash injuries and that diagnosis and temporary pain relief can be obtained with facet joint injections. The initial evaluation of any patient should follow an organized and stepwise approach, and more serious causes of neck pain must first be ruled out through the history, physical examination, and diagnostic testing. Treatment regimens should be evidence-based, focusing on treatments that have proven to be effective in treating acute and chronic whiplash injuries.

  3. Injury Prevention

    MedlinePlus

    ... a Dramatic Rise, Including Bath Salts Household (and Child & Elderly) Injuries Avoiding Household Burns Do I Need A Tetanus Shot? Falls Are The Leading Injury-Related Cause of ER Visits Prevent Poison! ACEP Observes ... on Children Swallowing Objects Like Magnets, Coins or Batteries School & ...

  4. Heart disease and depression

    MedlinePlus

    ... gov/ency/patientinstructions/000790.htm Heart disease and depression To use the sharing features on this page, ... a heart attack or heart surgery Signs of Depression It is pretty common to feel down or ...

  5. Heart disease and women

    MedlinePlus

    ... disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, ... the American Heart Association and American College of Cardiology Foundation endorsed by the World Heart Federation and ...

  6. Heart Health Tests

    MedlinePlus

    ... is easier to treat. Blood tests and heart health tests can help find heart diseases or identify ... diseases. There are several different types of heart health tests. Your doctor will decide which test or ...

  7. Honolulu Heart Program

    ClinicalTrials.gov

    2016-04-13

    Cardiovascular Diseases; Coronary Disease; Cerebrovascular Accident; Heart Diseases; Heart Failure, Congestive; Myocardial Infarction; Asthma; Emphysema; Lung Diseases, Obstructive; Aortic Aneurysm, Abdominal; Bronchitis; Dementia; Hypertension; Chronic Obstructive Pulmonary Disease; Heart Failure

  8. What Causes Heart Failure?

    MedlinePlus

    ... blood pressure Other heart conditions or diseases Other factors Coronary Heart Disease Coronary heart disease is a condition in which a waxy substance called plaque builds up inside the coronary arteries. These arteries supply oxygen- ...

  9. Heart Surgery Terms

    MedlinePlus

    ... This event is also known as a myocardial infarction . Heart failure Heart failure is a degenerative condition ... to let more blood into the ventricle. Myocardial infarction When the heart does not get enough blood ...

  10. Left heart catheterization

    MedlinePlus

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye (sometimes called "contrast") will be ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  11. Right heart ventriculography

    MedlinePlus

    Angiography - right heart ... moved forward into the right side of the heart. As the catheter is advanced, the doctor can ... is injected into the right side of the heart. It helps the cardiologist determine the size and ...

  12. Heart-Healthy Exercise

    MedlinePlus

    ... American Heart Association Cardiology Patient Page Heart-Healthy Exercise Lauren Healey Mellett , Gisele Bousquet Download PDF https:// ... if you already have heart disease. How Can Exercise Help? There are many modifiable risk factors for ...

  13. 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

  14. Surviving shot through the heart: Management in two cases.

    PubMed

    Siddiqui, Fraz Anwar; Kabeer, Jamal; Shahabuddin, Syed

    2015-01-01

    Penetrating cardiac injuries after gunshot are usually fatal and are very challenging to manage for surgeons even in fully- equipped centres. Such injuries can cause ventricular septal defect (VSD) or cardiac tamponade depending upon the distance, direction and velocity of the bullet. Stable patients can be subjected to investigations like computed tomography (CT) to avoid unnecessary intervention, but unstable patients should be rushed to the operating room. We discuss management in two cases of traversing bullet injury to the heart. In the first case, traumatic VSD was significant, requiring closure on cardiopulmonary bypass (CPB) along with repair of right and left ventricular injury. In the second case, only the repair of right and left ventricles was performed without CPB. They both had traversing bullet injury through the heart.

  15. Volleyball injuries.

    PubMed

    Eerkes, Kevin

    2012-01-01

    There has been a significant increase in the numbers of people playing indoor and beach volleyball since the early 1980s and, consequently, an increase in injuries. Most injuries are related to repetitive jumping and hitting the ball overhead. The ankle is the most commonly injured joint, but the knee, shoulder, low back, and fingers also are vulnerable. The shoulder in particular is subject to extreme torque when hitting and jump serving the ball. Some injuries have a predilection for those playing on sand versus those playing in an indoor court. The clinician caring for volleyball players should be aware of the types of injuries these players sustain and how to help them return to play promptly and appropriately. This article reviews the specific injuries that are most common as a result of participating in the sport of volleyball.

  16. A Heart of Stone: Cardiac Fibroblasts Turn to Bone in Calcified Hearts.

    PubMed

    Ivey, Kathryn N

    2017-02-02

    The identity of the cells and molecular events driving deleterious calcification of heart muscle remains elusive. In this issue of Cell Stem Cell, Pillai et al. (2017) report that cardiac fibroblasts respond to injury by adopting an osteogenic cell fate and creating damaging calcific deposits, which can be prevented by inhibiting the activated mineralization process.

  17. Pediatric heart surgery - discharge

    MedlinePlus

    Congenital heart surgery - discharge; Patent ductus arteriosus ligation - discharge; Hypoplastic left heart repair - discharge; Tetralogy of Fallot repair - discharge; Coarctation of the aorta repair - discharge; ...

  18. Heart failure - medicines

    MedlinePlus

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... You will need to take most of your heart failure medicines every day. Some medicines are taken ...

  19. Mild Traumatic Brain Injury

    MedlinePlus

    ... Questions Glossary Contact Us Visitor Feedback mild Traumatic Brain Injury mild Traumatic Brain Injury VIDEO STORIES What is TBI Measuring Severity ... most common deployment injuries is a mild Traumatic Brain Injury (TBI). A mild TBI is an injury ...

  20. Hypertension, hypertrophy, and reperfusion injury.

    PubMed

    Pagliaro, Pasquale; Penna, Claudia

    2017-03-01

    The heart of patients with hypertension and cardiac hypertrophy is more vulnerable to ischemia-reperfusion injury (IRI). Here we discuss the main mechanisms of IRI and possible targets for cardioprotection. In particular, we consider the viewpoint that hypertension and cardiac hypertrophy may act synergistically in increasing the predisposition to cardiovascular accidents and in worsening IRI. There is no doubt that hypertrophic hearts may be redirected to be less vulnerable to IRI. Some experimental evidences suggest that antihypertensive drugs may have beneficial effects, some of which are not directly related to hypertension-lowering effect. However, more thorough experimental and clinical studies are necessary to understand the mechanisms and to maximize the beneficial effects of reperfusion after a heart attack in the presence of comorbidities, such as hypertension and cardiac hypertrophy.

