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Sample records for acute cardiac damage

  1. Fabrication of Anti-human Cardiac Troponin I Immunogold Nanorods for Sensing Acute Myocardial Damage

    NASA Astrophysics Data System (ADS)

    Guo, Z. R.; Gu, C. R.; Fan, X.; Bian, Z. P.; Wu, H. F.; Yang, D.; Gu, N.; Zhang, J. N.

    2009-12-01

    A facile, rapid, solution-phase method of detecting human cardiac troponin I for sensing myocardial damage has been described using gold nanorods-based biosensors. The sensing is demonstrated by the distinct change of the longitudinal surface plasmon resonance wavelength of the gold nanorods to specific antibody-antigen binding events. For a higher sensitivity, the aspect ratio of gold nanorods is increased up to ca 5.5 by simply adding small amount of HCl in seed-mediated growth solution. Experimental results show that the detecting limit of the present method is 10 ng/mL. Contrast tests reveal that these gold nanorods-based plasmonic biosensors hold much higher sensitivity than that of conventionally spherical gold nanoparticles.

  2. The involvement of immune reactions in cardiac damage during acute myocardial infarction: role of cell-mediated immune response.

    PubMed

    Dimitrijevic, M; Vasiljevic, Z; Vuckovic-Dekic, L; Spasic, S

    1997-06-01

    This study was undertaken with the aim of investigating humoral and cell-mediated immune response in acute myocardial infarction (AMI) as possible mechanisms involved in the infarction enlargement. Twenty three patients with first AMI and 15 healthy volunteers were examined. Of the AMI patients, 14 had extensive infarction (group A), while 9 patients had small infarction (group B). Immunologic analyses were performed at admission, and repeated after 3, 7, 14 and 21 days of the acute event. Following parameters were tested: number of CD3+, CD4+, CD8+ and CD20+ cells; serum IgG, IgA, IgM, C3, C4, immune complex and anticardiac antibody levels; polymorphonuclear cell (PMN) function (chemotaxis, phagocytosis, metabolic activity); leukocyte migration in vitro in the presence of water-soluble homologous heart extract. It was demonstrated that the number of B cells, serum IgG, C3, immune complex and anticardiac antibody levels were elevated from 7th-14th days after AMI. Concerning these parameters, however, no significant differences were obtained between group A and group B of AMI patients. Chemotaxis and metabolic activity of peripheral blood PMN, but not phagocytosis, were enhanced during AMI, again changes of PMN did not correlate with the extension of infarction. In contrast, leukocyte migration inhibition in vitro revealed that only patients with extensive AMI have developed positive reaction during the first 14 days after the onset of the disease, while leukocyte inhibition reaction appeared in patients with nonextensive AMI not earlier than the 21st day after the infarction. These findings demonstrate generation of immune reactivity during AMI and indicate that humoral immune response seems more likely to be an epiphenomenon related to tissue necrosis, while cell-mediated immune reactions could influence the extensiveness of cardiac damage.

  3. The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome.

    PubMed

    Xu, Lin; Zhao, Hui; Qiu, Jian; Zhu, Wei; Lei, Hongqiang; Cai, Zekun; Lin, Wan-Hua; Huang, Wenhua; Zhang, Heye; Zhang, Yuan-Ting

    2015-01-01

    One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson's test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future. PMID:26247035

  4. The Different Effects of BMI and WC on Organ Damage in Patients from a Cardiac Rehabilitation Program after Acute Coronary Syndrome.

    PubMed

    Xu, Lin; Zhao, Hui; Qiu, Jian; Zhu, Wei; Lei, Hongqiang; Cai, Zekun; Lin, Wan-Hua; Huang, Wenhua; Zhang, Heye; Zhang, Yuan-Ting

    2015-01-01

    One of the purposes of cardiac rehabilitation (CR) after acute coronary syndrome (ACS) is to monitor and control weight of the patient. Our study is to compare the different obesity indexes, body mass index (BMI), and waist circumference (WC), through one well-designed CR program (CRP) with ACS in Guangzhou city of Guangdong Province, China, in order to identify different effects of BMI and WC on organ damage. In our work, sixty-one patients between October 2013 and January 2014 fulfilled our study. We collected the vital signs by medical records, the clinical variables of body-metabolic status by fasting blood test, and the organ damage variables by submaximal exercise treadmill test (ETT) and ultrasonic cardiogram (UCG) both on our inpatient and four-to-five weeks of outpatient part of CRP after ACS. We mainly used two-tailed Pearson's test and liner regression to evaluate the relationship of BMI/WC and organ damage. Our results confirmed that WC could be more accurate than BMI to evaluate the cardiac function through the changes of left ventricular structure on the CRP after ACS cases. It makes sense of early diagnosis, valid evaluation, and proper adjustment to ACS in CRP of the obesity individuals in the future.

  5. Acute emotional stress and cardiac arrhythmias.

    PubMed

    Ziegelstein, Roy C

    2007-07-18

    Episodes of acute emotional stress can have significant adverse effects on the heart. Acute emotional stress can produce left ventricular contractile dysfunction, myocardial ischemia, or disturbances of cardiac rhythm. Although these abnormalities are often only transient, their consequences can be gravely damaging and sometimes fatal. Despite the many descriptions of catastrophic cardiovascular events in the setting of acute emotional stress, the anatomical substrate and physiological pathways by which emotional stress triggers cardiovascular events are only now being characterized, aided by the advent of functional neuroimaging. Recent evidence indicates that asymmetric brain activity is particularly important in making the heart more susceptible to ventricular arrhythmias. Lateralization of cerebral activity during emotional stress may stimulate the heart asymmetrically and produce areas of inhomogeneous repolarization that create electrical instability and facilitate the development of cardiac arrhythmias. Patients with ischemic heart disease who survive an episode of sudden cardiac death in the setting of acute emotional stress should receive a beta-blocker. Nonpharmacological approaches to manage emotional stress in patients with and without coronary artery disease, including social support, relaxation therapy, yoga, meditation, controlled slow breathing, and biofeedback, are also appropriate to consider and merit additional investigation in randomized trials.

  6. Myocardin-related transcription factor-A-overexpressing bone marrow stem cells protect cardiomyocytes and alleviate cardiac damage in a rat model of acute myocardial infarction.

    PubMed

    Zhong, Ze; Hu, Jia-Qing; Wu, Xin-Dong; Sun, Yong; Jiang, Jun

    2015-09-01

    Myocardin-related transcription factor-A (MRTF-A) can transduce biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction (AMI). In the clinic, bone marrow stem cell (BMSC) therapy is being increasingly utilized for AMI; however, the effects of BMSC transplantation remain to be optimized. Therefore, a novel strategy to enhance BMSC‑directed myocardial repair is particularly important. The present study was performed to assess the efficacy of MRTF‑A-overexpressing BMSCs in a rat model of AMI. Primary cardiomyocytes were prepared from neonatal Sprague-Dawley rats and BMSCs were isolated from male Sprague-Dawley rats (aged 8-12 weeks). Annexin V-phycoerythrin/7-actinomycin D staining was used to evaluate BMSC and cardiomyocyte survival after exposure to hydrogen peroxide in vitro. B-cell lymphoma 2 (Bcl-2) protein expression was measured by flow cytometric and western blot analyses. The effects of MRTF-A‑overexpressing BMSCs in a rat model of AMI were investigated by hematoxylin and eosin staining and western blot analysis of Bcl-2 expression in myocardial tissue sections. MRTF-A enhanced the migration of BMSCs, and overexpression of MRTF-A in BMSCs prevented hydrogen peroxide-induced apoptosis in primary cardiomyocytes ex vivo. In addition, co-culture of cardiomyocytes with MRTF‑A-overexpressing BMSCs inhibited hydrogen peroxide-induced apoptosis and the enhanced expression of Bcl-2. Furthermore, in vivo, enhanced cell survival was observed in the MRTF-A-modified BMSC group compared with that in the control group. These observations indicated that MRTF-A-overexpressing BMSCs have the potential to exert cardioprotective effects against hydrogen peroxide-induced injury and that treatment with MRTF‑A‑modified BMSCs is able to reverse cardiac dysfunction after AMI.

  7. Acute kidney injury after pediatric cardiac surgery.

    PubMed

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  8. Cardiac surgery-associated acute kidney injury.

    PubMed

    Mao, Huijuan; Katz, Nevin; Ariyanon, Wassawon; Blanca-Martos, Lourdes; Adýbelli, Zelal; Giuliani, Anna; Danesi, Tommaso Hinna; Kim, Jeong Chul; Nayak, Akash; Neri, Mauro; Virzi, Grazia Maria; Brocca, Alessandra; Scalzotto, Elisa; Salvador, Loris; Ronco, Claudio

    2013-10-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common and serious postoperative complication of cardiac surgery requiring cardiopulmonary bypass (CPB), and it is the second most common cause of AKI in the intensive care unit. Although the complication has been associated with the use of CPB, the etiology is likely multifactorial and related to intraoperative and early postoperative management including pharmacologic therapy. To date, very little evidence from randomized trials supporting specific interventions to protect from or prevent AKI in broad cardiac surgery populations has been found. The definition of AKI employed by investigators influences not only the incidence of CSA-AKI, but also the identification of risk variables. The advent of novel biomarkers of kidney injury has the potential to facilitate the subclinical diagnosis of CSA-AKI, the assessment of its severity and prognosis, and the early institution of interventions to prevent or reduce kidney damage. Further studies are needed to determine how to optimize cardiac surgical procedures, CPB parameters, and intraoperative and early postoperative blood pressure and renal blood flow to reduce the risk of CSA-AKI. No pharmacologic strategy has demonstrated clear efficacy in the prevention of CSA-AKI; however, some agents, such as the natriuretic peptide nesiritide and the dopamine agonist fenoldopam, have shown promising results in renoprotection. It remains unclear whether CSA-AKI patients can benefit from the early institution of such pharmacologic agents or the early initiation of renal replacement therapy. PMID:24454314

  9. Cardiac damage presenting late after road accidents.

    PubMed Central

    Mackintosh, A F; Fleming, H A

    1981-01-01

    Six examples of cardiac damage secondary to non-penetrating trauma in road accidents are described. In all six cases the lesion was not recognised at the time of the accident but became clinically important two days to 17 years later. As the patients were young or had unusual lesions, the damage could be attributed to the accident. In older patients with common cardiac problems the trauma might not be recognised as the underlying cause. PMID:7330802

  10. Cardiac surgery-associated acute kidney injury

    PubMed Central

    Ortega-Loubon, Christian; Fernández-Molina, Manuel; Carrascal-Hinojal, Yolanda; Fulquet-Carreras, Enrique

    2016-01-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is a well-recognized complication resulting with the higher morbid-mortality after cardiac surgery. In its most severe form, it increases the odds ratio of operative mortality 3–8-fold, length of stay in the Intensive Care Unit and hospital, and costs of care. Early diagnosis is critical for an optimal treatment of this complication. Just as the identification and correction of preoperative risk factors, the use of prophylactic measures during and after surgery to optimize renal function is essential to improve postoperative morbidity and mortality of these patients. Cardiopulmonary bypass produces an increased in tubular damage markers. Their measurement may be the most sensitive means of early detection of AKI because serum creatinine changes occur 48 h to 7 days after the original insult. Tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 are most promising as an early diagnostic tool. However, the ideal noninvasive, specific, sensitive, reproducible biomarker for the detection of AKI within 24 h is still not found. This article provides a review of the different perspectives of the CSA-AKI, including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment. We searched the electronic databases, MEDLINE, PubMed, EMBASE using search terms relevant including pathogenesis, risk factors, diagnosis, biomarkers, classification, postoperative management, and treatment, in order to provide an exhaustive review of the different perspectives of the CSA-AKI. PMID:27716701

  11. Fatty Heart, Cardiac Damage, and Inflammation

    PubMed Central

    Guzzardi, Maria A.; Iozzo, Patricia

    2011-01-01

    Type 2 diabetes and obesity are associated with systemic inflammation, generalized enlargement of fat depots, and uncontrolled release of fatty acids (FA) into the circulation. These features support the occurrence of cardiac adiposity, which is characterized by an increase in intramyocardial triglyceride content and an enlargement of the volume of fat surrounding the heart and vessels. Both events may initially serve as protective mechanisms to portion energy, but their excessive expansion can lead to myocardial damage and heart disease. FA overload promotes FA oxidation and the accumulation of triglycerides and metabolic intermediates, which can impair calcium signaling, β-oxidation, and glucose utilization. This leads to damaged mitochondrial function and increased production of reactive oxygen species, pro-apoptotic, and inflammatory molecules, and finally to myocardial inflammation and dysfunction. Triglyceride accumulation is associated with left ventricular hypertrophy and dysfunction. The enlargement of epicardial fat in patients with metabolic disorders, and coronary artery disease, is associated with the release of proinflammatory and proatherogenic cytokines to the subtending tissues. In this review, we examine the evidence supporting a causal relationship linking FA overload and cardiac dysfunction. Also, we disentangle the separate roles of FA oxidation and triglyceride accumulation in causing cardiac damage. Finally, we focus on the mechanisms of inflammation development in the fatty heart, before summarizing the available evidence in humans. Current literature confirms the dual (protective and detrimental) role of cardiac fat, and suggests prospective studies to establish the pathogenetic (when and how) and possible prognostic value of this potential biomarker in humans. PMID:22262077

  12. Cardiac BMIPP imaging in acute myocardial infarction.

    PubMed

    Nakata, T; Hashimoto, A; Eguchi, M

    1999-02-01

    Fatty acid metabolism functions as a major energy-producing system under aerobic conditions, but it is impaired immediately after myocardial ischaemia. This imaging can provide intracellular information which cannot be obtained by angiographical, perfusional or functional analysis. 123I-BMIPP and perfusion imagings in patients with acute myocardial infarction have demonstrated three different correlations between myocardial perfusion and fatty acid metabolism: concordant defects of perfusion and BMIPP which represent scar or non-viable tissue; lower BMIPP uptake relative to perfusion (perfusion-BMIPP mismatch) which implicates metabolically damaged, often dysynergic, but viable myocardium; and equivalently normal uptakes of perfusion and BMIPP in completely salvaged myocardium. Identification of these perfusion-metabolism correlations contributes to the detection of ischaemia-related myocardial injury in viable and non-viable myocardium, to the prediction of post-ischaemic or post-interventional functional recovery and to the identification of patients who have myocardium at ischaemic risk. Further clinical investigations might reveal more clearly the pathophysiological and prognostic implications of cardiac BMIPP imaging in patients with acute myocardial infarction.

  13. Cardiac Biomarkers and Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Bucholz, Emily M.; Whitlock, Richard P.; Zappitelli, Michael; Devarajan, Prasad; Eikelboom, John; Garg, Amit X.; Philbrook, Heather Thiessen; Devereaux, Philip J.; Krawczeski, Catherine D.; Kavsak, Peter; Shortt, Colleen

    2015-01-01

    OBJECTIVES: To examine the relationship of cardiac biomarkers with postoperative acute kidney injury (AKI) among pediatric patients undergoing cardiac surgery. METHODS: Data from TRIBE-AKI, a prospective study of children undergoing cardiac surgery, were used to examine the association of cardiac biomarkers (N-type pro–B-type natriuretic peptide, creatine kinase-MB [CK-MB], heart-type fatty acid binding protein [h-FABP], and troponins I and T) with the development of postoperative AKI. Cardiac biomarkers were collected before and 0 to 6 hours after surgery. AKI was defined as a ≥50% or 0.3 mg/dL increase in serum creatinine, within 7 days of surgery. RESULTS: Of the 106 patients included in this study, 55 (52%) developed AKI after cardiac surgery. Patients who developed AKI had higher median levels of pre- and postoperative cardiac biomarkers compared with patients without AKI (all P < .01). Preoperatively, higher levels of CK-MB and h-FABP were associated with increased odds of developing AKI (CK-MB: adjusted odds ratio 4.58, 95% confidence interval [CI] 1.56–13.41; h-FABP: adjusted odds ratio 2.76, 95% CI 1.27–6.03). When combined with clinical models, both preoperative CK-MB and h-FABP provided good discrimination (area under the curve 0.77, 95% CI 0.68–0.87, and 0.78, 95% CI 0.68–0.87, respectively) and improved reclassification indices. Cardiac biomarkers collected postoperatively did not significantly improve the prediction of AKI beyond clinical models. CONCLUSIONS: Preoperative CK-MB and h-FABP are associated with increased risk of postoperative AKI and provide good discrimination of patients who develop AKI. These biomarkers may be useful for risk stratifying patients undergoing cardiac surgery. PMID:25755241

  14. Cardiac Arrhythmias and Abnormal Electrocardiograms After Acute Stroke.

    PubMed

    Ruthirago, Doungporn; Julayanont, Parunyou; Tantrachoti, Pakpoom; Kim, Jongyeol; Nugent, Kenneth

    2016-01-01

    Cardiac arrhythmias and electrocardiogram (ECG) abnormalities occur frequently but are often underrecognized after strokes. Acute ischemic and hemorrhagic strokes in some particular area of brain can disrupt central autonomic control of the heart, precipitating cardiac arrhythmias, ECG abnormalities, myocardial injury and sometimes sudden death. Identification of high-risk patients after acute stroke is important to arrange appropriate cardiac monitoring and effective management of arrhythmias, and to prevent cardiac morbidity and mortality. More studies are needed to better clarify pathogenesis, localization of areas associated with arrhythmias and practical management of arrhythmias and abnormal ECGs after acute stroke.

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

    PubMed

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

    2010-10-01

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

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

    PubMed

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

    2016-10-01

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

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

    PubMed

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

    2016-10-01

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

  18. Neuroanatomical correlates of severe cardiac arrhythmias in acute ischemic stroke.

    PubMed

    Seifert, Frank; Kallmünzer, Bernd; Gutjahr, Isabell; Breuer, Lorenz; Winder, Klemens; Kaschka, Iris; Kloska, Stephan; Doerfler, Arnd; Hilz, Max-Josef; Schwab, Stefan; Köhrmann, Martin

    2015-05-01

    Neurocardiological interactions can cause severe cardiac arrhythmias in patients with acute ischemic stroke. The relationship between the lesion location in the brain and the occurrence of cardiac arrhythmias is still discussed controversially. The aim of the present study was to correlate the lesion location with the occurrence of cardiac arrhythmias in patients with acute ischemic stroke. Cardiac arrhythmias were systematically assessed in patients with acute ischemic stroke during the first 72 h after admission to a monitored stroke unit. Voxel-based lesion-symptom mapping (VLSM) was used to correlate the lesion location with the occurrence of clinically relevant severe arrhythmias. Overall 150 patients, 56 with right-hemispheric and 94 patients with a left-hemispheric lesion, were eligible to be included in the VLSM study. Severe cardiac arrhythmias were present in 49 of these 150 patients (32.7%). We found a significant association (FDR correction, q < 0.05) between lesions in the right insular, right frontal and right parietal cortex as well as the right amygdala, basal ganglia and thalamus and the occurrence of cardiac arrhythmias. Because left- and right-hemispheric lesions were analyzed separately, the significant findings rely on the 56 patients with right-hemispheric lesions. The data indicate that these areas are involved in central autonomic processing and that right-hemispheric lesions located to these areas are associated with an elevated risk for severe cardiac arrhythmias.

  19. Reduction in mitochondrial iron alleviates cardiac damage during injury.

    PubMed

    Chang, Hsiang-Chun; Wu, Rongxue; Shang, Meng; Sato, Tatsuya; Chen, Chunlei; Shapiro, Jason S; Liu, Ting; Thakur, Anita; Sawicki, Konrad T; Prasad, Sathyamangla V N; Ardehali, Hossein

    2016-03-01

    Excess cellular iron increases reactive oxygen species (ROS) production and causes cellular damage. Mitochondria are the major site of iron metabolism and ROS production; however, few studies have investigated the role of mitochondrial iron in the development of cardiac disorders, such as ischemic heart disease or cardiomyopathy (CM). We observe increased mitochondrial iron in mice after ischemia/reperfusion (I/R) and in human hearts with ischemic CM, and hypothesize that decreasing mitochondrial iron protects against I/R damage and the development of CM. Reducing mitochondrial iron genetically through cardiac-specific overexpression of a mitochondrial iron export protein or pharmacologically using a mitochondria-permeable iron chelator protects mice against I/R injury. Furthermore, decreasing mitochondrial iron protects the murine hearts in a model of spontaneous CM with mitochondrial iron accumulation. Reduced mitochondrial ROS that is independent of alterations in the electron transport chain's ROS producing capacity contributes to the protective effects. Overall, our findings suggest that mitochondrial iron contributes to cardiac ischemic damage, and may be a novel therapeutic target against ischemic heart disease. PMID:26896449

  20. Acute effects of firefighting on cardiac performance.

    PubMed

    Fernhall, Bo; Fahs, Christopher A; Horn, Gavin; Rowland, Thomas; Smith, Denise

    2012-02-01

    This study examined standard echocardiographic measures of cardiac size and performance in response to a 3-h firefighting training exercise. Forty experienced male personnel completed a standardized 3 h live firefighting exercise. Before and after the firefighting activities, participants were weighed, height, heart rate, blood pressure and blood samples were obtained, and echocardiographic measurements were made. Firefighting produced significant decreases in left ventricular diastolic dimension, stroke volume, fractional shortening, and mitral E velocity, tachycardia, a rise in core temperature, and a reduction in calculated plasma volume. On tissue Doppler imaging, there were no changes in systolic contractile function, but a decreased lateral wall diastolic velocity was observed. These findings show that 3 h of live firefighting produced cardiac changes consistent with cardiac fatigue, coupled with a decrease in systemic arterial compliance. These data show that live firefighting produces significant cardiovascular changes and future work is needed to evaluate if these changes are related to the increase in cardiovascular risk during live firefighting.

  1. MOEMS-based cardiac enzymes detector for acute myocardial infarction

    NASA Astrophysics Data System (ADS)

    Amritsar, Jeetender; Stiharu, Ion G.; Packirisamy, Muthukumaran; Balagopal, Ganesharam; Li, Xing

    2004-10-01

    Biomedical applications of MOEMS are limited only by the mankind imagination. Precision measurements on minute amounts of biological material could be performed by optical means with a remarkable accuracy. Although available in medical laboratories for general purposes, such analyzers are making their way directly to the users in the form of dedicated equipment. Such an example is a test kit to detect the existence of cardiac enzymes in the blood stream. Apart from the direct users, the medical personnel will make use of such tools given the practicality of the kit. In a large proportion of patients admitted to the hospital suspected of Acute Myocardial Infarction (AMI), the symptoms and electrocardiographic changes are inconclusive. This necessitates the use of biochemical markers of myocardial damage for correct exclusion or conformation of AMI. In this study the concept of MOEMS is applied for the detection of enzyme reaction, in which glass spectrums are scanned optically when enzyme molecules adsorb on their surface. This paper presents the optical behavior of glass spectrums under Horseradish Peroxide (HRP) enzyme reaction. The reported experimental results provide valuable information that will be useful in the development of biosensors for enzymatic detection. This paper also reports the dynamic behavior of different glass spectrums.

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

    PubMed Central

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

    2014-01-01

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

  3. Perspectives on the value of biomarkers in acute cardiac care and implications for strategic management.

    PubMed

    Kossaify, Antoine; Garcia, Annie; Succar, Sami; Ibrahim, Antoine; Moussallem, Nicolas; Kossaify, Mikhael; Grollier, Gilles

    2013-01-01

    Biomarkers in acute cardiac care are gaining increasing interest given their clinical benefits. This study is a review of the major conditions in acute cardiac care, with a focus on biomarkers for diagnostic and prognostic assessment. Through a PubMed search, 110 relevant articles were selected. The most commonly used cardiac biomarkers (cardiac troponin, natriuretic peptides, and C-reactive protein) are presented first, followed by a description of variable acute cardiac conditions with their relevant biomarkers. In addition to the conventional use of natriuretic peptides, cardiac troponin, and C-reactive protein, other biomarkers are outlined in variable critical conditions that may be related to acute cardiac illness. These include ST2 and chromogranin A in acute dyspnea and acute heart failure, matrix metalloproteinase in acute chest pain, heart-type fatty acid binding protein in acute coronary syndrome, CD40 ligand and interleukin-6 in acute myocardial infarction, blood ammonia and lactate in cardiac arrest, as well as tumor necrosis factor-alpha in atrial fibrillation. Endothelial dysfunction, oxidative stress and inflammation are involved in the physiopathology of most cardiac diseases, whether acute or chronic. In summary, natriuretic peptides, cardiac troponin, C-reactive protein are currently the most relevant biomarkers in acute cardiac care. Point-of-care testing and multi-markers use are essential for prompt diagnostic approach and tailored strategic management.

  4. Leptin, a mediator of cardiac damage associated with obesity.

    PubMed

    Martínez-Martínez, E; Jurado-López, R; Cervantes-Escalera, P; Cachofeiro, V; Miana, M

    2014-04-01

    Obesity and excess of adipose tissue are associated with the development of cardiovascular risk factors such as diabetes, hypertension, and hyperlipidemia. At the cardiac level, various morphological adaptations in cardiac structure and function occur in obese individuals. Different mechanisms linking obesity to these modifications have been postulated. Adipose tissue and epicardial fat releases a large number of cytokines and bioactive mediators such as leptin. Leptin circulates in proportion to body fat mass, thus serving as a satiety signal and informing central metabolic control centers as to the status of peripheral energy stores. It participates in numerous other functions both peripherally and centrally, as indicated by the wide distribution of leptin and the different isoforms of its receptor in different tissues including the heart. This hormone has distinct effects on the reproductive, cardiovascular, and immune systems; however, its role in the heart could mediate wide physiological effects observed in obese individuals. Oxidative stress is associated with obesity and may be considered to be a unifying mechanism in the development of obesity-related comorbidities. It has been reported that obesity may induce systemic oxidative stress; in turn, oxidative stress is associated with an irregular production of adipokines. We herein review the current knowledge of cardiac effects of leptin and the possible mechanisms that are involved, including oxidative stress that plays a major role in the development of cardiovascular damage. PMID:25389996

  5. Galectin-1 controls cardiac inflammation and ventricular remodeling during acute myocardial infarction.

    PubMed

    Seropian, Ignacio M; Cerliani, Juan P; Toldo, Stefano; Van Tassell, Benjamín W; Ilarregui, Juan M; González, Germán E; Matoso, Mirian; Salloum, Fadi N; Melchior, Ryan; Gelpi, Ricardo J; Stupirski, Juan C; Benatar, Alejandro; Gómez, Karina A; Morales, Celina; Abbate, Antonio; Rabinovich, Gabriel A

    2013-01-01

    Galectin-1 (Gal-1), an evolutionarily conserved β-galactoside-binding lectin, plays essential roles in the control of inflammation and neovascularization. Although identified as a major component of the contractile apparatus of cardiomyocytes, the potential role of Gal-1 in modulating heart pathophysiology is uncertain. Here, we aimed to characterize Gal-1 expression and function in the infarcted heart. Expression of Gal-1 was substantially increased in the mouse heart 7 days after acute myocardial infarction (AMI) and in hearts from patients with end-stage chronic heart failure. This lectin was localized mainly in cardiomyocytes and inflammatory infiltrates in peri-infarct areas, but not in remote areas. Both simulated hypoxia and proinflammatory cytokines selectively up-regulated Gal-1 expression in mouse cardiomyocytes, whereas anti-inflammatory cytokines inhibited expression of this lectin or had no considerable effect. Compared with their wild-type counterpart, Gal-1-deficient (Lgals1(-/-)) mice showed enhanced cardiac inflammation, characterized by increased numbers of macrophages, natural killer cells, and total T cells, but reduced frequency of regulatory T cells, leading to impaired cardiac function at baseline and impaired ventricular remodeling 7 days after nonreperfused AMI. Treatment of mice with recombinant Gal-1 attenuated cardiac damage in reperfused AMI. Taken together, our results indicate a protective role for Gal-1 in normal cardiac homeostasis and postinfarction remodeling by preventing cardiac inflammation. Thus, Gal-1 treatment represents a potential novel strategy to attenuate heart failure in AMI.

  6. Endothelial RAGE exacerbates acute postischaemic cardiac inflammation.

    PubMed

    Ziegler, Tilman; Horstkotte, Melanie; Lange, Philipp; Ng, Judy; Bongiovanni, Dario; Hinkel, Rabea; Laugwitz, Karl-Ludwig; Sperandio, Markus; Horstkotte, Jan; Kupatt, Christian

    2016-08-01

    Advanced glycation end-products (AGEs) interact with their receptor RAGE, leading to an inflammatory state. We investigated the role of RAGE in postischaemic leukocyte adhesion after myocardial infarction and its effect on postischaemic myocardial function. Wildtype (WT), ICAM-1-/-, RAGE-/- or ICAM-1/RAGE-/- mice underwent 20 minutes (min) of LAD-occlusion followed by 15 min of reperfusion. We applied in vivo fluorescence microscopy visualising Rhodamine-6G labelled leukocytes. To differentiate between endothelial and leukocyte RAGE, we generated bone marrow chimeric mice. Invasive hemodynamic measurements were performed in mice undergoing 45 min of myocardial ischaemia (via LAD-occlusion) followed by 24 hours of reperfusion. Left-ventricular developed pressure (LVDP) was assessed by insertion of a millar-tip catheter into the left ventricle. In the acute model of myocardial ischaemia, leukocyte retention (WT 68 ± 4 cells/hpf) was significantly reduced in ICAM-1-/- (40 ± 3 cells/hpf) and RAGE-/- mice (38 ± 4 cells/hpf). ICAM-1/RAGE-/- mice displayed an additive reduction of leukocyte retention (ICAM-1/RAGE-/- 15 ± 3 cells/hpf). Ly-6G+ neutrophil were predominantly reduced in ICAM-1/RAGE-/- hearts (28 %), whereas Ly-6C+ proinflammatory monocytes decreased to a lesser extent (55 %). Interestingly, PMN recruitment was not affected in chimeric mice with RAGE deficiency in BM cells (WT mice reconstituted with ICAM-1/RAGE-/- BM: 55 ± 4 cells/hpf) while in mice with global RAGE deficiency (ICAM-1/RAGE-/- mice reconstituted with ICAM-1/RAGE-/- BM) leucocyte retention was significantly reduced (13 ± 1 cells/hpf), similar to non-transplanted ICAM/RAGE-/- mice. Furthermore, postischaemic LVDP increased in ICAM-1/RAGE-/- animals (98 ± 4 mmHg vs 86 ± 4 mmHg in WT mice). In conclusion, combined deficiency of ICAM-1 and RAGE reduces leukocyte influx into infarcted myocardium and improves LV function during the acute phase after myocardial ischaemia and reperfusion

  7. Cardiac CT: atherosclerosis to acute coronary syndrome

    PubMed Central

    Munnur, Ravi Kiran; Cameron, James D.; Ko, Brian S.; Meredith, Ian T.

    2014-01-01

    Coronary computed tomographic angiography (CCTA) is a robust non-invasive method to assess coronary artery disease (CAD). Qualitative and quantitative assessment of atherosclerotic coronary stenosis with CCTA has been favourably compared with invasive coronary angiography (ICA) and intravascular ultrasound (IVUS). Importantly, it allows the study of preclinical stages of atherosclerotic disease, may help improve risk stratification and monitor the progressive course of the disease. The diagnostic accuracy of CCTA in the assessment of coronary artery bypass grafts (CABG) is excellent and the constantly improving technology is making the evaluation of stents feasible. Novel techniques are being developed to assess the functional significance of coronary stenosis. The excellent negative predictive value of CCTA in ruling out disease enables early and safe discharge of patients with suspected acute coronary syndromes (ACS) in the Emergency Department (ED). In addition, CCTA is useful in predicting clinical outcomes based on the extent of coronary atherosclerosis and also based on individual plaque characteristics such as low attenuation plaque (LAP), positive remodelling and spotty calcification. In this article, we review the role of CCTA in the detection of coronary atherosclerosis in native vessels, stented vessels, calcified arteries and grafts; the assessment of plaque progression, evaluation of chest pain in the ED, assessment of functional significance of stenosis and the prognostic significance of CCTA. PMID:25610801

  8. Metabonomics of acute kidney injury in children after cardiac surgery.

    PubMed

    Beger, Richard D; Holland, Ricky D; Sun, Jinchun; Schnackenberg, Laura K; Moore, Page C; Dent, Catherine L; Devarajan, Prasad; Portilla, Didier

    2008-06-01

    Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery.

  9. Early detection of acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Jefferies, John Lynn; Devarajan, Prasad

    2016-01-01

    Acute kidney injury (AKI) is increasingly recognized as a common problem in children undergoing cardiac surgery, with well documented increases in morbidity and mortality in both the short and the long term. Traditional approaches to the identification of AKI such as changes in serum creatinine have revealed a large incidence in this population with significant negative impact on clinical outcomes. However, the traditional diagnostic approaches to AKI diagnosis have inherent limitations that may lead to under-diagnosis of this pathologic process. There is a dearth of randomized controlled trials for the prevention and treatment of AKI associated with cardiac surgery, at least in part due to the paucity of early predictive biomarkers. Novel non-invasive biomarkers have ushered in a new era that allows for earlier detection of AKI. With these new diagnostic tools, a more consistent approach can be employed across centers that may facilitate a more accurate representation of the actual prevalence of AKI and more importantly, clinical investigation that may minimize the occurrence of AKI following pediatric cardiac surgery. A thoughtful management approach is necessary to mitigate the effects of AKI after cardiac surgery, which is best accomplished in close collaboration with pediatric nephrologists. Long-term surveillance for improvement in kidney function and potential development of chronic kidney disease should also be a part of the comprehensive management strategy. PMID:27429538

  10. Cardiac computed tomography in patients with acute chest pain.

    PubMed

    Nieman, Koen; Hoffmann, Udo

    2015-04-14

    The efficient and reliable evaluation of patients with acute chest pain is one of the most challenging tasks in the emergency department. Coronary computed tomography (CT) angiography may play a major role, since it permits ruling out coronary artery disease with high accuracy if performed with expertise in properly selected and prepared patients. Several randomized trials have established early cardiac CT as a viable safe and potentially more efficient alternative to functional testing in the evaluation of acute chest pain. Ongoing investigations explore whether advanced anatomic and functional assessments such as high-risk coronary plaque, resting myocardial perfusion, and left ventricular function, or the simulation of the fractional coronary flow reserve will add information to the anatomic assessment for stenosis, which would allow expanding the benefits of cardiac CT from triage to treatment decisions. Especially, the combination of high-sensitive troponins and coronary computed tomography angiography may play a valuable role in future strategies for the management of patients presenting with acute chest pain.

  11. Thrombolytic therapy in acute cerebral infarction complicating diagnostic cardiac catheterization.

    PubMed

    Chen, Yu-Wei; Sim, Ming-Ming; Smith, Eric E

    2006-10-01

    Diagnostic and interventional percutaneous coronary catheterization is associated with stroke. Many of such strokes are asymptomatic, but some are devastating. Once the diagnosis of acute cerebral infarction is confirmed, thrombolytic therapy should be administrated within the time window of 3 hours. We report a 61-year-old woman who suffered from an acute cerebral infarction during diagnostic cardiac catheterization for unstable angina, which manifested as sudden onset of global aphasia, right hemiplegia and gaze preponderance to the left side. Computed tomography of the head performed immediately after recognition of the symptoms showed a hyperdense middle cerebral artery (MCA) sign. Following prompt recognition and diagnosis, intravenous thrombolytic therapy was administered 2 hours after symptom onset. The patient had a favorable outcome. Initially, National Institutes of Health Stroke Scale score was 21, and 24 hours later it improved to 9. The hyperdense MCA lesion had resolved on the 24-hour follow-up scan. This case illustrates the clinical benefit of thrombolytic therapy in the setting of acute stroke associated with cardiac catheterization.

  12. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-07-04

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI.

  13. Acute kidney injury following cardiac surgery: current understanding and future directions.

    PubMed

    O'Neal, Jason B; Shaw, Andrew D; Billings, Frederic T

    2016-01-01

    Acute kidney injury (AKI) complicates recovery from cardiac surgery in up to 30 % of patients, injures and impairs the function of the brain, lungs, and gut, and places patients at a 5-fold increased risk of death during hospitalization. Renal ischemia, reperfusion, inflammation, hemolysis, oxidative stress, cholesterol emboli, and toxins contribute to the development and progression of AKI. Preventive strategies are limited, but current evidence supports maintenance of renal perfusion and intravascular volume while avoiding venous congestion, administration of balanced salt as opposed to high-chloride intravenous fluids, and the avoidance or limitation of cardiopulmonary bypass exposure. AKI that requires renal replacement therapy occurs in 2-5 % of patients following cardiac surgery and is associated with 50 % mortality. For those who recover from renal replacement therapy or even mild AKI, progression to chronic kidney disease in the ensuing months and years is more likely than for those who do not develop AKI. Cardiac surgery continues to be a popular clinical model to evaluate novel therapeutics, off-label use of existing medications, and nonpharmacologic treatments for AKI, since cardiac surgery is fairly common, typically elective, provides a relatively standardized insult, and patients remain hospitalized and monitored following surgery. More efficient and time-sensitive methods to diagnose AKI are imperative to reduce this negative outcome. The discovery and validation of renal damage biomarkers should in time supplant creatinine-based criteria for the clinical diagnosis of AKI. PMID:27373799

  14. Cyclophosphamide-induced immunosuppression protects cardiac noradrenergic nerve terminals from damage by Trypanosoma cruzi infection in adult rats.

    PubMed

    Guerra, L B; Andrade, L O; Galvão, L M; Macedo, A M; Machado, C R

    2001-01-01

    Trypanosoma cruzi-infected juvenile rats develop severe cardiac sympathetic denervation in parallel with acute myocarditis. This aspect has not been studied in adult rats, thought to be resistant to this infection. The mechanism involved in T. cruzi-induced neuronal damage remains to be completely elucidated. In juvenile rats, the mortality during the acute phase depends on T. cruzi populations, ranging from 30% to 100%. Therefore, studies of mechanisms through hazardous procedures such as immunosuppression are restricted. The current paper shows that adult rats infected with T. cruzi (Y strain) develop severe acute myocarditis and cardiac sympathetic denervation, despite null mortality and virtual absence of patent parasitaemia followed by negative haemoculture. Recovery from the myocarditis and denervation occurred but PCR studies showed persistence of parasite DNA at least until day 111 post inoculation. Immunosuppression by cyclophosphamide treatment increased the parasitaemia, prevented the acute myocarditis and the sympathetic denervation without significant alteration of the myocardial parasitism. These results argue against a direct role for parasite-derived products and implicate the inflammatory cells in the denervation process. As previous studies in juvenile animals have discarded an essential role for radiosensitive cells, the macrophages remain as the possible effectors for the T. cruzi-induced neuronal damage.

  15. Acute effects of carbon monoxide on cardiac electrical stability

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A. )

    1990-10-01

    The objective of this project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability. To obtain a comprehensive assessment, diverse biological models were employed. These involved cardiac electrical testing in the normal and ischemic heart in anesthetized and conscious dogs. The experimental plan was designed both to examine the direct effects of carbon monoxide exposure on the myocardium and to evaluate possible indirect influences through alterations in platelet aggregability or changes in central nervous system activity in the conscious animal. Our results indicate that exposure to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, is without significant effect on ventricular electrical stability. This appears to be the case in the acutely ischemic heart as well as in the normal heart. It is important to note that the total exposure period was in the range of 90 to 124 minutes. The possibility that longer periods of exposure or exacerbation from nicotine in cigarette smoke could have a deleterious effect cannot be excluded. We also examined whether or not alterations in platelet aggregability due to carbon monoxide exposure could be a predisposing factor for cardiac arrhythmias. A model involving partial coronary artery stenosis was used to simulate the conditions under which platelet plugs could lead to myocardial ischemia and life-threatening arrhythmias. We found no changes either in the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Thus, carbon monoxide exposure does not appear to alter platelet aggregability or its effect on coronary blood flow during stenosis. In the final series of experiments, we examined the effects of carbon monoxide exposure in the conscious state.

  16. [Non-cardiac causes of acute ischemia in the arms].

    PubMed

    d'Addato, M; Pedrini, L

    1996-01-01

    Among a series of 286 cases of acute ischemia of the upper limb, we analyzed the files of 176 patients (61.5%) with noncardiac ischemia in order to identify the causes and treatment. Trauma was the most frequent cause (126 cases) including trauma of the forearm especially due to stab wounds. Lesions with a subclavian-axillary localization were predominantly due to tear wounds or blunt trauma. We analyzed two groups among the trauma cases: iatrogenic lesions (9 cases) usually resulted from orthopedic surgery (5 cases) or vascular catheterization (3 cases) as well as near-total limb amputations (13) cases. Thrombosis of the subclavian artery occurred in 33 patients; 9 had acute ischemia including 3 due to a cervical rib and 6 due to compression by the rib and the clavicle. Only 4 of these 33 patients suffered ischemia of the hand due to embolization. Acute ischemia was caused by arteriopathy of the hand in 8 patients including 2 volley ball players, 1 baseball player and 3 subjects with occupational microtrauma and 1 with thrombosis of the palmar arch. Finally 1 patient had thrombosis after intravenous drug injection. These files demonstrated the variety of non-cardiac causes of acute ischemia of the upper limb. During the acute phase, we propose locoregional thrombolysis in case of thrombosis and embolectomy for emboli followed by treatment of the casual lesion. An arteriography is essential for correct diagnosis and should include the subclavian artery in the hyperabduction position and the hand. Duplex scanning of the subclavian artery is indicated in case of ischemia of the hand using the Adson, McGowan and Wright maneuvers in order to guide the radiologist for invasive radiography before initiating appropriate treatment.

  17. Bronchogenic Carcinoma with Cardiac Invasion Simulating Acute Myocardial Infarction

    PubMed Central

    Das, Anirban; Das, Sibes K.; Pandit, Sudipta; Karmakar, Rathindra Nath

    2016-01-01

    Cardiac metastases in bronchogenic carcinoma may occur due to retrograde lymphatic spread or by hematogenous dissemination of tumour cells, but direct invasion of heart by adjacent malignant lung mass is very uncommon. Pericardium is frequently involved in direct cardiac invasion by adjacent lung cancer. Pericardial effusion, pericarditis, and tamponade are common and life threatening presentation in such cases. But direct invasion of myocardium and endocardium is very uncommon. Left atrial endocardium is most commonly involved in such cases due to anatomical contiguity with pulmonary hilum through pulmonary veins, and in most cases left atrial involvement is asymptomatic. But myocardial compression and invasion by adjacent lung mass may result in myocardial ischemia and may present with retrosternal, oppressive chest pain which clinically may simulate with the acute myocardial infarction (AMI). As a result, it leads to misdiagnosis and delayed diagnosis of lung cancer. Here we report a case of non-small-cell carcinoma of right lung which was presented with asymptomatic invasion in left atrium and retrosternal chest pain simulating AMI due to myocardial compression by adjacent lung mass, in a seventy-four-year-old male smoker. PMID:27042370

  18. Acute exercise modifies titin phosphorylation and increases cardiac myofilament stiffness

    PubMed Central

    Müller, Anna E.; Kreiner, Matthias; Kötter, Sebastian; Lassak, Philipp; Bloch, Wilhelm; Suhr, Frank; Krüger, Martina

    2014-01-01

    Titin-based myofilament stiffness is largely modulated by phosphorylation of its elastic I-band regions N2-Bus (decreases passive stiffness, PT) and PEVK (increases PT). Here, we tested the hypothesis that acute exercise changes titin phosphorylation and modifies myofilament stiffness. Adult rats were exercised on a treadmill for 15 min, untrained animals served as controls. Titin phosphorylation was determined by Western blot analysis using phosphospecific antibodies to Ser4099 and Ser4010 in the N2-Bus region (PKG and PKA-dependent. respectively), and to Ser11878 and Ser 12022 in the PEVK region (PKCα and CaMKIIδ-dependent, respectively). Passive tension was determined by step-wise stretching of isolated skinned cardiomyocytes to sarcomere length (SL) ranging from 1.9 to 2.4 μm and showed a significantly increased PT from exercised samples, compared to controls. In cardiac samples titin N2-Bus phosphorylation was significantly decreased by 40% at Ser4099, however, no significant changes were observed at Ser4010. PEVK phosphorylation at Ser11878 was significantly increased, which is probably mediated by the observed exercise-induced increase in PKCα activity. Interestingly, relative phosphorylation of Ser12022 was substantially decreased in the exercised samples. Surprisingly, in skeletal samples from acutely exercised animals we detected a significant decrease in PEVK phosphorylation at Ser11878 and an increase in Ser12022 phosphorylation; however, PKCα activity remained unchanged. In summary, our data show that a single exercise bout of 15 min affects titin domain phosphorylation and titin-based myocyte stiffness with obviously divergent effects in cardiac and skeletal muscle tissues. The observed changes in titin stiffness could play an important role in adapting the passive and active properties of the myocardium and the skeletal muscle to increased physical activity. PMID:25477822

  19. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  20. BATF inhibition prevent acute allograft rejection after cardiac transplantation.

    PubMed

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection. PMID:27648151

  1. BATF inhibition prevent acute allograft rejection after cardiac transplantation

    PubMed Central

    Yang, Bo; He, Fan; Dai, Chen; Tan, Rumeng; Ma, Dongxia; Wang, Zhimin; Zhang, Bo; Feng, Jincheng; Wei, Lai; Zhu, Hua; Chen, Zhishui

    2016-01-01

    Acute allograft rejection is a serious and life-threatening complication of organ transplantation. Th17 cells induced inflammation has been described to play an important role in allograft rejection. Since there is a plenty of evidence indicating that transcriptional factor BATF regulates the differentiation of Th17 and follicular T helper cells both in vitro and in vivo, we investigated whether is BATF involved in acute rejection and allograft survival by injecting lentivirus containing BATF shRNA through tail vein before the cardiac transplantation operation. We found that the allograft survival time of the mice treated with BATF shRNA was significantly prolonged compared with that of negative shRNA treated group and the control group. Further pathological analysis revealed that the BATF shRNA treatment group had significantly lower rejection degree than the negative shRNA group, while there was no significant difference between the negative shRNA group and the control group. Furthermore, flow cytometry analysis and quantitative polymerase chain reaction and enzyme-linked immuno sorbent assay were used to determine the proportion of T helper cells, the expression of specific transcription factor and the inflammatory cytokines respectively. Data showed that BATF regulated Th17 and Treg responses during allograft rejection. And BATF inhibition led to reduction of the expression level of Rorγ-t and enhancement of the Foxp-3. In addition, cytokines IL-17A and IL-4 were found decreased. This may indicate BATF as a novel therapy target for treatment of acute allograft rejection.

  2. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

    PubMed Central

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-01-01

    Background Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Methods and Results Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). Conclusions ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. PMID:26304941

  3. INHALATION OF OZONE AND DIESEL EXHAUST PARTICLES (DEP) INDUCES ACUTE AND REVERSIBLE CARDIAC GENE EXPRESSION CHANGES

    EPA Science Inventory

    We have recently shown that episodic but not acute exposure to ozone or DEP induces vascular effects that are associated with the loss of cardiac mitochondrial phospholipid fatty acids (DEP 2.0 mg/m3 > ozone, 0.4 ppm). In this study we determined ozone and DEP-induced cardiac gen...

  4. Acute liver damage and anorexia nervosa: a case report.

    PubMed

    Bridet, Lionel; Martin, Juan Jose Beitia; Nuno, Jose Luis Cabriada

    2014-04-01

    Anorexia nervosa is an eating disorder predominantly affecting young women and characterized by an intense fear of gaining weight and becoming fat. Liver injury with mild elevation of hepatic enzymes is a frequent complication, and steatosis of the liver is thought to be the major underlying pathology. However, acute hepatic failure with transaminase levels over 1000 u/L is a very rare complication, and the precise mechanism of the liver injury is still unclear. We report a case of a 35-year-old woman with a history of anorexia nervosa who developed acute liver damage with deep coma in relation to profound hypoglycemia. The treatment was hydration, correction of electrolyte and fluid imbalance, and gradual nutritional support to prevent refeeding syndrome. Our patient's consciousness was significantly improved with the recovery of liver function and normalization of transaminase levels. Although the mechanism of pathogenesis is largely unknown, we discuss the two principal hypotheses: starvation-induced autophagy and acute hypoperfusion.

  5. Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

    PubMed

    Puukila, Stephanie; Bryan, Sean; Laakso, Anna; Abdel-Malak, Jessica; Gurney, Carli; Agostino, Adrian; Belló-Klein, Adriane; Prasad, Kailash; Khaper, Neelam

    2015-01-01

    Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG), a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

  6. Cardiac peroxisome proliferator-activated receptor-γ expression is modulated by oxidative stress in acutely infrasound-exposed cardiomyocytes.

    PubMed

    Pei, Zhaohui; Meng, Rongsen; Zhuang, Zhiqiang; Zhao, Yiqiao; Liu, Fangpeng; Zhu, Miao-Zhang; Li, Ruiman

    2013-12-01

    The aim of the present study was to examine the effects of acute infrasound exposure on oxidative damage and investigate the underlying mechanisms in rat cardiomyocytes. Neonatal rat cardiomyocytes were cultured and exposed to infrasound for several days. In the study, the expression of CAT, GPx, SOD1, and SOD2 and their activities in rat cardiomyocytes in infrasound exposure groups were significantly decreased compared to those in the various time controls, along with significantly higher levels of O2 (-) and H2O2. Decreased cardiac cell viability was not observed in various time controls. A significant reduction in cardiac cell viability was observed in the infrasound group compared to the control, while significantly increased cardiac cell viability was observed in the infrasound exposure and rosiglitazone pretreatment group. Compared to the control, rosiglitazone significantly upregulated CAT, GPx, SOD1, and SOD2 expression and their activities in rat cardiomyocytes exposed to infrasound, while the levels of O2 (-) or H2O2 were significantly decreased. A potential link between a significant downregulation of PPAR-γ expression in rat cardiomyocytes in the infrasound group was compared to the control and infrasound-induced oxidative stress. These findings indicate that infrasound can induce oxidative damage in rat cardiomyocytes by inactivating PPAR-γ. PMID:23632742

  7. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass.

  8. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J.; Llanos-Gómez, Juan M.; Cabello-Rodríguez, Ana I.; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called “sanctuaries,” are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  9. Cardiac Relapse of Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    Facenda-Lorenzo, María; Sánchez-Quintana, Ana; Quijada-Fumero, Alejandro; Laynez-Carnicero, Ana; Breña-Atienza, Joaquín; Poncela-Mireles, Francisco J; Llanos-Gómez, Juan M; Cabello-Rodríguez, Ana I; Ramos-López, María

    2016-01-01

    Secondary or metastatic cardiac tumors are much more common than primary benign or malignant cardiac tumors. Any tumor can cause myocardial or pericardial metastasis, although isolated or combined tumor invasion of the pericardium is more common. Types of neoplasia with the highest rates of cardiac or pericardial involvement are melanoma, lung cancer, and breast and mediastinal carcinomas. Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Initial treatment involves chemotherapy followed by consolidation treatment to reduce the risk of relapse. In high-risk patients, the treatment of choice for consolidation is hematopoietic stem cell transplantation (HSCT). Relapse of AML is the most common cause of HSCT failure. Extramedullary relapse is rare. The organs most frequently affected, called "sanctuaries," are the testes, ovaries, and central nervous system. We present a case with extramedullary relapse in the form of a solid cardiac mass. PMID:27642531

  10. SPR detection of cardiac troponin T for acute myocardial infarction.

    PubMed

    Pawula, Maria; Altintas, Zeynep; Tothill, Ibtisam E

    2016-01-01

    A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive and specific detection of cardiac troponin T (cTnT) in serum samples is reported in this work. An extensive optimisation of assay parameters was conducted to achieve optimal detection strategy. Both direct and sandwich immunoassay formats were investigated and optimised. The response obtained was enhanced further by the use of gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. A regeneration method was developed to enable the reuse of the SPR sensor for multiple sample application. The SPR immunosensor showed good reproducibility for cTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ng mL(-1) for the direct and sandwich assays in buffer, respectively. The linear regression analysis was performed and R(2) value was found as 0.99 for both assays. In order to optimise the sensor for serum analysis, nonspecific binding of serum proteins was reduced through the use of additives in the dilution buffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serum was assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ng mL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) M using Langmuir binding model which indicates high affinity between cTnT and its antibody. The proposed SPR immunosensor has a promising potential to be developed for point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers in central nervous system diseases. PMID:26695335

  11. SPR detection of cardiac troponin T for acute myocardial infarction.

    PubMed

    Pawula, Maria; Altintas, Zeynep; Tothill, Ibtisam E

    2016-01-01

    A surface plasmon resonance (SPR) sensor developed for the rapid, sensitive and specific detection of cardiac troponin T (cTnT) in serum samples is reported in this work. An extensive optimisation of assay parameters was conducted to achieve optimal detection strategy. Both direct and sandwich immunoassay formats were investigated and optimised. The response obtained was enhanced further by the use of gold nanoparticles (AuNPs) conjugated to the anti-cTnT detection antibody. A regeneration method was developed to enable the reuse of the SPR sensor for multiple sample application. The SPR immunosensor showed good reproducibility for cTnT detection in the concentration range of 25-1000 ng mL(-1) and 5-400 ng mL(-1) for the direct and sandwich assays in buffer, respectively. The linear regression analysis was performed and R(2) value was found as 0.99 for both assays. In order to optimise the sensor for serum analysis, nonspecific binding of serum proteins was reduced through the use of additives in the dilution buffer. To achieve greater sensitivity, the performance of the cTnT immunosensor sandwich assay in human serum was evaluated using non-modified and AuNP modified detector antibodies. A detection limit (LOD) for the immunosensor in 50% serum was assessed as 5 ng mL(-1) cTnT for the standard sandwich assay and 0.5 ng mL(-1) cTnT when using AuNP conjugated detector antibodies with a linear dynamic range of 0.5-40 ng mL(-1). The dissociation constant was found as 3.28 × 10(-9) M using Langmuir binding model which indicates high affinity between cTnT and its antibody. The proposed SPR immunosensor has a promising potential to be developed for point-of-care testing for the early diagnosis of acute myocardial infarction (AMI). This method can also be used for the rapid detection of biomarkers in central nervous system diseases.

  12. Acute cardiac arrhythmias following surgery for congenital heart disease: mechanisms, diagnostic tools, and management.

    PubMed

    Payne, Linda; Zeigler, Vicki L; Gillette, Paul C

    2011-06-01

    This article focuses on the management of those cardiac arrhythmias most commonly seen in the immediate postoperative period. They include ventricular tachycardia, ventricular fibrillation, atrial flutter, junctional ectopic tachycardia, bradycardia, and atrioventricular block. The mechanisms of cardiac arrhythmias are reviewed followed by a brief overview of the predominant acute arrhythmias, tools used for the diagnostic evaluation of these arrhythmias, management strategies, and, finally, nursing considerations.

  13. Cardiac Damage Biomarkers Following a Triathlon in Elite and Non-elite Triathletes.

    PubMed

    Park, Chan-Ho; Kim, Kwi-Baek; Han, Jin; Ji, Jin-Goo; Kwak, Yi-Sub

    2014-10-01

    The purpose of the present study was to investigate cardiac damage biomarkers after a triathlon race in elite and non-elite athlete groups. Fifteen healthy men participated in the study. Based on performance, they were divided into elite athlete group (EG: n=7) and non-elite athlete group (NEG: n=8). Participants' blood samples were obtained during four periods: before, immediately, 2 hours and 7 days after finishing the race. creatine kinase (CK), creatine kinase-myoglobin (CK-MB), myoglobin, and lactate dehydrogenase (LDH) were significantly increased in both groups immediately after, and 2 hours after finishing the race (p<.05). CK, CK-MB, and myoglobin were completely recovered after 7 days (p<.05). Hematocrit (Hct) was significantly decreased in both groups (p<.05) 7 days after the race. LDH was significantly decreased in the EG (p<.05) only 7 days after the race. Homoglobin (Hb) was significantly decreased in the NEG (p<.05) only 2 hours after the race. Although cardiac troponin T (cTnT) was significantly increased in the EG but not in the NEG 2hours after the race (p<.05), there was no group-by-time interaction. cTnT was completely recovered in both groups 7 days after the race. In conclusion, cardiac damage occurs during a triathlon race and, is greater in elite than in non-elite. However, all cardiac damage markers return to normal range within 1 week.

  14. Cardiac Damage Biomarkers Following a Triathlon in Elite and Non-elite Triathletes

    PubMed Central

    Park, Chan-Ho; Kim, Kwi-Baek; Han, Jin; Ji, Jin-Goo

    2014-01-01

    The purpose of the present study was to investigate cardiac damage biomarkers after a triathlon race in elite and non-elite athlete groups. Fifteen healthy men participated in the study. Based on performance, they were divided into elite athlete group (EG: n=7) and non-elite athlete group (NEG: n=8). Participants' blood samples were obtained during four periods: before, immediately, 2 hours and 7 days after finishing the race. creatine kinase (CK), creatine kinase-myoglobin (CK-MB), myoglobin, and lactate dehydrogenase (LDH) were significantly increased in both groups immediately after, and 2 hours after finishing the race (p<.05). CK, CK-MB, and myoglobin were completely recovered after 7 days (p<.05). Hematocrit (Hct) was significantly decreased in both groups (p<.05) 7 days after the race. LDH was significantly decreased in the EG (p<.05) only 7 days after the race. Homoglobin (Hb) was significantly decreased in the NEG (p<.05) only 2 hours after the race. Although cardiac troponin T (cTnT) was significantly increased in the EG but not in the NEG 2hours after the race (p<.05), there was no group-by-time interaction. cTnT was completely recovered in both groups 7 days after the race. In conclusion, cardiac damage occurs during a triathlon race and, is greater in elite than in non-elite. However, all cardiac damage markers return to normal range within 1 week. PMID:25352762

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

    PubMed Central

    2009-01-01

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

  16. [Organ damage and cardiorenal syndrome in acute heart failure].

    PubMed

    Casado Cerrada, Jesús; Pérez Calvo, Juan Ignacio

    2014-03-01

    Heart failure is a complex syndrome that affects almost all organs and systems of the body. Signs and symptoms of organ dysfunction, in particular kidney dysfunction, may be accentuated or become evident for the first time during acute decompensation of heart failure. Cardiorenal syndrome has been defined as the simultaneous dysfunction of both the heart and the kidney, regardless of which of the two organs may have suffered the initial damage and regardless also of their previous functional status. Research into the mechanisms regulating the complex relationship between the two organs is prompting the search for new biomarkers to help physicians detect renal damage in subclinical stages. Hence, a preventive approach to renal dysfunction may be adopted in the clinical setting in the near future. This article provides a general overview of cardiorenal syndrome and an update of the physiopathological mechanisms involved. Special emphasis is placed on the role of visceral congestion as an emergent mechanism in this syndrome.

  17. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection

    SciTech Connect

    Carrio, I.; Berna, L.; Ballester, M.; Estorch, M.; Obrador, D.; Cladellas, M.; Abadal, L.; Ginjaume, M.

    1988-12-01

    Indium-111 antimyosin scans were used to assess myocardial damage in patients with suspected myocarditis and cardiac transplant rejection. The calculation of a myocardium to lung ratio (AM index) to quantify antimyosin uptake was performed. AM index in normal subjects (n = 8) at 48 hr postinjection was 1.46 +/- 0.04. In patients with suspected myocarditis (16 studies in 13 patients), AM index was 2.0 +/- 0.5 (p less than 0.001); suggesting a considerable incidence of ongoing cell damage in this group, despite the small proportion of positive right ventricular endomyocardial biopsy (RVbx) (4/13). In patients studied after cardiac transplantation (37 studies in 17 patients), AM indexes correlated with RVbx. In patients with RVbx proven rejection (n = 14), AM index was 1.87 +/- 0.19 (p less than 0.001). In patients with RVbx showing infiltrates but not myocyte damage (n = 13), AM index was 1.80 +/- 0.27 (p = 0.02). In patients with normal RVbx (n = 10), AM index was 1.56 +/- 0.17 (p = NS versus controls; p = 0.001 versus those with positive RVbx). Calculated AM indexes correlated with graded visual analysis of the scans (r = 0.823; p = 0.001). Antimyosin scans are an appropriate method to assess myocardial damage in patients with suspected myocarditis and cardiac rejection.

  18. Role of androgens in sex differences in cardiac damage during myocardial infarction.

    PubMed

    Le, Thi Y L; Ashton, Anthony W; Mardini, Mahidi; Stanton, Peter G; Funder, John W; Handelsman, David J; Mihailidou, Anastasia S

    2014-02-01

    Age-specific incidence of ischemic heart disease in men is higher than in women, although women die more frequently without previous symptoms; the molecular mechanism(s) are poorly understood. Most studies focus on protection by estrogen, with less attention on androgen receptor-mediated androgen actions. Our aim was to determine the role of androgens in the sex differences in cardiac damage during myocardial infarction. Mature age-matched male and female Sprague Dawley rats, intact or surgically gonadectomized (Gx), received testosterone (T) or 17β-estradiol (E2) via subdermal SILASTIC (Dow Corning Corp.) implants; a subset of male rats received dihydrotestosterone. After 21 days, animals were anesthetized, and hearts were excised and subjected to ex vivo regional ischemia-reperfusion (I-R). Hearts from intact males had larger infarcts than those from females following I-R; Gx produced the opposite effect, confirming a role for sex steroids. In Gx males, androgens (dihydrotestosterone, T) and E2 aggravated I-R-induced cardiac damage, whereas in Gx females, T had no effect and E2 reduced infarct area. Increased circulating T levels up-regulated androgen receptor and receptor for advanced glycation end products, which resulted in enhanced apoptosis aggravating cardiac damage in both males and females. In conclusion, our study demonstrates, for the first time, that sex steroids regulate autophagy during myocardial infarction and shows that a novel mechanism of action for androgens during I-R is down-regulation of antiapoptotic protein Bcl-xL (B cell lymphoma-extra large), a key controller for cross talk between autophagy and apoptosis, shifting the balance toward apoptosis and leading to aggravated cardiac damage.

  19. Cardiac manifestations of acute carbamate and organophosphate poisoning.

    PubMed Central

    Saadeh, A. M.; Farsakh, N. A.; al-Ali, M. K.

    1997-01-01

    OBJECTIVE: To study the frequency, extent, and pathogenesis of the cardiac complications accompanying organophosphate and carbamate poisoning. DESIGN: Retrospective study. SETTING: A medical intensive care unit (MICU) of a general hospital. SUBJECTS: 46 adult patients admitted over a five year period with a diagnosis of organophosphate or carbamate poisoning. RESULTS: Cardiac complications developed in 31 patients (67%). These were: non-cardiogenic pulmonary oedema, 20 (43%); cardiac arrhythmias, 11 (24%); electrocardiographic abnormalities including prolonged Q-Tc interval, 31 (67%); ST-T changes, 19 (41%); and conduction defects, 4 (9%). Sinus tachycardia occurred in 16 patients (35%) and sinus bradycardia in 13 (28%). Hypertension developed in 10 patients (22%) and hypotension in eight (17%). Eight patients (17%) needed respiratory support because of respiratory depression. Although more than two thirds of the patients (67%) had a prolonged Q-Tc interval, none had polymorphic ventricular tachycardia of the torsade de pointes type. Two patients died from ventricular fibrillation, an in hospital mortality of 4%. CONCLUSIONS: Cardiac complications often accompany poisoning with these compounds, particularly during the first few hours. Hypoxaemia, acidosis, and electrolyte derangements are major predisposing factors. Intensive supportive treatment in intensive or coronary care facilities with administration of atropine in adequate doses early in the course of the illness will reduce the mortality. PMID:9196418

  20. Bupivacaine induced cardiac toxicity mimicking an acute non-ST segment elevation myocardial infarction.

    PubMed

    Ryu, Ho Yoel; Kim, Jang-Young; Lim, Hyun Kyo; Yoon, Junghan; Yoo, Byung-Su; Choe, Kyung-Hoon; Lee, Seung-Hwan

    2007-04-30

    Bupivacaine is widely used as a local anesthetic. Central nervous system (CNS) and cardiovascular toxicity are well known side effects. However, there has been no report of bupivacaine-induced myocardial injury. We present a case of bupivacaine cardiac toxicity mimicking an acute non-ST segment elevation myocardial infarction, which was eventually diagnosed as bupivacaine-induced cardiac toxicity without CNS toxicity. As soon as a healthy young woman at a private clinic was given a spinal anesthesia of 6mg bupivacaine for hemorrhoidectomy, she developed arrhythmia and hypotension. She was transferred to our emergency room. There was an accelerated idioventricular rhythm with ST segment depression on electrocardiogram, coarse breathing sounds with rales on whole lung field and a butterfly sign on the chest radiograph. 2D transthoracic echocardiography (TTE) revealed reduced left ventricle systolic ejection fraction (approximately 27%). There was regional wall motion abnormality of the left ventricle on 2D TTE and the cardiac marker was increased. We diagnosed the patient as having acute non-ST segment elevation myocardial infarction but her impaired cardiac function improved gradually. On the seventh day from admission, there was a complete spontaneous recovery of cardiac function, and coronary angiography revealed a normal coronary artery. Therefore, we firmly believe that bupivacaine directly injures the cardiac cell.

  1. PULMONARY AND CARDIAC GENE EXPRESSION FOLLOWING ACUTE ULTRAFINE CARBON PARTICLE INHALATION IN HYPERTENSIVE RATS

    EPA Science Inventory

    Inhalation of ultrafine carbon particles (ufCP) causes cardiac physiological changes without marked pulmonary injury or inflammation. We hypothesized that acute ufCP exposure of 13 months old Spontaneously Hypertensive (SH) rats will cause differential effects on the lung and hea...

  2. Strategies for prevention of acute kidney injury in cardiac surgery: an integrative review

    PubMed Central

    Santana-Santos, Eduesley; Marcusso, Marila Eduara Fátima; Rodrigues, Amanda Oliveira; de Queiroz, Fernanda Gomes; de Oliveira, Larissa Bertacchini; Rodrigues, Adriano Rogério Baldacin; Palomo, Jurema da Silva Herbas

    2014-01-01

    Acute kidney injury is a common complication after cardiac surgery and is associated with increased morbidity and mortality and increased length of stay in the intensive care unit. Considering the high prevalence of acute kidney injury and its association with worsened prognosis, the development of strategies for renal protection in hospitals is essential to reduce the associated high morbidity and mortality, especially for patients at high risk of developing acute kidney injury, such as patients who undergo cardiac surgery. This integrative review sought to assess the evidence available in the literature regarding the most effective interventions for the prevention of acute kidney injury in patients undergoing cardiac surgery. To select the articles, we used the CINAHL and MedLine databases. The sample of this review consisted of 16 articles. After analyzing the articles included in the review, the results of the studies showed that only hydration with saline has noteworthy results in the prevention of acute kidney injury. The other strategies are controversial and require further research to prove their effectiveness. PMID:25028954

  3. Cardiac Gab1 deletion leads to dilated cardiomyopathy associated with mitochondrial damage and cardiomyocyte apoptosis.

