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Sample records for acute cardiac death

  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. 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.

  3. 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

  4. 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

  5. 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.

  6. Sudden Cardiac Death in Athletes.

    PubMed

    Wasfy, Meagan M; Hutter, Adolph M; Weiner, Rory B

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  7. Sudden Cardiac Death in Athletes

    PubMed Central

    Wasfy, Meagan M.; Hutter, Adolph M.; Weiner, Rory B.

    2016-01-01

    There are clear health benefits to exercise; even so, patients with cardiac conditions who engage in exercise and athletic competition may on rare occasion experience sudden cardiac death (SCD). This article reviews the epidemiology and common causes of SCD in specific athlete populations. There is ongoing debate about the optimal mechanism for SCD prevention, specifically regarding the inclusion of the ECG and/or cardiac imaging in routine preparticipation sports evaluation. This controversy and contemporary screening recommendations are also reviewed. PMID:27486488

  8. Sudden cardiac death in athletes.

    PubMed

    Schmied, C; Borjesson, M

    2014-02-01

    A 'paradox of sport' is that in addition to the undisputed health benefits of physical activity, vigorous exertion may transiently increase the risk of acute cardiac events. In general, the risk of sudden cardiac death (SCD) approximately doubles during physical activity and is 2- to 3-fold higher in athletes compared to nonathletes. The incidence of SCD in young athletes is in fact very low, at around 1-3 per 100,000, but attracts much public attention. Variations in incidence figures may be explained by the methodology used for data collection and more importantly by differences between subpopulations of athletes. The incidence of SCD in older (≥ 35 years) athletes is higher and may be expected to rise, as more and older individuals take part in organized sports. SCD is often the first clinical manifestation of a potentially fatal underlying cardiovascular disorder and usually occurs in previously asymptomatic athletes. In the young (<35 years), SCD is mainly due to congenital/inherited cardiac abnormalities, whilst coronary artery disease (CAD) is the most common cause in older athletes. Cardiac screening including family/personal history, physical examination and resting electrocardiogram (ECG) may identify individuals at risk and has the potential to decrease the risk of SCD in young athletes. Screening including the ECG has a high sensitivity for underlying disease in young athletes, but the specificity needs to be improved, whereas the sensitivity of screening without the use of ECG is very low. The screening modality recommended for young athletes is of limited value in older athletes, who should receive individualized screening with cardiac stress testing for patients with high risk of underlying CAD. As cardiovascular screening will never be able to identify all athletes at risk, adequate preparedness is vital in case of a potentially fatal event at the sporting arena/facility. Firstly, we will review the magnitude of the problem of SCD in athletes of

  9. Cardiac Innervation and Sudden Cardiac Death

    PubMed Central

    Fukuda, Keiichi; Kanazawa, Hideaki; Aizawa, Yoshiyasu; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2015-01-01

    Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem and higher centers) which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes-hours) and long term (days-years). This important neurovisceral /autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death (SCD). Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extra-cardiac neural remodeling have also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provides a rational mechanistic basis for development of neuraxial therapies for preventing SCD and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention. PMID:26044253

  10. Sudden cardiac death from the perspective of coronary artery disease.

    PubMed

    Sara, Jaskanwal D; Eleid, Mackram F; Gulati, Rajiv; Holmes, David R

    2014-12-01

    Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death. PMID:25440727

  11. Sudden cardiac death risk stratification.

    PubMed

    Deyell, Marc W; Krahn, Andrew D; Goldberger, Jeffrey J

    2015-06-01

    Arrhythmic sudden cardiac death (SCD) may be caused by ventricular tachycardia/fibrillation or pulseless electric activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our healthcare and research resources to tackle this important public health issue. Although our understanding of SCD because of pulseless electric activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-ventricular tachycardia/ventricular fibrillation. This review focuses on existing and novel risk stratification tools for SCD-ventricular tachycardia/ventricular fibrillation. For patients with left ventricular dysfunction or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-ventricular tachycardia/ventricular fibrillation occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized.

  12. Sudden Cardiac Death Risk Stratification

    PubMed Central

    Deyell, Marc W.; Krahn, Andrew D.; Goldberger, Jeffrey J.

    2015-01-01

    Arrhythmic sudden cardiac death (SCD) may be due to ventricular tachycardia/fibrillation (SCD-VT/VF) or pulseless electrical activity/asystole. Effective risk stratification to identify patients at risk of arrhythmic SCD is essential for targeting our health care and research resources to tackle this important public health issue. Although our understanding of SCD due to pulseless electrical activity/asystole is growing, the overwhelming majority of research in risk stratification has focused on SCD-VT/VF. This review focuses on existing and novel risk stratification tools for SCD-VT/VF. For patients with left ventricular dysfunction and/or myocardial infarction, advances in imaging, measures of cardiac autonomic function, and measures of repolarization have shown considerable promise in refining risk. Yet the majority of SCD-VT/VF occurs in patients without known cardiac disease. Biomarkers and novel imaging techniques may provide further risk stratification in the general population beyond traditional risk stratification for coronary artery disease alone. Despite these advances, significant challenges in risk stratification remain that must be overcome before a meaningful impact on SCD can be realized. PMID:26044247

  13. Sudden cardiac death – Historical perspectives

    PubMed Central

    Abhilash, S.P.; Namboodiri, Narayanan

    2014-01-01

    Sudden cardiac death (SCD) is an unexpected death due to cardiac causes that occurs in a short time period (generally within 1 h of symptom onset) in a person with known or unknown cardiac disease. It is believed to be involved in nearly a quarter of human deaths, with ventricular fibrillation being the most common mechanism. It is estimated that more than 7 million lives per year are lost to SCD worldwide. Historical perspectives of SCD are analyzed with a brief description on how the developments in the management of sudden cardiac arrest evolved over time. PMID:24568828

  14. Athletes at Risk for Sudden Cardiac Death

    ERIC Educational Resources Information Center

    Subasic, Kim

    2010-01-01

    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to…

  15. 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.

  16. 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.

  17. Athletes at risk for sudden cardiac death.

    PubMed

    Subasic, Kim

    2010-02-01

    High school athletes represent the largest group of individuals affected by sudden cardiac death, with an estimated incidence of once or twice per week. Structural cardiovascular abnormalities are the most frequent cause of sudden cardiac death. Athletes participating in basketball, football, track, soccer, baseball, and swimming were found to have the highest incidence of sudden cardiac death. Screening of athletes prior to participation in competitive sports usually falls short of recommended guidelines. Poorly defined legislation and the absence of a national standard for sports physicals have contributed to inadequate health screenings of athletes. This article will describe the incidence and causes of sudden cardiovascular death in young athletes as well as guidelines intended to prevent this unfortunate problem.

  18. 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.

  19. Racial differences in sudden cardiac death.

    PubMed

    Fender, Erin A; Henrikson, Charles A; Tereshchenko, Larisa

    2014-01-01

    There is an increased risk of sudden cardiac death (SCD) and sudden cardiac arrest (SCA), in African Americans, the basis of which is likely multifactorial. African Americans have higher rates of traditional cardiac risk factors including hypertension, left ventricular hypertrophy, diabetes, coronary heart disease, and heart failure. There are also significant disparities in health care delivery. While these factors undoubtedly affect health outcomes, there is also growing evidence that genetics may have a significant impact as well. In this paper, we discuss data and hypotheses in support of both sides of the controversy around racial differences in SCD/SCA.

  20. Pathological view of sudden cardiac death.

    PubMed Central

    Davies, M J

    1981-01-01

    The common cause of sudden cardiac death is ischaemic heart disease. Such patients may have an occlusive recent thrombosis in a major coronary artery but the largest group has no recent occlusion. Comparison of such patients without occlusion with non-cardiac death control hearts suggests that an area of stenosis of 85 per cent is the best discriminating level. Most subjects who die of ischaemic heart disease suddenly have this degree of stenosis in two or three major arteries. Non-ischaemic sudden cardiac death occurs in hypertrophic obstructive cardiomyopathy and in severe left ventricular hypertrophy particularly from aortic valve stenosis. When the heart is macroscopically normal, review of previous electrocardiograms is the most helpful guide and may disclose conditions such as a long QT interval or pre-excitation. When no such data are available examination of the conduction system histologically may be helpful but is often non-specific. Use of the term "cardiomyopathy" by pathologists to cover all non-ischaemic sudden cardiac death is clinically misleading. PMID:6450599

  1. Dying, sudden cardiac death and resuscitation technology.

    PubMed

    Walker, Wendy M

    2008-04-01

    Many nurses will be familiar with the demanding role of caring for a patient who requires cardiopulmonary resuscitation following a sudden, life-threatening illness or event. This paper examines the phenomenon of sudden cardiac death and in particular, focuses on the medical-technical discourse of dying and death in the context of resuscitation for the victims of sudden cardiac arrest. The process of dying is distinguished from the end point of death by drawing upon biomedical determinants and definitions of death. Comparison is made between the use of resuscitation techniques in an attempt to reverse 'clinical death' and the notion of a 'natural death' that is proffered as a means to a 'good' or 'ideal' death. The humanistic versus technological imperative is further deliberated by examining the role of the emergency team in end of life care and includes consideration of the effects that medical dominance may have on the dying process. The practice of family witnessed resuscitation is recognised as one way in which a holistic approach to emergency resuscitative care may be achieved.

  2. 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

  3. Secondary prevention of sudden cardiac death.

    PubMed

    Curnis, Antonio; Mascioli, Giosuè; Bontempi, Luca; Bordonali, Tania; Dei Cas, Livio

    2005-03-01

    Sudden cardiac death is still the largest cause of natural death in western countries, especially in patients with coronary artery disease and in those who have already experienced an episode of resuscitated out-of-hospital cardiac arrest or ventricular tachycardia. Prevention of arrhythmia recurrences (i.e. secondary prevention) in these patients remains a challenge for the cardiologist. To date no studies have demonstrated that drug therapy can be of some value in preventing arrhythmia recurrences or sudden death in these patients, and only cardioverter-defibrillator (ICD) implantation resulted effective in reducing mortality rate. It remains, however, to be defined which patients who survived an out-of-hospital cardiac arrest or who already experienced a sustained ventricular tachycardia could benefit the most from an ICD, but to date no invasive or non-invasive tests have proven to be effective for this stratification. Vaughan-Williams class II and III drugs could be of some value in reducing tachycardia cycle length thus increasing antitachycardia pacing efficacy and reducing ICD shocks.

  4. Sudden cardiac death after modified electroconvulsive therapy.

    PubMed

    Wang, Zhihui; Wang, Jiyu

    2015-10-01

    Sudden deaths associated with the use of electroconvulsive therapy are rare. In this case report a 58-year-old male with a 20-year history of bipolar disorder and no history or signs of cardiac illness died from cardiac arrest within one hour of receiving an initial session of modified electroconvulsive therapy (MECT) to treat a recurrent episode of non-psychotic mania. The patient regained consciousness and was medically stable immediately after the MECT session (which did not produce a convulsion) but deteriorated rapidly after transfer to the recovery room. It was not possible to conduct an autopsy, but the authors surmise that the most probable cause was that the use of haloperidol 17 hours prior to MECT exacerbated the cardiac effects of nonconvulsive MECT. The case highlights the need for a thorough cardiac work-up on patients being considered for MECT (possibly including assessment of cardiac enzymes in older individuals) and careful consideration of the concurrent use of antipsychotic medications and MECT.

  5. The Debate in Cuba's Scientific Community on Sudden Cardiac Death.

    PubMed

    Vilches, Ernesto; Ochoa, Luis A; Ramos, Lianne

    2015-10-01

    Sudden cardiac death poses a challenge to modern medicine because of its high incidence, the unexpected and dramatic nature of the event, and years of potential life lost. What's more, despite modest decreases in global mortality attributed to cardiovascular diseases, incidence of sudden cardiac death has not declined. Cuba, like most of the Americas, suffers from knowledge gaps that hamper adequate strategies to address sudden cardiac death as a population health problem. We suggest that a generally accepted operational definition of sudden cardiac death be agreed upon, and a national registry developed that recognizes this cause of death on death certificates. These two actions will enable Cuba's public health authorities to assess the extent of the problem and to design intervention strategies for the population with intermediate and lower cardiovascular risk, the group in which most cases occur. KEYWORDS Sudden cardiac death, cardiovascular disease, sudden death, sudden cardiac arrest, risk reduction, prevention and control, Cuba.

  6. Sudden cardiac death athletes: a systematic review

    PubMed Central

    2010-01-01

    Previous events evidence that sudden cardiac death (SCD) in athletes is still a reality and it keeps challenging cardiologists. Considering the importance of SCD in athletes and the requisite for an update of this matter, we endeavored to describe SCD in athletes. The Medline (via PubMed) and SciELO databases were searched using the subject keywords "sudden death, athletes and mortality". The incidence of SCD is expected at one case for each 200,000 young athletes per year. Overall it is resulted of complex dealings of factors such as arrhythmogenic substrate, regulator and triggers factors. In great part of deaths caused by heart disease in athletes younger than 35 years old investigations evidence cardiac congenital abnormalities. Athletes above 35 years old possibly die due to impairments of coronary heart disease, frequently caused by atherosclerosis. Myocardial ischemia and myocardial infarction are responsible for the most cases of SCD above this age (80%). Pre-participatory athletes' evaluation helps to recognize situations that may put the athlete's life in risk including cardiovascular diseases. In summary, cardiologic examinations of athletes' pre-competition routine is an important way to minimize the risk of SCD. PMID:20682064

  7. Risk stratification for sudden cardiac death.

    PubMed

    Sabir, Ian N; Usher-Smith, Juliet A; Huang, Christopher L-H; Grace, Andrew A

    2008-01-01

    Recent advances in pharmacological and device-based therapies have provided a range of management options for patients at risk of sudden cardiac death (SCD). Since all such interventions come with their attendant risks, however, stratification procedures aimed at identifying those who stand to benefit overall have gained a new degree of importance. This review assesses the value of risk stratification measures currently available in clinical practice, as well as of others that may soon enter the market. Parameters that may be obtained only by performing invasive cardiac catheterisation procedures are considered separately from those that may be derived using more readily available non-invasive techniques. It is concluded that effective stratification is likely to require the use of composite parameters and that invasive procedures might only be justified in specific sub-groups of patients.

  8. Risk stratification for sudden cardiac death.

    PubMed

    Sabir, Ian N; Usher-Smith, Juliet A; Huang, Christopher L-H; Grace, Andrew A

    2008-01-01

    Recent advances in pharmacological and device-based therapies have provided a range of management options for patients at risk of sudden cardiac death (SCD). Since all such interventions come with their attendant risks, however, stratification procedures aimed at identifying those who stand to benefit overall have gained a new degree of importance. This review assesses the value of risk stratification measures currently available in clinical practice, as well as of others that may soon enter the market. Parameters that may be obtained only by performing invasive cardiac catheterisation procedures are considered separately from those that may be derived using more readily available non-invasive techniques. It is concluded that effective stratification is likely to require the use of composite parameters and that invasive procedures might only be justified in specific sub-groups of patients. PMID:19351522

  9. Sudden cardiac death: epidemiology and risk factors

    PubMed Central

    Adabag, A. Selcuk; Luepker, Russell V.; Roger, Véronique L.; Gersh, Bernard J.

    2016-01-01

    Sudden cardiac death (SCD) is an important public-health problem with multiple etiologies, risk factors, and changing temporal trends. Substantial progress has been made over the past few decades in identifying markers that confer increased SCD risk at the population level. However, the quest for predicting the high-risk individual who could be a candidate for an implantable cardioverter-defibrillator, or other therapy, continues. In this article, we review the incidence, temporal trends, and triggers of SCD, and its demographic, clinical, and genetic risk factors. We also discuss the available evidence supporting the use of public-access defibrillators. PMID:20142817

  10. Risk stratification for sudden cardiac death

    PubMed Central

    Cutler, Michael J; Rosenbaum, David S.

    2009-01-01

    The proportion of cardiovascular deaths attributable to sudden cardiac death (SCD) is on the rise. Herein lies the rationale for developing risk stratification strategies to predict who will benefit from prophylactic ICD implantation. Current guidelines recommend prophylactic ICD therapy in patients with reduced left ventricular ejection fraction (LVEF). However, there are clear limitations in using LVEF alone to decide who should receive an ICD. There is mounting evidence that microvolt-level T wave alternans (TWA) is an important marker of arrhythmic risk. TWA is appealing because it non-invasively probes underlying electrophysiological substrate and has been linked to cellular mechanisms for arrhythmias. This review considers the clinical role of TWA for risk stratification of SCD. PMID:19631909

  11. Stroke and cardiac cell death: Two peas in a pod.

    PubMed

    Gonzales-Portillo, Chiara; Ishikawa, Hiroto; Shinozuka, Kazutaka; Tajiri, Naoki; Kaneko, Yuji; Borlongan, Cesar V

    2016-03-01

    A close pathological link between stroke brain and heart failure may exist. Here, we discuss relevant laboratory and clinical reports demonstrating neural and cardiac myocyte cell death following ischemic stroke. Although various overlapping risk factors exist between cerebrovascular incidents and cardiac incidents, stroke therapy has largely neglected the cardiac pathological consequences. Recent preclinical stroke studies have implicated an indirect cell death pathway, involving toxic molecules, that originates from the stroke brain and produces cardiac cell death. In concert, previous laboratory reports have revealed a reverse cell death cascade, in that cardiac arrest leads to ischemic cell death in the brain. A deeper understanding of the crosstalk of cell death pathways between stroke and cardiac failure will facilitate the development of novel treatments designed to arrest the global pathology of both diseases thereby improving the clinical outcomes of patients diagnosed with stroke and heart failure.