  1. Sequential Analysis of Autonomic Arousal and Self-Injurious Behavior

    ERIC Educational Resources Information Center

    Hoch, John; Symons, Frank; Sng, Sylvia

    2013-01-01

    There have been limited direct tests of the hypothesis that self-injurious behavior (SIB) regulates arousal. In this study, two autonomic biomarkers for physiological arousal (heart rate [HR] and the high-frequency [HF] component of heart rate variability [HRV]) were investigated in relation to SIB for 3 participants with intellectual…

  2. Sequential Analysis of Autonomic Arousal and Self-Injurious Behavior

    ERIC Educational Resources Information Center

    Hoch, John; Symons, Frank; Sng, Sylvia

    2013-01-01

    There have been limited direct tests of the hypothesis that self-injurious behavior (SIB) regulates arousal. In this study, two autonomic biomarkers for physiological arousal (heart rate [HR] and the high-frequency [HF] component of heart rate variability [HRV]) were investigated in relation to SIB for 3 participants with intellectual…

  3. Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

    PubMed

    Pillai, Indulekha C L; Li, Shen; Romay, Milagros; Lam, Larry; Lu, Yan; Huang, Jie; Dillard, Nathaniel; Zemanova, Marketa; Rubbi, Liudmilla; Wang, Yibin; Lee, Jason; Xia, Ming; Liang, Owen; Xie, Ya-Hong; Pellegrini, Matteo; Lusis, Aldons J; Deb, Arjun

    2017-02-02

    Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.

  4. Ophthalmologic injuries.

    PubMed

    Diamond, G R; Quinn, G E; Pashby, T J; Easterbrook, M

    1982-11-01

    Increasing numbers of young people are being attracted to organized sports. Racquet sports, as they are individual sports, will give a lifetime of continual pleasure. Increasing numbers of eye injuries are being seen, however. Now that adequate eye protection is available, it behooves all physicians who are interested in prevention of eye injury to encourage players to wear polycarbonate or industrial safety thickness lenses, or protective face cages in suitable sports frames, to prevent any of the catastrophic, serious, and blinding eye injuries seen in the past.

  5. A new nonpenetrating ballistic injury.

    PubMed Central

    Carroll, A W; Soderstrom, C A

    1978-01-01

    A new, nonpenetrating ballistic injury mechanism involving individuals protected by soft body armor is described. Experimental studies using laboratory animals have demonstrated that despite stopping missile penetration, the heart, liver, spleen, and spinal cord are vulnerable to injury. The rapid jolting force of an impacting bullet is contrasted with the usually encountered mechanisms producing blunt trauma injury. The experimental methodology used to assess a 20% increase in survival probability and an 80% decrease in the need for surgical intervention with a new soft body armor is reviewed. Five cases of ballistic assaults on law enforcement personnel protected by soft body armor are presented. Four emphasize the potentially lifesaving qualities of the armor, while the fifth indicates the need for torso encircling design. Hospitalization should follow all assaults, regardless of the innocuous appearance of the skin lesion and the apparent well being on the assaulted individual. Therapeutic guidelines for patient management are suggested. Images Fig. 1. Fig. 2. Fig. 3. PMID:736653

  6. A new nonpenetrating ballistic injury.

    PubMed

    Carroll, A W; Soderstrom, C A

    1978-12-01

    A new, nonpenetrating ballistic injury mechanism involving individuals protected by soft body armor is described. Experimental studies using laboratory animals have demonstrated that despite stopping missile penetration, the heart, liver, spleen, and spinal cord are vulnerable to injury. The rapid jolting force of an impacting bullet is contrasted with the usually encountered mechanisms producing blunt trauma injury. The experimental methodology used to assess a 20% increase in survival probability and an 80% decrease in the need for surgical intervention with a new soft body armor is reviewed. Five cases of ballistic assaults on law enforcement personnel protected by soft body armor are presented. Four emphasize the potentially lifesaving qualities of the armor, while the fifth indicates the need for torso encircling design. Hospitalization should follow all assaults, regardless of the innocuous appearance of the skin lesion and the apparent well being on the assaulted individual. Therapeutic guidelines for patient management are suggested.

  7. Applying rigor and reproducibility standards to assay donor-derived cell-free DNA as a non-invasive method for detection of acute rejection and graft injury after heart transplantation.

    PubMed

    Agbor-Enoh, Sean; Tunc, Ilker; De Vlaminck, Iwijn; Fideli, Ulgen; Davis, Andrew; Cuttin, Karen; Bhatti, Kenneth; Marishta, Argit; Solomon, Michael A; Jackson, Annette; Graninger, Grace; Harper, Bonnie; Luikart, Helen; Wylie, Jennifer; Wang, Xujing; Berry, Gerald; Marboe, Charles; Khush, Kiran; Zhu, Jun; Valantine, Hannah

    2017-09-01

    Use of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts. After developing and validating the %ddcfDNA assay, we subjected the method to a rigorous test of its reproducibility. We measured %ddcfDNA in technical replicates performed by 2 independent laboratories and verified the reproducibility of %ddcfDNA patterns of 2 rejection phenotypes: acute cellular rejection and antibody-mediated rejection in distinct patient cohorts. We observed strong concordance of technical-replicate %ddcfDNA measurements across 2 independent laboratories (slope = 1.02, R(2) > 0.99, p < 10(-6)), as well as across manual and automated platforms (slope = 0.80, R(2) = 0.92, p < 0.001). The %ddcfDNA measurements in distinct heart transplant cohorts had similar baselines and error rates. The %ddcfDNA temporal patterns associated with rejection phenotypes were similar in both patient cohorts; however, the quantity of ddcfDNA was significantly higher in samples with severe vs mild histologic rejection grade (2.73% vs 0.14%, respectively; p < 0.001). The %ddcfDNA assay is precise and reproducible across laboratories and in samples from 2 distinct types of heart transplant rejection. These findings pave the way for larger studies to assess the clinical utility of %ddcfDNA as a marker of acute rejection after heart transplantation. Copyright © 2017. Published by Elsevier Inc.

  8. Heart failure.

    PubMed

    Braunwald, Eugene

    2013-02-01

    Despite major improvements in the treatment of virtually all cardiac disorders, heart failure (HF) is an exception, in that its prevalence is rising, and only small prolongations in survival are occurring. An increasing fraction, especially older women with diabetes, obesity, and atrial fibrillation exhibit HF with preserved systolic function. Several pathogenetic mechanisms appear to be operative in HF. These include increased hemodynamic overload, ischemia-related dysfunction, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Biomarkers released as a consequence of myocardial stretch, imbalance between formation and breakdown of extracellular matrix, inflammation, and renal failure are useful in the identification of the pathogenetic mechanism and, when used in combination, may become helpful in estimating prognosis and selecting appropriate therapy. Promising new therapies that are now undergoing intensive investigation include an angiotensin receptor neprilysin inhibitor, a naturally-occurring vasodilator peptide, a myofilament sensitizer and several drugs that enhance Ca++ uptake by the sarcoplasmic reticulum. Cell therapy, using autologous bone marrow and cardiac progenitor cells, appears to be promising, as does gene therapy. Chronic left ventricular assistance with continuous flow pumps is being applied more frequently and successfully as destination therapy, as a bridge to transplantation, and even as a bridge to recovery and explantation. While many of these therapies will improve the care of patients with HF, significant reductions in prevalence will require vigorous, multifaceted, preventive approaches.