    PubMed

    Zhao, J; Yin, M; Deng, H; Jin, F Q; Xu, S; Lu, Y; Mastrangelo, M A; Luo, H; Jin, Z G

    2016-04-01

    A vital step in the development of heart failure is the transition from compensatory cardiac hypertrophy to decompensated dilated cardiomyopathy (DCM) during cardiac remodeling under mechanical or pathological stress. However, the molecular mechanisms underlying the development of DCM and heart failure remain incompletely understood. In the present study, we investigate whether Gab1, a scaffolding adaptor protein, protects against hemodynamic stress-induced DCM and heat failure. We first observed that the protein levels of Gab1 were markedly reduced in hearts from human patients with DCM and from mice with experimental viral myocarditis in which DCM developed. Next, we generated cardiac-specific Gab1 knockout mice (Gab1-cKO) and found that Gab-cKO mice developed DCM in hemodynamic stress-dependent and age-dependent manners. Under transverse aorta constriction (TAC), Gab1-cKO mice rapidly developed decompensated DCM and heart failure, whereas Gab1 wild-type littermates exhibited adaptive left ventricular hypertrophy without changes in cardiac function. Mechanistically, we showed that Gab1-cKO mouse hearts displayed severe mitochondrial damages and increased cardiomyocyte apoptosis. Loss of cardiac Gab1 in mice impaired Gab1 downstream MAPK signaling pathways in the heart under TAC. Gene profiles further revealed that ablation of Gab1 in heart disrupts the balance of anti- and pro-apoptotic genes in cardiomyocytes. These results demonstrate that cardiomyocyte Gab1 is a critical regulator of the compensatory cardiac response to aging and hemodynamic stress. These findings may provide new mechanistic insights and potential therapeutic target for DCM and heart failure.

  4. Cell and gene therapy for arrhythmias: Repair of cardiac conduction damage

    PubMed Central

    Xiao, Yong-Fu

    2011-01-01

    Action potentials generated in the sinoatrial node (SAN) dominate the rhythm and rate of a healthy human heart. Subsequently, these action potentials propagate to the whole heart via its conduction system. Abnormalities of impulse generation and/or propagation in a heart can cause arrhythmias. For example, SAN dysfunction or conduction block of the atrioventricular node can lead to serious bradycardia which is currently treated with an implanted electronic pacemaker. On the other hand, conduction damage may cause reentrant tachyarrhythmias which are primarily treated pharmacologically or by medical device-based therapies, including defibrillation and tissue ablation. However, drug therapies sometimes may not be effective or are associated with serious side effects. Device-based therapies for cardiac arrhythmias, even with well developed technology, still face inadequacies, limitations, hardware complications, and other challenges. Therefore, scientists are actively seeking other alternatives for antiarrhythmic therapy. In particular, cells and genes used for repairing cardiac conduction damage/defect have been investigated in various studies both in vitro and in vivo. Despite the complexities of the excitation and conduction systems of the heart, cell and gene-based strategies provide novel alternatives for treatment or cure of cardiac arrhythmias. This review summarizes some highlights of recent research progress in this field. PMID:22783301

  5. Acute sun damage and photoprotective responses in whales.

    PubMed

    Martinez-Levasseur, Laura M; Gendron, Diane; Knell, Rob J; O'Toole, Edel A; Singh, Manuraj; Acevedo-Whitehouse, Karina

    2011-05-22

    Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife.

  6. β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury.

    PubMed

    Kim, Ki-Seok; Abraham, Dennis; Williams, Barbara; Violin, Jonathan D; Mao, Lan; Rockman, Howard A

    2012-10-15

    Pharmacological blockade of the ANG II type 1 receptor (AT1R) is a common therapy for treatment of congestive heart failure and hypertension. Increasing evidence suggests that selective engagement of β-arrestin-mediated AT1R signaling, referred to as biased signaling, promotes cardioprotective signaling. Here, we tested the hypothesis that a β-arrestin-biased AT1R ligand TRV120023 would confer cardioprotection in response to acute cardiac injury compared with the traditional AT1R blocker (ARB), losartan. TRV120023 promotes cardiac contractility, assessed by pressure-volume loop analyses, while blocking the effects of endogenous ANG II. Compared with losartan, TRV120023 significantly activates MAPK and Akt signaling pathways. These hemodynamic and biochemical effects were lost in β-arrestin-2 knockout (KO) mice. In response to cardiac injury induced by ischemia reperfusion injury or mechanical stretch, pretreatment with TRV120023 significantly diminishes cell death compared with losartan, which did not appear to be cardioprotective. This cytoprotective effect was lost in β-arrestin-2 KO mice. The β-arrestin-biased AT1R ligand, TRV120023, has cardioprotective and functional properties in vivo, which are distinct from losartan. Our data suggest that this novel class of drugs may provide an advantage over conventional ARBs by supporting cardiac function and reducing cellular injury during acute cardiac injury.

  7. Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension.

    PubMed

    Milazzo, Valeria; Maule, Simona; Di Stefano, Cristina; Tosello, Francesco; Totaro, Silvia; Veglio, Franco; Milan, Alberto

    2015-12-01

    Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m(2), P=0.59) and carotid-femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four-hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.

  8. Ichthyophonus-induced cardiac damage: a mechanism for reduced swimming stamina in salmonids

    USGS Publications Warehouse

    Kocan, R.; LaPatra, S.; Gregg, J.; Winton, J.; Hershberger, P.

    2006-01-01

    Swimming stamina, measured as time-to-fatigue, was reduced by approximately two-thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of Ichthyophonus infection was most severe in cardiac muscle but multiple organs were infected to a lesser extent. The mean heart weight of infected fish was 40% greater than that of uninfected fish, the result of parasite biomass, infiltration of immune cells and fibrotic (granuloma) tissue surrounding the parasite. Diminished swimming stamina is hypothesized to be due to cardiac failure resulting from the combination of parasite-damaged heart muscle and low myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in Ichthyophonus-infected salmonids could explain the poor performance previously reported for wild Chinook and sockeye salmon stocks during their spawning migration. ?? 2006 Blackwell Publishing Ltd.

  9. TGF-{beta}{sub 1}-induced cardiac myofibroblasts are nonproliferating functional cells carrying DNA damages

    SciTech Connect

    Petrov, Victor V. Pelt, Jos F. van; Vermeesch, Joris R.; Van Duppen, Viktor J.; Vekemans, Katrien; Fagard, Robert H.; Lijnen, Paul J.

    2008-04-15

    TGF-{beta}{sub 1} induces differentiation and total inhibition of cardiac MyoFb cell division and DNA synthesis. These effects of TGF-{beta}{sub 1} are irreversible. Inhibition of MyoFb proliferation is accompanied with the expression of Smad1, Mad1, p15Ink4B and total inhibition of telomerase activity. Surprisingly, TGF-{beta}{sub 1}-activated MyoFbs are growth-arrested not only at G1-phase but also at S-phase of the cell cycle. Staining with TUNEL indicates that these cells carry DNA damages. However, the absolute majority of MyoFbs are non-apoptotic cells as established with two apoptosis-specific methods, flow cytometry and caspase-dependent cleavage of cytokeratin 18. Expression in MyoFbs of proliferative cell nuclear antigen even in the absence of serum confirms that these MyoFbs perform repair of DNA damages. These results suggest that TGF-{beta}{sub 1}-activated MyoFbs can be growth-arrested by two checkpoints, the G1/S checkpoint, which prevents cells from entering S-phase and the intra-S checkpoint, which is activated by encountering DNA damage during the S phase or by unrepaired damage that escapes the G1/S checkpoint. Despite carrying of the DNA damages TGF-{beta}{sub 1}-activated MyoFbs are highly functional cells producing lysyl oxidase and contracting the collagen matrix.

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

    SciTech Connect

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

    2010-07-09

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

  11. National Heart Attack Alert Program position paper: chest pain centers and programs for the evaluation of acute cardiac ischemia.

    PubMed

    Zalenski, R J; Selker, H P; Cannon, C P; Farin, H M; Gibler, W B; Goldberg, R J; Lambrew, C T; Ornato, J P; Rydman, R J; Steele, P

    2000-05-01

    The National Heart Attack Alert Program (NHAAP), which is coordinated by the National Heart, Lung, and Blood Institute (NHLBI), promotes the early detection and optimal treatment of patients with acute myocardial infarction and other acute coronary ischemic syndromes. The NHAAP, having observed the development and growth of chest pain centers in emergency departments with special interest, created a task force to evaluate such centers and make recommendations pertaining to the management of patients with acute cardiac ischemia. This position paper offers recommendations to assist emergency physicians in EDs, including those with chest pain centers, in providing comprehensive care for patients with acute cardiac ischemia. PMID:10783408

  12. Acute dissociation and cardiac reactivity to script-driven imagery in trauma-related disorders

    PubMed Central

    Sack, Martin; Cillien, Melanie; Hopper, James W.

    2012-01-01

    Background Potential acute protective functions of dissociation include modulation of stress-induced psychophysiological arousal. This study was designed to explore whether acute dissociative reactions during a stress experiment would override the effects of reexperiencing. Methods Psychophysiological reactions during exposure to script-driven trauma imagery were studied in relation to acute responses of reexperiencing and dissociative symptoms in 61 patients with histories of exposure to a variety of traumas. Acute symptomatic responses were assessed with the Responses to Script-Driven Imagery Scale (RSDI), and participants were divided into four groups by median splits of RSDI reexperiencing and dissociation subscale scores. Results In a comparison of the high RSDI reexperiencing groups with low versus high acute dissociative symptoms, the high dissociators exhibited significantly lower heart rate (HR) during trauma script and a significantly smaller script-induced decrease in parasympathetic cardiac activity. HR reactivity to the trauma script was negatively correlated with acute dissociative symptom severity. Conclusions Acute dissociative reactions are a potential moderator of response to experimental paradigms investigating psychologically traumatized populations. We therefore suggest that future research on psychophysiological stress reactions in traumatized samples should routinely assess for acute dissociative symptoms. PMID:23198029

  13. Acute effects of carbon monoxide on cardiac electrical stability. Research report, Sep 85-Jul 88

    SciTech Connect

    Verrier, R.L.; Mills, A.K.; Skornik, W.A.

    1990-01-01

    The objective of the project was to determine the effects of acute carbon monoxide exposure on cardiac electrical stability in the normal and ischemic heart of anesthetized and conscious dogs. Exposure (90 to 120 minutes) to relatively high levels of carbon monoxide, leading to carboxyhemoglobin concentrations of up to 20 percent, was without significant effect on ventricular electrical stability in laboratory dogs. This appears to be the case in the acutely ischemic heart as well as in the normal heart. Using a model involving partial coronary artery stenosis, no changes were found in either the cycle frequency of coronary blood flow oscillations or in platelet aggregability during carbon monoxide exposure. Also examined were the effects of carbon monoxide exposure in the conscious state in order to take into consideration possible adverse consequences mediated by the central nervous system. The study found no adverse effects on the cardiac-excitable properties in response to either a 2-hour- or 24-hour-exposure paradigm.

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

    PubMed Central

    Kališnik, Jurij Matija

    2016-01-01

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

  15. Risk prediction of acute kidney injury in cardiac surgery and prevention using aminophylline.

    PubMed

    Mahaldar, A R; Sampathkumar, K; Raghuram, A R; Kumar, S; Ramakrishnan, M; Mahaldar, D A C

    2012-05-01

    The incidence of acute kidney injury (AKI) after cardiac surgery remains high. The nonspecific adenosine receptor antagonist aminophylline has been shown to confer benefit in experimental and clinical acute renal failure (ARF) due to ischemia, contrast media, and various nephrotoxic agents. We conducted a prospective open label trial to assess the effectiveness of aminophylline for prevention of renal impairment after cardiac surgery. One hundred and thirty-eight patients undergoing cardiac surgery were risk stratified as per Cleveland score to assess for prediction of AKI. Sixty-three patients received a bolus aminophylline of 5 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h for up to 72 h, while 75 patients received usual postoperative care. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery and the glomerular filtration rate estimated using Cockcroft and Gault formula. Hourly urine output was recorded and patients assigned to respective RIFLE stage of AKI. Cleveland score ≥6 was associated with higher incidence of AKI: I and F (P<0.005). Number needed to treat, an insight into the clinical relevance of a specific treatment, is 8. These results suggest that the perioperative use of aminophylline infusion is associated with lower incidence of deterioration in renal function following cardiac surgery in high-risk patients. PMID:23087551

  16. Risk prediction of acute kidney injury in cardiac surgery and prevention using aminophylline

    PubMed Central

    Mahaldar, A. R.; Sampathkumar, K.; Raghuram, A. R.; Kumar, S.; Ramakrishnan, M.; Mahaldar, D. A. C.

    2012-01-01

    The incidence of acute kidney injury (AKI) after cardiac surgery remains high. The nonspecific adenosine receptor antagonist aminophylline has been shown to confer benefit in experimental and clinical acute renal failure (ARF) due to ischemia, contrast media, and various nephrotoxic agents. We conducted a prospective open label trial to assess the effectiveness of aminophylline for prevention of renal impairment after cardiac surgery. One hundred and thirty-eight patients undergoing cardiac surgery were risk stratified as per Cleveland score to assess for prediction of AKI. Sixty-three patients received a bolus aminophylline of 5 mg/kg and a subsequent continuous infusion of 0.25 mg/kg/h for up to 72 h, while 75 patients received usual postoperative care. Serum creatinine concentrations were measured preoperatively and daily until day 5 after surgery and the glomerular filtration rate estimated using Cockcroft and Gault formula. Hourly urine output was recorded and patients assigned to respective RIFLE stage of AKI. Cleveland score ≥6 was associated with higher incidence of AKI: I and F (P<0.005). Number needed to treat, an insight into the clinical relevance of a specific treatment, is 8. These results suggest that the perioperative use of aminophylline infusion is associated with lower incidence of deterioration in renal function following cardiac surgery in high-risk patients. PMID:23087551

  17. The Complex Role of iNOS in Acutely-Rejecting Cardiac Transplants

    PubMed Central

    Pieper, Galen M.; Roza, Allan M.

    2008-01-01

    This review summarizes the evidence for a detrimental role of nitric oxide (NO) derived from inducible NO synthase (iNOS) and/or reactive nitrogen species such as peroxynitrite in acutely-rejecting cardiac transplants. In chronic cardiac transplant rejection, iNOS may have an opposing beneficial component. The purpose of this review is primarily to address issues related to acute rejection which is a recognized risk factor for chronic rejection. The evidence for a detrimental role is based upon strategies involving non-selective NOS inhibitors, NO neutralizers, selective iNOS inhibitors and iNOS gene deletion in rodent models of cardiac rejection. The review is discussed in the context of the impact on various components including graft survival, histological rejection and cardiac function which may contribute in toto to the process of graft rejection. Possible limitations of each strategy are discussed in order to understand better the variance in published findings including issues related to the potential importance of cell localization of iNOS expression. Finally, the concept of a dual role of NO and its down-stream product, peroxynitrite, in rejection vs. immune regulation is discussed. PMID:18291116

  18. Galectin-1 Prevents Infection and Damage Induced by Trypanosoma cruzi on Cardiac Cells

    PubMed Central

    Benatar, Alejandro F.; García, Gabriela A.; Bua, Jacqeline; Cerliani, Juan P.; Postan, Miriam; Tasso, Laura M.; Scaglione, Jorge; Stupirski, Juan C.; Toscano, Marta A.

    2015-01-01

    Background Chronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection. Methodology and Principal Findings Here we investigated the contribution of galectin–1 (Gal–1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL–1 cardiac cells to Gal–1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal–1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL–1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal–1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal–1 to the cell surface. Consistent with these data, Gal–1 deficient (Lgals1-/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain. Conclusion/Significance Our results indicate that Gal–1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions. PMID:26451839

  19. A new model to predict acute kidney injury requiring renal replacement therapy after cardiac surgery

    PubMed Central

    Pannu, Neesh; Graham, Michelle; Klarenbach, Scott; Meyer, Steven; Kieser, Teresa; Hemmelgarn, Brenda; Ye, Feng; James, Matthew

    2016-01-01

    Background: Acute kidney injury after cardiac surgery is associated with adverse in-hospital and long-term outcomes. Novel risk factors for acute kidney injury have been identified, but it is unknown whether their incorporation into risk models substantially improves prediction of postoperative acute kidney injury requiring renal replacement therapy. Methods: We developed and validated a risk prediction model for acute kidney injury requiring renal replacement therapy within 14 days after cardiac surgery. We used demographic, and preoperative clinical and laboratory data from 2 independent cohorts of adults who underwent cardiac surgery (excluding transplantation) between Jan. 1, 2004, and Mar. 31, 2009. We developed the risk prediction model using multivariable logistic regression and compared it with existing models based on the C statistic, Hosmer–Lemeshow goodness-of-fit test and Net Reclassification Improvement index. Results: We identified 8 independent predictors of acute kidney injury requiring renal replacement therapy in the derivation model (adjusted odds ratio, 95% confidence interval [CI]): congestive heart failure (3.03, 2.00–4.58), Canadian Cardiovascular Society angina class III or higher (1.66, 1.15–2.40), diabetes mellitus (1.61, 1.12–2.31), baseline estimated glomerular filtration rate (0.96, 0.95–0.97), increasing hemoglobin concentration (0.85, 0.77–0.93), proteinuria (1.65, 1.07–2.54), coronary artery bypass graft (CABG) plus valve surgery (v. CABG only, 1.25, 0.64–2.43), other cardiac procedure (v. CABG only, 3.11, 2.12–4.58) and emergent status for surgery booking (4.63, 2.61–8.21). The 8-variable risk prediction model had excellent performance characteristics in the validation cohort (C statistic 0.83, 95% CI 0.79–0.86). The net reclassification improvement with the prediction model was 13.9% (p < 0.001) compared with the best existing risk prediction model (Cleveland Clinic Score). Interpretation: We have developed

  20. The protective role of neocuproine against cardiac damage in isolated perfused rat hearts.

    PubMed

    Applebaum, Y J; Kuvin, J; Borman, J B; Uretzky, G; Chevion, M

    1990-01-01

    The effect of neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where hydrogen peroxide-induced damage was studied, neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where ischemia/reperfusion-induced arrhythmias were studied, neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible ventricular fibrillation, by decreasing the duration of ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt. Free radicals have already been implicated as causative agents in cardiac injury resulting from either hydrogen peroxide or ischemia followed by reperfusion. Additionally, iron and copper have already been shown to drastically exacerbate the injurious effects of free radicals. Thus, the results reported here with neocuproine, a highly effective chelator for both iron and copper, as well as with adventitious copper and with the combination of neocuproine and copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by free radicals.

  1. Acute Targeting of General Transcription Factor IIB Restricts Cardiac Hypertrophy via Selective Inhibition of Gene Transcription

    PubMed Central

    Sayed, Danish; Yang, Zhi; He, Minzhen; Pfleger, Jessica M.; Abdellatif, Maha

    2014-01-01

    Background We previously reported that specialized and housekeeping genes are differentially regulated via de novo recruitment and pause-release of RNA polymerase II (pol II), respectively, during cardiac hypertrophy. However, the significance of this finding remains to be examined. Therefore, the purpose of this study was to determine the mechanisms that differentially regulate these gene groups and exploit them for therapeutic targeting. Methods and Results Here we show that general transcription factor IIB (TFIIB) and cyclin-dependent kinase 9 are upregulated during hypertrophy, both targeted by miR-1, and play preferential roles in regulating those two groups of genes. Chromatin immunoprecipitation-sequencing reveals that TFIIB is constitutively bound to all paused, housekeeping, promoters, whereas, de novo recruitment of TFIIB and pol II is required for specialized genes that are induced during hypertrophy. We exploited this dichotomy to acutely inhibit induction of the latter set, which encompasses cardiomyopathy, immune reaction, and extracellular matrix genes, using locked nucleic acid (LNA)-modified antisense TFIIB oligonucleotide treatment. This resulted in suppression of all specialized genes, while sparing the housekeeping ones, and, thus, attenuated pathological hypertrophy. Conclusions The data for the first time reveal distinct general transcription factor IIB dynamics that regulate specialized vs. housekeeping genes during cardiac hypertrophy. Thus, by acutely targeting TFIIB we were able to selectively inhibit the former set of genes and ameliorate pressure overload hypertrophy. We also demonstrate the feasibility of acutely and reversibly targeting cardiac mRNA for therapeutic purposes using LNA-modified antisense oligonucleotides. PMID:25398966

  2. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    PubMed

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

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

    PubMed

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

    2015-02-01

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

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

    PubMed Central

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

    2015-01-01

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

  5. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-03-01

    Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective

  6. Cardiac arrhythmias the first month after acute traumatic spinal cord injury

    PubMed Central

    Bartholdy, Kim; Biering-Sørensen, Tor; Malmqvist, Lasse; Ballegaard, Martin; Krassioukov, Andrei; Hansen, Birgitte; Svendsen, Jesper Hastrup; Kruse, Anders; Welling, Karen-Lise; Biering-Sørensen, Fin

    2014-01-01

    Objective Cardiovascular complications including cardiac arrest and arrhythmias remain a clinical challenge in the management of acute traumatic spinal cord injury (SCI). Still, there is a lack of knowledge regarding the characteristics of arrhythmias in patients with acute traumatic SCI. The aim of this prospective observational study was to investigate the occurrence of cardiac arrhythmias and cardiac arrests in patients with acute traumatic SCI. Methods As early as possible after SCI 24-hour Holter monitoring was performed. Additional Holter recordings were performed 1, 2, 3, and 4 weeks after SCI. Furthermore, 12-lead electrocardiograms (ECGs) were obtained shortly after SCI and at 4 weeks. Results Thirty patients were included. Bradycardia (heart rate (HR) <50 b.p.m.) was present in 17–35% of the patients with cervical (C1–C8) SCI (n = 24) within the first 14 days. In the following 14 days, the occurrence was 22–32%. Bradycardia in the thoracic (Th1–Th12) SCI group (n = 6) was present in 17–33% during the observation period. The differences between the two groups were not statistically significant. The mean minimum HR was significantly lower in the cervical group compared with the thoracic group both on 12-lead ECGs obtained shortly after SCI (P = 0.030) and at 4 weeks (P = 0.041). Conclusion Many patients with cervical SCI experience arrhythmias such as bradycardia, sinus node arrest, supraventricular tachycardia, and more rarely cardiac arrest the first month after SCI. Apart from sinus node arrests and limited bradycardia, no arrhythmias were seen in patients with thoracic SCI. Standard 12-lead ECGs will often miss the high prevalence these arrhythmias have. PMID:24559419

  7. Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin.

    PubMed

    Mukherjee, Debasri; Ghosh, Arnab K; Dutta, Mousumi; Mitra, Elina; Mallick, Sanjaya; Saha, Bhaskar; Reiter, Russel J; Bandyopadhyay, Debasish

    2015-04-01

    Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury. PMID:25652673

  8. Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS).

    PubMed

    Mukhopadhyay, Sanjay; Parambil, Joseph G

    2012-10-01

    Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF).

  9. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  10. Intricacies of cardiac damage in coxsackievirus B3 infection: Implications for therapy

    PubMed Central

    Reddy, Jay

    2015-01-01

    Heart disease is the leading cause of death in humans, and myocarditis is one predominant cause of heart failure in young adults. Patients affected with myocarditis can develop dilated cardiomyopathy (DCM), a common reason for heart transplantation, which to date is the only viable option for combatting DCM. Myocarditis/DCM patients show antibodies to coxsackievirus B (CVB)3 and cardiac antigens, suggesting a role for CVB-mediated autoimmunity in the disease pathogenesis; however, a direct causal link remains to be determined clinically. Experimentally, myocarditis can be induced in susceptible strains of mice using the human isolates of CVB3, and the disease pathogenesis of postinfectious myocarditis resembles that of human disease, making the observations made in animals relevant to humans. In this review, we discuss the complex nature of CVB3-induced myocarditis as it relates to the damage caused by both the virus and the host's response to infection. Based on recent data we obtained in the mouse model of CVB3 infection, we provide evidence to suggest that CVB3 infection accompanies the generation of cardiac myosin-specific CD4 T cells that can transfer the disease to naïve recipients. The therapeutic implications of these observations are also discussed. PMID:25449464

  11. Acute cardiac sympathetic disruption and left ventricular wall motion abnormality in takotsubo syndrome.

    PubMed

    Y-Hassan, Shams

    2015-03-01

    Takotsubo syndrome (TS) is characterized by a unique pattern of transient circumferential left ventricular wall motion abnormality (LVWMA). The LVWMA in TS may be localized to the apical, mid-apical, mid-ventricular, mid-basal or basal regions of the left ventricle. Focal and generialized (global) LVWMA have also been reported. In the acute phase of TS, the hyperkinetic valve-like motion of the basal segments and/or the hyperkinetic slingshot-like motion of the apical segments combined with the firm stunned a-, hypokinetic segments result in a conspicuous left ventricular ballooning during systole. The LVWMA in TS follows most probably the local cardiac sympathetic nerve distribution and caused by local cardiac sympathetic disruption and noradrenaline spillover. PMID:25535745

  12. Inflammatory Cytokines as Risk Factors for Mortality After Acute Cardiac Events

    PubMed Central

    Hamzic-Mehmedbasic, Aida

    2016-01-01

    Introduction: Inflammatory markers have been identified as potential indicators of future adverse outcome after acute cardiac events. Aim: This study aimed to analyze baseline inflammatory cytokines levels in patients with acute heart failure (AHF) and/or acute coronary syndrome (ACS) according to survival. The main objective was to identify risk factors for mortality after an episode of AHF and/or ACS. Methods: In this prospective longitudinal study 75 patients with the diagnosis of AHF and/or ACS were enrolled. Baseline laboratory and clinical data were retrieved. Serum and urine interleukin-6 (IL-6) and interleukin-18 (IL-18) levels, plasma B-type natriuretic peptide (BNP) and serum cystatin C values were determined. The primary outcome was in-hospital mortality while secondary outcome was six-month mortality. Results: Median serum and urine IL-6 levels, serum and urine IL-18 levels, as well as median concentrations of plasma BNP and serum cystatin C, were significantly increased in deceased in comparison to surviving AHF and/or ACS patients. Univariate Cox regression analysis identified serum IL-6, serum IL-18, urine IL-6, urine IL-18 as well as serum cystatin C and Acute Physiology and Chronic Health Evaluation (APACHE) II score as risk factors for mortality after an episode of AHF and/or ACS. Multivariate Cox regression analysis revealed that only serum IL-6 is the independent risk factor for mortality after acute cardiac events (HR 61.7, 95% CI 2.1-1851.0; p=0.018). Conclusion: Present study demonstrated the strong prognostic value of serum IL-6 in predicting mortality of patients with AHF and/or ACS. PMID:27703283

  13. Methamphetamine causes acute hyperthermia-dependent liver damage.

    PubMed

    Halpin, Laura E; Gunning, William T; Yamamoto, Bryan K

    2013-10-01

    Methamphetamine-induced neurotoxicity has been correlated with damage to the liver but this damage has not been extensively characterized. Moreover, the mechanism by which the drug contributes to liver damage is unknown. This study characterizes the hepatocellular toxicity of methamphetamine and examines if hyperthermia contributes to this liver damage. Livers from methamphetamine-treated rats were examined using electron microscopy and hematoxylin and eosin staining. Methamphetamine increased glycogen stores, mitochondrial aggregation, microvesicular lipid, and hydropic change. These changes were diffuse throughout the hepatic lobule, as evidenced by a lack of hematoxylin and eosin staining. To confirm if these changes were indicative of damage, serum aspartate and alanine aminotransferase were measured. The functional significance of methamphetamine-induced liver damage was also examined by measuring plasma ammonia. To examine the contribution of hyperthermia to this damage, methamphetamine-treated rats were cooled during and after drug treatment by cooling their external environment. Serum aspartate and alanine aminotransferase, as well as plasma ammonia were increased concurrently with these morphologic changes and were prevented when methamphetamine-induced hyperthermia was blocked. These findings support that methamphetamine produces changes in hepatocellular morphology and damage persisting for at least 24 h after drug exposure. At this same time point, methamphetamine treatment significantly increases plasma ammonia concentrations, consistent with impaired ammonia metabolism and functional liver damage. Methamphetamine-induced hyperthermia contributes significantly to the persistent liver damage and increases in peripheral ammonia produced by the drug. PMID:25505562

  14. Selective Blockade of Periostin Exon 17 Preserves Cardiac Performance in Acute Myocardial Infarction.

    PubMed

    Taniyama, Yoshiaki; Katsuragi, Naruto; Sanada, Fumihiro; Azuma, Junya; Iekushi, Kazuma; Koibuchi, Nobutaka; Okayama, Keita; Ikeda-Iwabu, Yuka; Muratsu, Jun; Otsu, Rei; Rakugi, Hiromi; Morishita, Ryuichi

    2016-02-01

    We previously reported that overexpression of full-length periostin, Pn-1, resulted in ventricular dilation with enhanced interstitial collagen deposition in a rat model. However, other reports have documented that the short-form splice variants Pn-2 (lacking exon 17) and Pn-4 (lacking exons 17 and 21) promoted cardiac repair by angiogenesis and prevented cardiac rupture after acute myocardial infarction. The apparently differing findings from those reports prompted us to use a neutralizing antibody to selectively inhibit Pn-1 by blockade of exon 17 in a rat acute myocardial infarction model. Administration of Pn neutralizing antibody resulted in a significant decrease in the infarcted and fibrotic areas of the myocardium, which prevented ventricular wall thinning and dilatation. The inhibition of fibrosis by Pn neutralizing antibody was associated with a significant decrease in gene expression of fibrotic markers, including collagen I, collagen III, and transforming growth factor-β1. Importantly, the number of α-smooth muscle actin-positive myofibroblasts was significantly reduced in the hearts of animals treated with Pn neutralizing antibody, whereas cardiomyocyte proliferation and angiogenesis were comparable in the IgG and neutralizing antibody groups. Moreover, the level of Pn-1 expression was significantly correlated with the severity of myocardial infarction. In addition, Pn-1, but not Pn-2 or Pn-4, inhibited fibroblast and myocyte attachment, which might account for the cell slippage observed during cardiac remodeling. Collectively, these results indicate that therapeutics that specifically inhibit Pn exon-17, via a neutralizing antibody or drug, without suppressing other periostin variants might offer a new class of medication for the treatment of acute myocardial infarction patients.

  15. Serum and salivary cardiac analytes in acute myocardial infarction related to oral health status

    NASA Astrophysics Data System (ADS)

    Ebersole, Jeffrey L.; Kryscio, Richard J.; Campbell, Charles; Kinane, Denis F.; McDevitt, John T.; Christodoulides, Nicolaos; Floriano, Pierre N.; Miller, Craig S.

    2014-06-01

    With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient's oral inflammation status confound biomarker levels used in diagnosis of acute myocardial infarction (AMI). The results demonstrated that multiple serum biomarkers and a few salivary biomarkers reflected the cardiac event. Importantly, oral health of the individual had minimal impact on the validity of the serum or salivary biomarker effectiveness.

  16. Approaches to Improving Cardiac Structure and Function During and After an Acute Myocardial Infarction: Acute and Chronic Phases.

    PubMed

    Kloner, Robert A; Dai, Wangde; Hale, Sharon L; Shi, Jianru

    2016-07-01

    While progress has been made in improving survival following myocardial infarction, this injury remains a major source of mortality and morbidity despite modern reperfusion therapy. While one approach has been to develop therapies to reduce lethal myocardial cell reperfusion injury, this concept has not translated to the clinics, and several recent negative clinical trials raise the question of whether reperfusion injury is important in humans undergoing reperfusion for acute ST segment elevation myocardial infarction. Therapy aimed at reducing myocardial cell death while the myocytes are still ischemic is more likely to further reduce myocardial infarct size. Developing new therapies to further reduce left ventricular remodeling after the acute event is another approach to preserving structure and function of the heart after infarction. Such therapy may include chronic administration of pharmacologic agents and/or therapies developed from the field of regenerative cardiology, including cellular or non-cellular materials such as extracellular matrix. The optimal therapy will be to administer agents that both reduce myocardial infarct size in the acute phase of infarction as well as reduce adverse left ventricular remodeling during the chronic or healing phase of myocardial infarction. Such a dual approach will help optimize the preservation of both cardiac structure and function.

  17. Ultra-rapid manufacturing of engineered epicardial substitute to regenerate cardiac tissue following acute ischemic injury.

    PubMed

    Serpooshan, Vahid; Ruiz-Lozano, Pilar

    2014-01-01

    Considering the impaired regenerative capacity of adult mammalian heart tissue, cardiovascular tissue engineering aims to create functional substitutes that can restore the structure and function of the damaged cardiac tissue. The success of cardiac regenerative therapies has been limited mainly due to poor control on the structure and properties of the tissue substitute, lack of vascularization, and immunogenicity. In this study we introduce a new approach to rapidly engineer dense biomimetic scaffolds consisting of type I collagen, to protect the heart against severe ischemic injury. Scaffold biomechanical properties are adjusted to mimic embryonic epicardium which is shown to be optimal to support cardiomyocyte contractile work. Moreover, the designed patch can serve as a delivery device for targeted, controlled release of cells or therapeutic macromolecules into the lesion area.

  18. Post-Acute Care Services Received by Older Adults Following a Cardiac Event: A Population-Based Analysis

    PubMed Central

    Xu, Fang; Zullo, Melissa; Shishehbor, Mehdi; Moore, Shirley M.; Rimm, Alfred A.

    2010-01-01

    Background Post-acute care (PAC) is available for older adults who need additional services after hospitalization for acute cardiac events. With the aging population and an increase in the prevalence of cardiac disease, it is important to determine current PAC use for cardiac patients to assist health care workers to meet the needs of older cardiac patients. The purpose of this study was to determine the current PAC use and factors associated with PAC use for older adults following hospitalization for a cardiac event that includes coronary artery bypass graph (CABG) and valve surgeries, myocardial infarction (MI), percutaneous coronary intervention (PCI), and heart failure (HF). Methods and Results A cross-sectional design and the 2003 Medicare Part A database were used for this study. The sample (n=1,493,521) consisted of patients aged 65 years and older discharged after their first cardiac event. Multinomial logistic regression was used to examine factors associated with PAC use. Overall, PAC use was 55% for cardiac valve surgery, 50% for MI, 45% for HF, 44% for CABG, and 5% for PCI. Medical patients use more skilled nursing facility care and surgical patients use more home health care. Only 0.1–3.4% of the cardiac patients use intermediate rehabilitation facilities. Compared to those who do not use PAC, those who use home health care and skilled nursing facility care are older, female, have a longer hospital length of stay, and more comorbidity. Asians, Hispanics and Native Americans were less likely to use PAC after hospitalization for an MI or HF. Conclusions The current rate of PAC use indicates that almost half of non-disabled Medicare patients discharged from the hospital following a cardiac event use one of these services. Healthcare professionals can increase PAC use for Asians, Hispanics and Native Americans by including culturally targeted communication. Optimizing recovery for cardiac patients who use PAC may require focused cardiac rehabilitation

  19. Prognostic implications of cardiac scintigraphic parameters obtained in the early phase of acute myocardial infarction

    SciTech Connect

    Suzuki, A.; Matsushima, H.; Satoh, A.; Hayashi, H.; Sotobata, I.

    1988-06-01

    A cohort of 76 patients with acute myocardial infarction was studied with infarct-avid scan, radionuclide ventriculography, and thallium-201 myocardial perfusion scintigraphy. Infarct area, left ventricular ejection fraction, and defect score were calculated as radionuclide indices of the extent of myocardial infarction. The correlation was studied between these indices and cardiac events (death, congestive heart failure, postinfarction angina, and recurrence of myocardial infarction) in the first postinfarction year. High-risk patients (nonsurvivors and patients who developed heart failure) had a larger infarct area, a lower left ventricular ejection fraction, and a larger defect score than the others. Univariate linear discriminant analysis was done to determine the optimal threshold of these parameters for distinguishing high-risk patients from others. Radionuclide parameters obtained in the early phase of acute myocardial infarction were useful for detecting both patients with grave complications and those with poor late prognosis during a mean follow-up period of 2.6 years.

  20. [Cardiac Angiosarcoma with Acute Myocardial Infarction due to Tumor Embolism;Report of a Case].

    PubMed

    Date, Yusuke; Miyazu, Katsuyuki; Ikeda, Masahiro

    2016-09-01

    We report the case of a 28-year-old man with a rare angiosarcoma complicated by acute myocardial infarction secondary to tumor embolism. He was transported to our emergency unit because of sudden onset of chest pain. The echocardiography showed a 42×60 mm mass in the left ventricle, and the coronary angiography showed embolic occlusion of the proximal left anterior descending and circumflex arteries. Emergent surgical removal of the mass was attempted under cardiopulmonary bypass, concomitant with double coronary artery bypass grafting and mitral valve replacement with a mechanical prosthesis. However, complete tumor excision was impossible. The postoperative pathological examination revealed undifferentiated angiosarcoma. Twenty days after the operation, the patient suffered acute cerebral hemorrhage from a metastatic tumor in the brain. He died at 37 days after the initial cardiac surgery. PMID:27586319

  1. [Preventive antifibrillatory treatment of sudden cardiac death in acute myocardial infarct].

    PubMed

    Thale, J; Gülker, H; Hindricks, G; Haverkamp, W; Pollock, B; Buchwalsky, R

    1988-01-01

    The pathophysiological basis of sudden cardiac death due to ventricular arrhythmias in acute myocardial infarction has been extensively investigated in experimental as well as in some clinical studies. Numerous clinical studies have been performed with the aim to establish the feasibility of antifibrillatory prophylaxis of sudden cardiac death by pretreatment with antiarrhythmic drugs. Using class I-antiarrhythmic drugs the reported findings were contradictory. While the antiarrhythmic efficacy of Lidocaine and other, newer class I-antiarrhythmic drugs is well established, the antifibrillatory effects of these drugs in the early phase of acute myocardial infarction remain uncertain. In clinical studies with the endpoint of mortality in patients at risk, longterm administration of orally effective class I-antiarrhythmic drugs did not prove to be superior to placebo. However, beta-sympatholytic agents have been shown to reduce mortality in patients at risk in several large clinical studies. The basic mechanism seems to be primarily a reduction in sudden cardiac death which is caused predominantly by ventricular fibrillation. The antifibrillatory properties of beta-blockers was demonstrated as well by a reduction in the number of episodes of ventricular fibrillation. The recognition of patients at risk who profit most from chronic beta-blocker therapy remains the main problem when treatment of numerous low-risk patients is avoided. In the ISIS I-study with Atenolol intravenous administration of a beta-blocker in the early phase of acute myocardial infarction has been shown to be beneficial if hemodynamic monitoring, for example using flow-directed heart catherization is performed. In general this does not apply to the treatment with calciumantagonists, especially with Verapamil and Nifedipine. These drugs do not improve prognosis of acute myocardial ischemia, obviously because of hemodynamic side effects. The antifibrillatory efficacy of Verapamil

  2. Impact of cardiac magnet resonance imaging on management of ventricular septal rupture after acute myocardial infarction

    PubMed Central

    Gassenmaier, Tobias; Gorski, Armin; Aleksic, Ivan; Deubner, Nikolas; Weidemann, Frank; Beer, Meinrad

    2013-01-01

    A 74-year-old man was admitted to the cardiac catheterization laboratory with acute myocardial infarction. After successful angioplasty and stent implantation into the right coronary artery, he developed cardiogenic shock the following day. Echocardiography showed ventricular septal rupture. Cardiac magnet resonance imaging (MRI) was performed on the critically ill patient and provided detailed information on size and localization of the ruptured septum by the use of fast MRI sequences. Moreover, the MRI revealed that the ventricular septal rupture was within the myocardial infarction area, which was substantially larger than the rupture. As the patient’s condition worsened, he was intubated and had intra-aortic balloon pump implanted, and extracorporeal membrane oxygenation was initiated. During the following days, the patient’s situation improved, and surgical correction of the ventricular septal defect could successfully be performed. To the best of our knowledge, this case report is the first description of postinfarction ventricular septal rupture by the use of cardiac MRI in an intensive care patient with cardiogenic shock and subsequent successful surgical repair. PMID:23710303

  3. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression.

    PubMed

    Miró-Murillo, Marta; Elorza, Ainara; Soro-Arnáiz, Inés; Albacete-Albacete, Lucas; Ordoñez, Angel; Balsa, Eduardo; Vara-Vega, Alicia; Vázquez, Silvia; Fuertes, Esther; Fernández-Criado, Carmen; Landázuri, Manuel O; Aragonés, Julián

    2011-01-01

    Von Hippel Lindau (Vhl) gene inactivation results in embryonic lethality. The consequences of its inactivation in adult mice, and of the ensuing activation of the hypoxia-inducible factors (HIFs), have been explored mainly in a tissue-specific manner. This mid-gestation lethality can be also circumvented by using a floxed Vhl allele in combination with an ubiquitous tamoxifen-inducible recombinase Cre-ER(T2). Here, we characterize a widespread reduction in Vhl gene expression in Vhl(floxed)-UBC-Cre-ER(T2) adult mice after dietary tamoxifen administration, a convenient route of administration that has yet to be fully characterized for global gene inactivation. Vhl gene inactivation rapidly resulted in a marked splenomegaly and skin erythema, accompanied by renal and hepatic induction of the erythropoietin (Epo) gene, indicative of the in vivo activation of the oxygen sensing HIF pathway. We show that acute Vhl gene inactivation also induced Epo gene expression in the heart, revealing cardiac tissue to be an extra-renal source of EPO. Indeed, primary cardiomyocytes and HL-1 cardiac cells both induce Epo gene expression when exposed to low O(2) tension in a HIF-dependent manner. Thus, as well as demonstrating the potential of dietary tamoxifen administration for gene inactivation studies in UBC-Cre-ER(T2) mouse lines, this data provides evidence of a cardiac oxygen-sensing VHL/HIF/EPO pathway in adult mice.

  4. Acute Mesenteric Ischemia after Cardiac Surgery: An Analysis of 52 Patients

    PubMed Central

    Gucu, Arif; Toktas, Faruk; Erdolu, Burak; Ozyazıcıoglu, Ahmet

    2013-01-01

    Objective. Acute mesenteric ischemia (AMI) is a rare but serious complication after cardiac surgery. The aim of this retrospective study was to evaluate the incidence, outcome, and perioperative risk factors of AMI in the patients undergoing elective cardiac surgery. Methods. From January 2005 to May 2013, all patients who underwent cardiac surgery were screened for participation, and patients with registered gastrointestinal complications were retrospectively reviewed. Univariate analyses were performed. Results. The study included 6013 patients, of which 52 (0.86%) patients suffered from AMI, 35 (67%) of whom died. The control group (150 patients) was randomly chosen from among cases undergoing cardiopulmonary bypass (CPB). Preoperative parameters including age (P = 0.03), renal insufficiency (P = 0.004), peripheral vascular disease (P = 0.04), preoperative inotropic support (P < 0.001), poor left ventricular ejection fraction (P = 0.002), cardiogenic shock (P = 0.003), and preoperative intra-aortic balloon pump (IABP) support (P = 0.05) revealed significantly higher levels in the AMI group. Among intra- and postoperative parameters, CPB time (P < 0.001), dialysis (P = 0.04), inotropic support (P = 0.007), prolonged ventilator time (P < 0.001), and IABP support (P = 0.007) appeared significantly higher in the AMI group than the control group. Conclusions. Prompt diagnosis and early treatment should be initiated as early as possible in any patient suspected of AMI, leading to dramatic reduction in the mortality rate. PMID:24288499

  5. Advances in acute kidney injury associated with cardiac surgery: the unfolding revolution in early detection.

    PubMed

    Wyckoff, Tygh; Augoustides, John G T

    2012-04-01

    Cardiac surgery-associated acute kidney injury (CSA-AKI) is important because it remains common and serious. A major limitation in the management of CSA-AKI has been ongoing delayed diagnosis by standard clinical approaches, including serum creatinine and calculated glomerular filtration rate. Recent advances in the understanding of CSA-AKI have highlighted the utility of novel biomarkers that diagnose CSA-AKI within the first 24 hours. The biomarkers that have been evaluated in clinical trials include neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule 1 and interleukin-18. The biomarker with the greatest clinical promise is NGAL. Although it has multiple advantages over serum creatinine, it is still not the ideal biomarker for CSA-AKI. It is likely that a panel of early biomarkers will be developed to facilitate rapid and reliable detection of CSA-AKI, combining their different characteristics to optimize patient management. Future clinical trials likely will focus on whether these biomarkers predict adverse outcomes independent of serum creatinine fluctuations and whether therapies guided by biomarker profiles improve renal salvage and overall clinical outcomes. Given their clinical utility, these novel biomarkers have been evaluated beyond cardiac surgery for AKI in multiple clinical environments, including the emergency department, the operating room, the cardiac catheterization laboratory, and the intensive care unit. Their integration into clinical practice seems likely in the near future.

  6. Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction

    SciTech Connect

    Leppo, J.A.; O'Brien, J.; Rothendler, J.A.; Getchell, J.D.; Lee, V.W.

    1984-04-19

    To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction.

  7. Role and importance of ultrasound lung comets in acute cardiac care.

    PubMed

    Ricci, Fabrizio; Aquilani, Roberta; Radico, Francesco; Bianco, Francesco; Dipace, Gioacchino Giuseppe; Miniero, Ester; De Caterina, Raffaele; Gallina, Sabina

    2015-04-01

    Lung ultrasonography is an emerging, user-friendly and easy-to-use technique that can be performed quickly at the patient's bedside to evaluate several pathologic conditions affecting the lung. Ultrasound lung comets (ULCs) are an echographic sign of uncertain biophysical characterisation mostly attributed to water-thickened subpleural interlobular septa, but invariably associated with increased extravascular lung water. ULCs have thus been proposed as a complementary tool for the assessment and monitoring of acute heart failure and are now entering into statements in international recommendation documents. Adding lung ultrasonography to conventional echocardiography allows for performing an integrated cardiopulmonary ultrasound examination, and this is an important opportunity for the cardiologist. The technique allows the simultaneous gathering of considerable information about the heart and the lungs to investigate acute and chronic cardio-pulmonary conditions within a non-invasive, radiation-free, single-probe, all-in-one examination. We have here reviewed the pertinent literature on the physical origin of ULCs and on their role and importance in intensive and acute cardiac care settings. We also here propose a new algorithm aimed at implementing evaluation in the diagnostic work-up of patients with suspected acute heart failure. PMID:25267879

  8. Preoperative Low Serum Bicarbonate Levels Predict Acute Kidney Injury After Cardiac Surgery

    PubMed Central

    Jung, Su-Young; Park, Jung Tak; Kwon, Young Eun; Kim, Hyung Woo; Ryu, Geun Woo; Lee, Sul A.; Park, Seohyun; Jhee, Jong Hyun; Oh, Hyung Jung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook

    2016-01-01

    Abstract Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23 mEq/L; group 2 (normal levels) 23 to 24 mEq/L; and group 3 (elevated levels) >24 mEq/L. The primary outcome was the predicated incidence of AKI 48 hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48 hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P < 0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a

  9. Cardiac Autonomic Effects of Acute Exposures to Airborne Particulates in Men and Women

    NASA Technical Reports Server (NTRS)

    Howarth, M. S.; Schlegel, T. T.; Knapp, C. F.; Patwardhan, A. R.; Jenkins, R. A.; Ilgner, R. H.; Evans, J. M.

    2007-01-01

    The aim of this research was to investigate cardiac autonomic changes associated with acute exposures to airborne particulates. Methods: High fidelity 12-lead ECG (CardioSoft, Houston, TX) was acquired from 19 (10 male / 9 female) non-smoking volunteers (age 33.6 +/- 6.6 yrs) during 10 minutes pre-exposure, exposure and post-exposure to environmental tobacco smoke (ETS), cooking oil fumes, wood smoke and sham (water vapor). To control exposure levels, noise, subject activity, and temperature, all studies were conducted inside an environmental chamber. Results: The short-term fractal scaling exponent (Alpha-1) and the ratio of low frequency to high frequency Heart Rate Variability (HRV) powers (LF/HF, a purported sympathetic index) were both higher in males (p<0.017 and p<0.05, respectively) whereas approximate entropy (ApEn) and HF/(LF+HF) (a purported parasympathetic index) were both lower in males (p<0.036, and p<0.044, respectively). Compared to pre-exposure (p<0.0002) and sham exposure (p<0.047), male heart rates were elevated during early ETS post-exposure. Our data suggest that, in addition to tonic HRV gender differences, cardiac responses to some acute airborne particulates are gender related.

  10. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.

    PubMed

    Huang, Chien-Hua; Tsai, Min-Shan; Chiang, Chih-Yen; Su, Yu-Jen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2015-11-01

    While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity. PMID:26471891

  11. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.

    PubMed

    Huang, Chien-Hua; Tsai, Min-Shan; Chiang, Chih-Yen; Su, Yu-Jen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2015-11-01

    While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity.

  12. Near-Infrared Optical Imaging Noninvasively Detects Acutely Damaged Muscle.

    PubMed

    Chrzanowski, Stephen M; Batra, Abhinandan; Lee-McMullen, Brittany; Vohra, Ravneet S; Forbes, Sean C; Jiang, Huabei; Vandenborne, Krista; Walter, Glenn A

    2016-10-01

    Muscle damage is currently assessed through methods such as muscle biopsy, serum biomarkers, functional testing, and imaging procedures, each with its own inherent limitations, and a pressing need for a safe, repeatable, inexpensive, and noninvasive modality to assess the state of muscle health remains. Our aim was to develop and assess near-infrared (NIR) optical imaging as a novel noninvasive method of detecting and quantifying muscle damage. An immobilization-reambulation model was used for inducing muscle damage and recovery in the lower hindlimbs in mice. Confirmation of muscle damage was obtained using in vivo indocyanine green-enhanced NIR optical imaging, magnetic resonance imaging, and ex vivo tissue analysis. The soleus of the immobilized-reambulated hindlimb was found to have a greater amount of muscle damage compared to that in the contralateral nonimmobilized limb, confirmed by in vivo indocyanine green-enhanced NIR optical imaging (3.86-fold increase in radiant efficiency), magnetic resonance imaging (1.41-fold increase in T2), and an ex vivo spectrophotometric assay of indocyanine green uptake (1.87-fold increase in normalized absorbance). Contrast-enhanced NIR optical imaging provides a sensitive, rapid, and noninvasive screening method that can be used for imaging and quantifying muscle damage and recovery in vivo. PMID:27565039

  13. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

    SciTech Connect

    Chen, Lijuan; Wang, Yingjie; Pan, Yaohua; Zhang, Lan; Shen, Chengxing; Qin, Gangjian; Ashraf, Muhammad; Weintraub, Neal; Ma, Genshan; Tang, Yaoliang

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  14. Vasopressin, renin, and cortisol responses to hemorrhage during acute blockade of cardiac nerves in conscious dogs

    NASA Technical Reports Server (NTRS)

    O'Donnell, C. P.; Keil, L. C.; Thrasher, T. N.

    1993-01-01

    The effect of acute cardiac nerve blockade (CNB) on the increases in plasma renin activity (PRA), arginine vasopressin (AVP), and cortisol in response to a 30 ml/kg hemorrhage was determined in conscious dogs (n = 9). Procaine was infused into the pericardial space to produce acute reversible CNB, or saline was infused in the control hemorrhage. Blood was removed from the inferior vena cava at a rate of 1 ml.kg-1.min-1. In the control hemorrhage, plasma AVP increased from 1.8 +/- 0.3 to 219 +/- 66 pg/ml, PRA increased from 0.63 +/- 0.20 to 3.08 +/- 0.91 ng angiotensin I (ANG I).ml-1.3 h-1, and cortisol increased from 1.4 +/- 0.2 to 4.0 +/- 0.7 micrograms/dl. When the hemorrhage was repeated during acute CNB, plasma AVP increased from 2.8 +/- 1.6 to 185 +/- 59 pg/ml, PRA increased from 0.44 +/- 0.14 to 2.24 +/- 0.27 ng ANG I.ml-1.3 h-1, and cortisol increased from 1.9 +/- 0.3 to 5.4 +/- 0.6 micrograms/dl, and none of the increases differed significantly from the responses during the control hemorrhage. Left atrial pressure fell significantly after removal of 6 ml/kg of blood, but mean arterial pressure was maintained at control levels until blood loss reached 20 ml/kg during pericardial infusion of either saline or procaine. The declines in MAP at the 30 ml/kg level of hemorrhage in both treatments were similar. These results demonstrate that acutely blocking input from cardiac receptors does not reduce the increases in plasma AVP, cortisol, and PRA in response to a 30 ml/kg hemorrhage. The results of this study do not support the hypothesis that input from cardiac receptors is required for a normal AVP response to hemorrhage and suggest that other receptors, presumably arterial baroreceptors, can stimulate AVP and cortisol secretion in the absence of signals from the heart.

  15. Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood Transfusions After Cardiac Surgery

    PubMed Central

    Goldberg, Joshua; Paugh, Paugh; Dickinson, Timothy A.; Fuller, John; Paone, Gaetano; Theurer, Patty F.; Shann, Kenneth G.; Sundt, Thoralf M.; Prager, Richard L.; Likosky, Donald S.

    2016-01-01

    Background Perioperative red blood cell transfusions (RBC) are associated with increased morbidity and mortality after cardiac surgery. Acute normovolemic hemodilution (ANH) is recommended to reduce perioperative transfusions; however, supporting data are limited and conflicting. We describe the relationship between ANH and RBC transfusions after cardiac surgery using a multi-center registry. Methods We analyzed 13,534 patients undergoing cardiac surgery between 2010 and 2014 at any of the 26 hospitals participating in a prospective cardiovascular perfusion database. The volume of ANH (no ANH, <400mL, 400–799mL, ≥800mL) was recorded and linked to each center’s surgical data. We report adjusted relative risks reflecting the association between the use and amount of ANH and the risk of perioperative RBC transfusion. Results were adjusted for preoperative risk factors, procedure, BSA, preoperative HCT, and center. Results ANH was used in 17% of the patients. ANH was associated with a reduction in RBC transfusions (RRadj 0.74, p <0.001). Patients having ≥800mL of ANH had the most profound reduction in RBC transfusions (RRadj 0.57, p<0.001). Platelet and plasma transfusions were also significantly lower with ANH. The ANH population had superior postoperative morbidity and mortality compared to the no ANH population. Conclusions There is a significant association between ANH and reduced perioperative RBC transfusion in cardiac surgery. Transfusion reduction is most profound with larger volumes of ANH. Our findings suggest the volume of ANH, rather than just its use, may be an important feature of a center’s blood conservation strategy. PMID:26206721

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

    PubMed Central

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

    2015-01-01

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

  17. Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult.

    PubMed

    Moreira-Gonçalves, Daniel; Henriques-Coelho, Tiago; Fonseca, Hélder; Ferreira, Rita; Padrão, Ana Isabel; Santa, Cátia; Vieira, Sara; Silva, Ana Filipa; Amado, Francisco; Leite-Moreira, Adelino; Duarte, José Alberto

    2015-09-01

    The present study aimed to test whether a chronic intermittent workload could induce an adaptive cardiac phenotype Chronic intermittent workload induced features of adaptive hypertrophy This was paralleled by protection against acute pressure overload insult The heart may adapt favourably to balanced demands, regardless of the nature of the stimuli. The present study aimed to test whether submitting the healthy heart to intermittent and tolerable amounts of workload, independently of its nature, could result in an adaptive cardiac phenotype. Male Wistar rats were subjected to treadmill running (Ex) (n = 20), intermittent cardiac overload with dobutamine (ITO) (2 mg kg(-1) , s.c.; n = 20) or placebo administration (Cont) (n = 20) for 5 days week(-1) for 8 weeks. Animals were then killed for histological and biochemical analysis or subjected to left ventricular haemodynamic evaluation under baseline conditions, in response to isovolumetric contractions and to sustained LV acute pressure overload (35% increase in peak systolic pressure maintained for 2 h). Baseline cardiac function was enhanced only in Ex, whereas the response to isovolumetric heartbeats was improved in both ITO and Ex. By contrast to the Cont group, in which rats developed diastolic dysfunction with sustained acute pressure overload, ITO and Ex showed increased tolerance to this stress test. Both ITO and Ex developed cardiomyocyte hypertrophy without fibrosis, no overexpression of osteopontin-1 or β-myosin heavy chain, and increased expression of sarcoplasmic reticulum Ca(2+) protein. Regarding hypertrophic pathways, ITO and Ex showed activation of the protein kinase B/mammalian target of rapamycin pathway but not calcineurin. Mitochondrial complex IV and V activities were also increased in ITO and Ex. Chronic submission to controlled intermittent cardiac overload, independently of its nature, results in an adaptive cardiac phenotype. Features of the cardiac overload, such as the duration and

  18. Acute renal failure after cardiac transplantation: a case report and review of the literature.

    PubMed Central

    Cruz, D. N.; Perazella, M. A.

    1996-01-01

    Acute renal failure (ARF) is a relatively frequent complication associated with heart transplantation. It develops in the first few days postoperatively and is characterized by oliguria with laboratory and urinary indices typical of pre-renal azotemia. Cyclosporine, especially with higher doses, is one of the many factors which play an integral part in the nephrotoxicity following cardiac transplant. Poor preoperative renal function and perioperative hemodynamic compromise may also contribute to ARF. The actual incidence of ARF now encountered by transplant centers may be lower than previously reported, the result of lower cyclosporine doses. Currently, management is entirely supportive, but novel therapeutic approaches with atrial natriuretic peptide-like substances are being explored. A case illustrating the typical clinical presentation of ARF after heart transplant will be presented and the clinical features will be reviewed. PMID:9381741

  19. The Effect of Glucose-Insulin-Potassium on Cardiac Ultrastructure Following Acute Experimental Coronary Occlusion

    PubMed Central

    Sybers, H. D.; Maroko, P. R.; Ashraf, M.; Libby, P.; Braunwald, E.

    1973-01-01

    The effects of glucose-insulin-potassium (GIK) on cardiac ultrastructure following acute experimental coronary occlusion were studied in dogs. Epicardial ST segment elevations at multiple sites on the anterior surface of the left ventricle 15 minutes after ligation of the left anterior descending coronary artery were used to predict infarct development. Biopsies removed from sites of known ST segment elevation were examined with the electron microscope, and the degree of injury was correlated with the ST segment elevation. The animals receiving GIK showed significantly less necrosis than was seen in dogs with occlusion alone at corresponding levels of ST segment elevation. Other evidence suggesting a beneficial effect of GIK was the presence of a fibrillar material in several biopsies from the treated animals, which may indicate the regeneration of myofilaments. ImagesFig 3Fig 4Fig 8Fig 9Fig 5Fig 6Fig 10Fig 7p[417]-aFig 1Fig 2 PMID:4570076

  20. In Emergency Department Patients with Acute Chest Pain, Stress Cardiac MRI Observation Unit Care Reduces 1- year Cardiac-Related Health Care Expenditures: A Randomized Trial

    PubMed Central

    Miller, Chadwick D.; Hwang, Wenke; Case, Doug; Hoekstra, James W.; Lefebvre, Cedric; Blumstein, Howard; Hamilton, Craig A.; Harper, Erin N.; Hundley, W. Gregory

    2013-01-01

    Objective To compare the direct cost of medical care and clinical events during the first year after patients with intermediate risk acute chest pain were randomized to stress cardiovascular magnetic resonance (CMR) observation unit (OU) testing, versus inpatient care. Background In a recent study, randomization to OU-CMR reduced median index hospitalization cost compared to inpatient care in patients presenting to the emergency department with intermediate risk acute chest pain. Methods Emergency department patients with intermediate risk chest pain were randomized to OU-CMR (OU care, cardiac markers, stress CMR) or inpatient care (admission, care per admitting provider). This analysis reports the direct cost of cardiac-related care and clinical outcomes (MI, revascularization, cardiovascular death) during the first year of follow-up subsequent to discharge. Consistent with health economics literature, provider cost was calculated from work-related relative value units using the Medicare conversion factor; facility charges were converted to cost using departmental specific cost-to-charge ratios. Linear models were used to compare cost accumulation among study groups. Results One-hundred nine (109) randomized subjects were included in this analysis (52 OU-CMR, 57 inpatient care). The median age was 56 years; baseline characteristics were similar in both groups. At 1 year, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p=0.72) with 1 patient in each group experiencing a cardiac event after discharge. First-year cardiac-related costs were significantly lower for participants randomized to OU-CMR compared to participants receiving inpatient care (geometric mean = $3101 vs $4742 including the index visit (p = .004) and $29 vs $152 following discharge (p = .012)). During the year following randomization, 6% of OU-CMR and 9% of inpatient care participants experienced a major cardiac event (p=0.72). Conclusions An OU-CMR strategy

  1. Acute and late gastrointestinal toxicity after radiotherapy in prostate cancer patients: Consequential late damage

    SciTech Connect

    Heemsbergen, Wilma D. . E-mail: w.heemsbergen@nki.nl; Peeters, Stephanie T.H.; Koper, Peter; Hoogeman, Mischa S.; Lebesque, Joos V.

    2006-09-01

    Purpose: Late gastrointestinal (GI) toxicity after radiotherapy can be partly explained by late effects of acute toxicity (consequential late damage). We studied whether there is a direct relationship between acute and late GI toxicity. Patients and Methods: A total of 553 evaluable patients from the Dutch dose escalation trial (68 Gy vs. 78 Gy) were included. We defined three outcomes for acute reactions: 1) maximum Radiation Therapy Oncology Group acute toxicity, 2) maximum acute mucous discharge (AMD), and 3) maximum acute proctitis. Within a multivariable model, late endpoints (overall toxicity and five toxicity indicators) were studied as a function of acute toxicity, pretreatment symptoms, and relevant dose parameters. Results: At multivariable analysis, AMD and acute proctitis were strong predictors for overall toxicity, 'intermittent bleeding,' and 'incontinence pads' (p {<=} 0.01). For 'stools {>=}6/day' all three were strong predictors. No significant associations were found for 'severe bleeding' and 'use of steroids.' The predictive power of the dose parameters remained at the same level or became weaker for most late endpoints. Conclusions: Acute GI toxicity is an independent significant predictor of late GI toxicity. This suggests a significant consequential component in the development of late GI toxicity.

  2. Epicardial delivery of VEGF and cardiac stem cells guided by 3-dimensional PLLA mat enhancing cardiac regeneration and angiogenesis in acute myocardial infarction.

    PubMed

    Chung, Hye-Jin; Kim, Jong-Tae; Kim, Hee-Jung; Kyung, Hei-Won; Katila, Pramila; Lee, Jeong-Han; Yang, Tae-Hyun; Yang, Young-Il; Lee, Seung-Jin

    2015-05-10

    Congestive heart failure is mostly resulted in a consequence of the limited myocardial regeneration capacity after acute myocardial infarction. Targeted delivery of proangiogenic factors and/or stem cells to the ischemic myocardium is a promising strategy for enhancing their local and sustained therapeutic effects. Herein, we designed an epicardial delivery system of vascular endothelial growth factor (VEGF) and cardiac stem cells (CSCs) using poly(l-lactic acid) (PLLA) mat applied to the acutely infarcted myocardium. The fibrous VEGF-loaded PLLA mat was fabricated by an electrospinning method using PLLA solution emulsified VEGF. This mat not only allowed for sustained release of VEGF for 4weeks but boosted migration and proliferation of both endothelial cells and CSCs in vitro. Furthermore, sustained release of VEGF showed a positive effect on in vitro capillary-like network formation of endothelial cells compared with bolus treatment of VEGF. PLLA mat provided a permissive 3-dimensional (3D) substratum that led to spontaneous cardiomyogenic differentiation of CSCs in vitro. Notably, sustained stimulation by VEGF-loaded PLLA mat resulted in a substantial increase in the expression of proangiogenic mRNAs of CSCs in vitro. The epicardially implanted VEGF-loaded PLLA mat showed modest effects on angiogenesis and cardiomyogenesis in the acutely infarcted hearts. However, co-implantation of VEGF and CSCs using the PLLA mat showed meaningful therapeutic effects on angiogenesis and cardiomyogenesis compared with controls, leading to reduced cardiac remodeling and enhanced global cardiac function. Collectively, the PLLA mat allowed a smart cargo that enabled the sustained release of VEGF and the delivery of CSCs, thereby synergistically inducing angiogenesis and cardiomyogenesis in acute myocardial infarction.

  3. Postoperative blood transfusion is an independent predictor of acute kidney injury in cardiac surgery patients

    PubMed Central

    Freeland, Kristofer; Hamidian Jahromi, Alireza; Duvall, Lucas Maier; Mancini, Mary Catherine

    2015-01-01

    Background: Acute kidney injury (AKI) is a serious complication of cardiac surgery with cardiopulmonary bypass (CPB) which increases postoperative morbidity and mortality. Objectives: The study was designed to assess the incidence of AKI and associated risk factors in patients undergoing CPB ancillary to coronary artery bypass grafting (CABG), valve surgery, and combined CABG and valve surgery. Patients and Methods: This Intuitional Review Board (IRB) approved retrospective study included patients with normal preoperative kidney function (Serum creatinine [sCr] <2.0 mg/dl) who underwent cardiac surgery with CPB between 2012 and 2014. Patients were divided into 2 groups: group I: Patients with cardiac surgery associated AKI (CS-AKI) (postoperative sCr >2 mg/dl with a minimal doubling of baseline sCr) and group II: Patients with a normal postoperative kidney function. Demographic data, body mass index (BMI), co-morbidities, hematologic/biochemical profiles, preoperative ejection fraction (%EF), blood transfusion history, and operative data were compared between the groups. Mean arterial pressure (MAP) was recorded during the operation and in the postoperative period. Δ-MAP was defined as the difference between pre-CPB-MAP and the CPB-MAP. Results: 241 patients matched the inclusion criteria (CS-AKI incidence = 8.29%). Age, gender, BMI, %EF, and co-morbidities were not predictors of CS-AKI (P > 0.05). High preoperative sCr (P = 0.047), type of procedure (P = 0.04), clamp time (P = 0.003), pump time (P = 0.005) and history of blood transfusion within 14 days postsurgery (P = 0.0004) were associated with risk of CS-AKI. Pre-CPB-MAP, CPB-MAP, Δ-MAP, and ICU-MAP were not significantly different between the 2 groups. Male gender (OR: 5.53; P = 0.048), age>60 (OR: 4.54; P = 0.027) and blood transfusion after surgery (OR: 5.25; P = 0.0054) were independent predictors for postoperative AKI. Conclusions: Age, gender and blood transfusion were independent predictors of

  4. Role of cardiac volume receptors in the control of ADH release during acute simulated weightlessness in man

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Benjamin, B. A.; Keil, L. C.; Sandler, H.