  12. Cardiac ganglionitis associated with sudden unexpected death.

    PubMed

    James, T N; Zipes, D P; Finegan, R E; Eisele, J W; Carter, J E

    1979-11-01

    In a postmortem study of the hearts of two young women who died suddenly and unexpectedly, we found a remarkably similar and distinctive ganglionitis, predominantly in the region of the sinus node. Both women had ventricular fibrillation at the time of collapse. Vesicular neuritis and older neural degeneration were present in other regions of the heart. Except for focal fibromuscular dysplasia of the sinus node artery and atrioventricular node artery of one heart, there was no other significant anatomic abnormality in either heart. The functional significance of this cardiac ganglionitis is unclear, but its location in and around the conduction system makes it a possible cause of the fatal electrical instability. Recognition that ganglionitis of the heart may be associated with sudden death should stimulate a number of additionally useful studies.

  13. Acute stress cardiomyopathy and deaths associated with electronic weapons.

    PubMed

    Cevik, Cihan; Otahbachi, Mohammad; Miller, Elizabeth; Bagdure, Satish; Nugent, Kenneth M

    2009-03-01

    Deaths associated with the use of electronic weapons almost always occur in young men involved in either civil disturbances or criminal activity. These situations are associated with high levels of circulating catecholamines and frequently associated with drug intoxication. The mechanism for these deaths is unclear. Clinical studies indicate that these high voltage electrical pulses do not cause cardiac arrhythmia. Acute stress cardiomyopathy provides an alternative explanation for deaths associated with electronic weapons and may provide a better explanation for the usual time course associated with taser deaths. Patients with acute stress cardiomyopathy usually have had an emotional or physical stress, have high circulating levels of catecholamines, present with an acute coronary syndrome but have normal coronary vessels without significant thrombus formation. They have unusual left ventricular dysfunction with so-called apical ballooning. This presentation has been attributed to the direct effects of catecholamines on myocardial cell function. Alternative explanations include vasospasm in the coronary microcirculation and/or acute thrombosis followed by rapid thrombolysis. Similar events could occur during the high stress situations associated with the use of electronic weapons. These events also likely explain restraint-related deaths which occur in independent of any use of electronic weapons. Forensic pathologists have the opportunity to provide important details about the pathogenesis of these deaths through histological studies and careful evaluation of coronary vessels.

  14. Sudden unexpected death, epilepsy and familial cardiac pathology.

    PubMed

    Eastaugh, A J; Thompson, T; Vohra, J K; O'Brien, T J; Winship, I

    2015-10-01

    We evaluated the prevalence of epilepsy in a cohort of patients who suffered a sudden unexpected death (SUDEP), and determined the proportion of the deaths that were related to an identifiable underlying familial cardiac pathology. Epilepsy is common in people who experience a sudden unexpected death, with approximately a quarter having identifiable familial electrophysiological abnormalities. Familial cardiac pathology may be an important cause of SUDEP. A retrospective evaluation was performed of 74 families that were referred to the Royal Melbourne Hospital Cardiac Genetic Clinic over a 5 year period for investigation following a family member's sudden, presumed cardiac, death. This state-wide referral clinic includes all patients who have died from a sudden unexpected death in whom the cause of death is unascertained. An epilepsy diagnosis was categorised as either definite, probable, possible or unlikely. The family members underwent comprehensive clinical evaluations and investigations in an attempt to identify a familial cardiac cause for the sudden unexpected death. Our findings suggest that systematic referral to a cardiac genetics service is warranted for the first degree relatives of people with epilepsy who experience a sudden unexplained death, for further evaluation and to identify those who are at higher risk for sudden death. Interventions may then be instituted to potentially reduce this risk.

  15. [Sudden cardiac death in individuals with normal hearts: an update].

    PubMed

    González-Melchor, Laila; Villarreal-Molina, Teresa; Iturralde-Torres, Pedro; Medeiros-Domingo, Argelia

    2014-01-01

    Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event.

  16. [Sudden cardiac death in individuals with normal hearts: an update].

    PubMed

    González-Melchor, Laila; Villarreal-Molina, Teresa; Iturralde-Torres, Pedro; Medeiros-Domingo, Argelia

    2014-01-01

    Sudden death (SD) is a tragic event and a world-wide health problem. Every year, near 4-5 million people experience SD. SD is defined as the death occurred in 1h after the onset of symptoms in a person without previous signs of fatality. It can be named "recovered SD" when the case received medical attention, cardiac reanimation effective defibrillation or both, surviving the fatal arrhythmia. Cardiac channelopathies are a group of diseases characterized by abnormal ion channel function due to genetic mutations in ion channel genes, providing increased susceptibility to develop cardiac arrhythmias and SD. Usually the death occurs before 40 years of age and in the autopsy the heart is normal. In this review we discuss the main cardiac channelopathies involved in sudden cardiac death along with current management of cases and family members that have experienced such tragic event. PMID:25128006

  17. Sudden cardiac death in adults: causes, incidence and interventions.

    PubMed

    Walker, Wendy Marina

    Many nurses will be familiar with the unexpected death of an adult patient following a sudden, life-threatening cardiac event. It is a situation that demands sensitive nursing care and skilled interventions to provide a foundation for recovery and promote healthy bereavement. This article examines the causes and incidence of sudden cardiac death in adults. Possible reactions of those who are suddenly bereaved are described and immediate care interventions aimed at dealing with the grief process are discussed. The article concludes by identifying ways in which the incidence of sudden cardiac death may be reduced.

  18. 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

  19. 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

  20. [EPIDEMIOLOGY OF SUDDEN CARDIAC DEATH: DATA FROM THE PARIS SUDDEN DEATH EXPERTISE CENTER REGISTRY].

    PubMed

    Jouven, Xavier; Bougouin, Wulfran; Karam, Nicole; Marijon, Eloi

    2015-09-01

    Sudden cardiac death is an unexpected cardiac arrest without obvious extra-cardiac cause. Epidemiology of sudden cardiac death has been poorly documented in France, mainly because of challenging requirement in order to capture all cases in a specific area. The Parisian registry (Sudden Death Expertise Center, European Georges Pompidou Hospital, Paris) was initiated in May 2011 and analyzed data of all sudden death in Paris and suburbs (6.6 millions inhabitants). Over 3 years, the annual incidence estimated to 50-70 per 100,000. Those occurred mainly in men (69%), with a mean age of 65 year, and at home (75%). The event was witnessed in 80% of cases, but bystander cardiopulmonary resuscitation was initiated in only half of cases. Initial cardiac rhythm was ventricular fibrillation in 25%. Survival to hospital discharge remains low (8%).

  1. Mechanisms of Sudden Cardiac Death: Oxidants and Metabolism

    PubMed Central

    Yang, Kai-Chien; Kyle, John W.; Makielski, Jonathan C.; Dudley, Samuel C.

    2015-01-01

    Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. As conventional anti-arrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD. PMID:26044249

  2. Sudden cardiac death in 13 captive chimpanzees (Pan troglodytes).

    PubMed

    Lammey, Michael L; Lee, D Rick; Ely, John J; Sleeper, Meg M

    2008-02-01

    Sudden cardiac death (SCD), presumed secondary to fatal arrhythmias, is a common cause of mortality in captive chimpanzees at the Alamogordo Primate Facility. Over the 6-year period at the Alamogordo Primate Facility between 2001 and 2006, 13 animals were defined as sudden cardiac death (11 male and 2 female) on the basis of clinical presentation which was 38% of all deaths. All animals had annual physical exams, including electrocardiograms and serial blood pressures. Six of the 13 animals underwent a complete cardiac evaluation by a veterinary cardiologist and all six of these animals were diagnosed with various degrees of cardiomyopathy. Systemic hypertension was noted in two of the 13 cases and antemortem cardiac arrhythmias were seen in all 13 animals. Histological examination of the hearts revealed myocardial fibrosis in 12 chimpanzees. Most of the animals (10/13) that died of sudden cardiac death had cardiomegaly (increased heart weight/body weight ratio) and some degree of myocardial fibrosis noted. Additional data as well as serial diagnostic evaluations will be needed to identify the possible causes of sudden cardiac death in captive chimpanzees. PMID:18269527

  3. [Sudden cardiac death in non-professional athletes].

    PubMed

    Nappo, A; Varesi, C; Rossi, L; Matturri, L

    1997-10-01

    Sudden death during sports activities in non-professional athletes is a rare occurrence, however it is of great interest in clinical pathology and forensic medicine. We performed chemico-toxicologic and histopathologic investigations in three cases of sudden cardiac death in non-professional athletes, focusing in particular on the cardiac conduction system. Examination of conduction tissue was performed on sections seriated every 150 microns, stained alternately with hematoxylin-eosin and Heidenhain's trichrome (azan). In all three cases diagnostic evidence showed hyperacute myocardial infarction, due to spasm of coronaries with mild atherosclerosis, and myocardial lesions due to reperfusive necrosis. The pathogenesis of sudden death in young athletes is not related only to ischemic-coronary damage that is not exclusively mechanical, but also a dynamic event (spasm and reperfusion), but also to fatal arrhythmias related to abnormal findings in the conduction system. Such findings can therefore be considered the morphologic substrate of sudden cardiac death.

  4. CAP2 in cardiac conduction, sudden cardiac death and eye development.

    PubMed

    Field, Jeffrey; Ye, Diana Z; Shinde, Manasi; Liu, Fang; Schillinger, Kurt J; Lu, MinMin; Wang, Tao; Skettini, Michelle; Xiong, Yao; Brice, Angela K; Chung, Daniel C; Patel, Vickas V

    2015-11-30

    Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2(-)/cap2(-) males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2(-)/cap2(-) females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease.

  5. CAP2 in cardiac conduction, sudden cardiac death and eye development

    PubMed Central

    Field, Jeffrey; Ye, Diana Z.; Shinde, Manasi; Liu, Fang; Schillinger, Kurt J.; Lu, MinMin; Wang, Tao; Skettini, Michelle; Xiong, Yao; Brice, Angela K.; Chung, Daniel C.; Patel, Vickas V.

    2015-01-01

    Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2−/cap2− males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2−/cap2− females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease. PMID:26616005

  6. The Spectrum of Epidemiology Underlying Sudden Cardiac Death

    PubMed Central

    Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M.

    2015-01-01

    Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15–20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who suffer a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly due to inherited disorders. Coronary heart disease (CHD) is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. Over the past three decades, declines in SCD rates have not been as steep as for other causes of CHD deaths, and there is a growing fraction of SCDs not due to CHD and/or ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition prior to death. Multifaceted preventative approaches, which address risk factors in seemingly low risk and known high-risk populations will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies. PMID:26044246

  7. The spectrum of epidemiology underlying sudden cardiac death.

    PubMed

    Hayashi, Meiso; Shimizu, Wataru; Albert, Christine M

    2015-06-01

    Sudden cardiac death (SCD) from cardiac arrest is a major international public health problem accounting for an estimated 15%-20% of all deaths. Although resuscitation rates are generally improving throughout the world, the majority of individuals who experience a sudden cardiac arrest will not survive. SCD most often develops in older adults with acquired structural heart disease, but it also rarely occurs in the young, where it is more commonly because of inherited disorders. Coronary heart disease is known to be the most common pathology underlying SCD, followed by cardiomyopathies, inherited arrhythmia syndromes, and valvular heart disease. During the past 3 decades, declines in SCD rates have not been as steep as for other causes of coronary heart disease deaths, and there is a growing fraction of SCDs not due to coronary heart disease and ventricular arrhythmias, particularly among certain subsets of the population. The growing heterogeneity of the pathologies and mechanisms underlying SCD present major challenges for SCD prevention, which are magnified further by a frequent lack of recognition of the underlying cardiac condition before death. Multifaceted preventative approaches, which address risk factors in seemingly low-risk and known high-risk populations, will be required to decrease the burden of SCD. In this Compendium, we review the wide-ranging spectrum of epidemiology underlying SCD within both the general population and in high-risk subsets with established cardiac disease placing an emphasis on recent global trends, remaining uncertainties, and potential targeted preventive strategies.

  8. Donation after cardiac death and the emergency department: ethical issues.

    PubMed

    Simon, Jeremy R; Schears, Raquel M; Padela, Aasim I

    2014-01-01

    Organ donation after cardiac death (DCD) is increasingly considered as an option to address the shortage of organs available for transplantation, both in the United States and worldwide. The procedures for DCD differ from procedures for donation after brain death and are likely less familiar to emergency physicians (EPs), even as this process is increasingly involving emergency departments (EDs). This article explores the ED operational and ethical issues surrounding this procedure. PMID:24552527

  9. Genetics of channelopathies associated with sudden cardiac death

    PubMed Central

    Campuzano, Oscar; Sarquella-Brugada, Georgia; Brugada, Ramon; Brugada, Josep

    2015-01-01

    Recent technological advances in cardiology have resulted in new guidelines for the diagnosis, treatment and prevention of diseases. Despite these improvements, sudden death remains one of the main challenges to clinicians because the majority of diseases associated with sudden cardiac death are characterized by incomplete penetrance and variable expressivity. Hence, patients may be unaware of their illness, and physical activity can be the trigger for syncope as first symptom of the disease. Most common causes of sudden cardiac death are congenital alterations and structural heart diseases, although a significant number remain unexplained after comprehensive autopsy. In these unresolved cases, channelopathies are considered the first potential cause of death. Since all these diseases are of genetic origin, family members could be at risk, despite being asymptomatic. Genetics has also benefited from technological advances, and genetic testing has been incorporated into the sudden death field, identifying the cause in clinically affected patients, asymptomatic family members and post-mortem cases without conclusive diagnosis. This review focuses on recent advances in the genetics of channelopathies associated with sudden cardiac death. PMID:26566530

  10. 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

  11. Causes and prevention of sudden cardiac death in the elderly.

    PubMed

    Tung, Patricia; Albert, Christine M

    2013-03-01

    Sudden cardiac death (SCD) is a major cause of mortality in elderly individuals owing to a high prevalence of coronary heart disease, systolic dysfunction, and congestive heart failure (CHF). Although the incidence of SCD increases with age, the proportion of cardiac deaths that are sudden decreases owing to high numbers of other cardiac causes of death in elderly individuals. Implantable cardioverter-defibrillator (ICD) therapy has been demonstrated to improve survival and prevent SCD in selected patients with systolic dysfunction and CHF. However, ICD therapy in elderly patients might not be effective because of a greater rate of pulseless electrical activity underlying SCD and other competing nonarrhythmic causes of death in this population. Although under-represented in randomized trials of ICD use, elderly patients comprise a substantial proportion of the population that qualifies for and receives an ICD for primary prevention under current guidelines. Cardiac resynchronization therapy (CRT), which has been demonstrated to reduce mortality in selected populations with heart failure, is also more commonly used in this group of patients than in younger individuals. In this Review, we examine the causes of SCD in elderly individuals, and discuss the existing evidence for effectiveness of ICD therapy and CRT in this growing population.

  12. Sudden cardiac death secondary to antidepressant and antipsychotic drugs

    PubMed Central

    Sicouri, Serge; Antzelevitch, Charles

    2008-01-01

    A number of antipsychotic and antidepressant drugs are known to increase the risk of ventricular arrhythmias and sudden cardiac death. Based largely on a concern over QT prolongation and the development of life-threatening arrhythmias, a number of antipsychotic drugs have been temporarily or permanently withdrawn from the market or their use restricted. Some antidepressants and antipsychotics have been linked to QT prolongation and the development of Torsade de pointes arrhythmias, whereas others have been associated with a Brugada syndrome phenotype and the development of polymorphic ventricular arrhythmias. This review examines the mechanisms and predisposing factors underlying the development of cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and antipsychotic drugs in clinical use. PMID:18324881

  13. Pathophysiology of sudden cardiac death as demonstrated by molecular pathology of natriuretic peptides in the myocardium.