  9. Hypoplastic left heart syndrome (image)

    MedlinePlus

    Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

  10. Golf Injuries

    MedlinePlus

    ... main causes of these injuries include: Lack of flexibility Poor conditioning Excessive play or practice Poor swing mechanics Ground impact forces Intermittent play Poor flexibility is a key risk factor for a golf ...

  11. Testicular Injuries

    MedlinePlus

    ... Also, the location of the testicles makes them prime targets to be accidentally struck on the playing ... you might also feel nauseated for a short time. If it's a minor testicular injury, the pain ...

  12. Inhalation Injuries

    MedlinePlus

    ... devastating types of trauma resulting from exposure to fire and smoke. PREVENT you and your loved ones! ... people die annually in the United States from fire injuries. • Over half of these deaths result from ...

  13. Spinal injury

    MedlinePlus

    ... and drive. Do not dive into pools, lakes, rivers, and other bodies of water, particularly if you cannot determine the depth of the ... Central nervous system Spinal cord injury Spinal anatomy Two person roll - ...

  14. [Thorax injuries].

    PubMed

    Schelzig, H; Kick, J; Orend, K H; Sunder-Plassmann, L

    2006-03-01

    Thorax injuries may be divided etiologically into blunt and penetrating types, depending on the nature of the insult. In European practice, the former predominates by far, and in only about 5% of cases thoracotomy provides the necessary thorax drainage. Morbidity in this type of injury typically involves concomitant lung contusion, sometimes with fatal acute respiratory distress syndrome. In these cases, special ventilation forms, optimal reduction of pain, and organ replacement are the decisive therapeutic methods. In contrast, about 80% of penetrating trauma to the thorax require prompt transpleural or trans-sternal surgery, depending on the type of injury. Emergency first aid must follow the principle of "scoop and run". Each minute elapsed until emergent thoracotomy can be decisive to survival in these cases, and the fastest possible transport from the place of injury takes priority over time-consuming stabilization.

  15. Head Injuries

    MedlinePlus

    ... object that's stuck in the wound. previous continue Concussions Concussions — the temporary loss of normal brain function due ... also a type of internal head injury. Repeated concussions can permanently damage the brain. In many cases, ...

  16. Cold injuries.

    PubMed

    Kruse, R J

    1995-01-01

    There are two categories of cold injury. The first is hypothermia, which is a systemic injury to cold, and the second is frostbite, which is a local injury. Throughout history, entire armies, from George Washington to the Germans on the Russian Front in World War II, have fallen prey to prolonged cold exposure. Cold injury is common and can occur in all seasons if ambient temperature is lower than the core body temperature. In the 1985 Boston Marathon, even though it was 76 degrees and sunny, there were 75 runners treated for hypothermia. In general, humans adapt poorly to cold exposure. Children are at particular risk because of their relatively greater surface area/body mass ratio, causing them to cool even more rapidly than adults. Because of this, the human's best defense against cold injury is to limit his/her exposure to cold and to dress appropriately. If cold injury has occurred and is mild, often simple passive rewarming such as dry blankets and a warm room are sufficient treatment.

  17. Electric injury, Part II: Specific injuries.

    PubMed

    Fish, R M

    2000-01-01

    Electric injury can cause disruption of cardiac rhythm and breathing, burns, fractures, dislocations, rhabdomyolysis, eye and ear injury, oral and gastrointestinal injury, vascular damage, disseminated intravascular coagulation, peripheral and spinal cord injury, and Reflex Sympathetic Dystrophy. Secondary trauma from falls, fires, flying debris, and inhalation injury can complicate the clinical picture. Diagnostic and treatment considerations for electric injuries are described in this article, which is the second part of a three-part series on electric injuries.

  18. Congenital complete heart block.

    PubMed Central

    Agarwala, B.; Sheikh, Z.; Cibils, L. A.

    1996-01-01

    Congenital complete heart block in utero has become diagnosed more frequently with the clinical use of fetal echocardiography. The fetus with complete heart block may remain asymptomatic or may develop congestive heart failure. Congenital complete heart block is more frequently seen in infants of mothers with systemic lupus erythematosus, both clinically manifested and subclinical systemic lupus erythematosus with positive antibodies (SS-A and SS-B antibodies). At birth, the neonate with complete heart block may remain asymptomatic and may not require a pacemaker to increase the heart rate. The indications for a pacemaker in neonates with complete heart block have been discussed. Both in-utero and neonatal management of congenital complete heart block are discussed to manage congestive heart failure in a fetus. Four patients with congenital complete heart block are presented covering a broad spectrum of clinical presentation, diagnosis, and management both in the fetal and neonatal period. Images Figure 1 PMID:8961692

  19. [Implantable artificial heart].

    PubMed

    Nojiri, Chisato

    2005-11-01

    Heart transplants have been decreasing globally due to the lack of available donor hearts. As a result, the increased use of artificial hearts is anticipated as an alternative therapy. Although biocompatibility issues, such as thrombus formation/thromboembolism and infection, are still the main cause of mortality associated with artificial hearts, more than 20 different types are now clinically available after a half-century of development and experimental trials. These devices range from extracorporeal pneumatic to implantable battery-powered artificial hearts. The early development of artificial hearts logically focused on volumetric pump designs incorporating functions similar to the natural heart. Today, development has shifted toward designs that are significantly different from the natural heart. These pumps utilize axial or centrifugal flow allowing for a much simpler design, which is smaller in size and has very few moving parts. With rapid advances in technology, this new generation of artificial heart pumps is beginning to emerge as an alternative to heart transplants.