    1984-01-01

    Hemodynamic responses and antidiuretic hormone (ADH) were measured during body position changes, designed to induce central blood volume shifts in ten cardiac and one heart-lung transplant recipients, to assess the contribution of cardiac volume receptors in the control of ADH release during the initial acute phase of exposure to weightlessness. Each subject underwent 15 min of a sitting-control period (C) followed by 30 min of 6 deg headdown tilt (T) and 30 min of resumed sitting (S). Venous blood samples and cardiac dimensions were taken at 0 and 15 min of C; 5, 15, and 30 min of T; and 5, 15, and 30 min of S. Blood samples were analyzed for hematocrit, plasma osmolality, plasma renin activity (PRA), and ADH. Heart rate and blood pressure were recorded every two min. Plasma osmolality was not altered by posture changes. Mean left ventricular end-diastolic volume increased (P less than 0.05) from 90 ml in C to 106 ml in T and returned to 87 ml in S. Plasma ADH was reduced by 20 percent (P less than 0.05) with T, and returned to control levels with S. These responses were similar in six normal cardiac-innervated control subjects. These data may suggest that cardiac volume receptors are not the primary mechanism for the control of ADH release during acute central volume shifts in man.

  5. Acute cardiac sympathetic disruption in the pathogenesis of the takotsubo syndrome: a systematic review of the literature to date.

    PubMed

    Y-Hassan, Shams

    2014-01-01

    Takotsubo syndrome (TS), also known as broken heart syndrome and neurogenic stunned myocardium, is an acute cardiac disease entity characterized by a clinical picture mimicking that of an acute coronary syndrome. The pathogenesis of TS has not been established yet. Among the most often debated pathologic mechanisms of TS are as follows: first, multi-vessel coronary spasm; second, myocardial microvascular dysfunction; third, aborted myocardial infarction caused by transient thrombotic occlusion of a long wrap-around left anterior descending artery; fourth, left ventricular outflow tract obstruction; fifth, blood-borne catecholamine cardiac toxicity; and sixth, cardiac sympathetic disruption and norepinephrine seethe and spillover. The aim of this review is to provide a thorough analysis of the literature data coming mainly from the neurological literature and dealing with the pathogenesis of TS. Substantial evidence challenging the first five hypotheses and arguing in favor of the hypothesis that acute cardiac sympathetic eruption and norepinephrine seethe and spillover is causing TS in predisposed patients is presented. PMID:24140050

  6. EGFR inhibition protects cardiac damage and remodeling through attenuating oxidative stress in STZ-induced diabetic mouse model.

    PubMed

    Liang, Dandan; Zhong, Peng; Hu, Jie; Lin, Feng; Qian, Yuanyuan; Xu, Zheng; Wang, Jingying; Zeng, Chunlai; Li, Xiaokun; Liang, Guang

    2015-05-01

    Diabetes mellitus is strongly associated with cardiomyopathy. The underlying mechanisms for the development of diabetic cardiomyopathy are complex and not completely understood. Recent studies showed that epidermal growth factor receptors (EGFRs) are involved in diabetes-induced cardiac injury. However, the role of EGFR in the diabetic heart has yet to be confirmed. The aim of the present study is to further determine the role of EGRF in the pathogenesis of diabetic heart injury. The type 1 diabetic mice induced by streptozotocin were treated with EGFR inhibitors (AG1478 and 451) for 8 weeks, respectively. It was observed that diabetes induced phospohorylation of EGFR and AKT, increased cardiac ROS levels, and ultimately led to cardiac remodeling including cardiac hypertrophy, disorganization, apoptosis, and fibrosis, while all these molecular and pathological alterations were attenuated by the treatment with EGFR inhibitors. In vitro, either pharmacological inhibition of EGFR/AKT or sh-RNA silencing of EGFR significantly inhibited high concentration glucose (HG)-induced ROS generation and subsequently cell apoptosis in both cardiac H9C2 cells and primary rat cardiomyocytes, respectively. The ROS reduction by EGFR inhibitor was associated with the decreased NADPH oxidase activity and expression in H9c2 cells. HG-induced cardiomyocyte injuries were also reduced by NAC, an inhibitor of ROS. This study provides evidence that EGFR has a key role in the pathogenesis of STZ-induced diabetic cardiac damage and remodeling via ROS generation, and suggests that EGFR may be a potential target in treating diabetic cardiomyopathy. PMID:25758431

  7. Diagnostic and Prognostic Properties of Osteoprotegerin in Patients with Acute Dyspnoea: Observations from the Akershus Cardiac Examination (ACE) 2 Study

    PubMed Central

    Pervez, Mohammed Osman; Pedersen, Marit Holmefjord; Brynildsen, Jon; Høiseth, Arne Didrik; Hagve, Tor-Arne; Røsjø, Helge; Omland, Torbjørn

    2016-01-01

    Background Circulating osteoprotegerin (OPG) levels are increased in patients with chronic heart failure (HF). The diagnostic and prognostic merit of OPG measurement in patients admitted with acute dyspnoea is unknown. Objectives To evaluate the diagnostic and prognostic value of measuring OPG in patients admitted to hospital with acute dyspnoea. Methods OPG was analysed by ELISA in 308 patients admitted due to acute dyspnoea. Investigators blinded to OPG results adjudicated the diagnosis for the index hospitalization. Clinical outcomes were obtained from hospital records. Results In total, 139 patients (45%) were hospitalized with acute HF. OPG levels on hospital admission were higher in patients with acute HF vs. no acute HF, 7.8 (5.5–10.4) vs. 5.4 (3.8–7.2) pmol/L, p<0.001. The area under the receiver operator characteristic curve (ROC AUC) of OPG to discriminate between HF vs. non-HF was 0.695 [95% CI 0.636–0.754]. OPG did not provide incremental information to the ED physician’s prediction or N-terminal pro-B-type natriuretic peptide regarding the diagnosis of acute HF. OPG levels (log transformed) were associated with mortality in crude analysis (HR (95% CI) 1.87 (1.34 to 2.61), p<0.001), but this association was attenuated and no longer significant after including established cardiac biomarkers into the model. Conclusion In patients admitted to hospital with acute dyspnoea, OPG levels are higher in patients with acute HF than in those with dyspnoea from other causes. However, OPG does not provide incremental information beyond ED physician assessment for the diagnosis of acute HF or beyond clinical risk variables and established cardiac biomarkers concerning prognosis. PMID:27463973

  8. Cardiac oxygen limitation during an acute thermal challenge in the European perch: effects of chronic environmental warming and experimental hyperoxia.

    PubMed

    Ekström, Andreas; Brijs, Jeroen; Clark, Timothy D; Gräns, Albin; Jutfelt, Fredrik; Sandblom, Erik

    2016-08-01

    Oxygen supply to the heart has been hypothesized to limit cardiac performance and whole animal acute thermal tolerance (CTmax) in fish. We tested these hypotheses by continuously measuring venous oxygen tension (Pvo2) and cardiovascular variables in vivo during acute warming in European perch (Perca fluviatilis) from a reference area during summer (18°C) and a chronically heated area (Biotest enclosure) that receives warm effluent water from a nuclear power plant and is normally 5-10°C above ambient (24°C at the time of experiments). While CTmax was 2.2°C higher in Biotest compared with reference perch, the peaks in cardiac output and heart rate prior to CTmax occurred at statistically similar Pvo2 values (2.3-4.0 kPa), suggesting that cardiac failure occurred at a common critical Pvo2 threshold. Environmental hyperoxia (200% air saturation) increased Pvo2 across temperatures in reference fish, but heart rate still declined at a similar temperature. CTmax of reference fish increased slightly (by 0.9°C) in hyperoxia, but remained significantly lower than in Biotest fish despite an improved cardiac output due to an elevated stroke volume. Thus, while cardiac oxygen supply appears critical to elevate stroke volume at high temperatures, oxygen limitation may not explain the bradycardia and arrhythmia that occur prior to CTmax Acute thermal tolerance and its thermal plasticity can, therefore, only be partially attributed to cardiac failure from myocardial oxygen limitations, and likely involves limiting factors on multiple organizational levels. PMID:27280433

  9. Acute Auditory Stimulation with Different Styles of Music Influences Cardiac Autonomic Regulation in Men

    PubMed Central

    da Silva, Sheila Ap. F.; Guida, Heraldo L.; dos Santos Antonio, Ana Marcia; de Abreu, Luiz Carlos; Monteiro, Carlos B. M.; Ferreira, Celso; Ribeiro, Vivian F.; Barnabe, Viviani; Silva, Sidney B.; Fonseca, Fernando L. A.; Adami, Fernando; Petenusso, Marcio; Raimundo, Rodrigo D.; Valenti, Vitor E.

    2014-01-01

    Background: No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. Objectives: The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. Patients and Methods: In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. Results: While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms2 and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms2) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Conclusions: Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart. PMID:25177673

  10. [ROLE OF MICROFLORA OF THE ABDOMINAL CAVITY EXUDATE IN THE ENDOGENIC INTOXICATION OCCURRENCE IN PATIENTS, SUFFERING COMPLICATED ACUTE CHOLECYSTITIS WITH CONCURRENT CARDIAC INSUFFICIENCY OF ISCHEMIC GENESIS].

    PubMed

    Ivantsok, V M

    2015-05-01

    While complicated acute cholecystitis (ACH) course the focus of infection constitutes one of the main causes of the endogenic intoxication (EI) occurrence, what leads to ischemic and hypoxic myocardial damage. There were presented the treatment results analysis in 213 patients, ageing 60 years old and older, managed for an ACH, complicated by peritonitis, paravesical abscess, with concurrent cardiac insufficiency of ischemic genesis, to whom laparoscopic cholecytectomy (LCHE) was conducted. Microflora of the abdominal cavity exudates in the patients, suffering an ACH of various severity, was studied. More rapid regression of inflammatory process, the EI severity and the ischemic-hypoxic myocardial affection reduction, positive impact on hemodynamics, reduction of myocardial ischemia severity were noted while local affection, when bacteriophages for treatment were applied.

  11. Oxidative stress, DNA damage, and the telomeric complex as therapeutic targets in acute neurodegeneration

    PubMed Central

    Smith, Joshua A.; Park, Sookyoung; Krause, James S.; Banik, Naren L.

    2013-01-01

    Oxidative stress has been identified as an important contributor to neurodegeneration associated with acute CNS injuries and diseases such as spinal cord injury (SCI), traumatic brain injury (TBI), and ischemic stroke. In this review, we briefly detail the damaging effects of oxidative stress (lipid peroxidation, protein oxidation, etc.) with a particular emphasis on DNA damage. Evidence for DNA damage in acute CNS injuries is presented along with its downstream effects on neuronal viability. In particular, unchecked oxidative DNA damage initiates a series of signaling events (e.g. activation of p53 and PARP-1, cell cycle re-activation) which have been shown to promote neuronal loss following CNS injury. These findings suggest that preventing DNA damage might be an effective way to promote neuronal survival and enhance neurological recovery in these conditions. Finally, we identify the telomere and telomere-associated proteins (e.g. telomerase) as novel therapeutic targets in the treatment of neurodegeneration due to their ability to modulate the neuronal response to both oxidative stress and DNA damage. PMID:23422879

  12. Cardiac Mitochondrial Respiratory Dysfunction and Tissue Damage in Chronic Hyperglycemia Correlate with Reduced Aldehyde Dehydrogenase-2 Activity

    PubMed Central

    Deshpande, Mandar; Thandavarayan, Rajarajan A.; Xu, Jiang; Yang, Xiao-Ping; Palaniyandi, Suresh S.

    2016-01-01

    Aldehyde dehydrogenase (ALDH) 2 is a mitochondrial isozyme of the heart involved in the metabolism of toxic aldehydes produced from oxidative stress. We hypothesized that hyperglycemia-mediated decrease in ALDH2 activity may impair mitochondrial respiration and ultimately result in cardiac damage. A single dose (65 mg/kg; i.p.) streptozotocin injection to rats resulted in hyperglycemia with blood glucose levels of 443 ± 9 mg/dl versus 121 ± 7 mg/dl in control animals, p<0.0001, N = 7–11. After 6 months of diabetes mellitus (DM) induction, the rats were sacrificed after recording the functionality of their hearts. Increase in the cardiomyocyte cross sectional area (446 ± 32 μm2 Vs 221 ± 10 μm2; p<0.0001) indicated cardiac hypertrophy in DM rats. Both diastolic and systolic dysfunctions were observed with DM rats compared to controls. Most importantly, myocardial ALDH2 activity and levels were reduced, and immunostaining for 4HNE protein adducts was increased in DM hearts compared to controls. The mitochondrial oxygen consumption rate (OCR), an index of mitochondrial respiration, was decreased in mitochondria isolated from DM hearts compared to controls (p<0.0001). Furthermore, the rate of mitochondrial respiration and the increase in carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)-induced maximal respiration were also decreased with chronic hyperglycemia. Chronic hyperglycemia reduced mitochondrial OXPHOS proteins. Reduced ALDH2 activity was correlated with mitochondrial dysfunction, pathological remodeling and cardiac dysfunction, respectively. Our results suggest that chronic hyperglycemia reduces ALDH2 activity, leading to mitochondrial respiratory dysfunction and consequently cardiac damage and dysfunction. PMID:27736868

  13. ErbB4 localization to cardiac myocyte nuclei, and its role in myocyte DNA damage response

    SciTech Connect

    Icli, Basak; Bharti, Ajit; Pentassuglia, Laura; Peng, Xuyang; Sawyer, Douglas B.

    2012-02-03

    Highlights: Black-Right-Pointing-Pointer ErbB4 localizes to cardiac myocyte nuclei as a full-length receptor. Black-Right-Pointing-Pointer Cardiac myocytes express predominantly JM-a/CYT-1 ErbB4. Black-Right-Pointing-Pointer Myocyte p53 activation in response to doxorubicin requires ErbB4 activity. -- Abstract: The intracellular domain of ErbB4 receptor tyrosine kinase is known to translocate to the nucleus of cells where it can regulate p53 transcriptional activity. The purpose of this study was to examine whether ErbB4 can localize to the nucleus of adult rat ventricular myocytes (ARVM), and regulate p53 in these cells. We demonstrate that ErbB4 does locate to the nucleus of cardiac myocytes as a full-length protein, although nuclear location occurs as a full-length protein that does not require Protein Kinase C or {gamma}-secretase activity. Consistent with this we found that only the non-cleavable JM-b isoform of ErbB4 is expressed in ARVM. Doxorubicin was used to examine ErbB4 role in regulation of a DNA damage response in ARVM. Doxorubicin induced p53 and p21 was suppressed by treatment with AG1478, an EGFR and ErbB4 kinase inhibitor, or suppression of ErbB4 expression with small interfering RNA. Thus ErbB4 localizes to the nucleus as a full-length protein, and plays a role in the DNA damage response induced by doxorubicin in cardiac myocytes.

  14. Synthesis of a novel photopolymerized nanocomposite hydrogel for the treatment of acute mechanical damage to cartilage

    NASA Astrophysics Data System (ADS)

    Schlichting, Kathryn; Copeland-Johnson, Trishelle; Goodman, Matthew; Lipert, Robert; McKinley, Todd; Martin, James; Mallapragada, Surya; Lin, Zhiqun

    2011-03-01

    Posttraumatic osteoarthritis is caused by a cascade of pathobiologic and pathomechanical events starting with intraarticular fractures in the cartilage. Currently, treatment of fractures is completely focused on restoration of the macroanatomy of the joint. The premise is that restoring the macroanatomy will prevent ongoing stresses and in turn prevent cartilage degeneration. However, current treatment ignores acute mechanical damage sustained by cartilage at the time of injury. This study describes the initial development of a novel nanocomposite photopolymerizing copolymer that has potential to restore local structural integrity to acutely injured cartilage, and subsequently act as a carrier for chondrocyte-enhancing bioactive agents.

  15. Cardiac Rhythm Monitoring After Acute Decompensation for Heart Failure: Results from the CARRYING ON for HF Pilot Study

    PubMed Central

    Mortara, Andrea; Diotallevi, Paolo; Gallone, Giuseppe; Mariconti, Barbara; Gronda, Edoardo; Gentili, Alessandra; Bisetti, Silvia; Botto, Giovanni Luca

    2016-01-01

    Background There’s scarce evidence about cardiovascular events (CV) in patients with hospitalization for acute heart failure (HF) and no indication for immediate device implant. Objective The CARdiac RhYthm monitorING after acute decompensatiON for Heart Failure study was designed to assess the incidence of prespecified clinical and arrhythmic events in this patient population. Methods In this pilot study, 18 patients (12 (67%) male; age 72±10; 16 (89%) NYHA II-III), who were hospitalized for HF with low left ventricular ejection fraction (LVEF) (<40%) and no immediate indication for device implant received an implantable loop recorder (ILR) before hospital discharge. Follow-up visits were scheduled at 3 and 6 months, and at every 6 months until study closure; device data were remotely reviewed monthly. CV mortality, unplanned CV hospitalization, and major arrhythmic events during follow-up were analyzed. Results During a median follow-up of 593 days, major CV occurred in 13 patients (72%); of those, 7 patients had at least 1 cardiac arrhythmic event, 2 had at least a clinical event (CV hospitalization or CV death), and 4 had both an arrhythmic and a CV event. Six (33%) patients experienced 10 major clinical events, 5 of them (50%) were HF related. During follow-up, 2 (11%) patients died due to a CV cause and 3 (16%) patients received a permanent cardiac device. Conclusions After an acute HF hospitalization, patients with LVEF<40% and who are not readily eligible for permanent cardiac device implant have a known high incidence of major CV event. In these patients, ILR allows early detection of major cardiac arrhythmias and the ability to react appropriately in a timely manner. Trial Registration ClinicalTrials.gov NCT01216670; https://clinicaltrials.gov/ct2/show/NCT01216670 PMID:27118481

  16. 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

  17. SYSTEMIC IMBALANCE OF ESSENTIAL METALS AND CARDIAC GENE EXPRESSION IN RATS FOLLOWING ACUTE PULMONARY ZINC EXPOSURE

    EPA Science Inventory

    We have recently demonstrated that PM containing water-soluble zinc may cause cardiac injury following pulmonary exposure. To investigate if pulmonary zinc exposure causes systemic metal imbalance and direct cardiac effects, we intratracheally (IT) instilled male Wistar Kyoto (WK...

  18. Evaluation of plasma von Willebrand factor as a biomarker for acute arterial damage in rats.

    PubMed

    Newsholme, S J; Thudium, D T; Gossett, K A; Watson, E S; Schwartz, L W

    2000-01-01

    Plasma von Willebrand factor (vWF) was evaluated as a potential biomarker of acute arterial damage in rats after a vasotoxic dose of the dopaminergic vasodilator, fenoldopam (FP). Male Sprague-Dawley rats were given FP or isotonic saline by subcutaneous injection, and plasma vWF was measured at 2, 6, and 24 hours after challenge. Mean plasma vWF values increased in FP-treated rats compared to controls at 2 hours (167 vs 122%; p < 0.05) and 6 hours postdose (172 vs 130%; p < 0.01) but were comparable to control values after 24 hours. Mesenteric arterial lesions were observed microscopically in all FP-treated rats 24 hours postdose but were not present in rats at 1, 2, 4, 6, or 8 hours after FP challenge. Further, plasma vWF concentrations increased in saline-treated rats after only the minimal perturbation of repeated venipuncture. These results indicate an early, minimal, and transient release of vWF that precedes the onset of morphologically evident vascular damage. The minimal increases in plasma vWF concentrations were of limited predictive value, may be more reflective of an acute-phase reactant response, and were not considered a reliable biomarker of acute FP-induced arterial damage in the rat.

  19. DJ-1 protects against cell death following acute cardiac ischemia–reperfusion injury

    PubMed Central

    Dongworth, R K; Mukherjee, U A; Hall, A R; Astin, R; Ong, S-B; Yao, Z; Dyson, A; Szabadkai, G; Davidson, S M; Yellon, D M; Hausenloy, D J

    2014-01-01

    Novel therapeutic targets are required to protect the heart against cell death from acute ischemia–reperfusion injury (IRI). Mutations in the DJ-1 (PARK7) gene in dopaminergic neurons induce mitochondrial dysfunction and a genetic form of Parkinson's disease. Genetic ablation of DJ-1 renders the brain more susceptible to cell death following ischemia–reperfusion in a model of stroke. Although DJ-1 is present in the heart, its role there is currently unclear. We sought to investigate whether mitochondrial DJ-1 may protect the heart against cell death from acute IRI by preventing mitochondrial dysfunction. Overexpression of DJ-1 in HL-1 cardiac cells conferred the following beneficial effects: reduced cell death following simulated IRI (30.4±4.7% with DJ-1 versus 52.9±4.7% in control; n=5, P<0.05); delayed mitochondrial permeability transition pore (MPTP) opening (a critical mediator of cell death) (260±33 s with DJ-1 versus 121±12 s in control; n=6, P<0.05); and induction of mitochondrial elongation (81.3±2.5% with DJ-1 versus 62.0±2.8% in control; n=6 cells, P<0.05). These beneficial effects of DJ-1 were absent in cells expressing the non-functional DJ-1L166P and DJ-1Cys106A mutants. Adult mice devoid of DJ-1 (KO) were found to be more susceptible to cell death from in vivo IRI with larger myocardial infarct sizes (50.9±3.5% DJ-1 KO versus 41.1±2.5% in DJ-1 WT; n≥7, P<0.05) and resistant to cardioprotection by ischemic preconditioning. DJ-1 KO hearts showed increased mitochondrial fragmentation on electron microscopy, although there were no differences in calcium-induced MPTP opening, mitochondrial respiratory function or myocardial ATP levels. We demonstrate that loss of DJ-1 protects the heart from acute IRI cell death by preventing mitochondrial dysfunction. We propose that DJ-1 may represent a novel therapeutic target for cardioprotection. PMID:24577080

  20. Ambulatory and Challenge-Associated Heart Rate Variability Measures Predict Cardiac Responses to “Real-World” Acute Emotional Stress

    PubMed Central

    Dikecligil, GN; Mujica-Parodi, LR

    2010-01-01

    Background Heart rate variability (HRV) measures homeostatic regulation of the autonomic nervous system in response to perturbation, and has been previously shown to quantify risk for cardiac events. In spite of known interactions between stress vulnerability, psychiatric illness, and cardiac health, however, to our knowledge this is the first study to directly compare the value of laboratory HRV in predicting autonomic modulation of “real-world” emotional stress. Methods We recorded ECG on 56 subjects: first, within the laboratory, and then during an acute emotional stressor: a first-time skydive. Laboratory sessions included two five-minute ECG recordings separated by one ambulatory 24-hour recording. To test the efficacy of introducing a mild emotional challenge, during each of the five-minute laboratory recordings subjects viewed either aversive or benign images. Following the laboratory session, subjects participated in the acute stressor wearing a holter ECG. Artifact-free ECGs (N=33) were analyzed for HRV, then statistically compared across laboratory and acute stress sessions. Results There were robust correlations (r=0.7-0.8) between the laboratory and acute stress HRV, indicating that the two most useful paradigms (long-term wake, followed by short-term challenge) also were most sensitive to distinct components of the acute stressor: the former correlated with the fine-tuned regulatory modulation occurring immediately prior and following the acute stressor, while the latter correlated with gross amplitude and recovery. Conclusions Our results confirmed the efficacy of laboratory-acquired HRV in predicting autonomic response to acute emotional stress, and suggest that ambulatory and challenge protocols enhance predictive value. PMID:20299007

  1. Cardiac-Specific Overexpression of Metallothionein Rescues against Cigarette Smoking Exposure-Induced Myocardial Contractile and Mitochondrial Damage

    PubMed Central

    Hu, Nan; Han, Xuefeng; Lane, Erin K.; Gao, Feng; Zhang, Yingmei; Ren, Jun

    2013-01-01

    Objectives Second hand cigarette smoke is an independent risk factor for cardiovascular disease. Although a tie between smoking and cardiovascular disease is well established, the underlying mechanisms still remains elusive due to the lack of adequate animal models. This study was designed to use a mouse model of exposure to cigarette smoke, a surrogate of environmental tobacco smoke, to evaluate the impact of cardiac overexpression of heavy metal scavenger metallothionein on myocardial geometry, contractile and intracellular Ca2+ properties and apoptosis following side-stream smoke exposure. Methods Adult male wild-type FVB and metallothionein transgenic mice were placed in a chamber exposed to cigarette smoke for 1 hour daily for 40 days. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties, fibrosis, apoptosis and mitochondrial damage were examined. Results Our data revealed that smoke exposure enlarged ventricular end systolic and diastolic diameters, reduced myocardial and cardiomyocyte contractile function, disrupted intracellular Ca2+ homeostasis, facilitated fibrosis, apoptosis and mitochondrial damage (cytochrome C release and aconitase activity), the effects of which were attenuated or mitigated by metallothionein. In addition, side-stream smoke expose enhanced phosphorylation of Akt and GSK3β without affecting pan protein expression in the heart, the effect of which was abolished or ameliorated by metallothionein. Cigarette smoke extract interrupted cardiomyocyte contractile function and intracellular Ca2+ properties, the effect of which was mitigated by wortmannin and NAC. Conclusions These data suggest that side-stream smoke exposure led to myocardial dysfunction, intracellular Ca2+ mishandling, apoptosis, fibrosis and mitochondrial damage, indicating the therapeutic potential of antioxidant against in second smoking-induced cardiac defects possibly via mitochondrial damage and apoptosis. PMID:23431404

  2. Referrals in Acute Coronary Events for CARdiac Catheterization: The RACE CAR trial

    PubMed Central

    Kreatsoulas, Catherine; Sloane, Debi; Pogue, Janice; Velianou, James L; Anand, Sonia S

    2010-01-01

    BACKGROUND: Women with acute coronary syndromes have lower rates of cardiac catheterization (CC) than men. OBJECTIVE: To determine whether sex/gender, age, risk level and patient preference influence physician decision making to refer patients for CC. METHODS: Twelve clinical scenarios controlling for sex/gender, age (55 or 75 years of age), Thrombolysis in Myocardial Infarction risk score (low, moderate or high) and patient preference for CC (agreeable or refused/no preference expressed) were designed. Scenarios were administered to specialists across Canada using a web-based computerized survey instrument. Questions were standardized using a five-point Likert scale ranging from 1 (very unlikely to benefit from CC) to 5 (very likely to benefit from CC). Outcomes were assessed using a two-tailed mixed linear regression model. RESULTS: Of 237 scenarios, physicians rated men as more likely to benefit from CC than women (mean [± SE] 4.44±0.07 versus 4.25±0.07, P=0.03), adjusted for age, risk and patient preference. Low-risk men were perceived to benefit more than low-risk women (4.20±0.13 versus 3.54±0.14, P<0.01), and low-risk younger patients were perceived to benefit more than low-risk older patients (4.52±0.17 versus 3.22±0.16, P<0.01). Regardless of risk, patients who agreed to CC were perceived as more likely to benefit from CC than patients who were disagreeable or made no comment at all (5.0±0.23, 3.67±0.21, 2.95±0.14, respectively, P<0.01). CONCLUSION: Canadian specialists’ decisions to refer patients for CC appear to be influenced by sex/gender, age and patient preference in clinical scenarios in which cardiac risk is held constant. Future investigation of possible age and sex/gender biases as proxies for risk is warranted. PMID:20931097

  3. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    PubMed Central

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  4. Role of cardiac output and the autonomic nervous system in the antinatriuretic response to acute constriction of the thoracic superior vena cava.

    NASA Technical Reports Server (NTRS)

    Schrier, R. W.; Humphreys, M. H.; Ufferman, R. C.

    1971-01-01

    Study of the differential characteristics of hepatic congestion and decreased cardiac output in terms of potential afferent stimuli in the antinatriuretic effect of acute thoracic inferior vena cava (TIVC) constriction. An attempt is made to see if the autonomic nervous system is involved in the antinatriuretic effect of acute TIVC or thoracic superior vena cava constriction.

  5. Difference in molecular pathology of natriuretic peptides in the myocardium between acute asphyxial and cardiac deaths.

    PubMed

    Chen, Jian-Hua; Michiue, Tomomi; Ishikawa, Takaki; Maeda, Hitoshi

    2012-07-01

    In investigating death due to mechanical asphyxiation and drowning, a cardiac attack is important for discriminating between possible causes of death and as a contributory factor in death processes; however, general pathologies involving visceral congestion are often similar. The present study compared terminal cardiac dysfunction in these fatalities using the molecular pathology of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain. Both mechanical asphyxiation (n=27) and drowning (n=23) showed significantly lower ANP and BNP mRNA expressions in bilateral ventricular walls than sudden cardiac deaths (n=36). In addition, right atrial wall BNP mRNA expression was lower in asphyxiation; however, immunostaining did not demonstrate any difference among these fatalities. Differences among the subtypes of asphyxiation or between fresh- and saltwater drowning were insignificant. These observations suggest a difference between primary heart failure in sudden cardiac death and terminal cardiac dysfunction secondary to fatal asphyxiation or drowning.

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

    PubMed

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

    2016-01-01

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

  7. Interleukin-6 and Interleukin-10 as Acute Kidney Injury Biomarkers after Pediatric Cardiac Surgery

    PubMed Central

    Greenberg, Jason H.; Whitlock, Richard; Zhang, William R.; Thiessen-Philbrook, Heather R.; Zappitelli, Michael; Devarajan, Prasad; Eikelboom, John; Kavsak, Peter A.; Devereaux, PJ; Shortt, Colleen; Garg, Amit X.; Parikh, Chirag R.

    2015-01-01

    Background Children undergoing cardiac surgery may exhibit a pronounced inflammatory response to cardiopulmonary bypass (CPB). Inflammation is recognized as an important pathophysiologic process leading to acute kidney injury (AKI). The aim of this study was to evaluate the association of two inflammatory cytokines interleukin (IL)-6 and IL-10 with AKI and other adverse outcomes in children after CPB surgery. Methods This is a sub-study of the Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) cohort, including 106 children from 1 month to 18 years old undergoing CPB. Plasma IL-6 and IL-10 were measured preoperatively and postoperatively on days 1 (within 6 hours after surgery) and 3. Results Stage 2/3 AKI, defined by atleast a doubling of baseline serum creatinine or dialysis, was diagnosed in 24 (23%) patients. Preoperative IL-6 was significantly higher in patients with stage 2/3 AKI vs. without stage 2/3 AKI (median (IQR), 2.6 (0.6-4.9) vs. 0.6 (0.6-2.2), p=0.03). After adjustment for clinical and demographic variables, the highest preoperative IL-6 tertile was associated with a six-fold increased risk for stage 2/3 AKI compared with the lowest tertile (adjusted OR 6.41 (CI: 1.16-35.35)). IL-6 and IL-10 increased significantly after surgery, peaking postoperatively on day 1. First postoperative IL-6 and IL-10 did not significantly differ between patients with vs. without stage 2/3 AKI. Elevated IL-6 on day 3 was associated with longer hospital stay (p=0.0001). Conclusions Preoperative plasma IL-6 is associated with development of stage 2/3 AKI and may be prognostic of resource utilization. PMID:25877915

  8. The clinical challenge of preventing sudden cardiac death immediately after acute ST-elevation myocardial infarction.

    PubMed

    Manolis, Antonis S

    2014-12-01

    Unfortunately, of all patients experiencing acute myocardial infarction (MI), usually in the form of ST-elevation MI, 25-35% will die of sudden cardiac death (SCD) before receiving medical attention, most often from ventricular fibrillation. For patients who reach the hospital, prognosis is considerably better and has improved over the years. Reperfusion therapy, best attained with primary percutaneous coronary intervention compared to thrombolysis, has made a big difference in reducing the risk of SCD early and late after ST-elevation MI. In-hospital SCD due to ventricular tachyarrhythmias is manageable, with either preventive measures or drugs or electrical cardioversion. There is general agreement for secondary prevention of SCD post-MI with implantation of a cardioverter defibrillator (ICD) when malignant ventricular arrhythmias occur late (>48 h) after an MI, and are not due to reversible or correctable causes. The major challenge remains that of primary prevention, that is, how to prevent SCD during the first 1-3 months after ST-elevation MI for patients who have low left ventricular ejection fraction and are not candidates for an ICD according to current guidelines, due to the results of two studies, which did not show any benefits of early (<40 days after an MI) ICD implantation. Two recent documents may provide direction as to how to bridge the gap for this early post-MI period. Both recommend an electrophysiology study to guide implantation of an ICD, at least for those developing syncope or non-sustained ventricular tachycardia, who have an inducible sustained ventricular tachycardia at the electrophysiology study. An ICD is also recommended for patients with indication for a permanent pacemaker due to bradyarrhythmias, who also meet primary prevention criteria for SCD.

  9. Regional cardiac adrenergic function using I-123 meta-iodobenzylguanidine tomographic imaging after acute myocardial infarction

    SciTech Connect

    McGhie, A.I.; Corbett, J.R.; Akers, M.S.; Kulkarni, P.; Sills, M.N.; Kremers, M.; Buja, L.M.; Durant-Reville, M.; Parkey, R.W.; Willerson, J.T. )

    1991-02-01

    The effect of acute myocardial infarction (AMI) on regional cardiac adrenergic function was studied in 27 patients mean +/- standard deviation 10 +/- 4 days after AMI. Regional adrenergic function was evaluated noninvasively with I-123 meta-iodobenzylguanidine (MIBG) using a dedicated 3-detector tomograph. Four hours after its administration, there was reduced MIBG uptake in the region of infarction, 0.38 +/- 0.31 counts/pixel/mCi x 103 compared with 0.60 +/- 0.30 counts/pixel/mCi x 103 and 0.92 +/- 0.35 counts/pixel/mCi x 103 in the zones bordering and distant from the infarct area, respectively, p less than 0.001. In all patients, the area of reduced MIBG uptake after 4 hours was more extensive that the associated thallium-201 perfusion defect with defect scores of 52 +/- 22 and 23 +/- 18%, respectively, p less than 0.001. After anterior wall AMI, the 4-hour MIBG defect score was 70 +/- 13% and the degree of mismatch between myocardial perfusion and MIBG uptake was 30 +/- 9% compared with 39 +/- 17 and 21 +/- 17% after inferior AMI, p less than 0.001 and p = 0.016, respectively. The 4-hour MIBG defect score correlated inversely with the predischarge left ventricular ejection fraction, r = -0.73, p less than 0.001. Patients with ventricular arrhythmia of greater than or equal to 1 ventricular premature complexes per hour, paired ventricular premature complexes or ventricular tachycardia detected during the late hospital phase had higher 4-hour MIBG defect scores, 62.5 +/- 15.0%, than patients with no detectable complex ventricular ectopic activity and a ventricular premature complex frequency of less than 1 per hour, 44.6 +/- 23.4%, p = 0.036.

  10. Sudden cardiac death after acute ST elevation myocardial infarction: insight from a developing country

    PubMed Central

    Rao, Hygriv B; Sastry, B K S; Korabathina, Radhika; Raju, Krishnam P

    2012-01-01

    Background There is no data concerning sudden cardiac death (SCD) following acute ST elevation myocardial infarction (STEMI) in India. We assessed the incidence and factors influencing SCD following STEMI. Methods Patients with STEMI admitted in our hospital from 2006 to 2009 were prospectively entered into a database. In the period 2010–2011, patients or their kin were periodically contacted and administered a questionnaire to ascertain their survival, and mode of death if applicable. Results Study population comprised of 929 patients with STEMI (mean age 55±17 years) having a mean follow-up of 41±16 months. The total number of deaths was 159, of which 78 were SCD (mean age 62.2±10 years). The cumulative incidence of total deaths and SCD at 1 month, 1, 2, 3 years and at conclusion of the study was 10.1%, 13.2%, 14.6%, 15.8%, 17.3% and 4.9%, 6.5%, 8.0%, 8.9% and 9.7%, respectively. The temporal distribution of SCD was 53.9% at first month, 19.2% at 1 month to 1 year, 15.4% in 1–2 years, 7.6% in 2–3 years and 3.8% beyond 3 years. Comparison between SCD and survivor cohorts by multivariate analysis showed five variables were found to be associated with SCD (age p=0.0163, female gender p=0.0042, severe LV dysfunction p=0.0292, absence of both reperfusion and revascularisation p=0.0373 and lack of compliance with medications p <0.0001). Conclusions SCD following STEMI accounts for about half of the total deaths. It involves younger population and most of these occur within the first month. This data has relevance in prioritising healthcare strategies in India. PMID:27326036

  11. Obesity negatively impacts aerobic capacity improvements both acutely and 1-year following cardiac rehabilitation.

    PubMed

    Martin, Billie-Jean; Aggarwal, Sandeep G; Stone, James A; Hauer, Trina; Austford, Leslie D; Knudtson, Merril; Arena, Ross

    2012-12-01

    Cardiac rehabilitation (CR) produces a host of health benefits related to modifiable cardiovascular risk factors. The purpose of the present investigation was to determine the influence of body weight, assessed through BMI, on acute and long-term improvements in aerobic capacity following completion of CR. Three thousand nine hundred and ninety seven subjects with coronary artery disease (CAD) participated in a 12-week multidisciplinary CR program. Subjects underwent an exercise test to determine peak estimated metabolic equivalents (eMETs) and BMI assessment at baseline, immediately following CR completion and at 1-year follow-up. Normal weight subjects at 1-year follow-up demonstrated the greatest improvement in aerobic fitness and best retention of those gains (gain in peak METs: 0.95 ± 1.1, P < 0.001). Although the improvement was significant (P < 0.001), subjects who were initially classified as obese had the lowest aerobic capacity and poorest retention in CR fitness gains at 1-year follow-up (gain in peak eMETs: 0.69 ± 1.2). Subjects initially classified as overweight by BMI had a peak eMET improvement that was also significantly better (P < 0.05) than obese subjects at 1-year follow-up (gain in peak eMETs: 0.82 ± 1.1). Significant fitness gains, one of the primary beneficial outcomes of CR, can be obtained by all subjects irrespective of BMI classification. However, obese patients have poorer baseline fitness and are more likely to "give back" fitness gains in the long term. Obese CAD patients may therefore benefit from additional interventions to enhance the positive adaptations facilitated by CR.

  12. [Recent treatment of postischaemic anoxic brain damage after cardiac arrest by using therapeutic hypothermia].

    PubMed

    Andjelić, Sladjana

    2008-01-01

    Organ injury caused by ischaemia and anoxia during prolonged cardiac arrest is compounded by reperfusion injury that occurs when spontaneous circulation is restored. Mild hypothermia (32-35 degrees C) is neuroprotective through several mechanisms, including suppression of apoptosis, reduced production of excitotoxins and free radicals, and anti-inflammatory actions. Experimental studies show that hypothermia is more effective the earlier it is started after return of spontaneous circulation (ROSC). Two randomised clinical trials show improved survival and neurological outcome in adults who remained comatose after initial resuscitation from prehospital VF cardiac arrest, and who were cooled after ROSC. Different strategies can be used to induce hypothermia. Optimal timing of therapeutic hypothermia for cardiac ischaemia is unknown. In patients who failed to respond to standard cardiopulmonary resuscitation, intra-arrest cooling using ice-cold intravenous (i.v.) fluid improved the chance of survival. Recently, fasudil, a Rho kinase inhibitor, was reported to prevent cerebral ischaemia in vivo by increasing cerebral blood flow and inhibiting inflammatory responses. In future, two different kinds of protective therapies, BCL-2 overexpression and hypothermia,will both inhibit aspects of apoptotic cell death cascades, and that combination treatment can prolong the temporal "therapeutic window" for gene therapy. PMID:19069351

  13. Association between Peripheral Oxidative Stress and White Matter Damage in Acute Traumatic Brain Injury

    PubMed Central

    Lin, Wei-Ming; Chen, Meng-Hsiang; Wang, Hung-Chen; Lu, Cheng-Hsien; Chen, Pei-Chin; Chen, Hsiu-Ling; Tsai, Nai-Wen; Su, Yu-Jih; Li, Shau-Hsuan; Kung, Chia-Te; Chiu, Tsui-Min; Weng, Hsu-Huei; Lin, Wei-Che

    2014-01-01

    The oxidative stress is believed to be one of the mechanisms involved in the neuronal damage after acute traumatic brain injury (TBI). However, the disease severity correlation between oxidative stress biomarker level and deep brain microstructural changes in acute TBI remains unknown. In present study, twenty-four patients with acute TBI and 24 healthy volunteers underwent DTI. The peripheral blood oxidative biomarkers, like serum thiol and thiobarbituric acid-reactive substances (TBARS) concentrations, were also obtained. The DTI metrics of the deep brain regions, as well as the fractional anisotropy (FA) and apparent diffusion coefficient, were measured and correlated with disease severity, serum thiol, and TBARS levels. We found that patients with TBI displayed lower FAs in deep brain regions with abundant WMs and further correlated with increased serum TBARS level. Our study has shown a level of anatomic detail to the relationship between white matter (WM) damage and increased systemic oxidative stress in TBI which suggests common inflammatory processes that covary in both the peripheral and central reactions after TBI. PMID:24804213

  14. Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

    PubMed

    Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

    2011-06-01

    Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

  15. Acute toxicity and superficial damage to goldfish from the ionic liquid 1-methyl-3-octylimidazolium bromide.

    PubMed

    Li, Xiao-Yu; Zeng, Shi-Hu; Zhang, Wei-Hong; Liu, Li; Ma, Shuai; Wang, Jian-Ji

    2013-04-01

    In the present study, goldfish toxicity and superficial damage from 1-methyl-3-octylimidazolium bromide ([C8 mim]Br) exposure were evaluated by an acute toxicity test. These results show that the 24-h 50% lethal concentration for [C8 mim]Br in goldfish is 244 mg L(-1) , and this indicates that [C8 mim]Br is a chemical with moderate or low toxicity to organisms. Scanning electronic microscope and histological observations revealed that acute exposure to [C8 mim]Br induced obvious superficial damage to the skin, gill filaments, and intestinal villi of the goldfish, and this suggests that the skin, gills, and intestines may be the first direct targets of the ionic liquid in this fish. Histological examination also indicated that [C8 mim]Br-exposure caused damage to the goldfish's hepatopancreas and kidney, consisting mainly of hepatic cords in a loose connection, hepatic cytoplasmic vacuolation, renal parenchyma vacuolization, and intumescence of the renal tubule. In addition, we found that [C8 mim]Br caused a significant increase in malondialdehyde (MDA) level in the hepatopancreases from these goldfish, and thus we suggest that the MDA level may be a biomarker of [C8 mim]Br-toxicity in goldfish.

  16. Metabolic fingerprinting to understand therapeutic effects and mechanisms of silybin on acute liver damage in rat

    PubMed Central

    Liang, Qun; Wang, Cong; Li, Binbing; Zhang, Ai-hua

    2015-01-01

    Background: Metabolic fingerprinting is a rapid and noninvasive analysis, representing a powerful approach for the characterization of phenotypes and the distinction of specific metabolic states due to environmental alterations. It has become a valuable analytical approach for the characterization of phenotypes and is the rapidly evolving field of the comprehensive measurement of ideally all endogenous metabolites in bio-samples. Silybin has displayed bright prospects in the prevention and therapy of liver injury, and we had conducted a preliminary exploration on the molecular mechanism of the hepatoprotective effects of silybin. Because the knowledge on the metabolic responses of an acute liver damage rat to the silybin is still scarce, metabolic fingerprinting can provide relevant information on the intrinsic metabolic adjustments. Materials and Methods: Here, the physiological and metabolic changes in the acute liver damage rat were investigated by performing a metabolic analysis. The phenotypic response was assessed by liquid chromatography/mass spectrometry (LC/MS) combined with pattern recognition approaches such as principal components analysis and partial least squares projection to supervised latent structures and discriminant analysis. Multivariate analysis of the data showed trends in scores plots that were related to the concentration of the silybin. Results: Results indicate 10 ions (7 upregulated and 3 downregulated) as differentiating metabolites. Key observations include perturbations of metabolic pathways linked to glutathione metabolism, tryptophan metabolism, cysteine and methionine metabolism, etc., Overall, this investigation illustrates the power of the LC/MS combined with the pattern recognition methods that can engender new insights into silybin affecting on metabolism pathways of an acute liver damage rat. Conclusion: The present study demonstrates that the combination of metabolic fingerprinting with appropriate chemometric analysis is a

  17. Acute Cardiac Failure in a Pregnant Woman due to Thyrotoxic Crisis

    PubMed Central

    Okuda, Nao; Onodera, Mutsuo; Tsunano, Yumiko; Nakataki, Emiko; Oto, Jun; Imanaka, Hideaki; Nishimura, Masaji

    2012-01-01

    Introduction. Cardiac failure during pregnancy is usually related to preeclampsia/eclampsia, rarely to hyperthyroidism. While hyperthyroidism can easily lead to hypertensive cardiac failure and may harm the fetus, it is sometimes difficult to distinguish hyperthyroidism from normal pregnancy. Case Presentation. We encountered a case of 41-year-old pregnant woman with hypertensive cardiac failure. Because we initially diagnosed as pre-eclampsia/eclampsia, Caesarian section was performed. However, her symptoms still persisted after delivery. After thyroid function test results taken on the day of admission were obtained on the fourth day, we could diagnose that her cardiac failure was caused by thyrotoxic crisis. Conclusions. Hypertensive cardiac failure due to hyperthyroidism during pregnancy is rare and difficult to diagnose because of similar presentation of normal pregnancy. However, physicians should be aware of the risks posed by hyperthyroidism during pregnancy. PMID:24804110

  18. Cardiac Amyloidosis: Typical Imaging Findings and Diffuse Myocardial Damage Demonstrated by Delayed Contrast-Enhanced MRI

    SciTech Connect

    Sueyoshi, Eijun Sakamoto, Ichiro; Okimoto, Tomoaki; Hayashi, Kuniaki; Tanaka, Kyouei; Toda, Genji

    2006-08-15

    Amyloidosis is a rare systemic disease. However, involvement of the heart is a common finding and is the most frequent cause of death in amyloidosis. We report the sonographic, scintigraphic, and MRI features of a pathologically proven case of cardiac amyloidosis. Delayed contrast-enhanced MR images, using an inversion recovery prepped gradient-echo sequence, revealed diffuse enhancement in the wall of both left and right ventricles. This enhancement suggested expansion of the extracellular space of the myocardium caused by diffuse myocardial necrosis secondary to deposition of amyloid.

  19. High-dose perioperative atorvastatin and acute kidney injury following cardiac surgery: a randomized clinical trial

    PubMed Central

    Billings, Frederic T.; Hendricks, Patricia A.; Schildcrout, Jonathan S.; Shi, Yaping; Petracek, Michael R.; Byrne, John G.; Brown, Nancy J.

    2016-01-01

    Importance Hydroxy-methylglutaryl-coenzyme A reductase inhibitors affect several mechanisms underlying acute kidney injury (AKI). Objective To test the hypothesis that short-term high-dose perioperative atorvastatin would reduce AKI following cardiac surgery Design, Setting, Participants Double-blinded, placebo-controlled, randomized trial of adult cardiac surgery patients conducted November 2009 to October 2014 at Vanderbilt University Medical Center Intervention Statin-naïve patients (n=199) were randomly assigned 80mg atorvastatin the day before surgery, 40mg the morning of surgery, and 40mg daily following surgery (n=102) or matching placebo (n=97). Patients using statins prior to study enrollment (n=416) continued their pre-enrollment statin until the day of surgery, were randomly assigned 80mg atorvastatin the morning of surgery and 40mg the morning after (n=206) or matching placebo (n=210), and resumed their statin on postoperative day 2. Main Outcome AKI, defined as 0.3 mg/dl rise in serum creatinine within 48 hours of surgery (AKIN criteria) Results The DSMB recommended stopping the statin-naïve group due to increased AKI among statin-naïve participants with chronic kidney disease (CKD, estimated glomerular filtration rate <60 ml/min/1.73 m2) receiving atorvastatin and then recommended stopping for futility after 615 participants (median age, 67 years; 188 [30.6%] women, and 202 [32.8%] diabetic) completed the study. Among all participants (n=615), AKI occurred in 64 of 308 participants (20.8%) randomized to atorvastatin versus 60 of 307 participants (19.5%) randomized to placebo (risk ratio [RR], 1.06 [95% CI, 0.78–1.46]; P=0.75). Among statin-naïve participants (n=199), AKI occurred in 22 of 102 (21.6%) receiving atorvastatin versus 13 of 97 (13.4%) receiving placebo (RR, 1.61 [0.86–3.01]; P=0.15), and serum creatinine increased 0.11mg/dl (−0.11 to 0.56) (median [10th to 90th percentile]) in those randomized to atorvastatin versus 0.05 (−0

  20. α1A-Adrenergic receptor prevents cardiac ischemic damage through PKCδ/GLUT1/4-mediated glucose uptake.

    PubMed

    Shi, Ting; Papay, Robert S; Perez, Dianne M

    2016-01-01

    While α(1)-adrenergic receptors (ARs) have been previously shown to limit ischemic cardiac damage, the mechanisms remain unclear. Most previous studies utilized low oxygen conditions in addition to ischemic buffers with glucose deficiencies, but we discovered profound differences if the two conditions are separated. We assessed both mouse neonatal and adult myocytes and HL-1 cells in a series of assays assessing ischemic damage under hypoxic or low glucose conditions. We found that α(1)-AR stimulation protected against increased lactate dehydrogenase release or Annexin V(+) apoptosis under conditions that were due to low glucose concentration not to hypoxia. The α(1)-AR antagonist prazosin or nonselective protein kinase C (PKC) inhibitors blocked the protective effect. α(1)-AR stimulation increased (3)H-deoxyglucose uptake that was blocked with either an inhibitor to glucose transporter 1 or 4 (GLUT1 or GLUT4) or small interfering RNA (siRNA) against PKCδ. GLUT1/4 inhibition also blocked α(1)-AR-mediated protection from apoptosis. The PKC inhibitor rottlerin or siRNA against PKCδ blocked α(1)-AR stimulated GLUT1 or GLUT4 plasma membrane translocation. α(1)-AR stimulation increased plasma membrane concentration of either GLUT1 or GLUT4 in a time-dependent fashion. Transgenic mice overexpressing the α(1A)-AR but not α(1B)-AR mice displayed increased glucose uptake and increased GLUT1 and GLUT4 plasma membrane translocation in the adult heart while α(1A)-AR but not α(1B)-AR knockout mice displayed lowered glucose uptake and GLUT translocation. Our results suggest that α(1)-AR activation is anti-apoptotic and protective during cardiac ischemia due to glucose deprivation and not hypoxia by enhancing glucose uptake into the heart via PKCδ-mediated GLUT translocation that may be specific to the α(1A)-AR subtype.

  1. Direct acute tubular damage contributes to Shigatoxin-mediated kidney failure.

    PubMed

    Porubsky, Stefan; Federico, Giuseppina; Müthing, Johannes; Jennemann, Richard; Gretz, Norbert; Büttner, Stefan; Obermüller, Nicholas; Jung, Oliver; Hauser, Ingeborg A; Gröne, Elisabeth; Geiger, Helmut; Gröne, Hermann-Josef; Betz, Christoph

    2014-09-01

    The pathogenesis and therapy of Shigatoxin 2 (Stx2)-mediated kidney failure remain controversial. Our aim was to test whether, during an infection with Stx2-producing E. coli (STEC), Stx2 exerts direct effects on renal tubular epithelium and thereby possibly contributes to acute renal failure. Mice represent a suitable model because they, like humans, express the Stx2-receptor Gb3 in the tubular epithelium but, in contrast to humans, not in glomerular endothelia, and are thus free of glomerular thrombotic microangiopathy (TMA). In wild-type mice, Stx2 caused acute tubular dysfunction with consequent electrolyte disturbance, which was most likely the cause of death. Tubule-specific depletion of Gb3 protected the mice from acute renal failure. In vitro, Stx2 induced secretion of proinflammatory cytokines and apoptosis in human tubular epithelial cells, thus implicating a direct effect of Stx2 on the tubular epithelium. To correlate these results to human disease, kidney biopsies and outcome were analysed in patients with Stx2-associated kidney failure (n = 11, aged 22-44 years). The majority of kidney biopsies showed different stages of an ongoing TMA; however, no glomerular complement activation could be demonstrated. All biopsies, including those without TMA, showed severe acute tubular damage. Due to these findings, patients were treated with supportive therapy without complement-inhibiting antibodies (eculizumab) or immunoadsorption. Despite the severity of the initial disease [creatinine 6.34 (1.31-17.60) mg/dl, lactate dehydrogenase 1944 (753-2792) U/l, platelets 33 (19-124)/nl and haemoglobin 6.2 (5.2-7.8) g/dl; median (range)], all patients were discharged after 33 (range 19-43) days with no neurological symptoms and no dialysis requirement [creatinine 1.39 (range 0.84-2.86) mg/dl]. The creatinine decreased further to 0.90 (range 0.66-1.27) mg/dl after 24 months. Based on these data, one may surmise that acute tubular damage represents a separate

  2. Acute Cardiac Impairment Associated With Concurrent Chemoradiotherapy for Esophageal Cancer: Magnetic Resonance Evaluation

    SciTech Connect

    Hatakenaka, Masamitsu; Yonezawa, Masato; Nonoshita, Takeshi; Nakamura, Katsumasa; Yabuuchi, Hidetake; Shioyama, Yoshiyuki; Nagao, Michinobu; Matsuo, Yoshio; Kamitani, Takeshi; Higo, Taiki; Nishikawa, Kei; Setoguchi, Taro; Honda, Hiroshi

    2012-05-01

    Purpose: To evaluate acute cardiac effects of concurrent chemoradiotherapy (CCRT) for esophageal cancer. Methods and Materials: This prospective study was approved by the institutional review board, and written informed consent was obtained from all participants. The left ventricular function (LVF) of 31 patients with esophageal cancer who received cisplatin and 5-fluorouracil-based CCRT was evaluated using cardiac cine magnetic resonance imaging. The patients were classified into two groups according to mean LV dose. The parameters related to LVF were compared between before and during (40 Gy) or between before and after CCRT using a Wilcoxon matched-pairs single rank test, and parameter ratios (during/before CCRT, after/before CCRT) were also compared between the groups with a t test. Data were expressed as mean {+-} SE. Results: In the low LV-dose group (n = 10; mean LV dose <0.6 Gy), LV ejection fraction decreased significantly (before vs. during vs. after CCRT; 62.7% {+-} 2.98% vs. 59.8% {+-} 2.56% vs. 60.6% {+-} 3.89%; p < 0.05). In the high LV-dose group (n = 21; mean LV dose of 3.6-41.2 Gy), LV end-diastolic volume index (before vs. after CCRT; 69.1 {+-} 2.93 vs. 57.0 {+-} 3.23 mL/m{sup 2}), LV stroke volume index (38.6 {+-} 1.56 vs. 29.9 {+-} 1.60 mL/m{sup 2}), and LV ejection fraction (56.9% {+-} 1.79% vs. 52.8% {+-} 1.15%) decreased significantly (p < 0.05) after CCRT. Heart rate increased significantly (before vs. during vs. after CCRT; 66.8 {+-} 3.05 vs. 72.4 {+-} 4.04 vs. 85.4 {+-} 3.75 beats per minute, p < 0.01). Left ventricle wall motion decreased significantly (p < 0.05) in segments 8 (before vs. during vs. after CCRT; 6.64 {+-} 0.54 vs. 4.78 {+-} 0.43 vs. 4.79 {+-} 0.50 mm), 9 (6.88 {+-} 0.45 vs. 5.04 {+-} 0.38 vs. 5.27 {+-} 0.47 mm), and 10 (9.22 {+-} 0.48 vs. 8.08 {+-} 0.34 vs. 8.19 {+-} 0.56 mm). The parameter ratios of LV end-diastolic volume index, stroke volume index, wall motion in segment 9, and heart rate showed significant difference

  3. Mitochondrial ROS Induces Cardiac Inflammation via a Pathway through mtDNA Damage in a Pneumonia-Related Sepsis Model.

    PubMed

    Yao, Xiao; Carlson, Deborah; Sun, Yuxiao; Ma, Lisha; Wolf, Steven E; Minei, Joseph P; Zang, Qun S

    2015-01-01

    We have previously shown that mitochondria-targeted vitamin E (Mito-Vit-E), a mtROS specific antioxidant, improves cardiac performance and attenuates inflammation in a pneumonia-related sepsis model. In this study, we applied the same approaches to decipher the signaling pathway(s) of mtROS-dependent cardiac inflammation after sepsis. Sepsis was induced in Sprague Dawley rats by intratracheal injection of S. pneumoniae. Mito-Vit-E, vitamin E or vehicle was administered 30 minutes later. In myocardium 24 hours post-inoculation, Mito-Vit-E, but not vitamin E, significantly protected mtDNA integrity and decreased mtDNA damage. Mito-Vit-E alleviated sepsis-induced reduction in mitochondria-localized DNA repair enzymes including DNA polymerase γ, AP endonuclease, 8-oxoguanine glycosylase, and uracil-DNA glycosylase. Mito-Vit-E dramatically improved metabolism and membrane integrity in mitochondria, suppressed leakage of mtDNA into the cytoplasm, inhibited up-regulation of Toll-like receptor 9 (TLR9) pathway factors MYD88 and RAGE, and limited RAGE interaction with its ligand TFAM in septic hearts. Mito-Vit-E also deactivated NF-κB and caspase 1, reduced expression of the essential inflammasome component ASC, and decreased inflammatory cytokine IL-1β. In vitro, both Mito-Vit-E and TLR9 inhibitor OND-I suppressed LPS-induced up-regulation in MYD88, RAGE, ASC, active caspase 1, and IL-1β in cardiomyocytes. Since free mtDNA escaped from damaged mitochondria function as a type of DAMPs to stimulate inflammation through TLR9, these data together suggest that sepsis-induced cardiac inflammation is mediated, at least partially, through mtDNA-TLR9-RAGE. At last, Mito-Vit-E reduced the circulation of myocardial injury marker troponin-I, diminished apoptosis and amended morphology in septic hearts, suggesting that mitochondria-targeted antioxidants are a potential cardioprotective approach for sepsis. PMID:26448624

  4. Sensitivity Analysis of Vagus Nerve Stimulation Parameters on Acute Cardiac Autonomic Responses: Chronotropic, Inotropic and Dromotropic Effects

    PubMed Central

    Ojeda, David; Le Rolle, Virginie; Romero-Ugalde, Hector M.; Gallet, Clément; Bonnet, Jean-Luc; Henry, Christine; Bel, Alain; Mabo, Philippe; Carrault, Guy; Hernández, Alfredo I.

    2016-01-01

    Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset). These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS configurations were estimated using a Gaussian process regression (GPR) model. In order to quantitatively analyze the effect of each parameter and their combinations on the cardiac response, the Sobol sensitivity method was applied to the obtained GPR model and inter-individual sensitivity markers were estimated using a bootstrap approach. Results highlight the dominant effect of pulse current, pulse width and number of pulses, which explain respectively 49.4%, 19.7% and 6.0% of the mean global cardiovascular variability provoked by VNS. More interestingly, results also quantify the effect of the interactions between VNS parameters. In particular, the interactions between current and pulse width provoke higher cardiac effects than the changes on the number of pulses alone (between 6 and 25% of the variability). Although the sensitivity of individual VNS parameters seems similar for chronotropic, dromotropic and inotropic responses, the interacting effects of VNS parameters provoke

  5. Acute Cardiac Rejection Requires Directly Cytotoxic CD4 T cells: A Parallel Pathway between Fas and Perforin1

    PubMed Central

    Grazia, Todd J.; Plenter, Robert J.; Weber, Sarah M.; Lepper, Helen M.; Victorino, Francisco; Zamora, Martin R.; Pietra, Biagio A.; Gill, Ronald G.

    2009-01-01

    Background CD4 T cells can suffice as effector cells to mediate primary acute cardiac allograft rejection. While CD4 T cells can readily kill appropriate target cells in vitro, the corresponding role of such cytolytic activity for mediating allograft rejection in vivo is unknown. Therefore, we determined whether the cytolytic effector molecules perforin and/or FasL (CD95L) were necessary for CD4 T cell-mediated rejection in vivo. Methods Wild type C3H(H-2k) or Fas (CD95)-deficient C3Hlpr (H-2k) hearts were transplanted into immune-deficient C57B6rag−/− (H-2b) mice. Recipients then were reconstituted with naïve purified CD4 T cells from either wild-type, perforin (pfp)-deficient, or FasL (gld)-deficient T cell donors. Results In vitro, alloreactive CD4 T cells were competent to lyse donor MHC class II+ target cells, largely by a Fas-dependent mechanism. In vivo, the individual disruption of either donor Fas expression (lpr) or CD4 T cell-derived perforin had no signifcant impact on acute rejection. However, FasL-deficient (gld) CD4 T cells demonstrated delayed allograft rejection. Importantly, the simultaneous removal of both donor Fas expression and CD4 T cell perforin completely abrograted acute rejection, despite the persistence of CD4 T cells within the graft. Conclusions Results demonstrate that the direct rejection of cardiac allografts by CD4 effector T cells requires the alternative contribution of graft Fas expression and T cell perforin expression. To our knowledge, this is the first demonstration that cytolytic activity by CD4 T cells can play an obligate role for primary acute allograft rejection in vivo. PMID:20061916

  6. The impact of beat-to-beat variability in optimising the acute hemodynamic response in cardiac resynchronisation therapy

    PubMed Central

    Niederer, Steven; Walker, Cameron; Crozier, Andrew; Hyde, Eoin R.; Blazevic, Bojan; Behar, Jonathan M.; Claridge, Simon; Sohal, Manav; Shetty, Anoop; Jackson, Tom; Rinaldi, Christopher

    2015-01-01

    Background Acute indicators of response to cardiac resynchronisation therapy (CRT) are critical for developing lead optimisation algorithms and evaluating novel multi-polar, multi-lead and endocardial pacing protocols. Accounting for beat-to-beat variability in measures of acute haemodynamic response (AHR) may help clinicians understand the link between acute measurements of cardiac function and long term clinical outcome. Methods and results A retrospective study of invasive pressure tracings from 38 patients receiving an acute pacing and electrophysiological study was performed. 602 pacing protocols for left ventricle (LV) (n = 38), atria–ventricle (AV) (n = 9), ventricle–ventricle (VV) (n = 12) and endocardial (ENDO) (n = 8) optimisation were performed. AHR was measured as the maximal rate of LV pressure development (dP/dtMx) for each beat. The range of the 95% confidence interval (CI) of mean AHR was ~ 7% across all optimisation protocols compared with the reported CRT response cut off value of 10%. A single clear optimal protocol was identifiable in 61%, 22%, 25% and 50% for LV, AV, VV and ENDO optimisation cases, respectively. A level of service (LOS) optimisation that aimed to maximise the expected AHR 5th percentile, minimising variability and maximising AHR, led to distinct optimal protocols from conventional mean AHR optimisation in 34%, 78%, 67% and 12.5% of LV, AV, VV and ENDO optimisation cases, respectively. Conclusion The beat-to-beat variation in AHR is significant in the context of CRT cut off values. A LOS optimisation offers a novel index to identify the optimal pacing site that accounts for both the mean and variation of the baseline measurement and pacing protocol. PMID:26844303

  7. Neuroprotection by gonadal steroid hormones in acute brain damage requires cooperation with astroglia and microglia.

    PubMed

    Johann, Sonja; Beyer, Cordian

    2013-09-01

    The neuroactive steroids 17β-estradiol and progesterone control a broad spectrum of neural functions. Besides their roles in the regulation of classical neuroendocrine loops, they strongly influence motor and cognitive systems, behavior, and modulate brain performance at almost every level. Such a statement is underpinned by the widespread and lifelong expression pattern of all types of classical and non-classical estrogen and progesterone receptors in the CNS. The life-sustaining power of neurosteroids for tattered or seriously damaged neurons aroused interest in the scientific community in the past years to study their ability for therapeutic use under neuropathological challenges. Documented by excellent studies either performed in vitro or in adequate animal models mimicking acute toxic or chronic neurodegenerative brain disorders, both hormones revealed a high potency to protect neurons from damage and saved neural systems from collapse. Unfortunately, neurons, astroglia, microglia, and oligodendrocytes are comparably target cells for both steroid hormones. This hampers the precise assignment and understanding of neuroprotective cellular mechanisms activated by both steroids. In this article, we strive for a better comprehension of the mutual reaction between these steroid hormones and the two major glial cell types involved in the maintenance of brain homeostasis, astroglia and microglia, during acute traumatic brain injuries such as stroke and hypoxia. In particular, we attempt to summarize steroid-activated cellular signaling pathways and molecular responses in these cells and their contribution to dampening neuroinflammation and neural destruction. This article is part of a Special Issue entitled 'CSR 2013'. PMID:23196064

  8. Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage.