    PubMed

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

    2012-11-30

    Various heart diseases present with sudden death; however, it is difficult to interpret the severity of or difference in respective preexisting and terminal cardiac dysfunction based on conventional morphology. The present study investigated the cardiac pathophysiology employing quantitative mRNA measurement of atrial and brain natriuretic peptides (ANP and BNP) in the myocardium as markers of cardiac strain, using autopsy materials consisting of acute ischemic heart disease (AIHD, n=40) with/without the pathology of apparent myocardial necrosis (n=19/21), recurrent myocardial infarction (RMI, n=19), chronic congestive heart disease (CHD, n=11) and right ventricular cardiomyopathy (RVC, n=5), as well as hemopericardium (HP, n=11) due to myocardial infarction (n=5) and aortic rupture (n=6), and acute pulmonary thromboembolism (PTE, n=5). Cardiac death groups showed higher ANP and/or BNP mRNA expressions in the left ventricle than acute fatal bleeding (sharp instrumental injury; n=15) and/or mechanical asphyxiation (strangulation; n=10). AIHD and RMI cases had similar ANP and BNP mRNA expressions in bilateral ventricular walls, but their bilateral atrial levels were lower in RMI. RVC showed higher mRNA expressions of posterior left ventricular BNP, and right ventricular and bilateral atrial ANP and BNP. HP cases had lower BNP mRNA expression in the right ventricular wall, but PTE showed lower ANP and BNP mRNA expressions in the left ventricular wall; however, these mRNA expressions at other sites were similar to those of AIHD. CHD presented findings similar to those of AIHD, but the pericardial BNP level was significantly increased. These observations indicate characteristic molecular biological responses of myocardial natriuretic peptides in individual heart diseases and suggest the possible application of molecular pathology to demonstrate cardiac dysfunction even after death.

  14. Cardiac Pseudoaneurysm- A Death Defying Entity

    PubMed Central

    Gupta, Saryu

    2016-01-01

    A pseudoaneurysm refers to a contained rupture of the myocardium with a tenuous pericardium walling off the leak. It needs to be differentiated from a true aneurysm by the fact that there is lack of myocardial tissue in the wall of a pseudoaneurysm. The differentiation between the two is pertinent as true aneurysms can be treated medically while pseudoaneurysms require urgent surgical treatment. Untreated pseudoaneurysms carry a high risk of rupture and mortality. We report a case of cardiac pseudoaneurysm developing in a 46-year-old male who had suffered myocardial infarction four months back. The patient now presented with chest pain and dyspnoea. CECT chest revealed a partially thrombosed large pseudoaneurysm arising from the posterior wall of left ventricle. While the clinical diagnosis of this entity is difficult, CECT plays a pivotal role in the non-invasive detection of pseudoaneurysms. PMID:27504379

  15. Ebstein's Anomaly, Left Ventricular Noncompaction, and Sudden Cardiac Death

    PubMed Central

    McGee, Michael; Warner, Luke; Collins, Nicholas

    2015-01-01

    Ebstein's anomaly is a congenital disorder characterized by apical displacement of the septal leaflet of the tricuspid valve. Ebstein's anomaly may be seen in association with other cardiac conditions, including patent foramen ovale, atrial septal defect, and left ventricular noncompaction (LVNC). LVNC is characterized by increased trabeculation within the left ventricular apex. Echocardiography is often used to diagnose LVNC; however, magnetic resonance (MR) imaging offers superior characterization of the myocardium. We report a case of sudden cardiac death in a patient with Ebstein's anomaly with unrecognized LVNC noted on post mortem examination with screening documenting the presence of LVNC in one of the patient's twin sons. PMID:26240764

  16. Tissue and Animal Models of Sudden Cardiac Death

    PubMed Central

    Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

    2015-01-01

    Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

  17. Analyses of cardiac blood cells and serum proteins with regard to cause of death in forensic autopsy cases.

    PubMed

    Quan, Li; Ishikawa, Takaki; Michiue, Tomomi; Li, Dong-Ri; Zhao, Dong; Yoshida, Chiemi; Chen, Jian-Hua; Komatsu, Ayumi; Azuma, Yoko; Sakoda, Shigeki; Zhu, Bao-Li; Maeda, Hitoshi

    2009-04-01

    To investigate hematological and serum protein profiles of cadaveric heart blood with regard to the cause of death, serial forensic autopsy cases (n=308, >18 years of age, within 48 h postmortem) were examined. Red blood cells (Rbc), hemoglobin (Hb), platelets (Plt), white blood cells (Wbc), total protein (TP) and albumin (Alb) were examined in bilateral cardiac blood. Blood cell counts, collected after turning the bodies at autopsy, approximated to the clinical values. Postmortem changes were not significant for these markers. In non-head blunt injury cases, Rbc counts, Hb, TP and Alb levels in bilateral cardiac blood were lower in subacute deaths (survival time, 1-12 h) than in acute deaths (survival time <1 h). Wbc counts of left cardiac blood were significantly higher for non-head injury than for head injury in subacute deaths. In fire fatality cases, Plt count was markedly higher with an automated hematology analyzer than by using a blood smear test, suggesting Rbc fragmentation caused by deep burns, while increases in Wbc count and decreases in Alb levels were seen for subacute deaths. For asphyxiation, Rbc count, Hb, TP and Alb levels in bilateral cardiac blood were higher than other groups, and TP and Alb levels in the right cardiac blood were higher for hanging than for strangulation. These findings suggest that analyses of blood cells and proteins are useful for investigating the cause of death.

  18. 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

  19. Death due to acute tetrachloroethylene intoxication in a chronic abuser.

    PubMed

    Amadasi, Alberto; Mastroluca, Lavinia; Marasciuolo, Laura; Caligara, Marina; Sironi, Luca; Gentile, Guendalina; Zoja, Riccardo

    2015-05-01

    Volatile substances are used widespread, especially among young people, as a cheap and easily accessible drug. Tetrachloroethylene is one of the solvents exerting effects on the central nervous system with experiences of disinhibition and euphoria. The case presented is that of a 27-year-old female, found dead by her father at home with cotton swabs dipped in the nostrils. She was already known for this type of abuse and previously admitted twice to the hospital for nonfatal acute poisonings. The swabs were still soaked in tetrachloroethylene. Toxicological and histological investigations demonstrated the presence of an overlap between chronic intake of the substance (with high concentrations in sites of accumulation, e.g., the adipose tissue, and contemporary tissue damage, as histologically highlighted) and acute intoxication as final cause of death, with a concentration of 158 mg/L in cardiac blood and 4915 mg/kg in the adipose tissue. No other drugs or medicines were detected in body fluids or tissues, and to our knowledge, this is the highest concentration ever detected in forensic cases. This peculiar case confirms the toxicity of this substance and focuses on the importance of complete histological and toxicological investigations in the distinction between chronic abuse and acute intoxication.

  20. Death due to acute tetrachloroethylene intoxication in a chronic abuser.

    PubMed

    Amadasi, Alberto; Mastroluca, Lavinia; Marasciuolo, Laura; Caligara, Marina; Sironi, Luca; Gentile, Guendalina; Zoja, Riccardo

    2015-05-01

    Volatile substances are used widespread, especially among young people, as a cheap and easily accessible drug. Tetrachloroethylene is one of the solvents exerting effects on the central nervous system with experiences of disinhibition and euphoria. The case presented is that of a 27-year-old female, found dead by her father at home with cotton swabs dipped in the nostrils. She was already known for this type of abuse and previously admitted twice to the hospital for nonfatal acute poisonings. The swabs were still soaked in tetrachloroethylene. Toxicological and histological investigations demonstrated the presence of an overlap between chronic intake of the substance (with high concentrations in sites of accumulation, e.g., the adipose tissue, and contemporary tissue damage, as histologically highlighted) and acute intoxication as final cause of death, with a concentration of 158 mg/L in cardiac blood and 4915 mg/kg in the adipose tissue. No other drugs or medicines were detected in body fluids or tissues, and to our knowledge, this is the highest concentration ever detected in forensic cases. This peculiar case confirms the toxicity of this substance and focuses on the importance of complete histological and toxicological investigations in the distinction between chronic abuse and acute intoxication. PMID:25605280

  1. Sudden cardiac death markers in non-ischemic cardiomyopathy.

    PubMed

    Pimentel, Mauricio; Rohde, Luis Eduardo; Zimerman, André; Zimerman, Leandro Ioschpe

    2016-01-01

    Heart failure is an increasingly prevalent disease associated with high morbidity and mortality. In 30-40% of patients, the etiology is non-ischemic. In this group of patients, the implantable cardioverter-defibrillator (ICD) prevents sudden death and decreases total mortality. However, due to burden of cost, the fact that many ICD patients will never need any therapy, and possible complications involved in implant and follow-up, the device should not be implanted in every patient with non-ischemic heart failure. There is an urgent need to adequately identify patients with highest sudden death risk, in whom the implant is most cost-effective. In the present paper, the authors discuss current available tests for risk stratification of sudden cardiac death in patients with non-ischemic heart failure. PMID:27016256

  2. [Sudden cardiac death during a city marathon run].

    PubMed

    Beutler, J; Schmid, E; Fischer, S; Hürlimann, S; Konrad, C

    2015-06-01

    Sudden cardiac death (SCD) in young athletes during physical stress is a rare event with an incidence of 1-3 deaths per 100,000 athletes per year. A coronary anomaly is the second most common cause of death following hypertrophic cardiomyopathy. Symptomatic prodromes occur in 20% of cases prior to the SCD event. This case report describes a 35-year-old male who collapsed near the finishing line of a half marathon run. Despite immediate resuscitation attempts and initial return of spontaneous circulation (ROSC), a pulseless electrical activity (PEA) followed and the patient died 1 h after arrival in the resuscitation unit. The autopsy revealed an anomalous left coronary artery (ALCA), which can lead to ischemia of the respective heart muscles under severe stress.

  3. 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.

  4. Genetic etiology and evaluation of sudden cardiac death.

    PubMed

    Dolmatova, Elena; Mahida, Saagar; Ellinor, Patrick T; Lubitz, Steven A

    2013-08-01

    A wide range of inherited syndromes can result in ventricular arrhythmias and sudden cardiac death (SCD). The natural histories of inherited arrhythmia syndromes are highly variable and current risk stratification techniques are limited. Thus, the management of these conditions can be difficult and often involves a combination of risk assessment, lifestyle modification, cardiac interventions, counselling, and family screening. Recent advances in high throughput sequencing have enabled routine testing in patients with a high clinical index of suspicion for an inherited arrhythmia condition, and cascade screening in relatives of mutation carriers. Given the complexity in screening and data interpretation that has been introduced by recent genomic advances, individuals with inherited arrhythmia syndromes are encouraged to seek care at specialized centers with cardiovascular genetics expertise. In this review, we discuss the etiologies of SCD syndromes and discuss strategies for the evaluation of patients at risk for SCD with a focus on the role of genetic testing and family screening. PMID:23812838

  5. Cell Death and DAMPs in Acute Pancreatitis

    PubMed Central

    Kang, Rui; Lotze, Michael T; Zeh, Herbert J; Billiar, Timothy R; Tang, Daolin

    2014-01-01

    Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP. Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP. DAMPs might be an attractive therapeutic target in AP. PMID:25105302

  6. Nonlinear dynamics, fractals, cardiac physiology and sudden death

    NASA Technical Reports Server (NTRS)

    Goldberger, Ary L.

    1987-01-01

    The authors propose a diametrically opposite viewpoint to the generally accepted tendency of equating healthy function with order and disease with chaos. With regard to the question of sudden cardiac death and chaos, it is suggested that certain features of dynamical chaos related to fractal structure and fractal dynamics may be important organizing principles in normal physiology and that certain pathologies, including ventricular fibrillation, represent a class of 'pathological periodicities'. Some laboratory work bearing on the relation of nonlinear analysis to physiological and pathophysiological data is briefly reviewed, with tentative theories and models described in reference to the mechanism of ventricular fibrillation.

  7. Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

    PubMed Central

    Naesgaard, Patrycja A.; León De La Fuente, Ricardo A.; Nilsen, Stein Tore; Woie, Leik; Aarsland, Torbjoern; Brede, Cato; Staines, Harry; Nilsen, Dennis W. T.

    2012-01-01

    Background Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum. Methods We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis. Results There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release. Conclusion Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS. Trial registration ClinicalTrials.gov NCT01377402 PMID:22970121

  8. [Sudden cardiac death in acromegaly. Anatomopathological observation of a case].

    PubMed

    Matturri, L; Varesi, C; Nappo, A; Cuttin, M S; Rossi, L

    1998-01-01

    Involvement of the cardiovascular system in patients affected by acromegaly is an important factor in morbidity and mortality. The diagnosis in these subjects is acromegalic cardiomyopathy with cardiac decompensation, arrhythmias and sudden death. The pathologic substrate has rarely been described. The present study reports the findings in a case of sudden death in a 54-year-old man, affected by acromegaly. Subsequent diagnostic investigation revealed the characteristic aspects of acromegalic cardiomyopathy in the common myocardium and the presence of hyperacute myocardial infarct of the antero-septal wall of the left ventricle. Examination of conduction tissue revealed slight fibrolipomatosis and dispersion of the atrio-ventricular node (AVN), which extended to the His bundle and bifurcation. The right branch was prematurely intramural with sclerosis and lipomatosis. This location in atrio-ventricular conduction system has seldom been reported in the literature and if so, with different lesions from those found in the case we investigated. The results of microscopic examination convalidate the hypothesis of electrical instability in the heart, as confirmed by the subject's history of ventricular extrasystoles, left branch block and attacks of angina after effort. Death was correlated to hyperacute myocardial infarction of the anteroseptal wall of the left ventricle, in a subject with history of angina, affected by acromegalic cardiomegaly and electric instability. In this case, sudden death could also be considered arrhythmogenic in relation to the additional workload by persistent hormonal stimulation.

  9. Sudden cardiac death in haemodialysis patients: preventative options.

    PubMed

    Chiu, Diana Yuan Yng; Sinha, Smeeta; Kalra, Philip A; Green, Darren

    2014-12-01

    Sudden cardiac death (SCD) is the most common cause of death in haemodialysis patients, accounting for 25% of all-cause mortality. There are many potential pathological precipitants as most patients with end-stage renal disease have structurally or functionally abnormal hearts. For example, at initiation of dialysis, 74% of patients have left ventricular hypertrophy. The pathophysiological and metabolic milieu of patients with end-stage renal disease, allied to the regular stresses of dialysis, may provide the trigger to a fatal cardiac event. Prevention of SCD can be seen as a legitimate target to improve survival in this patient group. In the general population, this is most effective by reducing the burden of ischaemic heart disease. However, the aetiology of SCD in haemodialysis patients appears to be different, with myocardial fibrosis, vascular calcification and autonomic dysfunction implicated as possible causes. Thus, the range of therapies is different to the general population. There are potential preventative measures emerging as our understanding of the underlying mechanisms progresses. This article aims to review the evidence for therapies to prevent SCD effective in the general population when applied to dialysis patients, as well as promising new treatments specific to this population group.

  10. Ibogaine-associated cardiac arrest and death: case report and review of the literature

    PubMed Central

    Meisner, Jessica A.; Wilcox, Susan R.; Richards, Jeremy B.

    2016-01-01

    A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine’s clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

  11. Ibogaine-associated cardiac arrest and death: case report and review of the literature.

    PubMed

    Meisner, Jessica A; Wilcox, Susan R; Richards, Jeremy B

    2016-04-01

    A naturally occurring hallucinogenic plant alkaloid, ibogaine has been used as an adjuvant for opiate withdrawal for the past 50 years. In the setting of an escalating nationwide opiate epidemic, use of substances such as ibogaine may also increase. Therefore, familiarity with the mechanisms and potential adverse effects of ibogaine is important for clinicians. We present the case report of a man whose use of ibogaine resulted in cardiac arrest and death, complemented by a review of the literature regarding ibogaine's clinical effects. A 40-year-old man who used ibogaine for symptoms of heroin withdrawal suffered acute cardiac arrest leading to cerebral edema and brain death. His presentation was consistent with ibogaine-induced cardiotoxicity and ibogaine-induced cardiac arrest, and a review of the literature regarding the history, mechanisms, risks and clinical outcomes associated with ibogaine is presented. The case presented underscores the significant potential clinical risks of ibogaine. It is important the healthcare community be aware of the possible effects of ibogaine such that clinicians can provide informed counseling to their patients regarding the risks of attempting detoxification with ibogaine. PMID:27141291

  12. Ventricular fibrillation and sudden cardiac death during myocardial infarction.

    PubMed

    Jabbari, Reza

    2016-05-01

    In this PhD thesis, we report that VF is still a common complication of STEMI, with an incidence of 11.6% in the population of Danish STEMI patients who survive to reach the hospital. In this STEMI population, we identified several risk factors associated with VF independent of MI. We identified and confirmed findings from several previous studies and found several risk factors, such as younger age, a family history of sudden death, a TIMI flow grade of 0, the absence of angina, anterior infarction (i.e., VF before PPCI), and inferior infarction (i.e., VF during PPCI) that were associated with VF in a Danish cohort. Furthermore, a history of atrial fibrillation and alcohol intake were identified as novel risk factors for VF. To the best of our knowledge, this study contains data on the largest VF cohort with the longest reported follow-up published; we found that VF mortality is significantly higher within the first 30 days for patients who experience VF before and during PPCI compared with STEMI patients without VF. However, the long-term mortality rates of the three groups are the same. Importantly, our results contradict the previous understanding that VF during PPCI is "benign"; the mortality rate within the first 30 days was as high for patients with VF during PPCI as the mortality rate of patients with VF before PPCI. Finally, although it is difficult to draw clinical implications from a descriptive study, due to the comprehensiveness of Danish death certificates, we reported a high incidence of cardiac symptoms and contact with healthcare professionals based on cardiac symptoms in young SCD patients who died due to CAD, although death was not avoided. PMID:27127021

  13. Acute mesenteric ischaemia and unexpected death.

    PubMed

    Byard, Roger W

    2012-05-01

    Acute mesenteric ischaemia is a vascular emergency that arises when blood flow to the intestine is compromised leading to tissue necrosis. It is primarily a condition of the elderly associated with significant morbidity and mortality. Causes include arterial thromboembolism, venous thrombosis and splanchnic vasoconstriction (so-called nonocclusive mesenteric ischaemia). Reperfusion injury and breakdown of the intestinal mucosal barrier lead to metabolic derangements, sepsis and death from multiorgan failure. The diagnosis may be difficult to make clinically and numbers of cases are increasing due to ageing of the population. The clinical and pathological features are reviewed with discussion of predisposing conditions. Careful dissection of the mesenteric vasculature is required at autopsy with appropriate histologic sampling and documentation of associated comorbidities. Other organs need to be checked for thrombi and the possibility of testing for inherited thombophilias should be considered. Toxicological evaluation, particularly in younger individuals, may reveal evidence of cocaine use. On occasion no obstructive lesions will be demonstrated, however the confounding effects of post-mortem autolytic and putrefactive changes may mean that nonocclusive mesenteric ischaemia may be difficult to diagnose.