  20. Aquatic Exercise and Heat-Related Injuries.

    ERIC Educational Resources Information Center

    Sova, Ruth

    1991-01-01

    Heat-related injuries in aquatics classes are possible, though 100 percent preventable. The article discusses heat-related syndromes; how bodies generate and dissipate heat; how elevated heart rates that burn calories differ from those that dissipate heat; and modification of exercise intensity to provide calorie-burning workouts without…

  1. Aquatic Exercise and Heat-Related Injuries.

    ERIC Educational Resources Information Center

    Sova, Ruth

    1991-01-01

    Heat-related injuries in aquatics classes are possible, though 100 percent preventable. The article discusses heat-related syndromes; how bodies generate and dissipate heat; how elevated heart rates that burn calories differ from those that dissipate heat; and modification of exercise intensity to provide calorie-burning workouts without…

  2. Intracardiac Penetrating Injury with Right Femoral Artery Embolism due to Blast Injury

    PubMed Central

    Abuzaid, Ahmed Abdulaziz; Al-Abbasi, Thamer; Arekat, Zaid

    2016-01-01

    Embolization due to blast injury with projectiles entering the bloodstream from the heart is a rare event that is unlikely to be suspected during the initial assessment of trauma patients. We report a case in which a missile penetrating the heart chambers managed to embolize and occlude the right common femoral artery. This was successfully managed by means of a multidisciplinary approach that included exploration, cardiorrhaphy, and embolectomy. PMID:28400939

  3. Myocardial protection in heart surgery.

    PubMed

    Mentzer, Robert M

    2011-01-01

    One of the unmet clinical needs in heart surgery is the prevention of myocardial stunning and necrosis that occurs as a result of ischemia-reperfusion. Myocardial stunning, a frequent consequence after heart surgery, is characterized by a requirement for postoperative inotropic support despite a technically satisfactory heart operation. In high-risk patients with marginal cardiac reserve, stunning is a major cause of prolonged critical care and may be associated with as much as a 5-fold increase in mortality. In contrast, the frequency of myocardial necrosis (myocardial infarction [MI]) after cardiac surgery is less appreciated and its consequences are much more subtle. The consequences may not be apparent for months to years. While we now have a much better understanding of the molecular mechanisms underlying myocardial stunning and MI, we still have no effective way to prevent these complications, nor a consistently effective means to engage the well-studied endogenous mechanisms of cardioprotection. The failure to develop clinically effective interventions is multifactorial and can be attributed to reliance on findings obtained from subcellular and cellular studies, to drawing conclusions from preclinical large animal studies that have been conducted in a disease-free state, and to accepting less than robust surrogate markers of injury in phase II clinical trials. These factors also explain the disappointing failure to identify effective adjuvant therapy in the setting of percutaneous coronary revascularization for acute MI (AMI) and reperfusion injury. These issues have contributed to the disappointing outcomes of large and costly phase III trials, resulting in a lack of enthusiasm on the part of the pharmaceutical industry to engage in further drug development for this indication. The purpose of this review is to (1) define the scope of the clinical problem; (2) summarize the outcomes of selected phases II and III clinical trials; and (3) identify the gap that

  4. Mitochondrial Metabolism in Aging Heart

    PubMed Central

    Lesnefsky, Edward J.; Chen, Qun; Hoppel, Charles L.

    2016-01-01

    Altered mitochondrial metabolism is the underlying basis for the increased sensitivity in the aged heart to stress. The aged heart exhibits impaired metabolic flexibility, with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism. Aging impairs mitochondrial oxidative phosphorylation, with a greater role played by the mitochondria located between the myofibrils, the interfibrillar mitochondria. With aging, there is a decrease in activity of complexes III and IV, which account for the decrease in respiration. Furthermore, aging decreases mitochondrial content among the myofibrils. The end result is that in the interfibrillar area there is an approximate 50% decrease in mitochondrial function, affecting all substrates. The defective mitochondria persist in the aged heart, leading to enhanced oxidant production and oxidative injury and the activation of oxidant signaling for cell death. Aging defects in mitochondria represent new therapeutic targets, whether by manipulation of the mitochondrial proteome, modulation of electron transport, activation of biogenesis or mitophagy, or the regulation of mitochondrial fission and fusion. These mechanisms provide new ways to attenuate cardiac disease in elders by preemptive treatment of age-related defects, in contrast to the treatment of disease-induced dysfunction. PMID:27174952

  5. Oxidative Stress after Surgery on the Immature Heart

    PubMed Central

    Fudulu, Daniel; Angelini, Gianni

    2016-01-01

    Paediatric heart surgery is associated with increased inflammation and the production of reactive oxygen species. Use of the extracorporeal cardiopulmonary bypass during correction of congenital heart defects generates reactive oxygen species by various mechanisms: haemolysis, neutrophil activation, ischaemia reperfusion injury, reoxygenation injury, or depletion of the endogenous antioxidants. The immature myocardium is more vulnerable to reactive oxygen species because of developmental differences compared to the adult heart but also because of associated congenital heart diseases that can deplete its antioxidant reserve. Oxidative stress can be manipulated by various interventions: exogenous antioxidants, use of steroids, cardioplegia, blood prime strategies, or miniaturisation of the cardiopulmonary bypass circuit. However, it is unclear if modulation of the redox pathways can alter clinical outcomes. Further studies powered to look at clinical outcomes are needed to define the role of oxidative stress in paediatric patients. PMID:27123154

  6. Building and re-building the heart by cardiomyocyte proliferation

    PubMed Central

    Foglia, Matthew J.; Poss, Kenneth D.

    2016-01-01

    The adult human heart does not regenerate significant amounts of lost tissue after injury. Rather than making new, functional muscle, human hearts are prone to scarring and hypertrophy, which can often lead to fatal arrhythmias and heart failure. The most-cited basis of this ineffective cardiac regeneration in mammals is the low proliferative capacity of adult cardiomyocytes. However, mammalian cardiomyocytes can avidly proliferate during fetal and neonatal development, and both adult zebrafish and neonatal mice can regenerate cardiac muscle after injury, suggesting that latent regenerative potential exists. Dissecting the cellular and molecular mechanisms that promote cardiomyocyte proliferation throughout life, deciphering why proliferative capacity normally dissipates in adult mammals, and deriving means to boost this capacity are primary goals in cardiovascular research. Here, we review our current understanding of how cardiomyocyte proliferation is regulated during heart development and regeneration. PMID:26932668

  7. Cold injuries.

    PubMed

    Long, William B; Edlich, Richard F; Winters, Kathryne L; Britt, L D

    2005-01-01

    Exposure to cold can produce a variety of injuries that occur as a result of man's inability to adapt to cold. These injuries can be divided into localized injury to a body part, systemic hypothermia, or a combination of both. Body temperature may fall as a result of heat loss by radiation, evaporation, conduction, and convection. Hypothermia or systemic cold injury occurs when the core body temperature has decreased to 35 degrees C (95 degrees F) or less. The causes of hypothermia are either primary or secondary. Primary, or accidental, hypothermia occurs in healthy individuals inadequately clothed and exposed to severe cooling. In secondary hypothermia, another illness predisposes the individual to accidental hypothermia. Hypothermia affects multiple organs with symptoms of hypothermia that vary according to the severity of cold injury. The diagnosis of hypothermia is easy if the patient is a mountaineer who is stranded in cold weather. However, it may be more difficult in an elderly patient who has been exposed to a cold environment. In either case, the rectal temperature should be checked with a low-reading thermometer. The general principals of prehospital management are to (1) prevent further heat loss, (2) rewarm the body core temperature in advance of the shell, and (3) avoid precipitating ventricular fibrillation. There are two general techniques of rewarming--passive and active. The mechanisms of peripheral cold injury can be divided into phenomena that affect cells and extracellular fluids (direct effects) and those that disrupt the function of the organized tissue and the integrity of the circulation (indirect effects). Generally, no serious damage is seen until tissue freezing occurs. The mildest form of peripheral cold injury is frostnip. Chilblains represent a more severe form of cold injury than frostnip and occur after exposure to nonfreezing temperatures and damp conditions. Immersion (trench) foot, a disease of the sympathetic nerves and blood