    PubMed

    Suzuki, Takehiro; Yamaguchi, Hiroaki; Kikusato, Motoi; Hashizume, Osamu; Nagatoishi, Satoru; Matsuo, Akihiro; Sato, Takeya; Kudo, Tai; Matsuhashi, Tetsuro; Murayama, Kazutaka; Ohba, Yuki; Watanabe, Shun; Kanno, Shin-Ichiro; Minaki, Daichi; Saigusa, Daisuke; Shinbo, Hiroko; Mori, Nobuyoshi; Yuri, Akinori; Yokoro, Miyuki; Mishima, Eikan; Shima, Hisato; Akiyama, Yasutoshi; Takeuchi, Yoichi; Kikuchi, Koichi; Toyohara, Takafumi; Suzuki, Chitose; Ichimura, Takaharu; Anzai, Jun-Ichi; Kohzuki, Masahiro; Mano, Nariyasu; Kure, Shigeo; Yanagisawa, Teruyuki; Tomioka, Yoshihisa; Toyomizu, Masaaki; Tsumoto, Kohei; Nakada, Kazuto; Bonventre, Joseph V; Ito, Sadayoshi; Osaka, Hitoshi; Hayashi, Ken-Ichi; Abe, Takaaki

    2016-07-01

    Mitochondrial dysfunction causes increased oxidative stress and depletion of ATP, which are involved in the etiology of a variety of renal diseases, such as CKD, AKI, and steroid-resistant nephrotic syndrome. Antioxidant therapies are being investigated, but clinical outcomes have yet to be determined. Recently, we reported that a newly synthesized indole derivative, mitochonic acid 5 (MA-5), increases cellular ATP level and survival of fibroblasts from patients with mitochondrial disease. MA-5 modulates mitochondrial ATP synthesis independently of oxidative phosphorylation and the electron transport chain. Here, we further investigated the mechanism of action for MA-5. Administration of MA-5 to an ischemia-reperfusion injury model and a cisplatin-induced nephropathy model improved renal function. In in vitro bioenergetic studies, MA-5 facilitated ATP production and reduced the level of mitochondrial reactive oxygen species (ROS) without affecting activity of mitochondrial complexes I-IV. Additional assays revealed that MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane. In Hep3B cells, overexpression of mitofilin increased the basal ATP level, and treatment with MA-5 amplified this effect. In a unique mitochondrial disease model (Mitomice with mitochondrial DNA deletion that mimics typical human mitochondrial disease phenotype), MA-5 improved the reduced cardiac and renal mitochondrial respiration and seemed to prolong survival, although statistical analysis of survival times could not be conducted. These results suggest that MA-5 functions in a manner differing from that of antioxidant therapy and could be a novel therapeutic drug for the treatment of cardiac and renal diseases associated with mitochondrial dysfunction. PMID:26609120

  9. DNA Damage Focus Analysis in Blood Samples of Minipigs Reveals Acute Partial Body Irradiation

    PubMed Central

    Lamkowski, Andreas; Forcheron, Fabien; Agay, Diane; Ahmed, Emad A.; Drouet, Michel; Meineke, Viktor; Scherthan, Harry

    2014-01-01

    Radiation accidents frequently involve acute high dose partial body irradiation leading to victims with radiation sickness and cutaneous radiation syndrome that implements radiation-induced cell death. Cells that are not lethally hit seek to repair ionizing radiation (IR) induced damage, albeit at the expense of an increased risk of mutation and tumor formation due to misrepair of IR-induced DNA double strand breaks (DSBs). The response to DNA damage includes phosphorylation of histone H2AX in the vicinity of DSBs, creating foci in the nucleus whose enumeration can serve as a radiation biodosimeter. Here, we investigated γH2AX and DNA repair foci in peripheral blood lymphocytes of Göttingen minipigs that experienced acute partial body irradiation (PBI) with 49 Gy (±6%) Co-60 γ-rays of the upper lumbar region. Blood samples taken 4, 24 and 168 hours post PBI were subjected to γ-H2AX, 53BP1 and MRE11 focus enumeration. Peripheral blood lymphocytes (PBL) of 49 Gy partial body irradiated minipigs were found to display 1–8 DNA damage foci/cell. These PBL values significantly deceed the high foci numbers observed in keratinocyte nuclei of the directly γ-irradiated minipig skin regions, indicating a limited resident time of PBL in the exposed tissue volume. Nonetheless, PBL samples obtained 4 h post IR in average contained 2.2% of cells displaying a pan-γH2AX signal, suggesting that these received a higher IR dose. Moreover, dispersion analysis indicated partial body irradiation for all 13 minipigs at 4 h post IR. While dose reconstruction using γH2AX DNA repair foci in lymphocytes after in vivo PBI represents a challenge, the DNA damage focus assay may serve as a rapid, first line indicator of radiation exposure. The occurrence of PBLs with pan-γH2AX staining and of cells with relatively high foci numbers that skew a Poisson distribution may be taken as indicator of acute high dose partial body irradiation, particularly when samples are available early after

  10. Assessment of microembolization associated with revascularization in acute myocardial infarction: MDCT cardiac perfusion and function study.

    PubMed

    Saeed, Maythem; Hetts, Steven W; Do, Loi; Wilson, Mark W

    2013-12-01

    To use multi-detector computed tomography (MDCT) for assessing the effects of coronary microemboli on pre-existing acute myocardial infarct (AMI) and to compare this pathology to LAD microembolization and occlusion/reperfusion. An angioplasty balloon catheter was placed in the LAD coronary artery of pigs under X-ray guidance. Four animals served as controls without intervention (group A) and an additional 24 animals (8/group) were subjected to microembolization (group B), occlusion/reperfusion (group C) or combination of the two insults (group D). MDCT was used to assess perfusion, LV function and viability. At postmortem, the LV sections were stained with hematoxylin/eosin and triphenyltetrazolium chloride (TTC). Dynamic perfusion and helical cine MDCT demonstrated decline in regional LV perfusion and function, respectively, after all interventions. MDCT showed significant differences in ejection fraction between groups: A = 57.5 ± 4.7%, B = 40.3 ± 0.5% P < 0.05, C = 34.9 ± 1.3% P < 0.05 and D = 30.7 ± 1.2% P < 0.05, while viability MDCT demonstrated differences in enhancement patterns and extents of damage between the groups (B = 9.1 ± 0.4% LV mass, C = 11.9 ± 0.7% and D = 16.2 ± 1.2%, P < 0.05) and extent of microvascular obstruction (MVO) (group C = 3.2 ± 1.0% LV mass versus D = 5.2 ± 0.7%, P < 0.01). DE-MDCT overestimated all types of myocardial damage compared with TTC, but showed a close correlation (r > 0.7). Microscopic examination confirmed the presence of patchy and contiguous necrosis, MVO, edema and calcium deposits. Dynamic and helical cine MDCT imaging can grade LV dysfunction and perfusion deficit, respectively. DE-MDCT demonstrated a large and persistent MVO zone after microembolization of pre-existing AMI. Furthermore, it has the potential to visualize patchy microinfarct, detect perfusion deficits and dysfunction at the border zone after microembolization of pre-existing AMI.

  11. PEDF improves cardiac function in rats with acute myocardial infarction via inhibiting vascular permeability and cardiomyocyte apoptosis.

    PubMed

    Zhang, Hao; Wang, Zheng; Feng, Shou-Jie; Xu, Lei; Shi, He-Xian; Chen, Li-Li; Yuan, Guang-Da; Yan, Wei; Zhuang, Wei; Zhang, Yi-Qian; Zhang, Zhong-Ming; Dong, Hong-Yan

    2015-03-11

    Pigment epithelium-derived factor (PEDF) is a pleiotropic gene with anti-inflammatory, antioxidant and anti-angiogenic properties. However, recent reports about the effects of PEDF on cardiomyocytes are controversial, and it is not known whether and how PEDF acts to inhibit hypoxic or ischemic endothelial injury in the heart. In the present study, adult Sprague-Dawley rat models of acute myocardial infarction (AMI) were surgically established. PEDF-small interfering RNA (siRNA)-lentivirus (PEDF-RNAi-LV) or PEDF-LV was delivered into the myocardium along the infarct border to knockdown or overexpress PEDF, respectively. Vascular permeability, cardiomyocyte apoptosis, myocardial infarct size and animal cardiac function were analyzed. We also evaluated PEDF's effect on the suppression of the endothelial permeability and cardiomyocyte apoptosis under hypoxia in vitro. The results indicated that PEDF significantly suppressed the vascular permeability and inhibited hypoxia-induced endothelial permeability through PPARγ-dependent tight junction (TJ) production. PEDF protected cardiomyocytes against ischemia or hypoxia-induced cell apoptosis both in vivo and in vitro via preventing the activation of caspase-3. We also found that PEDF significantly reduced myocardial infarct size and enhanced cardiac function in rats with AMI. These data suggest that PEDF could protect cardiac function from ischemic injury, at least by means of reducing vascular permeability, cardiomyocyte apoptosis and myocardial infarct size.

  12. High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study

    PubMed Central

    Shah, Anoop S V; Anand, Atul; Sandoval, Yader; Lee, Kuan Ken; Smith, Stephen W; Adamson, Philip D; Chapman, Andrew R; Langdon, Timothy; Sandeman, Dennis; Vaswani, Amar; Strachan, Fiona E; Ferry, Amy; Stirzaker, Alexandra G; Reid, Alan; Gray, Alasdair J; Collinson, Paul O; McAllister, David A; Apple, Fred S; Newby, David E; Mills, Nicholas L

    2015-01-01

    Summary Background Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits. Methods We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123). Findings 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3–99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8–99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21–0·80; p<0·0001). Interpretation Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from

  13. Combined ECG, Echocardiographic, and Biomarker Criteria for Diagnosing Acute Myocardial Infarction in Out-of-Hospital Cardiac Arrest Patients

    PubMed Central

    Lee, Sang-Eun; Uhm, Jae-Sun; Kim, Jong-Youn; Pak, Hui-Nam; Lee, Moon-Hyoung

    2015-01-01

    Purpose Acute coronary lesions commonly trigger out-of-hospital cardiac arrest (OHCA). However, the prevalence of coronary artery disease (CAD) in Asian patients with OHCA and whether electrocardiogram (ECG) and other findings might predict acute myocardial infarction (AMI) have not been fully elucidated. Materials and Methods Of 284 consecutive resuscitated OHCA patients seen between January 2006 and July 2013, we enrolled 135 patients who had undergone coronary evaluation. ECGs, echocardiography, and biomarkers were compared between patients with or without CAD. Results We included 135 consecutive patients aged 54 years (interquartile range 45-65) with sustained return of spontaneous circulation after OHCA between 2006 and 2012. Sixty six (45%) patients had CAD. The initial rhythm was shockable and non-shockable in 110 (81%) and 25 (19%) patients, respectively. ST-segment elevation predicted CAD with 42% sensitivity, 87% specificity, and 65% accuracy. ST elevation and/or regional wall motion abnormality (RWMA) showed 68% sensitivity, 52% specificity, and 70% accuracy in the prediction of CAD. Finally, a combination of ST elevation and/or RWMA and/or troponin T elevation predicted CAD with 94% sensitivity, 17% specificity, and 55% accuracy. Conclusion In patients with OHCA without obvious non-cardiac causes, selection for coronary angiogram based on the combined criterion could detect 94% of CADs. However, compared with ECG only criteria, the combined criterion failed to improve diagnostic accuracy with a lower specificity. PMID:26069108

  14. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

    PubMed

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  15. Subclinical arterial and cardiac damage in white-coat and masked hypertension.

    PubMed

    Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Olszanecka, Agnieszka; Klima, Łukasz; Gąsowski, Jerzy; Grodzicki, Tomasz; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2016-08-01

    The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians. PMID:26953075

  16. Renal and Cardiac Endothelial Heterogeneity Impact Acute Vascular Rejection in Pig-to-Baboon Xenotransplantation

    PubMed Central

    Knosalla, C.; Yazawa, K.; Behdad, A.; Bodyak, N.; Shang, H.; Bühler, L.; Houser, S.; Gollackner, B.; Griesemer, A.; Schmitt-Knosalla, I.; Schuurman, H.-J.; Awwad, M.; Sachs, D. H.; Cooper, D. K. C.; Yamada, K.; Usheva, A.; Robson, S. C.

    2010-01-01

    Xenograft outcomes are dictated by xenoantigen expression, for example, Gal α 1, 3Gal (Gal), but might also depend on differing vascular responses. We investigated whether differential vascular gene expression in kidney and cardiac xenografts correlate with development of thrombotic microangiopathy (TM) and consumptive coagulation (CC). Immunosuppressed baboons underwent miniswine or hDAF pig kidney (n = 6) or heart (n = 7), or Gal-transferase gene-knockout (GalT-KO) (thymo)kidney transplantation (n = 14). Porcine cDNA miniarrays determined donor proinflammatory, apoptosis-related and vascular coagulant/fibrinolytic gene expression at defined time points; validated by mRNA, protein levels and immunopathology. hDAF-transgenic and GalT-KO xenografts, (particularly thymokidneys) exhibited prolonged survival. CC was seen with Gal-expressing porcine kidneys (3 of 6), only 1 of 7 baboons post-cardiac xenotransplantation and was infrequent following GalT-KO grafts (1 of 14). Protective-type genes (heme oxygenase-I, superoxide dismutases and CD39) together with von Willebrand factor and P-selectin were upregulated in all renal grafts. Transcriptional responses in Gal-expressing xenografts were comparable to those seen in the infrequent GalT-KO rejection. In cardiac xenografts, fibrin deposition was associated with increased plasminogen activator inhibitor-1 expression establishing that gene expression profiles in renal and cardiac xenografts differ in a quantitative manner. These findings suggest that therapeutic targets may differ for renal and cardiac xenotransplants. PMID:19422330

  17. Inactivation of GSK-3β by Metallothionein Prevents Diabetes-Related Changes in Cardiac Energy Metabolism, Inflammation, Nitrosative Damage, and Remodeling

    PubMed Central

    Wang, Yuehui; Feng, Wenke; Xue, Wanli; Tan, Yi; Hein, David W.; Li, Xiao-Kun; Cai, Lu

    2009-01-01

    OBJECTIVE Glycogen synthase kinase (GSK)-3β plays an important role in cardiomyopathies. Cardiac-specific metallothionein-overexpressing transgenic (MT-TG) mice were highly resistant to diabetes-induced cardiomyopathy. Therefore, we investigated whether metallothionein cardiac protection against diabetes is mediated by inactivation of GSK-3β. RESEARCH DESIGN AND METHODS Diabetes was induced with streptozotocin in both MT-TG and wild-type mice. Changes of energy metabolism–related molecules, lipid accumulation, inflammation, nitrosative damage, and fibrotic remodeling were examined in the hearts of diabetic mice 2 weeks, 2 months, and 5 months after the onset of diabetes with Western blotting, RT-PCR, and immunohistochemical assays. RESULTS Activation (dephosphorylation) of GSK-3β was evidenced in the hearts of wild-type diabetic mice but not MT-TG diabetic mice. Correspondingly, cardiac glycogen synthase phosphorylation, hexokinase II, PPARα, and PGC-1α expression, which mediate glucose and lipid metabolisms, were significantly changed along with cardiac lipid accumulation, inflammation (TNF-α, plasminogen activator inhibitor 1 [PAI-1], and intracellular adhesion molecule 1 [ICAM-1]), nitrosative damage (3-nitrotyrosin accumulation), and fibrosis in the wild-type diabetic mice. The above pathological changes were completely prevented either by cardiac metallothionein in the MT-TG diabetic mice or by inhibition of GSK-3β activity in the wild-type diabetic mice with a GSK-3β–specific inhibitor. CONCLUSIONS These results suggest that activation of GSK-3β plays a critical role in diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Metallothionein inactivation of GSK-3β plays a critical role in preventing diabetic cardiomyopathy. PMID:19324938

  18. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  19. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice

    PubMed Central

    Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  20. Low Doses of Oxygen Ion Irradiation Cause Acute Damage to Hematopoietic Cells in Mice.

    PubMed

    Chang, Jianhui; Luo, Yi; Wang, Yingying; Pathak, Rupak; Sridharan, Vijayalakshmi; Jones, Tamako; Mao, Xiao Wen; Nelson, Gregory; Boerma, Marjan; Hauer-Jensen, Martin; Zhou, Daohong; Shao, Lijian

    2016-01-01

    One of the major health risks to astronauts is radiation on long-duration space missions. Space radiation from sun and galactic cosmic rays consists primarily of 85% protons, 14% helium nuclei and 1% high-energy high-charge (HZE) particles, such as oxygen (16O), carbon, silicon, and iron ions. HZE particles exhibit dense linear tracks of ionization associated with clustered DNA damage and often high relative biological effectiveness (RBE). Therefore, new knowledge of risks from HZE particle exposures must be obtained. In the present study, we investigated the acute effects of low doses of 16O irradiation on the hematopoietic system. Specifically, we exposed C57BL/6J mice to 0.1, 0.25 and 1.0 Gy whole body 16O (600 MeV/n) irradiation and examined the effects on peripheral blood (PB) cells, and bone marrow (BM) hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) at two weeks after the exposure. The results showed that the numbers of white blood cells, lymphocytes, monocytes, neutrophils and platelets were significantly decreased in PB after exposure to 1.0 Gy, but not to 0.1 or 0.25 Gy. However, both the frequency and number of HPCs and HSCs were reduced in a radiation dose-dependent manner in comparison to un-irradiated controls. Furthermore, HPCs and HSCs from irradiated mice exhibited a significant reduction in clonogenic function determined by the colony-forming and cobblestone area-forming cell assays. These acute adverse effects of 16O irradiation on HSCs coincided with an increased production of reactive oxygen species (ROS), enhanced cell cycle entry of quiescent HSCs, and increased DNA damage. However, none of the 16O exposures induced apoptosis in HSCs. These data suggest that exposure to low doses of 16O irradiation induces acute BM injury in a dose-dependent manner primarily via increasing ROS production, cell cycling, and DNA damage in HSCs. This finding may aid in developing novel strategies in the protection of the hematopoietic

  1. Ultrastructure damage of oviduct telocytes in rat model of acute salpingitis

    PubMed Central

    Yang, Jian; Chi, Chi; Liu, Zhen; Yang, Gang; Shen, Zong-Ji; Yang, Xiao-Jun

    2015-01-01

    Acute salpingitis (AS) is an inflammatory disease which causes severe damage to a subset of classically described cells lining in oviduct wall and contributes to interstitial fibrosis and fertility problems. Telocytes (TCs), a newly discovered peculiar type of stromal cells, have been identified in many organs, including oviduct, with proposed multiple potential bio-functions. However, with recent increasing reports regarding TCs alterations in disease-affected tissues, there is still lack of evidence about TCs involvement in AS-affected oviduct tissues and potential pathophysiological roles. We presently identified normal TCs by their characteristic ultrastructural features and immunophenotype. However, in AS-affected oviduct tissues, TCs displayed multiple ultrastructural damage both in cellular body and prolongations, with obvious loss of TCs and development of tissue fibrosis. Furthermore, TCs lose their interstitial 3-D network connected by homocellular or heterocellular junctions between TCs and adjacent cells. And especially, TCs connected to the activated immunocytes (mononuclear cells, eosinophils) and affected local immune state (repression or activation). Meanwhile, massive neutrophils infiltration and overproduced Inducible Nitric Oxide Synthase (iNOS), COX-2, suggested mechanism of inflammatory-induced TCs damage. Consequently, TCs damage might contribute to AS-induced structural and reproductive functional abnormalities of oviduct, probably via: (i) substances, energy and functional insufficiency, presumably, e.g. TC-specific genetic material profiles, ion channels, cytoskeletal elements, Tps dynamics, etc., (ii) impaired TCs-mediated multicellular signalling, such as homeostasis/angiogenesis, tissue repair/regeneration, neurotransmission, (iii) derangement of 3-D network and impaired mechanical support for TCs-mediated multicellular signals within the stromal compartment, consequently induced interstitial fibrosis, (iv) involvement in local

  2. Acute O 3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment.

    PubMed

    Darbah, Joseph N T; Jones, Wendy S; Burton, Andrew J; Nagy, John; Kubiske, Mark E

    2011-09-01

    We studied the effect of high ozone (O(3)) concentration (110-490 nmol mol(-1)) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O(3) pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O(3) exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O(3) and/or CO(2) for 12 years, were harvested. Acute O(3) damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O(3) damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O(3) damage as it directly controlled O(3) uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O(3) exposure. Moreover, elevated CO(2) did not ameliorate the adverse effects of acute O(3) dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O(3) levels.

  3. Acute O3 damage on first year coppice sprouts of aspen and maple sprouts in an open-air experiment

    SciTech Connect

    Darbah, J.N.; Nagy, J.; Jones, W. S.; Burton, A. J.; Kubiske, M. E.

    2011-10-01

    We studied the effect of high ozone (O{sub 3}) concentration (110-490 nmol mol{sup -1}) on regenerating aspen (Populus tremuloides) and maple (Acer saccharum) trees at an open-air O{sub 3} pollution experiment near Rhinelander WI USA. This study is the first of its kind to examine the effects of acute O{sub 3} exposure on aspen and maple sprouts after the parent trees, which were grown under elevated O{sub 3} and/or CO{sub 2} for 12 years, were harvested. Acute O{sub 3} damage was not uniform within the crowns of aspen suckers; it was most severe in the mature, fully expanded photosynthesizing leaves. Young expanding leaves showed no visible signs of acute O{sub 3} damage contrary to expectations. Stomatal conductance played a primary role in the severity of acute O{sub 3} damage as it directly controlled O{sub 3} uptake. Maple sprouts, which had lower stomatal conductance, smaller stomatal aperture, higher stomatal density and larger leaf surface area, were tolerant of acute O{sub 3} exposure. Moreover, elevated CO{sub 2} did not ameliorate the adverse effects of acute O{sub 3} dose on aspen and maple sprouts, in contrast to its ability to counteract the effects of long-term chronic exposure to lower O{sub 3} levels.

  4. The role of thyroid hormone therapy in acutely ill cardiac patients

    PubMed Central

    Wyne, Kathleen L

    2005-01-01

    The presence of a 'low T3 syndrome' in the setting of nonthyroidal illness has long been recognized as the 'euthyroid sick syndrome', with the recommendation to observe and not treat with thyroid hormone replacement therapy. That approach has recently been challenged in the setting of critical cardiac illness. Research demonstrating that thyroid hormone therapy may improve hemodynamic parameters has rekindled interest in the use of thyroid hormone therapy in critical illness. Continued improvements in survival after critical cardiac illness provokes the question of whether thyroid hormone therapy would provide further incremental benefit. PMID:16137376

  5. Arterial damages in acute elbow dislocations: which diagnostic tests are required?

    PubMed

    Lutter, Christoph; Pfefferkorn, Ronny; Schoeffl, Volker

    2016-07-19

    Blunt vessel injuries of peripheral arteries caused by a direct trauma are rare. Studies have described the frequency of arterial ruptures following closed elbow dislocations in 0.3-1.7% of all cases. However, arterial damage does not always necessarily appear as a complete rupture of the vessel with a loss of peripheral circulation and ischaemic symptoms; a relatively strong periarticular system of collaterals can maintain circulation. Furthermore, the traumatic dislocation can also cause intimal tears, arterial dissections and aneurysms or thrombosis. In all cases of vessel injury, including total disruption, a peripheral pulse might still be palpable. 3 weeks after an acute elbow dislocation, we have diagnosed a patient with a long-segment stenosis of the brachial artery and a thrombosis of the radial artery. Therefore, the close anatomic proximity to the neurovascular structures should always be considered in cases of elbow dislocations, even if peripheral pulses are traceable.

  6. The Association of Acute Kidney Injury and Atrial Fibrillation after Cardiac Surgery in an Asian Prospective Cohort Study.

    PubMed

    Ng, Roderica Rui Ge; Tan, Gabriel Hong Jie; Liu, Weiling; Ti, Lian Kah; Chew, Sophia Tsong Huey

    2016-03-01

    Acute kidney injury (AKI) and atrial fibrillation (AF) after cardiac surgery are common occurrences and increase patient morbidity and mortality. Inflammation plays a role in increased incidence of AF in patients with chronic kidney disease (CKD); reactive oxygen species and inflammatory markers which are increased in patients with CKD were found to affect the proper functioning of the intracellular ion channels, connexions (transmembrane proteins found in intercellular gap junctions), and electrical homogeneity of the extracellular matrix which are essential for electrical stability and proper conduction of electrical impulses in the atrium. However, it is not known if similar mechanisms are also involved in AKI. We tested the hypothesis that patients with AKI after cardiac surgery have a higher incidence of postoperative AF.Data from 2885 patients, who had undergone cardiac surgery between August 2008 and July 2012 from the Singapore's 2 major heart centers, were obtained prospectively. Postoperative AKI was defined using the Acute Kidney Injury Network criteria. The primary outcome was postoperative AF, and subjects were considered to have postoperative AF if the AF lasted more than an hour, affected hemodynamics, or required medical treatment.The incidence of AKI was 29.7% and the incidence of postoperative AF was 16.8%. A total of 27.7% of AKI patients developed AF. Patients with AKI had a 2-fold increased risk of developing AF (relative risk [RR], 1.716; 95% confidence interval [CI], 1.433-2.055; P < 0.001). The following factors were found to independently increase the risk of AF in patients with AKI: age (RR, 1.011; 95% CI, 1.000-1.022; P = 0.04), low preoperative hemoglobin (RR, 0.942; 95% CI, 0.888-1.000; P = 0.05), low preoperative estimated glomerular filtration rate (eGFR) (RR, 0.987; 95% CI, 0.980-0.994; P < 0.001), and lowest hematocrit during bypass (RR, 0.943; 95% CI, 0.910-0.978; P < 0.001).Patients with AKI are more likely to

  7. Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study.

    PubMed

    Tschakert, Gerhard; Kroepfl, Julia M; Mueller, Alexander; Harpf, Hanns; Harpf, Leonhard; Traninger, Heimo; Wallner-Liebmann, Sandra; Stojakovic, Tatjana; Scharnagl, Hubert; Meinitzer, Andreas; Pichlhoefer, Patriz; Hofmann, Peter

    2016-03-01

    Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn't show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key pointsHigh-intensity interval exercise (HIIE

  8. Acute Physiological Responses to Short- and Long-Stage High-Intensity Interval Exercise in Cardiac Rehabilitation: A Pilot Study

    PubMed Central

    Tschakert, Gerhard; Kroepfl, Julia M.; Mueller, Alexander; Harpf, Hanns; Harpf, Leonhard; Traninger, Heimo; Wallner-Liebmann, Sandra; Stojakovic, Tatjana; Scharnagl, Hubert; Meinitzer, Andreas; Pichlhoefer, Patriz; Hofmann, Peter

    2016-01-01

    Despite described benefits of aerobic high-intensity interval exercise (HIIE), the acute responses during different HIIE modes and associated health risks have only been sparsely discovered in heart disease patients. Therefore, the aim of this study was to investigate the acute responses for physiological parameters, cardiovascular and inflammatory biomarkers, and catecholamines yielded by two different aerobic HIIE protocols compared to continuous exercise (CE) in phase III cardiac rehabilitation. Eight cardiac patients (7 with coronary heart disease, 1 with myocarditis; 7 males, 1 female; age: 63.0 ± 9.4 years; height: 1.74 ± 0.05 m; weight: 83.6 ± 8.7 kg), all but one treated with ß-blocking agents, performed a maximal symptom-limited incremental exercise test (IET) and three different exercise tests matched for mean load (Pmean) and total duration: 1) short HIIE with a peak workload duration (tpeak) of 20 s and a peak workload (Ppeak) equal to the maximum power output (Pmax) from IET; 2) long HIIE with a tpeak of 4 min, Ppeak was corresponding to the power output at 85 % of maximal heart rate (HRmax) from IET; 3) CE with a target workload equal to Pmean of both HIIE modes. Acute metabolic and peak cardiorespiratory responses were significantly higher during long HIIE compared to short HIIE and CE (p < 0.05) except HRpeak which tended to be higher in long HIIE than in short HIIE (p = 0.08). Between short HIIE and CE, no significant difference was found for any parameter. Acute responses of cardiovascular and inflammatory biomarkers and catecholamines didn’t show any significant difference between tests (p > 0.05). All health-related variables remained in a normal range in any test except NT-proBNP, which was already elevated at baseline. Despite a high Ppeak particularly in short HIIE, both HIIE modes were as safe and as well tolerated as moderate CE in cardiac patients by using our methodological approach. Key points High-intensity interval exercise (HIIE

  9. Genotoxic Evaluation of Mikania laevigata Extract on DNA Damage Caused by Acute Coal Dust Exposure

    SciTech Connect

    Freitas, T.P.; Heuser, V.D.; Tavares, P.; Leffa, D.D.; da Silva, G.A.; Citadini-Zanette, V.; Romao, P.R.T.; Pinho, R.A.; Streck, E.L.; Andrade,V.M.

    2009-06-15

    We report data on the possible antigenotoxic activity of Mikania laevigata extract (MLE) after acute intratracheal instillation of coal dust using the comet assay in peripheral blood, bone marrow, and liver cells and the micronucleus test in peripheral blood of Wistar rats. The animals were pretreated for 2 weeks with saline solution (groups 1 and 2) or MLE (100 mg/kg) (groups 3 and 4). On day 15, the animals were anesthetized with ketamine (80 mg/kg) and xylazine (20 mg/kg), and gross mineral coal dust (3 mg/0.3 mL saline) (groups 2 and 4) or saline solution (0.3 mL) (groups 1 and 3) was administered directly in the lung by intratracheal administration. Fifteen days after coal dust or saline instillation, the animals were sacrificed, and the femur, liver, and peripheral blood were removed. The results showed a general increase in the DNA damage values at 8 hours for all treatment groups, probably related to surgical procedures that had stressed the animals. Also, liver cells from rats treated with coal dust, pretreated or not with MLE, showed statistically higher comet assay values compared to the control group at 14 days after exposure. These results could be expected because the liver metabolizes a variety of organic compounds to more polar by-products. On the other hand, the micronucleus assay results did not show significant differences among groups. Therefore, our data do not support the antimutagenic activity of M. laevigata as a modulator of DNA damage after acute coal dust instillation.

  10. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma

    PubMed Central

    Lee, Chang-Lung; Castle, Katherine D.; Moding, Everett J.; Blum, Jordan M.; Williams, Nerissa; Luo, Lixia; Ma, Yan; Borst, Luke B.; Kim, Yongbaek; Kirsch, David G.

    2015-01-01

    Genotoxic cancer therapies, such as chemoradiation, cause haematological toxicity primarily by activating the tumour suppressor p53. While inhibiting p53-mediated cell death during cancer therapy ameliorates haematologic toxicity, whether it also impacts carcinogenesis remains unclear. Here we utilize a mouse model of inducible p53 short hairpin RNA (shRNA) to show that temporarily blocking p53 during total-body irradiation (TBI) not only ameliorates acute toxicity, but also improves long-term survival by preventing lymphoma development. Using KrasLA1 mice, we show that TBI promotes the expansion of a rare population of thymocytes that express oncogenic KrasG12D. However, blocking p53 during TBI significantly suppresses the expansion of KrasG12D-expressing thymocytes. Mechanistically, bone marrow transplant experiments demonstrate that TBI activates p53 to decrease the ability of bone marrow cells to suppress lymphoma development through a non-cell-autonomous mechanism. Together, our results demonstrate that the p53 response to acute DNA damage promotes the development of radiation-induced lymphoma. PMID:26399548

  11. Use of a Simply Modified Drainage Catheter for Peritoneal Dialysis Treatment of Acute Renal Failure Associated With Cardiac Surgery in Infants

    PubMed Central

    Chen, Qiang; Cao, Hua; Hu, Yun-Nan; Chen, Liang-Wan; He, Jia-jun

    2014-01-01

    Abstract Acute renal failure (ARF) is a common complication in infants who undergo cardiac surgery in the intensive care unit. We report on a modified drainage catheter used in peritoneal dialysis (PD) for the treatment of ARF associated with cardiac surgery in infants. Thirty-nine infants with congenital heart disease undergoing cardiac surgery who developed ARF at our center between January 2009 and January 2012 were assessed. A modified drainage catheter for PD was used in these infants. Their demographic, clinical, and surgical data were analyzed. Thirty infants with ARF were cured by PD, and the other 9 died in the first 48 hours because of the severity of the acute cardiac dysfunction. All these infants were dependent upon mechanical ventilation during the postoperative period and used vasoactive drugs. In the survival group, the interval between the procedure and initiation of PD was 13.6 ± 6.5 (range, 6–30) hours. PD duration was 3.9 ± 0.9 (3–6) days. Minor complications were encountered in some patients (asymptomatic hypokalemia, hyperglycemia, and thrombocytopenia). These complications were readily treated by drugs or resolved spontaneously. Hemodynamics, cardiac function, and renal function improved significantly during PD. These data suggest that PD using a modified drainage catheter for ARF after cardiac surgery in infants is safe, feasible, inexpensive, and yields good results. PMID:25255020

  12. A pilot study of prognostic value of non-invasive cardiac parameters for major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention

    PubMed Central

    Yuan, Min-Jie; Pan, Ye-Sheng; Hu, Wei-Guo; Lu, Zhi-Gang; Zhang, Qing-Yong; Huang, Dong; Huang, Xiao-Li; Wei, Meng; Li, Jing-Bo

    2015-01-01

    The objective of this study was to determine the combination of left ventricular ejection fraction (LVEF) and individual electrocardiographic parameters related to abnormal depolarization/repolarization or baroreceptor sensitivity that had the best predictive value for major adverse cardiac events (MACE) in patients with acute coronary syndrome (ACS). Patients with ACS who underwent coronary angiography and percutaneous coronary intervention (PCI) were included in this prospective study. Ventricular late potential (VLP), heart rate turbulence (HRT), heart rate variability (HRV), and T wave alternans (TWA) parameters were measured using 24 h Holter monitoring 2-4 weeks after onset of ACS. Initial and follow-up LVEF was measured by ultrasound. Patients were followed for at least 6 months to record the occurrence of MACE. Models using combinations of the individual independent prognostic factors found by multivariate analysis were then constructed to use for estimation of risk of MACE. In multivariate analysis, VLP measured as QRS duration, HRV measured as standard deviation of normal RR intervals, and followup LVEF, but none of the other parameters studied, were independent risk factors for MACE. Areas under ROC curve (AUCs) for combinations of 2 or all 3 factors ranged from 0.73 to 0.76. Combinations of any of the three independent risk factors for MACE in ACS patients with PCI improved prediction and, because these risk factors were obtained non-invasively, may have future clinical usefulness. PMID:26885226

  13. Cardiac and mitochondrial dysfunction following acute pulmonary exposure to mountaintop removal mining particulate matter.

    PubMed

    Nichols, Cody E; Shepherd, Danielle L; Knuckles, Travis L; Thapa, Dharendra; Stricker, Janelle C; Stapleton, Phoebe A; Minarchick, Valerie C; Erdely, Aaron; Zeidler-Erdely, Patti C; Alway, Stephen E; Nurkiewicz, Timothy R; Hollander, John M

    2015-12-15

    Throughout the United States, air pollution correlates with adverse health outcomes, and cardiovascular disease incidence is commonly increased following environmental exposure. In areas surrounding active mountaintop removal mines (MTM), a further increase in cardiovascular morbidity is observed and may be attributed in part to particulate matter (PM) released from the mine. The mitochondrion has been shown to be central in the etiology of many cardiovascular diseases, yet its roles in PM-related cardiovascular effects are not realized. In this study, we sought to elucidate the cardiac processes that are disrupted following exposure to mountaintop removal mining particulate matter (PM MTM). To address this question, we exposed male Sprague-Dawley rats to PM MTM, collected within one mile of an active MTM site, using intratracheal instillation. Twenty-four hours following exposure, we evaluated cardiac function, apoptotic indices, and mitochondrial function. PM MTM exposure elicited a significant decrease in ejection fraction and fractional shortening compared with controls. Investigation into the cellular impacts of PM MTM exposure identified a significant increase in mitochondrial-induced apoptotic signaling, as reflected by an increase in TUNEL-positive nuclei and increased caspase-3 and -9 activities. Finally, a significant increase in mitochondrial transition pore opening leading to decreased mitochondrial function was identified following exposure. In conclusion, our data suggest that pulmonary exposure to PM MTM increases cardiac mitochondrial-associated apoptotic signaling and decreases mitochondrial function concomitant with decreased cardiac function. These results suggest that increased cardiovascular disease incidence in populations surrounding MTM mines may be associated with increased cardiac cell apoptotic signaling and decreased mitochondrial function.

  14. Ca2+ toxicity and mitochondrial damage in acute pancreatitis: translational overview

    PubMed Central

    Maléth, József; Hegyi, Péter

    2016-01-01

    Acute pancreatitis (AP) is a leading cause of hospitalization among non-malignant gastrointestinal disorders. The mortality of severe AP can reach 30–50%, which is most probably owing to the lack of specific treatment. Therefore, AP is a major healthcare problem, which urges researchers to identify novel drug targets. Studies from the last decades highlighted that the toxic cellular Ca2+ overload and mitochondrial damage are key pathogenic steps in the disease development affecting both acinar and ductal cell functions. Moreover, recent observations showed that modifying the cellular Ca2+ signalling might be beneficial in AP. The inhibition of Ca2+ release from the endoplasmic reticulum or the activity of plasma membrane Ca2+ influx channels decreased the severity of AP in experimental models. Similarly, inhibition of mitochondrial permeability transition pore (MPTP) opening also seems to improve the outcome of AP in in vivo animal models. At the moment MPTP blockers are under detailed clinical investigation to test whether interventions in MPTP openings and/or Ca2+ homeostasis of the cells can be specific targets in prevention or treatment of cell damage in AP. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377719

  15. Acute skin sun damage in children and its consequences in adults.

    PubMed

    Pustisek, Nives; Sikanić-Dugić, Nives; Hirsl-Hećej, Vlasta; Domljan, Mislav Luka

    2010-04-01

    Children spend more time outdoors than adults and there is compelling evidence that childhood is a particularly vulnerable time for the photocarcinogenic effects of the sun. The negative effects of solar radiation are accumulated during the entire lifetime; however 80% of total lifetime sun exposure is taking place before the age of 18 years. Child skin is more sensitive than adult skin because natural defense mechanisms are not fully developed. A short exposure to midday sun will result in sunburns. Epidemiologic studies show a higher incidence of malignant melanoma in persons with a history of sunburns during childhood and adolescence. Sun exposure among infants and pre-school children is largely dependent on the discretion of adult care providers. Sun protective habits of mothers may predict the level of sun exposure in children. It is very important to transfer the knowledge and positive habits of proper sun protection to children. The purpose of sun-safety behavior is not to avoid outdoor activities, but rather to protect the skin from detrimental sun effects. Proper sun protection of children includes protection from excessive sun exposure, sunburns and other forms of skin damage caused by sun, which may lead to the future development of skin cancers. This paper reviews acute skin reactivity to sun in childhood and adolescence that causes damage in skin structure and function and produces undesirable chronic changes in adults.

  16. Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

    PubMed Central

    Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

    2015-01-01

    The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

  17. Gastroprotective Effects of PMK-S005 against Ethanol-Induced Acute Gastric Damage in Rats

    PubMed Central

    Choi, Yoon Jeong; Kim, Nayoung; Lee, Ju Yup; Nam, Ryoung Hee; Seo, Ji Hyung; Lee, Seonmin; Kim, Hee Jin; Choi, Yoon Jin; Lee, Hye Seung; Lee, Dong Ho

    2016-01-01

    Background/Aims This study aimed to examine the gastroprotective effects of PMK-S005, which is a synthetic S-allyl-l-cysteine (SAC; a sulfur-containing amino acid), against acute ethanol-induced gastric damage in rats. Methods Sprague-Dawley rats were divided into six groups, including a nonethanol group, groups treated with absolute ethanol 1 hour after pretreatment with various doses of PMK-S005 (1, 5, and 10 mg/kg) or rebamipide (50 mg/kg), and an absolute ethanol-only group. Ethanol-induced gross ulcer and mucus levels were measured. Myeloperoxidase, tumor necrosis factor α, interleukin 1β, PGE2, LTB4, cPLA2, COX-1, and COX-2 levels were estimated by enzyme-linked immunosorbent assay or Western blot analysis. Furthermore, the protein expression levels of antioxidant enzymes, including heme oxygenase-1 (HO-1), NAD(P)H:quinine oxidoreductase 1 (NQO-1), GCLC, and GCLM, were assessed. Results PMK-S005 significantly attenuated the ethanol-induced gastric damage; it reduced mucosal inflammatory cytokine production and increased mucus levels. The expression levels of cPLA2, COX-1, and COX-2 were decreased by PMK-S005. PMK-S005 did not affect PGE2 synthesis, but LTB4 production was significantly suppressed. In addition, long-term administration of PMK-S005 significantly increased the expression of HO-1, NQO-1, GCLC, and GCLM. Conclusions These results strongly suggest that PMK-S005 prevents gastric mucosal damage and that these gastroprotective activities are due to anti-inflammatory effects and enhancement of the gastric defense system, including antioxidant enzymes. PMID:26347516

  18. Effects of acute and chronic administration of fenproporex on DNA damage parameters in young and adult rats.

    PubMed

    Gonçalves, Cinara L; Rezin, Gislaine T; Ferreira, Gabriela K; Jeremias, Isabela C; Cardoso, Mariane R; Valvassori, Samira S; Munhoz, Bruna J P; Borges, Gabriela D; Bristot, Bruno N; Leffa, Daniela D; Andrade, Vanessa M; Quevedo, João; Streck, Emilio L

    2013-08-01

    Obesity is a chronic and multifactorial disease, whose prevalence is increasing in many countries. Pharmaceutical strategies for the treatment of obesity include drugs that regulate food intake, thermogenesis, fat absorption, and fat metabolism. Fenproporex is the second most commonly consumed amphetamine-based anorectic worldwide; this drug is rapidly converted in vivo into amphetamine, which is associated with neurotoxicity. In this context, the present study evaluated DNA damage parameters in the peripheral blood of young and adult rats submitted to an acute administration and chronic administration of fenproporex. In the acute administration, both young and adult rats received a single injection of fenproporex (6.25, 12.5 or 25 mg/kg i.p.) or vehicle. In the chronic administration, both young and adult rats received one daily injection of fenproporex (6.25, 12.5, or 25 mg/kg i.p.) or Tween for 14 days. 2 h after the last injection, the rats were killed by decapitation and their peripheral blood removed for evaluation of DNA damage parameters by alkaline comet assay. Our study showed that acute administration of fenproporex in young and adult rats presented higher levels of damage index and frequency in the DNA. However, chronic administration of fenproporex in young and adult rats did not alter the levels of DNA damage in both parameters of comet assay. The present findings showed that acute administration of fenproporex promoted damage in DNA, in both young and adult rats. Our results are consistent with other reports which showed that other amphetamine-derived drugs also caused DNA damage. We suggest that the activation of an efficient DNA repair mechanism may occur after chronic exposition to fenproporex. Our results are consistent with other reports that showed some amphetamine-derived drugs also caused DNA damage. PMID:23636618

  19. Mood disturbance and depression in Arab women following hospitalisation from acute cardiac conditions: a cross-sectional study from Qatar

    PubMed Central

    Donnelly, Tam Truong; Al Suwaidi, Jassim Mohd; Al-Qahtani, Awad; Asaad, Nidal; Fung, Tak; Singh, Rajvir; Qader, Najlaa Abdul

    2016-01-01

    Objectives Depression is associated with increased morbidity and mortality rates among cardiovascular patients. Depressed patients have three times higher risk of death than those who are not. We sought to determine the presence of depressive symptoms, and whether gender and age are associated with depression among Arab patients hospitalised with cardiac conditions in a Middle Eastern country. Setting Using a non-probability convenient sampling technique, a cross-sectional survey was conducted with 1000 Arab patients ≥20 years who were admitted to cardiology units between 2013 and 2014 at the Heart Hospital in Qatar. Patients were interviewed 3 days after admission following the cardiac event. Surveys included demographic and clinical characteristics, and the Arabic version of the Beck Depression Inventory Second Edition (BDI-II). Depression was assessed by BDI-II clinical classification scale. Results 15% of the patients had mild mood disturbance and 5% had symptoms of clinical depression. Twice as many females than males suffered from mild mood disturbance and clinical depression symptoms, the majority of females were in the age group 50 years and above, whereas males were in the age group 40–49 years. χ2 Tests and multivariate logistic regression analyses indicated that gender and age were statistically significantly related to depression (p<0.001 for all). Conclusions Older Arab women are more likely to develop mood disturbance and depression after being hospitalised with acute cardiac condition. Gender and age differences approach, and routine screening for depression should be conducted with all cardiovascular patients, especially for females in the older age groups. Mental health counselling should be available for all cardiovascular patients who exhibit depressive symptoms. PMID:27388362

  20. Outcome of veno-venous extracorporeal membrane oxygenation use in acute respiratory distress syndrome after cardiac surgery with cardiopulmonary bypass

    PubMed Central

    Song, Joo Han; Woo, Won Ki; Song, Seung Hwan; Kim, Hyo Hyun; Kim, Bong Joon; Kim, Ha Eun; Kim, Do Jung; Suh, Jee Won; Shin, Yu Rim; Park, Han Ki; Lee, Seung Hyun; Joo, Hyun Chel; Lee, Sak; Chang, Byung Chul; Yoo, Kyung Jong; Kim, Young Sam

    2016-01-01

    Background Cardiac surgery with cardiopulmonary bypass (CPB) is a known risk factor for acute respiratory distress syndrome (ARDS). We aimed to analyze the treatment outcome in patients who required veno-venous extracorporeal membrane oxygenation (VV-ECMO) for postcardiotomy ARDS despite other rescue modalities. Methods We retrospectively reviewed the outcomes in 13 patients (mean age, 54.7±5.9 years) who received VV-ECMO support for refractory ARDS after cardiac surgery between March 2013 and February 2016 at Severance Hospital, Yonsei University (Seoul, Korea). Results At the start of VV-ECMO, the average lung injury score was 3.0±0.2, and the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score was −4±1.1. Although 7 patients initiated VV-ECMO support within 24 h from operation, the remaining 6 started at a median of 8.5 days (range, 5−16 days). Nine (69.3%) patients were successfully weaned from VV-ECMO. After a median follow-up duration of 14.5 months (range, 1.0−33.0 months) for survivors, the 1-year overall survival was 58.6%±14.4%. The differences in the overall survival from VV-ECMO according to the RESP score risk classes were borderline significant (100% in class III, 50%±25% in class IV, and 20%±17.9% in class V; P=0.088). Conclusions VV-ECMO support can be a feasible rescue strategy for adult patients who develop refractory ARDS after a cardiac surgery. Additionally, the RESP score seems a valuable prognostic tool for post-ECMO survival outcome in this patient population as well. PMID:27499972

  1. Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics

    NASA Technical Reports Server (NTRS)

    Engelke, K. A.; Shea, J. D.; Doerr, D. F.; Convertino, V. A.

    1992-01-01

    To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg).

  2. Intravenous administration of atorvastatin-pretreated mesenchymal stem cells improves cardiac performance after acute myocardial infarction: role of CXCR4

    PubMed Central

    Li, Na; Yang, Yue-Jin; Qian, Hai-Yan; Li, Qing; Zhang, Qian; Li, Xiang-Dong; Dong, Qiu-Ting; Xu, Hui; Song, Lei; Zhang, Hao

    2015-01-01

    Background: The interaction between stromal cell-derived factor 1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) plays an important role in mesenchymal stem cells (MSCs) migration and engraftment. Statins can increase the survival of MSCs. However, whether statins could enhance MSCs migration and engraftment is still unknown. Therefore, we designed the study to investigate whether atorvastatin (ATV) could enhance CXCR4 expression of MSCs and promote them homing toward the injured myocardium. Methods and results: Expression of CXCR4 was evaluated by flow cytometry and real time PCR. A transwell system was used to assess MSCs migration ability. Recruitment of systematically delivered MSCs to the infarcted heart was evaluated in Sprague-Dawley rats with acute myocardial infarction (AMI). ATV pretreatment enhanced the expression of CXCR4 and stimulated MSCs migration in vitro. However, the effect was largely abolished by CXCR4 neutralizing antibody. In AMI models, we found much more ATV-pretreated MSCs homing toward the infarcted myocardium than non-treated cells and this was accompanied by improved cardiac performance. Conclusions: ATV increases the migration ability of MSCs and improves cardiac performance due to up-regulated expression of CXCR4. These results suggest that ATV pretreatment of donor MSCs is an effective way to promote cell therapeutic potential for AMI. PMID:26279750

  3. Lipopolysaccharide Binding Protein and sCD14 are Not Produced as Acute Phase Proteins in Cardiac Surgery

    PubMed Central

    Kudlova, Manuela; Kunes, Pavel; Kolackova, Martina; Lonsky, Vladimir; Mandak, Jiri; Andrys, Ctirad; Jankovicova, Karolina; Krejsek, Jan

    2007-01-01

    Objectives. The changes in the serum levels of lipopolysaccharide binding protein (LBP) and sCD14 during cardiac surgery were followed in this study. Design. Thirty-four patients, 17 in each group, were randomly assigned to coronary artery bypass grafting surgery performed either with (“on-pump”) or without (“off-pump”) cardiopulmonary bypass. LBP and sCD14 were evaluated by ELISA. Results. The serum levels of LBP were gradually increased from the 1st postoperative day and reached their maximum on the 3rd postoperative day in both “on-pump” and “off-pump” patients (30.33±9.96 μg/mL; 37.99±16.58 μg/mL), respectively. There were no significant differences between “on-pump” and “off-pump” patients regarding LBP. The significantly increased levels of sCD14 from the 1st up to the 7th postoperative day in both “on-pump” and “off-pump” patients were found with no significant differences between these groups. No correlations between LBP and sCD14 and IL-6, CRP and long pentraxin PTX3 levels were found. Conclusions. The levels of LBP and sCD14 are elevated in cardiac surgical patients being similar in both groups. These molecules are not produced as acute phase proteins in these patients. PMID:18288274

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. The role of acute hyperinsulinemia in the development of cardiac arrhythmias.

    PubMed

    Drimba, László; Döbrönte, Róbert; Hegedüs, Csaba; Sári, Réka; Di, Yin; Németh, Joseph; Szilvássy, Zoltán; Peitl, Barna

    2013-05-01

    Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak-Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak-Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

  6. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay

    PubMed Central

    Reichlin, Tobias; Twerenbold, Raphael; Wildi, Karin; Gimenez, Maria Rubini; Bergsma, Nathalie; Haaf, Philip; Druey, Sophie; Puelacher, Christian; Moehring, Berit; Freese, Michael; Stelzig, Claudia; Krivoshei, Lian; Hillinger, Petra; Jäger, Cedric; Herrmann, Thomas; Kreutzinger, Philip; Radosavac, Milos; Weidmann, Zoraida Moreno; Pershyna, Kateryna; Honegger, Ursina; Wagener, Max; Vuillomenet, Thierry; Campodarve, Isabel; Bingisser, Roland; Miró, Òscar; Rentsch, Katharina; Bassetti, Stefano; Osswald, Stefan; Mueller, Christian

    2015-01-01

    Background: We aimed to prospectively validate a novel 1-hour algorithm using high-sensitivity cardiac troponin T measurement for early rule-out and rule-in of acute myocardial infarction (MI). Methods: In a multicentre study, we enrolled 1320 patients presenting to the emergency department with suspected acute MI. The high-sensitivity cardiac troponin T 1-hour algorithm, incorporating baseline values as well as absolute changes within the first hour, was validated against the final diagnosis. The final diagnosis was then adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data and serial measurements of high-sensitivity cardiac troponin T levels. Results: Acute MI was the final diagnosis in 17.3% of patients. With application of the high-sensitivity cardiac troponin T 1-hour algorithm, 786 (59.5%) patients were classified as “rule-out,” 216 (16.4%) were classified as “rule-in” and 318 (24.1%) were classified to the “observational zone.” The sensitivity and the negative predictive value for acute MI in the rule-out zone were 99.6% (95% confidence interval [CI] 97.6%–99.9%) and 99.9% (95% CI 99.3%–100%), respectively. The specificity and the positive predictive value for acute MI in the rule-in zone were 95.7% (95% CI 94.3%–96.8%) and 78.2% (95% CI 72.1%–83.6%), respectively. The 1-hour algorithm provided higher negative and positive predictive values than the standard interpretation of highsensitivity cardiac troponin T using a single cut-off level (both p < 0.05). Cumulative 30-day mortality was 0.0%, 1.6% and 1.9% in patients classified in the rule-out, observational and rule-in groups, respectively (p = 0.001). Interpretation: This rapid strategy incorporating high-sensitivity cardiac troponin T baseline values and absolute changes within the first hour substantially accelerated the management of suspected acute MI by allowing safe rule-out as well as accurate

  7. Acute regulation of glucose uptake in cardiac muscle of the American eel Anguilla rostrata.

    PubMed

    Rodnick; Bailey; West; Driedzic

    1997-01-01

    We investigated the effects of anoxia and contractile activity on glucose uptake and the intracellular location of hexokinase in cardiac muscle of the American eel Anguilla rostrata. Uptake of 2-deoxyglucose (2-DG) by ventricle strips at 15 °C was increased by 45 % by anoxia and by 85 % by contractile activity over basal conditions. The anoxia- and contraction-induced increase in basal 2-DG uptake was inhibited completely by 25 µmol l-1 cytochalasin B, suggesting that facilitated glucose transporters are involved. Maximal activity of hexokinase in whole homogenates (approximately 10 µmol min-1 g-1 tissue) was 200 times higher than the maximal rate of 2-DG uptake measured in vitro (46 nmol min-1 g-1 tissue). Only 20­25 % of hexokinase activity was localized to the mitochondrial fraction, and this was not altered by perfusion of the hearts with anoxic media. It is therefore unlikely that anoxia-induced stimulation of 2-DG uptake is mediated by intracellular translocation of hexokinase. As in the case of mammalian muscle, glucose 6-phosphate is a potent inhibitor of hexokinase in eel cardiac muscle (IC50=0.44 mmol l-1). In summary, anoxia and contractile activity significantly increase 2-DG uptake in cardiac muscle of American eels, and glucose transport may be rate-limiting for glucose utilization. Increased utilization of glucose during anoxia or contractile activity may involve the recruitment of facilitative glucose transport proteins to the cell surface of myocytes or an increase in the intrinsic activity of glucose transporters already residing at the cell surface.

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

    PubMed Central

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

    2016-01-01

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

  9. A novel fluorinated stilbene exerts hepatoprotective properties in CCl(4)-induced acute liver damage.

    PubMed

    Rivera, Horacio; Morales-Ríos, Martha S; Bautista, Wendy; Shibayama, Mineko; Tsutsumi, Víctor; Muriel, Pablo; Pérez-Álvarez, Víctor

    2011-10-01

    There has been a recently increase in the development of novel stilbene-based compounds with in vitro anti-inflamatory properties. For this study, we synthesized and evaluated the anti-inflammatory properties of 2 fluorinated stilbenes on carbon tetrachloride (CCl₄)-induced acute liver damage. To achieve this, CCl₄ (4 g·kg(-1), per os) was administered to male Wistar rats, followed by either 2-fluoro-4'-methoxystilbene (FME) or 2,3-difluoro-4'-methoxystilbene (DFME) (10 mg·kg(-1), per os). We found that although both of the latter compounds prevented cholestatic damage (γ-glutamyl transpeptidase activity), only DFME showed partial but consistent results in the prevention of necrosis, as assessed by both alanine aminotransferase activity and histological analysis. Since inflammatory responses are mediated by cytokines, mainly tumour necrosis factor α (TNF-α), we used the Western blot technique to determine the action of FME and DFME on the expression level of this cytokine. The observed increase in the level of TNF-α caused by CCl₄ administration was only prevented by treatment with DFME, in agreement with our biochemical findings. This result was confirmed by measuring interleukin-6 (IL-6) levels, since the expression of this protein depends on the level of TNF-α. In this case, DFME completely blocked the CCl₄-induced increase of IL-6. Our results suggest that DFME possesses greater anti-inflammatory properties in vivo than FME. DFME constitutes a possible therapeutic agent for liver disease and could serve as a template for structure optimization.

  10. Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates.

    PubMed Central

    Thorgeirsson, U P; Farb, A; Virmani, R; Adamson, R H

    1994-01-01

    The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights, and no abnormalities were observed upon gross inspection of the hearts. Microscopically, focal myocardial lesions were observed in 8 of 10 monkeys dosed with IQ. Light microscopic abnormalities included myocyte necrosis with or without chronic inflammatory infiltrates, interstitial fibrosis with myocyte hypertrophy or atrophy, and vasculitis. Electron microscopic findings included disruption of the mitochondrial architecture (i.e., mitochondrial swelling and clearing of matrix densities), myofibrillar loss, disorganization of the normal alignment of sarcomeres, and occasional myocytes showing nuclear hypertrophy or peripheral clumping of the nuclear chromatin. There was some correlation between the cumulative dose of IQ and the extent of the myocardial abnormalities. These findings suggest that chronic exposure to IQ can lead to myocardial damage in monkeys. Although focal and not associated with clinical evidence of heart failure, these abnormalities may represent the initial stages of IQ-induced toxic cardiomyopathy. Images Figure 1. A Figure 1. B Figure 1. C Figure 1. D Figure 2. A Figure 2. B Figure 3. A Figure 3. B Figure 3. C Figure 3. D Figure 4. A Figure 4. B Figure 5. A Figure 5. B PMID:8033851

  11. Ultra-low dose comprehensive cardiac CT imaging in a patient with acute myocarditis.

    PubMed

    Tröbs, Monique; Brand, Michael; Achenbach, Stephan; Marwan, Mohamed

    2014-01-01

    The ability of contrast-enhanced CT to detect "late enhancement" in a fashion similar to magnetic resonance imaging has been previously reported. We report a case of acute myocarditis with coronary CT angiography as well as "late enhancement" imaging with ultra-low effective radiation dose. PMID:25439792

  12. Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.

    PubMed

    Fogarty, Mark C; Hughes, Ciara M; Burke, George; Brown, John C; Davison, Gareth W

    2013-01-28

    Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as β-carotene and α-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H₂O₂ accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (α-tocopherol, γ-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation.

  13. Stress testing for risk stratification of patients with low to moderate probability of acute cardiac ischemia.

    PubMed

    Chandra, A; Rudraiah, L; Zalenski, R J

    2001-02-01

    In summary, this article focused on the use of stress testing to risk-stratify patients at the conclusion of their emergency evaluation for ACI. As discussed, those patients in the probably not ACI category require additional risk stratification prior to discharge. It should be kept in mind that patients in this category are heterogeneous, containing subgroups at both higher and lower risk of ACI and cardiac events. The patients with lower pretest probability for ACI may only need exercise testing in the ED. Patients with higher pretest probability should undergo myocardial perfusion or echocardiographic stress testing to maximize diagnostic and prognostic information. Prognostic information is the key to provocative testing in the ED. Prognostic information is the component that will help emergency physicians identify the patients who may be discharged home safely without having to worry about a 6% annual cardiac death rate and a 10% overall death rate over the next 30 months. Stress testing provides this key prognostic data, and it can be obtained in short-stay chest pain observation units in a safe, timely, and cost-effective fashion. PMID:11214405

  14. Terbufos-sulfone exacerbates cardiac lesions in diabetic rats: a sub-acute toxicity study.

    PubMed

    Nurulain, Syed M; Shafiullah, Mohamed; Yasin, Javed; Adem, Abdu; Kaabi, Juma Al; Tariq, Saeed; Adeghate, Ernest; Ojha, Shreesh

    2016-06-01

    Organophosphorus compounds (OPCs) have a wide range of applications, from agriculture to warfare. Exposure to these brings forward a varied kind of health issues globally. Terbufos is one of the leading OPCs used worldwide. The present study investigates the cardiac effect of no observable dose of a metabolite of terbufos, terbufos-sulfone (TS), under non-diabetic and streptozotocin-induced diabetic condition. One hundred nanomoles per rat (1/20 of LD50) was administered intraperitoneally to adult male Wister rats daily for fifteen days. The left ventricle was collected for ultrastructural changes by transmission electron microscopy. The blood samples were collected for biochemical tests including RBC acetylcholinesterase, creatinine kinase (CK), lactate dehydrogenase (LDH), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, ALT, AST, and GGT. The study revealed about 10 % inhibition of RBC-AChE in two weeks of TS treatment in non-diabetic rats whereas RBC-AChE activity was significantly decreased in diabetic TS treated rats. CK, LDH, and triglycerides were significantly higher in diabetic TS treated rats. Electron microscopy of the heart showed derangement and lesions of the mitochondria of cardiomyocytes in the TS treated groups. The present study concludes that a non-lethal dose of TS causes cardiac lesions which exacerbate under diabetic condition. Biochemical tests confirmed the ultrastructural changes. It is concluded that a non-lethal dose of TS may be a risk factor for a cardiovascular disease, which may be fatal under diabetic condition. PMID:27331300

  15. γ-Oryzanol protects against acute cadmium-induced oxidative damage in mice testes.

    PubMed

    Spiazzi, Cristiano C; Manfredini, Vanusa; Barcellos da Silva, Fabiana E; Flores, Erico M M; Izaguirry, Aryele P; Vargas, Laura M; Soares, Melina B; Santos, Francielli W

    2013-05-01

    Cadmium is a non-essential heavy metal that is present at low levels mainly in food and water and also in cigar smoke. The present study evaluated the testicular damage caused by acute cadmium exposure and verified the protective role of γ-oryzanol (ORY). Mice were administrated with a single dose of 2.5mg/kg of CdCl2, and then treated with ORY (50mM in canola oil, 5mL/kg). Testes were removed after 24h and tested for lipid peroxidation (TBARS), protein carbonylation, DNA breakage, ascorbic acid, cadmium and non-proteic thiols contents, and for the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and δ-aminolevulic acid dehydratase (δ-ALA-D). Cadmium presented a significant alteration in all parameters, except GPx and CAT activities. Therapy reduced in a slight degree cadmium concentration in testes (around 23%). ORY restored SOD and GST activities as well as TBARS production to the control levels. Furthermore, ORY partially recovered δ-ALA-D activity inhibited by cadmium. This study provides the first evidence on the therapeutic properties of ORY in protecting against cadmium-induced testicular toxicity. PMID:23395783

  16. Study of Cardiac Arrest Caused by Acute Pulmonary Thromboembolism and Thrombolytic Resuscitation in a Porcine Model

    PubMed Central

    Zhao, Lian-Xing; Li, Chun-Sheng; Yang, Jun; Tong, Nan; Xiao, Hong-Li; An, Le

    2016-01-01

    Background: The success rate of resuscitation in cardiac arrest (CA) caused by pulmonary thromboembolism (PTE) is low. Furthermore, there are no large animal models that simulate clinical CA. The aim of this study was to establish a porcine CA model caused by PTE and to investigate the pathophysiology of CA and postresuscitation. Methods: This model was induced in castrated male pigs (30 ± 2 kg; n = 21) by injecting thrombi (10–15 ml) via the left external jugular vein. Computed tomographic pulmonary angiography (CTPA) was performed at baseline, CA, and return of spontaneous circulation (ROSC). After CTPA during CA, cardiopulmonary resuscitation (CPR) with thrombolysis (recombinant tissue plasminogen activator 50 mg) was initiated. Hemodynamic, respiratory, and blood gas data were monitored. Cardiac troponins T, cardiac troponin I, creatine kinase-MB, myoglobin, and brain natriuretic peptide (BNP) were measured by enzyme-linked immunosorbent assay. Data were compared between baseline and CA with paired-sample t-test and compared among different time points for survival animals with repeated measures analysis of variance. Results: Seventeen animals achieved CA after emboli injection, while four achieved CA after 5–8 ml more thrombi. Nine animals survived 6 h after CPR. CTPA showed obstruction of the pulmonary arteries. Mean aortic pressure data showed occurrence of CA caused by PTE (Z = −2.803, P = 0.002). The maximal rate of mean increase of left ventricular pressure (dp/dtmax) was statistically decreased (t = 6.315, P = 0.000, variation coefficient = 0.25), and end-tidal carbon dioxide partial pressure (PetCO2) decreased to the lowest value (t = 27.240, P = 0.000). After ROSC (n = 9), heart rate (HR) and mean right ventricular pressure (MRVP) remained different versus baseline until 2 h after ROSC (HR, P = 0.036; MRVP, P = 0.027). Myoglobin was statistically increased from CA to 1 h after ROSC (P = 0.036, 0.026, 0.009, respectively), and BNP was increased

  17. A novel role for epidermal growth factor receptor tyrosine kinase and its downstream endoplasmic reticulum stress in cardiac damage and microvascular dysfunction in type 1 diabetes mellitus.

    PubMed

    Galán, Maria; Kassan, Modar; Choi, Soo-Kyoung; Partyka, Megan; Trebak, Mohamed; Henrion, Daniel; Matrougui, Khalid

    2012-07-01

    Epidermal growth factor receptor tyrosine kinase (EGFRtk) and endoplasmic reticulum (ER) stress are important factors in cardiovascular complications. Understanding whether enhanced EGFRtk activity and ER stress induction are involved in cardiac damage, and microvascular dysfunction in type 1 diabetes mellitus is an important question that has remained unanswered. Cardiac fibrosis and microvascular function were determined in C57BL/6J mice injected with streptozotocin only or in combination with EGFRtk inhibitor (AG1478), ER stress inhibitor (Tudca), or insulin for 2 weeks. In diabetic mice, we observed an increase in EGFRtk phosphorylation and ER stress marker expression (CHOP, ATF4, ATF6, and phosphorylated-eIF2α) in heart and mesenteric resistance arteries, which were reduced with AG1478, Tudca, and insulin. Cardiac fibrosis, enhanced collagen type I, and plasminogen activator inhibitor 1 were decreased with AG1478, Tudca, and insulin treatments. The impaired endothelium-dependent relaxation and -independent relaxation responses were also restored after treatments. The inhibition of NO synthesis reduced endothelium-dependent relaxation in control and treated streptozotocin mice, whereas the inhibition of NADPH oxidase improved endothelium-dependent relaxation only in streptozotocin mice. Moreover, in mesenteric resistance arteries, the mRNA levels of Nox2 and Nox4 and the NADPH oxidase activity were augmented in streptozotocin mice and reduced with treatments. This study unveiled novel roles for enhanced EGFRtk phosphorylation and its downstream ER stress in cardiac fibrosis and microvascular endothelial dysfunction in type 1 diabetes mellitus.

  18. Are Surrogate Assumptions and Use of Diuretics Associated with Diagnosis and Staging of Acute Kidney Injury after Cardiac Surgery?

    PubMed Central

    Hussein, Hayder K.; Prabhu, Mahesh; Kanagasundaram, N. Suren

    2012-01-01

    Summary Background and objectives This study measured the association between the Acute Kidney Injury Network (AKIN) diagnostic and staging criteria and surrogates for baseline serum creatinine (SCr) and body weight, compared urine output (UO) with SCr criteria, and assessed the relationships between use of diuretics and calibration between criteria and prediction of outcomes. Design, setting, participants, & measurements This was a retrospective cohort study using prospective measurements of SCr, hourly UO, body weight, and drug administration records from 5701 patients admitted, after cardiac surgery, to a cardiac intensive care unit between 1995 and 2006. Results More patients (n=2424, 42.5%) met SCr diagnostic criteria with calculated SCr assuming a baseline estimated GFR of 75 ml/min per 1.73 m2 than with known baseline SCr (n=1043, 18.3%). Fewer patients (n=484, 8.5%) met UO diagnostic criteria with assumed body weight (70 kg) than with known weight (n=624, 10.9%). Agreement between SCr and UO criteria was fair (κ=0.28; 95% confidence interval 0.25–0.31). UO diagnostic criteria were specific (0.95; 0.94–0.95) but insensitive (0.36; 0.33–0.39) compared with SCr. Intravenous diuretics were associated with higher probability of falling below the UO diagnostic threshold compared with SCr, higher 30-day mortality (relative risk, 2.27; 1.08–4.76), and the need for renal support (4.35; 1.82–10.4) compared with no diuretics. Conclusions Common surrogates for baseline estimated GFR and body weight were associated with misclassification of AKIN stage. UO criteria were insensitive compared with SCr. Intravenous diuretic use further reduced agreement and confounded association between AKIN stage and 30-day mortality or need for renal support. PMID:22246280

  19. The risk factors and prognostic implication of acute pulmonary edema in resuscitated cardiac arrest patients

    PubMed Central

    Kang, Dae-hyun; Kim, Joonghee; Rhee, Joong Eui; Kim, Taeyun; Kim, Kyuseok; Jo, You Hwan; Lee, Jin Hee; Lee, Jae Hyuk; Kim, Yu Jin; Hwang, Seung Sik

    2015-01-01

    Objective Pulmonary edema is frequently observed after a successful resuscitation in out-of-hospital cardiac arrest (OHCA) patients. Currently, its risk factors and prognostic implications are mostly unknown. Methods Adult OHCA patients with a presumed cardiac etiology who achieved sustained return of spontaneous circulation (ROSC) in emergency department were retrospectively analyzed. The patients were grouped according to the severity of consolidation on their initial chest X-ray (group I, no consolidation; group II, patchy consolidations; group III, consolidation involving an entire lobe; group IV, total white-out of any lung). The primary objective was to identify the risk factors of developing severe pulmonary edema (group III or IV). The secondary objective was to evaluate the association between long-term prognosis and the severity of pulmonary edema. Results One hundred and seven patients were included. Total duration of cardiopulmonary resuscitation (CPR) and initial pCO2 level were both independent predictors of developing severe pulmonary edema with their odds ratio (OR) being 1.02 (95% confidence interval [CI], 1.00 to 1.04; per 1 minute) and 1.04 (95% CI, 1.01 to 1.07; per 1 mmHg), respectively. The long term prognosis was significantly poor in patients with severe pulmonary edema with a OR for good outcome (6-month cerebral performance category 1 or 2) being 0.22 (95% CI, 0.06 to 0.79) in group III and 0.16 (95% CI, 0.04 to 0.63) in group IV compared to group I. Conclusion The duration of CPR and initial pCO2 level were both independent predictors for the development of severe pulmonary edema after resuscitation in emergency department. The severity of the pulmonary edema was significantly associated with long-term outcome.