  14. Multiple Antioxidants Improve Cardiac Complications and Inhibit Cardiac Cell Death in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Kumar, Santosh; Prasad, Sahdeo; Sitasawad, Sandhya L.

    2013-01-01

    Diabetic cardiomyopathy, a disorder of the heart muscle in diabetic patients, is one of the major causes of heart failure. Since diabetic cardiomyopathy is now known to have a high prevalence in the asymptomatic diabetic patient, prevention at the earliest stage of development by existing molecules would be appropriate in order to prevent the progression of heart failure. In this study, we investigated the protective role of multiple antioxidants (MA), on cardiac dysfunction and cardiac cell apoptosis in streptozotocin (STZ)-induced diabetic rat. Diabetic cardiomyopathy in STZ-treated animals was characterized by declined systolic, diastolic myocardial performance, oxidative stress and apoptosis in cardiac cells. Diabetic rats on supplementation with MA showed decreased oxidative stress evaluated by the content of reduced levels of lipid per-oxidation and decreased activity of catalase with down-regulation of heme-oxygenase-1 mRNA. Supplementation with MA also resulted in a normalized lipid profile and decreased levels of pro-inflammatory transcription factor NF-kappaB as well as cytokines such as TNF-α, IFN-γ, TGF-β, and IL-10. MA was found to decrease the expression of ROS-generating enzymes like xanthine oxidase, monoamine oxidase-A along with 5-Lipoxygenase mRNA and/or protein expression. Further, left ventricular function, measured by a microtip pressure transducer, was re-established as evidenced by increase in ±dp/dtmax, heart rate, decreased blood pressure, systolic and diastolic pressure as well as decrease in the TUNEL positive cardiac cells with increased Bcl-2/Bax ratio. In addition, MA supplementation decreased cell death and activation of NF-kappaB in cardiac H9c2 cells. Based on our results, we conclude that MA supplementation significantly attenuated cardiac dysfunction in diabetic rats; hence MA supplementation may have important clinical implications in terms of prevention and management of diabetic cardiomyopathy. PMID:23843977

  15. Overexpression of KCNN3 results in sudden cardiac death

    PubMed Central

    Mahida, Saagar; Mills, Robert W.; Tucker, Nathan R.; Simonson, Bridget; Macri, Vincenzo; Lemoine, Marc D.; Das, Saumya; Milan, David J.; Ellinor, Patrick T.

    2014-01-01

    Background A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. Methods and results We characterized the cardiac electrophysiological phenotype of a mouse line with overexpression of the SK3 channel. We generated homozygote (SK3T/T) and heterozygote (SK3+/T) mice with overexpression of the channel and compared them with wild-type (WT) controls. We observed a high incidence of sudden death among SK3T/T mice (7 of 19 SK3T/T mice). Ambulatory monitoring demonstrated that sudden death was due to heart block and bradyarrhythmias. SK3T/T mice displayed normal body weight, temperature, and cardiac function on echocardiography; however, histological analysis demonstrated that these mice have abnormal atrioventricular node morphology. Optical mapping demonstrated that SK3T/T mice have slower ventricular conduction compared with WT controls (SK3T/T vs. WT; 0.45 ± 0.04 vs. 0.60 ± 0.09 mm/ms, P = 0.001). Programmed stimulation in 1-month-old SK3T/T mice demonstrated inducible atrial arrhythmias (50% of SK3T/T vs. 0% of WT mice) and also a shorter atrioventricular nodal refractory period (SK3T/T vs. WT; 43 ± 6 vs. 52 ± 9 ms, P = 0.02). Three-month-old SK3T/T mice on the other hand displayed a trend towards a more prolonged atrioventricular nodal refractory period (SK3T/T vs. WT; 61 ± 1 vs. 52 ± 6 ms, P = 0.06). Conclusion Overexpression of the SK3 channel causes an increased risk of sudden death associated with bradyarrhythmias and heart block, possibly due to atrioventricular nodal dysfunction. PMID:24296650

  16. 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.

  17. Intra-beat Scaling Properties of Cardiac Arrhythmias and Sudden Cardiac Death

    NASA Astrophysics Data System (ADS)

    Rodríguez, Eduardo; Lerma, Claudia; Echeverría, Juan C.; Alvarez-Ramirez, Jose

    2008-02-01

    We applied detrended fluctuation analysis (DFA) to characterize the intra-beat scaling dynamics of electrocardiographic (ECG) recordings from the PhysioNet Sudden Cardiac Death Holter Database. The main finding of this contribution is that, in such recordings involving different types of arrhythmias; the ECG waveform, besides showing a less-random intra-beat dynamics, becomes more regular during bigeminy, ventricular tachycardia (VT) or even atrial fibrillation (AFIB) and ventricular fibrillation (VF) despite the appearance of erratic traces. Thus, notwithstanding that these cardiac rhythm abnormalities are generally considered as irregular and some of them generated by random impulses or wavefronts, the intra-beat scaling properties suggest that regularity dominates the underlying mechanisms of arrhythmias. Among other explanations, this may result from shorted or restricted -less complex- pathways of conduction of the electrical activity within the ventricles.

  18. Cardiac and other abnormalities in the sudden infant death syndrome.

    PubMed Central

    Naeye, R. L.; Whalen, P.; Ryser, M.; Fisher, R.

    1976-01-01

    Many victims of the sudden infant death syndrome (SIDS) have abnormally heavy cardiac right ventricles. The degree of this abnormality is directly proportional to: a) the mass of muscle about small pulmonary arteries, b) the amount of brown fat retention about adrenal glands, and c) the presence of hepatic erythropoiesis. The pulmonary arterial abnormality is probably the result of chronic alveolar hypoventilation, while brown fat retention and hepatic erythropoiesis are likely consequences of chronic hypoxemia. These abnormalities are found in both SIDS victims who die with and those who die without mild respiratory tract infections. However, there are some differences between the two SIDS groups. Infected victims die at an older age and have smaller thymus glands and larger spleens; there is a greater proportion of males in the infected victims than in the noninfected victims. PMID:1247080

  19. Cardiac imaging in evaluating patients prone to sudden death

    PubMed Central

    Tamene, Ashenafi; Tholakanahalli, Venkatakrishna N.; Chandrashekhar, Y.

    2014-01-01

    Identifying subjects who are at risk for SCD and stratifying them correctly into low or high-risk groups is the holy grail of Cardiology. While imaging shows a lot of promise, it is plagued by the fact that most SCD occurs in relatively healthy subjects, a massive group who would not ordinarily be subjected to imaging. Left ventricular ejection fraction (LVEF) currently is our primary parameter for risk stratification for sudden cardiac death but is a poor marker with low sensitivity and specificity. Current data shows that sophisticated imaging with techniques, mainly Cardiac magnetic resonance Imaging (CMR), have the potential to identify novel high-risk markers underlying SCD, beyond ejection fraction. Imaging seems to further refine risk in patients with low LVEF as well as in those with normal EF; this is a major strength of advanced imaging. Clinical application has been slow and not fully prime time. It is important to remember that while promising, imaging techniques including CMR, have not been tested in rigorous prospective studies and thus have not as yet replaced EF as the gatekeeper to ICD implantation. PMID:24568832

  20. Early repolarization syndrome: A cause of sudden cardiac death

    PubMed Central

    Ali, Abdi; Butt, Nida; Sheikh, Azeem S

    2015-01-01

    Early repolarization syndrome (ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life - threatening arrhythmias and sudden cardiac death (SCD). Early repolarization characteristics associated with SCD include high - amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation (0.05 mV vs 0.1 mV) being the main determinants. ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life - threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS. PMID:26322186

  1. Sudden cardiac death: ethical considerations in the return to play.

    PubMed

    Piantanida, Nicholas A; Oriscello, Ralph G; Pettrone, Frank A; O'Connor, Francis G

    2004-04-01

    The team physician-athlete relationship prompts many basic questions in medical ethics. Return-to-play decisions form many of the core responsibilities facing team physicians, and occasionally these decisions can have overriding ethical dilemmas. Therefore, a structured ethical decision-making process is a valuable skill for every successful sports medicine physician. An ethical question is confronted here in a case presentation that weighs the risk of repeat sudden cardiac death and the potential for failed cardiac resuscitation against the athlete's interest to play competitive basketball. The article applies a four-step framework for ethical decision making in sports medicine. The important first step includes gathering medical information and understanding the preferences of the athlete. Step 2 brings together the decision-making stakeholders, the team physician as a member, to define ethical issues and apply ethical principles: beneficence, non-maleficence, and patient autonomy. Step 3 selects a course of action with unbiased analysis and arrives at a good choice that merits an action plan in step 4. This decision need not be perfect, but should reinforce the team physician's responsibilities to the athlete and center on the athlete's welfare.

  2. Cell death and serum markers of collagen metabolism during cardiac remodeling in Cavia porcellus experimentally infected with Trypanosoma cruzi.

    PubMed

    Castro-Sesquen, Yagahira E; Gilman, Robert H; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  3. Cell Death and Serum Markers of Collagen Metabolism during Cardiac Remodeling in Cavia porcellus Experimentally Infected with Trypanosoma cruzi

    PubMed Central

    Castro-Sesquen, Yagahira E.; Gilman, Robert H.; Paico, Henry; Yauri, Verónica; Angulo, Noelia; Ccopa, Fredy; Bern, Caryn

    2013-01-01

    We studied cell death by apoptosis and necrosis in cardiac remodeling produced by Trypanosoma cruzi infection. In addition, we evaluated collagen I, III, IV (CI, CIII and CIV) deposition in cardiac tissue, and their relationship with serum levels of procollagen type I carboxy-terminal propeptide (PICP) and procollagen type III amino-terminal propeptide (PIIINP). Eight infected and two uninfected guinea pigs were necropsied at seven time points up to one year post-infection. Cell death by necrosis and apoptosis was determined by histopathological observation and terminal deoxynucleotidyl transferase dUTP nick end labeling, respectively. Deposition of cardiac collagen types was determined by immunohistochemistry and serum levels of PICP, PIIINP, and anti-T. cruzi IgG1 and IgG2 by ELISA. IgG2 (Th1 response) predominated throughout the course of infection; IgG1 (Th2 response) was detected during the chronic phase. Cardiac cell death by necrosis predominated over apoptosis during the acute phase; during the chronic phase, both apoptosis and necrosis were observed in cardiac cells. Apoptosis was also observed in lymphocytes, endothelial cells and epicardial adipose tissue, especially in the chronic phase. Cardiac levels of CI, CIII, CIV increased progressively, but the highest levels were seen in the chronic phase and were primarily due to increase in CIII and CIV. High serum levels of PICP and PIIINP were observed throughout the infection, and increased levels of both biomarkers were associated with cardiac fibrosis (p = 0.002 and p = 0.038, respectively). These results confirm the role of apoptosis in cell loss mainly during the chronic phase and the utility of PICP and PIIINP as biomarkers of fibrosis in cardiac remodeling during T. cruzi infection. PMID:23409197

  4. The role of pharmacotherapy in the prevention of sudden cardiac death in patients with heart failure.

    PubMed

    Weeks, Phillip A; Sieg, Adam; Gass, Jennifer Ann; Rajapreyar, Indranee

    2016-07-01

    Sudden cardiac death remains a significant threat to the survival of patients with heart failure. Long-term cardiac remodeling predisposes these patients to develop malignant ventricular arrhythmias. Permanent implantable and temporary external defibrillators remain a mainstay for the prevention of sudden cardiac death in this population. For decades, researchers have attempted to identify reliable drug therapies to avoid such arrhythmias; however, to date, success has been inconsistent. This review aims to explore the evidence defining the role of drug therapies for direct and indirect suppression of arrhythmias that may cause sudden cardiac death in patients with heart failure. PMID:27003591

  5. Near-death experiences in cardiac arrest survivors.

    PubMed

    French, Christopher C

    2005-01-01

    Near-death experiences (NDEs) have become the focus of much interest in the last 30 years or so. Such experiences can occur both when individuals are objectively near to death and also when they simply believe themselves to be. The experience typically involves a number of different components including a feeling of peace and well-being, out-of-body experiences (OBEs), entering a region of darkness, seeing a brilliant light, and entering another realm. NDEs are known to have long-lasting transformational effects upon those who experience them. An overview is presented of the various theoretical approaches that have been adopted in attempts to account for the NDE. Spiritual theories assume that consciousness can become detached from the neural substrate of the brain and that the NDE may provide a glimpse of an afterlife. Psychological theories include the proposal that the NDE is a dissociative defense mechanism that occurs in times of extreme danger or, less plausibly, that the NDE reflects memories of being born. Finally, a wide range of organic theories of the NDE has been put forward including those based upon cerebral hypoxia, anoxia, and hypercarbia; endorphins and other neurotransmitters; and abnormal activity in the temporal lobes. Finally, the results of studies of NDEs in cardiac arrest survivors are reviewed and the implications of these results for our understanding of mind-brain relationships are discussed.

  6. Prevention of sudden cardiac death in hemodialysis patients.

    PubMed

    O'Shaughnessy, Michelle M; O'Regan, John A; Lavin, Peter J

    2014-01-01

    One quarter of all hemodialysis patients will succumb to sudden cardiac death (SCD), a rate far exceeding that observed in the general population. A high prevalence of atherosclerotic coronary artery disease amongst patients with end-stage kidney disease (ESKD) partly explains this exaggerated risk. However, uremia and dialysis related factors are also of critical importance. Interventions aimed at preventing SCD have been inadequately studied in patients with ESKD. Data extrapolated from non-renal populations cannot necessarily be applied to hemodialysis patients, who possess relatively unique risk factors for SCD including "uremic cardiomyopathy", electrolyte shifts, fluctuations in intravascular volume and derangements of mineral and bone metabolism. Pending data derived from proposed randomized controlled clinical trials, critical appraisal of existing evidence and the selective application of guidelines developed for the general population to dialysis patients are required if therapeutic nihilism, or excessive intervention, are to be avoided. We discuss the evidence supporting a role for medical therapies, dialysis prescription refinements, revascularization procedures and electrical therapies as potential interventions to prevent SCD amongst hemodialysis patients. Based on current best available evidence, we present suggested strategies for the prevention of arrhythmia-mediated death in this highly vulnerable patient population. PMID:24720456

  7. Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death.

    PubMed

    Foster, D Brian; Liu, Ting; Kammers, Kai; O'Meally, Robert; Yang, Ni; Papanicolaou, Kyriakos N; Talbot, C Conover; Cole, Robert N; O'Rourke, Brian

    2016-09-01

    Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances from sham-operated HYP and HF hearts were assessed by iTRAQ LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using mRNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation, and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial procsses, were downregulated in HF but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, acylcarnitines were downregulated in HYP and fatty acids accumulated in HF. The correlation of transcript and protein changes in HF was weak (R(2) = 0.23), suggesting post-transcriptional gene regulation in HF. Proteome/metabolome integration indicated metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. On the basis of these findings, we present a model of cardiac decompensation involving impaired nuclear integration of Ca(2+) and cyclic nucleotide signals that are coupled to mitochondrial metabolic and antioxidant defects through the CREB/PGC1α transcriptional axis.