  8. Renal neurohormonal regulation in heart failure decompensation.

    PubMed

    Jönsson, Sofia; Agic, Mediha Becirovic; Narfström, Fredrik; Melville, Jacqueline M; Hultström, Michael

    2014-09-01

    Decompensation in heart failure occurs when the heart fails to balance venous return with cardiac output, leading to fluid congestion and contributing to mortality. Decompensated heart failure can cause acute kidney injury (AKI), which further increases mortality. Heart failure activates signaling systems that are deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin-angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal blood flow (RBF) and increase tubular sodium reabsorption, which may increase renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin contributes to venous congestion through aquaporin-mediated water retention. Additional water retention may be mediated through vasopressin-induced medullary urea transport and hyaluronan but needs further study. In addition, there are several systems that could protect the kidneys and reduce fluid retention such as natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of natriuretic peptides and nitric oxide are blunted in decompensation, partly due to oxidative stress. This review considers how neurohormonal signaling in heart failure drives fluid retention by the kidneys and thus exacerbates decompensation. It further identifies areas where there is limited data, such as signaling systems 20-HETE, purines, endothelin, the role of renal water retention mechanisms for congestion, and renal hypoxia in AKI during heart failure.

  9. Lightning injuries.

    PubMed

    O'Keefe Gatewood, Medley; Zane, Richard D

    2004-05-01

    Lightning is persistently one of the leading causes of death caused by environmental or natural disaster. To understand the pathophysiology and treatment of lightning injuries one must first discount the innumerable myths, superstitions, and misconceptions surrounding lightning. The fundamental difference between high voltage electrical injury and lightning is the duration of exposure to current. Reverse triage should be instituted in lightning strike victims because victims in cardiopulmonary arrest might gain the greatest benefit from resuscitation efforts, although there is no good evidence suggesting that lightning strike victims might benefit from longer than usual resuscitation times. Many of the injuries suffered by lightning strike victims are unique to lightning, and long-term sequelae should be anticipated and addressed in the lightning victim.

  10. Blast Injury

    PubMed Central

    de Candole, C. A.

    1967-01-01

    The shock wave generated by an explosion (“blast wave”) may cause injury in any or all of the following: (1) direct impact on the tissues of variations in environmental pressure; (2) flying glass and other debris set in motion by it; (3) propulsion of the body. Injuries in the first category affect gas-containing organs (ears, lungs and intestines), and acute death is attributed to air forced into the coronary vessels via damaged pulmonary alveoli. It is estimated that overpressure sufficient to cause lung injury may occur up to five miles from a 20-megaton nuclear explosion. The greatest single hazard from blast is, however, flying glass, and serious wounding from this cause is possible up to 12 miles from an explosion of this magnitude. PMID:6015742

  11. Hamstring injuries

    PubMed Central

    Guanche, Carlos A.

    2015-01-01

    There is a continuum of hamstring injuries that can range from musculotendinous strains to avulsion injuries. Although the proximal hamstring complex has a strong bony attachment on the ischial tuberosity, hamstring injuries are common in athletic population and can affect all levels of athletes. Nonoperative treatment is mostly recommended in the setting of low-grade partial tears and insertional tendinosis. However, failure of nonoperative treatment of partial tears may benefit from surgical debridement and repair. The technique presented on this article allows for the endoscopic management of proximal hamstring tears and chronic ischial bursitis, which until now has been managed exclusively with much larger open approaches. The procedure allows for complete exposure of the posterior aspect of the hip in a safe, minimally invasive fashion. PMID:27011828

  12. Risks for Heart Valve Problems

    MedlinePlus

    ... Cholesterol Tools & Resources Congenital Defects Children & Adults About Congenital Heart Defects The Impact of Congenital Heart Defects Understand Your Risk for Congenital Heart Defects Symptoms & ...

  13. Heart failure - fluids and diuretics

    MedlinePlus

    ... Heart failure - discharge Heart failure - home monitoring Heart failure - what to ask ... Medical Center, University of Washington Medical School, Seattle, WA. Also reviewed by David Zieve, MD, ...

  14. Radiation-associated valvular heart disease.

    PubMed

    Ong, Daniel S; Aertker, Robert A; Clark, Alexandra N; Kiefer, Todd; Hughes, G Chad; Harrison, J Kevin; Bashore, Thomas M

    2013-11-01

    Therapeutic ionizing radiation, such as that used in the treatment of Hodgkin's lymphoma, can cause cardiac valvular damage that may take several years to manifest as radiation-associated valvular heart disease. Treatment can be complicated by comorbid radiation injury to other cardiac and mediastinal structures that lead to traditional surgical valve replacement or repair becoming high-risk. A representative case is presented that demonstrates the complexity of radiation-associated valvular heart disease and its successful treatment with percutaneous transcatheter valve replacement. The prevalence and pathophysiologic mechanism of radiation-associated valvular injury are reviewed. Anthracycline adjuvant therapy appears to increase the risk of valvular fibrosis. Left-sided heart valves are more commonly affected than right-sided heart valves. A particular pattern of calcification has been noted in some patients, and experimental data suggest that radiation induction of an osteogenic phenotype may be responsible. A renewed appreciation of the cardiac valvular effects of therapeutic ionizing radiation for mediastinal malignancies is important, and the treatment of such patients may be assisted by the development of novel, less-invasive approaches.