  20. The importance of analytical quality specifications for biomarker assays currently used in acute cardiac care.

    PubMed

    Panteghini, Mauro

    2006-01-01

    It is very important that cardiac biomarkers on which clinically relevant decisions will rest are measured with highly reliable assays. Adequate studies are needed before new methods can be implemented in the laboratory routine, and only well-documented assays should be considered for clinical use. Therefore, it is critical that, as new biomarkers are proposed, quality specifications are developed. Only after appropriate analytical quality specifications are addressed, the issues pertaining to methodological differences that result in non-harmonized concentration values, and clinical interpretation of biomarker concentrations will be reconciled. Today, the technology to address many analytic problems is at hand, but commitment on the part of manufacturers and their customers in the laboratory and clinical communities is essential. The design control loop is not closed until the finished in vitro diagnostic system is adequately validated to meet the customer needs, including analytical quality specifications. It is essential to determine the attributes and performance characteristics of relevant competitive systems and their degree of acceptance by clinical laboratories in order to demonstrate that user needs are definitely met. The responsibility of defining and implementing these issues must be a shared responsibility among laboratorians, clinicians, industry, and regulatory agencies on an international front. To date, two sets of quality specifications have been published, one for cardiac troponin assays and one for B-type natriuretic peptide assays. Both address analytical factors, such as calibrator characterization, antibody specificity, assay sensitivity and imprecision, and interferents, as well as preanalytical factors, such as sample type and stability. It would be ideal if regulatory agencies, such as FDA in the United States, accept these criteria for premarket approval clearance applications.

  1. Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events?

    PubMed

    Campia, Umberto; Nodari, Savina; Gheorghiade, Mihai

    2010-09-01

    Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

  2. Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology

    PubMed Central

    Oudkerk, Matthijs; Bluemke, David; Bremerich, Jens; Esteves, Fabio P.; Garcia, Ernest V.; Gutberlet, Matthias; Hundley, W. Gregory; Jerosch-Herold, Michael; Kuijpers, Dirkjan; Kwong, Raymond K.; Nagel, Eike; Lerakis, Stamatios; Oshinski, John; Paul, Jean-François; Underwood, Richard; Wintersperger, Bernd J.; Rees, Michael R.

    2010-01-01

    There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required. PMID:20972835

  3. Physical therapy for airway clearance improves cardiac autonomic modulation in children with acute bronchiolitis

    PubMed Central

    Jacinto, Cynthia P.; Gastaldi, Ada C.; Aguiar, Daniela Y.; Maida, Karina D.; Souza, Hugo C. D.

    2013-01-01

    Background The effects of physical therapy on heart rate variability (HRV), especially in children, are still inconclusive. Objective We investigated the effects of conventional physical therapy (CPT) for airway clearance and nasotracheal suction on the HRV of pediatric patients with acute bronchiolitis. Method 24 children were divided into two groups: control group (CG, n=12) without respiratory diseases and acute bronchiolitis group (BG, n=12). The heart rate was recorded in the BG at four different moments: basal recording (30 minutes), 5 minutes after the CPT (10 minutes), 5 minutes after nasotracheal suction (10 minutes), and 40 minutes after nasotracheal suction (30 minutes). The CG was subjected to the same protocol, except for nasotracheal suction. To assess the HRV, we used spectrum analysis, which decomposes the heart rate oscillations into frequency bands: low frequency (LF=0.04-0.15Hz), which corresponds mainly to sympathetic modulation; and high frequency (HF=0.15-1.2Hz), corresponding to vagal modulation. Results Under baseline conditions, the BG showed higher values in LF oscillations, lower values in HF oscillations, and increased LF/HF ratio when compared to the CG. After CPT, the values for HRV in the BG were similar to those observed in the CG during basal recording. Five minutes after nasotracheal suction, the BG showed a decrease in LF and HF oscillations; however, after 40 minutes, the values were similar to those observed after application of CPT. Conclusions The CPT and nasotracheal suction, both used for airway clearance, promote improvement in autonomic modulation of HRV in children with acute bronchiolitis. PMID:24271093

  4. Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats

    SciTech Connect

    Zordoky, Beshay N.M.; Anwar-Mohamed, Anwar; Aboutabl, Mona E.

    2010-01-01

    Doxorubicin (DOX) is a potent anti-neoplastic antibiotic used to treat a variety of malignancies; however, its use is limited by dose-dependent cardiotoxicity. Moreover, there is a strong correlation between cytochrome P450 (CYP)-mediated arachidonic acid metabolites and the pathogenesis of many cardiovascular diseases. Therefore, in the current study, we have investigated the effect of acute DOX toxicity on the expression of several CYP enzymes and their associated arachidonic acid metabolites in the heart of male Sprague-Dawley rats. Acute DOX toxicity was induced by a single intraperitoneal injection of 15 mg/kg of the drug. Our results showed that DOX treatment for 24 h caused a significant induction of CYP1A1, CYP1B1, CYP2C11, CYP2J3, CYP4A1, CYP4A3, CYP4F1, CYP4F4, and EPHX2 gene expression in the heart of DOX-treated rats as compared to the control. Similarly, there was a significant induction of CYP1A1, CYP1B1, CYP2C11, CYP2J3, CYP4A, and sEH proteins after 24 h of DOX administration. In the heart microsomes, acute DOX toxicity significantly increased the formation of 20-HETE which is consistent with the induction of the major CYP omega-hydroxylases: CYP4A1, CYP4A3, CYP4F1, and CYP4F4. On the other hand, the formation of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EETs) was significantly reduced, whereas the formation of their corresponding dihydroxyeicosatrienoic acids was significantly increased. The decrease in the cardioprotective EETs can be attributed to the increase of sEH activity parallel to the induction of the EPHX2 gene expression in the heart of DOX-treated rats. In conclusion, acute DOX toxicity alters the expression of several CYP and sEH enzymes with a consequent alteration in arachidonic acid metabolism. These results may represent a novel mechanism by which this drug causes progressive cardiotoxicity.

  5. Influence of HMGB1 and MSCs transplantation on rat cardiac angiogenesis with acute myocardial infarction.

    PubMed

    Jiang, Youxu; Wang, Xiaoman; Jiang, Xiaodong; Niu, Shaohui; Zhang, Lihua

    2016-07-01

    To observe whether HMGB1could enhance the paracrine effect of MSCs when the Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are pre-proccessed by High Mobility Group Box-1 (High Mobility Group Box-1, HMGB1). And to observe whether it can further increase the quantity of local angiogenesis in myocardial infarcts on the rat model with acute myocardial infarction, HMGB1 was combined with MSCs transplantation. MSCs in rats were cultivated with adherence and centrifugation method. Receptors of TLR4and RAGE in HMGB1 were tested. The MSCs were interfered by HMGB1 with different concentration gradient respectively, then the expression of VEGF was tested with ELISA method. SD male rats were divided into four groups: the model group, the MSCs transplantation group, the HMGB1 injection group, the HMGB1 injection plus MSCs transplantation group (n = 24), preparing rat model with acute myocardial infarction. The serum VEGF concentration levels were detected on the 3rd day, 7th and 28th day with ELISA method. On the 28th day after post operation the density of angiogenesis in infarction area was detected by immunohistochemal. (1) MSCs owned the expression of TLR4 and RAGE. (2) the secretion of VEGF increased significantly after the intervention of HMGB1 with concentration of 12.5 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL and 200ng/ml on MSCs compared with the control group. While the concentration was 400ng/ml or 800ng/ml, the secretion of VEGF decreased compared with the control group (P < 0.05). (3) detection of the serum VEGF on the 3rd or7th day after post operation was arranged: The results showed that: HMGB1 injection plus MSCs transplantation group > MSCs transplantation group >HMGB1 injection group >model group (P < 0.05). (4) the quantity of CD31 stained angiogenesis in HMGB1 injection plus MSCs transplantation group increased obviously. Combining MSCs transplantation, contributed to new angiogenesis of rats with acute myocardial infarction in myocardial infarction

  6. Cardiac Extracellular Vesicles in Normal and Infarcted Heart

    PubMed Central

    Chistiakov, Dimitry A.; Orekhov, Alexander N.; Bobryshev, Yuri V.

    2016-01-01

    Heart is a complex assembly of many cell types constituting myocardium, endocardium and epicardium that intensively communicate to each other in order to maintain the proper cardiac function. There are many types of intercellular intracardiac signals, with a prominent role of extracellular vesicles (EVs), such as exosomes and microvesicles, for long-distant delivering of complex messages. Cardiomyocytes release EVs, whose content could significantly vary depending on the stimulus. In stress, such as hypoxia, inflammation or injury, cardiomyocytes increase secretion of EVs. In hypoxic conditions, cardiac EVs are enriched with angiogenic and prosurvival factors. In acute myocardial infarction (AMI), damaged cardiac muscle cells produce EVs with increased content of angiogenic, anti-apoptotic, mitogenic and growth factors in order to induce repair and healing of the infarcted myocardium. Exosomal microRNAs play a central role in cardiac regeneration. In AMI, circulating cardiac EVs abundantly contain cardiac-specific miRNAs that serve as indicators of cardiac damage and have a big diagnostic potential as AMI biomarkers. Cardioprotective and regenerative properties of exosomes derived from cardiac and non-cardiac stem/progenitor cells are very helpful to be used in cell-free cardiotherapy and regeneration of post-infarct myocardium. PMID:26742038

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

    SciTech Connect

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

    2011-04-01

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

  8. Korean red ginseng ameliorates acute 3-nitropropionic acid-induced cochlear damage in mice.

    PubMed

    Tian, Chunjie; Kim, Young Ho; Kim, Young Chul; Park, Kyung Tae; Kim, Seung Won; Kim, Youn Ju; Lim, Hye Jin; Choung, Yun-Hoon

    2013-01-01

    3-Nitropropionic acid (3-NP), a mitochondrial toxin, has been reported to induce an acute cochlear damage. Korean red ginseng (KRG) is known to have protective effects from some types of hearing loss. This study aimed to observe the protective effect of KRG in an ototoxic animal model using 3-NP intratympanic injection. BALB/c mice were classified into 5 groups (n=15) and dose-dependent toxic effects after intratympanic injection with 3-NP (300-5000 mM) on the left ear were investigated to determine the appropriate toxicity level of 3-NP. For observation of the protective effects of KRG, 23 mice were grouped into 3-NP (500 mM, n=12) and KRG+3-NP groups (300 mg/kg KRG for 7 days before 500 mM 3-NP administration, n=11). Auditory brain response (ABR) and cochlear morphological evaluations were performed before and after drug administration. The ABR thresholds in the 800-5000 mM groups exceeded the maximum recording limit at 16 and 32 kHz 1 day after 3-NP administration. The ABR threshold in the 500 mM 3-NP+KRG group was significantly lower than that in the 500 mM 3-NP group from post 1 week to 1 month. The mean type II fibrocyte counts significantly differed between the control and 3-NP groups and between the 3-NP and 3-NP+KRG groups. Spiral ganglion cell degeneration in the 3-NP group was more severe than that in the 3-NP+KRG group. This animal model exhibited a dose-dependent hearing loss with histological changes. KRG administration ameliorated the deterioration of hearing by 3-NP. PMID:23164932

  9. Vitamin D deficiency contributes to vascular damage in sustained ischemic acute kidney injury.

    PubMed

    de Bragança, Ana C; Volpini, Rildo A; Mehrotra, Purvi; Andrade, Lúcia; Basile, David P

    2016-07-01

    Reductions in renal microvasculature density and increased lymphocyte activity may play critical roles in the progression of chronic kidney disease (CKD) following acute kidney injury (AKI) induced by ischemia/reperfusion injury (IRI). Vitamin D deficiency is associated with tubulointerstitial damage and fibrosis progression following IRI-AKI We evaluated the effect of vitamin D deficiency in sustained IRI-AKI, hypothesizing that such deficiency contributes to the early reduction in renal capillary density or alters the lymphocyte response to IRI Wistar rats were fed vitamin D-free or standard diets for 35 days. On day 28, rats were randomized into four groups: control, vitamin D deficient (VDD), bilateral IRI, and VDD+IRI Indices of renal injury and recovery were evaluated for up to 7 days following the surgical procedures. VDD rats showed reduced capillary density (by cablin staining), even in the absence of renal I/R. In comparison with VDD and IRI rats, VDD+IRI rats manifested a significant exacerbation of capillary rarefaction as well as higher urinary volume, kidney weight/body weight ratio, tissue injury scores, fibroblast-specific protein-1, and alpha-smooth muscle actin. VDD+IRI rats also had higher numbers of infiltrating activated CD4(+) and CD8(+) cells staining for interferon gamma and interleukin-17, with a significant elevation in the Th17/T-regulatory cell ratio. These data suggest that vitamin D deficiency impairs renal repair responses to I/R injury, exacerbates changes in renal capillary density, as well as promoting fibrosis and inflammation, which may contribute to the transition from AKI to CKD.

  10. Cardiac power index, mean arterial pressure, and Simplified Acute Physiology Score II are strong predictors of survival and response to revascularization in cardiogenic shock.

    PubMed

    Popovic, Batric; Fay, Renaud; Cravoisy-Popovic, Aurelie; Levy, Bruno

    2014-07-01

    Short-term prognostic factors in patients with cardiogenic shock (CS) have previously been established using only hemodynamic parameters without taking into account classic intensive care unit (ICU) severity score or organ failure/support. The aim of this study was to assess early predictors of in-hospital mortality of a monocentric cohort of patients with ST-elevation myocardial infarction complicated by early CS. We retrospectively studied 85 consecutive patients with CS complicating acute myocardial infarction and Thrombolysis in Myocardial Infarction flow grade 3 after percutaneous coronary revascularization. All patients were managed according to the following algorithm: initial resuscitation by a mobile medical unit or in-hospital critical care physician unit followed by percutaneous coronary revascularization and CS management in the ICU. Prehospital CS was diagnosed in 69% of cases, initially complicated by an out-of-hospital cardiac arrest in 64% of cases. All patients were treated with vasopressors, 82% were ventilated, and 22% underwent extrarenal epuration. The 28-day mortality rate was 39%. Under multivariate analysis, initial cardiac power index, mean arterial pressure of less than 75 mmHg at hour 6 of ICU management, and Simplified Acute Physiology Score II were independent predictive factors of in-hospital mortality. In conclusion, parameters directly related to cardiac performance and vascular response to vasopressors and admission Simplified Acute Physiology Score II are strong predictors of in-hospital mortality.

  11. China Patient-centered Evaluative Assessment of Cardiac Events Prospective Study of Acute Myocardial Infarction: Study Design

    PubMed Central

    Li, Jing; Dreyer, Rachel P; Li, Xi; Du, Xue; Downing, Nicholas S; Li, Li; Zhang, Hai-Bo; Feng, Fang; Guan, Wen-Chi; Xu, Xiao; Li, Shu-Xia; Lin, Zhen-Qiu; Masoudi, Frederick A; Spertus, John A; Krumholz, Harlan M; Jiang, Li-Xin

    2016-01-01

    Background: Despite the rapid growth in the incidence of acute myocardial infarction (AMI) in China, there is limited information about patients’ experiences after AMI hospitalization, especially on long-term adverse events and patient-reported outcomes (PROs). Methods: The China Patient-centered Evaluative Assessment of Cardiac Events (PEACE)-Prospective AMI Study will enroll 4000 consecutive AMI patients from 53 diverse hospitals across China and follow them longitudinally for 12 months to document their treatment, recovery, and outcomes. Details of patients’ medical history, treatment, and in-hospital outcomes are abstracted from medical charts. Comprehensive baseline interviews are being conducted to characterize patient demographics, risk factors, presentation, and healthcare utilization. As part of these interviews, validated instruments are administered to measure PROs, including quality of life, symptoms, mood, cognition, and sexual activity. Follow-up interviews, measuring PROs, medication adherence, risk factor control, and collecting hospitalization events are conducted at 1, 6, and 12 months after discharge. Supporting documents for potential outcomes are collected for adjudication by clinicians at the National Coordinating Center. Blood and urine samples are also obtained at baseline, 1- and 12-month follow-up. In addition, we are conducting a survey of participating hospitals to characterize their organizational characteristics. Conclusion: The China PEACE-Prospective AMI study will be uniquely positioned to generate new information regarding patient's experiences and outcomes after AMI in China and serve as a foundation for quality improvement activities. PMID:26712436

  12. CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac troponin I for acute myocardial infarction diagnosis.

    PubMed

    Kong, Tao; Su, Ruigong; Zhang, Beibei; Zhang, Qi; Cheng, Guosheng

    2012-04-15

    A label-free biosensor for electrical detection of cardiac troponin I (cTnI), a highly sensitive and selective biomarker of acute myocardial infarction (AMI), is demonstrated using silicon nanowire (SiNW) based field-effect transistors (FETs). The FET devices were fabricated by a complementary metal oxide semiconductor (CMOS) compatible top-down approach to define the SiNW followed by tetramethylammonium hydroxide (TMAH) wet etching. Electrical characterizations of the SiNW FET revealed an ambipolar conduction characteristic with an on/off ratio of 10(5)-10(6). CTnI monoclonal antibodies were then covalently immobilized on the SiNW surfaces. By integrating with a homemade biosensor measurement system, the biosensor exhibited rapid and sensitive response to cTnI proteins. The current response showed a nature of logarithm relationship against the cTnI concentration from 46 ng/mL down to 0.092 ng/mL. Moreover, an anti-interference capability of the fabricated biosensor was also assessed. By utilizing the top-down fabrication method, this work provides an efficient way for the cTnI proteins detection with an enormous potential of mass-production, which definitely facilitate the practical applications.

  13. Haploinsufficiency of Hand1 improves mice survival after acute myocardial infarction through preventing cardiac rupture.

    PubMed

    Lu, Shuangshuang; Du, Pan; Shan, Congjia; Wang, Yaohe; Ma, Changsheng; Dong, Jianzeng

    2016-09-30

    Previous studies have demonstrated a significantly lower level of Hand1 in ischemic cardiomyopathy than in normal heart tissue. The role of decreased Hand1 in myocardial infarction remains unclear. This study was designed to investigate the effects of haploinsufficiency of Hand1 on mouse heart after myocardial infarction. 8-10 weeks old male heterozygous Hand1-deficient (Hand1(+/-)) mice and wild-type littermates (control) were subjected to sham operation or ligation of the left anterior descending coronary artery to induce acute myocardial infarction (AMI). Hand1(+/-) mice have low incidence of left ventricular free wall rupture in the first week after operation than control mice. Then we found lower MMP9 activity and less cardiomyocytes apoptosis in Hand1(+/-) than in control mice. All of these contribute to the protection role of haploinsufficiency of Hand1 after AMI.

  14. Cardiac catheterization

    MedlinePlus

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

  15. Acute acidic exposure induces p53-mediated oxidative stress and DNA damage in tilapia (Oreochromis niloticus) blood cells.

    PubMed

    Mai, Wei-jun; Yan, Jun-lun; Wang, Lei; Zheng, Ying; Xin, Yu; Wang, Wei-na

    2010-11-01

    Acid rain and inputs of acidic effluent can result in increased acidity in aquatic ecosystems, where it is known to have a significant impact and possibly, to cause the decline of some populations of aquatic organisms. In previous studies, intracellular acid-induced oxidative stress has been shown to cause DNA damage, and cooperatively activate the expression of the p53 gene. The acute effects of acidic environments on shrimp and fish have been widely studied. However, the molecular mechanism of acid-induced injury remains largely unknown. In this study, we examined the cellular responses of tilapia to acidic exposure-induced oxidative stress and antioxidant enzyme gene expression. Furthermore, we determined how acute acid stress activates the ATM-p53 signal pathway. We measured the upregulation of reactive oxygen species (ROS) production, the intracellular Ca(2)(+) concentration ([Ca(2)(+)](i)), the tail DNA values, the malondialdehyde (MDA) level in the blood cells and the percentage of dead and damaged blood cells. Our results suggest that oxidative stress and DNA damage occurred in tilapia in conditions where the pH was 5.3. Apoptosis was detected by Hoechst staining, which was mainly associated with changes in cell viability. The parameters that we measured were related to acid-induced DNA damage, and all parameters changed in the blood cells through time. The effects of acute acid exposure (pH 5.3) on the expression of ATM, p53, p21, Bax, manganese superoxide dismutase (MnSOD), glutathione peroxidase (GPx) were investigated in tilapia blood cells. The results showed that acute acid stress induced upregulation of ATM, p53 and p21, associated with increasing of DNA damage and apoptosis in blood cells. Additionally, the expression of Bax was slightly increased. Moreover, consensus p53-binding sequences were identified in tilapia MnSOD and GPx gene promoter regions and increased levels of ROS in the blood cells coincided with increased mRNA expression of p53, Mn

  16. Acute effects of nonexcitatory electrical stimulation during systole in isolated cardiac myocytes and perfused heart

    PubMed Central

    Blinova, Ksenia; Stohlman, Jayna; Krauthamer, Victor; Knapton, Alan; Bloomquist, Erik; Gray, Richard A.

    2014-01-01

    Abstract Application of electrical field to the heart during the refractory period of the beat has been shown to increase the force of contraction both in animal models and in heart failure patients (cardiac contractility modulation, or CCM). A direct increase in intracellular calcium during CCM has been suggested to be the mechanism behind the positive inotropic effect of CCM. We studied the effect of CCM on isolated rabbit cardiomyocytes and perfused whole rat hearts. The effect of CCM was observed in single cells via fluorescent measurements of intracellular calcium concentration ([Ca2+]i) and cell length (L). Cells were paced once per second throughout these recordings, and CCM stimulation was delivered via biphasic electric fields of 20 ms duration applied during the refractory period. CCM increased the peak amplitude of both [Ca2+]i and L for the first beat during CCM compared to control, but then [Ca2+]i and L decayed to levels lower than the control. During CCM, all contractions had a faster time to peak for both [Ca2+]i and L; after stopping CCM the rise times returned to control levels. In the whole rat heart, the positive inotropic effect of CCM stimulation on left ventricular pressure was completely abolished in the presence of metoprolol, a beta‐1 adrenergic blocker. In summary, the CCM‐induced changes in intracellular calcium handling by cardiomyocytes did not explain the sustained positive inotropic effect in the whole heart and the β‐adrenergic pathway may be involved in the CCM mechanism of action. PMID:25096553

  17. Cardiac complications in thalassemia major.

    PubMed

    Auger, Dominique; Pennell, Dudley J

    2016-03-01

    The myocardium is particularly susceptible to complications from iron loading in thalassemia major. In the first years of life, severe anemia leads to high-output cardiac failure and death if not treated. The necessary supportive blood transfusions create loading of iron that cannot be naturally excreted, and this iron accumulates within tissues, including the heart. Free unbound iron catalyzes the formation of toxic hydroxyl radicals, which damage cells and cause cardiac dysfunction. Significant cardiac siderosis may present by the age of 10 and may lead to acute clinical heart failure, which must be treated urgently. Atrial fibrillation is the most frequently encountered iron-related arrhythmia. Iron chelation is effective at removing iron from the myocardium, at the expense of side effects that hamper compliance to therapy. Monitoring of myocardial iron content is mandatory for clinical management of cardiac risk. T2* cardiac magnetic resonance measures myocardial iron and is the strongest biomarker for prediction of heart failure and arrhythmic events. It has been calibrated to human myocardial tissue iron concentration and is highly reproducible across all magnetic resonance scanner vendors. As survival and patient age increases, endothelial dysfunction and diabetes may become new factors in the cardiovascular health of thalassemia patients. Promising new imaging technology and therapies could ameliorate the long-term prognosis.

  18. [Clinical value of rapid clearance in resting sestamibi cardiac SPECT in patients with acute myocardial infarction].

    PubMed

    Itagane, H; Yamagishi, H; Otsuka, M; Minami, S; Suto, Y; Hato, K; Tojo, O; Okumachi, F; Haze, K

    1995-07-01

    Resting 99mTc sestamibi (MIBI) SPECT and exercise-reinjection thallium-201 (T1) SPECT were performed in fourteen patients with acute myocardial infarction (AMI). MIBI SPECT were obtained 90 min (MIBI-90) and 300 min (MIBI-300) after injection of 370 MBq of MIBI at rest. MIBI-90 and MIBI-300 were compared with exercise T1 imaging (T1-EX) and T1 reinjection imaging (REINJ). Each SPECT image was divided into 22 segments and myocardial uptake was scored visually. Abnormal perfusion defects were observed in 94 myocardial regions. Worsening of the score was observed in 79 segments (84%) on MIBI-300 compared with MIBI-90. Total MIBI-300 uptake score per person was significantly greater than that at MIBI-90 (14.8 +/- 8.6 vs. 7.7 +/- 7.9, p = 0.001). The concordance rate of defect score between MIBI-90 and REINJ was significantly higher than that between MIBI-300 and REINJ (55% vs. 17%, p = 0.001). In nine patients without recanalization of an infarct-related artery, perfusion defects were seen in 74 segments. The concordance rate of defect scores between MIBI-300 and T1-EX was significantly higher than that between MIBI-90 and T1-EX (45% vs. 16%, p = 0.001). In conclusion, rapid clearance of MIBI was observed frequently in patients with AMI. MIBI-90 and MIBI-300 may reflect myocardial viability and areas at risk for AMI, respectively.

  19. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway

    SciTech Connect

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit

    2009-10-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-{kappa}B (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-{kappa}B and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-{kappa}B activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-{kappa}B activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection

  20. Acute and Chronic Changes and Predictive Value of Tpeak-Tend for Ventricular Arrhythmia Risk in Cardiac Resynchronization Therapy Patients

    PubMed Central

    Xue, Cong; Hua, Wei; Cai, Chi; Ding, Li-Gang; Liu, Zhi-Min; Fan, Xiao-Han; Zhao, Yun-Zi; Zhang, Shu

    2016-01-01

    Background: Prolongation of the Tpeak-Tend (TpTe) interval as a measurement of transmural dispersion of repolarization (TDR) is an independent risk factor for chronic heart failure mortality. However, the cardiac resynchronization therapy's (CRT) effect on TDR is controversial. Therefore, this study aimed to evaluate CRTs acute and chronic effects on repolarization dispersion. Furthermore, we aimed to investigate the relationship between TpTe changes and ventricular arrhythmia. Methods: The study group consisted of 101 patients treated with CRT-defibrillator (CRT-D). According to whether TpTe was shortened, patients were grouped at immediate and 1-year follow-up after CRT, respectively. The echocardiogram index and ventricular arrhythmia were observed and compared in these subgroups. Results: For all patients, TpTe slightly increased immediately after CRT-D implantation, and then decreased at the 1-year follow-up (from 107 ± 23 to 110 ± 21 ms within 24 h, to 94 ± 24 ms at 1-year follow-up, F = 19.366, P < 0.001). No significant difference in the left ventricular reverse remodeling and ventricular tachycardia/ventricular fibrillation (VT/VF) episodes between the TpTe immediately shortened and TpTe immediately nonshortened groups. However, patients in the TpTe at 1-year shorten had a higher rate of the left ventricular (LV) reverse remodeling (65% vs. 44%, χ2 = 4.495, P = 0.038) and less VT/VF episodes (log-rank test, χ2 = 10.207, P = 0.001) compared with TpTe 1-year nonshortened group. TpTe immediately after CRT-D independently predicted VT/VF episodes at 1-year follow-up (hazard ratio [HR], 1.030; P = 0.001). Conclusions: Patients with TpTe shortened at 1-year after CRT had a higher rate of LV reverse remodeling and less VT/VF episodes. The acute changes of TpTe after CRT have minimal value on mechanical reverse remodeling and ventricular arrhythmia. PMID:27625093

  1. System for the diagnosis and monitoring of coronary artery disease, acute coronary syndromes, cardiomyopathy and other cardiac conditions

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T. (Inventor); Arenare, Brian (Inventor)

    2008-01-01

    Cardiac electrical data are received from a patient, manipulated to determine various useful aspects of the ECG signal, and displayed and stored in a useful form using a computer. The computer monitor displays various useful information, and in particular graphically displays various permutations of reduced amplitude zones and kurtosis that increase the rapidity and accuracy of cardiac diagnoses. New criteria for reduced amplitude zones are defined that enhance the sensitivity and specificity for detecting cardiac abnormalities.

  2. Purple sweet potato (Ipomoea batatas L.) anthocyanins: preventive effect on acute and subacute alcoholic liver damage and dealcoholic effect.

    PubMed

    Sun, Hongnan; Mu, Taihua; Liu, Xingli; Zhang, Miao; Chen, Jingwang

    2014-03-19

    This study aimed to investigate the dealcoholic effect and preventive effect of anthocyanins from purple sweet potato (PSPAs) on acute and subacute alcoholic liver damage (ALD). Seven-week-old male inbred mice were grouped into five groups: control group (without PSPAs and ethanol treatments), model group (with ethanol treatment only), low-dose group (50 mg PSPAs/kg body weight), middle-dose group (125 mg PSPAs/kg body weight), and high-dose group (375 mg PSPAs/kg body weight), and the mice in all groups were administered intragastrically. Biochemical parameters of serum and liver were determined, and the histopathological changes of liver tissue were also analyzed. Results showed that all tested parameters were ameliorated after consumption of PSPAs. Therefore, PSPAs have preventive effect on acute and subacute ALD. It is suggested that PSPAs could be used as a supplementary reagent during prophylactic and curative managements of ALD.

  3. Chagas cardiomyopathy: The potential effect of benznidazole treatment on diastolic dysfunction and cardiac damage in dogs chronically infected with Trypanosoma cruzi.

    PubMed

    Santos, Fabiane M; Mazzeti, Ana L; Caldas, Sérgio; Gonçalves, Karolina R; Lima, Wanderson G; Torres, Rosália M; Bahia, Maria Terezinha

    2016-09-01

    Cardiac involvement represents the main cause of mortality among patients with Chagas disease, and the relevance of trypanocidal treatment to improving diastolic dysfunction is still doubtful. In the present study, we used a canine model infected with the benznidazole-sensitive Berenice-78 Trypanosoma cruzi strain to verify the efficacy of an etiologic treatment in reducing the parasite load and ameliorating cardiac muscle tissue damage and left ventricular diastolic dysfunction in the chronic phase of the infection. The effect of the treatment on reducing the parasite load was monitored by blood PCR and blood culture assays, and the effect of the treatment on the outcome of heart tissue damage and on diastolic function was evaluated by histopathology and echo Doppler cardiogram. The benefit of the benznidazole-treatment in reducing the parasite burden was demonstrated by a marked decrease in positive blood culture and PCR assay results until 30days post-treatment. At this time, the PCR and blood culture assays yielded negative results for 82% of the treated animals, compared with only 36% of the untreated dogs. However, a progressive increase in the parasite load could be detected in the peripheral blood for one year post-treatment, as evidenced by a progressive increase in positive results for both the PCR and the blood culture assays at follow-up. The parasite load reduction induced by treatment was compatible with the lower degree of tissue damage among animals euthanized in the first month after treatment and with the increased cardiac damage after this period, reaching levels similar to those in untreated animals at the one-year follow-up. The two infected groups also presented similar, significantly smaller values for early tissue septal velocity (E' SIV) than the non-infected dogs did at this later time. Moreover, in the treated animals, an increase in the E/E' septal tissue filling pressure ratio was observed when compared with basal values as well as with

  4. Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles

    PubMed Central

    Nemmar, Abderrahim; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Kazzam, Elsadig E; Ali, Badreldin H

    2016-01-01

    The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings. PMID:27022259

  5. Bone marrow mesenchymal stem cell implantation for the treatment of radioactivity‑induced acute skin damage in rats.

    PubMed

    Zheng, Kai; Wu, Weizhen; Yang, Shunliang; Huang, Lianghu; Chen, Jin; Gong, Chungui; Fu, Zhichao; Zhang, Linlin; Tan, Jianming

    2015-11-01

    The present study aimed to observe the role of mesenchymal stem cells (MSCs) in the repair of acute skin damage caused by radiation. Rat bone marrow MSCs (BMSCs) were isolated and cultured in vitro. A rat model of radiation‑induced acute skin damage was established by irradiation of the hind legs of Sprague-Dawley rats using a linear accelerator (45 Gy). After irradiation, rats were randomly divided into two groups: BMSC group and control group. Rats in the BMSC group were treated with a tail vein injection of 2x106 BMSCs (1 ml) immediately after irradiation and a local multipoint injection of 2x106 BMSCs at the injured area two weeks later. Then the wound healing of each rat was observed. The expression of transforming growth factor (TGF)‑β1, stromal cell‑derived factor-1 (SDF‑1) and prostaglandin E2 (PGE2) in the wounded tissues was determined by immunohistochemistry. The results demonstrated that skin damage was milder in the BMSC group than in the control group. Moreover, the speed of healing in the BMSC group was better than that in the control group. In addition, the wound score, it was significantly lower in the BMSC group than in the control group (P<0.05). The expression of PGE2 and TGF‑β1 in the BMSC group was also significantly lower than that in the control group (P<0.05), whereas the SDF‑1 expression was significantly higher in the BMSC group than that in the control group (P<0.05). BMSCs can effectively reduce inflammation and fibrosis in the wounded skin and promote the repair of acute radioactive skin injury. Thus, may be developed as a novel treatment for wound healing. PMID:26323987

  6. Triphasic multinutrient supplementation during acute resistance exercise improves session volume load and reduces muscle damage in strength-trained athletes.

    PubMed

    Bird, Stephen P; Mabon, Tom; Pryde, Mitchell; Feebrey, Sarah; Cannon, Jack

    2013-05-01

    We hypothesized that triphasic multinutrient supplementation during acute resistance exercise would enhance muscular performance, produce a more favorable anabolic profile, and reduce biochemical markers of muscle damage in strength-trained athletes. Fifteen male strength-trained athletes completed two acute lower-body resistance exercise sessions to fatigue 7 days apart. After a 4-hour fast, participants consumed either a multinutrient supplement (Musashi 1-2-3 Step System, Notting Hill, Australia) (SUPP) or placebo (PLA) beverage preexercise (PRE), during (DUR), and immediately postexercise (IP). Session volume loads were calculated as kilograms × repetitions. Lower-body peak power was measured using unloaded repeated countermovement jumps, and blood samples were collected to assess biochemistry, serum hormones, and muscle damage markers at PRE, DUR, IP, 30 minutes postexercise (P30), and 24 hours postexercise (P24h). The SUPP demonstrated increased glucose concentrations at DUR and IP compared with at PRE (P < .01), whereas PLA demonstrated higher glucose at P30 compared with at PRE (P < .001). Session volume load was higher for SUPP compared with PLA (P < .05). Cortisol increased at DUR, IP, and P30 compared with at PRE in both treatments (P < .05); however, SUPP also displayed lower cortisol at P24h compared with at PRE and PLA (P < .01). The total testosterone response to exercise was higher for PLA compared with SUPP (P < .01); however, total creatine kinase and C-reactive protein responses to exercise were lower for SUPP compared with PLA (P < .05). These data indicate that although triphasic multinutrient supplementation did not produce a more favorable anabolic profile, it improved acute resistance exercise performance while attenuating muscle damage in strength-trained athletes.

  7. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

    PubMed

    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  8. Ablation of C/EBP homologous protein increases the acute phase mortality and doesn't attenuate cardiac remodeling in mice with myocardial infarction.

    PubMed

    Luo, Guangjin; Li, Qingman; Zhang, Xiajun; Shen, Liang; Xie, Jiahe; Zhang, Jingwen; Kitakaze, Masafumi; Huang, Xiaobo; Liao, Yulin

    2015-08-14

    Endoplasmic reticulum stress is a proapoptotic and profibrotic stimulus. Ablation of C/EBP homologous protein (CHOP) is reported to reverse cardiac dysfunction by attenuating cardiac endoplasmic reticulum stress in mice with pressure overload or ischemia/reperfusion, but it is unclear whether loss of CHOP also inhibits cardiac remodeling induced by permanent-infarction. In mice with permanent ligation of left coronary artery, we found that ablation of CHOP increased the acute phase mortality. For the mice survived to 4 weeks, left ventricular anterior (LV) wall thickness was larger in CHOP knockout mice than in the wildtype littermates, while no difference was noted on posterior wall thickness, LV dimensions, LV fractional shortening and ejection fraction. Similarly, invasive assessment of LV hemodynamics, morphological analysis of heart and lung weight indexes, myocardial fibrosis and TUNEL-assessed apoptosis showed no significant differences between CHOP knockout mice and their wildtype ones, while in mice with ischemia for 45 min and reperfusion for 1 week, myocardial fibrosis and apoptosis in the infarct area were significantly attenuated in CHOP knockout mice. These findings indicate that ablation of CHOP doesn't ameliorate cardiac remodeling induced by permanent-myocardial infarction, which implicates that early reperfusion is a prerequisite for ischemic myocardium to benefit from CHOP inhibition.

  9. Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a "healthy" tobacco-free alternative.

    PubMed

    Cobb, Caroline O; Sahmarani, Kamar; Eissenberg, Thomas; Shihadeh, Alan

    2012-11-23

    Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for "health-conscious" users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p<0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p<0.01), while CO increased with both products (p<0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine. PMID:23059956

  10. Acute toxicant exposure and cardiac autonomic dysfunction from smoking a single narghile waterpipe with tobacco and with a “healthy” tobacco-free alternative

    PubMed Central

    Cobb, Caroline O.; Sahmarani, Kamar; Eissenberg, Thomas; Shihadeh, Alan

    2012-01-01

    Tobacco smoking using a waterpipe (narghile, hookah, shisha) has become a global epidemic. Unlike cigarette smoking, little is known about the health effects of waterpipe use. One acute effect of cigarette smoke inhalation is dysfunction in autonomic regulation of the cardiac cycle, as indicated by reduction in heart rate variability (HRV). Reduced HRV is implicated in adverse cardiovascular health outcomes, and is associated with inhalation exposure-induced oxidative stress. Using a 32 participant cross-over study design, we investigated toxicant exposure and effects of waterpipe smoking on heart rate variability when, under controlled conditions, participants smoked a tobacco-based and a tobacco-free waterpipe product promoted as an alternative for “health-conscious” users. Outcome measures included HRV, exhaled breath carbon monoxide (CO), plasma nicotine, and puff topography, which were measured at times prior to, during, and after smoking. We found that waterpipe use acutely decreased HRV (p<0.01 for all measures), independent of product smoked. Plasma nicotine, blood pressure, and heart rate increased only with the tobacco-based product (p<0.01), while CO increased with both products (p<0.01). More smoke was inhaled during tobacco-free product use, potentially reflecting attempted regulation of nicotine intake. The data thus indicate that waterpipe smoking acutely compromises cardiac autonomic function, and does so through exposure to smoke constituents other than nicotine. PMID:23059956

  11. Systematic analysis of axonal damage and inflammatory response in different white matter tracts of acutely injured rat spinal cord.

    PubMed

    Gomes-Leal, W; Corkill, D J; Picanço-Diniz, C W

    2005-12-20

    The mechanisms of white matter (WM) damage during secondary degeneration are a fundamental issue in the pathophysiology of central nervous system (CNS) diseases. Our main goal was to describe the pattern of an acute inflammatory response and secondary damage to axons in different WM tracts of acutely injured rat spinal cord. Adult rats were deeply anesthetized and injected with 20 nmol of NMDA into the spinal cord ventral horn on T7. Animals were perfused after survival times of 1 day, 3 days and 7 days. Ten micrometer sections were submitted to immunocytochemical analysis for activated macrophages/microglia, neutrophils and damaged axons. There were inflammatory response and progressive tissue destruction of ventral WM (VWM) with formation of microcysts in both VWM and lateral WM (LWM). In the VWM, the number of beta-amyloid precursor protein (beta-APP) end-bulbs increased from 1 day with a peak at 3 days, decreasing by 7 days following the injection. APP end-bulbs were present in the dorsal WM (DWM) at 3 days survival time but were not in the LWM. Electron microscopic analysis revealed different degrees of myelin disruption and axonal pathology in the vacuolated WM up to 14 mm along the rostrocaudal axis. Quantitative analysis revealed a significant loss of medium and large axons (P < 0.05), but not of small axons (P > 0.05). Our results suggest that bystander axonal damage and myelin vacuolation are important secondary component of the pathology of WM tracts following rat SCI. Further studies are needed to understand the mechanisms of these pathological events.

  12. Emergency Cardiac Surgery in Patients with Acute Coronary Syndromes: A Review of the Evidence and Perioperative Implications of Medical and Mechanical Therapeutics

    PubMed Central

    Brown, Charles; Joshi, Brijen; Faraday, Nauder; Shah, Ashish; Yuh, David; Rade, Jeffrey J.; Hogue, Charles W.

    2011-01-01

    Patients with acute coronary syndromes who require emergency cardiac surgery present complex management challenges. The early administration of antiplatelet and antithrombotic drugs has improved overall survival for patients with acute myocardial infarction, but to achieve maximal benefit, these drugs are given before coronary anatomy is known and before the decision to perform percutaneous coronary interventions or surgical revascularization has been made. A major bleeding event secondary to these drugs is associated with a high rate of death in medically treated patients with acute coronary syndrome possibly due to subsequent withholding of antiplatelet and antithrombotic therapies that otherwise reduce the rate of death, stroke, or recurrent myocardial infarcation. Whether the added risk of bleeding and blood transfusion in cardiac surgical patients receiving such potent antiplatelet or antithrombotic therapy before surgery specifically for acute coronary syndromes affects long-term mortality has not been clearly established. For patients who do proceed to surgery, strategies to minimize bleeding include stopping the anticoagulation therapy and considering platelet and/or coagulation factor transfusion and possibly rFVIIa administration for refractory bleeding. Mechanical hemodynamic support has emerged as an important option for patients with acute coronary syndromes in cardiogenic shock. For these patients, perioperative considerations include maintaining appropriate anticoagulation, ensuring suitable device flow, and periodically verifying correct device placement. Data supporting the use of these devices are derived from small trials that did not address long-term postoperative outcomes. Future directions of research will seek to optimize the balance between reducing myocardial ischemic risk with antiplatelet and antithrombotics versus the higher rate perioperative bleeding by better risk-stratifying surgical candidates and by assessing the effectiveness of

  13. Emergency cardiac surgery in patients with acute coronary syndromes: a review of the evidence and perioperative implications of medical and mechanical therapeutics.

    PubMed

    Brown, Charles; Joshi, Brijen; Faraday, Nauder; Shah, Ashish; Yuh, David; Rade, Jeffrey J; Hogue, Charles W

    2011-04-01

    Patients with acute coronary syndromes who require emergency cardiac surgery present complex management challenges. The early administration of antiplatelet and antithrombotic drugs has improved overall survival for patients with acute myocardial infarction, but to achieve maximal benefit, these drugs are given before coronary anatomy is known and before the decision to perform percutaneous coronary interventions or surgical revascularization has been made. A major bleeding event secondary to these drugs is associated with a high rate of death in medically treated patients with acute coronary syndrome possibly because of subsequent withholding of antiplatelet and antithrombotic therapies that otherwise reduce the rate of death, stroke, or recurrent myocardial infarction. Whether the added risk of bleeding and blood transfusion in cardiac surgical patients receiving such potent antiplatelet or antithrombotic therapy before surgery specifically for acute coronary syndromes affects long-term mortality has not been clearly established. For patients who do proceed to surgery, strategies to minimize bleeding include stopping the anticoagulation therapy and considering platelet and/or coagulation factor transfusion and possibly recombinant-activated factor VIIa administration for refractory bleeding. Mechanical hemodynamic support has emerged as an important option for patients with acute coronary syndromes in cardiogenic shock. For these patients, perioperative considerations include maintaining appropriate anticoagulation, ensuring suitable device flow, and periodically verifying correct device placement. Data supporting the use of these devices are derived from small trials that did not address long-term postoperative outcomes. Future directions of research will seek to optimize the balance between reducing myocardial ischemic risk with antiplatelet and antithrombotics versus the higher rate perioperative bleeding by better risk stratifying surgical candidates and by

  14. Increased 4-hydroxy-2-nonenal-induced proteasome dysfunction is correlated with cardiac damage in streptozotocin-injected rats with isoproterenol infusion.

    PubMed

    Deshpande, Mandar; Mali, Vishal R; Pan, Guodong; Xu, Jiang; Yang, Xiao-Ping; Thandavarayan, Rajarajan A; Palaniyandi, Suresh Selvaraj

    2016-07-01

    Increase in 4-hydroxy-2-nonenal (4HNE) due to oxidative stress has been observed in a variety of cardiac diseases such as diabetic cardiomyopathy. 4HNE exerts a damaging effect in the myocardium by interfering with subcellular organelles like mitochondria by forming adducts. Therefore, we hypothesized that increased 4HNE adduct formation in the heart results in proteasome inactivation in isoproterenol (ISO)-infused type 1 diabetes mellitus (DM) rats. Eight-week-old male Sprague Dawley rats were injected with streptozotocin (STZ, 65 mg kg(-1) ). The rats were infused with ISO (5 mg kg(-1) ) for 2 weeks by mini pumps, after 8 weeks of STZ injection. We studied normal control (n = 8) and DM + ISO (n = 10) groups. Cardiac performance was assessed by echocardiography and Millar catheter at the end of the protocol at 20 weeks. Initially, we found an increase in 4HNE adducts in the hearts of the DM + ISO group. There was also a decrease in myocardial proteasomal peptidase (chymotrypsin and trypsin-like) activity. Increases in cardiomyocyte area (446 ± 32·7 vs 221 ± 10·83) (µm(2) ), per cent area of cardiac fibrosis (7·4 ± 0·7 vs 2·7 ± 0·5) and cardiac dysfunction were also found in DM + ISO (P < 0·05) relative to controls. We also found increased 4HNE adduct formation on proteasomal subunits. Furthermore, reduced aldehyde dehydrogenase 2 activity was observed in the myocardium of the DM + ISO group. Treatment with 4HNE (100 μM) for 4 h on cultured H9c2 cardiomyocytes attenuated proteasome activity. Therefore, we conclude that the 4HNE-induced decrease in proteasome activity may be involved in the cardiac pathology in STZ-injected rats infused with ISO. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27273517

  15. A patient with possible TRALI who developed pulmonary hypertensive crisis and acute pulmonary edema during cardiac surgery.

    PubMed

    Kojima, Taiki; Nishisako, Ryo; Sato, Hideo

    2012-06-01

    There are very few case reports of transfusion-related acute lung injury (TRALI) under close hemodynamic monitoring. We encountered a case of possible TRALI during on-pump coronary artery bypass grafting (CABG). A 66-year-old man who had undergone on-pump CABG was administered fresh frozen plasma (FFP). One hour after FFP transfusion, pulmonary hypertensive crisis and subsequent hypoxic decompensation occurred. A second cardiopulmonary bypass (CPB) was needed for circulatory and respiratory deterioration. Extracorporeal life support (ECLS), intraaortic balloon pumping (IABP), and nitric oxide therapy were required after the surgery. Despite the severity of the initial state, his recovery was comparatively smooth. ECLS and IABP were removed on postoperative day (POD)1; the patient was extubated and discharged from the ICU on POD7 and POD12, respectively. The diagnosis of TRALI was confirmed by human leukocyte antigen antibody detection in the administered FFP. In addition, lymphocytic immunofluorescence test showed that a cross-match of the plasma from the pooled FFP against the recipient leukocytes was positive. The clinical course of the pulmonary artery hypertension was followed by a decrease in dynamic lung compliance. The mechanism of this phenomenon is unclear. However, it might suggest the possibility of vasoconstriction or obstruction of the peripheral pulmonary artery preceding lung damage, as in the case in animal models reported previously.

  16. Inhibition of pancreatic oxidative damage by stilbene derivative dihydro-resveratrol: implication for treatment of acute pancreatitis

    PubMed Central

    Tsang, Siu Wai; Guan, Yi-Fu; Wang, Juan; Bian, Zhao-Xiang; Zhang, Hong-Jie

    2016-01-01

    Trans-resveratrol is a natural stilbenoid possessing multifarious pharmacological benefits; however, when orally consumed, it is rapidly metabolised by colonic microflora and converted to dihydro-resveratrol. Thus, this microbial metabolite is of great therapeutic relevance. In the present study, upon the oral administration of dihydro-resveratrol (10–50 mg/kg), the severity of acute pancreatitis in the cerulein-treated rats was significantly ameliorated as evidenced by decreased α-amylase activities in the plasma and lessened oedema formation in the pancreatic parenchyma. In addition, the generation of intracellular reactive oxidative products, including malondialdehyde and protein carbonyls, was accordingly reduced, so as the production of pro-inflammatory cytokines. While inhibiting the activities of NADPH oxidase and myeloperoxidase, the depletion of glutathione was considerably restored. Importantly, the attenuation of pancreatic oxidative damage by dihydro-resveratrol was associated with a down-regulation of the nuclear factor-kappaB and phosphatidylinositol 3′-kinase-serine/threonine kinase signalling pathways. Furthermore, we demonstrated that the solubility of dihydro-resveratrol was at least 5 times higher than trans-resveratrol whilst exhibiting a much lower cytotoxicity. Collectively, the current findings accentuate new mechanistic insight of dihydro-resveratrol in pancreatic oxidative damage, and advocate its therapeutic potential for the management of acute pancreatitis, particularly for patients unresponsive to trans-resveratrol due to the lack of proper microbial strains. PMID:26971398

  17. Acute exposure of uranyl nitrate causes lipid peroxidation and histopathological damage in brain and bone of Wistar rat.

    PubMed

    Ghosh, Somnath; Kumar, Amit; Pandey, Badri Narain; Mishra, Kaushala Prasad

    2007-01-01

    Although the kidneys are the main target organs for uranium (U) toxicity, recent studies have shown that U can cross the blood-brain barrier to accumulate in the brain. Uranyl nitrate (U-238)induced oxidative damage was investigated in brain and bone of Wistar rats after intraperitoneal injection of uranyl nitrate at acute doses either nephrotoxic (576 microg of U/kg body weight) or subnephrotoxic (144 microg U/kg body weight). The health effects of U administration at 576 microg of U/kg body weight were seen in terms of decrease in food intake and no gain in body weight compared to respective controls. These alterations were correlated with increased lipid peroxidation as measured by thiobarbituric acid reactive substances in rat brain and bone. However, at lower dosage of U (144 microg U/kg body weight), no significant lipid peroxidation was observed in brain and bone. Histological examination of U-treated (576 microg of U/kg body weight) rat brain tissues showed marked and diffuse cystic degeneration and a similar pattern in histological alterations was observed in kidneys in treated animals; whereas no significant histological change was observed in rat brains and kidney treated with a lower dose of U (144 microg U/kg body weight). It is concluded that administration of U at an acute nephrotoxic dose caused oxidative stress in brain and bone manifested as lipid peroxidation and histopathological damage.

  18. Delivery of primary percutaneous coronary intervention for the management of acute ST segment elevation myocardial infarction: Summary of the Cardiac Care Network of Ontario Consensus Report

    PubMed Central

    Labinaz, Marino; Swabey, Terri; Watson, Randal; Natarajan, Madhu; Fucile, Wendy; Lubelsky, Bruce; Sawadsky, Bruce; Cohen, Eric; Glasgow, Kevin

    2006-01-01

    Tremendous debate has developed over the efficacy of primary percutaneous coronary intervention (PCI) compared with fibrinolysis as the preferred treatment for acute ST segment elevation myocardial infarction (STEMI). In 2002, the Ontario Ministry of Heath and Long-Term Care commissioned the Cardiac Care Network of Ontario to develop consensus recommendations regarding the provincial coordination and provision of urgent PCI for STEMI patients. The panel’s work has provided important insights into the acute treatment of STEMI that may be useful to other jurisdictions and may provide a reference for other regions considering the implementation of primary PCI for the management of STEMI patients in their community. In the present report, the evidence for primary PCI is reviewed, the important barriers to implementing this strategy are summarized and several recommendations and models of care for the delivery of primary PCI for STEMI on a wide scale are presented. PMID:16520856

  19. The potential of FDG PET/CT for early diagnosis of cardiac device and prosthetic valve infection before morphologic damages ensue.

    PubMed

    Chen, Wengen; Kim, Jongho; Molchanova-Cook, Olga P; Dilsizian, Vasken

    2014-03-01

    Diagnosis of cardiac mechanical device or prosthesis valve infection, and more importantly accurate localization of the infection site, such as defibrillator pocket, pacemaker lead, annular or peri-annular valve ring abscesses remain clinically challenging. Inconclusive diagnosis can lead to delayed antibiotic therapy, device extraction or surgical intervention, which may have dire consequences to the patient. Among patients with suspected cardiac mechanical device or prosthetic valve infection, recent publications advocate the use of (18)F-fluoro-2-deoxyglucose positron emission tomography computed tomography (FDG PET/CT), particularly when anatomy based imaging studies, such as echocardiography or CT, are uncertain or negative. A potential advantage of FDG PET/CT is in its detection of inflammatory cells early in the infection process, before morphologic damages ensue. However, there are many unanswered questions in the literature. There is a need for standardization amongst the various imaging studies, such as dietary preparation, duration and timing of image acquisition, image processing with and without CT attenuation correction, and more importantly image interpretation criteria. The answer for these issues awaits well designed, prospective studies.

  20. Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage.

    PubMed

    Medeiros, Gabriela A; Silvério, Jaline C; Marino, Ana Paula M P; Roffê, Ester; Vieira, Valeska; Kroll-Palhares, Karina; Carvalho, Cristiano E; Silva, Andréa Alice; Teixeira, Mauro M; Lannes-Vieira, Joseli

    2009-02-01

    The comprehension of the molecular mechanisms leading to Trypanosoma cruzi-elicited heart dysfunction might contribute to design novel therapeutic strategies aiming to ameliorate chronic Chagas disease cardiomyopathy. In C3H/He mice infected with the low virulence T. cruzi Colombian strain, the persistent cardiac inflammation composed mainly of CCR5(+) T lymphocytes parallels the expression of CC-chemokines in a pro-inflammatory IFN-gamma and TNF-alpha milieu. The chronic myocarditis is accompanied by increased frequency of peripheral CCR5(+)LFA-1(+) T lymphocytes. The treatment of chronically T. cruzi-infected mice with Met-RANTES, a selective CCR1/CCR5 antagonist, led to a 20-30% decrease in CD4(+) cell numbers as well as IL-10, IL-13 and TNF-alpha expression. Further, Met-RANTES administration impaired the re-compartmentalization of the activated CD4(+)CCR5(+) lymphocytes. Importantly, Met-RANTES treatment resulted in significant reduction in parasite load and fibronectin deposition in the heart tissue. Moreover, Met-RANTES treatment significantly protected T. cruzi-infected mice against connexin 43 loss in heart tissue and CK-MB level enhancement, markers of heart dysfunction. Thus, our results corroborate that therapeutic strategies based on the modulation of CCR1/CCR5-mediated cell migration and/or effector function may contribute to cardiac tissue damage limitation during chronic Chagas disease.

  1. Biological Signatures of Brain Damage Associated with High Serum Ferritin Levels in Patients with Acute Ischemic Stroke and Thrombolytic Treatment

    PubMed Central

    Millán, Mónica; Sobrino, Tomás; Arenillas, Juan Francisco; Rodríguez-Yáñez, Manuel; García, María; Nombela, Florentino; Castellanos, Mar; de la Ossa, Natalia Pérez; Cuadras, Patricia; Serena, Joaquín; Castillo, José; Dávalos, Antoni

    2008-01-01

    Background and purpose: Increased body iron stores have been related to greater oxidative stress and brain injury in clinical and experimental cerebral ischemia and reperfusion. We aimed to investigate the biological signatures of excitotoxicity, inflammation and blood brain barrier disruption potentially associated with high serum ferritin levels-related damage in acute stroke patients treated with i.v. t-PA. Methods: Serum levels of ferritin (as index of increased cellular iron stores), glutamate, interleukin-6, matrix metalloproteinase-9 and cellular fibronectin were determined in 134 patients treated with i.v. t-PA within 3 hours from stroke onset in blood samples obtained before t-PA treatment, at 24 and 72 hours. Results: Serum ferritin levels before t-PA infusion correlated to glutamate (r = 0.59, p < 0.001) and interleukin-6 (r = 0.55, p <0.001) levels at baseline, and with glutamate (r = 0.57,p <0.001), interleukin-6 (r = 0.49,p <0.001), metalloproteinase-9 (r = 0.23, p = 0.007) and cellular fibronectin (r = 0.27, p = 0.002) levels measured at 24 hours and glutamate (r = 0.415, p < 0.001), interleukin-6 (r = 0.359, p < 0.001) and metalloproteinase-9 (r = 0.261, p = 0.004) at 72 hours. The association between ferritin and glutamate levels remained after adjustment for confounding factors in generalized linear models. Conclusions: Brain damage associated with increased iron stores in acute ischemic stroke patients treated with iv. tPA may be mediated by mechanisms linked to excitotoxic damage. The role of inflammation, blood brain barrier disruption and oxidative stress in this condition needs further research. PMID:19096131

  2. Effects of carvedilol treatment on cardiac cAMP response element binding protein expression and phosphorylation in acute coxsackievirus B3-induced myocarditis

    PubMed Central

    2013-01-01

    Background The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models of viral myocarditis. Excess stimulation of β-adrenergic receptors by catecholamines causes phosphorylation/activation of cAMP response element binding protein (CREB) by the cAMP signaling pathway. CREB as an important regulator of gene expression mediates the cardiovascular remodeling process and promotes anti-inflammatory immune responses. However, the CREB expression and phosphorylation have not been studied, and the effects of carvedilol (a nonselective β-adrenoceptor antagonist) on the CREB has not been investigated in the setting of acute viral myocarditis. Methods This study was therefore designed to examine the effects of carvedilol on the transcriptional factor CREB in a murine model of acute viral myocarditis. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol on plasma noradrenaline, heart rate and blood pressure, myocardial histopathological changes and fibrosis, cardiomyocyte apoptosis, cardiac CREB and phosphorylated CREB, cytokine levels, and viral RNA were studied. Results The expression and phosphorylation of CREB were decreased with concomitant increase of IL-6 and TNF-α in murine coxsackievirus-induced acute viral myocarditis. The levels of IL-6 and TNF-α were correlated with the expression of CREB or phosphorylated CREB. Carvedilol increased the cardiac CREB expression and phosphorylation and decreased the plasma catecholamine levels and the production of IL-6 and TNF-α with amelioration of acute viral myocarditis. Conclusion These results show that CREB may be involved in the pathophysiology of viral myocarditis and carvedilol exerts some of its beneficial effects by increasing the CREB expression and phosphorylation. PMID:24225056

  3. Interaction of MIF Family Proteins in Myocardial Ischemia/Reperfusion Damage and Their Influence on Clinical Outcome of Cardiac Surgery Patients

    PubMed Central

    Rex, Steffen; Goetzenich, Andreas; Kraemer, Sandra; Emontzpohl, Christoph; Soppert, Josefin; Averdunk, Luisa; Sun, Yu; Rossaint, Rolf; Lue, Hongqi; Huang, Caleb; Song, Yan; Pantouris, Georgios; Lolis, Elias; Leng, Lin; Schulte, Wibke; Bucala, Richard; Weber, Christian

    2015-01-01

    Abstract Aims: Cardiac surgery involves myocardial ischemia/reperfusion (I/R) with potentially deleterious consequences. Macrophage migration inhibitory factor (MIF) is a stress-regulating chemokine-like cytokine that protects against I/R damage, but functional links with its homolog, d-dopachrome tautomerase (MIF-2), and the circulating soluble receptor CD74 (sCD74) are unknown. In this study, we investigate the role of MIF, MIF-2, sCD74, and MIF genotypes in patients scheduled for elective single or complex surgical procedures such as coronary artery bypass grafting or valve replacement. Results: MIF and MIF-2 levels significantly increased intraoperatively, whereas measured sCD74 decreased correspondingly. Circulating sCD74/MIF complexes were detectable in 50% of patients and enhanced MIF antioxidant activity. Intraoperative MIF levels were independently associated with a reduced risk for the development of atrial fibrillation (AF) (odds ratio 0.99 [0.98–1.00]; p=0.007). Circulating levels of MIF-2, but not MIF, were associated with an increased frequency of organ dysfunction and predicted the occurrence of AF (area under the curve [AUC]=0.663; p=0.041) and pneumonia (AUC=0.708; p=0.040). Patients with a high-expression MIF genotype exhibited a reduced incidence of organ dysfunction compared with patients with low-expression MIF genotypes (3 vs. 25; p=0.042). Innovation: The current study comprehensively highlights the kinetics and clinical relevance of MIF family proteins and the MIF genotype in cardiac surgery patients. Conclusion: Our findings suggest that increased MIF levels during cardiac surgery feature organ-protective properties during myocardial I/R, while the soluble MIF receptor, sCD74, may enhance MIF antioxidant activity. In contrast, high MIF-2 levels are predictive of the development of organ dysfunction. Importantly, we provide first evidence for a gene–phenotype relationship between variant MIF alleles and clinical outcome in cardiac

  4. The CC Chemokine Receptor 5 Is Important in Control of Parasite Replication and Acute Cardiac Inflammation following Infection with Trypanosoma cruzi

    PubMed Central

    Hardison, Jenny L.; Wrightsman, Ruth A.; Carpenter, Philip M.; Kuziel, William A.; Lane, Thomas E.; Manning, Jerry E.

    2006-01-01

    Infection of susceptible mice with the Colombiana strain of Trypanosoma cruzi results in an orchestrated expression of chemokines and chemokine receptors within the heart that coincides with parasite burden and cellular infiltration. CC chemokine receptor 5 (CCR5) is prominently expressed during both acute and chronic disease, suggesting a role in regulating leukocyte trafficking and accumulation within the heart following T. cruzi infection. To better understand the functional role of CCR5 and its ligands with regard to both host defense and/or disease, CCR5−/− mice were infected with T. cruzi, and the disease severity was evaluated. Infected CCR5−/− mice develop significantly higher levels of parasitemia (P ≤ 0.05) and cardiac parasitism (P ≤ 0.01) during acute infection that correlated with reduced survival. Further, we show that CCR5 is essential for directing the migration of macrophages and T cells to the heart early in acute infection with T. cruzi. In addition, data are provided demonstrating that CCR5 does not play an essential role in maintaining inflammation in the heart during chronic infection. Collectively, these studies clearly demonstrate that CCR5 contributes to the control of parasite replication and the development of a protective immune response during acute infection but does not ultimately participate in maintaining a chronic inflammatory response within the heart. PMID:16368966

  5. The CC chemokine receptor 5 is important in control of parasite replication and acute cardiac inflammation following infection with Trypanosoma cruzi.

    PubMed

    Hardison, Jenny L; Wrightsman, Ruth A; Carpenter, Philip M; Kuziel, William A; Lane, Thomas E; Manning, Jerry E

    2006-01-01

    Infection of susceptible mice with the Colombiana strain of Trypanosoma cruzi results in an orchestrated expression of chemokines and chemokine receptors within the heart that coincides with parasite burden and cellular infiltration. CC chemokine receptor 5 (CCR5) is prominently expressed during both acute and chronic disease, suggesting a role in regulating leukocyte trafficking and accumulation within the heart following T. cruzi infection. To better understand the functional role of CCR5 and its ligands with regard to both host defense and/or disease, CCR5(-/-) mice were infected with T. cruzi, and the disease severity was evaluated. Infected CCR5(-/-) mice develop significantly higher levels of parasitemia (P < or = 0.05) and cardiac parasitism (P < or = 0.01) during acute infection that correlated with reduced survival. Further, we show that CCR5 is essential for directing the migration of macrophages and T cells to the heart early in acute infection with T. cruzi. In addition, data are provided demonstrating that CCR5 does not play an essential role in maintaining inflammation in the heart during chronic infection. Collectively, these studies clearly demonstrate that CCR5 contributes to the control of parasite replication and the development of a protective immune response during acute infection but does not ultimately participate in maintaining a chronic inflammatory response within the heart.

  6. Gastroprotective effect of 2-mercaptoethane sulfonate against acute gastric mucosal damage induced by ethanol.

    PubMed

    Amirshahrokhi, Keyvan; Khalili, Ali-Reza

    2016-05-01

    Gastric mucosal damage induced by ethanol is a serious medical problem. Recent evidences suggest that reactive oxygen species and inflammatory mediators play a key role in the destruction of gastric mucosa. The present study was aimed to evaluate the potential beneficial effect of MESNA (2-mercaptoethane sulfonate) against ethanol-induced gastric mucosal damage in mice. The animals were orally pretreated with vehicle or MESNA and then treated with acidified ethanol to induce gastric mucosal damage. One hour after ethanol ingestion mice were euthanized and stomach samples were collected for biochemical analysis. Macroscopic and histopathological evaluation of gastric mucosa showed that pretreatment with MESNA attenuated gastric lesions induced by ethanol. Administration of MESNA significantly increased glutathione content and superoxide dismutase and catalase activity in the gastric tissues. In addition, MESNA markedly reduced ethanol-induced lipid peroxidation, myeloperoxidase activity, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1 levels. These findings suggest that the thiol-containing compound MESNA is able to decrease alcohol-induced oxidative stress and inflammation in the gastric tissue. It seems that MESNA may have a protective effect against ethanol-induced gastric mucosal damage. PMID:26967742

  7. Dexrazoxane Diminishes Doxorubicin-Induced Acute Ovarian Damage and Preserves Ovarian Function and Fecundity in Mice

    PubMed Central

    Ringelstetter, Ashley; Khatib, Hasan; Abbott, David H.; Salih, Sana M.