  8. Integrated Omic Analysis of a Guinea Pig Model of Heart Failure and Sudden Cardiac Death.

    PubMed

    Foster, D Brian; Liu, Ting; Kammers, Kai; O'Meally, Robert; Yang, Ni; Papanicolaou, Kyriakos N; Talbot, C Conover; Cole, Robert N; O'Rourke, Brian

    2016-09-01

    Here, we examine key regulatory pathways underlying the transition from compensated hypertrophy (HYP) to decompensated heart failure (HF) and sudden cardiac death (SCD) in a guinea pig pressure-overload model by integrated multiome analysis. Relative protein abundances from sham-operated HYP and HF hearts were assessed by iTRAQ LC-MS/MS. Metabolites were quantified by LC-MS/MS or GC-MS. Transcriptome profiles were obtained using mRNA microarrays. The guinea pig HF proteome exhibited classic biosignatures of cardiac HYP, left ventricular dysfunction, fibrosis, inflammation, and extravasation. Fatty acid metabolism, mitochondrial transcription/translation factors, antioxidant enzymes, and other mitochondrial procsses, were downregulated in HF but not HYP. Proteins upregulated in HF implicate extracellular matrix remodeling, cytoskeletal remodeling, and acute phase inflammation markers. Among metabolites, acylcarnitines were downregulated in HYP and fatty acids accumulated in HF. The correlation of transcript and protein changes in HF was weak (R(2) = 0.23), suggesting post-transcriptional gene regulation in HF. Proteome/metabolome integration indicated metabolic bottlenecks in fatty acyl-CoA processing by carnitine palmitoyl transferase (CPT1B) as well as TCA cycle inhibition. On the basis of these findings, we present a model of cardiac decompensation involving impaired nuclear integration of Ca(2+) and cyclic nucleotide signals that are coupled to mitochondrial metabolic and antioxidant defects through the CREB/PGC1α transcriptional axis. PMID:27399916

  9. Incidence and correlates of near-death experiences in a cardiac care unit.

    PubMed

    Greyson, Bruce

    2003-01-01

    Near-death experiences, unusual experiences during a close brush with death, may precipitate pervasive attitudinal and behavior changes. The incidence and psychological correlates of such experiences, and their association with proximity to death, are unclear. We conducted a 30-month survey to identify near-death experiences in a tertiary care center cardiac inpatient service. In a consecutive sample of 1595 patients admitted to the cardiac inpatient service (mean age 63 years, 61% male), of whom 7% were admitted with cardiac arrest, patients who described near-death experiences were matched with comparison patients on diagnosis, gender, and age. Near-death experiences were reported by 10% of patients with cardiac arrest and 1% of other cardiac patients (P<.001). Near-death experiencers were younger than other patients (P=.001), were more likely to have lost consciousness (P<.001) and to report prior purportedly paranormal experiences (P=.009), and had greater approach-oriented death acceptance (P=.01). Near-death experiencers and comparison patients did not differ in sociodemographic variables, social support, quality of life, acceptance of their illness, cognitive function, capacity for physical activities, degree of cardiac dysfunction, objective proximity to death, or coronary prognosis.

  10. Sudden cardiac death in patients with diabetes mellitus and chronic heart failure.

    PubMed

    Walker, Andrew Mn; Cubbon, Richard M

    2015-07-01

    In patients with diabetes mellitus, around 50% of deaths due to cardiovascular causes are sudden cardiac deaths. The prevalence of diabetes in cohorts with chronic heart failure is increasing, and while sudden cardiac death is an increasingly rare mode of death in chronic heart failure patients as a whole, the risk of this outcome remains high in those with diabetes. This review summarises the current knowledge on the incidence of sudden cardiac death in patients with diabetes and chronic heart failure, before discussing the causes of the excess risk seen in those with these coexistent conditions. We then describe current strategies for risk stratification and prevention of sudden cardiac death in these patients before discussing the priorities for further study in this area.

  11. Genetic and toxicologic investigation of Sudden Cardiac Death in a patient with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) under cocaine and alcohol effects.

    PubMed

    Cittadini, Francesca; De Giovanni, Nadia; Alcalde, Mireia; Partemi, Sara; Carbone, Arnaldo; Campuzano, Oscar; Brugada, Ramon; Oliva, Antonio

    2015-01-01

    Cocaine and alcohol toxicity is well known, especially when simultaneously abused. These drugs perform both acute and chronic harmfulness, with significant cardiac events such as ventricular arrhythmias, tachycardia, systemic hypertension, acute myocardial infarction, ventricular hypertrophy, and acute coronary syndrome. The present report refers about a patient who died after a documented episode of psychomotor agitation followed by cardiac arrest. At the autopsy investigation, arrhythmogenic right ventricular cardiomyopathy (ARVC) was diagnosed and confirmed by postmortem molecular analysis revealing a mutation in the DSG2 gene. Postmortem toxicological analysis demonstrated a recent intake of cocaine, and the death was attributed to cardiac arrhythmias. The detection of cocaine and cocaethylene in hair samples proved chronic simultaneous intake of cocaine and alcohol at least in the last month. The authors discuss the role of these drugs and genetic predisposition of the ARVC in causing the death of the patient. PMID:25399050

  12. A New Insight Into Sudden Cardiac Death in Young People

    PubMed Central

    Wang, Yueyue; Xia, Lei; Shen, Xiaodong; Han, Guoxin; Feng, Dan; Xiao, Hongju; Zhai, Yongzhi; Chen, Xin; Miao, Yuanyuan; Zhao, Chunhong; Wang, Yingchan; Guo, Mingguang; Li, Tanshi; Zhu, Hai Yan

    2015-01-01

    Abstract Takotsubo cardiomyopathy (TTC) causes sudden cardiac death and has garnered increased attention worldwide in recent years. However, few studies have clearly classified the risk factors for this disease, including gender, race and morbidity, as well as the physical and mental stressors that can exacerbate the disease, particularly in young patients. To better analyze the characteristics of young TTC patients, we performed a systematic review of reported cases involving young patients. A computer-assisted search was performed using prominent electronic medical information sources to identify literature published between January 1965 and December 2013. Relevant studies containing clinical data of young TTC patients were included. Ninety-six records that included information about 104 cases were ultimately selected for our review. Several of the following results were noted: First, physical stress was more likely to exacerbate TTC than was mental stress in young patients. Second, more female than male TTC patients were noted among both young patients and the general population. Third, ethnicity appears to play no role in the disease, as no significant differences were noted among individuals of different races with respect to clinical characteristics, morbidity or stressors. Fourth, the clinical manifestations of TTC were similar to those of other cardiac diseases, including coronary heart disease. However, TTC may be detected using the combination of echocardiography and ventriculography. Clinicians should consider TTC if young patients present with symptoms similar to those of coronary heart disease so that harmful treatments such as coronary artery stent placement may be avoided. Moreover, the answers to questions regarding the clinical diagnostic criteria, etiology, pathophysiology, and the management of this syndrome in youth remain unclear; therefore, further research is needed. PMID:26266349

  13. 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.

  14. [Morphological prerequisites of heart ventricles fibrillation in sudden cardiac death].

    PubMed

    Reznik, A G

    2009-01-01

    We studied morphological changes in the myocardium and content of glucose, magnesium, calcium, sodium in pericardial fluid of victims of out of hospital sudden death due to acute coronary insufficiency and prenecrotic stage of myocardial infarction. We established that both in regions of ischemic injury appearing as III degree contracture lesions of cardiomyocytes, zones of intracellular myocytolysis and primary breakdown of myofibrils, as will as in zones of relaxation myocardium loses its contractile properties. This in turn leads to asynchronous contraction of left and right ventricles. As fibrillation develops in both ventricles simultaneously there are all grounds to believe that morphological prerequisite (source of origin) of fibrillation is the presence of areas of ischemic injury and relaxation in the myocardium.

  15. 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.

  16. Sudden death due to an unrecognized cardiac hydatid cyst: three medicolegal autopsy cases.

    PubMed

    Pakis, Isil; Akyildiz, Elif Ulker; Karayel, Ferah; Turan, Arzu Akcay; Senel, Berna; Ozbay, Mehmet; Cetin, Gursel

    2006-03-01

    Echinococcosis is a human infection caused by the larval stage of Echinococcocus granulosus. The most common sites of infection are the liver and the lungs. Cardiac hydatid cysts are very rare, even in regions where hydatic cysts are endemic (the Mediterranean, South America, Africa, and Australia). It has been reported that cardiac involvement is seen in about 0.5-3% of human echinococcosis cases. Three cases of cardiac hydatid disease that caused sudden death and which were histopathologically diagnosed are reported. Cardiac echinococcosis is rare, but due to its insidious presentation and affinity to cause sudden death, it is important that it be identified in the histopathological examination.

  17. Sudden cardiac death in China: current status and future perspectives.

    PubMed

    Zhang, Shu

    2015-10-01

    Sudden cardiac death (SCD) is a major cause of mortality worldwide. Similar to the number of SCDs in western countries including the USA, the number of SCDs in China is ∼544,000 annually. However, there are significant differences in patient characteristics between Chinese primary prevention population and U.S. primary prevention population. In contrast to western countries where implantable cardioverter-defibrillator (ICD) devices have been well adopted as a major effective method for both primary and secondary prevention of SCD, China has a low prevalence of ICD utilization (∼1.5 device per 1 million people). Socioeconomic and political factors, awareness and knowledge of SCD, and the difference in disease patterns have led to the underutilization of ICD in China. China, as the most populated and the second largest economic country in the world, has now taken variable approaches to address this pressing health problem and enhances the delivery of lifesaving therapies, including arrhythmia ablation and medical treatment besides ICD, to patients who are at risk of SCD.

  18. Risk of sudden cardiac death in chronic kidney disease.

    PubMed

    Poulikakos, Dimitrios; Banerjee, Debasish; Malik, Marek

    2014-02-01

    The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end-stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes. PMID:24256575

  19. Peruvoside, a Cardiac Glycoside, Induces Primitive Myeloid Leukemia Cell Death.

    PubMed

    Feng, Qian; Leong, Wa Seng; Liu, Liang; Chan, Wai-In

    2016-01-01

    Despite the available chemotherapy and treatment, leukemia remains a difficult disease to cure due to frequent relapses after treatment. Among the heterogeneous leukemic cells, a rare population referred as the leukemic stem cell (LSC), is thought to be responsible for relapses and drug resistance. Cardiac glycosides (CGs) have been used in treating heart failure despite its toxicity. Recently, increasing evidence has demonstrated its new usage as a potential anti-cancer drug. Ouabain, one of the CGs, specifically targeted CD34⁺CD38(-) leukemic stem-like cells, but not the more mature CD34⁺CD38⁺ leukemic cells, making this type of compounds a potential treatment for leukemia. In search of other potential anti-leukemia CGs, we found that Peruvoside, a less studied CG, is more effective than Ouabain and Digitoxin at inducing cell death in primitive myeloid leukemia cells without obvious cytotoxicity on normal blood cells. Similar to Ouabain and Digitoxin, Peruvoside also caused cell cycle arrest at G₂/M stage. It up-regulates CDKN1A expression and activated the cleavage of Caspase 3, 8 and PARP, resulting in apoptosis. Thus, Peruvoside showed potent anti-leukemia effect, which may serve as a new anti-leukemia agent in the future. PMID:27110755

  20. 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.

  1. Sudden cardiac death due to physical exercise in male competitive athletes. A report of six cases.

    PubMed

    Durakovic, Z; Misigoj-Durakovic, M; Vuori, I; Skavic, J; Belicza, M

    2005-12-01

    In the period of 30 years, i.e. from 1973 to 2002, we noticed in Croatia 6 sudden and unexpected cardiac deaths in male athletes during or after training. Two were soccer players, 2 athletic runners, one was a rugby player and one was a basketball player. All of them were without cardiovascular symptoms. At the forensic autopsy, the first athlete, aged 29, had chronic myocarditis and thickened left ventricular wall of 15 mm. The second, aged 21, had an acute myocardial infarction of the posterior wall with normal coronaries and thickened left ventricular wall of 15 mm. The third aged 17, had hypoplastic right coronary artery and narrowed ascending aorta, suppurant tonsillitis and subacute myocarditis. Two athletes, aged 29 and 15, had hypertrophic cardiomyopathy and normal coronaries, and one dilated aorta. The sixth, aged 24, had arrhythmogenic cardiomyopathy of the right ventricle. All the 6 athletes died suddenly, obviously because of malignant ventricular arrhythmias. In Croatia the death rate among athletes reached 0.15/100 000, in others who practice exercise reached 0.74/100,000 and the difference is highly significant (c2=14.487, Poisson rates=3.81, P=0.00014) and in physicians-specialists reached 33.6/100,000. Preventive medical examinations are essential, especially in athletes before physical exercise, as are other investigations in every case suspicious of heart disease, including electrocardiogram (ECG), stress ECG, echocardiography and stress-echocardiography and other findings if indicated. Physical exercise is contraindicated in acute respiratory infection: in 2 of those cases had been a cause of death as a trigger.

  2. Roadway Proximity and Risk of Sudden Cardiac Death in Women

    PubMed Central

    Hart, Jaime E; Chiuve, Stephanie E; Laden, Francine; Albert, Christine M

    2015-01-01

    Background Sudden cardiac death (SCD) is a major source of mortality and is the first manifestation of heart disease for the majority of cases. Thus, there is a definite need to identify risk factors for SCD that can be modified on the population level. Exposure to traffic, measured by residential roadway proximity, has been shown to be associated with an increased risk of cardiovascular disease. Our objective was to determine if roadway proximity was associated with an increased risk of SCD and to compare to the risk of other coronary heart disease (CHD) outcomes. Methods and Results A total of 523 cases of SCD were identified over 26 years of follow-up among 107,130 members of the prospective Nurses’ Health Study. We calculated residential distance to roadways at all residential addresses from 1986–2012. In age- and race-adjusted models, women living within 50 meters of a major roadway had an elevated risk of SCD (HR=1.56; 95%CI: 1.18–2.05). The association was attenuated but still statistically significant after controlling for potential confounders and mediators (HR=1.38; 95%CI:1.04–1.82). The equivalent adjusted HRs for nonfatal myocardial infarction and fatal CHD were 1.08 (95%CI: 0.96–1.23) and 1.24 (95%CI: 1.03–1.50), respectively. Conclusions Among this sample of middle-aged and older women, roadway proximity was associated with an elevated and statistically significant risks of SCD and fatal CHD, even after controlling for other cardiovascular risk factors. PMID:25332277

  3. Sudden infant death syndrome caused by cardiac arrhythmias: only a matter of genes encoding ion channels?

    PubMed

    Sarquella-Brugada, Georgia; Campuzano, Oscar; Cesar, Sergi; Iglesias, Anna; Fernandez, Anna; Brugada, Josep; Brugada, Ramon

    2016-03-01

    Sudden infant death syndrome is the unexpected demise of a child younger than 1 year of age which remains unexplained after a complete autopsy investigation. Usually, it occurs during sleep, in males, and during the first 12 weeks of life. The pathophysiological mechanism underlying the death is unknown, and the lethal episode is considered multifactorial. However, in cases without a conclusive post-mortem diagnosis, suspicious of cardiac arrhythmias may also be considered as a cause of death, especially in families suffering from any cardiac disease associated with sudden cardiac death. Here, we review current understanding of sudden infant death, focusing on genetic causes leading to lethal cardiac arrhythmias, considering both genes encoding ion channels as well as structural proteins due to recent association of channelopathies and desmosomal genes. We support a comprehensive analysis of all genes associated with sudden cardiac death in families suffering of infant death. It allows the identification of the most plausible cause of death but also of family members at risk, providing cardiologists with essential data to adopt therapeutic preventive measures in families affected with this lethal entity.

  4. Acute myocardial infarction and sudden death in Sioux Indians.

    PubMed Central

    Hrabovsky, S L; Welty, T K; Coulehan, J L

    1989-01-01

    While some Indian tribes have low rates of acute myocardial infarction, Northern Plains Indians, including the Sioux, have rates of morbidity and mortality from acute myocardial infarction higher than those reported for the United States population in general. In a review of diagnosed cases of acute myocardial infarction over a 3-year period in 2 hospitals serving predominantly Sioux Indians, 8% of cases were found misclassified, and 22% failed to meet rigorous diagnostic criteria, although the patients did indeed have ischemic heart disease. Patients had high frequencies of complications and risk factors and a fatality rate of 16% within a month of admission. Sudden deaths likely due to ischemic heart disease but in persons not diagnosed as having acute myocardial infarction by chart review occurred 3 times more frequently than deaths occurring within a month of clinical diagnosis. PMID:2735047

  5. Motivation to Pursue Genetic Testing in Individuals with a Personal or Family History of Cardiac Events or Sudden Cardiac Death

    PubMed Central

    Erskine, Kathleen E.; Hidayatallah, Nadia Z.; Walsh, Christine A.; McDonald, Thomas V.; Cohen, Lilian; Marion, Robert W.; Dolan, Siobhan M.