  15. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy

    PubMed Central

    Fillmore, N; Mori, J; Lopaschuk, G D

    2014-01-01

    Heart disease is a leading cause of death worldwide. In many forms of heart disease, including heart failure, ischaemic heart disease and diabetic cardiomyopathies, changes in cardiac mitochondrial energy metabolism contribute to contractile dysfunction and to a decrease in cardiac efficiency. Specific metabolic changes include a relative increase in cardiac fatty acid oxidation rates and an uncoupling of glycolysis from glucose oxidation. In heart failure, overall mitochondrial oxidative metabolism can be impaired while, in ischaemic heart disease, energy production is impaired due to a limitation of oxygen supply. In both of these conditions, residual mitochondrial fatty acid oxidation dominates over mitochondrial glucose oxidation. In diabetes, the ratio of cardiac fatty acid oxidation to glucose oxidation also increases, although primarily due to an increase in fatty acid oxidation and an inhibition of glucose oxidation. Recent evidence suggests that therapeutically regulating cardiac energy metabolism by reducing fatty acid oxidation and/or increasing glucose oxidation can improve cardiac function of the ischaemic heart, the failing heart and in diabetic cardiomyopathies. In this article, we review the cardiac mitochondrial energy metabolic changes that occur in these forms of heart disease, what role alterations in mitochondrial fatty acid oxidation have in contributing to cardiac dysfunction and the potential for targeting fatty acid oxidation to treat these forms of heart disease. LINKED ARTICLES This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24147975

  16. Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.

    PubMed

    Patterson, Michaela; Barske, Lindsey; Van Handel, Ben; Rau, Christoph D; Gan, Peiheng; Sharma, Avneesh; Parikh, Shan; Denholtz, Matt; Huang, Ying; Yamaguchi, Yukiko; Shen, Hua; Allayee, Hooman; Crump, J Gage; Force, Thomas I; Lien, Ching-Ling; Makita, Takako; Lusis, Aldons J; Kumar, S Ram; Sucov, Henry M

    2017-09-01

    Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.

  17. Targeting calcium transport in ischaemic heart disease

    PubMed Central

    Talukder, M.A. Hassan; Zweier, Jay L.; Periasamy, Muthu

    2009-01-01

    Ischaemic heart disease (IHD) is the leading cause of morbidity and mortality worldwide. While timely reperfusion of acutely ischaemic myocardium is essential for myocardial salvage, it leads to a unique type of injury known as ‘myocardial ischaemia/reperfusion (I/R) injury’. Growing evidence suggests that a defect in myocardial Ca2+ transport system with cytosolic Ca2+ overload is a major contributor to myocardial I/R injury. Progress in molecular genetics and medicine in past years has clearly demonstrated that modulation of Ca2+ handling pathways in IHD could be cardioprotective. The potential benefits of these strategies in limiting I/R injury are vast, and the time is right for challenging in vivo systemic work both at pre-clinical and clinical levels. PMID:19640931

  18. Stimulation of Oxytocin Receptor during Early Reperfusion Period Protects the Heart against Ischemia/Reperfusion Injury: the Role of Mitochondrial ATP-Sensitive Potassium Channel, Nitric Oxide, and Prostaglandins.

    PubMed

    Imani, Alireza; Khansari, Maryam; Azizi, Yaser; Rakhshan, Kamran; Faghihi, Mahdieh

    2015-08-01

    Postconditioning is a simple and safe strategy for cardioprotection and infarct size limitation. Our previous study showed that oxytocin (OT) exerts postconditioning effect on ischemic/reperfused isolated rat heart. The aim of this study was to investigate the involvement of OT receptor, mitochondrial ATP-sensitive potassium channel (mKATP), nitric oxide (NO) and cyclooxygenase (COX) pathways in OT postconditioning. Isolated rat hearts were divided into10 groups and underwent 30 min of regional ischemia followed by 120 min of reperfusion (n =6). In I/R (ischemia/reperfusion) group, ischemia and reperfusion were induced without any treatment. In OT group, oxytocin was perfused 5 min prior to beginning of reperfusion for 25 min. In groups 3-6, atosiban (oxytocin receptor blocker), L-NAME (N-Nitro-L-Arginine Methyl Ester, non-specific nitric oxide synthase inhibitor), 5-HD (5-hydroxydecanoate, mKATP inhibitor) and indomethacin (cyclooxygenase inhibitor) were infused prior to oxytocin administration. In others, the mentioned inhibitors were perfused prior to ischemia without oxytocin infusion. Infarct size, ventricular hemodynamic, coronary effluent, malondialdehyde (MDA) and lactate dehydrogenase (LDH) were measured at the end of reperfusion. OT perfusion significantly reduced infarct size, MDA and LDH in comparison with IR group. Atosiban, 5HD, L-NAME and indomethacin abolished the postconditioning effect of OT. Perfusion of the inhibitors alone prior to ischemia had no effect on infarct size, hemodynamic parameters, coronary effluent and biochemical markers as compared with I/R group. In conclusion, this study indicates that postconditioning effects of OT are mediated by activation of mKATP and production of NO and Prostaglandins (PGs).

  19. Heart transplantation in adult congenital heart disease.

    PubMed

    Burchill, Luke J

    2016-12-01

    Heart failure (HF) in adult congenital heart disease (ACHD) is vastly different to that observed in acquired heart disease. Unlike acquired HF in which pharmacological strategies are the cornerstone for protecting and improving ventricular function, ACHD-related HF relies heavily upon structural and other interventions to achieve these aims. patients with ACHD constitute a small percentage of the total adult heart transplant population (∼3%), although the number of ACHD heart transplant recipients is growing rapidly with a 40% increase over the last two decades. The worldwide experience to date has confirmed heart transplantation as an effective life-extending treatment option in carefully selected patients with ACHD with end-stage cardiac disease. Opportunities for improving outcomes in patients with ACHD-related HF include (i) earlier recognition and referral to centres with combined expertise in ACHD and HF, (ii) increased awareness of arrhythmia and sudden cardiac death risk in this population, (iii) greater collaboration between HF and ACHD specialists at the time of heart transplant assessment, (iv) expert surgical planning to reduce ischaemic time and bleeding risk at the time of transplant, (v) tailored immunosuppression in the post-transplant period and (vi) development and validation of ACHD-specific risk scores to predict mortality and guide patient selection. The purpose of this article is to review current approaches to diagnosing and treating advanced HF in patients with ACHD including indications, contraindications and clinical outcomes after heart transplantation.

  20. Ear Injury

    MedlinePlus

    ... Brain Damage in Boxers (News) Which High School Sport Has the Most Concussions? Additional Content Medical News Ear Injury By Sam ... often... More News News HealthDay Which High School Sport Has the Most Concussions? WEDNESDAY, March 15, 2017 (HealthDay News) -- Female soccer ...

  1. Pediatric Injury

    MedlinePlus

    ... Control and Prevention’s Safe Child website . What is pediatric critical care? Children who have severe or life-threatening injuries ... are staffed by physicians with specialized training in pediatric critical care medicine ("pediatric intensivists"). Because children can experience a ...

  2. Electrical Injuries

    MedlinePlus

    ... your injuries are depends on how strong the electric current was, what type of current it was, how it moved through your body, and how long you were exposed. Other factors include how ... you should see a doctor. You may have internal damage and not realize it.