    2015-01-01

    Advances in cancer treatment utilizing multiple chemotherapies have dramatically increased cancer survivorship. Female cancer survivors treated with doxorubicin (DXR) chemotherapy often suffer from an acute impairment of ovarian function, which can persist as long-term, permanent ovarian insufficiency. Dexrazoxane (Dexra) pretreatment reduces DXR-induced insult in the heart, and protects in vitro cultured murine and non-human primate ovaries, demonstrating a drug-based shield to prevent DXR insult. The present study tested the ability of Dexra pretreatment to mitigate acute DXR chemotherapy ovarian toxicity in mice through the first 24 hours post-treatment, and improve subsequent long-term fertility throughout the reproductive lifespan. Adolescent CD-1 mice were treated with Dexra 1 hour prior to DXR treatment in a 1:1 mg or 10:1 mg Dexra:DXR ratio. During the acute injury period (2–24 hours post-injection), Dexra pretreatment at a 1:1 mg ratio decreased the extent of double strand DNA breaks, diminished γH2FAX activation, and reduced subsequent follicular cellular demise caused by DXR. In fertility and fecundity studies, dams pretreated with either Dexra:DXR dose ratio exhibited litter sizes larger than DXR-treated dams, and mice treated with a 1:1 mg Dexra:DXR ratio delivered pups with birth weights greater than DXR-treated females. While DXR significantly increased the “infertility index” (quantifying the percentage of dams failing to achieve pregnancy) through 6 gestations following treatment, Dexra pretreatment significantly reduced the infertility index following DXR treatment, improving fecundity. Low dose Dexra not only protected the ovaries, but also bestowed a considerable survival advantage following exposure to DXR chemotherapy. Mouse survivorship increased from 25% post-DXR treatment to over 80% with Dexra pretreatment. These data demonstrate that Dexra provides acute ovarian protection from DXR toxicity, improving reproductive health in a mouse

  8. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage.

    PubMed

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  9. Oral Supplementation of Glucosamine Fails to Alleviate Acute Kidney Injury in Renal Ischemia-Reperfusion Damage

    PubMed Central

    Johnsen, Marc; Späth, Martin Richard; Denzel, Martin S.; Göbel, Heike; Kubacki, Torsten; Hoyer, Karla Johanna Ruth; Hinze, Yvonne; Benzing, Thomas; Schermer, Bernhard; Antebi, Adam; Burst, Volker; Müller, Roman-Ulrich

    2016-01-01

    Acute kidney injury is a leading contributor to morbidity and mortality in the ageing population. Proteotoxic stress response pathways have been suggested to contribute to the development of acute renal injury. Recent evidence suggests that increased synthesis of N-glycan precursors in the hexosamine pathway as well as feeding of animals with aminosugars produced in the hexosamine pathway may increase stress resistance through reducing proteotoxic stress and alleviate pathology in model organisms. As feeding of the hexosamine pathway metabolite glucosamine to aged mice increased their life expectancy we tested whether supplementation of this aminosugar may also protect mice from acute kidney injury after renal ischemia and reperfusion. Animals were fed for 4 weeks ad libitum with standard chow or standard chow supplemented with 0.5% N-acetylglucosamine. Preconditioning with caloric restriction for four weeks prior to surgery served as a positive control for protective dietary effects. Whereas caloric restriction demonstrated the known protective effect both on renal function as well as survival in the treated animals, glucosamine supplementation failed to promote any protection from ischemia-reperfusion injury. These data show that although hexosamine pathway metabolites have a proven role in enhancing protein quality control and survival in model organisms oral glucosamine supplementation at moderate doses that would be amenable to humans does not promote protection from ischemia-reperfusion injury of the kidney. PMID:27557097

  10. Common micro-RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia.

    PubMed

    Greco, Simona; De Simone, Marco; Colussi, Claudia; Zaccagnini, Germana; Fasanaro, Pasquale; Pescatori, Mario; Cardani, Rosanna; Perbellini, Riccardo; Isaia, Eleonora; Sale, Patrizio; Meola, Giovanni; Capogrossi, Maurizio C; Gaetano, Carlo; Martelli, Fabio

    2009-10-01

    The aim of this work was to identify micro-RNAs (miRNAs) involved in the pathological pathways activated in skeletal muscle damage and regeneration by both dystrophin absence and acute ischemia. Eleven miRNAs were deregulated both in MDX mice and in Duchenne muscular dystrophy patients (DMD signature). Therapeutic interventions ameliorating the mdx-phenotype rescued DMD-signature alterations. The significance of DMD-signature changes was characterized using a damage/regeneration mouse model of hind-limb ischemia and newborn mice. According to their expression, DMD-signature miRNAs were divided into 3 classes. 1) Regeneration miRNAs, miR-31, miR-34c, miR-206, miR-335, miR-449, and miR-494, which were induced in MDX mice and in DMD patients, but also in newborn mice and in newly formed myofibers during postischemic regeneration. Notably, miR-206, miR-34c, and miR-335 were up-regulated following myoblast differentiation in vitro. 2) Degenerative-miRNAs, miR-1, miR-29c, and miR-135a, that were down-modulated in MDX mice, in DMD patients, in the degenerative phase of the ischemia response, and in newborn mice. Their down-modulation was linked to myofiber loss and fibrosis. 3) Inflammatory miRNAs, miR-222 and miR-223, which were expressed in damaged muscle areas, and their expression correlated with the presence of infiltrating inflammatory cells. These findings show an important role of miRNAs in physiopathological pathways regulating muscle response to damage and regeneration.

  11. Early predictors of acute kidney injury in patients with cirrhosis and bacterial infection: urinary neutrophil gelatinase-associated lipocalin and cardiac output as reliable tools

    PubMed Central

    Ximenes, Rafael O.; Farias, Alberto Q.; Helou, Claudia M.B.

    2015-01-01

    Background Hemodynamic abnormalities and acute kidney injury (AKI) are often present in infected cirrhotic patients. Hence, an early diagnosis of AKI is necessary, which might require the validation of new predictors as the determinations of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cardiac output. Methods We evaluated 18 infected cirrhotic patients subdivided into two groups at admission (0 hours). In Group I, we collected urine samples at 0 hours, 6 hours, 24 hours, and 48 hours for uNGAL and fractional excretion of sodium determinations. In Group II, we measured cardiac output using echocardiography. Results The age of patients was 55.0±1.9 years, and 11 patients were males. The Model for End-Stage Liver Disease score was 21±1, whereas the Child–Pugh score was C in 11 patients and B in 7 patients. Both patients in Group I and Group II showed similar baseline characteristics. In Group I, we diagnosed AKI in 5 of 9 patients, and the mean time to this diagnosis by measuring serum creatinine was 5.4 days. Patients with AKI showed higher uNGAL levels than those without AKI from 6 hours to 48 hours. The best accuracy using the cutoff values of 68 ng uNGAL/mg creatinine was achieved at 48 hours when we distinguished patients with and without AKI in all cases. In Group II, we diagnosed AKI in 4 of 9 patients, and cardiac output was significantly higher in patients who developed AKI at 0 hours. Conclusion Both uNGAL and cardiac output determinations allow the prediction of AKI in infected cirrhotic patients earlier than increments in serum creatinine. PMID:26484038

  12. Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

    SciTech Connect

    Cheshchevik, V.T.; Lapshina, E.A.; Dremza, I.K.; Zabrodskaya, S.V.; Reiter, R.J.; Prokopchik, N.I.; Zavodnik, I.B.

    2012-06-15

    In current societies, the risk of toxic liver damage has markedly increased. The aim of the present work was to carry out further research into the mechanism(s) of liver mitochondrial damage induced by acute (0.8 g/kg body weight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride – induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, p < 0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxic mitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of liver mitochondria was observed, despite marked changes in the redox-balance of mitochondria. The activities of the mitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl{sub 4} displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl{sub 4}, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg) plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of toxic liver injury and liver mitochondria damage

  13. Effects of acute resistance exercise on muscle damage and perceptual measures between men who are lean and obese.

    PubMed

    Comstock, Brett A; Thomas, Gwendolyn A; Dunn-Lewis, Courtenay; Volek, Jeff S; Szivak, Tunde K; Hooper, David R; Kupchak, Brian R; Flanagan, Shawn D; Denegar, Craig R; Kraemer, William J

    2013-12-01

    The purpose of this investigation was to assess indices of muscle damage and psychological stress between young, untrained, lean, and obese men. Using a between-subject design, 19 young men (9 lean men [age, 20.1 ± 2.1 years; body mass, 71.7 ± 5.8 kg; height, 177.8 ± 8.7 cm; body fat (BF), 14.7 ± 3.5%], 5 World Health Organization [WHO] class 1 obese men [age, 21.6 ± 2.5 years; body mass, 97.8 ± 8.6 kg; height, 176.3 ± 3.7 cm; BF, 34.7 ± 3.0%], and 5 WHO class 2 or 3 men [age, 20.0 ± 1.4 years; body mass, 120.8 ± 10.5 kg; height, 177.7 ± 5.2 cm; BF, 40.5 ± 5.8%]) volunteered and completed an acute resistance exercise (RE) protocol (6 exercises performed for 3 sets of 10 repetitions at an intensity of 85-95% of a 10 repetition maximum). Plasma myoglobin and serum creatine kinase were obtained before and immediately after exercise, and in recovery (at +110 minutes and +24 hours). Perceptual measures including rating of perceived exertion, pain and soreness, fatigue, and general soreness were assessed at different time points (during exercise for rating of perceived exertion, and for the fatigue and soreness measures before, immediately after, and at 24 hours of recovery from exercise). The primary findings of this investigation were that lean and obese, sedentary, young men do not significantly differ from each other in terms of indirect, humoral measures of muscle damage, or perceptual scales in response to a moderate-intensity acute RE bout, despite using significantly more exercise volume relative to fat mass (FM). We conclude that excess FM during daily activities of life provides a protective effect for muscle damage. When strength training individuals who are obese, practitioners should be aware of how excess FM affects muscle damage and total volume. But these considerations do not preclude individuals who are obese from using well-designed RE workouts which use free-weight, multijoint movements that stimulate all of the major muscle groups.

  14. Acute ZnO nanoparticles exposure induces developmental toxicity, oxidative stress and DNA damage in embryo-larval zebrafish.

    PubMed

    Zhao, Xuesong; Wang, Shutao; Wu, Yuan; You, Hong; Lv, Lina

    2013-07-15

    Nano-scale zinc oxide (nano-ZnO) is widely used in various industrial and commercial applications. However, the available toxicological information was inadequate to assess the potential ecological risk of nano-ZnO to aquatic organisms and the publics. In this study, the developmental toxicity, oxidative stress and DNA damage of nano-ZnO embryos were investigated in the embryo-larval zebrafish, the toxicity of Zn(2+) releasing from nano-ZnO were also investigated to ascertain the relationship between the nano-ZnO and corresponding Zn(2+). Zebrafish embryos were exposed to 1, 5, 10, 20, 50, and 100mg/L nano-ZnO and 0.59, 2.15, 3.63, 4.07, 5.31, and 6.04 mg/L Zn(2+) for 144 h post-fertilisation (hpf), respectively. Up to 144 hpf, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and malondialdehyde (MDA) contents, the genes related to oxidative damage, reactive oxygen species (ROS) generation and DNA damage in zebrafish embryos were measured. The nano-ZnO was found to exert a dose-dependent toxicity to zebrafish embryos and larvae, reducing the hatching rate and inducing malformation and the acute toxicity to zebrafish embryos was greater than that of the Zn(2+) solution. The generation of ROS was significantly increased at 50 and 100mg/L nano-ZnO. DNA damage of zebrafish embryo was evaluated by single-cell gel electrophoresis and was enhanced with increasing nano-ZnO concentration. Moreover, the transcriptional expression of mitochondrial inner membrane genes related to ROS production, such as Bcl-2, in response to oxidative damage, such as Nqo1, and related to antioxidant response element such as Gstp2 were significantly down-regulated in the nano-ZnO treatment groups. However, the nano-ZnO up-regulated the transcriptional expression of Ucp2-related to ROS production. In conclusion, nano-ZnO induces developmental toxicity, oxidative stress and DNA damage on zebrafish embryos and the dissolved Zn(2+) only partially

  15. Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs.

    PubMed

    Cordero, Mario David; Sánchez-Alcázar, José Antonio; Bautista-Ferrufino, María Rosa; Carmona-López, María Inés; Illanes, Matilde; Ríos, María José; Garrido-Maraver, Juan; Alcudia, Ana; Navas, Plácido; de Miguel, Manuel

    2010-11-01

    Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  18. Dogs infected with the blood trypomastigote form of Trypanosoma cruzi display an increase expression of cytokines and chemokines plus an intense cardiac parasitism during acute infection.

    PubMed

    de Souza, Sheler Martins; Vieira, Paula Melo de Abreu; Roatt, Bruno Mendes; Reis, Levi Eduardo Soares; da Silva Fonseca, Kátia; Nogueira, Nívia Carolina; Reis, Alexandre Barbosa; Tafuri, Washington Luiz; Carneiro, Cláudia Martins

    2014-03-01

    The recent increase in immigration of people from areas endemic for Chagas disease (Trypanosoma cruzi) to the United States and Europe has raised concerns about the transmission via blood transfusion and organ transplants in these countries. Infection by these pathways occurs through blood trypomastigotes (BT), and these forms of T. cruzi are completely distinct of metacyclic trypomastigotes (MT), released by triatomine vector, in relation to parasite-host interaction. Thus, research comparing infection with these different infective forms is important for explaining the potential impacts on the disease course. Here, we investigated tissue parasitism and relative mRNA expression of cytokines, chemokines, and chemokine receptors in the heart during acute infection by MT or BT forms in dogs. BT-infected dogs presented a higher cardiac parasitism, increased relative mRNA expression of pro-inflammatory and immunomodulatory cytokines and of the chemokines CCL3/MIP-1α, CCL5/RANTES, and the chemokine receptor CCR5 during the acute phase of infection, as compared to MT-infected dogs. These results suggest that infection with BT forms may lead to an increased immune response, as revealed by the cytokines ratio, but this kind of immune response was not able to control the cardiac parasitism. Infection with the MT form presented an increase in the relative mRNA expression of IL-12p40 as compared to that of IL-10 or TGF-β1. Correlation analysis showed increased relative mRNA expression of IFN-γ as well as IL-10, which may be an immunomodulatory response, as well as an increase in the correlation of CCL5/RANTES and its CCR5 receptor. Our findings revealed a difference between inoculum sources of T. cruzi, as vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase, which may influence immunopathological aspects of Chagas disease.

  19. Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) imaging in the assessment of patients presenting with chest pain suspected for acute coronary syndrome

    PubMed Central

    De Filippo, Massimo; Capasso, Raffaella

    2016-01-01

    Acute chest pain is an important clinical challenge and a major reason for presentation to the emergency department. Although multiple imaging techniques are available to assess patients with suspected acute coronary syndrome (ACS), considerable interest has been focused on the use of non-invasive imaging options as coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR). According to several recent evidences, CCTA has been shown to represent a useful tool to rapidly and accurately diagnose coronary artery disease (CAD) in patients with low to intermediate cardiovascular risk. CCTA examination has the unique ability to non-invasively depict the coronary anatomy, not only allowing visualization of the lumen of the arteries in order to detect severe stenosis or occlusion responsible of myocardial ischemia, but also allows the assessment of coronary artery wall by demonstrating the presence or absence of CAD. However, routine CCTA is not able to differentiate ischemic from non-ischemic chest pain in patients with known CAD and it does not provide any functional assessment of the heart. Conversely, CMR is considered the gold standard in the evaluation of morphology, function, viability and tissue characterization of the heart. CMR offers a wide range of tools for diagnosing myocardial infarction (MI) at least at the same time of the elevation of cardiac troponin values, differentiating infarct tissue and ischemic myocardium from normal myocardium or mimicking conditions, and distinguishing between new and old ischemic events. In high-risk patients, with acute and chronic manifestations of CAD, CMR may be preferable to CCTA, since it would allow detection, differential diagnosis, prognostic evaluation and management of MI. PMID:27500156

  20. [How to Apply Bayesian Theorem to the Evaluation of Myocardial Injury by Measuring High Sensitive Cardiac Troponins in the Patients with Suspected Acute Myocardial Infarction].

    PubMed

    Shimada, Toshio; Yokochi, Tsunehiro; Ikoma, Yoko; Sonoda, Akihiro; Amemiya, Naoki; Murakoshi, Daiki; Kuzumi, Hirotoshi; Kosugiyama, Haruka

    2016-02-01

    118 consecutive patients of suspected acute myocardial infarction with acute chest pain and shortness of breath visiting our emergency room were subjected for this clinical study. Based on final diagnosis of acute myocardial infarction (AMI) comprehensively determined by medical record, physical examination, ECG, echocardiography, cardiac catheterization, etc., except for cardiac biomarkers, the patients were classified into two groups, with AMI group (1) and without AMI group (0) and then ROC curve analysis was performed between without AMI group (1) and with AMI group (0). As a result of ROC curve analysis, AUC, cutoff value, sensitivity, specificity and likelihood ratio (LR) were calculated as shown in Fig. 4 (1-7) and Table 2 (1-7). Based on calculating equation led from Bayesian rules, post-test odds were calculated as product of pre-test odds and LR at the cutoff value in each biomarker such as hsCTnT, hsCTnI, h-FABP CK, CKMB activity and CKMB mass. As a result, post-test probability was improved from predictive pre-test probability 30% to post-test probability 89% and 86% in hsCTnT and hsTnI, respectively but less improved from 30% to 68% in h-FABP and unexpectedly improved from 30% to 82% in CKMB mass compared with hsCTnT and hsTnI. Based on Bayesian rule, it is very valuable to predict post-test probability from predictive pre-test probability 30% by calculation in particular, when post-test probability is over 85-90%. In conclusion, we believe that prediction of post-test probability by Bayesian rule can be surely used to evaluate clinical quality of biomarkers which are not depend on at least, specialty and experience of physicians. PMID:27311276

  1. Exendin-4 therapy still offered an additional benefit on reducing transverse aortic constriction-induced cardiac hypertrophy-caused myocardial damage in DPP-4 deficient rats.

    PubMed

    Lu, Hung-I; Chung, Sheng-Ying; Chen, Yi-Ling; Huang, Tein-Hung; Zhen, Yen-Yi; Liu, Chu-Feng; Chang, Meng-Wei; Chen, Yung-Lung; Sheu, Jiunn-Jye; Chua, Sarah; Yip, Hon-Kan; Lee, Fan-Yen

    2016-01-01

    Inhibition of dipeptidyl peptidase-IV (DPP-4) enzyme activity has been revealed to protect myocardium from ischemia-reperfusion through enhancing the endogenous glucagon-like peptide-1 (GLP-1) level. However, whether exogenous supply of exendin-4, an analogue of GLP-1, would still offer benefit for protecting myocardial damage from trans-aortic constriction (TAC)-induced hypertrophic cardiomyopathy in preexistence of DPP-4 deficiency (DPP-4(D)) remained unclear. Male-adult (DPP-4(D)) rats (n = 32) were randomized into group 1 [sham control (SC)], group 2 (DPP-4(D) + TAC), group 3 [DPP-4(D) + TAC + exendin-4 10 µg/day], and group 4 [DPP-4(D) + TAC + exendin-4 10 µg + exendin-9-39 10 µg/day]. The rats were sacrificed by day 60 after last echocardiographic examination. By day 60 after TAC, left ventricular ejection fraction (LVEF) (%) was highest in group 1 and lowest in group 2, and significantly lower in group 4 than that in group 3 (all p < 0.001). The protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), inflammatory (MMP-9, TNF-α, NF-κB), apoptotic (Bax, cleaved caspase 3 and PARP), fibrotic (TGF-β, Smad3), heart failure (BNP, β-MHC), DNA damaged (γ-H2AX) and ischemic stress (p-P38, p-Akt, p53, ATM) biomarkers showed an opposite pattern of LVEF among the four groups (all p < 0.03). Fibrotic area (by Masson's trichrome, Sirius red), and cellular expressions of DNA-damaged markers (Ki-67+, γ-H2AX+, CD90+/53BP1+) displayed an identical pattern, whereas cellular expressions of angiogenesis (CD31+, α-SMA+) and sarcomere length exhibited an opposite pattern compared to that of oxidative stress among the four groups (all p < 0.001). Take altogether, Exendin-4 effectively suppressed TAC-induced pathological cardiac hypertrophy in DPP-4(D) rat.

  2. Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury.

    PubMed

    Moodley, Yuben; Sturm, Marian; Shaw, Kathryn; Shimbori, Chiko; Tan, Dino B A; Kolb, Martin; Graham, Ruth

    2016-07-01

    Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation and hMSC infusion, while the controls (n=5) had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1h after the administration of OA. The animals were monitored for additional 4h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB), a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p=0.04). There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p=0.063). There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term.

  3. Acute Oxidative Effect and Muscle Damage after a Maximum 4 Min Test in High Performance Athletes

    PubMed Central

    Fernandes Filho, José; Fernandes, Luiz Cláudio

    2016-01-01

    The purpose of this investigation was to determine lipid peroxidation markers, physiological stress and muscle damage in elite kayakers in response to a maximum 4-min kayak ergometer test (KE test), and possible correlations with individual 1000m kayaking performances. The sample consisted of twenty-three adult male and nine adult female elite kayakers, with more than three years’ experience in international events, who voluntarily took part in this study. The subjects performed a 10-min warm-up, followed by a 2-min passive interval, before starting the test itself, which consisted of a maximum 4-min work paddling on an ergometer; right after the end of the test, an 8 ml blood sample was collected for analysis. 72 hours after the test, all athletes took part in an official race, when then it was possible to check their performance in the on site K1 1000m test (P1000m). The results showed that all lipoproteins and hematological parameters tested presented a significant difference (p≤0.05) after exercise for both genders. In addition, parameters related to muscle damage such as lactate dehydrogenase (LDH) and creatine kinase (CK) presented significant differences after stress. Uric acid presented an inverse correlation with the performance (r = -0.76), while CK presented a positive correlation (r = 0.46) with it. Based on these results, it was possible to verify muscle damage and the level of oxidative stress caused by indoor training with specific ergometers for speed kayaking, highlighting the importance of analyzing and getting to know the physiological responses to this type of training, in order to provide information to coaches and optimize athletic performance. PMID:27111088

  4. Myocardial changes in acute Trypanosoma cruzi infection. Ultrastructural evidence of immune damage and the role of microangiopathy.

    PubMed Central

    Andrade, Z. A.; Andrade, S. G.; Correa, R.; Sadigursky, M.; Ferrans, V. J.

    1994-01-01

    Histological and ultrastructural studies of the hearts of dogs sacrificed 18 to 26 days after intraperitoneal inoculation with 4 x 10(5) blood forms of the 12 SF strain of Trypanosoma cruzi/kg of body weight disclosed myocarditis characterized by parasitic invasion of some myocytes, damage and necrosis of nonparasitized myocytes, and interstitial infiltration by mononuclear cells. Nonparasitized myocytes showed alterations ranging from mild edema to severe myocytolysis. These changes often were accompanied by contacts of myocytes with lymphocytes (both granular and agranular) and macrophages. These contacts were characterized by focal loss of the myocyte basement membrane and close approximation of the plasma membranes of the two cells. Contacts between lymphocytes and capillary endothelial cells were also frequent. Platelet aggregates and fibrin microthrombi were observed in some capillaries. Our findings suggest that immune effector cells play a major role in the pathogenesis of the myocyte damage and the microangiopathy in acute Chagas' disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:8203476

  5. Cgnz1 allele confers kidney resistance to damage preventing progression of immune complex-mediated acute lupus glomerulonephritis.

    PubMed

    Ge, Yan; Jiang, Chao; Sung, Sun-Sang J; Bagavant, Harini; Dai, Chao; Wang, Hongyang; Kannapell, Carol C; Cathro, Helen P; Gaskin, Felicia; Fu, Shu Man

    2013-10-21

    Cgnz1 and Agnz1 on the distal region of mouse chromosome 1 are associated with chronic glomerulonephritis (cGN) and acute GN (aGN). NZM2328.Lc1R27 (R27) was generated by introgressing a C57L/J region where Cgnz1 is located to NZM2328. R27 female mice developed aGN mediated by immune complex (IC) deposition and complement activation without progression to cGN with severe proteinuria. End stage renal disease (ESRD) was not seen in R27 mice as old as 15 mo. Thus, aGN and cGN are under separate genetic control, and IC-mediated proliferative GN need not progress to cGN and ESRD. NZM2328 and R27 female mice have comparable immune and inflammatory parameters. In contrast to NZM2328, R27 mice were resistant to sheep anti-mouse GBM serum-induced nephritis, supporting the hypothesis that aGN is mediated by autoimmunity and resistance to the development of cGN is mediated by end organ resistance to damage. Thus, autoimmunity should be considered distinct from end organ damage. The Cgnz1 region has been mapped to a 1.34 MB region with 45 genes. Nine candidate genes were identified. Clinical relevance of these observations is supported by case studies. Clinical implications and the significance to human lupus and other diseases are presented.

  6. Temporal trends in the use of invasive cardiac procedures for non-ST segment elevation acute coronary syndromes according to initial risk stratification

    PubMed Central

    Jedrzkiewicz, Sean; Goodman, Shaun G; Yan, Raymond T; Welsh, Robert C; Kornder, Jan; DeYoung, J Paul; Wong, Graham C; Rose, Barry; Grondin, François R; Gallo, Richard; Huang, Wei; Gore, Joel M; Yan, Andrew T

    2009-01-01

    BACKGROUND: Current guidelines support an early invasive strategy in the management of high-risk non-ST elevation acute coronary syndromes (NSTE-ACS). Although studies in the 1990s suggested that high-risk patients received less aggressive treatment, there are limited data on the contemporary management patterns of NSTE-ACS in Canada. OBJECTIVE: To examine the in-hospital use of coronary angiography and revascularization in relation to risk among less selected patients with NSTE-ACS. METHODS: Data from the prospective, multicentre Global Registry of Acute Coronary Events (main GRACE and expanded GRACE2) were used. Between June 1999 and September 2007, 7131 patients from across Canada with a final diagnosis of NSTE-ACS were included the study. The study population was stratified into low-, intermediate- and high-risk groups, based on their calculated GRACE risk score (a validated predictor of in-hospital mortality) and according to time of enrollment. RESULTS: While rates of in-hospital death and reinfarction were significantly (P<0.001) greater in higher-risk patients, the in-hospital use of cardiac catheterization in low- (64.7%), intermediate- (60.3%) and high-risk (42.3%) patients showed an inverse relationship (P<0.001). This trend persisted despite the increase in the overall rates of cardiac catheterization over time (47.9% in 1999 to 2003 versus 51.6% in 2004 to 2005 versus 63.8% in 2006 to 2007; P<0.001). After adjusting for confounders, intermediate-risk (adjusted OR 0.80 [95% CI 0.70 to 0.92], P=0.002) and high-risk (adjusted OR 0.38 [95% CI 0.29 to 0.48], P<0.001) patients remained less likely to undergo in-hospital cardiac catheterization. CONCLUSION: Despite the temporal increase in the use of invasive cardiac procedures, they remain paradoxically targeted toward low-risk patients with NSTE-ACS in contemporary practice. This treatment-risk paradox needs to be further addressed to maximize the benefits of invasive therapies in Canada. PMID:19898699

  7. Protective Role of Nuclear Factor E2-Related Factor 2 against Acute Oxidative Stress-Induced Pancreatic β -Cell Damage.

    PubMed

    Fu, Jingqi; Zheng, Hongzhi; Wang, Huihui; Yang, Bei; Zhao, Rui; Lu, Chunwei; Liu, Zhiyuan; Hou, Yongyong; Xu, Yuanyuan; Zhang, Qiang; Qu, Weidong; Pi, Jingbo

    2015-01-01

    Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantially reduced levels of antioxidant enzymes in response to a variety of stressors. In scramble MIN6 cells or wild-type islets, acute exposure to oxidative stressors, including hydrogen peroxide (H2O2) and S-nitroso-N-acetylpenicillamine, resulted in cell damage as determined by decrease in cell viability, reduced ATP content, morphology changes of islets, and/or alterations of apoptotic biomarkers in a concentration- and/or time-dependent manner. In contrast, silencing of Nrf2 sensitized MIN6 cells or islets to the damage. In addition, pretreatment of MIN6 β-cells with NRF2 activators, including CDDO-Im, dimethyl fumarate (DMF), and tert-butylhydroquinone (tBHQ), protected the cells from high levels of H2O2-induced cell damage. Given that reactive oxygen species (ROS) are involved in regulating glucose-stimulated insulin secretion (GSIS) and persistent activation of NRF2 blunts glucose-triggered ROS signaling and GSIS, the present study highlights the distinct roles that NRF2 may play in pancreatic β-cell dysfunction that occurs in different stages of diabetes. PMID:25949772

  8. Acute toxicity of heavy metals to Tetrahymena in an in vitro experiment and envelope damage study.

    PubMed

    Zhang, Tian; Li, Xi; Lu, Yang; Wu, Chunyun; Fang, Tingting; Liu, Peng; Zhang, Chaocan; Liang, Wei

    2013-07-01

    The toxicity of Cr³⁺, Cu²⁺ and Cd²⁺ to Tetrahymena growth metabolism was studied by microcalorimetry at 28°C, and the growth constant (k), peak time (T) and generation times (T(G)) were calculated. The metal ion concentrations that resulted in 50% inhibition (IC₅₀) of population growth were obtained through the dynamic parameters. The results indicated that the order of toxicity was Cd²⁺> Cr³⁺> Cu²⁺. Inductively coupled plasma-atomic emission spectrometry results suggested that the metal ions affected the permeability of the cell membrane. Observations of the Cd-exposed organisms by scanning electron microscopy revealed damage to the cell membrane in the form of an altered surface appearance. The cells suffered serious damage after sufficient acting time. Attenuated total reflection Fourier transform infrared spectra revealed that amide groups and PO₂⁻ of the phospholipid phospho-diester, both located in the hydrophobic end of the outer layer of the cell membrane, were most readily affected.

  9. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

    PubMed

    Yang, Ming-Chen; Chang, Chih-Peng; Lei, Huan-Yao

    2010-08-01

    We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.

  10. Pre-transplantation specification of stem cells to cardiac lineage for regeneration of cardiac tissue.

    PubMed

    Mayorga, Maritza; Finan, Amanda; Penn, Marc

    2009-03-01

    Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.

  11. Preoperative Preparation for Cardiac Surgery Facilitates Recovery, Reduces Psychological Distress, and Reduces the Incidence of Acute Postoperative Hypertension.

    ERIC Educational Resources Information Center

    Anderson, Erling A.

    1987-01-01

    Cardiac surgery patients were assigned to information-only, information-plus-coping, or control preoperative preparation groups. Preoperatively, both experimental groups were significantly less anxious than were controls. Both experimental groups increased patients' belief in control over recovery. Postoperatively, experimental patients were less…

  12. Remote Ischemic Preconditioning for Prevention of Acute Kidney Injury in Patients Undergoing On-Pump Cardiac Surgery: A Systematic Review and Meta-Analysis.

    PubMed

    Zhang, Yabing; Zhang, Xiyang; Chi, Dongmei; Wang, Siyang; Wei, Hua; Yu, Hong; Li, Qian; Liu, Bin

    2016-09-01

    Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory.The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery.The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through December 2015.We considered for inclusion all randomized controlled trials that the role of RIPC in reducing AKI and renal replacement therapy (RRT) among patients underwent on-pump cardiac surgical procedures.We collected the data on AKI, initiation of RRT, serum creatinine (sCr) levels, and in-hospital mortality. Random- and fixed-effect models were used for pooling data.Nineteen trials including 5100 patients were included. The results of this meta-analysis showed a significant benefit of RIPC for reducing the incidence of AKI after cardiac interventions (odds ratio [OR] = 0.84; 95% confidence interval [CI], 0.73-0.98; P = 0.02). No significant difference was found in the incidence of RRT between RIPC and control (OR, 0.76, 95% CI, 0.46-1.24; P = 0.36). In addition, compared with standard medical care, RIPC showed no significant difference in postoperative sCr (IV 0.07; 95% CI, -0.03 to 0.16; P = 0.20; postoperative day 1; IV 0.00; 95% CI, -0.08 to 0.09; P = 0.92; postoperative day 2; IV 0.04; 95% CI, -0.05 to 0.12; P = 0.39; postoperative day 3), and in-hospital mortality (OR, 1.21, 95% CI, 0.64-2.30; P = 0.56).According to the results from present meta-analysis, RIPC was associated with a significant reduction AKI after on-pump cardiac surgery but incidence of RRT, postoperative sCr, and in-hospital mortality. Further high-quality randomized controlled trials and experimental researches comparing RIPC are desirable. PMID:27631199

  13. Multi-Marker Approach with the Use of Biochip Cardiac Array Technology for Early Diagnosis in Patients with Acute Coronary Syndromes

    PubMed Central

    Sawicki, Marcin; Sypniewska, Grazyna; Krintus, Magdalena; Kozinski, Marek; Ostrowska-Nowak, Joanna; Pilaczyńska-Cemel, Marta; Budzbon, Dominika; Jacek, Kubica

    2008-01-01

    Introduction Diagnosis of acute coronary syndrome (ACS) is frequently a challenging task while immediate risk stratification remains crucial for the prompt implementation of appropriate therapy in this setting. The prolonged release pattern of both CK-MB mass and cardiac troponins makes it difficult to identify the origin of recent chest pain, thus a combination of early and later biomarkers might further facilitate the differential diagnosis. The study was designed to evaluate the efficacy of multi-marker approach using biochip array technology in identifying ACS shortly after the symptom onset. Material and methods The study group consisted of 42 patients suspected for ACS. Subjects were diagnosed as presenting with unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI). Biomarkers in the serum were determined twice: on admission (≤6 hours from the chest pain onset) and after next 6 hours. Cardiac troponin I was measured by routine sensitive automated assay (STAT cTnI) while other 6 cardiac markers (heart-fatty acid binding protein - H-FABP, myoglobin, glycogen phosphorylase BB, cTn I, CK-MB mass and carbonic anhydrase III) were assessed using biochip array technology. Results STAT cTnI concentrations within 6 hours from the symptom onset were elevated over the 99th percentile for reference population in 83.3% of subjects but none reached the cut-off value for myocardial infarction. Instead, H-FABP demonstrated a very good efficacy in early detection of ACS (90.5%), better than myoglobin and CK-MB mass. Sensitivity of H-FABP calculated for NSTEMI/STEMI subjects reached 100%. The diagnostic efficacy of troponin, myoglobin and CK-MB mass assay markedly increased within 12 hours. It was only for the patients with UA that the cardiac panel was not efficient in the early stratification of risk. Conclusions A multi-marker strategy with H-FABP and highly sensitive troponin included enhances the early

  14. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF.

    PubMed

    Adibzadeh, F; van Rhoon, G C; Verduijn, G M; Naus-Postema, N C; Paulides, M M

    2016-01-21

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg(-1)) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients' feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R (2) =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature simulations as a

  15. Absence of acute ocular damage in humans after prolonged exposure to intense RF EMF

    NASA Astrophysics Data System (ADS)

    Adibzadeh, F.; van Rhoon, G. C.; Verduijn, G. M.; Naus-Postema, N. C.; Paulides, M. M.

    2016-01-01

    The eye is considered to be a critical organ when determining safety standards for radio frequency (RF) radiation. Experimental data obtained using animals showed that RF heating of the eye, particularly over a specific threshold, can induce cataracts. During the treatment of cancer in the head and neck by hyperthermia, the eyes receive a considerable dose of RF radiation due to stray radiation from the prolonged (60 min) and intense exposure at 434 MHz of this region. In the current study, we verified the exposure guidelines for humans by determining the association between the electromagnetic and thermal dose in the eyes with the reported ocular effects. We performed a simulation study to retrospectively assess the specific absorption rate (SAR) and temperature increase in the eyes of 16 selected patients (encompassing a total of 74 treatment sessions) whose treatment involved high power delivery as well as a minimal distance between the tumor site and the eye. Our results show that the basic restrictions on the peak 10 g spatial-averaged SAR (10 W kg-1) and peak tissue temperature increase (1 °C) are exceeded by up to 10.4 and 4.6 times, on average, and by at least 6.2 and 1.8 times when considering the lower limit of the 95% confidence interval. Evaluation of the acute effects according to patients’ feedback (all patients), the common toxicity criteria scores (all patients) and an ophthalmology investigation (one patient with the highest exposure) revealed no indication of any serious acute ocular effect, even though the eyes were exposed to high electromagnetic fields, leading to a high thermal dose. We also found that, although there is a strong correlation (R 2  =  0.88) between the predicted induced SAR and temperature in the eye, there are large uncertainties regarding the temperature-SAR relationship. Given this large uncertainty (129%) compared with the uncertainty of 3D temperature simulations (61%), we recommend using temperature

  16. Severe acute oxidant exposure: morphological damage and aerobic metabolism in the lung

    SciTech Connect

    Montgomery, M.R.; Teuscher, F.; LaSota, I.; Niewoehner, D.E.

    1986-09-01

    Groups of male rats were exposed to acute doses of oxygen, ozone, or paraquat which produced equivalent mortality (25-30%) over a 28 day post-exposure period. Quantitative evaluation of morphological changes indicated the primary response to be edema and inflammation with only slight fibrosis being apparent by the end of the observation period. Aerobic pulmonary metabolism was inhibited in lungs from animals exposed to oxygen and ozone as evidenced by decreased oxygen consumption; however, this was transient and O/sub 2/ consumption returned to normal within 24 hours after removal from the exposure chamber. Conversely, treatment with paraquat caused an immediate, transient stimulation of O/sub 2/ consumption. Glucose metabolism was unaltered by the gas exposures and, as previously reported, was initially stimulated by paraquat treatment. In vitro, only paraquat altered both O/sub 2/ consumption and glucose metabolism when added to lung slice preparations; ozone had no effect. Oxygen did not alter O/sub 2/ consumption but caused a slight biphasic response in glucose metabolism. Aerobic metabolism is relatively unchanged by these doses of oxygen and ozone which result in the death of 25-30% of all treated animals. Even though paraquat produces similar morphologic changes, it may represent a more severe metabolic insult than ''equivalent'' doses of oxygen or ozone. Also, if interstitial pulmonary fibrosis is a desired result of experimental exposure, rats may not be a suitable model for oxidant induced lung injury.

  17. Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

    PubMed

    Mohamed, Fahim; Buckley, Nicholas A; Jayamanne, Shaluka; Pickering, John W; Peake, Philip; Palangasinghe, Chathura; Wijerathna, Thilini; Ratnayake, Indira; Shihana, Fathima; Endre, Zoltan H

    2015-09-01

    Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC). The 95th centile in healthy subjects defined the urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)]; 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning. PMID:26071311

  18. Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

    PubMed Central

    González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

    2016-01-01

    Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-l-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800 mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20 mmol/L APAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF. PMID:27782042

  19. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    ClinicalTrials.gov

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  20. Association of Lower Fractional Flow Reserve Values With Higher Risk of Adverse Cardiac Events for Lesions Deferred Revascularization Among Patients With Acute Coronary Syndrome

    PubMed Central

    Masrani Mehta, Shriti; Depta, Jeremiah P; Novak, Eric; Patel, Jayendrakumar S; Patel, Yogesh; Raymer, David; Facey, Gabrielle; Zajarias, Alan; Lasala, John M; Singh, Jasvindar; Bach, Richard G; Kurz, Howard I

    2015-01-01

    Background The safety of deferring revascularization based on fractional flow reserve (FFR) during acute coronary syndrome (ACS) is unclear. We evaluated the association of FFR and adverse cardiac events among patients with coronary lesions deferred revascularization based on FFR in the setting of ACS versus non-ACS. Methods and Results The study population (674 patients; 816 lesions) was divided into ACS (n=334) and non-ACS (n=340) groups based on the diagnosis when revascularization was deferred based on FFR values >0.80 between October 2002 and July 2010. The association and interaction between FFR and clinical outcomes was evaluated using Cox proportional hazards models within each group (mean follow-up of 4.5±2.1 years). Subsequent revascularization of a deferred lesion was classified as a deferred lesion intervention (DLI), whereas the composite of DLI or myocardial infarction (MI) attributed to a deferred lesion was designated as deferred lesion failure (DLF). In the non-ACS group, lower FFR values were not associated with any increase in adverse cardiac events. In the ACS group, every 0.01 decrease in FFR was associated with a significantly higher rate of cardiovascular death, MI, or DLI (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03 to 1.12), MI or DLI (HR, 1.09; 95% CI: 1.04 to 1.14), DLF (HR, 1.12; 95% CI, 1.06 to 1.18), MI (HR, 1.07; 95% CI, 1.00 to 1.14), and DLI (HR, 1.12; 95% CI, 1.06 to 1.18). Conclusion Lower FFR values among ACS patients with coronary lesions deferred revascularization based on FFR are associated with a significantly higher rate of adverse cardiac events. This association was not observed in non-ACS patients. PMID:26289346

  1. RNA Profiling in Human and Murine Transplanted Hearts: Identification and Validation of Therapeutic Targets for Acute Cardiac and Renal Allograft Rejection

    PubMed Central

    Van Aelst, L. N. L.; Summer, G.; Li, S.; Gupta, S. K.; Heggermont, W.; De Vusser, K.; Carai, P.; Naesens, M.; Van Cleemput, J.; Van de Werf, F.; Vanhaecke, J.; Thum, T.; Waer, M.; Papageorgiou, A.‐P.; Schroen, B.

    2015-01-01

    Acute cellular rejection (ACR) is the adverse response of the recipient's immune system against the allogeneic graft. Using human surveillance endomyocardial biopsies (EMBs) manifesting ACR and murine allogeneic grafts, we profiled implicated microRNAs (miRs) and mRNAs. MiR profiling showed that miR‐21, ‐142‐3p, ‐142‐5p, ‐146a, ‐146b, ‐155, ‐222, ‐223, and ‐494 increased during ACR in humans and mice, whereas miR‐149‐5p decreased. mRNA profiling revealed 70 common differentially regulated transcripts, all involved in immune signaling and immune‐related diseases. Interestingly, 33 of 70 transcripts function downstream of IL‐6 and its transcription factor spleen focus forming virus proviral integration oncogene (SPI1), an established target of miR‐155, the most upregulated miR in human EMBs manifesting rejection. In a mouse model of cardiac transplantation, miR‐155 absence and pharmacological inhibition attenuated ACR, demonstrating the causal involvement and therapeutic potential of miRs. Finally, we corroborated our miR signature in acute cellular renal allograft rejection, suggesting a nonorgan specific signature of acute rejection. We concluded that miR and mRNA profiling in human and murine ACR revealed the shared significant dysregulation of immune genes. Inflammatory miRs, for example miR‐155, and transcripts, in particular those related to the IL‐6 pathway, are promising therapeutic targets to prevent acute allograft rejection. PMID:26249758

  2. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    SciTech Connect

    Qu, Wei Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  3. The iOSC3 System: Using Ontologies and SWRL Rules for Intelligent Supervision and Care of Patients with Acute Cardiac Disorders

    PubMed Central

    Martínez-Romero, Marcos; Vázquez-Naya, José M.; Pereira, Javier; Pereira, Miguel; Pazos, Alejandro; Baños, Gerardo

    2013-01-01

    Physicians in the Intensive Care Unit (ICU) are specially trained to deal constantly with very large and complex quantities of clinical data and make quick decisions as they face complications. However, the amount of information generated and the way the data are presented may overload the cognitive skills of even experienced professionals and lead to inaccurate or erroneous actions that put patients' lives at risk. In this paper, we present the design, development, and validation of iOSC3, an ontology-based system for intelligent supervision and treatment of critical patients with acute cardiac disorders. The system analyzes the patient's condition and provides a recommendation about the treatment that should be administered to achieve the fastest possible recovery. If the recommendation is accepted by the doctor, the system automatically modifies the quantity of drugs that are being delivered to the patient. The knowledge base is constituted by an OWL ontology and a set of SWRL rules that represent the expert's knowledge. iOSC3 has been developed in collaboration with experts from the Cardiac Intensive Care Unit (CICU) of the Meixoeiro Hospital, one of the most significant hospitals in the northwest region of Spain. PMID:23476717

  4. Change in myocardial oxygen consumption employing continuous-flow LVAD with cardiac beat synchronizing system, in acute ischemic heart failure models.

    PubMed

    Umeki, Akihide; Nishimura, Takashi; Takewa, Yoshiaki; Ando, Masahiko; Arakawa, Mamoru; Kishimoto, Yuichiro; Tsukiya, Tomonori; Mizuno, Toshihide; Kyo, Shunei; Ono, Minoru; Taenaka, Yoshiyuki; Tatsumi, Eisuke

    2013-06-01

    Aiming the 'Bridge to Recovery' course, we have developed a novel left ventricular assist device (LVAD) controlling system. It can change the rotational speed of the continuous flow LVAD, EVAHEART, synchronized with the cardiac beat. Employing this system, we have already demonstrated that myocardial oxygen consumption (MVO2), which is considered to be equivalent to native heart load, changes in the hearts of normal goats. Herein, we examined changes in goats with acute ischemic heart failure. We studied 14 goats (56.1 ± 6.9 kg) with acute ischemic heart failure due to coronary microsphere embolization. We installed the EVAHEART and drive in four modes: "circuit-clamp", "continuous support", "counter-pulse", and "co-pulse", with 50 and 100 % bypass. In comparison to the circuit-clamp mode, MVO2 was reduced to 70.4 ± 17.9 % in the counter-pulse mode and increased to 90.3 ± 14.5 % in the co-pulse mode, whereas it was 80.0 ± 14.5 % in the continuous mode, with 100 % bypass (p < 0.05). The same difference was confirmed with 50 % bypass. This means that we may have a chance to change the native heart load by controlling the LVAD rotation in synchrony with the cardiac rhythm, so we named our controller as the Native Heart Load Control System (NHLCS). Employing changeable MVO2 with NHLCS according to the patient's condition may provide more opportunity for native heart recovery with LVAD, especially for patients with ischemic heart diseases.

  5. Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database

    PubMed Central

    Shiraishi, Yasuyuki; Kohsaka, Shun; Harada, Kazumasa; Sakai, Tetsuro; Takagi, Atsutoshi; Miyamoto, Takamichi; Iida, Kiyoshi; Tanimoto, Shuzou; Fukuda, Keiichi; Nagao, Ken; Sato, Naoki; Takayama, Morimasa

    2015-01-01

    Aims There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear. Methods The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality. Results The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51−0.99; P = 0.043). Conclusions Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients. PMID:26562780

  6. Influence of age and renal function on high-sensitivity cardiac troponin T diagnostic accuracy for the diagnosis of acute myocardial infarction.

    PubMed

    Chenevier-Gobeaux, Camille; Meune, Christophe; Freund, Yonathan; Wahbi, Karim; Claessens, Yann-Erick; Doumenc, Benoit; Zuily, Stéphane; Riou, Bruno; Ray, Patrick

    2013-06-15

    Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infarction (AMI), particularly in non-ST segment elevation (NSTEMI), in elderly patients, and in patients with renal failure. We evaluated whether increased age and low estimated glomerular filtration rate (eGFR) alter diagnostic performance of high-sensitivity cardiac troponin T (HScTnT). In a prospective multicentric study, HScTnT levels were measured blindly at presentation in patients with acute chest pain. Three hundred and sixty-seven patients were enrolled, including 84 patients ≥70 years. Final diagnosis was AMI for 57 patients (16%) and NSTEMI for 43 patients (12%). NSTEMI was more frequent in elderly patients (p = 0.008). Sensitivity and specificity of HScTnT >14 ng/L at admission for AMI were 96% and 51% in patients ≥70 years versus 91% (NS) and 88% (p <0.0001) in younger patients; the same observations were done for the diagnosis of NSTEMI. Given an HScTnT >53.5 ng/L for the diagnosis of AMI and NSTEMI, respective sensitivities were 87% and 84% and respective specificities were 87% and 87% in elderly patients. Using a cutoff at 35.8 ng/L (for AMI) or 43.2 ng/L (for NSTEMI), sensitivities were 94% and 92%, and specificities were 86% and 88% in patients with low eGFR. Older age, but not low eGFR, was an independent predictive factor of an elevated HScTnT at admission (odds ratio 2.2 [1.2-3.9], p = 0.007). In conclusion, adapted thresholds of HScTnT are required for an accurate diagnosis of AMI/NSTEMI in patients aged ≥70 and in those with low eGFR.

  7. NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage

    PubMed Central

    Xiong, Wenjun; MacColl Garfinkel, Alexandra E.; Li, Yiqing; Benowitz, Larry I.; Cepko, Constance L.

    2015-01-01

    Oxidative stress contributes to the loss of neurons in many disease conditions as well as during normal aging; however, small-molecule agents that reduce oxidation have not been successful in preventing neurodegeneration. Moreover, even if an efficacious systemic reduction of reactive oxygen and/or nitrogen species (ROS/NOS) could be achieved, detrimental side effects are likely, as these molecules regulate normal physiological processes. A more effective and targeted approach might be to augment the endogenous antioxidant defense mechanism only in the cells that suffer from oxidation. Here, we created several adeno-associated virus (AAV) vectors to deliver genes that combat oxidation. These vectors encode the transcription factors NRF2 and/or PGC1a, which regulate hundreds of genes that combat oxidation and other forms of stress, or enzymes such as superoxide dismutase 2 (SOD2) and catalase, which directly detoxify ROS. We tested the effectiveness of this approach in 3 models of photoreceptor degeneration and in a nerve crush model. AAV-mediated delivery of NRF2 was more effective than SOD2 and catalase, while expression of PGC1a accelerated photoreceptor death. Since the NRF2-mediated neuroprotective effects extended to photoreceptors and retinal ganglion cells, which are 2 very different types of neurons, these results suggest that this targeted approach may be broadly applicable to many diseases in which cells suffer from oxidative damage. PMID:25798616

  8. Sustained release of a p38 inhibitor from non-inflammatory microspheres inhibits cardiac dysfunction

    NASA Astrophysics Data System (ADS)

    Sy, Jay C.; Seshadri, Gokulakrishnan; Yang, Stephen C.; Brown, Milton; Oh, Teresa; Dikalov, Sergey; Murthy, Niren; Davis, Michael E.

    2008-11-01

    Cardiac dysfunction following acute myocardial infarction is a major cause of death in the world and there is a compelling need for new therapeutic strategies. In this report we demonstrate that a direct cardiac injection of drug-loaded microparticles, formulated from the polymer poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK), improves cardiac function following myocardial infarction. Drug-delivery vehicles have great potential to improve the treatment of cardiac dysfunction by sustaining high concentrations of therapeutics within the damaged myocardium. PCADK is unique among currently used polymers in drug delivery in that its hydrolysis generates neutral degradation products. We show here that PCADK causes minimal tissue inflammatory response, thus enabling PCADK for the treatment of inflammatory diseases, such as cardiac dysfunction. PCADK holds great promise for treating myocardial infarction and other inflammatory diseases given its neutral, biocompatible degradation products and its ability to deliver a wide range of therapeutics.

  9. Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction.

    PubMed

    Mayorga, Mari; Kiedrowski, Matthew; Shamhart, Patricia; Forudi, Farhad; Weber, Kristal; Chilian, William M; Penn, Marc S; Dong, Feng

    2016-01-01

    The stromal cell-derived factor-1 (SDF-1):CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early upregulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the hypoxia inducible factor (HIF) hydroxylase inhibitor dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild-type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29 and 42% at 15 and 24 h, respectively. In vivo DMOG treatment increased CM-CXCR4 expression at 15 h post-MI in control mice but not in CM-CXCR4 null mice. DMOG resulted in increased ejection fraction in control mice but not in CM-CXCR4 null mice 21 days after MI. Consistent with greater cardiomyocyte survival with DMOG treatment, we observed a significant increase in cardiac myosin-positive area within the infarct zone after DMOG treatment in control mice, but no increase in CM-CXCR4 null mice. Inhibition of cardiomyocyte death in MI through the stabilization of HIF-1α requires downstream CM-CXCR4 expression. These data suggest that engagement of the SDF-1:CXCR4 axis through the early upregulation of CM-CXCR4 is a strategy for improving cardiac repair after MI.

  10. Global sensitivity analysis of a mathematical model of acute inflammation identifies nonlinear dependence of cumulative tissue damage on host interleukin-6 responses.

    PubMed

    Mathew, Shibin; Bartels, John; Banerjee, Ipsita; Vodovotz, Yoram

    2014-10-01

    The precise inflammatory role of the cytokine interleukin (IL)-6 and its utility as a biomarker or therapeutic target have been the source of much debate, presumably due to the complex pro- and anti-inflammatory effects of this cytokine. We previously developed a nonlinear ordinary differential equation (ODE) model to explain the dynamics of endotoxin (lipopolysaccharide; LPS)-induced acute inflammation and associated whole-animal damage/dysfunction (a proxy for the health of the organism), along with the inflammatory mediators tumor necrosis factor (TNF)-α, IL-6, IL-10, and nitric oxide (NO). The model was partially calibrated using data from endotoxemic C57Bl/6 mice. Herein, we investigated the sensitivity of the area under the damage curve (AUCD) to the 51 rate parameters of the ODE model for different levels of simulated LPS challenges using a global sensitivity approach called Random Sampling High Dimensional Model Representation (RS-HDMR). We explored sufficient parametric Monte Carlo samples to generate the variance-based Sobol' global sensitivity indices, and found that inflammatory damage was highly sensitive to the parameters affecting the activity of IL-6 during the different stages of acute inflammation. The AUCIL6 showed a bimodal distribution, with the lower peak representing healthy response and the higher peak representing sustained inflammation. Damage was minimal at low AUCIL6, giving rise to a healthy response. In contrast, intermediate levels of AUCIL6 resulted in high damage, and this was due to the insufficiency of damage recovery driven by anti-inflammatory responses from IL-10 and the activation of positive feedback sustained by IL-6. At high AUCIL6, damage recovery was interestingly restored in some population of simulated animals due to the NO-mediated anti-inflammatory responses. These observations suggest that the host's health status during acute inflammation depends in a nonlinear fashion on the magnitude of the inflammatory stimulus

  11. Association between neuroserpin and molecular markers of brain damage in patients with acute ischemic stroke

    PubMed Central

    2011-01-01

    Background Neuroserpin has shown neuroprotective effects in animal models of cerebral ischemia and has been associated with functional outcome after ischemic stroke. Our aim was to study whether neuroserpin serum levels could be associated to biomarkers of excitotoxicity, inflammation and blood brain barrier disruption. Methods We prospectively included 129 patients with ischemic stroke (58.1% male; mean age, 72.4 ± 9.6 years) not treated with tPA within 12 hours (h) of symptoms onset (mean time, 4.7 ± 2.1 h). Poor functional outcome at 3 months was considered as a modified Rankin scale score >2. Serum levels of neuroserpin, Interleukin 6 (IL-6), Intercellular adhesion molecule-1 (ICAM-1), active Matrix metalloproteinase 9 (MMP-9), and cellular fibronectin (cFn) (determined by ELISA) and glutamate (determined by HPLC) were measured on admission, 24 and 72 h. The main variable was considered the decrease of neuroserpin levels within the first 24 h. ROC analysis was used to select the best predictive value for neuroserpin to predict poor functional outcome due to a lack of linearity. Results The decrease of neuroserpin levels within the first 24 h was negatively correlated with serum levels at 24 hours of glutamate (r = -0.642), IL-6 (r = -0.678), ICAM-1 (r = -0.345), MMP-9 (r = -0.554) and cFn (r = -0.703) (all P < 0.0001). In the multivariate analysis, serum levels of glutamate (OR, 1.04; CI95%, 1.01-1.06, p = 0.001); IL-6 (OR, 1.4; CI95%, 1.1-1.7, p = 0.001); and cFn (OR, 1.3; CI95%, 1.1-1.6, p = 0.002) were independently associated with a decrease of neuroserpin levels <70 ng/mL at 24 h after adjusting for confounding factors. Conclusions These findings suggest that neuroprotective properties of neuroserpin may be related to the inhibition of excitotoxicity, inflammation, as well as blood brain barrier disruption that occur after acute ischemic stroke. PMID:21569344

  12. Cardiac Rehabilitation

    MedlinePlus

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

  13. Postoperative Fluid Overload is a Useful Predictor of the Short-Term Outcome of Renal Replacement Therapy for Acute Kidney Injury After Cardiac Surgery.

    PubMed

    Xu, Jiarui; Shen, Bo; Fang, Yi; Liu, Zhonghua; Zou, Jianzhou; Liu, Lan; Wang, Chunsheng; Ding, Xiaoqiang; Teng, Jie

    2015-08-01

    To analyze the predictive value of postoperative percent fluid overload (PFO) of renal replacement therapy (RRT) for acute kidney injury (AKI) patients after cardiac surgery.Data from 280 cardiac surgery patients between 2005 January and 2012 April were collected for retrospective analyses. A receiver operating characteristic (ROC) curve was used to compare the predictive values of cumulative PFO at different times after surgery for 90-day mortality.The cumulative PFO before RRT initiation was 7.9% ± 7.1% and the median PFO 6.1%. The cumulative PFO before and after RRT initiation in intensive care unit (ICU) was higher in the death group than in the survival group (8.8% ± 7.6% vs 6.1% ± 5.6%, P = 0.001; -0.5[-5.6, 5.1]% vs 6.9[2.2, 14.6]%, P < 0.001). The cumulative PFO during the whole ICU stay was 14.3% ± 15.8% and the median PFO was 10.7%. The areas under the ROC curves to predict the 90-day mortality by PFO at 24 hours, cumulative PFO before and after RRT initiation, and PFO during the whole ICU stay postoperatively were 0.625, 0.627, 0.731, and 0.752. PFO during the whole ICU stay ≥7.2% was determined as the cut-off point for 90-day mortality prediction with a sensitivity of 77% and a specificity of 64%. Kaplan-Meier survival estimates showed a significant difference in survival among patients with cumulative PFO ≥ 7.2% and PFO < 7.2% after cardiac surgery (log-rank P < 0.001).Postoperative cumulative PFO during the whole ICU stay ≥7.2% would have an adverse effect on 90-day short-term outcome, which may provide a strategy for the volume control of AKI-RRT patients after cardiac surgery.

  14. Time-dependent changes in the expression of thyroid hormone receptor alpha 1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling.

    PubMed

    Pantos, Constantinos; Mourouzis, Iordanis; Xinaris, Christodoulos; Kokkinos, Alexandros D; Markakis, Konstantinos; Dimopoulos, Antonios; Panagiotou, Matthew; Saranteas, Theodosios; Kostopanagiotou, Georgia; Cokkinos, Dennis V

    2007-04-01

    The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TR alpha 1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T(3) and T(4) levels in plasma were not changed at 2 weeks but T(3) was significantly lower and T(4) remained unchanged at 13 weeks. A twofold increase in TR alpha 1 expression was observed after 13 weeks in the non-infarcted area, P<0.05 versus sham operated, while TR alpha 1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TR beta 1 expression was found in the non-infarcted area at 13 weeks, P<0.05, while no change in TR beta 1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TR alpha 1 and 1.6-fold decrease in TR beta 1 expression versus untreated, P<0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TR alpha 1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TR alpha 1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TR beta 1 also contributes to fetal phenotypic changes. alpha1-adrenergic signalling is, at least in part, involved in this response.

  15. Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle.

    PubMed

    Kavazis, Andreas N; Smuder, Ashley J; Powers, Scott K

    2014-08-01

    Doxorubicin (DOX) is a potent antitumor agent used in cancer treatment. Unfortunately, DOX can induce myopathy in both cardiac and skeletal muscle, which limits its clinical use. Importantly, exercise training has been shown to protect against DOX-mediated cardiac and skeletal muscle myopathy. However, the mechanisms responsible for this exercise-induced muscle protection remain elusive. These experiments tested the hypothesis that short-term exercise training protects against acute DOX-induced muscle toxicity, in part, due to decreased forkhead-box O (FoxO) transcription of atrophy genes. Rats (n = 6 per group) were assigned to sedentary or endurance exercise-trained groups and paired with either placebo or DOX treatment. Gene expression and protein abundance were measured in both cardiac and skeletal muscles to determine the impact of DOX and exercise on FoxO gene targets. Our data demonstrate that DOX administration amplified FoxO1 and FoxO3 mRNA expression and increased transcription of FoxO target genes [i.e., atrogin-1/muscle atrophy F-box (MaFbx), muscle ring finger-1 (MuRF-1), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] in heart and soleus muscles. Importantly, exercise training protected against DOX-induced increases of FoxO1 and MuRF-1 in cardiac muscle and also prevented the rise of FoxO3, MuRF-1, and BNIP3 in soleus muscle. Furthermore, our results indicate that exercise increased peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) in both the heart and soleus muscles. This is important because increased PGC-1α expression is known to suppress FoxO activity resulting in reduced expression of FoxO target genes. Together, these results are consistent with the hypothesis that exercise training protects against DOX-induced myopathy in both heart (FoxO1 and MuRF-1) and skeletal muscles (FoxO3, MuRF-1, and BNIP3).

  16. Flaxseed Mitigates Acute Oxidative Lung Damage in a Mouse Model of Repeated Radiation and Hyperoxia Exposure Associated with Space Exploration

    PubMed Central

    Pietrofesa, Ralph A.; Solomides, Charalambos C.; Christofidou-Solomidou, Melpo

    2015-01-01

    Background Spaceflight missions may require crewmembers to conduct extravehicular activities (EVA). Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours and be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health. We have developed a mouse model of total body radiation and hyperoxia exposure and identified acute damage of lung tissues. In the current study we evaluated the usefulness of dietary flaxseed (FS) as a countermeasure agent for such double-hit exposures. Methods We evaluated lung tissue changes 2 weeks post-initiation of exposure challenges. Mouse cohorts (n=5/group) were pre-fed diets containing either 0% FS or 10% FS for 3 weeks and exposed to: a) normoxia (Untreated); b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) 3 times per week for 2 consecutive weeks, where 8-hour hyperoxia treatments were spanned by normoxic intervals. Results At 2 weeks post challenge, while control-diet fed mice developed significant lung injury and inflammation across all challenges, FS protected lung tissues by decreasing bronchoalveolar lavage fluid (BALF) neutrophils (p<0.003) and protein levels, oxidative tissue damage, as determined by levels of malondialdehyde (MDA) (p<0.008) and nitrosative stress as determined by nitrite levels. Lung hydroxyproline levels, a measure of lung fibrosis, were significantly elevated in mice fed 0% FS (p<0.01) and exposed to hyperoxia/radiation or the combination treatment, but not in FS-fed mice. FS also decreased levels of a pro-inflammatory, pro-fibrogenic cytokine (TGF-β1) gene expression levels in lung. Conclusion Flaxseed mitigated adverse effects in lung of repeat exposures to radiation/hyperoxia. This data will provide useful information in the design of countermeasures to early

  17. Effect on short- and long-term major adverse cardiac events of statin treatment in patients with acute myocardial infarction and renal dysfunction.

    PubMed

    Lim, Sang Yup; Bae, Eun Hui; Choi, Joon Seok; Kim, Chang Seong; Park, Jeong Woo; Ma, Seong Kwon; Jeong, Myung Ho; Kim, Soo Wan

    2012-05-15

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduce major adverse cardiac events (MACE) and mortality in patients with acute coronary syndrome. We investigated the effectiveness of statin therapy in reducing MACE in patients with acute myocardial infarction (AMI) and renal dysfunction (RD). In the present retrospective study of 12,853 patients with AMI, the patients were categorized into 4 groups: group I, statin therapy and no RD (estimated glomerular filtration rate ≥60 ml/min/1.73 m(2)); group II, neither statin therapy nor RD; group III, statin therapy and RD; group IV, no statin therapy but RD. The primary end points were death and complications during the hospital course. The secondary end points were MACE during 1 year of follow-up after AMI. Significant differences in the composite MACE during 12 months of follow-up were observed among the 4 groups (group I, 11.7%; group II, 19.0%; group III, 26.7%; and group IV, 45.5%; p <0.001). In a Cox proportional hazards model, mortality at 12 months increased stepwise from group II to IV compared to group I. Moreover, MACE-free survival in the severe RD group (estimated glomerular filtration rate <30 mL/min/1.73 m(2)) was also greater in the statin-treated group. In conclusion, statin therapy reduced MACE at 1 year of follow-up in patients with AMI regardless of RD.

  18. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis.

    PubMed

    Xu, Chang; Chang, Anthony; Hack, Bradley K; Eadon, Michael T; Alper, Seth L; Cunningham, Patrick N

    2014-01-01

    Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abundance of endothelial surface layer heparan sulfate proteoglycans and sialic acid, and led to albuminuria likely reflecting altered glomerular filtration permselectivity. LPS treatment decreased the glomerular filtration rate (GFR), while also causing significant ultrastructural alterations in the glomerular endothelium. The density of glomerular endothelial cell fenestrae was 5-fold lower, whereas the average fenestrae diameter was 3-fold higher in LPS-treated than in control mice. The effects of LPS on the glomerular endothelial surface layer, endothelial cell fenestrae, GFR, and albuminuria were diminished in TNF receptor 1 (TNFR1) knockout mice, suggesting that these LPS effects are mediated by TNF-α activation of TNFR1. Indeed, intravenous administration of TNF decreased GFR and led to loss of glomerular endothelial cell fenestrae, increased fenestrae diameter, and damage to the glomerular endothelial surface layer. LPS treatment decreased kidney expression of vascular endothelial growth factor (VEGF). Thus, our findings confirm the important role of glomerular endothelial injury, possibly by a decreased VEGF level, in the development and progression of AKI and albuminuria in the LPS model of sepsis in the mouse.

  19. DIGE Proteome Analysis Reveals Suitability of Ischemic Cardiac In Vitro Model for Studying Cellular Response to Acute Ischemia and Regeneration

    PubMed Central

    Haas, Sina; Jahnke, Heinz-Georg; Moerbt, Nora; von Bergen, Martin; Aharinejad, Seyedhossein; Andrukhova, Olena; Robitzki, Andrea A.

    2012-01-01

    Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy. With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research. PMID:22384053

  20. Effective ADAPT Thrombectomy in a Patient with Acute Stroke due to Cardiac Papillary Elastofibroma: Histological Thrombus Confirmation.