    2014-01-01

    Genetic testing is becoming increasingly available for cardiac channelopathies, such as long QT syndrome and Brugada syndrome, which can lead to sudden cardiac death. Test results can be used to shape an individual’s medical management and to identify at-risk family members. In our qualitative study, all participants had a personal or family history of a diagnosed cardiac arrhythmia syndrome or sudden cardiac death. Open-ended interviews were conducted individually and in focus groups. Interviews were audio recorded, transcribed verbatim, and analyzed using a qualitative grounded-theory approach. Of 50 participants, 37 described their motivations for pursuing genetic testing for long QT syndrome or another cardiac channelopathy. Participants’ motivations included: to find an explanation for a family member’s sudden death, to relieve uncertainty regarding a diagnosis, to guide future medical management, to allay concern about children or other family members, and to comply with recommendations of physicians or family members. Perceived reasons not to pursue genetic testing included denial, fear, and lack of information. The genetic counseling and informed consent process can be enhanced by understanding and addressing an individual’s internal and external motivations either for or against pursuing genetic testing. PMID:24664857

  6. Motivation to pursue genetic testing in individuals with a personal or family history of cardiac events or sudden cardiac death.

    PubMed

    Erskine, Kathleen E; Hidayatallah, Nadia Z; Walsh, Christine A; McDonald, Thomas V; Cohen, Lilian; Marion, Robert W; Dolan, Siobhan M

    2014-10-01

    Genetic testing is becoming increasingly available for cardiac channelopathies, such as long QT syndrome and Brugada syndrome, which can lead to sudden cardiac death. Test results can be used to shape an individual's medical management and to identify at-risk family members. In our qualitative study, all participants had a personal or family history of a diagnosed cardiac arrhythmia syndrome or sudden cardiac death. Open-ended interviews were conducted individually and in focus groups. Interviews were audio recorded, transcribed verbatim, and analyzed using a qualitative grounded-theory approach. Of 50 participants, 37 described their motivations for pursuing genetic testing for long QT syndrome or another cardiac channelopathy. Participants' motivations included: to find an explanation for a family member's sudden death, to relieve uncertainty regarding a diagnosis, to guide future medical management, to allay concern about children or other family members, and to comply with recommendations of physicians or family members. Perceived reasons not to pursue genetic testing included denial, fear, and lack of information. The genetic counseling and informed consent process can be enhanced by understanding and addressing an individual's internal and external motivations either for or against pursuing genetic testing.

  7. Sudden cardiac death in epilepsy disappoints, but epileptologists keep faith.

    PubMed

    Scorza, Fulvio A; Cavalheiro, Esper A; Costa, Jaderson Costa da

    2016-07-01

    Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with intractable epilepsy. Probably, optimization of seizure control will prevent some of these deaths. Briefly, we integrated in this paper some data about the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP. PMID:27487377

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

    PubMed

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

    2007-08-01

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

  9. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL.

  10. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL. PMID:24862130

  11. 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

  12. 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

  13. Physical exertion as a trigger of myocardial infarction and sudden cardiac death.

    PubMed

    Mittleman, M A; Siscovick, D S

    1996-05-01

    The data reviewed in this article indicate that physical exertion can trigger the onset of nonfatal myocardial infarction and sudden cardiac death. In addition, it is clear that although the relative risk associated with heavy exertion may be high, the absolute risk is actually quite small. It also is clear that regular exercise reduces the risk of triggering of myocardial infarction and sudden cardiac death by isolated bouts of exertion. Thus, these data provide further support for encouragement of regular exercise, as recommended by the American Heart Association. Such a program is likely to lower the overall risk of myocardial infarction and sudden cardiac death because it may lower the baseline risk and also decrease the relative risk that an episode of exertion will trigger a myocardial infarction or sudden cardiac death. Specific recommendations for patients with a history of myocardial infarction or angina are complex. Patients with coronary artery disease have the same relative risk of myocardial infarction and sudden cardiac death as those with no such history. Because of their elevated and variable baseline risk, however, specific recommendations regarding the risks and benefits of heavy physical exertion must be provided by their individual physicians, acting on recommended guidelines for exercise in such patients.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

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

    PubMed

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

    2006-12-01

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

  20. Sudden unexpected death under acute influence of cannabis.

    PubMed

    Hartung, Benno; Kauferstein, Silke; Ritz-Timme, Stefanie; Daldrup, Thomas

    2014-04-01

    The acute toxicity of cannabinoids is said to be low and there is little public awareness of the potentially hazardous cardiovascular effects of cannabis, e.g. marked increase in heart rate or supine blood pressure. We describe the cases of two young, putative healthy men who died unexpectedly under the acute influence of cannabinoids. To our knowledge, these are the first cases of suspected fatal cannabis intoxications where full postmortem investigations, including autopsy, toxicological, histological, immunohistochemical and genetical examinations, were carried out. The results of these examinations are presented. After exclusion of other causes of death we assume that the young men experienced fatal cardiovascular complications evoked by smoking cannabis. PMID:24598271

  1. Analysis of knowledge of the general population and health professionals on organ donation after cardiac death

    PubMed Central

    Bedenko, Ramon Correa; Nisihara, Renato; Yokoi, Douglas Shun; Candido, Vinícius de Mello; Galina, Ismael; Moriguchi, Rafael Massayuki; Ceulemans, Nico; Salvalaggio, Paolo

    2016-01-01

    Objective To evaluate the knowledge and acceptance of the public and professionals working in intensive care units regarding organ donation after cardiac death. Methods The three hospitals with the most brain death notifications in Curitiba were selected, and two groups of respondents were established for application of the same questionnaire: the general public (i.e., visitors of patients in intensive care units) and health professionals working in the same intensive care unit. The questionnaire contained questions concerning demographics, intention to donate organs and knowledge of current legislation regarding brain death and donation after cardiac death. Results In total, 543 questionnaires were collected, including 442 from family members and 101 from health professionals. There was a predominance of women and Catholics in both groups. More females intended to donate. Health professionals performed better in the knowledge comparison. The intention to donate organs was significantly higher in the health professionals group (p = 0.01). There was no significant difference in the intention to donate in terms of education level or income. There was a greater acceptance of donation after uncontrolled cardiac death among Catholics than among evangelicals (p < 0.001). Conclusion Most of the general population intended to donate, with greater intentions expressed by females. Education and income did not affect the decision. The type of transplant that used a donation after uncontrolled cardiac death was not well accepted in the study population, indicating the need for more clarification for its use in our setting. PMID:27626950

  2. Rare Titin (TTN) Variants in Diseases Associated with Sudden Cardiac Death.

    PubMed

    Campuzano, Oscar; Sanchez-Molero, Olallo; Mademont-Soler, Irene; Riuró, Helena; Allegue, Catarina; Coll, Monica; Pérez-Serra, Alexandra; Mates, Jesus; Picó, Ferran; Iglesias, Anna; Brugada, Ramon

    2015-01-01

    A leading cause of death in western countries is sudden cardiac death, and can be associated with genetic disease. Next-generation sequencing has allowed thorough analysis of genes associated with this entity, including, most recently, titin. We aimed to identify potentially pathogenic genetic variants in titin. A total of 1126 samples were analyzed using a custom sequencing panel including major genes related to sudden cardiac death. Our cohort was divided into three groups: 432 cases from patients with cardiomyopathies, 130 cases from patients with channelopathies, and 564 post-mortem samples from individuals showing anatomical healthy hearts and non-conclusive causes of death after comprehensive autopsy. None of the patients included had definite pathogenic variants in the genes analyzed by our custom cardio-panel. Retrospective analysis comparing the in-house database and available public databases also was performed. We identified 554 rare variants in titin, 282 of which were novel. Seven were previously reported as pathogenic. Of these 554 variants, 493 were missense variants, 233 of which were novel. Of all variants identified, 399 were unique and 155 were identified at least twice. No definite pathogenic variants were identified in any of genes analyzed. We identified rare, mostly novel, titin variants that seem to play a potentially pathogenic role in sudden cardiac death. Additional studies should be performed to clarify the role of these variants in sudden cardiac death.

  3. 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.

  4. 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.

  5. [Sudden cardiac death during sports due to coronariitis].

    PubMed

    Bilkenroth, B; Wegmann, W

    2000-07-01

    A case of sudden and unexpected death of a 29-year-old man during a basketball game is reported. Six years before death a transient ischemic attack and a membranous glomerulonephritis were diagnosed. The autopsy revealed as cause of death to be a severe lymphoplasmocytic coronariitis and, in addition, a small single focus of a lymphoplasmocytic aortitis, indicating a systemic disease. A suspected syphilitic vasculitis could not be confirmed. In the literature there are few cases of similar coronary arteriitis are described, such as Takayasu's type of arteriitis in men of young and middle age.

  6. Apoptotic tubular cell death during acute renal allograft rejection.

    PubMed

    Wever, P C; Aten, J; Rentenaar, R J; Hack, C E; Koopman, G; Weening, J J; ten Berge, I J

    1998-01-01

    Tubular cells are important targets during acute renal allograft rejection and induction of apoptosis might be a mechanism of tubular cell destruction. Susceptibility to induction of apoptosis is regulated by the homologous Bcl-2 and Bax proteins. Expression of Bcl-2 and Bax is regulated by p53, which down-regulates expression of Bcl-2, while simultaneously up-regulating expression of Bax. We studied apoptotic tubular cell death in 10 renal allograft biopsies from transplant recipients with acute rejection by in situ end-labelling and the DNA-binding fluorochrome propidium iodide. Tubular expression of p53, Bcl-2 and Bax was studies by immunohistochemistry. Five renal allograft biopsies from transplant recipients with uncomplicated clinical course and histologically normal renal tissue present in nephrectomy specimens from 4 patients with renal adenocarcinoma served as control specimens. Apoptotic cells and apoptotic bodies were detected in tubular epithelia and tubular lumina in 9 out of 10 acute rejection biopsies. In control renal tissue, apoptotic cells were detected in 1 biopsy only. Compared to control renal tissue, acute renal allograft rejection was, furthermore, associated with a shift in the ratio of Bcl-2 to Bax in favour of Bax in tubular epithelia and increased expression of p53 in tubular nuclei. These observations demonstrate that apoptosis contributes in part to tubular cell destruction during acute renal allograft rejection. In accordance, the shift in the ratio of Bcl-2 to Bax in favour of Bax indicates increased susceptibility of tubular epithelia to induction of apoptosis. The expression of p53 in tubular nuclei during acute renal allograft rejection indicates the presence of damaged DNA, which can be important in initiation of part of the observed apoptosis. These findings elucidate part of the mechanisms controlling apoptotic tubular cell death during acute renal allograft rejection.

  7. [Acute liver failure after ingestion of death cap mushrooms].

    PubMed

    Zuliani, Anna-Maria; Kabar, Iyad; Mitchell, Todd; Heinzow, Hauke Sebastian

    2016-07-01

    Amatoxins, which are mainly found in Amanita phalloides, Amanita virosa, and Galerina autumnalis, are responsible for the majority of fatal intoxication with green death cap. The intoxication is associated with acute liver failure, which explains the poor prognosis. Acute liver injury is generally preceeded by a gastrointestinal phase with nausea, vomiting and diarrhea. In the course, pre-renal kidney failure due to the associated fluid deficit and fulminant liver failure may occur. General guidelines for the treatment of amatoxin poisoning are yet not available. We report on three patients who suffered from amatoxin mushroom poisoning after ingestion of green death cap mushrooms. Based on the pathophysiology of amatoxin poisoning, we discuss a potential therapeutic approach. PMID:27359312

  8. [Treatment of ventricular tachyarrhythmias and prevention of sudden cardiac death: commentary on the 2016 ESC guideline].

    PubMed

    Eckardt, Lars; Köbe, Julia; Wasmer, Kristina

    2016-08-01

    The 2016 ESC guideline on prevention and therapy of ventricular tachyarrhythmias and sudden cardiac death present an excellent recommendation and summary for all forms of ventricular tachyarrhythmias in patients with and without structural or electrical heart disease. This includes cardiomyopathies as well as conditions such as proarrhythmia, neurologic/psychaitric disorders, or pregnancy. Some aspects are novel; (1) the guideline emphasizes for the first time genetic work-up in sudden cardiac death victims; (2) for prevention of sudden cardiac death systematic re-evaluation 6-12 weeks after myocardial infarction is recommended; (3) subcutaneous ICD as well as the wearable cardioverter/defibrillator are for the first time included in the guidelines; (4) automatic external defibrillators are recommended for public places; (5) for patients with recurrent ventricular tachyarrhythmias the role of catheter ablation has been upgraded. PMID:27509343

  9. Risk Stratification for Sudden Cardiac Death In Patients With Non-ischemic Dilated Cardiomyopathy

    PubMed Central

    Shekha, Karthik; Ghosh, Joydeep; Thekkoott, Deepak; Greenberg, Yisachar

    2005-01-01

    Non ischemic dilated cardiomyopathy (NIDCM) is a disorder of myocardium. It has varying etiologies. Albeit the varying etiologies of this heart muscle disorder, it presents with symptoms of heart failure, and rarely as sudden cardiac death (SCD). Manifestations of this disorder are in many ways similar to its counterpart, ischemic dilated cardiomyopathy (IDCM). A proportion of patients with NIDCM carries a grave prognosis and is prone to sudden cardiac death from sustained ventricular arrhythmias. Identification of this subgroup of patients who carry the risk of sudden cardiac death despite adequate medical management is a challenge .Yet another method is a blanket treatment of patients with this disorder with anti arrhythmic medications or anti tachyarrhythmia devices like implantable cardioverter defibrillators (ICD). However this modality of treatment could be a costly exercise even for affluent economies. In this review we try to analyze the existing data of risk stratification of NIDCM and its clinical implications in practice. PMID:16943952

  10. Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

    PubMed

    Myerburg, Robert J; Ullmann, Steven G

    2015-04-01

    Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise.

  11. Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

    PubMed

    Myerburg, Robert J; Ullmann, Steven G

    2015-04-01

    Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise. PMID:25669654

  12. Postmortem mRNA Expression Patterns in Left Ventricular Myocardial Tissues and Their Implications for Forensic Diagnosis of Sudden Cardiac Death

    PubMed Central

    Son, Gi Hoon; Park, Seong Hwan; Kim, Yunmi; Kim, Ji Yeon; Kim, Jin Wook; Chung, Sooyoung; Kim, Yu-Hoon; Kim, Hyun; Hwang, Juck-Joon; Seo, Joong-Seok

    2014-01-01

    Sudden cardiac death (SCD), which is primarily caused by lethal heart disorders resulting in structural and arrhythmogenic abnormalities, is one of the prevalent modes of death in most developed countries. Myocardial ischemia, mainly due to coronary artery disease, is the most common type of heart disease leading to SCD. However, postmortem diagnosis of SCD is frequently complicated by obscure histological evidence. Here, we show that certain mRNA species, namely those encoding hemoglobin A1/2 and B (Hba1/2 and Hbb, respectively) as well as pyruvate dehydrogenase kinase 4 (Pdk4), exhibit distinct postmortem expression patterns in the left ventricular free wall of SCD subjects when compared with their expression patterns in the corresponding tissues from control subjects with non-cardiac causes of death. Hba1/2 and Hbb mRNA expression levels were higher in ischemic SCD cases with acute myocardial infarction or ischemic heart disease without recent infarction, and even in cardiac death subjects without apparent pathological signs of heart injuries, than control subjects. By contrast, Pdk4 mRNA was expressed at lower levels in SCD subjects. In conclusion, we found that altered myocardial Hba1/2, Hbb, and Pdk4 mRNA expression patterns can be employed as molecular signatures of fatal cardiac dysfunction to forensically implicate SCD as the primary cause of death. PMID:24642708

  13. [Nursing management of a refractory cardiac death donor].

    PubMed

    Kaufmann, Marion

    2016-09-01

    The nursing management of a refractory circulatory death donor is a new procedure which forms an integral part of patient care. It comprises technical and organisational aspects, and requires a conceptual, ethical and deontological effort. PMID:27596504

  14. Near-death-experiences in out-of-hospital cardiac arrest survivors. Meaningful phenomena or just fantasy of death?

    PubMed

    Martens, P R

    1994-03-01

    Frequent criticism concerning the investigation of near-death-experiences (NDEs) has been the lack of uniform nomenclature and the failure to control the studied population with an elimination of interfering factors such as administration of sedatives and nonspecific stress responses. Greyson's NDE Scale is a 16-item questionnaire developed to standardize further research into mechanisms and effects of NDEs. Using this scale, we interviewed good out-of-hospital cardiac arrest survivors, with documented time-intervals between call for help and restoration of spontaneous circulation, yet without obvious brain damage or known, psychiatric history. The incidence of such experiences appeared to be extremely low among survivors of genuine cardiac arrest events. Alteration of information processing under the influence of hypoxia and hypercarbia only occurs after several minutes of brain ischaemia. International multicentric data collection within the framework for standardized reporting of cardiac arrest events will be the only satisfying method to address this fascinating and intriguing issue.