  3. Pericarditis - after heart attack

    MedlinePlus

    ... medlineplus.gov/ency/article/000166.htm Pericarditis - after heart attack To use the sharing features on this page, ... occur in the days or weeks following a heart attack . Causes Two types of pericarditis can occur after ...

  4. Heart PET scan

    MedlinePlus

    Heart nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... Udelson JE, Dilsizian V, Bonow RO. Nuclear cardiology. In: Mann DL, ... A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, ...

  5. What Causes Heart Block?

    MedlinePlus

    ... of Intramural Research Research Resources Research Meeting Summaries Technology Transfer Clinical Trials What Are Clinical Trials? Children & ... acquired heart block. Coronary heart disease , also called coronary artery disease. Myocarditis (MI-o-kar-DI-tis), or inflammation ...

  6. Nuclear Heart Scan

    MedlinePlus

    ... into your blood and travels to your heart. Nuclear heart scans use single photon emission computed tomography (SPECT) or cardiac positron emission tomography (PET) to detect the energy from the tracer to make pictures of your ...

  7. Men and Heart Disease

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ... this? Submit What's this? Submit Button Related CDC Web Sites Heart Disease Stroke High Blood Pressure Salt ...

  8. Heart Disease Risk Factors

    MedlinePlus

    ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ... this? Submit What's this? Submit Button Related CDC Web Sites Division for Heart Disease and Stroke Prevention ...

  9. Tachycardia | Fast Heart Rate

    MedlinePlus

    ... heart disease and stroke. Start exploring today ! Printable Arrhythmia Information Sheets What is Arrhythmia? What is Atrial ... Card See all Answers by Heart patient sheets Arrhythmia • Home • About Arrhythmia Introduction Atrial Fibrillation Bradycardia Conduction ...

  10. Heart attack - discharge

    MedlinePlus

    ... syndromes: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. ... disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice ...

  11. Left heart ventricular angiography

    MedlinePlus

    ... catheterization: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, Society for ... American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, ...

  12. Heart valve surgery - discharge

    MedlinePlus

    ... summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ...

  13. Know Your Heart's Numbers

    MedlinePlus

    ... of body fat based on height and weight), waist circumference, blood sugar and weight. The telephone survey of ... for heart health. Just 36 percent knew that waist circumference is important measure of heart disease risk. The ...

  14. Heart failure - discharge

    MedlinePlus

    ... Heart failure - overview Heart pacemaker High blood pressure Implantable cardioverter-defibrillator Smoking - tips on how to quit Ventricular assist ... ask your doctor How to read food labels Implantable cardioverter defibrillator - discharge Low-salt diet Mediterranean diet Taking warfarin ( ...

  15. Aspirin and heart disease

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features on this page, ... healthy people who are at low risk for heart disease. You provider will consider your overall medical condition ...

  16. Heart failure - tests

    MedlinePlus

    CHF - tests; Congestive heart failure - tests; Cardiomyopathy - tests; HF - tests ... An echocardiogram (echo) is a test that uses sound waves to create a moving picture of the heart. The picture is much more detailed than a plain ...

  17. Living with Heart Block

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Living With Heart Block First-degree heart block may ... whether you need ongoing care for your condition. Living With a Pacemaker People who have third-degree ...

  18. Congenital Heart Defects

    MedlinePlus

    ... Treatment can include medicines, catheter procedures, surgery, and heart transplants. The treatment depends on the type of the defect, how severe it is, and a child's age, size, and general health. NIH: National Heart, Lung, and Blood Institute

  19. Problem: Heart Valve Regurgitation

    MedlinePlus

    ... Options • Recovery and Healthy Living Goals • Personal Stories Heart Valve Disease Symptoms Dr. Robert Bonow describes the symptoms that may alert you to heart valve disease. Support Network: You're Not Alone Popular Articles ...

  20. [Understanding heart failure].

    PubMed

    Boo, José Fernando Guadalajara

    2006-01-01

    Heart failure is a disease with several definitions. The term "heart failure" is used by has brougth about confusion in the terminology. For this reason, the value of the ejection fraction (< 0.40 or < 0.35) is used in most meganalyses on the treatment of heart failure, avoiding the term "heart failure" that is a confounding concept. In this paper we carefully analyze the meaning of contractility, ventricular function or performance, preload, afterload, heart failure, compensation mechanisms in heart failure, myocardial oxygen consumption, inadequate, adequate and inappropriate hypertrophy, systole, diastole, compliance, problems of relaxation, and diastolic dysfunction. Their definitions are supported by the original scientific descriptions in an attempt to clarify the concepts about ventricular function and heart failure and, in this way, use the same scientific language about the meaning of ventricular function, heart failure, and diastolic dysfunction.

  1. Heart disease - risk factors

    MedlinePlus

    Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...

  2. Heart bypass surgery

    MedlinePlus

    Off-pump coronary artery bypass; OPCAB; Beating heart surgery; Bypass surgery - heart; CABG; Coronary artery bypass graft; Coronary artery bypass surgery; Coronary bypass surgery; Coronary artery disease - CABG; CAD - CABG; Angina - ...

  3. How the Heart Works

    MedlinePlus

    ... Your heart is at the center of your circulatory system. This system consists of a network of blood ... the walls contract, blood is pumped into your circulatory system. Inlet and outlet valves in your heart chambers ...

  4. Heart and Stroke Encyclopedia

    MedlinePlus

    ... Venous Thromboembolism Aortic Aneurysm More The Heart and Stroke Encyclopedia Click a letter below to get a ... dozens of cardiovascular terms from our Heart and Stroke Encyclopedia and get links to in-depth information. ...

  5. Heart failure overview

    MedlinePlus

    ... The most common causes of heart failure are: Coronary artery disease (CAD), a narrowing of the small blood vessels that ... at the same time. A defibrillator sends an electrical pulse to stop life-threatening abnormal heart rhythms. ...