    PubMed

    Biraschi, Francesco; Diana, Francesco; Alesini, Francesco; Guidetti, Giulio; Peschillo, Simone

    2016-10-01

    A 75-year-old man with hypertension and atrial fibrillation was admitted to our emergency room with right-sided hemiplegia and complete aphasia (National Institutes of Health Stroke Scale [NIHSS] score = 18). A noncontrast computed tomography scan showed a slight hypodensity in the left insular region and a bright hyperdense sign in the M1 tract of the left middle cerebral artery (MCA). Angio-CT confirmed an occlusion of the M1 tract of the MCA. Magnetic resonance diffusion-weighted imaging/perfusion-weighted imaging was obtained and revealed a mismatch in the left parietal cortical region. Complete revascularization was achieved by thromboaspiration with the A Direct ASPIRATION first PASS TECHNIQUE (ADAPT) technique. Histological examination of the embolic material revealed its nonthrombotic nature: cardiac embolic papillary elastofibroma (PEF). At discharge, good recovery of right-side hemiplegia was observed. This case report is the second in literature in which a histological confirmed cardiac embolic PEF is reported as a cause of embolic stroke. PEF is a rare but potentially treatable cause of embolic stroke. Understanding the nature of the embolic material would help in choosing the best revascularization approach. PMID:27539711

  1. Gastroprotective Effect of Cochinchina momordica Seed Extract in Nonsteroidal Anti-Inflammatory Drug-Induced Acute Gastric Damage in a Rat Model

    PubMed Central

    Lim, Ji Hwan; Kim, Joo-Hyun; Lee, Byoung Hwan; Seo, Pyoung Ju; Kang, Jung Mook; Jo, So Young; Park, Ji Hyun; Nam, Ryoung Hee; Chang, Hyun; Kwon, Jin-Won; Lee, Dong Ho

    2014-01-01

    Background/Aims The major compounds of Cochinchina momordica seed extract (SK-MS10) include momordica saponins. We report that the gastroprotective effect of SK-MS10 in an ethanol-induced gastric damage rat model is mediated by suppressing proinflammatory cytokines and downregulating cytosolic phospholipase A2 (cPLA2), 5-lipoxygenase (5-LOX), and the activation of calcitonin gene-related peptide. In this study, we evaluated the gastroprotective effects of SK-MS10 in the nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage rat model. Methods The pretreatment effect of SK-MS10 was evaluated in the NSAID-induced gastric damage rat model using aspirin, indomethacin, and diclofenac in 7-week-old rats. Gastric damage was evaluated based on the gross ulcer index by gastroenterologists, and the damage area (%) was measured using the MetaMorph 7.0 video image analysis system. Myeloperoxidase (MPO) was measured by enzyme-linked immunosorbent assay, and Western blotting was used to analyze the levels of cyclooxygenase (COX)-1, COX-2, cPLA2, and 5-LOX. Results All NSAIDs induced gastric damage based on the gross ulcer index and damage area (p<0.05). Gastric damage was significantly attenuated by SK-MS10 pretreatment compared with NSAID treatment alone (p<0.05). The SK-MS10 pretreatment group exhibited lower MPO levels than the diclofenac group. The expression of cPLA2 and 5-LOX was decreased by SK-MS10 pretreatment in each of the three NSAID treatment groups. Conclusions SK-MS10 exhibited a gastroprotective effect against NSAID-induced acute gastric damage in rats. However, its protective mechanism may be different across the three types of NSAID-induced gastric damage models in rats. PMID:24516701

  2. Cardiovascular devices; reclassification of intra-aortic balloon and control systems for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure; effective date of requirement for premarket approval for intra-aortic balloon and control systems for septic shock or pulsatile flow generation. Final order.

    PubMed

    2013-12-30

    The Food and Drug Administration (FDA) is issuing a final order to reclassify intra-aortic balloon and control system (IABP) devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure, a preamendments class III device, into class II (special controls), and to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for IABPs when indicated for septic shock or pulsatile flow generation. PMID:24383147

  3. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    PubMed

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer. PMID:26877198

  4. Cardiac tissue engineering and regeneration using cell-based therapy

    PubMed Central

    Alrefai, Mohammad T; Murali, Divya; Paul, Arghya; Ridwan, Khalid M; Connell, John M; Shum-Tim, Dominique

    2015-01-01

    Stem cell therapy and tissue engineering represent a forefront of current research in the treatment of heart disease. With these technologies, advancements are being made into therapies for acute ischemic myocardial injury and chronic, otherwise nonreversible, myocardial failure. The current clinical management of cardiac ischemia deals with reestablishing perfusion to the heart but not dealing with the irreversible damage caused by the occlusion or stenosis of the supplying vessels. The applications of these new technologies are not yet fully established as part of the management of cardiac diseases but will become so in the near future. The discussion presented here reviews some of the pioneering works at this new frontier. Key results of allogeneic and autologous stem cell trials are presented, including the use of embryonic, bone marrow-derived, adipose-derived, and resident cardiac stem cells. PMID:25999743

  5. Cardiac anaphylaxis: a case of acute ST-segment elevation myocardial infarction after IM epinephrine for anaphylactic shock.

    PubMed

    Tummala, Karthik; Maniyal, Vijay K; Chandrashekaran, Rajiv; Mathew, Navin; Ganeshwala, Gaurav

    2013-07-01

    A 62-year-old male smoker with no other comorbidities presented to emergency department with systemic anaphylaxis, due to oral diclofenac for toothache. He developed acute anterior wall myocardial infarction following IM epinephrine 1 mg 1:1000. Primary percutaneous coronary intervention was done, which showed a thrombus in the mid left anterior descending artery with no evidence of obstructive coronary artery disease after thrombus aspiration.

  6. Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography.

    PubMed

    Lee, Ling; Genge, Christine E; Cua, Michelle; Sheng, Xiaoye; Rayani, Kaveh; Beg, Mirza F; Sarunic, Marinko V; Tibbits, Glen F

    2016-01-01

    The zebrafish (Danio rerio) is an important organism as a model for understanding vertebrate cardiovascular development. However, little is known about adult ZF cardiac function and how contractile function changes to cope with fluctuations in ambient temperature. The goals of this study were to: 1) determine if high resolution echocardiography (HRE) in the presence of reduced cardiodepressant anesthetics could be used to accurately investigate the structural and functional properties of the ZF heart and 2) if the effect of ambient temperature changes both acutely and chronically could be determined non-invasively using HRE in vivo. Heart rate (HR) appears to be the critical factor in modifying cardiac output (CO) with ambient temperature fluctuation as it increases from 78 ± 5.9 bpm at 18°C to 162 ± 9.7 bpm at 28°C regardless of acclimation state (cold acclimated CA- 18°C; warm acclimated WA- 28°C). Stroke volume (SV) is highest when the ambient temperature matches the acclimation temperature, though this difference did not constitute a significant effect (CA 1.17 ± 0.15 μL at 18°C vs 1.06 ± 0.14 μl at 28°C; WA 1.10 ± 0.13 μL at 18°C vs 1.12 ± 0.12 μl at 28°C). The isovolumetric contraction time (IVCT) was significantly shorter in CA fish at 18°C. The CA group showed improved systolic function at 18°C in comparison to the WA group with significant increases in both ejection fraction and fractional shortening and decreases in IVCT. The decreased early peak (E) velocity and early peak velocity / atrial peak velocity (E/A) ratio in the CA group are likely associated with increased reliance on atrial contraction for ventricular filling. PMID:26730947

  7. Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in Patients with Acute Myocardial Infarction Based on Individual Patient Data

    PubMed Central

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D.; Traverse, Jay H.; Moyé, Lemuel A.; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W.; Atsma, Douwe E.; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P.; Maurer, Gerald

    2015-01-01

    Rationale The ACCRUE (Meta-Analysis of Cell-based CaRdiac stUdiEs) is the first prospectively declared collaborative multinational database including individual data of patients (IPD) with ischemic heart disease treated with cell therapy. Objective We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI) including IPDs from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). Methods and Results The primary endpoint was freedom from combined major adverse cardiac and cerebrovascular events (MACCE; including all-cause death, re-AMI, stroke, and target vessel revascularization). The secondary endpoint was freedom from hard clinical endpoints (death, re-AMI, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy endpoints included changes in end-diastolic volume (ΔEDV), end-systolic volume (ΔESV), and ejection fraction (ΔEF), analyzed with random-effects meta-analyses and analysis of covariance. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on MACCE (14.0% vs. 16.3%, hazard ratio 0.86, 95%CI: 0.63;1.18) or death (1.4% vs 2.1%) or death/re-AMI/stroke (2.9% vs 4.7%) was identified in comparison to controls. No change in ΔEF (mean difference: 0.96%, 95%CI: −0.2;2.1), ΔEDV, or ΔESV was observed compared to controls. These results were not influenced by anterior AMI location, reduced baseline EF, or the use of MRI for assessing left ventricular parameters. Conclusions This meta-analysis of IPD from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. PMID:25700037

  8. Peri-infarct zone characterized by cardiac magnetic resonance imaging is directly associated with the inflammatory activity during acute phase myocardial infarction.

    PubMed

    Quinaglia e Silva, Jose C; Coelho-Filho, Otavio Rizzi; Andrade, Joalbo M; Quinaglia, Thiago; Modolo, Rodrigo G P; Almeida, Breno O; van der Geest, Rob J; Jerosch-Herold, Michael; Coelho, Otavio Rizzi; Sposito, Andrei C

    2014-06-01

    Enhanced systemic inflammatory activity (SIA) during myocardial infarction (MI) and the extent of the peri-infarct zone characterized by cardiac magnetic resonance imaging (CMRi) are both associated with increased risk of life-threatening arrhythmias and sudden cardiac death. The present study investigated the existence of association between these two phenomena in 98 patients (55 ± 10 years) with ST segment elevation MI. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), and tumor necrosis factor (TNF) were measured on admission (D1) and on the fifth day post-MI (D5). CMRi was performed 2 weeks after MI to quantify peri-infarct zone (PIZ). Between D1 and D5, the increase in CRP (6.0 vs. 5.6 times; p = 0.02), IL-2 (3.6 vs. 3.4 times; p = 0.04) and tumor necrosis factor type α (TNF-α; 4.6 vs. 3.9 times; p = 0.001) were higher in patients with PIZ above the median than in the counterparts. PIZ was correlated with CRP-D5 (r = 0.69), delta-CRP (r = 0.7), IL-2-D5 (r = 0.5), delta-IL-2 (r = 0.6), TNF-α (r = 0.5), delta-TNF-α (r = 0.4; p = 0.0001). Enhanced activation of SIA during the acute phase of MI is directly related with generation of PIZ.

  9. Functional Assessment of Cardiac Responses of Adult Zebrafish (Danio rerio) to Acute and Chronic Temperature Change Using High-Resolution Echocardiography

    PubMed Central

    Cua, Michelle; Sheng, Xiaoye; Rayani, Kaveh; Beg, Mirza F.; Sarunic, Marinko V.; Tibbits, Glen F.

    2016-01-01

    The zebrafish (Danio rerio) is an important organism as a model for understanding vertebrate cardiovascular development. However, little is known about adult ZF cardiac function and how contractile function changes to cope with fluctuations in ambient temperature. The goals of this study were to: 1) determine if high resolution echocardiography (HRE) in the presence of reduced cardiodepressant anesthetics could be used to accurately investigate the structural and functional properties of the ZF heart and 2) if the effect of ambient temperature changes both acutely and chronically could be determined non-invasively using HRE in vivo. Heart rate (HR) appears to be the critical factor in modifying cardiac output (CO) with ambient temperature fluctuation as it increases from 78 ± 5.9 bpm at 18°C to 162 ± 9.7 bpm at 28°C regardless of acclimation state (cold acclimated CA– 18°C; warm acclimated WA– 28°C). Stroke volume (SV) is highest when the ambient temperature matches the acclimation temperature, though this difference did not constitute a significant effect (CA 1.17 ± 0.15 μL at 18°C vs 1.06 ± 0.14 μl at 28°C; WA 1.10 ± 0.13 μL at 18°C vs 1.12 ± 0.12 μl at 28°C). The isovolumetric contraction time (IVCT) was significantly shorter in CA fish at 18°C. The CA group showed improved systolic function at 18°C in comparison to the WA group with significant increases in both ejection fraction and fractional shortening and decreases in IVCT. The decreased early peak (E) velocity and early peak velocity / atrial peak velocity (E/A) ratio in the CA group are likely associated with increased reliance on atrial contraction for ventricular filling. PMID:26730947

  10. Difference between pre-operative and cardiopulmonary bypass mean arterial pressure is independently associated with early cardiac surgery-associated acute kidney injury

    PubMed Central

    2010-01-01

    Background Cardiac surgery-associated acute kidney injury (CSA-AKI) contributes to increased morbidity and mortality. However, its pathophysiology remains incompletely understood. We hypothesized that intra-operative mean arterial pressure (MAP) relative to pre-operative MAP would be an important predisposing factor for CSA-AKI. Methods We performed a prospective observational study of 157 consecutive high-risk patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The primary exposure was delta MAP, defined as the pre-operative MAP minus average MAP during CPB. Secondary exposure was CPB flow. The primary outcome was early CSA-AKI, defined by a minimum RIFLE class - RISK. Univariate and multivariate logistic regression were performed to explore for association between delta MAP and CSA-AKI. Results Mean (± SD) age was 65.9 ± 14.7 years, 70.1% were male, 47.8% had isolated coronary bypass graft (CABG) surgery, 24.2% had isolated valve surgery and 16.6% had combined procedures. Mean (± SD) pre-operative, intra-operative and delta MAP were 86.6 ± 13.2, 57.4 ± 5.0 and 29.4 ± 13.5 mmHg, respectively. Sixty-five patients (41%) developed CSA-AKI within in the first 24 hours post surgery. By multivariate logistic regression, a delta MAP≥26 mmHg (odds ratio [OR], 2.8; 95%CI, 1.3-6.1, p = 0.009) and CPB flow rate ≥54 mL/kg/min (OR, 0.2, 0.1-0.5, p < 0.001) were independently associated with CSA-AKI. Additional variables associated with CSA-AKI included use of a side-biting aortic clamp (OR, 3.0; 1.3-7.1, p = 0.012), and body mass index ≥25 (OR, 4.2; 1.6-11.2, p = 0.004). Conclusion A large delta MAP and lower CPB flow during cardiac surgery are independently associated with early post-operative CSA-AKI in high-risk patients. Delta MAP represents a potentially modifiable intra-operative factor for development of CSA-AKI that necessitates further inquiry. PMID:20825657

  11. Incidence, risk factors and prediction of post-operative acute kidney injury following cardiac surgery for active infective endocarditis: an observational study

    PubMed Central

    2013-01-01

    Introduction Cardiac surgery is frequently needed in patients with infective endocarditis (IE). Acute kidney injury (AKI) often complicates IE and is associated with poor outcomes. The purpose of the study was to determine the risk factors for post-operative AKI in patients operated on for IE. Methods A retrospective, non-interventional study of prospectively collected data (2000–2010) included patients with IE and cardiac surgery with cardio-pulmonary bypass. The primary outcome was post-operative AKI, defined as the development of AKI or progression of AKI based on the acute kidney injury network (AKIN) definition. We used ensemble machine learning (“Super Learning”) to develop a predictor of AKI based on potential risk factors, and evaluated its performance using V-fold cross validation. We identified clinically important predictors among a set of risk factors using Targeted Maximum Likelihood Estimation. Results 202 patients were included, of which 120 (59%) experienced a post-operative AKI. 65 (32.2%) patients presented an AKI before surgery while 91 (45%) presented a progression of AKI in the post-operative period. 20 patients (9.9%) required a renal replacement therapy during the post-operative ICU stay and 30 (14.8%) died during their hospital stay. The following variables were found to be significantly associated with renal function impairment, after adjustment for other risk factors: multiple surgery (OR: 4.16, 95% CI: 2.98-5.80, p<0.001), pre-operative anemia (OR: 1.89, 95% CI: 1.34-2.66, p<0.001), transfusion requirement during surgery (OR: 2.38, 95% CI: 1.55-3.63, p<0.001), and the use of vancomycin (OR: 2.63, 95% CI: 2.07-3.34, p<0.001), aminoglycosides (OR: 1.44, 95% CI: 1.13-1.83, p=0.004) or contrast iodine (OR: 1.70, 95% CI: 1.37-2.12, p<0.001). Post-operative but not pre-operative AKI was associated with hospital mortality. Conclusions Post-operative AKI following cardiopulmonary bypass for IE results from additive hits to the kidney. We

  12. Endothelial microparticles carrying hedgehog-interacting protein induce continuous endothelial damage in the pathogenesis of acute graft-versus-host disease.

    PubMed

    Nie, Di-Min; Wu, Qiu-Ling; Zheng, Peng; Chen, Ping; Zhang, Ran; Li, Bei-Bei; Fang, Jun; Xia, Ling-Hui; Hong, Mei

    2016-05-15

    Accumulating evidence suggests that endothelial microparticles (EMPs), a marker of endothelial damage, are elevated in acute graft-versus-host disease (aGVHD), and that endothelial damage is implicated in the pathogenesis of aGVHD, but the mechanisms remain elusive. In this study, we detected the plasma EMP levels and endothelial damage in patients and mice with aGVHD in vivo and then examined the effects of EMPs derived from injured endothelial cells (ECs) on endothelial damage and the role of hedgehog-interacting protein (HHIP) carried by EMPs in these effects in vitro. Our results showed that EMPs were persistently increased in the early posttransplantation phase in patients and mice with aGVHD. Meanwhile, endothelial damage was continuous in aGVHD mice, but was temporary in non-aGVHD mice after transplantation. In vitro, EMPs induced endothelial damage, including increased EC apoptosis, enhanced reactive oxygen species, decreased nitric oxide production and impaired angiogenic activity. Enhanced expression of HHIP, an antagonist for the Sonic hedgehog (SHH) signaling pathway, was observed in patients and mice with aGVHD and EMPs from injured ECs. The endothelial damage induced by EMPs was reversed when the HHIP incorporated into EMPs was silenced with an HHIP small interfering RNA or inhibited with the SHH pathway agonist, Smoothened agonist. This work supports a feasible vicious cycle in which EMPs generated during endothelial injury, in turn, aggravate endothelial damage by carrying HHIP into target ECs, contributing to the continuously deteriorating endothelial damage in the development of aGVHD. EMPs harboring HHIP would represent a potential therapeutic target for aGVHD. PMID:27009877

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

    PubMed Central

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

    2016-01-01

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

  14. Effect of exercise-based cardiac rehabilitation on non-culprit mild coronary plaques in the culprit coronary artery of patients with acute coronary syndrome.

    PubMed

    Kurose, Satoshi; Iwasaka, Junji; Tsutsumi, Hiromi; Yamanaka, Yutaka; Shinno, Hiromi; Fukushima, Yaeko; Higurashi, Kyoko; Imai, Masaru; Masuda, Izuru; Takeda, Shinichi; Kawai, Chuichi; Kimura, Yutaka

    2016-06-01

    Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P < 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P < 0.01). Peak VO2 in the CR group was significantly increased (P < 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS. PMID:25896129

  15. Measurement of cardiac troponins.

    PubMed

    Collinson, P O; Boa, F G; Gaze, D C

    2001-09-01

    The cardiac troponins form part of the regulatory mechanism for muscle contraction. Specific cardiac isoforms of cardiac troponin T and cardiac troponin I exist and commercially available immunoassay systems have been developed for their measurement. A large number of clinical and analytical studies have been performed and the measurement of cardiac troponins is now considered the 'gold standard' biochemical test for diagnosis of myocardial damage. There have been advances in understanding the development and structure of troponins and their degradation following myocardial cell necrosis. This has contributed to the understanding of the problems with current assays. Greater clinical use has also highlighted areas of analytical and clinical confusion. The assays are reviewed based on manufacturers' information, current published material as well as the authors' in-house experience.

  16. Cardiac rehabilitation in Germany.

    PubMed

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  17. Cardiac Arrest in a Heart Transplant Patient Receiving Dexmedetomidine During Cardiac Catheterization.

    PubMed

    Schwartz, Lawrence Israel; Miyamoto, Shelley D; Stenquist, Scott; Twite, Mark David

    2016-06-01

    Dexmedetomidine is an α-2 agonist with a sedative and cardiopulmonary profile that makes it an attractive anesthetic in pediatric cardiac patients. Cardiac transplant patients may suffer from acute cellular rejection of the cardiac conduction system and, therefore, are at an increased risk of the electrophysiological effect of dexmedetomidine. We present such a patient who had a cardiac arrest while receiving dexmedetomidine during cardiac catheterization. Because acute cellular rejection of the cardiac conduction system is difficult to diagnose, dexmedetomidine should be used with caution in pediatric heart transplant patients. PMID:26721807

  18. Cardiac rehabilitation

    MedlinePlus

    ... Coronary artery disease - cardiac rehab; Angina - cardiac rehab; Heart failure - cardiac rehab ... have had: Heart attack Coronary heart disease (CHD) Heart failure Angina (chest pain) Heart or heart valve surgery ...

  19. Effects of DHA-rich fish oil supplementation on the lipid profile, markers of muscle damage, and neutrophil function in wheelchair basketball athletes before and after acute exercise.

    PubMed

    Marques, Camila Garcia; Santos, Vinicius Coneglian; Levada-Pires, Adriana Cristina; Jacintho, Thiago Manzoni; Gorjão, Renata; Pithon-Curi, Tânia Cristina; Cury-Boaventura, Maria Fernanda

    2015-06-01

    We investigated the effects of docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on the lipid profile, levels of plasma inflammatory mediators, markers of muscle damage, and neutrophil function in wheelchair basketball players before and after acute exercise. We evaluated 8 male basketball wheelchair athletes before and after acute exercise both prior to (S0) and following (S1) FO supplementation. The subjects were supplemented with 3 g of FO daily for 30 days. The following components were measured: the plasma lipid profile (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides), plasma inflammatory mediators (C-reactive protein, interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, and tumor necrosis factor-α), markers of muscle damage (creatine kinase and lactate dehydrogenase (LDH)), and neutrophil function (cytokine production, phagocytic capacity, loss of membrane integrity, mitochondrial membrane potential, neutral lipid accumulation, phosphatidylserine externalization, DNA fragmentation, and production of reactive oxygen species (ROS)). Acute exercise increased the plasma levels of total cholesterol, LDH, IL1ra, and IL-6, led to the loss of membrane integrity, ROS production, and a high mitochondrial membrane potential in neutrophils, and reduced the phagocytic capacity and IL-6 production by the neutrophils (S0). However, supplementation prevented the increases in the plasma levels of LDH and IL-6, the loss of membrane integrity, and the alterations in ROS production and mitochondrial membrane potential in the neutrophils that were induced by exercise (S1). In conclusion, DHA-rich FO supplementation reduces the markers of muscle damage, inflammatory disturbances, and neutrophil death induced by acute exercise in wheelchair athletes.

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

    PubMed

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

    2013-03-01

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

  1. Acute inhibition of cardiac monoamine oxidase A after tobacco smoke inhalation: validation study of [11C]befloxatone in rats followed by a positron emission tomography application in baboons.

    PubMed

    Valette, Héric; Bottlaender, Michel; Dollé, Frédéric; Coulon, Christine; Ottaviani, Michèle; Syrota, André

    2005-07-01

    The in vivo characteristics of [11C]befloxatone were assessed in myocardium of rats and monkeys. A complete multicompartmental model was developed to quantify monkey cardiac monoamine oxidase A (MAO-A) binding sites using positron emission tomography (PET) and was applied to assess the acute effects of inhalation of tobacco smoke. Unknown compounds contained in tobacco smoke inhibit brain MAO. In vitro, befloxatone inhibits selectively, competitively, and reversibly MAO-A in human tissues. [11C]Befloxatone (1.85 MBq) was i.v. injected into rats. Animals were sacrificed, dissected, and samples were assessed for radioactivity. Another group of rats was pretreated with clorgyline (10 mg/kg i.v.). Monkeys were injected with [11C]befloxatone (222-370 MBq), and the chest was imaged with PET for 2 h. Presaturation and displacement experiments were performed using unlabeled befloxatone. For quantification of myocardial binding sites (Bmax), [11C]befloxatone was first injected as a tracer dose (2.7-9.3 nmol) and 20 min later injected as a mixture of labeled and unlabeled befloxatone (labeled, 10.3-41.9 nmol; unlabeled, 407-765 nmol). In rodents, cardiac uptake was high (3.39 +/- 0.5% injected dose/g tissue) and strongly inhibited (80%) by clorgyline. In monkeys, administration of unlabeled befloxatone displaced 85% of cardiac radioactivity. Bmax was found to be 208 +/- 13 pmol ml(-1) tissue. Inhalation of tobacco smoke decreased Bmax: 150 +/- 6.2 pmol ml(-1), whereas nicotine did not. [11C]Befloxatone allows a good visualization of the heart. Cardiac MAO-A Bmax was quantified and a clear effect of acute inhalation of tobacco smoke was evidenced. Therefore, a single cigarette can interfere with the cardiac turnover of catecholamines.

  2. Invasive treatment of non-ST-segment elevation acute coronary syndrome: cardiac catheterization/revascularization for all?

    PubMed

    Swahn, Eva; Alfredsson, Joakim

    2014-03-01

    Patients admitted to hospital with symptoms and signs of non-ST-segment elevation acute coronary syndromes have different risk profiles and are in need of an individualized approach that takes into consideration not only age and sex but also comorbidities such as diabetes, renal failure, hypertension, heart failure, peripheral artery disease, earlier revascularization, etc. According to evidence-based medicine and as documented in current guidelines, there is currently evidence for early catheterization and, if feasible, revascularization in high-risk patients, especially in men. Nevertheless, because of a lack of definitive evidence, there is uncertainty about treating women in the same way. Because women are usually older and have more comorbidities, they are frailer and revascularization should be indicated with greater caution. There is no evidence that catheterization as such is worse for women than for men; however, for both men and women with low risk, a less invasive approach, such as coronary computed tomography angiography, could be considered as a first diagnostic tool.

  3. The pathophysiology of hypertensive acute heart failure.

    PubMed

    Viau, David M; Sala-Mercado, Javier A; Spranger, Marty D; O'Leary, Donal S; Levy, Phillip D

    2015-12-01

    While acute heart failure (AHF) is often regarded as a single disorder, an evolving understanding recognises the existence of multiple phenotypes with varied pathophysiological alterations. Herein we discuss hypertensive AHF and provide insight into a mechanism where acute fluid redistribution is caused by a disturbance in the ventricular-vascular coupling relationship. In this relationship, acute alterations in vascular elasticity, vasoconstriction and reflected pulse waves lead to increases in cardiac work and contribute to decompensated LV function with associated subendocardial ischaemia and end-organ damage. Chronic predisposing factors (neurohormonal activity, nitric oxide insensitivity, arterial stiffening) and physiological stressors (sympathetic surge, volume overload, physical exertion) that are causally linked to acute symptom onset are discussed. Lastly, we review treatment options including both nitrovasodilators and promising novel therapeutics, and discuss future directions in the management of this phenotypic variant.

  4. Assessment of Left Ventricular Ejection Fraction Calculation on Long-axis Views From Cardiac Magnetic Resonance Imaging in Patients With Acute Myocardial Infarction

    PubMed Central

    Huttin, Olivier; Petit, Marie-Anaïs; Bozec, Erwan; Eschalier, Romain; Juillière, Yves; Moulin, Frédéric; Lemoine, Simon; Selton-Suty, Christine; Sadoul, Nicolas; Mandry, Damien; Beaumont, Marine; Felblinger, Jacques; Girerd, Nicolas; Marie, Pierre-Yves

    2015-01-01

    Abstract To assess left ventricular ejection fraction (LVEF) accurately, cardiac magnetic resonance (CMR) can be indicated and lays on the evaluation of multiple slices of the left ventricle in short axis (CMRSAX). The objective of this study was to assess another method consisting of the evaluation of 2 long-axis slices (CMRLAX) for LVEF determination in acute myocardial infarction. One hundred patients underwent CMR 2 to 4 days after acute myocardial infarction. LVEF was computed by the area-length method on horizontal and vertical CMRLAX images. Those results were compared to reference values obtained on contiguous CMRSAX images in one hand, and to values obtained from transthoracic echocardiography (TTE) in the other hand. For CMRSAX and TTE, LVEF was computed with Simpson method. Reproducibility of LVEF measurements was additionally determined. The accuracy of volume measurements was assessed against reference aortic stroke volumes obtained by phase-contrast MR imaging. LVEF from CMRLAX had a mean value of 47 ± 8% and were on average 5% higher than reference LVEF from CMRSAX (42 ± 8%), closer to routine values from TTELAX (49 ± 8%), much better correlated with the reference LVEF from CMRSAX (R = 0.88) than that from TTE (R = 0.58), obtained with a higher reproducibility than with the 2 other techniques (% of interobserver variability: CMRLAX 5%, CMRSAX 11%, and TTE 13%), and obtained with 4-fold lower recording and calculation times than for CMRSAX. Apart from this, CMRLAX stroke volume was well correlated with phase-contrast values (R = 0.81). In patients with predominantly regional contractility abnormalities, the determination of LVEF by CMRLAX is twice more reproducible than the reference CMRSAX method, even though the LVEF is consistently overestimated compared with CMRSAX. However, the CMRLAX LVEF determination provides values closer to TTE measurements, the most available and commonly used method in clinical practice, clinical

  5. Vasopressor requirement during targeted temperature management for out-of-hospital cardiac arrest caused by acute myocardial infarction without cardiogenic shock

    PubMed Central

    Song, Gyuho; You, Yeonho; Jeong, Wonjoon; Lee, Junwan; Cho, Yongchul; Lee, Seungwhan; Ryu, Seung; Lee, Jinwoong; Kim, Seungwhan; Yoo, Insool

    2016-01-01

    Objective We investigated whether patients with out-of-hospital cardiac arrest (OHCA) due to an acute myocardial infarction without cardiogenic shock required higher doses of vasopressors with low targeted temperature management (TTM) after return of spontaneous circulation. Methods We included consecutive comatose patients resuscitated from OHCA between January 2011 and December 2013. Patients with return of spontaneous circulation, regional wall motion abnormality on echocardiography, and coronary artery stenosis of ≥70% on percutaneous coronary artery angiography were enrolled. These patients received 36°C TTM or 33°C TTM following approval of TTM by patients’ next-of-kin (36°C and 33°C TTM groups, respectively). The cumulative vasopressor index was compared between groups. Results During induction phase, dose of vasopressors did not differ between groups. In the maintenance phase, the norepinephrine dose was 0.37±0.57 and 0.26±0.91 µg·kg-1·min-1 in the 33°C and 36°C TTM groups, respectively (P<0.01). During the rewarming phase, the norepinephrine and dopamine doses were 0.49±0.60 and 9.67±9.60 mcg·kg-1·min-1 in the 33°C TTM group and 0.14±0.46 and 3.13±7.19 mcg·kg-1·min-1 in the 36°C TTM group, respectively (P<0.01). The median cumulative vasopressor index was 8 (interquartile range, 3 to 8) and 4 (interquartile range, 0 to 8) in the 33°C and 36°C TTM groups, respectively (P=0.03). Conclusion In this study, patients with OHCA due to acute myocardial infarction without cardiogenic shock had an elevated vasopressor requirement with 33°C TTM compared to 36°C TTM during the maintenance and rewarming phases. PMID:27752611

  6. Phase I dynamics of cardiac output, systemic O2 delivery, and lung O2 uptake at exercise onset in men in acute normobaric hypoxia.

    PubMed

    Lador, Frédéric; Tam, Enrico; Azabji Kenfack, Marcel; Cautero, Michela; Moia, Christian; Morel, Denis R; Capelli, Carlo; Ferretti, Guido

    2008-08-01

    We tested the hypothesis that vagal withdrawal plays a role in the rapid (phase I) cardiopulmonary response to exercise. To this aim, in five men (24.6+/-3.4 yr, 82.1+/-13.7 kg, maximal aerobic power 330+/-67 W), we determined beat-by-beat cardiac output (Q), oxygen delivery (QaO2), and breath-by-breath lung oxygen uptake (VO2) at light exercise (50 and 100 W) in normoxia and acute hypoxia (fraction of inspired O2=0.11), because the latter reduces resting vagal activity. We computed Q from stroke volume (Qst, by model flow) and heart rate (fH, electrocardiography), and QaO2 from Q and arterial O2 concentration. Double exponentials were fitted to the data. In hypoxia compared with normoxia, steady-state fH and Q were higher, and Qst and VO2 were unchanged. QaO2 was unchanged at rest and lower at exercise. During transients, amplitude of phase I (A1) for VO2 was unchanged. For fH, Q and QaO2, A1 was lower. Phase I time constant (tau1) for QaO2 and VO2 was unchanged. The same was the case for Q at 100 W and for fH at 50 W. Qst kinetics were unaffected. In conclusion, the results do not fully support the hypothesis that vagal withdrawal determines phase I, because it was not completely suppressed. Although we can attribute the decrease in A1 of fH to a diminished degree of vagal withdrawal in hypoxia, this is not so for Qst. Thus the dual origin of the phase I of Q and QaO2, neural (vagal) and mechanical (venous return increase by muscle pump action), would rather be confirmed.

  7. A case of right renal infarction and subcapsular hematoma that simultaneously developed after cardiac angiography.

    PubMed

    Kwon, S H; Cho, H C; Lee, S W; Kim, D Y; Joo, W C; Lee, W H; Song, J H; Kim, M-J

    2009-01-01

    Of the several complications known to develop after cardiac catheterization, simultaneous acute renal infarction and renal subcapsular hematoma is rare. Here, the authors report a case of acute renal infarction with subcapsular hematoma that developed 4 hours after cardiac catheterization.

  8. Cardiac Physiology of Pregnancy.

    PubMed

    May, Linda

    2015-07-01

    Although the physiology of the heart and vascular system has not changed, there are many things we have learned and are still learning today. Research related to heart adaptations during pregnancy has been performed since the 1930s. Since the mid-1950s, researchers began to look at changes in the maternal cardiovascular system during exercise while pregnant. Research related to exercise during pregnancy and offspring heart development began and has continued since the 1970s. We will review the normal female cardiovascular system adaptations to pregnancy in general. Additionally, topics related to maternal cardiac adaptations to pregnancy during acute exercise, as well as the chronic conditioning response from exercise training will be explored. Since physical activity during pregnancy influences fetal development, the fetal cardiac development will be discussed in regards to acute and chronic maternal exercise. Similarly, the influence of various types of maternal exercise on acute and chronic fetal heart responses will be described. Briefly, the topics related to how and if there is maternal-fetal synchrony will be explained. Lastly, the developmental changes of the fetal cardiovascular system that persist after birth will be explored. Overall, the article will discuss maternal cardiac physiology related to changes with normal pregnancy, and exercise during pregnancy, as well as fetal cardiac physiology related to changes with normal development, and exercise during pregnancy as well as developmental changes in offspring after birth.

  9. Light damage in the rat retina: effect of a radioprotective agent (WR-77913) on acute rod outer segment disk disruptions.

    PubMed

    Remé, C E; Braschler, U F; Roberts, J; Dillon, J

    1991-07-01

    Primary events in the course of light induced retinal lesions are still not fully elucidated. Under chronic conditions, lipid peroxidation in the retina and death of photoreceptor cells are observed. The radioprotective agent WR-77913 scavenges singlet oxygen, hydrated electrons and free radicals. WR-77913 was used to protect against acute light induced photoreceptor outer segment membrane disruptions in the rat retina. There was a partial but not complete protection at higher illuminance levels (800 lx for 30 min), whereas threshold lesions (400 lx for 30 min) were almost completely prevented. These observations indicate an involvement of photodynamic reactions in causing acute photoreceptor lesions. PMID:1658823

  10. The impact of acute temperature stress on hemocytes of invasive and native mussels (Mytilus galloprovincialis and Mytilus californianus): DNA damage, membrane integrity, apoptosis and signaling pathways.

    PubMed

    Yao, Cui-Luan; Somero, George N

    2012-12-15

    We investigated the effects of acute heat stress and cold stress on cell viability, lysosome membrane stability, double- and single-stranded DNA breakage, and signaling mechanisms involved in cellular homeostasis and apoptosis in hemocytes of native and invasive mussels, Mytilus californianus and Mytilus galloprovincialis, respectively. Both heat stress (28, 32°C) and cold stress (2, 6°C) led to significant double- and single-stranded breaks in DNA. The type and extent of DNA damage were temperature and time dependent, as was caspase-3 activation, an indicator of apoptosis, which may occur in response to DNA damage. Hemocyte viability and lysosomal membrane stability decreased significantly under heat stress. Western blot analyses of hemocyte extracts with antibodies for proteins associated with cell signaling and stress responses [including members of the phospho-specific mitogen-activated protein kinase (MAPK) family c-JUN NH(2)-terminal kinase (JNK) and p38-MAPK, and apoptosis executor caspase-3] revealed that heat and cold stress induced a time-dependent activation of JNK, p38-MAPK and caspase-3 and that these signaling and stress responses differed between species. The thermal limits for activation of cell signaling processes linked to the repair of stress-induced damage may help determine cellular thermal tolerance limits. Our results show similarities in responses to cold and heat stress and suggest causal linkages between levels of DNA damage at both extremes of temperature and downstream regulatory responses, including induction of apoptosis. Compared with M. californianus, M. galloprovincialis might have a wider temperature tolerance due to a lower amount of single- and double-stranded DNA damage, faster signaling activation and transduction, and stronger repair ability against temperature stress.

  11. The effect of acute microgravity on mechanically-induced membrane damage and membrane-membrane fusion events

    NASA Technical Reports Server (NTRS)

    Clarke, M. S.; Vanderburg, C. R.; Feeback, D. L.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". Both membrane rupture and membrane resealing events mediated by membrane-membrane fusion characterize this response. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  12. The Effect of Acute Microgravity on Mechanically-Induced Membrane Damage and Membrane-Membrane Fusion Events

    NASA Technical Reports Server (NTRS)

    Clarke, Mark, S. F.; Vanderburg, Charles R.; Feedback, Daniel L.

    2001-01-01

    Although it is unclear how a living cell senses gravitational forces there is no doubt that perturbation of the gravitational environment results in profound alterations in cellular function. In the present study, we have focused our attention on how acute microgravity exposure during parabolic flight affects the skeletal muscle cell plasma membrane (i.e. sarcolemma), with specific reference to a mechanically-reactive signaling mechanism known as mechanically-induced membrane disruption or "wounding". This response is characterized by both membrane rupture and membrane resealing events mediated by membrane-membrane fusion. We here present experimental evidence that acute microgravity exposure can inhibit membrane-membrane fusion events essential for the resealing of sarcolemmal wounds in individual human myoblasts. Additional evidence to support this contention comes from experimental studies that demonstrate acute microgravity exposure also inhibits secretagogue-stimulated intracellular vesicle fusion with the plasma membrane in HL-60 cells. Based on our own observations and those of other investigators in a variety of ground-based models of membrane wounding and membrane-membrane fusion, we suggest that the disruption in the membrane resealing process observed during acute microgravity is consistent with a microgravity-induced decrease in membrane order.

  13. Effects of mir-21 on Cardiac Microvascular Endothelial Cells After Acute Myocardial Infarction in Rats: Role of Phosphatase and Tensin Homolog (PTEN)/Vascular Endothelial Growth Factor (VEGF) Signal Pathway

    PubMed Central

    Yang, Feng; Liu, Wenwei; Yan, Xiaojuan; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Yu, Ming; Zhu, Xiaoshan; Ma, Kezhong

    2016-01-01

    Background This study investigated how miR-21 expression is reflected in acute myocardial infarction and explored the role of miR-21 and the PTEN/VEGF signaling pathway in cardiac microvascular endothelial cells. Material/Methods We used an in vivo LAD rat model to simulate acute myocardial infarction. MiR-21 mimics and miR-21 inhibitors were injected and transfected into model rats in order to alter miR-21 expression. Cardiac functions were evaluated using echocardiographic measurement, ELISA, and Masson staining. In addition, lenti-PTEN and VEGF siRNA were transfected into CMEC cells using standard procedures for assessing the effect of PTEN and VEGE on cell proliferation, apoptosis, and angiogenesis. MiR-21, PTEN, and VEGF expressions were examined by RT-PCR and Western blot. The relationship between miR-21 and PTEN was determined by the luciferase activity assay. Results We demonstrated that miR-21 bonded with the 3′-UTR of PTEN and suppressed PTEN expressions. Established models significantly induced cardiac infarct volume and endothelial injury marker expressions as well as miR-21 and PTEN expressions (P<0.05). MiR-21 mimics exhibited significantly protective effects since they down-regulated both infarction size and injury marker expressions by increasing VEGF expression and inhibiting PTEN expression (P<0.05). In addition, results from in vitro research show that lenti-PTEN and VEGF siRNA can notably antagonize the effect of miR-21 on cell proliferation, apoptosis, and angiogenesis (P<0.05). Conclusions MiR-21 exerts protective effects on endothelial injury through the PTEN/VEGF pathway after acute myocardial infarction. PMID:27708252

  14. Alterations in the expression of the apurinic/apyrimidinic endonuclease-1/redox factor-1 (APE/ref-1) and DNA damage in the caudal region of acute and chronic spinal cord injured rats treated by embryonic neural stem cells.

    PubMed

    DAGCI, T; ARMAGAN, G; KONYALIOGLU, S; YALCIN, A

    2009-01-01

    The oxidative mechanisms of injury-induced damage of neurons within the spinal cord are not very well understood. We used a model of T8-T9 spinal cord injury (SCI) in the rat to induce neuronal degeneration. In this spinal cord injury model, unilateral avulsion of the spinal cord causes oxidative stress of neurons. We tested the hypothesis that apurinic/apyrimidinic endonuclease (or redox effector factor-1, APE/Ref-1) regulates this neuronal oxidation mechanism in the spinal cord region caudal to the lesion, and that DNA damage is an early upstream signal. The embryonic neural stem cell therapy significantly decreased DNA-damage levels in both study groups - acutely (followed up to 7 days after SCI), and chronically (followed up to 28 days after SCI) injured animals. Meanwhile, mRNA levels of APE/Ref-1 significantly increased after embryonic neural stem cell therapy in acutely and chronically injured animals when compared to acute and chronic sham groups. Our data has demonstrated that an increase of APE/Ref-1 mRNA levels in the caudal region of spinal cord strongly correlated with DNA damage after traumatic spinal cord injury. We suggest that DNA damage can be observed both in lesional and caudal regions of the acutely and chronically injured groups, but DNA damage is reduced with embryonic neural stem cell therapy.

  15. Cardiac arrest

    MedlinePlus

    ... Article.jsp. Accessed June 16, 2014. Myerburg RJ, Castellanos A. Approach to cardiac arrest and life-threatening ... PA: Elsevier Saunders; 2011:chap 63. Myerburg RJ, Castellanos A. Cardiac arrest and audden aardiac death. In: ...

  16. Red blood cell distribution width independently predicts medium-term mortality and major adverse cardiac events after an acute coronary syndrome

    PubMed Central

    Turcato, Gianni; Serafini, Valentina; Dilda, Alice; Bovo, Chiara; Caruso, Beatrice; Ricci, Giorgio

    2016-01-01

    Background The value of red blood cell distribution width (RDW), a simple and inexpensive measure of anisocytosis, has been associated with the outcome of many human chronic disorders. Therefore, this retrospective study was aimed to investigate whether RDW may be associated with medium-term mortality and major adverse cardiac events (MACE) after an acute coronary syndrome (ACS). Methods A total number of 979 patients diagnosed with ACS were enrolled from June 2014 to November 2014, and followed-up until June 2015. Results The RDW value in patients with 3-month MACE and in those who died was significantly higher than that of patients without 3-month MACE (13.3% vs. 14.0%; P<0.001) and those who were still alive at the end of follow-up (13.4% vs. 14.4%; P<0.001). In univariate analysis, RDW was found to be associated with 3-month MACE [odds ratio (OR), 1.70; 95% CI, 1.44–2.00, P<0.001]. In multivariate analysis, RDW remained independently associated with 3-month MACE (adjusted OR, 1.36; 95% CI, 1.19–1.55; P<0.001) and death (adjusted OR, 1.34; 95% CI, 1.05–1.71; P=0.020). The accuracy of RDW for predicting 3-month MACE was 0.67 (95% CI, 0.66–0.72; P<0.001). The most efficient discriminatory RDW value was 14.8%, which was associated with 3.8 (95% CI, 2.6–5.7; P<0.001) higher risk of 3-month MACE. Patients with RDW >14.8% exhibited a significantly short survival than those with RDW ≤14.8% (331 vs. 465 days; P<0.001). Conclusions The results of this study confirm that RDW may be a valuable, easy and inexpensive parameter for stratifying the medium-term risk in patients with ACS. PMID:27500155

  17. Prostaglandin E2 and reactive oxygen metabolite damage in the cecum in a pony model of acute colitis

    PubMed Central

    McConnico, Rebecca S.; Argenzio, Robert A.; Roberts, Malcolm C.

    2002-01-01

    The objective of this project was to determine early tissue biochemical events associated with increased colonic secretion during the acute stage of castor-oil-induced colitis by measuring cecal mucosal and submucosal malondialdehyde (MDA) and prostaglandin E2 (PGE2), levels in ponies. Intestinal tissue (inflamed or healthy) samples were obtained from 4 age- and sex-matched Shetland ponies. Biochemical methods were used to determine MDA and PGE2 levels in intestinal tissue samples from inflamed and healthy equine intestine. Inflamed tissue MDA and PGE2 levels increased with time after castor oil challenge and correlated with granulocyte infiltration, as determined by myeloperoxidase levels in a companion study. Elevated intestinal tissue MDA levels suggest that lipid peroxidation could be attributed to reactive oxygen metabolites (ROM) released from stimulated, recruited, and resident granulocytes. Tissue levels of MDA and PGE2 suggest a role for granulocyte-derived mediators of intestinal inflammation in the massive secretory response in cases of acute equine colitis. Tissue MDA and PGE2 levels may be useful laboratory tools to quantify and characterize intestinal secretory inflammatory responses in acute inflammatory conditions in the equine colon. PMID:11858649

  18. High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

    PubMed

    Yang, Qian; Wu, Wei; Li, Qian; Chen, Chan; Zhou, Ronghua; Qiu, Yanhua; Luo, Ming; Tan, Zhaoxia; Li, Shen; Chen, Gang; Zhou, Wentao; Liu, Jiaxin; Yang, Chengmin; Liu, Jin; Li, Tao

    2015-01-01

    Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde (MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction. PMID:26161234

  19. Organ protection possibilities in acute heart failure.

    PubMed

    Montero-Pérez-Barquero, M; Morales-Rull, J L

    2016-04-01

    Unlike chronic heart failure (HF), the treatment for acute HF has not changed over the last decade. The drugs employed have shown their ability to control symptoms but have not achieved organ protection or managed to reduce medium to long-term morbidity and mortality. Advances in our understanding of the pathophysiology of acute HF suggest that treatment should be directed not only towards correcting the haemodynamic disorders and achieving symptomatic relief but also towards preventing organ damage, thereby counteracting myocardial remodelling and cardiac and extracardiac disorders. Compounds that exert vasodilatory and anti-inflammatory action in the acute phase of HF and can stop cell death, thereby boosting repair mechanisms, could have an essential role in organ protection.

  20. Evidence of exercise-induced cardiac dysfunction and elevated cTnT in separate cohorts competing in an ultra-endurance mountain marathon race.

    PubMed

    Shave, R E; Dawson, E; Whyte, G; George, K; Ball, D; Gaze, D C; Collinson, P O

    2002-10-01

    Cardiac damage has recently been implicated in the aetiology of "exercise induced cardiac dysfunction". The humoral markers of cardiac damage that have been utilised to date are not sufficiently cardio-specific to investigate this hypothesis. The aim of the present study was to examine cardiac function following prolonged exercise, and investigate the contention of cardiac damage utilising a new highly cardio-specific marker. Thirty-seven competitors in the 2-day Lowe Alpine Mountain Marathon 2000 volunteered for the study. Competitors were sub-divided into 2 groups. Group 1 (n = 11) were examined using echocardiography pre and post the event, examining left ventricular diastolic and systolic function. Group 2 (n = 26) had venous blood samples drawn prior to the event and immediately following day-1 and day-2. Blood samples were analysed for total creatine kinase activity (CK), creatine kinase isoenzyme MB(mass) (CK-MB(mass)), and cardiac troponin T. Echocardiographic results indicated left ventricular diastolic and systolic dysfunction following cessation of exercise. CK and CK-MB(mass) were both elevated following day-1, and immediately following race completion. Cardiac troponin T levels were below the 99th percentile (0.01 microg/L) in all subjects prior to the event, following day-1 cTnT was elevated above 0.01 microg/L in 13 subjects, but returned to below 0.01 microg/L following race completion on day-2. However, no individual data reached clinical cut-off levels for acute myocardial infarction (AMI) (0.1 microg/L). Two days arduous exercise over mountainous terrain resulted in cardiac dysfunction, and significant skeletal muscular degradation. The elevation of cTnT above the 99th percentile in the present study is suggestive of minimal myocardial damage. The clinical significance of and exact mechanism responsible for such damage remains to be elucidated.

  1. Compensated overexpression of procollagens alpha 1(I) and alpha 1(III) following perilla mint ketone-induced acute pulmonary damage in horses.

    PubMed

    Schmidbauer, S-M; Venner, M; von Samson-Himmelstjerna, G; Drommer, W; Gruber, A D

    2004-01-01

    Interstitial lung disease with chronic fibrosis is a frequent cause of reduced performance in horses. The aim of this study was to establish a model of acute alveolar damage and interstitial lung disease in horses that could be used to monitor the histopathological lesions and changes in expression levels of genes relevant to pulmonary fibrosis. Six adult horses were given a single intravenous injection (6 mg per kg body weight) of perilla mint ketone (PMK). Transthoracic lung biopsy samples (1 x 0.2 x 0.2 cm) were collected before and after (days 1, 4, 8, 11, 15, 18, 22, 25 and 29) the administration of PMK. Light and electron microscopy revealed severe acute alveolar damage (days 1 to 4), proliferation of type II pneumocytes (days 4 to 11) and finally complete healing at about day 18. However, unexpectedly severe clinical signs necessitated euthanasia in two horses on days 9 and 11. The expression levels of the collagen genes COL1AI and COL3AI as well as transforming growth factor (TGF)-beta were examined in the biopsy samples by reverse transcription-real time quantitative polymerase chain reaction. COL1AI and COL3AI gene expressions were upregulated (3- and 17-fold, respectively) between days 1 and 29 in all six horses, whereas TGF-beta was upregulated in two horses (2- and 4-fold, respectively), between days 4 and 18. Although the gene expression analyses indicated a strong activation of the pro-fibrotic pathway, no interstitial fibrosis was seen in any horse. A complete necropsy performed on day 60 revealed complete recovery of the lungs of the four surviving horses, with no evidence of fibrosis. Unidentified compensatory mechanisms may have prevented pulmonary fibrosis, despite strong upregulation of pro-fibrotic genes.

  2. Ischemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts.

    PubMed

    Dashkevich, A; Raissadati, A; Syrjälä, S O; Zarkada, G; Keränen, M A I; Tuuminen, R; Krebs, R; Anisimov, A; Jeltsch, M; Leppänen, V-M; Alitalo, K; Nykänen, A I; Lemström, K B

    2016-04-01

    Organ damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia-reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lymphangiogenic VEGF-C/VEGFR3 pathway during cardiac allograft IRI regulates organ damage and subsequent interplay between innate and adaptive immunity. We found that cardiac allograft IRI, within hours, increased graft VEGF-C expression and lymphatic vessel activation in the form of increased lymphatic VEGFR3 and adhesion protein expression. Pharmacological VEGF-C/VEGFR3 stimulation resulted in early lymphatic activation and later increase in allograft inflammation. In contrast, pharmacological VEGF-C/VEGFR3 inhibition during cardiac allograft IRI decreased early lymphatic vessel activation with subsequent dampening of acute and chronic rejection. Genetic deletion of VEGFR3 specifically in the lymphatics of the transplanted heart recapitulated the survival effect achieved by pharmacological VEGF-C/VEGFR3 inhibition. Our results suggest that tissue damage rapidly changes lymphatic vessel phenotype, which, in turn, may shape the interplay of innate and adaptive immunity. Importantly, VEGF-C/VEGFR3 inhibition during solid organ transplant IRI could be used as lymphatic-targeted immunomodulatory therapy to prevent acute and chronic rejection. PMID:26689983

  3. Chronic Neuropsychological Sequelae of Cholinesterase Inhibitors in the Absence of Structural Brain Damage: Two Cases of Acute Poisoning

    PubMed Central

    Roldán-Tapia, Lola; Leyva, Antonia; Laynez, Francisco; Santed, Fernando Sánchez

    2005-01-01

    Here we describe two cases of carbamate poisoning. Patients AMF and PVM were accidentally poisoned by cholinesterase inhibitors. The medical diagnosis in both cases was overcholinergic syndrome, as demonstrated by exposure to cholinesterase inhibitors. The widespread use of cholinesterase inhibitors, especially as pesticides, produces a great number of human poisoning events annually. The main known neurotoxic effect of these substances is cholinesterase inhibition, which causes cholinergic overstimulation. Once AMF and PVM had recovered from acute intoxication, they were subjected to extensive neuropsychological evaluation 3 and 12 months after the poisoning event. These assessments point to a cognitive deficit in attention, memory, perceptual, and motor domains 3 months after intoxication. One year later these sequelae remained, even though the brain magnetic resonance imaging (MRI) and computed tomography (CT) scans were interpreted as being within normal limits. We present these cases as examples of neuropsychological profiles of long-term sequelae related to acute poisoning by cholinesterase inhibitor pesticides and show the usefulness of neuropsychological assessment in detecting central nervous system dysfunction in the absence of biochemical or structural markers. PMID:15929901

  4. Tissue-Specific Regulation of p38α-Mediated Inflammation in Con A-Induced Acute Liver Damage.

    PubMed

    Kang, Young Jun; Bang, Bo-Ram; Otsuka, Motoyuki; Otsu, Kinya

    2015-05-15

    Because p38α plays a critical role in inflammation, it has been an attractive target for the development of anti-inflammation therapeutics. However, p38α inhibitors showed side effects, including severe liver toxicity, that often prevailed over the benefits in clinical studies, and the mechanism of toxicity is not clear. In this study, we demonstrate that p38α regulates the inflammatory responses in acute liver inflammation in a tissue-specific manner, and liver toxicity by p38α inhibitors may be a result of the inhibition of protective activity of p38α in the liver. Genetic ablation of p38α in T and NKT cells protected mice from liver injury in Con A-induced liver inflammation, whereas liver-specific deletion of p38α aggravated liver pathology. We found that p38α deficiency in the liver increased the expression of chemokines to recruit more inflammatory cells, indicating that p38α in the liver plays a protective anti-inflammatory role during acute liver inflammation. Therefore, our results suggest that p38α regulates the inflammatory responses in a tissue-specific manner, and that the tissue-specific p38α targeting strategies can be used for the development of an effective anti-inflammation treatment with an improved side-effect profile.

  5. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks

    PubMed Central

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. PMID:26060589

  6. The Role of Inspiratory Muscle Training in Sickle Cell Anemia Related Pulmonary Damage due to Recurrent Acute Chest Syndrome Attacks.

    PubMed

    Camcıoğlu, Burcu; Boşnak-Güçlü, Meral; Karadallı, Müşerrefe Nur; Akı, Şahika Zeynep; Türköz-Sucak, Gülsan

    2015-01-01

    Background. The sickling of red blood cells causes a constellation of musculoskeletal, cardiovascular, and pulmonary manifestations. A 32-year-old gentleman with sickle cell anemia (SCA) had been suffering from recurrent acute chest syndrome (ACS). Aim. To examine the effects of inspiratory muscle training (IMT) on pulmonary functions, respiratory and peripheral muscle strength, functional exercise capacity, and quality of life in this patient with SCA. Methods. Functional exercise capacity was evaluated using six-minute walk test, respiratory muscle strength using mouth pressure device, hand grip strength using hand-held dynamometer, pain using Visual Analogue Scale, fatigue using Fatigue Severity Scale, dyspnea using Modified Medical Research Council Scale, and health related quality of life using European Organization for Research and Treatment of Cancer QOL measurement. Results. A significant improvement has been demonstrated in respiratory muscle strength, functional exercise capacity, pain, fatigue, dyspnea, and quality of life. There was no admission to emergency department due to acute chest syndrome in the following 12 months after commencing regular erythrocytapheresis. Conclusion. This is the first report demonstrating the beneficial effects of inspiratory muscle training on functional exercise capacity, respiratory muscle strength, pain, fatigue, dyspnea, and quality of life in a patient with recurrent ACS. PMID:26060589

  7. Biochemical and histological evaluation of kidney damage after sub-acute exposure to 2,4-dichlorophenoxyacetic herbicide in rats: involvement of oxidative stress.

    PubMed

    Tayeb, Wafa; Nakbi, Amel; Trabelsi, Mounir; Miled, Abdelhedi; Hammami, Mohamed

    2012-11-01

    The present study evaluated the effects of sub-acute exposure to different doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on rat kidney. Forty animals were divided into four equal groups and treated with different doses of 2,4-D: 0, 15, 75 and 150 mg/kg body weight per day via oral gavage for 28 consecutive days. Renal function, histopathology, tissue malondialdehyde and antioxidant enzyme activities were evaluated. The results showed a significant decrease (p < 0.01) in uric acid level and an increase in plasma levels of urea and creatinine (p < 0.01) in rats administered 2,4-D at the three studied doses. The activities of catalase and superoxide dismutase were significantly affected for all treated rats, while glutathione peroxidase significantly decreased in rats exposed to 2,4-D at a dose of 150 mg/kg. Through sub-acute treatment, starting from the low to the high doses of 2,4-D, there were significant increase in kidney MDA as compared to controls. The histopathological study revealed tubular damages, glomerular alterations, vascular congestion and increased number of pyknotic nuclei in kidneys of all 2,4-D treated groups. The severity of these alterations increase in a dose-dependent manner. Our findings confirm that sub-acute exposure to 2,4-D induced oxidative renal dysfunction in rats. Therefore, at higher doses, 2,4-D may be implicated in the pathogenesis of kidney failure via lipid peroxidation and oxidative stress.

  8. Mesenchymal-endothelial-transition contributes to cardiac neovascularization

    PubMed Central

    Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

    2014-01-01

    Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

  9. Hepatic failure and liver cell damage in acute Wilson's disease involve CD95 (APO-1/Fas) mediated apoptosis.

    PubMed

    Strand, S; Hofmann, W J; Grambihler, A; Hug, H; Volkmann, M; Otto, G; Wesch, H; Mariani, S M; Hack, V; Stremmel, W; Krammer, P H; Galle, P R

    1998-05-01

    Wilson's disease can result in fulminant liver failure due to hepatic copper overload. The CD95 system mediates apoptosis and has been demonstrated to be involved in liver disease. In this study CD95 mediated apoptosis was investigated in patients with fulminant hepatic failure in the course of Wilson's disease and in an in vitro model of copper treated human hepatoma cells. In patients, hepatic expression of CD95 and CD95L mRNA and apoptosis were detected. Copper overload in vitro resulted in hepatocytic apoptosis which could be reduced with a neutralizing anti-CD95L antibody. Copper treatment of hepatocytes results in activation of the CD95 system and induction of apoptosis which is operative during the course of hepatic failure in acute Wilson's disease.

  10. Inhibition of the group I mGluRs reduces acute brain damage and improves long-term histological outcomes after photothrombosis-induced ischaemia

    PubMed Central

    Li, Hailong; Zhang, Nannan; Sun, Grace; Ding, Shinghua

    2013-01-01

    Group I mGluRs (metabotropic glutamate receptors), including mGluR1 and mGluR5, are GPCRs (G-protein coupled receptors) and play important roles in physiology and pathology. Studies on their role in cerebral ischaemia have provided controversial results. In this study, we used a PT (photothrombosis)-induced ischaemia model to investigate whether antagonists to the group I mGluRs may offer acute and long-term protective effects in adult mice. Our results demonstrated that administration with mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)-pyridine] or mGluR1 antagonist LY367385 by intraperitoneal injection at 3 h after PT decreased brain infarct volume evaluated one day after ischaemia. Additive effects on infarct volume were observed upon co-injection with MPEP and LY367385. These antagonists also significantly alleviated neurodegeneration and apoptosis in the penumbra. In addition, when evaluated 2 weeks after PT, they reduced infarct volume and tissue loss, attenuated glial scar formation, and inhibited cell proliferation in the penumbra. Importantly, co-injection with MPEP and LY367385 reduced the expression levels of calpain, a Ca2+-activated protease known to mediate ischaemia-induced neuronal death. Injection of calpeptin, a calpain inhibitor, could inhibit neuronal death and brain damage after PT but injection of calpeptin together with MPEP and LY367385 did not further improve the protective effects mediated by MPEP and LY367385. These results suggest that inhibition of group I mGluRs is sufficient to protect ischaemic damage through the calpain pathway. Taken together, our results demonstrate that inhibition of group I mGluRs can mitigate PT-induced brain damage through attenuating the effects of calpain, and improve long-term histological outcomes. PMID:23772679

  11. Potential Effects of Phytoestrogen Genistein in Modulating Acute Methotrexate Chemotherapy-Induced Osteoclastogenesis and Bone Damage in Rats.

    PubMed

    King, Tristan J; Shandala, Tetyana; Lee, Alice M; Foster, Bruce K; Chen, Ke-Ming; Howe, Peter R; Xian, Cory J

    2015-08-06

    Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.

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

    PubMed

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

    2013-08-15

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

  13. Cardiac Sarcoidosis.

    PubMed

    Birnie, David; Ha, Andrew C T; Gula, Lorne J; Chakrabarti, Santabhanu; Beanlands, Rob S B; Nery, Pablo

    2015-12-01

    Studies suggest clinically manifest cardiac involvement occurs in 5% of patients with pulmonary/systemic sarcoidosis. The principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. Data indicate that an 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic (clinically silent) cardiac involvement. An international guideline for the diagnosis and management of CS recommends that patients be screened for cardiac involvement. Most studies suggest a benign prognosis for patients with clinically silent CS. Immunosuppression therapy is advocated for clinically manifest CS. Device therapy, with implantable cardioverter defibrillators, is recommended for some patients.

  14. A triad: cardiac rhabdomyosarcoma, stroke and tamponade.

    PubMed

    Ashraf, Tazeen; Day, Thomas George; Marek, Jan; Hughes, Marina; Giardini, Alessandro

    2013-03-01

    The case report describes a 9-year-old boy who presented with an acute cerebrovascular accident and was found to have cardiac tamponade caused by cardiac rhabdomyosarcoma. Symptoms of rhabdomyosarcoma can be indolent and nonspecific, even with metastatic disease. Echocardiography and cardiac magnetic resonance imaging are explored as adjuncts to diagnosis. The radiologic features that helped with the diagnosis of this rare condition are described.

  15. Acute kidney failure

    MedlinePlus

    Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...

  16. N-Terminal Pro-B-Type Natriuretic Peptide Plasma Levels as a Potential Biomarker for Cardiac Damage After Radiotherapy in Patients With Left-Sided Breast Cancer

    SciTech Connect

    D'Errico, Maria P.; Grimaldi, Luca; Petruzzelli, Maria F.; Gianicolo, Emilio A.L.; Tramacere, Francesco; Monetti, Antonio; Placella, Roberto; Pili, Giorgio; Andreassi, Maria Grazia; Sicari, Rosa; Picano, Eugenio; Portaluri, Maurizio

    2012-02-01

    Purpose: Adjuvant radiotherapy (RT) after breast-conserving surgery has been associated with increased cardiovascular mortality. Cardiac biomarkers may aid in identifying patients with radiation-mediated cardiac dysfunction. We evaluated the correlation between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and troponin (TnI) and the dose of radiation to the heart in patients with left-sided breast cancer. Methods and Materials: NT-proBNP and TnI plasma concentrations were measured in 30 left-sided breast cancer patients (median age, 55.0 years) 5 to 22 months after RT (Group I) and in 30 left-sided breast cancer patients (median age, 57.0 years) before RT as control group (Group II). Dosimetric and geometric parameters of heart and left ventricle were determined in all patients of Group I. Seventeen patients underwent complete two-dimensional echocardiography. Results: NT-proBNP levels were significantly higher (p = 0.03) in Group I (median, 90.0 pg/ml; range, 16.7-333.1 pg/ml) than in Group II (median, 63.2 pg/ml; range, 11.0-172.5 pg/ml). TnI levels remained below the cutoff threshold of 0.07 ng/ml in both groups. In patients with NT-proBNP values above the upper limit of 125 pg/ml, there were significant correlations between plasma levels and V{sub 3Gy}(%) (p = 0.001), the ratios D{sub 15cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.01), the ratios D{sub 15cm}{sup 3}/D{sub 50%} (Gy) (p = 0.008) for the heart and correlations between plasma levels and V{sub 2Gy} (%) (p = 0.002), the ratios D{sub 1cm{sup 3}}(Gy)/D{sub mean}(Gy) (p = 0.03), and the ratios D{sub 0.5cm{sup 3}}(Gy)/D{sub 50%}(Gy) (p = 0.05) for the ventricle. Conclusions: Patients with left-sided breast cancer show higher values of NT-pro BNP after RT when compared with non-RT-treated matched patients, increasing in correlation with high doses in small volumes of heart and ventricle. The findings of this study show that the most important parameters are not the mean doses but instead the small

  17. Cardiac transplantation.

    PubMed

    Shanewise, Jack

    2004-12-01

    Cardiac transplantation is a proven, accepted mode of therapy for selected patients with end-stage heart failure, but the inadequate number of suitable donor hearts available ultimately limits its application. This chapter reviews adult cardiac transplantation, with an emphasis on the anesthetic considerations of the heart transplant operation itself.

  18. 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

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

    PubMed

    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-Kit(TgD814Y) 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-Kit(TgD814Y) 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-Kit(TgD814Y) 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-Kit(TgD814Y) 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

  20. Cardiac metastases

    PubMed Central

    Bussani, R; De‐Giorgio, F; Abbate, A; Silvestri, F

    2007-01-01

    Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others—for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions. PMID:17098886

  1. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    PubMed Central

    Chen, Olivia; Qian, Li

    2015-01-01

    Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming. PMID:26176012

  2. Duration-dependent hepatoprotective effects of propolis extract against carbon tetrachloride-induced acute liver damage in rats.

    PubMed

    Bhadauria, Monika; Nirala, Satendra Kumar; Shukla, Sangeeta

    2007-01-01

    Propolis is a natural product produced by bees that was discovered through the study of traditional cures and knowledge of indigenous people throughout the world. It is rich in vitamins A, B, C, and E, and in amino acids, copper, iron, manganese, and zinc. The investigators studied the duration-dependent hepatoprotective effects of propolis extract (200 mg/kg, orally) against carbon tetrachloride (CCl 4; 1.5 mL/kg, intraperitoneally)-induced liver damage in rats. Administration of CCl 4 caused a sharp elevation in the activity of serum transaminases and serum alkaline phosphatase. A significant depletion in hepatically reduced glutathione was observed with significantly enhanced hepatic lipid peroxidation. After CCl 4 administration, glycogen contents and activities of alkaline phosphatase, adenosine triphosphatase, and succinic dehydrogenase were significantly decreased, whereas total protein contents and activity of acid phosphatase were increased in the liver and kidney. Propolis extract reversed alterations in all parameters when administered within 6, 12, and 24 h of toxicant exposure. Propolis therapy produced duration-dependent protection, with maximal protection achieved at 24 h after CCl 4 exposure. It is believed that propolis in its natural form has general pharmacologic value and marked hepatoprotective potential because of its composition of minerals, flavonoids, and phenolic compounds. PMID:18029340

  3. Interleukin-6 -174G/C gene polymorphism affects muscle damage response to acute eccentric resistance exercise in elderly obese women.