  15. Using QRS morphology and QTc interval to prevent complications and cardiac death.

    PubMed

    Attin, Mina; Davidson, Judy E

    2011-01-01

    Prevention of cardiac complications including death is influenced by the availability of diagnostic tools and technological advances. Cardiac telemetry as a diagnostic tool is widely used in hospitals because of an increased severity of illness and complex modality of treatments. QTc interval abnormalities in the electrocardiogram have been long recognized as a predictive precursor for life-threatening cardiac arrhythmias and cardiac arrest. QRS morphology has also been recognized as a reliable marker to prevent cardiac events in outpatient settings. However, the QTc and QRS morphology as electrocardiogram predictors are not routinely assessed in daily practice for hospitalized patients because of the slow advancement of technology in bedside monitoring systems and inadequate staff preparation. This article discusses the role of QRS morphology and QTc interval assessment in predicting risk of complications. The article also explores the need for further research and advancement in technology to overcome barriers to integrating these predictors into routine nursing practice.

  16. Cardiac Magnetic Resonance Scar Imaging for Sudden Cardiac Death Risk Stratification in Patients with Non-Ischemic Cardiomyopathy

    PubMed Central

    Kim, Eun Kyoung; Chattranukulchai, Pairoj

    2015-01-01

    In patients with non-ischemic cardiomyopathy (NICM), risk stratification for sudden cardiac death (SCD) and selection of patients who would benefit from prophylactic implantable cardioverter-defibrillators remains challenging. We aim to discuss the evidence of cardiac magnetic resonance (CMR)-derived myocardial scar for the prediction of adverse cardiovascular outcomes in NICM. From the 15 studies analyzed, with a total of 2747 patients, the average prevalence of myocardial scar was 41%. In patients with myocardial scar, the risk for adverse cardiac events was more than 3-fold higher, and risk for arrhythmic events 5-fold higher, as compared to patients without scar. Based on the available observational, single center studies, CMR scar assessment may be a promising new tool for SCD risk stratification, which merits further investigation. PMID:26175568

  17. Myocardial infarction, stroke, and sudden cardiac death may be prevented by influenza vaccination.

    PubMed

    Meyers, David G

    2003-03-01

    Acute myocardial infarction (AMI) and atherothrombotic stroke share a common pathogenesis involving disrupted atherosclerotic plaque and intravascular thrombosis. Both AMI and stroke have their peak incidence in winter months. Similarly, the incidence of upper respiratory infections (URIs), 38% of which are due to influenza, also peaks in winter (November and December). URIs result in many biochemical, cellular, and hemostatic changes that could predispose to plaque disruption and thrombosis. Infections, particularly URIs, frequently precede AMI and stroke. Up to 16% of persons older than 60 years of age experience a URI each year. Nineteen percent of those suffering an AMI recall a URI in the 2 weeks prior to their event. Three epidemiologic and one small clinical trial suggest that influenza vaccination is associated with a 50% reduction in incidence of sudden cardiac death, AMI, and ischemic stroke. Influenza vaccine is extremely safe and has a 50% efficacy. Theoretically, up to 104,500 AMIs and 192,000 nonembolic ischemic strokes could be prevented each year by influenza vaccination.

  18. Overzealous cardiac massage leading to unintentional infant death

    PubMed Central

    Sinani, Fatos; Ymaj, Besim; Vyshka, Gentian

    2011-01-01

    The case of an 18-month child is presented, with a picture demonstrating the thoracic trauma, caused from a hand pressure movement, perpetrated with an open right palm, in an attempt to perform an external cardiac massage. The child showed continuous episodes of ‘crying spells’ that the medical staff considered as benign, but an overprotective and mentally unstable mother kept on violently ‘resuscitating’ her son during such episodes. The last episode was characterised with a strenuous massage of the thoracic wall, causing evident bruises and leading to a cardiac contusion. The mother who perpetrated the trauma was sentenced for manslaughter, after the accidental character of the event, as well as the severity of her family situation and the precarious living environment of a socially abandoned single-acting parent, were all taken into account. The particular psychopathology of the care giver (mother) and the characteristics of the inflicted thoracic blow are described. PMID:22675032

  19. Overzealous cardiac massage leading to unintentional infant death.

    PubMed

    Sinani, Fatos; Ymaj, Besim; Vyshka, Gentian

    2011-01-01

    The case of an 18-month child is presented, with a picture demonstrating the thoracic trauma, caused from a hand pressure movement, perpetrated with an open right palm, in an attempt to perform an external cardiac massage. The child showed continuous episodes of 'crying spells' that the medical staff considered as benign, but an overprotective and mentally unstable mother kept on violently 'resuscitating' her son during such episodes. The last episode was characterised with a strenuous massage of the thoracic wall, causing evident bruises and leading to a cardiac contusion. The mother who perpetrated the trauma was sentenced for manslaughter, after the accidental character of the event, as well as the severity of her family situation and the precarious living environment of a socially abandoned single-acting parent, were all taken into account. The particular psychopathology of the care giver (mother) and the characteristics of the inflicted thoracic blow are described. PMID:22675032

  20. Identifying sudden cardiac death risk and specifying its occurrence time by analyzing electrocardiograms in natural time

    NASA Astrophysics Data System (ADS)

    Varotsos, P. A.; Sarlis, N. V.; Skordas, E. S.; Lazaridou, M. S.

    2007-08-01

    Sudden cardiac death (SCD) is a frequent cause of death and may occur even if the electrocardiogram seems to be similar to that of a healthy individual. A method which not only identifies the risk but also provides an estimate of the time of an impending cardiac arrest is proposed. Analyzing 159 electrocardiograms in natural time, the authors find that the key quantity is the entropy change under time reversal. After it becomes maximum at the scale of 13 heartbeats, ventricular fibrillation starts within ˜3h in 16 out of 18 SCDs. The method also distinguishes congestive heart failure patients from SCD.

  1. Physical and chemical injury as causes of sudden cardiac death: the forensic forum.

    PubMed

    Riddick, L

    1994-01-01

    Physical and chemical injuries account for the largest number of sudden, unexpected cardiac deaths in persons between the ages of 1 and 44 years. Blunt-force injuries, lacerations, avulsions, and contusions of the heart and great vessels sustained during motor vehicle crashes constitute the most prevalent type of lethal physical trauma to the cardiovascular system. The second most prevalent type of trauma is from penetrating and perforating wounds inflicted by firearms. The mechanisms of these injuries are discussed, with emphasis placed on those factors contributing to lethality. The three most prevalent chemicals associated with sudden cardiac death-ethyl alcohol, cocaine, and tricylic antidepressants-are briefly mentioned.

  2. A hierarchical communication model of the antecedents of health care professionals' support for donations after cardiac death.

    PubMed

    Peltier, J W; D'Alessandro, A M; Hsu, M; Schibrowsky, J A

    2011-03-01

    Using structural equation modeling, the direct and indirect impact of five variables on the support of donation after cardiac death from the perspective of health care professionals were investigated: knowledge, trust in the transplant team, whether patients are in a state of irreversibility, whether health care professionals participate in a patient's death, and perceptions about the brain death versus cardiac death donation process. In total, 10/15 relationships posited in the model had significant pathways. The results provide insight into sequential communication strategies for generating support for donations after cardiac death. PMID:21299836

  3. Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach.

    PubMed

    Wilhelm, Matthias; Bolliger, Stephan A; Bartsch, Christine; Fokstuen, Siv; Gräni, Christoph; Martos, Viktor; Medeiros Domingo, Argelia; Osculati, Antonio; Rieubland, Claudine; Sabatasso, Sara; Saguner, Ardan M; Schyma, Christian; Tschui, Joelle; Wyler, Daniel; Bhuiyan, Zahurul A; Fellmann, Florence; Michaud, Katarzyna

    2015-01-01

    Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

  4. Update: Causes and symptoms of sudden cardiac death in young athletes.

    PubMed

    Asif, Irfan M; Yim, Eugene S; Hoffman, Jacob M; Froelicher, Vic

    2015-02-01

    Abstract Sudden cardiac death (SCD) is the leading cause of death during exercise. While initial reports suggested that the most common cause of SCD in young athletes was due to hypertrophic cardiomyopathy (HCM), a critical review of investigations in several populations (athletes, non-athletes, military, national, and international) supports that the most common finding at autopsy of young individuals with SCD is actually a structurally normal heart (SNH). This information is vital for sports medicine clinicians, especially with regard to the pre-participation evaluation (PPE) since cardiac death associated with a SNH is likely attributed to disorders such as arrhythmia or ion channel diseases. This comprehensive review explores the causes of SCD, along with the symptoms preceding death, which ultimately may help refine the PPE and maximize the ability to detect potentially lethal disease prior to competition.

  5. Mechanisms of Cell Death in Acute Liver Failure

    PubMed Central

    Bantel, Heike; Schulze-Osthoff, Klaus

    2012-01-01

    Acute liver failure (ALF) can be the consequence of various etiologies, that might vary between different geographic regions. Most frequent are intoxications with acetaminophen, viral hepatitis, or liver damage of unknown origin. ALF occurs when the extent of hepatocyte death exceeds the regenerative capacity of the liver. The mode of liver cell death that is predominantly induced in ALF, i.e., apoptosis or necrosis, is still controversial and presumably determined by the etiology, duration, and magnitude of liver injury. Severe liver damage involves oxidative stress and depletion of ATP resulting in necrosis. In contrast, maintenance of ATP stores is required for the execution of apoptosis. Recent data suggest that necrosis resulting from severe liver damage is associated with poor outcome of ALF patients. Discrimination between apoptosis and necrosis might be therefore useful for the identification of ALF patients requiring liver transplantation. Identification of the molecular cell death mechanisms remains an important issue not only for early prediction of ALF outcome, but also for therapeutic interventions. In view of the pleiotropic functions of critical mediators of cell death and tissue regeneration, a particular challenge will be to reduce hepatocellular death without inhibiting the regenerative capacity of the liver. Here, we review the molecular mechanisms of hepatocyte injury and the pathways leading to apoptosis and necrosis, which might represent potential diagnostic and therapeutic targets in ALF. PMID:22485095

  6. Prevalence of HCM and long QT syndrome mutations in young sudden cardiac death-related cases.

    PubMed

    Allegue, Catarina; Gil, Rocio; Blanco-Verea, Alejandro; Santori, Montserrat; Rodríguez-Calvo, Marisol; Concheiro, Luis; Carracedo, Angel; Brion, María

    2011-07-01

    Cardiomyopathies and channelopathies are major causes of sudden cardiac death. The genetic study of these diseases is difficult because of their heterogenic nature not only in their genetic traits but also in their phenotypic expression. The purpose of the present study is the analysis of a wide spectrum of previously known genetic mutations in key genes related to hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), and Brugada syndrome (BrS) development. The samples studied include cases of sudden cardiac death (SCD) in young adults and their relatives in order to identify the real impact of genetic screening of SCD in forensic cases. Genetic screening of described variation in 16 genes implicated in the development of HCM and three more genes implicated in LQTS and BrS was performed by using MassARRAY technology. In addition, direct sequencing of the two most prevalent genes implicated in the development of SQTL type 1 and 2 was also carried out. Genetic screening allowed us to unmask four possibly pathogenic mutation carriers in the 49 SCD cases considered; carriers of mutation represent 9% (2/23) of the probands with structural anomalies found after autopsy and 7% (1/14) of the probands with structurally normal hearts after in depth autopsy protocol. One mutation was found among 12 of the recovered SCD cases considered. In people with direct family history of sudden cardiac death, but not themselves, 11 additional mutation carriers were found. Three different mutations were found in six of the 19 LQTS patients, representing three families and two different mutations were found among six patients with previous syncope. Genetic analysis in sudden cardiac death cases could help to elucidate the cause of death, but it also can help in the prevention of future deaths in families at risk. The study presented here shows the importance and relevance of genetic screening in patients with signs of cardiac hypertrophy and in family cases with more than one

  7. 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.

  8. Ion Channel Macromolecular Complexes in Cardiomyocytes: Roles in Sudden Cardiac Death

    PubMed Central

    Abriel, Hugues; Rougier, Jean-Sébastien; Jalife, José

    2015-01-01

    The movement of ions across specific channels embedded on the membrane of individual cardiomyocytes is crucial for the generation and propagation of the cardiac electrical impulse. Emerging evidence over the last 20 years strongly suggests that the normal electrical function of the heart is the result of dynamic interactions of membrane ion channels working in an orchestrated fashion as part of complex molecular networks. Such networks work together with exquisite temporal precision to generate each action potential and contraction. Macromolecular complexes play crucial roles in transcription, translation, oligomerization, trafficking, membrane retention, glycosylation, posttranslational modification, turnover, function and degradation of all cardiac ion channels known to date. In addition, the accurate timing of each cardiac beat and contraction demands, a comparable precision on the assembly and organizations of sodium, calcium and potassium channel complexes within specific subcellular microdomains, where physical proximity allows for prompt and efficient interaction. This review article, part of the Compendium on Sudden Cardiac Death, discusses the major issues related to the role of ion channel macromolecular assemblies in normal cardiac electrical function and the mechanisms of arrhythmias leading to sudden cardiac death. It provides an idea of how these issues are being addressed in the laboratory and in the clinic, which important questions remain unanswered, and what future research will be needed to improve knowledge and advance therapy. PMID:26044251

  9. Sudden Cardiac Death in Children and Adolescents: Can We Prevent It?

    ERIC Educational Resources Information Center

    Berger, Stuart

    2001-01-01

    Sudden cardiac death (SCD) can occur at any age in apparently healthy people. Early identification and intervention are essential. This article examines SCD in children and adolescents, explaining: who is at risk; the importance of training school personnel for SCD emergencies and having automated external defibrillators (AED) within the schools;…

  10. Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013.

    PubMed

    2013-12-13

    Lyme disease is a multisystem illness caused by Borrelia burgdorferi, a spirochete transmitted by certain species of Ixodes ticks. Approximately 30,000 confirmed and probable cases of Lyme disease were reported in the United States in 2012, primarily from high-incidence states in the Northeast (Connecticut, Delaware, Maine, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont) and upper Midwest (Minnesota and Wisconsin). Common manifestations include cutaneous, neurologic, and rheumatologic signs and symptoms. Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012-July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis. The three deaths were investigated by the Connecticut Department of Public Health, Massachusetts Department of Public Health, New Hampshire Department of Public Health, New York State Department of Health, and CDC. Donated corneas from two decedents had been transplanted to three recipients before the diagnosis of Lyme disease was established, but no evidence of disease transmission was found. Although death from Lyme carditis is rare, it should be considered in cases of sudden cardiac death in patients from high-incidence Lyme disease regions. Reducing exposure to ticks is the best method for preventing Lyme disease and other tickborne infections.

  11. 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.

  12. Commodio cordis: an underappreciated cause of sudden cardiac death in young patients: assessment and management in the ED.

    PubMed

    Perron, A D; Brady, W J; Erling, B F

    2001-09-01

    Commotio cordis is the condition of sudden cardiac death or near sudden cardiac death after blunt, low-impact chest wall trauma in the absence of structural cardiac abnormality. Ventricular fibrillation is the most commonly reported induced arrhythmia in commotio cordis. Blunt impact injury to the chest with a baseball is the most common mechanism. Survival rates for commotio cordis are low, even with prompt CPR and defibrillation.

  13. Sports-Related Sudden Cardiac Injury or Death.

    PubMed

    Greene, Elizabeth Anne; Punnoose, Ann

    2015-12-01

    Symptoms such as syncope and chest pain, especially if they are accompanied by palpitations or occur with exercise in any combination, require cardiac evaluation before adolescent athletes are allowed to return to the sports field. Some life-threatening conditions will likely be associated with a family history of HCM or LQTS, but the family history may not be discovered at the first medical visit. A family history of CPVT, for example, is hard to elicit unless this diagnosis has already been established in an affected family member. The keys will be the timing of symptoms and the documentation of arrhythmia with exercise. The ECG at baseline in CPVT may be deceptively normal. Hypertrophic cardiomyopathy is progressive, so evaluation during early childhood may be negative. Long QT syndrome may not always result in an abnormal ECG, even in genetically positive individuals. A high index of suspicion is needed to make these diagnoses, especially if the family history is not available.

  14. [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.

  15. [Sudden Cardiac Death of Young Persons: Risk Factors, Causes, Morphological Equivalents].