  6. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside protects murine hearts against ischemia/reperfusion injury by activating Notch1/Hes1 signaling and attenuating endoplasmic reticulum stress

    PubMed Central

    Zhang, Meng; Yu, Li-ming; Zhao, Hang; Zhou, Xuan-xuan; Yang, Qian; Song, Fan; Yan, Li; Zhai, Meng-en; Li, Bu-ying; Zhang, Bin; Jin, Zhen-xiao; Duan, Wei-xun; Wang, Si-wang

    2017-01-01

    2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a water-soluble active component extracted from Polygonum multiflorum Thunb. A number of studies demonstrate that TSG exerts cardioprotective effects. Since endoplasmic reticulum (ER) stress plays a key role in myocardial ischemia/reperfusion (MI/R)-induced cell apoptosis, we sought to determine whether modulation of the ER stress during MI/R injury was involved in the cardioprotective action of TSG. Male mice were treated with TSG (60 mg·kg−1·d−1, ig) for 2 weeks and then were subjected to MI/R surgery. Pre-administration of TSG significantly improved post-operative cardiac function, and suppressed MI/R-induced myocardial apoptosis, evidenced by the reduction in the myocardial apoptotic index, serum levels of LDH and CK after 6 h of reperfusion. TSG (0.1–1000 μmol/L) did not affect the viability of cultured H9c2 cardiomyoblasts in vitro, but pretreatment with TSG dose-dependently decreased simulated ischemia/reperfusion (SIR)-induced cell apoptosis. Furthermore, both in vivo and in vitro studies revealed that TSG treatment activated the Notch1/Hes1 signaling pathway and suppressed ER stress, as evidenced by increasing Notch1, Notch1 intracellular domain (NICD), Hes1, and Bcl-2 expression levels and by decreasing p-PERK/PERK ratio, p-eIF2α/eIF2α ratio, and ATF4, CHOP, Bax, and caspase-3 expression levels. Moreover, the protective effects conferred by TSG on SIR-treated H9c2 cardiomyoblasts were abolished by co-administration of DAPT (the Notch1 signaling inhibitor). In summary, TSG ameliorates MI/R injury in vivo and in vitro by activating the Notch1/Hes1 signaling pathway and attenuating ER stress-induced apoptosis. PMID:28112174

  7. Traumatic Brain Injury Creates Biphasic Systemic Hemodynamic and Organ Blood Flow Responses in Rats

    DTIC Science & Technology

    1990-01-01

    injury. Fluid percussion brain injury produced an immediate systemic hypertension followed by a hypotension and low cardiac output. Organ blood flows...37.5°C using a heating pad. The right femoral artery was cannulated for blood pressure monitoring using a quartz transducer (Hewlett Packard) and an...Since the hypertensive responses were usually maximal at 30 sec after injury, the mean arterial pressure and heart rate at 30 sec after sham injury

  8. Intravenous Adenosine for Surgical Management of Penetrating Heart Wounds

    PubMed Central

    Kokotsakis, John; Hountis, Panagiotis; Antonopoulos, Nikolaos; Skouteli, Elian; Athanasiou, Thanos; Lioulias, Achilleas

    2007-01-01

    Accurate suturing of penetrating cardiac injuries is difficult. Heart motion, ongoing blood loss, arrhythmias due to heart manipulation, and the near-death condition of the patient can all affect the outcome. Rapid intravenous injection of adenosine induces temporary asystole that enables placement of sutures in a motionless surgical field. Use of this technique improves surgical conditions, and it is faster than other methods. Herein, we describe our experience with the use of intravenous adenosine to successfully treat 3 patients who had penetrating heart wounds. PMID:17420798

  9. Heart bypass surgery

    MedlinePlus Videos and Cool Tools

    Heart bypass surgery begins with an incision made in the chest, with the breastbone cut exposing the heart. Next, a portion of the saphenous vein is ... used to bypass the blocked arteries in the heart. The venous graft is sewn to the aorta ...

  10. Working Model Hearts

    ERIC Educational Resources Information Center

    Brock, David

    2009-01-01

    Despite student interest, the heart is often a poorly understood topic in biology. To help students understand this vital organ's physiology, the author created this investigation activity involving the mammalian heart and its role in the circulatory system. Students design, build, and demonstrate working artificial "hearts" to exhibit what they…

  11. The Heart of Coaching

    ERIC Educational Resources Information Center

    Docheff, Dennis M.; Gerdes, Dan

    2015-01-01

    This article challenges coaches to address the more personal, human elements of coaching--the HEART of coaching. While there is much research on numerous aspects of coaching, this article provides ideas that make a lasting impact on the hearts of athletes. Using HEART as an acronym, five elements of effective coaching are presented: Humility,…

  12. Cancer and the heart

    SciTech Connect

    Kapoor, A.S.

    1986-01-01

    This book contains 28 chapters. Some of the titles are: Computed tomography of neoplastic disease of the pericardium; Radiation therapy and the heart; Valvular involvement in cancer; Smoking, lung cancer, and coronary heart disease; Carcinoid heart disease; Cardiac amyloidosis; and Anemia of cancer and its cardiac effects.

  13. Heart Valve Diseases

    MedlinePlus

    Your heart has four valves. Normally, these valves open to let blood flow through or out of your heart, and then shut to keep it from flowing ... close tightly. It's one of the most common heart valve conditions. Sometimes it causes regurgitation. Stenosis - when ...

  14. The Heart of Coaching

    ERIC Educational Resources Information Center

    Docheff, Dennis M.; Gerdes, Dan

    2015-01-01

    This article challenges coaches to address the more personal, human elements of coaching--the HEART of coaching. While there is much research on numerous aspects of coaching, this article provides ideas that make a lasting impact on the hearts of athletes. Using HEART as an acronym, five elements of effective coaching are presented: Humility,…

  15. Working Model Hearts

    ERIC Educational Resources Information Center

    Brock, David

    2009-01-01

    Despite student interest, the heart is often a poorly understood topic in biology. To help students understand this vital organ's physiology, the author created this investigation activity involving the mammalian heart and its role in the circulatory system. Students design, build, and demonstrate working artificial "hearts" to exhibit what they…

  16. Heart Disease in Women

    MedlinePlus

    ... United States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing ... the blood vessels that supply blood to the heart itself. This is called coronary artery disease, and ...

  17. Implantable Heart Aid

    NASA Technical Reports Server (NTRS)

    1984-01-01

    CPI's human-implantable automatic implantable defibrillator (AID) is a heart assist system, derived from NASA's space circuitry technology, that can prevent erratic heart action known as arrhythmias. Implanted AID, consisting of microcomputer power source and two electrodes for sensing heart activity, recognizes onset of ventricular fibrillation (VF) and delivers corrective electrical countershock to restore rhythmic heartbeat.

  18. Heart Disease and Stroke Prevention

    MedlinePlus

    ... Heart disease and stroke prevention Heart Health and Stroke Heart disease and stroke prevention Related information Learn more about healthy eating ... to top More information on Heart disease and stroke prevention Read more from womenshealth.gov A Lifetime ...

  19. Congenital Heart Disease in Adults

    MedlinePlus

    ... and genetics may play a role. Why congenital heart disease resurfaces in adulthood Some adults may find that ... in following adults with congenital heart disease. Congenital heart disease and pregnancy Women with congenital heart disease who ...

  20. Living with Heart Valve Disease

    MedlinePlus

    ... Clinical Trials Links Related Topics Congenital Heart Defects Endocarditis Heart Murmur How the Heart Works Mitral Valve ... your doctor if you have symptoms of infective endocarditis (IE). Symptoms of this heart infection include fever, ...