    PubMed

    Funghetto, Silvana Schwerz; Prestes, Jonato; Silva, Alessandro de Oliveira; Farias, Darlan L; Teixeira, Tatiane G; Vieira, Denis Cesar Leite; Souza, Vinícius C; Sousa, Nuno M F; Navalta, James W; Melo, Gislane F; Karnikowski, Margô Gomes de Oliveira

    2013-11-01

    The IL-6 gene polymorphism has been associated with disease prevalence and different physiological responses to exercise. Eccentric resistance exercise (ERE) is considered a nonpharmacological tool to prevent the chronic degenerative profile associated with aging and obesity. Consequently, the aim of the present study was to investigate the influence of IL-6 -174G/C polymorphism on acute interleukin-6 (IL-6) and creatine kinase (CK) temporal response to ERE in elderly obese women. Ninety women completed seven sets of ten repetitions (eccentric only) of an acute ERE session at 110% of the ten repetitions maximum (10RM). IL-6 genotypes displayed no difference at baseline. ERE induced changes in CK concentration over time occurred only in the GG group, F(2.619, 136.173)=5.199, p=0.003, with CK activity increased from 106.8±6.9 U/l pre-intervention to 122.7±11.2 U/l at 24 h and 131.9±14.4 U/l at 48 h post-exercise. IL-6 concentration in the GG group was lower than the CC/CG group only at 0 h post-exercise (3.78±0.58 pg/ml versus 6.51±1.91 pg/ml, p=0.030). Only the GG genotype group had higher CK activity 24-48 h following ERE and greater CK integral values, while IL-6 activity over 48 h was higher in the CC/CG genotype group. In conclusion, IL-6 genotype affects CK and IL-6 in response to ERE. It is of interest that the ERE protocol induced an elevation in CK, indicating possible muscle damage without exacerbating IL-6 and CK for the GG genotype.

  4. Prevention of cardiac damage induced by formyl-leurosine, a potent cytostatic agent, by radio-detoxified endotoxin (Tolerin) in dogs

    SciTech Connect

    Bertok, L.; Juhasz-Nagy, A.; Sotonyi, P.

    1984-08-01

    Radio-detoxified endotoxin (Tolerin), produced by /sup 60/Co-gamma irradiation of Escherichia coli 089 endotoxin, can protect dogs against the acute cardiotoxic side-effects of formyl-leurosine, a semi-synthetic Vinca derivative with promising antineoplastic potency. Formyl-leurosine induces a rapid decrease in arterial blood pressure and diminishes the contractile force of the myocardium in the anaesthetized dog. These responses indicate a direct pharmacologic relaxant effect of the drug on the heart and vasculature smooth muscle. The early cardiovascular depression is of short duration and is unaffected by Tolerin. Tolerin can prevent, however, the secondary, more dangerous phase of circulatory depression that is associated with the severe cardiotoxic manifestations of the drug, as demonstrated by hemodynamic and morphologic (light and electronmicroscopic) patterns.

  5. Schisandrin B Prevents Doxorubicin Induced Cardiac Dysfunction by Modulation of DNA Damage, Oxidative Stress and Inflammation through Inhibition of MAPK/p53 Signaling

    PubMed Central

    Arumugam, Somasundaram; Suzuki, Kenji; Ko, Kam Ming; Krishnamurthy, Prasanna; Watanabe, Kenichi; Konishi, Tetsuya

    2015-01-01

    Doxorubicin (Dox) is a highly effective antineoplastic drug. However, Dox-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy, which limits Dox clinical application. Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In current study, we investigated possible protective effects of Sch B against Dox-induced cardiomyopathy in mice. Mice received a single injection of Dox (20 mg/kg IP). Five days after Dox administration, left ventricular (LV) performance was significantly depressed and was improved by Sch B treatment. Sch B prevented the Dox-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart. In addition, the increased expression of phospho-p38 MAPK and phospho-MAPK activated mitogen kinase 2 levels by Dox were significantly suppressed by Sch B treatment. Sch B also attenuated Dox-induced higher expression of LV proinflammatory cytokines, cardiomyocyte DNA damage, myocardial apoptosis, caspase-3 positive cells and phopho-p53 levels in mice. Moreover, LV expression of NADPH oxidase subunits and reactive oxygen species were significantly less in Sch B treatment mice after Dox injection. These findings suggest that Sch B attenuates Dox-induced cardiotoxicity via antioxidative and anti-inflammatory effects. PMID:25742619

  6. Cardiac arrest during dipyridamole imaging

    SciTech Connect

    Blumenthal, M.S.; McCauley, C.S.

    1988-05-01

    A case of cardiac arrest and subsequent acute myocardial infarction occurring during thallium-201 imaging with oral dipyridamole augmentation is presented. Previous reports emphasizing the safety of this procedure are briefly reviewed and a recommendation for close hemodynamic and arrhythmia monitoring during the study is made. Large doses of oral dipyridamole may be contraindicated in patients with unstable angina.

  7. The novel histone deacetylase inhibitor, LBH589, induces expression of DNA damage response genes and apoptosis in Ph- acute lymphoblastic leukemia cells.

    PubMed

    Scuto, Anna; Kirschbaum, Mark; Kowolik, Claudia; Kretzner, Leo; Juhasz, Agnes; Atadja, Peter; Pullarkat, Vinod; Bhatia, Ravi; Forman, Stephen; Yen, Yun; Jove, Richard

    2008-05-15

    We investigated the mechanism of action of LBH589, a novel broad-spectrum HDAC inhibitor belonging to the hydroxamate class, in Philadelphia chromosome-negative (Ph(-)) acute lymphoblastic leukemia (ALL). Two model human Ph(-) ALL cell lines (T-cell MOLT-4 and pre-B-cell Reh) were treated with LBH589 and evaluated for biologic and gene expression responses. Low nanomolar concentrations (IC(50): 5-20 nM) of LBH589 induced cell-cycle arrest, apoptosis, and histone (H3K9 and H4K8) hyperacetylation. LBH589 treatment increased mRNA levels of proapoptosis, growth arrest, and DNA damage repair genes including FANCG, FOXO3A, GADD45A, GADD45B, and GADD45G. The most dramatically expressed gene (up to 45-fold induction) observed after treatment with LBH589 is GADD45G. LBH589 treatment was associated with increased histone acetylation at the GADD45G promoter and phosphorylation of histone H2A.X. Furthermore, treatment with LBH589 was active against cultured primary Ph(-) ALL cells, including those from a relapsed patient, inducing loss of cell viability (up to 70%) and induction of GADD45G mRNA expression (up to 35-fold). Thus, LBH589 possesses potent growth inhibitory activity against including Ph(-) ALL cells associated with up-regulation of genes critical for DNA damage response and growth arrest. These findings provide a rationale for exploring the clinical activity of LBH589 in the treatment of patients with Ph(-) ALL.

  8. Vitamin D Predicts All-Cause and Cardiac Mortality in Females with Suspected Acute Coronary Syndrome: A Comparison with Brain Natriuretic Peptide and High-Sensitivity C-Reactive Protein

    PubMed Central

    Naesgaard, Patrycja A.; León de la Fuente, Ricardo A.; Nilsen, Stein Tore; Woie, Leik; Aarsland, Torbjoern; Staines, Harry; Nilsen, Dennis W. T.

    2013-01-01

    Vitamin D may not only reflect disease but may also serve as a prognostic indicator. Our aim was to assess the gender-specific utility of vitamin D measured as 25-hydroxy-vitamin D [25(OH)D] to predict all-cause and cardiac death in patients with suspected acute coronary syndrome (ACS) and to compare its prognostic utility to brain natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hsCRP). Blood samples were harvested on admission in 982 patients. Forty percent were women (65.9 ± 12.6 years). Mortality was evaluated in quartiles of 25(OH)D, BNP, and hsCRP, respectively, during a 5-year follow-up, applying univariate and multivariate analyses. One hundred and seventy-three patients died; 78 were women. In 92 patients (37 women), death was defined as cardiac. In women, the univariate hazard ratio (HR) for total death of 25(OH)D in Quartile (Q) 2 versus Q1, Q3 versus Q1, and Q4 versus Q1 was 0.55 (95% CI 0.33–0.93), 0.29 (95% CI 0.15–0.55), and 0.13 (95% CI 0.06–0.32), respectively. In females, it was an independent predictor of total and cardiac death, whereas BNP and hsCRP were less gender-specific. No gender differences in 25(OH)D were noted in a reference material. Accordingly, vitamin D independently predicts mortality in females with suspected ACS. PMID:24349821

  9. Prevalence and Prognostic Significance of Hyponatremia in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Data from the Akershus Cardiac Examination (ACE) 2 Study

    PubMed Central

    Brynildsen, Jon; Høiseth, Arne Didrik; Følling, Ivar; Brekke, Pål H.; Christensen, Geir; Hagve, Tor-Arne; Verbalis, Joseph G.; Omland, Torbjørn; Røsjø, Helge

    2016-01-01

    Background Hyponatremia is prevalent and associated with mortality in patients with heart failure (HF). The prevalence and prognostic implications of hyponatremia in acute exacerbation of chronic obstructive pulmonary (AECOPD) have not been established. Method We included 313 unselected patients with acute dyspnea who were categorized by etiology of dyspnea according to established guidelines (derivation cohort). Serum Na+ was determined on hospital admission and corrected for hyperglycemia, and hyponatremia was defined as [Na+]<137 mmol/L. Survival was ascertained after a median follow-up of 816 days and outcome was analyzed in acute HF (n = 143) and AECOPD (n = 83) separately. Results were confirmed in an independent AECOPD validation cohort (n = 99). Results In the derivation cohort, median serum Na+ was lower in AECOPD vs. acute HF (138.5 [135.9–140.5] vs. 139.2 [136.7–141.3] mmol/L, p = 0.02), while prevalence of hyponatremia (27% [22/83] vs. 20% [29/143], p = 0.28) and mortality rate (42% [35/83] vs. 46% [66/143], p = 0.56) were similar. By univariate Cox regression analysis, hyponatremia was associated with increased mortality in acute HF (HR 1.85 [95% CI 1.08, 3.16], p = 0.02), but not in AECOPD (HR 1.00 [0.47, 2.15], p = 1.00). Analogous to the results of the derivation cohort, hyponatremia was prevalent also in the AECOPD validation cohort (25% [25/99]), but not associated with mortality. The diverging effect of hyponatremia on outcome between AECOPD and acute HF was statistically significant (p = 0.04). Conclusion Hyponatremia is prevalent in patients with acute HF and AECOPD, but is associated with mortality in patients with acute HF only. PMID:27529844

  10. Comparison of cancer risk associated with low-dose ionizing radiation from cardiac imaging and therapeutic procedures after acute myocardial infarction in women versus men.

    PubMed

    Lawler, Patrick R; Afilalo, Jonathan; Eisenberg, Mark J; Pilote, Louise

    2013-11-15

    Patients with cardiovascular disease are increasingly exposed to low-dose ionizing radiation (LDIR) from diagnostic and therapeutic procedures. Previous studies have suggested that the malignancy risk associated with LDIR may be greatest in women and in young patients. We sought to compare the effect of LDIR on incident cancer across gender and age strata in a population-based cohort of patients with myocardial infarction (MI). All initially cancer-free patients with MI from 1996 to 2006 were identified in a province-wide administrative database. Procedure-specific LDIR dose estimates were used to generate a cumulative cardiac LDIR exposure variable. Time-dependent multivariate Cox regression was used to determine the relation between cardiac LDIR and incident cancer. A time-lag covariate of 3 years was used wherein a de novo cancer could only be attributed to LDIR incurred at least 3 years earlier. The effect of age and gender on LDIR-associated risk of cancer was evaluated with stratified models and the addition of interaction terms. The study cohort consisted of 56,606 men and 26,255 women. For each millisievert of cardiac LDIR, women were more likely to develop a cancer (hazard ratio 1.005, 95% confidence interval 1.002 to 1.008) than men (hazard ratio 1.002, 95% confidence interval 1.001 to 1.004) after adjusting for age, noncardiac LDIR, and covariates (p for interaction = 0.014). Contrarily, over the range studied (predominantly patients aged >50 years), age was not a determinant of LDIR-associated risk of cancer. In conclusion, women exposed to LDIR from cardiac imaging and therapeutic procedures after MI are at a greater risk of incident cancer compared with men after similar exposure. The extrapolated absolute risk from LDIR exposure would nonetheless be expected to be low.

  11. Cardiac nuclear medicine

    SciTech Connect

    Gerson, M.C.

    1987-01-01

    The book begins with a review of the radionuclide methods available for evaluating cardiac perfusion and function. The authors discuss planar and tomographic thallium myocardial imaging, first-pass and equilibrium radionuclide angiography, and imaging with infarct-avid tracers. Several common but more specialized procedures are then reviewed: nonogemetric measurement of left ventricular volume, phase (Fourier) analysis, stroke volume ratio, right ventricular function, and diastolic function. A separate chapter is devoted to drug interventions and in particular the use of radionuclide ventriculography to monitor doxorubicin toxicity and therapy of congestive heart failure. The subsequent chapters provide a comprehensive guide to test selection, accuracy, and results in acute myocardial infarction, in postmyocardial infarction, in chronic coronary artery disease, before and after medical or surgical revascularization, in valvular heart disease, in cardiomyopathies, and in cardiac trauma.

  12. Cardiac arrhythmias in pregnancy.

    PubMed

    Knotts, Robert J; Garan, Hasan

    2014-08-01

    As more women with repaired congenital heart disease survive to their reproductive years and many other women are delaying pregnancy until later in life, a rising concern is the risk of cardiac arrhythmias during pregnancy. Naturally occurring cardiovascular changes during pregnancy increase the likelihood that a recurrence of a previously experienced cardiac arrhythmia or a de novo arrhythmia will occur. Arrhythmias should be thoroughly investigated to determine if there is a reversible etiology, and risks/benefits of treatment options should be fully explored. We discuss the approach to working up and treating various arrhythmias during pregnancy with attention to fetal and maternal risks as well as treatment of fetal arrhythmias. Acute management in stable patients includes close monitoring and intravenous pharmacologic therapy, while DC cardioversion should be used to terminate arrhythmias in hemodynamically unstable patients. Long-term management may require continued oral antiarrhythmic therapy, with particular attention to fetal safety, to prevent complications associated with arrhythmias.

  13. Unchain my heart: the scientific foundations of cardiac repair

    PubMed Central

    Dimmeler, Stefanie; Zeiher, Andreas M.; Schneider, Michael D.

    2005-01-01

    In humans, the biological limitations to cardiac regenerative growth create both a clinical imperative — to offset cell death in acute ischemic injury and chronic heart failure — and a clinical opportunity; that is, for using cells, genes, and proteins to rescue cardiac muscle cell number or in other ways promote more efficacious cardiac repair. Recent experimental studies and early-phase clinical trials lend credence to the visionary goal of enhancing cardiac repair as an achievable therapeutic target. PMID:15765139

  14. Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

    SciTech Connect

    Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun

    2012-07-01

    Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB

  15. Cardiac amyloidosis

    MedlinePlus

    ... the way electrical signals move through the heart (conduction system). This can lead to abnormal heartbeats ( arrhythmias ) ... due to medicine) Sick sinus syndrome Symptomatic cardiac conduction system disease (arrhythmias related to abnormal conduction of ...

  16. Cardiac Sarcoidosis

    MedlinePlus

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

  17. Pre- and/or Intra-Operative Prescription of Diuretics, but Not Renin-Angiotensin-System Inhibitors, Is Significantly Associated with Acute Kidney Injury after Non-Cardiac Surgery: A Retrospective Cohort Study

    PubMed Central

    Tagawa, Miho; Ogata, Ai; Hamano, Takayuki

    2015-01-01

    Background and Objectives Pre- and/or intra-operative use of diuretics, angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) constitutes a potentially modifiable risk factor for postoperative acute kidney injury (AKI). It has been studied whether use of these drugs predicts AKI after cardiac surgery. The objective of this study was to examine whether administration of these agents was independently associated with AKI after non-cardiac surgery. Design, Setting, Participants, and Measurements This was a retrospective observational study. Inclusion criteria were adult patients (age ≥ 18) who underwent non-cardiac surgery under general anesthesia from 2007 to 2009 at Kyoto Katsura Hospital. Exclusion criteria were urological surgery, missing creatinine values, and preoperative dialysis. The exposures of interest were pre- and/or intra-operative use of diuretics or ACE-I/ARB. Outcome variables were postoperative AKI as defined by the AKI Network (increase in creatinine ≥ 0.3 mg/dL or 150% within 48 hours, or urine output < 0.5 ml/kg/hour for > 6 hours). Multivariable logistic regression analyses were conducted and adjusted for potential confounders. Propensity scores (PS) for receiving diuretics or ACE-I/ARB therapy were estimated and PS adjustment, PS matching, and inverse probability weighting were performed. Results There were 137 AKI cases (5.0%) among 2,725 subjects. After statistical adjustment for patient and surgical characteristics, odds (95% CI) of postoperative AKI were 2.07 (1.10-3.89) (p = 0.02) and 0.89 (0.56-1.42) (p = 0.63) in users of diuretics and ACE-I/ARB, respectively, compared with non-users. PS adjustment, PS matching, and inverse probability weighting yielded similar results. The effect size of diuretics was significantly greater in the patients with lower propensity for diuretic use (p for interaction < 0.1). Conclusions Prescription of diuretics, but not ACE-I/ARB, was independently associated with

  18. The impact of juvenile coxsackievirus infection on cardiac progenitor cells and postnatal heart development.

    PubMed

    Sin, Jon; Puccini, Jenna M; Huang, Chengqun; Konstandin, Mathias H; Gilbert, Paul E; Sussman, Mark A; Gottlieb, Roberta A; Feuer, Ralph

    2014-07-01

    Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load.

  19. Combination of microRNA-21 and microRNA-146a Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction in Mice

    PubMed Central

    Huang, Wei; Tian, Shan-Shan; Hang, Peng-Zhou; Sun, Chuan; Guo, Jing; Du, Zhi-Min

    2016-01-01

    Recent studies have revealed the cytoprotective roles of microRNAs (miRNAs) miR-21 and miR-146a against ischemic cardiac injuries. While these studies investigated each of these miRNAs as an independent individual factor, our previous study has suggested the possible interaction between these two miRNAs. The present study was designed to investigate this possibility by evaluating the effects of miR-21 and miR-146a combination on cardiac ischemic injuries and the underlying mechanisms. MiR-21 and miR-146a synergistically decreased apoptosis under ischemia/hypoxic conditions in cardiomyocytes compared with either miR-21 or miR-146a alone. Mice coinjected with agomiR-21 and agomiR-146a had decreased infarct size, increased ejection fraction (EF), and fractional shortening (FS). These effects were greater than those induced by either of the two agomiRs. Furthermore, greater decreases in p38 mitogen-associated protein kinase phosphorylation (p-p38 MAPK) were observed with miR-21: miR-146a combination as compared to application of either of the miRNAs. These data suggest that combination of miR-21 and miR-146a has a greater protective effect against cardiac ischemia/hypoxia-induced apoptosis as compared to these miRNAs applied individually. This synergistic action is mediated by enhanced potency of inhibition of cardiomyocyte apoptosis by the miR-21—PTEN/AKT—p-p38—caspase-3 and miR-146a—TRAF6—p-p38—caspase-3 signal pathways. PMID:26978580

  20. Intra-aortic balloon pumping reduces the increased arterial load caused by acute cardiac depression, modifying central and peripheral load determinants in a time- and flow-related way.

    PubMed

    Bia, Daniel; Cabrera-Fischer, Edmundo I; Zócalo, Yanina; Armentano, Ricardo L

    2012-09-01

    The mechanisms that explain intra-aortic balloon pumping (IABP) effects are not completely understood, and attributing them only to pressure-associated changes in cardiac function would be an oversimplification. Since IABP modifies the aortic and systemic blood-flow pattern, flow-related effects could be expected. To characterize effects of acute heart failure (AHF) on the arterial biomechanics; IABP effects on the arterial biomechanics during AHF, and their potential time-dependence; the association between hemodynamics and biomechanical changes during AHF and IABP. Sheep (n = 6) aortic pressure, flow, and diameter were measured: (1) before (Basal) and (2) 1-3 (HF(1-3)) and 28-30 (HF(28-30)) min after starting halothane to induce AHF; and (3) at specific times (1-3, 14-15 and 28-30 min) during IABP assistance. Calculus: aortic characteristic impedance (Z(c)), beta stiffness (β), incremental (E(INC)) and pressure-strain elastic modulus (E(P)); total arterial compliance (C(G)), total systemic vascular resistance and wave propagation parameters. (1) AHF resulted in an acute increase in aortic and systemic stiffness (HF(28-30) % changes with respect to Basal conditions: β +217%, E (P) +143%, E(INC) +101%, Z(c) +52%, C(G) -13%), associated with the reduction in the aortic blood flow; (2) during AHF IABP resulted in acute beneficial changes aortic and systemic biomechanics (% changes in IABP(1-3) with respect HF(28-30): β -62%, E(P) -68%, E (INC) -66%, Z(c) -38%, C(G) 66%), and in wave propagation parameters, (3) IABP-related changes were time-dependent and associated with changes in aortic blood flow. Aortic and systemic biomechanical and impedance properties are detrimentally modified during AHF, being the changes rapidly reverted during IABP. IABP-related beneficial changes in arterial biomechanics were time-dependent and associated with IABP capability to increase blood flow.

  1. Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine.

    PubMed

    Fu, Ji-Dong; Srivastava, Deepak

    2015-01-01

    Cardiac fibroblasts play critical roles in maintaining normal cardiac function and in cardiac remodeling during pathological conditions such as myocardial infarction (MI). Adult cardiomyocytes (CMs) have little to no regenerative capacity; damaged CMs in the heart after MI are replaced by cardiac fibroblasts that become activated and transform into myofibroblasts, which preserves the structural integrity. Unfortunately, this process typically causes fibrosis and reduces cardiac function. Directly reprogramming adult cardiac fibroblasts into induced CM-like cells (iCMs) holds great promise for restoring heart function. Direct cardiac reprogramming also provides a new research model to investigate which transcription factors and microRNAs control the molecular network that guides cardiac cell fate. We review the approaches and characterization of in vitro and in vivo reprogrammed iCMs from different laboratories, and outline the future directions needed to translate this new approach into a practical therapy for damaged hearts.

  2. Lead accumulation, oxidative damage and histopathological alteration in testes and accessory glands of freshwater crab, Sinopotamon henanense, induced by acute lead exposure.

    PubMed

    Li, Na; Hou, Yu-hua; Ma, Dan-dan; Jing, Wei-xin; Dahms, Hans-Uwe; Wang, Lan

    2015-07-01

    Lead (Pb) is one of the most toxic environmental pollutants and known to exert multiple toxic effects including gonadotoxic and spermiotoxic effects. In order to understand toxic mechanisms of lead (Pb) on the testes and the accessory glands of crabs, we investigated Pb accumulation in testes and accessory glands and the survival rate of sperms of freshwater crab, Sinopotamon henanense. The tissue damaging effects of Pb was also investigated by histopathological examination and analyses of antioxidant enzymes as well as lipid peroxidation. Crabs were exposed to different Pb concentrations (0, 3.675, 7.35, 14.7, 29.4 and 58.8 mg/L) for 3, 5 and 7 days. The results showed that Pb levels in testes and accessory glands increased significantly following Pb exposure for 5 and 7 days in almost all treated groups, and survival rate of sperm decreased with increasing Pb concentrations at 5 and 7 days. Morphological changes identified histologically were discovered in testes, including a disordered arrangement of germ cells, a decreased number of sperm in the lumina of the seminiferous tubules, extensive necrosis in the germinal layer of the seminiferous tubules, etc. At the same time, histological abnormalities were discovered in accessory glands, the wall cells were separated from the basement membrane, and wall cells were missing partly. The activities of SOD, GPx and CAT in testes showed no statistically significant changes compared to the control for 3 days, and initially increased and subsequently decreased with increasing Pb concentrations at 5 and 7 days. The antioxidant enzyme activities in accessory glands initially increased and subsequently decreased with increasing Pb concentrations and Pb exposure. This was accompanied with an increase in malondialdehyde (MDA) content in a concentration-dependent manner. These results showed that acute Pb exposure led to a reduction of survival rate of sperm and harmful effects at the cellular level of crab testes and accessory

  3. Diffuse alveolar damage and acute interstitial pneumonitis: histochemical evaluation with lectins and monoclonal antibodies against surfactant apoprotein and collagen type IV.

    PubMed

    Sugiyama, K; Kawai, T

    1993-05-01

    Diffuse alveolar damage (DAD) and acute interstitial pneumonitis (AIP) often present clinically as the adult respiratory distress syndrome. To evaluate the usefulness of histochemical techniques and to better understand the histopathologic changes of these diffuse lung injuries, postmortem lung sections of 14 and 33 patients who had been diagnosed as having DAD in organizing stage and AIP, respectively, were studied with the use of lectins and monoclonal antibodies against surfactant apoprotein (PE-10) and collagen type IV. On hematoxylin-eosin stained sections, type II pneumocyte hyperplasia and hyaline membrane formation were the major histopathologic findings in both DAD and AIP. The binding rates of type II pneumocytes to Ulex europaeus agglutinin I (UEA-I) in both DAD (64%) and AIP (45%) cases were significantly higher than those of type I pneumocytes or alveolar macrophages (both P < 0.001). Reactions of type II pneumocytes to PE-10 varied from 40 to 44% in DAD and 0 to 100% in AIP cases depending on the use of respirator and steroid medication. Therefore, it may be said that UEA-I and PE-10 are useful methods for outlining hyperplastic type II pneumocytes in both DAD and AIP. Hyaline membrane coating alveolar septal surfaces and exudate in alveolar air spaces were also stainable with PE-10. Surfactant apoprotein remained demonstrable histochemically within type II pneumocytes and hyaline membrane despite severe inflammatory injuries of the lungs. The immunohistochemical stain using anti-collagen type IV antibody revealed discontinuous alveolar basement membrane in 50% of DAD patients with respirator use and 80% of AIP patients with steroid medication.

  4. Renal Integrin-Linked Kinase Depletion Induces Kidney cGMP-Axis Upregulation: Consequences on Basal and Acutely Damaged Renal Function

    PubMed Central

    Cano-Peñalver, José Luis; Griera, Mercedes; García-Jerez, Andrea; Hatem-Vaquero, Marco; Ruiz-Torres, María Piedad; Rodríguez-Puyol, Diego; de Frutos, Sergio; Rodríguez-Puyol, Manuel

    2015-01-01

    Soluble guanylyl cyclase (sGC) is activated by nitric oxide (NO) and produces cGMP, which activates cGMP-dependent protein kinases (PKG) and is hydrolyzed by specific phosphodiesterases (PDE). The vasodilatory and cytoprotective capacity of cGMP-axis activation results in a therapeutic strategy for several pathologies. Integrin-linked kinase (ILK), a major scaffold protein between the extracellular matrix and intracellular signaling pathways, may modulate the expression and functionality of the cGMP-axis–related proteins. We introduce ILK as a novel modulator in renal homeostasis as well as a potential target for cisplatin (CIS)-induced acute kidney injury (AKI) improvement. We used an adult mice model of depletion of ILK (cKD-ILK), which showed basal increase of sGC and PKG expressions and activities in renal cortex when compared with wildtype (WT) littermates. Twenty-four h activation of sGC activation with NO enhanced the filtration rate in cKD-ILK. During AKI, cKD-ILK maintained the cGMP-axis upregulation with consequent filtration rates enhancement and ameliorated CIS-dependent tubular epithelial-to-mesenchymal transition and inflammation and markers. To emphasize the role of cGMP-axis upregulation due to ILK depletion, we modulated the cGMP axis under AKI in vivo and in renal cultured cells. A suboptimal dose of the PDE inhibitor ZAP enhanced the beneficial effects of the ILK depletion in AKI mice. On the other hand, CIS increased contractility-related events in cultured glomerular mesangial cells and necrosis rates in cultured tubular cells; ILK depletion protected the cells while sGC blockade with ODQ fully recovered the damage. PMID:26562149

  5. Acute Cardiotoxicity Evaluation of the Marine Biotoxins OA, DTX-1 and YTX

    PubMed Central

    Ferreiro, Sara F.; Carrera, Cristina; Vilariño, Natalia; Louzao, M. Carmen; Santamarina, Germán; Cantalapiedra, Antonio G.; Botana, Luis M.

    2015-01-01

    Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA) and dynophysistoxins (DTXs) are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP). Yessotoxins (YTXs) are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene) channel activity and in vivo using electrocardiogram (ECG) recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term. PMID:25826053

  6. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    PubMed Central

    Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

    2016-01-01

    Purpose To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. Methods This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Conclusion Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery. PMID:27143905

  7. Recommendations for ensuring early thrombolytic therapy for acute myocardial infarction. The Heart and Stroke Foundation of Canada, the Canadian Cardiovascular Society and the Canadian Association of Emergency Physicians for the Emergency Cardiac Care Coalition.

    PubMed Central

    1996-01-01

    OBJECTIVE: To recommend practical steps to ensure early thrombolytic therapy and thereby reduce mortality and morbidity associated with acute myocardial infarction (AMI). OPTIONS: Various factors were considered that influence time to thrombolysis related to patients, independent practitioners and health care systems. OUTCOMES: Reduction in morbidity and mortality associated with AMI. EVIDENCE: Early initiation of thrombolytic therapy reduces morbidity and mortality associated with AMI. The ECC Coalition analysed the factors that might impede early implementation of thrombolytic therapy. VALUES: Published data were reviewed, and recommendations were based on consensus opinion of the Emergency Cardiac Care (ECC) Coalition. The ECC Coalition comprises 20 professional, nongovernment and government organizations and has a mandate to improve emergency cardiac care services through collaboration. BENEFITS, HARMS AND COSTS: Early thrombolytic therapy reduces morbidity and mortality associated with AMI. Implementation of the recommendations will result in reduced time to thrombolytic therapy, streamlining of current practices and enhanced cooperation among health care professionals to expedite care. Depending on existing practices, implementation may require protocol development, and public and professional education. Although costs are associated with educating the public and health care professionals, they are outweighed by the financial and social benefits of reduced morbidity and mortality. RECOMMENDATIONS: Early recognition of AMI symptoms by the public and health care professionals, early access to the emergency medical services system and early action by emergency care providers in administering thrombolytic therapy (within 30 minutes after the patient's arrival at the emergency department). VALIDATION: No similar consensus statements or practice guidelines for thrombolytic therapy in Canada are available for comparison. PMID:8630837

  8. Change in Growth Differentiation Factor 15, but Not C-Reactive Protein, Independently Predicts Major Cardiac Events in Patients with Non-ST Elevation Acute Coronary Syndrome

    PubMed Central

    Hernandez-Baldomero, Idaira F.; Bosa-Ojeda, Francisco

    2014-01-01

    Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and growth-differentiation factor-15 (GDF-15) have received widespread interest, with their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among others, by physiological variations, which are the natural, within-individual variation occurring over time. The aims of our study are: (a) to describe the changes in hsCRP and GDF-15 levels over a period of time and after an episode of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and (b) to examine whether the rate of change in hsCRP and GDF-15 after the acute event is associated with long-term major cardiovascular adverse events (MACE). Two hundred and Fifty five NSTE-ACS patients were included in the study. We measured hsCRP and GDF-15 concentrations, at admission and again 36 months after admission (end of the follow-up period). The present study shows that the change of hsCRP levels, measured after 36 months, does not predict MACE in NSTEACS-patients. However, the level of GDF-15 measured, after 36 months, was a stronger predictor of MACE, in comparison to the acute unstable phase. PMID:24839357

  9. Impact of traffic-related air pollution on acute changes in cardiac autonomic modulation during rest and physical activity: a cross-over study.

    PubMed

    Cole-Hunter, Tom; Weichenthal, Scott; Kubesch, Nadine; Foraster, Maria; Carrasco-Turigas, Glòria; Bouso, Laura; Martínez, David; Westerdahl, Dane; de Nazelle, Audrey; Nieuwenhuijsen, Mark

    2016-01-01

    People are often exposed to traffic-related air pollution (TRAP) during physical activity (PA), but it is not clear if PA modifies the impact of TRAP on cardiac autonomic modulation. We conducted a panel study among 28 healthy adults in Barcelona, Spain to examine how PA may modify the impact of TRAP on cardiac autonomic regulation. Participants completed four 2-h exposure scenarios that included either rest or intermittent exercise in high- and low-traffic environments. Time- and frequency-domain measures of heart rate variability (HRV) were monitored during each exposure period along with continuous measures of TRAP. Linear mixed-effects models were used to estimate the impact of TRAP on HRV as well as potential effect modification by PA. Exposure to TRAP was associated with consistent decreases in HRV; however, exposure-response relationships were not always linear over the broad range of exposures. For example, each 10 μg/m(3) increase in black carbon was associated with a 23% (95% CI: -31, -13) decrease in high frequency power at the low-traffic site, whereas no association was observed at the high-traffic site. PA modified the impact of TRAP on HRV at the high-traffic site and tended to weaken inverse associations with measures reflecting parasympathetic modulation (P ≤ 0.001). Evidence of effect modification at the low-traffic site was less consistent. The strength and direction of the relationship between TRAP and HRV may vary across exposure gradients. PA may modify the impact of TRAP on HRV, particularly at higher concentrations.

  10. Inducing valvular regurgitation in mice via thermal ablation of cardiac valves.

    PubMed

    Mulchrone, Ashley M; Brace, Christopher L; Hacker, Timothy A; Chesler, Naomi C

    2014-01-01

    This study presents early data in the development of a novel mouse model of heart failure utilizing thermal ablation on cardiac valves to induce valvular regurgitation. Thermal ablation of the valve was achieved through the application of radiofrequency (RF) electrical current. The objective was to apply enough energy to induce valve stiffening and retraction, which was hypothesized to produce valve insufficiency and blood regurgitation in vivo. Preliminary studies were performed to develop a workable energy delivery catheter that could be inserted through the carotid artery to the aortic valve. Catheter position between the aortic valve leaflets was verified by echocardiography. Valve function was evaluated before and after the thermal insult using Doppler measurements near the valve inflow and outflow, and early results demonstrate that the energy delivery catheter could successfully induce acute valve insufficiency. Further study is needed to refine the catheter to provide greater control over the degree of thermal damage and resulting changes in cardiac physiology.

  11. [Cardiac amyloidosis].

    PubMed

    Hoyer, Caroline; Angermann, Christiane E; Knop, Stefan; Ertl, Georg; Störk, Stefan

    2008-03-15

    Amyloidoses are a heterogeneous group of multisystem disorders, which are characterized by an extracellular deposition of amyloid fibrils. Typically affected are the heart, liver, kidneys, and nervous system. More than half of the patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein pressure, frequently in combination with dyspnea. There can also be chest pain, probably due to microvessel disease. Dysfunction of the autonomous nervous system or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The AL amyloidosis caused by the deposition of immunoglobulin light chains is the most common form. It can be performed by monoclonal gammopathy. The desirable treatment therapy consists of high-dose melphalan therapy twice followed by autologous stem cell transplantation. Due to the high peritransplantation mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis is an autosomal dominant disorder caused by the amyloidogenic form of transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver transplantation is the only curative therapy. The symptomatic treatment of cardiac amyloidosis is based on the current guidelines for chronic heart failure according to the patient's New York Heart Association (NYHA) state. Further types of amyloidosis with possible cardiac involvement comprise the senile systemic amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after long-term dialysis treatment. PMID:18344065

  12. A Feasibility Study of Smartphone-Based Telesonography for Evaluating Cardiac Dynamic Function and Diagnosing Acute Appendicitis with Control of the Image Quality of the Transmitted Videos.

    PubMed

    Kim, Changsun; Cha, Hyunmin; Kang, Bo Seung; Choi, Hyuk Joong; Lim, Tae Ho; Oh, Jaehoon

    2016-06-01

    Our aim was to prove the feasibility of the remote interpretation of real-time transmitted ultrasound videos of dynamic and static organs using a smartphone with control of the image quality given a limited internet connection speed. For this study, 100 cases of echocardiography videos (dynamic organ)-50 with an ejection fraction (EF) of ≥50 s and 50 with EF <50 %-and 100 cases of suspected pediatric appendicitis (static organ)-50 with signs of acute appendicitis and 50 with no findings of appendicitis-were consecutively selected. Twelve reviewers reviewed the original videos using the liquid crystal display (LCD) monitor of an ultrasound machine and using a smartphone, to which the images were transmitted from the ultrasound machine. The resolution of the transmitted echocardiography videos was reduced by approximately 20 % to increase the frame rate of transmission given the limited internet speed. The differences in diagnostic performance between the two devices when evaluating left ventricular (LV) systolic function by measuring the EF and when evaluating the presence of acute appendicitis were investigated using a five-point Likert scale. The average areas under the receiver operating characteristic curves for each reviewer's interpretations using the LCD monitor and smartphone were respectively 0.968 (0.949-0.986) and 0.963 (0.945-0.982) (P = 0.548) for echocardiography and 0.972 (0.954-0.989) and 0.966 (0.947-0.984) (P = 0.175) for abdominal ultrasonography. We confirmed the feasibility of remotely interpreting ultrasound images using smartphones, specifically for evaluating LV function and diagnosing pediatric acute appendicitis; the images were transferred from the ultrasound machine using image quality-controlled telesonography.

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

    PubMed

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

    2014-09-01

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

  14. Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis

    PubMed Central

    Yasuda, Masakazu; Iwanaga, Yoshitaka; Kato, Takao; Izumi, Toshiaki; Inuzuka, Yasutaka; Nakamura, Takashi; Miyaji, Yuki; Kawamura, Takayuki; Ikeguchi, Shigeru; Inoko, Moriaki; Kurita, Takashi; Miyazaki, Shunichi

    2016-01-01

    Background The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. Objective We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. Methods We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Results Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. Conclusions In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis. PMID:27547432

  15. Direct Cardiac Reprogramming: From Developmental Biology to Cardiac Regeneration

    PubMed Central

    Qian, Li; Srivastava, Deepak

    2013-01-01

    Heart disease affects millions worldwide and is a progressive condition involving loss of cardiomyocytes. The human heart has limited endogenous regenerative capacity and is thus an important target for novel regenerative medicine approaches. While cell-based regenerative therapies hold promise, cellular reprogramming of endogenous cardiac fibroblasts, which represent more than half of the cells in the mammalian heart, may be an attractive alternative strategy for regenerating cardiac muscle. Recent advances leveraging years of developmental biology point to the feasibility of generating de novo cardiomyocyte-like cells from terminally differentiated non-myocytes in the heart in situ after ischemic damage. Here, we review the progress in cardiac reprogramming methods and consider the opportunities and challenges that lie ahead in refining this technology for regenerative medicine. PMID:24030021

  16. [A new incentive for cardiac rehabilitation].

    PubMed

    Brügemann, Johan; Gerds-Ploeger, Hendyke Z R

    2015-01-01

    Only a minority of patients receive cardiac rehabilitation after acute coronary syndrome, coronary bypass grafting or heart valve operation. A recent study published in the European Heart Journal, presents the results from approximately 36,000 patients who participated in a rehabilitation program. It showed a 35% reduction in mortality during 4-year follow-up. Modern cardiac rehabilitation does not only focus on physical training but also includes interactive education, relaxation therapy, coping and self-management. Patients are also encouraged to participate in structural physical activity, which is incorporated into their daily life after the rehabilitation program. From other studies we know that not only is mortality reduced but also quality of life is improved as a result of cardiac rehabilitation. We both strongly recommend and encourage our colleagues to refer their cardiac patients to a multidisciplinary cardiac rehabilitation program. PMID:26288140

  17. Cardiac Surgery

    PubMed Central

    Weisse, Allen B.

    2011-01-01

    Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of coronary artery bypass grafting greatly aided the treatment of coronary heart disease. Cardiac transplantation, attempts to use the total artificial heart, and the application of ventricular assist devices have brought us to the present day. Although progress in the field of cardiovascular surgery appears to have slowed when compared with the halcyon times of the past, substantial challenges still face cardiac surgeons. It can only be hoped that sufficient resources and incentive can carry the triumphs of the 20th century into the 21st. This review covers past developments and future opportunities in cardiac surgery. PMID:22163121

  18. Sorbin and SH3 Domain‐Containing Protein 2 Is Released From Infarcted Heart in the Very Early Phase: Proteomic Analysis of Cardiac Tissues From Patients

    PubMed Central

    Kakimoto, Yu; Ito, Shinji; Abiru, Hitoshi; Kotani, Hirokazu; Ozeki, Munetaka; Tamaki, Keiji; Tsuruyama, Tatsuaki

    2013-01-01

    Background Few proteomic studies have examined human cardiac tissue following acute lethal infarction. Here, we applied a novel proteomic approach to formalin‐fixed, paraffin‐embedded human tissue and aimed to reveal the molecular changes in the very early phase of acute myocardial infarction. Methods and Results Heart tissue samples were collected from 5 patients who died within 7 hours of myocardial infarction and from 5 age‐ and sex‐matched control cases. Infarcted and control myocardia were histopathologically diagnosed and captured using laser microdissection. Proteins were extracted using an originally established method and analyzed using liquid chromatography–tandem mass spectrometry. The label‐free quantification demonstrated that the levels of 21 proteins differed significantly between patients and controls. In addition to known biomarkers, the sarcoplasmic protein sorbin and SH3 domain‐containing protein 2 (SORBS2) was greatly reduced in infarcted myocardia. Immunohistochemical analysis of cardiac tissues confirmed the decrease, and Western blot analysis showed a significant increase in serum sorbin and SH3 domain‐containing protein 2 in acute myocardial infarction patients (n=10) compared with control cases (n=11). Conclusions Our advanced comprehensive analysis using patient tissues and serums indicated that sarcoplasmic sorbin and SH3 domain‐containing protein 2 is released from damaged cardiac tissue into the bloodstream upon lethal acute myocardial infarction. The proteomic strategy presented here is based on precise microscopic findings and is quite useful for candidate biomarker discovery using human tissue samples stored in depositories. PMID:24342996

  19. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats

    EPA Science Inventory

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance...

  20. Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction†

    PubMed Central

    Huikuri, Heikki V.; Raatikainen, M.J. Pekka; Moerch-Joergensen, Rikke; Hartikainen, Juha; Virtanen, Vesa; Boland, Jean; Anttonen, Olli; Hoest, Nis; Boersma, Lucas V.A.; Platou, Eivind S.; Messier, Marc D.; Bloch-Thomsen, Poul-Erik

    2009-01-01

    Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (<5.7 ln ms2) adjusted for clinical variables was 7.0 (95% CI: 2.4–20.3, P < 0.001). Induction of sustained monomorphic VT during PES (adjusted HR = 4.8, 95% CI, 1.7–13.4, P = 0.003) also predicted the primary endpoint. Conclusion Fatal or near-fatal arrhythmias can be predicted by many risk stratification methods, especially by heart rate variability, in patients with reduced LVEF after AMI. PMID:19155249

  1. Animal models of cardiac cachexia.

    PubMed

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies. PMID:27317993

  2. Animal models of cardiac cachexia.

    PubMed

    Molinari, Francesca; Malara, Natalia; Mollace, Vincenzo; Rosano, Giuseppe; Ferraro, Elisabetta

    2016-09-15

    Cachexia is the loss of body weight associated with several chronic diseases including chronic heart failure (CHF). The cachectic condition is mainly due to loss of skeletal muscle mass and adipose tissue depletion. The majority of experimental in vivo studies on cachexia rely on animal models of cancer cachexia while a reliable and appropriate model for cardiac cachexia has not yet been established. A critical issue in generating a cardiac cachexia model is that genetic modifications or pharmacological treatments impairing the heart functionality and used to obtain the heart failure model might likely impair the skeletal muscle, this also being a striated muscle and sharing with the myocardium several molecular and physiological mechanisms. On the other hand, often, the induction of heart damage in the several existing models of heart failure does not necessarily lead to skeletal muscle loss and cachexia. Here we describe the main features of cardiac cachexia and illustrate some animal models proposed for cardiac cachexia studies; they include the genetic calsequestrin and Dahl salt-sensitive models, the monocrotaline model and the surgical models obtained by left anterior descending (LAD) ligation, transverse aortic constriction (TAC) and ascending aortic banding. The availability of a specific animal model for cardiac cachexia is a crucial issue since, besides the common aspects of cachexia in the different syndromes, each disease has some peculiarities in its etiology and pathophysiology leading to cachexia. Such peculiarities need to be unraveled in order to find new targets for effective therapies.

  3. Cardiac conduction system

    MedlinePlus

    The cardiac conduction system is a group of specialized cardiac muscle cells in the walls of the heart that send signals ... to contract. The main components of the cardiac conduction system are the SA node, AV node, bundle ...

  4. Using the Trajectory Framework: reconceptualizing cardiac illness.

    PubMed

    Hawthorne, M H

    1991-01-01

    Cardiac disease is known to be the leading cause of premature morbidity and mortality in the United States. Nursing management of cardiac illnesses, as such, is a primary concern for most practicing nurses. Dramatic changes in cardiac patient populations and associated technology available for treatment indicate a need to reconceptualize the nature of cardiac illness and to consider alternative approaches to guide the care of these patients. Traditional care, to a large degree, has focused upon acute illness, consequently limiting needed attention to the increasing group of patients suffering chronic illness and disability. In the present paper, the major changes in the cardiac patient population and in utilization of available technology are presented. The application of the Corbin and Strauss trajectory framework as an appropriate and useful framework for conceptualizing cardiac illness and care is then discussed. Five characteristics of the framework which render the model particularly well suited to address cardiac care are identified and discussed. These characteristics are: 1) comprehensiveness of care, 2) patient-centered care, 3) gender issues in care, 4) family-focused care, 5) technology and cardiac care. PMID:1763241

  5. microRNA and Cardiac Regeneration.

    PubMed

    Gnecchi, Massimiliano; Pisano, Federica; Bariani, Riccardo

    2015-01-01

    Heart diseases are a very common health problem in developed as well as developing countries. In particular, ischemic heart disease and heart failure represent a plague for the patients and for the society. Loss of cardiac tissue after myocardial infarction or dysfunctioning tissue in nonischemic cardiomyopathies may result in cardiac failure. Despite great advancements in the treatment of these diseases, there is a substantial unmet need for novel therapies, ideally addressing repair and regeneration of the damaged or lost myocardium. Along this line, cardiac cell based therapies have gained substantial attention. Three main approaches are currently under investigation: stem cell therapy with either embryonic or adult stem cells; generation of patient-specific induced pluripotent stem cells; stimulation of endogenous regeneration trough direct reprogramming of fibroblasts into cardiomyocytes, activation of resident cardiac stem cells or induction of native resident cardiomyocytes to reenter the cell cycle. All these strategies need to be optimized since their efficiency is low.It has recently become clear that cardiac signaling and transcriptional pathways are intimately intertwined with microRNA molecules which act as modulators of cardiac development, function, and disease. Moreover, miRNA also regulates stem cell differentiation. Here we describe how miRNA may circumvent hurdles that hamper the field of cardiac regeneration and stem cell therapy, and how miRNA may result as the most suitable solution for the damaged heart.

  6. Fractal analysis of heart rate dynamics as a predictor of mortality in patients with depressed left ventricular function after acute myocardial infarction. TRACE Investigators. TRAndolapril Cardiac Evaluation

    NASA Technical Reports Server (NTRS)

    Makikallio, T. H.; Hoiber, S.; Kober, L.; Torp-Pedersen, C.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

    1999-01-01

    A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.

  7. Role of Innate and Adaptive Immunity in Cardiac Injury and Repair

    PubMed Central

    Epelman, Slava; Liu, Peter P.; Mann, Douglas L.

    2015-01-01

    Despite significant advances, cardiovascular disease is the leading cause of world-wide mortality, highlighting an important yet unmet clinical need. Understanding the pathophysiological basis underlying cardiovascular tissue injury and repair in therefore of prime importance. Following cardiac tissue injury, the immune system plays an important and complex role throughout the acute inflammatory response and regenerative response. This review will summarize the role of the immune system in cardiovascular disease, and focus on the idea that the immune system evolved to promote tissue homeostasis following tissue injury and/or infection, and that the inherent cost of this evolutionary development is unwanted inflammatory mediated damage. While inflammation induced tissue damage is of little evolutionary consequence in organisms that have limited life spans, as will be discussed below, inflammation plays a major role in the development of cardiovascular disease worldwide in humans. PMID:25614321

  8. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit.

    PubMed

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-10-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure ( zhǐ yā) with valerian ( xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint ( xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1-1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate ( shén mén), hand Shenmen, glabella ( yìn táng), Wind Pool ( fēng chí), and Gushing Spring ( yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night. PMID:26587395

  9. Plasma neutrophil gelatinase-associated lipocalin predicts acute kidney injury, morbidity and mortality after pediatric cardiac surgery: a prospective uncontrolled cohort study

    PubMed Central

    Dent, Catherine L; Ma, Qing; Dastrala, Sudha; Bennett, Michael; Mitsnefes, Mark M; Barasch, Jonathan; Devarajan, Prasad

    2007-01-01

    Introduction Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers has impaired our ability to intervene in a timely manner. We previously showed in a small cohort of patients that plasma neutrophil gelatinase-associated lipocalin (NGAL), measured using a research enzyme-linked immunosorbent assay, is an early predictive biomarker of AKI after CPB. In this study we tested whether a point-of-care NGAL device can predict AKI after CPB in a larger cohort. Methods First, in a cross-sectional pilot study including 40 plasma samples (NGAL range 60 to 730 ng/ml) and 12 calibration standards (NGAL range 0 to 1,925 ng/ml), NGAL measurements by enzyme-linked immunosorbent assay and by Triage® NGAL Device (Biosite Inc., San Diego, CA, USA) were highly correlated (r = 0.94). Second, in a subsequent prospective uncontrolled cohort study, 120 children undergoing CPB were enrolled. Plasma was collected at baseline and at frequent intervals for 24 hours after CPB, and analyzed for NGAL using the Triage® NGAL device. The primary outcome was AKI, which was defined as a 50% or greater increase in serum creatinine. Results AKI developed in 45 patients (37%), but the diagnosis using serum creatinine was delayed by 2 to 3 days after CPB. In contrast, mean plasma NGAL levels increased threefold within 2 hours of CPB and remained significantly elevated for the duration of the study. By multivariate analysis, plasma NGAL at 2 hours after CPB was the most powerful independent predictor of AKI (β = 0.004, P < 0.0001). For the 2-hour plasma NGAL measurement, the area under the curve was 0.96, sensitivity was 0.84, and specificity was 0.94 for prediction of AKI using a cut-off value of 150 ng/ml. The 2 hour postoperative plasma NGAL levels strongly correlated with change in creatinine (r = 0.46, P < 0.001), duration of AKI (r = 0.57, P < 0.001), and length of hospital stay (r = 0.44, P < 0.001). The 12-hour plasma NGAL strongly

  10. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit

    PubMed Central

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-01-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure (指壓 zhǐ yā) with valerian (纈草 xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint (穴位 xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1–1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate (神門 shén mén), hand Shenmen, glabella (印堂 yìn táng), Wind Pool (風池 fēng chí), and Gushing Spring (湧泉 yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night. PMID:26587395

  11. Effect of acupressure with valerian oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome in a cardiac intensive care unit.

    PubMed

    Bagheri-Nesami, Masoumeh; Gorji, Mohammad Ali Heidari; Rezaie, Somayeh; Pouresmail, Zahra; Cherati, Jamshid Yazdani

    2015-10-01

    The purpose of this three-group double-blind clinical trial study was to investigate the effect of acupressure ( zhǐ yā) with valerian ( xié cǎo) oil 2.5% on the quality and quantity of sleep in patients with acute coronary syndrome (ACS) in a coronary intensive care unit (CCU). This study was conducted on 90 patients with ACS in Mazandaran Heart Center (Sari, Iran) during 2013. The patients were randomly assigned to one of three groups. Patients in the acupressure with valerian oil 2.5% group (i.e., valerian acupressure group) received bilateral acupoint ( xué wèi) massage with two drops of valerian oil for 2 minutes for three nights; including every point this treatment lasted in total 18 minutes. Patients in the acupressure group received massage at the same points with the same technique but without valerian oil. Patients in the control group received massage at points that were 1-1.5 cm from the main points using the same technique and for the same length of time. The quality and quantity of the patients' sleep was measured by the St. Mary's Hospital Sleep Questionnaire (SMHSQ). After the intervention, there was a significant difference between sleep quality and sleep quantity in the patients in the valerian acupressure group and the acupressure group, compared to the control group (p < 0.05). Patients that received acupressure with valerian oil experienced improved sleep quality; however, this difference was not statistically significant in comparison to the acupressure only group. Acupressure at the ear spirit gate ( shén mén), hand Shenmen, glabella ( yìn táng), Wind Pool ( fēng chí), and Gushing Spring ( yǒng quán) acupoints can have therapeutic effects and may improve the quality and quantity of sleep in patients with ACS. Using these techniques in combination with herbal medicines such valerian oil can have a greater impact on improving sleep and reducing waking during the night.

  12. The management of acute pericarditis.

    PubMed

    Wells, T A; Curzen, N P

    2005-01-01

    Acute pericarditis is usually a benign self-limiting condition, often of unexplained or viral aetiology, involving inflammation of the pericardial layers. It is often part of the differential diagnosis in patients admitted with acute chest pain and can be confused with acute myocardial infarction, acute pulmonary embolism and pleurisy. Occasionally it can result in cardiac tamponade and, if associated with myocarditis, in heart failure. This article sets out how to diagnose acute pericarditis, the common underlying causes, the possible treatment options and outcomes. PMID:21655516

  13. Putting cocaine use and cocaine-associated cardiac arrhythmias into epidemiological and clinical perspective

    PubMed Central

    Wood, David M; Dargan, Paul I

    2010-01-01

    This is the first article in a series of three articles on cocaine-related cardiac arrhythmias, following on from the 2008 British Pharmacological Society Winter Meeting Clinical Section Symposium entitled ‘Cocaine induced cardiac arrhythmias – from ion channel to clinical treatment’. We will summarize the epidemiology of cocaine use across the world and in particular will focus on UK, Europe and US use prevalence data. We will discuss the acute cardiac and non-cardiac toxicity associated with cocaine and highlight the lack of data on the true UK prevalence of acute cocaine toxicity and on the incidence of cocaine-related cardiac arrhythmias. PMID:20573079

  14. MicroRNAs and cardiac regeneration

    PubMed Central

    Hodgkinson, Conrad P.; Kang, Martin H.; Dal-Pra, Sophie; Mirotsou, Maria; Dzau, Victor J.

    2015-01-01

    The human heart has a very limited capacity to regenerate lost or damaged cardiomyocytes following cardiac insult. Instead, myocardial injury is characterized by extensive cardiac remodeling by fibroblasts, resulting in the eventual deterioration of cardiac structure and function. Cardiac function would be improved if these fibroblasts could be converted into cardiomyocytes. MicroRNAs (miRNAs), small non-coding RNAs that promote mRNA degradation and inhibit mRNA translation, have been shown to be important in cardiac development. Using this information various researchers have utilized miRNAs to promote the formation of cardiomyocytes through a number of approaches. Several miRNAs acting in combination promote the direct conversion of cardiac fibroblasts into cardiomyocytes. Moreover, a number of miRNAs have been identified that aid the formation of iPS cells and miRNAs also induce these cells to adopt a cardiac fate. MiRNAs have also been implicated in resident cardiac progenitor cell differentiation. In this review we will discuss the current literature as it pertains to these processes as well as discussing the therapeutic implications of these findings. PMID:25953925

  15. [Diagnosis of acute heart failure and relevance of biomarkers in elderly patients].

    PubMed

    Ruiz Ortega, Raúl Antonio; Manzano, Luis; Montero-Pérez-Barquero, Manuel

    2014-03-01

    Diagnosis of acute heart failure (HF) is difficult in elderly patients with multiple comorbidities. Risk scales and classification criteria based exclusively on clinical manifestations, such as the Framingham scales, lack sufficient specificity. In addition to clinical manifestations, diagnosis should be based on two key factors: natriuretic peptides and echocardiographic study. When there is clinical suspicion of acute HF, a normal natriuretic peptide level will rule out this process. When a consistent clinical suspicion is present, an echocardiographic study should also be performed. Diagnosis of HF with preserved ejection fraction (HF/pEF) requires detection of an enlarged left atrium or the presence of parameters of diastolic dysfunction. Elevation of cardiac biomarkers seems to be due to myocardial injury and the compensatory mechanisms of the body against this injury (hormone and inflammatory response and repair mechanisms). Elevation of markers of cardiac damage (troponins and natriuretic peptides) have been shown to be useful both in the diagnosis of acute HF and in prediction of outcome. MMP-2 could be useful in the diagnosis of HF/pEF. In addition to biomarkers with diagnostic value, other biomarkers are helpful in prognosis in the acute phase of HF, such as biomarkers of renal failure (eGFR, cystatin and urea), inflammation (cytokines and CRP), and the cell regeneration marker, galectin-3. A promising idea that is under investigation is the use of panels of biomarkers, which could allow more accurate diagnosis and prognosis of acute HF.

  16. Comparison of acute responses to isotonic or isokinetic eccentric muscle action: differential outcomes in skeletal muscle damage and implications for rehabilitation.

    PubMed

    Alemany, J A; Delgado-Díaz, D C; Mathews, H; Davis, J M; Kostek, M C

    2014-01-01

    Both isotonic and isokinetic eccentric muscle contractions are commonly used in muscle research laboratories to induce muscle damage, yet, the muscle damage outcomes between these 2 modes of eccentric contraction have not been compared. The purpose of this study was to compare modes of contraction for differences in muscle damage. 16 men were placed in the isotonic (IT: 110% of maximal isometric torque) or the isokinetic (IK: 120°/s) group, with each group performing 200 eccentric muscle actions of the knee extensors. Isometric peak torque, perceived soreness and CK activity were measured immediately pre and post exercise, and 48-h post exercise. Mean total work (~1700 J) and peak torque per set (~265 Nm) decreased over the 200 repetitions (p<0.01), and was not different between groups. Damage markers changed 48-h post exercise (p<0.05): peak isometric torque (-13%), creatine kinase activity (+200%) and self-perceived muscular soreness (+4 unit change). Significant group×time interactions (p<0.01) indicated that peak isometric torque was 22% lower, and creatine kinase and self-perceived muscular soreness were 330% and 3 unit difference higher in the IT as compared to the IK groups, 48-h post exercise. When equating for total work, skeletal muscle damage markers are higher during IT vs. IK modes. This reflects differences inherent in contraction type and suggests that this should be taken into account during physical rehabilitation.

  17. Sudden cardiac death due to coronary artery dissection as a complication of cardiac sarcoidosis.

    PubMed

    Kanaroglou, Savas; Nair, Vidhya; Fernandes, John R

    2015-01-01

    Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome (ACS), cardiac tamponade and sudden cardiac death that typically affects young women in the postpartum period. Rarely, it can be caused by systemic inflammatory conditions such as sarcoidosis. Sarcoidosis is an inflammatory disease most often affecting the lung and lymph nodes that can sometimes affect the heart. The authors report a case of sudden cardiac death caused by SCAD in the context of undiagnosed and subclinical cardiac sarcoidosis. The decedent was a 47-year-old male with a relatively innocuous past medical history. He was found dead in bed. At autopsy, there was a lethal hemopericardium resulting in cardiac tamponade. Gross examination of the heart revealed dissection of the posterior descending coronary branch of the right coronary artery. Histologically, the coronary artery showed acute and organizing dissection with evidence of vasculitis. A chronic inflammatory infiltrate consisting of lymphocytes, histiocytes, eosinophils and giant cells was seen. Sections of the myocardium showed myocarditis with a nonnecrotizing granuloma. The death was attributed to cardiac tamponade secondary to SCAD in the context of systemic sarcoidosis. The presented case demonstrates two concurrent rare pathologies and highlights the importance of considering SCAD in cases of sudden cardiac death at autopsy.

  18. The cardiac patient in Ramadan

    PubMed Central

    Chamsi-Pasha, Majed; Chamsi-Pasha, Hassan

    2016-01-01

    Ramadan is one of the five fundamental pillars of Islam. During this month, the majority of the 1.6 billion Muslims worldwide observe an absolute fast from dawn to sunset without any drink or food. Our review shows that the impact of fasting during Ramadan on patients with stable cardiac disease is minimal and does not lead to any increase in acute events. Most patients with the stable cardiac disease can fast safely. Most of the drug doses and their regimen are easily manageable during this month and may need not to be changed. Ramadan fasting is a healthy nonpharmacological means for improving cardiovascular risk factors. Most of the Muslims, who suffer from chronic diseases, insist on fasting Ramadan despite being exempted by religion. The Holy Quran specifically exempts the sick from fasting. This is particularly relevant if fasting worsens one's illness or delays recovery. Patients with unstable angina, recent myocardial infarction, uncontrolled hypertension, decompensated heart failure, recent cardiac intervention or cardiac surgery or any debilitating diseases should avoid fasting. PMID:27144139

  19. The Cardiac Complications of Methamphetamines.

    PubMed

    Paratz, Elizabeth D; Cunningham, Neil J; MacIsaac, Andrew I

    2016-04-01

    Methamphetamines are increasingly popular drugs of abuse in Australia, and are rising in purity. The rising popularity and purity of methamphetamines has notably increased demands upon Australian medical services. Methamphetamines are sympathomimetic amines with a range of adverse effects upon multiple organ systems. Cardiovascular complications are the second leading cause of death in methamphetamine abusers, and there appears to be a high prevalence of cardiac pathology. Cardiovascular pathology frequently seen in methamphetamine abusers includes hypertension, aortic dissection, acute coronary syndromes, pulmonary arterial hypertension and methamphetamine-associated cardiomyopathy. The rising prevalence of methamphetamine abuse is likely to increase the burden of cardiovascular pathology in Australians. A National Parliamentary Enquiry was opened in March 2015 to address concerns regarding the medical and social impacts of methamphetamine abuse. From April 2015, a National 'Ice Taskforce' was also created in parallel. Reversal of cardiac pathology appears to be achievable with abstinence from methamphetamines and initiation of appropriate treatment. It is key to appreciate that the pathogenesis of methamphetamine-induced cardiac complications arises as a result of the specific toxic effects of methamphetamines. Clinical management is hence individualised; suggested management approaches for methamphetamine-induced cardiac complications are detailed within this article.

  20. [Cardiac safety of electroconvulsive therapy in an elderly patient--a case report].

    PubMed

    Karakuła-Juchnowicz, Hanna; Próchnicki, Michał; Kiciński, Paweł; Olajossy, Marcin; Pelczarska-Jamroga, Agnieszka; Dzikowski, Michał; Jaroszyński, Andrzej

    2015-10-01

    Since electroconvulsive therapy (ECT) was introduced as treatment for psychiatric disorders in 1938, it has remained one of the most effective therapeutic methods. ECT is often used as a "treatment of last resort" when other methods fail, and a life-saving procedure in acute clinical states when a rapid therapeutic effect is needed. Mortality associated with ECT is lower, compared to the treatment with tricyclic antidepressants, and comparable to that observed in so-called minor surgery. In the literature, cases of effective and safe electroconvulsive therapy have been described in patients of advanced age, with a burden of many somatic disorders. However, cases of acute cardiac episodes have also been reported during ECT. The qualification of patients for ECT and the selection of a group of patients at the highest risk of cardiovascular complications remains a serious clinical problem. An assessment of the predictive value of parameters of standard electrocardiogram (ECG), which is a simple, cheap and easily available procedure, deserves special attention. This paper reports a case of a 74-year-old male patient treated with ECT for a severe depressive episode, in the context of cardiologic safety. Both every single ECT session and the full course were assessed to examine their impact on levels of troponin T, which is a basic marker of cardiac damage, and selected ECG parameters (QTc, QRS). In the presented case ECT demonstrated its high general and cardiac safety with no negative effect on cardiac troponin (TnT) levels, corrected QT interval (QTc) duration, or other measured ECG parameters despite initially increased troponin levels, the patient's advanced age, the burden of a severe somatic disease and its treatment (anticancer therapy). PMID:26608489

  1. [Cardiac safety of electroconvulsive therapy in an elderly patient--a case report].

    PubMed

    Karakuła-Juchnowicz, Hanna; Próchnicki, Michał; Kiciński, Paweł; Olajossy, Marcin; Pelczarska-Jamroga, Agnieszka; Dzikowski, Michał; Jaroszyński, Andrzej

    2015-10-01

    Since electroconvulsive therapy (ECT) was introduced as treatment for psychiatric disorders in 1938, it has remained one of the most effective therapeutic methods. ECT is often used as a "treatment of last resort" when other methods fail, and a life-saving procedure in acute clinical states when a rapid therapeutic effect is needed. Mortality associated with ECT is lower, compared to the treatment with tricyclic antidepressants, and comparable to that observed in so-called minor surgery. In the literature, cases of effective and safe electroconvulsive therapy have been described in patients of advanced age, with a burden of many somatic disorders. However, cases of acute cardiac episodes have also been reported during ECT. The qualification of patients for ECT and the selection of a group of patients at the highest risk of cardiovascular complications remains a serious clinical problem. An assessment of the predictive value of parameters of standard electrocardiogram (ECG), which is a simple, cheap and easily available procedure, deserves special attention. This paper reports a case of a 74-year-old male patient treated with ECT for a severe depressive episode, in the context of cardiologic safety. Both every single ECT session and the full course were assessed to examine their impact on levels of troponin T, which is a basic marker of cardiac damage, and selected ECG parameters (QTc, QRS). In the presented case ECT demonstrated its high general and cardiac safety with no negative effect on cardiac troponin (TnT) levels, corrected QT interval (QTc) duration, or other measured ECG parameters despite initially increased troponin levels, the patient's advanced age, the burden of a severe somatic disease and its treatment (anticancer therapy).

  2. Diagnosis and treatment of cardiac echinococcosis.

    PubMed

    Kahlfuß, Sascha; Flieger, Robert Rainer; Roepke, Torsten Kai; Yilmaz, Kadir

    2016-09-01

    Cardiac echinococcosis is a rare manifestation of cystic echinococcosis (CE) caused by the tapeworm Echinococcus granulosus Among all patients suffering from CE, only 0.5%-2% exhibit a cardiac involvement. In addition, during the past years the number of CE cases reported in Western Europe remained roughly unchanged. However, we postulate that cases of CE in Western Europe will increase due to a growing number of refugees coming from endemic areas such as Southern Europe, Eastern Europe and the Middle East. Importantly, although cardiac echinococcosis is rare the disease can lead to many clinical complications, for instance acute heart failure and life-threatening arrhythmias. With respect to the increasing relevance of