    PubMed

    Shilova, M A; Mamedov, M N

    2015-01-01

    The article contains literature review on the problem of causes of sudden cardiac death (SCD) among young people as well as results of author's own retrospective study of deaths of persons before 39 years based on forensic autopsies performed during 10 year period. The study of structure and dynamics of causes of death, its risk factors and the role of connective tissue dysplasia in development of terminal symptomocomlexes allowed to establish that main mechanism of SCD in young people was arrhythmogenic developing as a response to provoking factors--physical effort, psychoemotional stress, consumption of light alcoholic beverages. PMID:26688929

  16. Active surveillance of sudden cardiac death in young athletes by periodic Internet searches.

    PubMed

    Choi, Kristal; Pan, Yann Ping; Pock, Michelle; Chang, Ruey-Kang R

    2013-01-01

    The authors hypothesized that prospective, systematic Internet searches could identify occurrences of sudden cardiac death (SCD) in athletes and would be useful for establishing a system of active surveillance. Weekly advanced Google searches of the Internet were conducted for cases of SCD in young athletes during a 12-month period (2007-2008). Athletes ages 11-30 years who collapsed during a game, practice, or within an hour of exercise were included in the study. Individuals with known histories of cardiac issues and events occurring outside the United States were excluded. Verification of SCD was by autopsy reports and death certificates from county coroner offices and vital record agencies. Initially, 71 events were identified. Verification for the cause of death by coroner reports was possible in 45 cases, 43 (96 %) of which were confirmed to be SCDs. A total of 69 individuals 11-30 years of age (mean 17 ± 5 years) died suddenly of cardiovascular causes while participating in 15 different organized sports and a variety of nonorganized physical activities. The most common cause of death was hypertrophic cardiomyopathy (30 %), followed by coronary artery anomalies (9 %), and myocarditis (9 %). The incidence of athlete SCD, the types of sports involved, and the cardiac causes of death in our study were comparable with those of previous reports. Readily available Internet searches have the potential to be a powerful tool for identifying occurrences of athlete SCD. An active surveillance system using Google searches followed by coroner report verification can provide important epidemiologic and clinical information.

  17. Active Surveillance of Sudden Cardiac Death in Young Athletes by Periodic Internet Searches

    PubMed Central

    Choi, Kristal; Pan, Yann Ping; Pock, Michelle; Chang, Ruey-Kang R.

    2013-01-01

    Objective We hypothesized that prospective, systematic Internet searches could identify occurrences of sudden cardiac death (SCD) in athletes, and would be useful to establish a system of active surveillance. Methods Weekly advanced Google searches of the Internet were conducted for cases of SCD in young athletes over a 12-month period (2007–8). Athletes aged 11 to 30 years who collapsed during a game, practice, or within an hour of exercise were included. Individuals with known histories of cardiac issues and events occurring outside the United States were excluded. Verification of SCD was by autopsy reports and death certificates from county coroner offices and vital record agencies. Results A total of 71 events were initially identified. Verification of the cause of death by coroner reports was possible in 45 cases, of which 43 (96%) were confirmed to be SCDs. Sixty-nine individuals, 11 to 30 years of age (mean 17 ± 5), died suddenly from cardiovascular causes while participating in 15 different organized sports and a variety of non-organized physical activities. The most common cause of death was hypertrophic cardiomyopathy (30%), followed by coronary artery anomalies (9%), and myocarditis (9%). The incidence of athlete SCD, types of sports involved, and cardiac causes of death in our study were comparable to previous reports. Conclusions Readily available Internet searches have the potential to be a powerful tool for identifying occurrences of athlete SCD. An active surveillance system using Google searches followed by coroner report verification can provide important epidemiologic and clinical information. PMID:23681420

  18. How France launched its donation after cardiac death program.

    PubMed

    Antoine, C; Mourey, F; Prada-Bordenave, E

    2014-02-01

    On the basis of the literature and results presented at the 6th International Conference, donation after cardio-circulatory death provides a significant, practical, additional high quality source of transplantable organs. The vast majority of DCD are 'controlled' Maastricht category III donors. In 2010, the parliamentary information mission on the revision of the bioethics laws invited the Intensive Care Societies to debate and to make recommendations to implement controlled donation after circulatory death. They came to the conclusion that such retrieval is possible in France and insisted on the medical criteria that frame it: the writing of the medical procedures, the ethical aspects and the delay. The major recommendations of the ethics committees were firstly, The WLST decision is independent of the possibility of organ donation; secondly, the strict respect of "The dead donor and organ transplantation rule" and the updated national guidance for the WLST; thirdly, the drafting of a nationally agreed protocol defining the mandatory conditions to determine death and to perform procurement and transplantation. Organ donation after WLST will be authorised only in pilot centres with a locally agreed WLST policy including external second opinion and written transcript of the WLST decision, experienced intensive care staff, a local organ procurement coordination team familiar with DBD and DCD protocols and only in hospitals authorised for organ procurement. It is important to have an optimal and standardized national guidance to limit the known risk factors of graft failure (donor and recipient choice, warm and cold ischemia time), to increase acceptance by medical community and civil society and to improve results and allow more powerful analysis.

  19. Next-Generation Sequencing in Post-mortem Genetic Testing of Young Sudden Cardiac Death Cases

    PubMed Central

    Lahrouchi, Najim; Behr, Elijah R.; Bezzina, Connie R.

    2016-01-01

    Sudden cardiac death (SCD) in the young (<40 years) occurs in the setting of a variety of rare inherited cardiac disorders and is a disastrous event for family members. Establishing the cause of SCD is important as it permits the pre-symptomatic identification of relatives at risk of SCD. Sudden arrhythmic death syndrome (SADS) is defined as SCD in the setting of negative autopsy findings and toxicological analysis. In such cases, reaching a diagnosis is even more challenging and post-mortem genetic testing can crucially contribute to the identification of the underlying cause of death. In this review, we will discuss the current achievements of “the molecular autopsy” in young SADS cases and provide an overview of key challenges in assessing pathogenicity (i.e., causality) of genetic variants identified through next-generation sequencing. PMID:27303672

  20. Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death.

    PubMed

    Krown, K A; Page, M T; Nguyen, C; Zechner, D; Gutierrez, V; Comstock, K L; Glembotski, C C; Quintana, P J; Sabbadini, R A

    1996-12-15

    In the present study, it was shown that physiologically relevant levels of the proinflammatory cytokine TNFalpha induced apoptosis in rat cardiomyocytes in vitro, as quantified by single cell microgel electrophoresis of nuclei ("cardiac comets") as well as by morphological and biochemical criteria. It was also shown that TNFalpha stimulated production of the endogenous second messenger, sphingosine, suggesting sphingolipid involvement in TNFalpha-mediated cardiomyocyte apoptosis. Consistent with this hypothesis, sphingosine strongly induced cardiomyocyte apoptosis. The ability of the appropriate stimulus to drive cardiomyocytes into apoptosis indicated that these cells were primed for apoptosis and were susceptible to clinically relevant apoptotic triggers, such as TNFalpha. These findings suggest that the elevated TNFalpha levels seen in a variety of clinical conditions, including sepsis and ischemic myocardial disorders, may contribute to TNFalpha-induced cardiac cell death. Cardiomyocyte apoptosis is also discussed in terms of its potential beneficial role in limiting the area of cardiac cell involvement as a consequence of myocardial infarction, viral infection, and primary cardiac tumors.

  1. 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

  2. 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

  3. Basiliximab induction in kidney transplantation with donation after cardiac death donors

    PubMed Central

    YAO, XUPING; WENG, GUOBIN; WEI, JUNJUN; GAO, WENBO

    2016-01-01

    Basiliximab is a monoclonal antibody that binds to the α-chain of the interleukin (IL)-2 receptor. It is used as induction therapy in kidney transplantation. The objective of the present study was to evaluate induction therapy with single-dose basiliximab (Simulect®) in kidney transplantation with donation after cardiac death (DCD) donors. A total of 33 DCD kidney transplants were performed between December 2010 and July 2013 in patients who received single-dose basiliximab (20 mg) as induction therapy. The maintenance immunosuppression included calcineurin inhibitor (cyclosporine A or tacrolimus), mycophenolate mofetil and corticosteroids. The follow-up time was 1 year. The mean ages of the DCD donors and recipients were 29.3 and 41.1 years, respectively. Within the 1-year follow-up, the overall incidence of acute rejection was 9.1%. There were 10 cases of delayed graft function among the recipients. Mean serum creatinine values at 1 week and at 1, 3, 6, 9 and 12 months post-transplantation were 257.6, 238.2, 194.5, 159.3, 137.9 and 110.8 µmol/l, respectively, with a favorable trend to allograft function recovery over time. The 1-year patient and graft survival rates were 96.9 and 90.9%, respectively, with an infection rate of 24.2%. Increased alanine aminotransferase/aspartate transaminase levels in only 2 patients were considered to be associated with basiliximab. This experience with single-dose basiliximab for induction therapy in DCD kidney transplantation showed that favorable clinical outcomes were achieved in terms of graft survival and function within 1 year. PMID:27284346

  4. Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

    PubMed

    Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

    2015-01-01

    Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City.

  5. Next generation sequencing for molecular confirmation of hereditary sudden cardiac death syndromes.

    PubMed

    Márquez, Manlio F; Cruz-Robles, David; Ines-Real, Selene; Vargas-Alarcón, Gilberto; Cárdenas, Manuel

    2015-01-01

    Hereditary sudden cardiac death syndromes comprise a wide range of diseases resulting from alteration in cardiac ion channels. Genes involved in these syndromes represent diverse mutations that cause the altered encoding of the diverse proteins constituting these channels, thus affecting directly the currents of the corresponding ions. In the present article we will briefly review how to arrive to a clinical diagnosis and we will present the results of molecular genetic studies made in Mexican subjects attending the SCD Syndromes Clinic of the National Institute of Cardiology of Mexico City. PMID:25661095

  6. Differences in postmortem urea nitrogen, creatinine and uric acid levels between blood and pericardial fluid in acute death.

    PubMed

    Zhu, Bao-Li; Ishikawa, Takaki; Michiue, Tomomi; Tanaka, Sayaka; Zhao, Dong; Li, Dong-Ri; Quan, Li; Oritani, Shigeki; Maeda, Hitoshi

    2007-05-01

    Previous studies showed significant differences in postmortem urea nitrogen (UN), creatinine (Cr) and uric acid (UA) levels in heart blood depending on the causes of death, including acute death. In addition, the levels in pericardial fluid approximated the clinical serum reference ranges, and their elevations may be assessed based on clinical criteria. The present study investigated difference between blood and pericardial levels of these markers. Medicolegal autopsy cases (n=556, within 48h postmortem) of the following causes of death were examined: injury (n=136), asphyxiation (n=50), drowning (n=39), fire fatalities (n=99), hyperthermia (n=11), hypothermia (n=8), poisoning (n=26), delayed traumatic death (n=44) and natural diseases (n=143). When serum UN, Cr and UA levels were compared with the pericardial levels, there was an equivalency for delayed traumatic death and chronic renal failure, although each level was markedly elevated. Parallel increases in serum and pericardial UA and/or Cr levels were also observed for hypothermia and gastrointestinal bleeding. However, in drowning cases, the left cardiac and pericardial UN levels were lower than the right cardiac and peripheral levels, suggesting the influence of water aspiration. Significant elevations in serum and pericardial Cr and UA levels with a higher serum/pericardial UA ratio for fatal methamphetamine intoxication suggest progressive skeletal muscle damage due to advanced hypoxia/acidosis. Similar findings were often observed for other acute and subacute deaths. These findings suggest that a comparison between blood and pericardial nitrogenous compounds would be useful for investigating the cause and process of death.

  7. Chronic kidney disease and risk factors responsible for sudden cardiac death: a whiff of hope?

    PubMed Central

    Kiuchi, Márcio G.; Mion, Decio

    2015-01-01

    Several studies have shown a strong independent association between chronic kidney disease (CKD) and cardiovascular events, including death, heart failure, and myocardial infarction. Recent clinical trials extend this range of adverse cardiovascular events, also including ventricular arrhythmias and sudden cardiac death. Furthermore, other studies suggest structural remodeling of the heart and electrophysiological alterations in this population. These processes may explain the increased risk of arrhythmia in kidney disease and help to identify patients who are at increased risk of sudden cardiac death. Sympathetic hyperactivity is well known to increase cardiovascular risk in CKD patients and is a hallmark of essential hypertensive state that occurs early in the clinical course of the disease. In CKD, the sympathetic hyperactivity seems to be expressed at the earliest clinical stage of the disease, showing a direct relationship with the severity of the condition of renal failure, being more pronounced in the terminal stage of CKD. The sympathetic efferent and afferent neural activity in kidney failure is a key mediator for the maintenance and progression of the disease. The aim of this review was to show that the feedback loop of this cycle, due to adrenergic hyperactivity, also aggravates many of the risk factors responsible for causing sudden cardiac death and may be a potential target modifiable by percutaneous renal sympathetic denervation. If it is feasible and effective in end-stage renal disease, little is known. PMID:27069851

  8. Sudden unexpected death due to severe pulmonary and cardiac sarcoidosis.

    PubMed

    Ginelliová, Alžbeta; Farkaš, Daniel; Farkašová Iannaccone, Silvia; Vyhnálková, Vlasta

    2016-09-01

    In this paper we report the autopsy findings of a 57 year old woman who died unexpectedly at home. She had been complaining of shortness of breath, episodes of dry coughing, and nausea. Her past medical and social history was unremarkable. She had no previous history of any viral or bacterial disease and no history of oncological disorders. Autopsy revealed multiple grayish-white nodular lesions in the pleura and epicardial fat and areas resembling fibrosis on the cut surface of the anterior and posterior wall of the left ventricle and interventricular septum. Histological examination of the lungs and heart revealed multiple well-formed noncaseating epithelioid cell granulomas with multinucleated giant cells. Death was attributed to myocardial ischemia due to vasculitis of intramural coronary artery branches associated with sarcoidosis. Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of noncaseating epithelioid cell granulomas in the affected organs and tissues. The diagnosis of sarcoidosis in this case was established when other causes of granulomatous disease such as tuberculosis, berylliosis, hypersensitivity pneumonitis, and giant cell myocarditis had been reasonably excluded. PMID:27379608

  9. Sudden cardiac death in marathons: a systematic review.

    PubMed

    Waite, Oliver; Smith, Andy; Madge, Luke; Spring, Hannah; Noret, Nathalie

    2016-01-01

    The aim of this systematic review is to summarise the results of cohort studies that examined the incidence of SCD in marathons and to assess the quality of the methods used. A search of the PROSPERO international database revealed no prospective or published systematic reviews investigating SCD in marathons. The review was conducted using studies that reported and characterised the incidence of SCD in people participating in marathons. Studies were identified via electronic database searches (Medline, CINAHL, SPORTDiscus and Google Scholar) from January 1, 1966 to October 1, 2014 and through manual literature searches. 7 studies met the inclusion criteria and were included in this review. 6 of the studies were conducted in the USA and 1 in the UK. These studies covered a 34-year period involving between 215,413 and 3,949,000 runners. The SCD of between 4 and 28 people are recorded in the papers and the reported estimates of the incidence of SCD in marathons ranged widely from 0.6 to 1.9 per 100,000 runners. The proportion of those suffering SCD who were male ranged from 57.1% to 100% and the mean age reported in the papers, ranged from 37 to 48. This review raises 4 methodological concerns over i) collating reports of SCD in marathons; ii) time of death in relation to the marathon; iii) the use of registrants rather than runners in the estimates of sample size and iv) limited detail on runners exercise history. These four concerns all threaten the reliability and interpretation of any estimate of SCD incidence rates in marathons.  This review recommends that the methods used to collect data on SCD in marathons be improved and that a central reporting system be established. PMID:26765272

  10. 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

  11. 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

  12. 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.

  13. Deaths following acute diarrhoeal diseases among hospitalised infants in Kuala Lumpur.

    PubMed

    Lee, W S; Ooi, T L

    1999-09-01

    The risk factors and modes of death following acute diarrhoeal illness in children admitted to University Hospital, Kuala Lumpur between 1982 and 1997 were studied retrospectively. Among 4,689 cases of acute gastroenteritis admitted, ten deaths were noted. The case mortality rate was 2.1/1000 admissions. All deaths were infants below one year, with eight females and two males. Acute renal failure and acute pulmonary oedema were common preceding events. Female sex, infants less than twelve months, the presence of hyper or hyponatraemia and moderate to severe dehydration on admission were risk factors for deaths.

  14. Sudden cardiac death and chronic kidney disease: From pathophysiology to treatment strategies.

    PubMed

    Di Lullo, L; Rivera, R; Barbera, V; Bellasi, A; Cozzolino, M; Russo, D; De Pascalis, A; Banerjee, D; Floccari, F; Ronco, C

    2016-08-15

    Chronic kidney disease (CKD) patients demonstrate higher rates of cardiovascular mortality and morbidity; and increased incidence of sudden cardiac death (SCD) with declining kidney failure. Coronary artery disease (CAD) associated risk factors are the major determinants of SCD in the general population. However, current evidence suggests that in CKD patients, traditional cardiovascular risk factors may play a lesser role. Complex relationships between CKD-specific risk factors, structural heart disease, and ventricular arrhythmias (VA) contribute to the high risk of SCD. In dialysis patients, the occurrence of VA and SCD could be exacerbated by electrolyte shifts, divalent ion abnormalities, sympathetic overactivity, inflammation and iron toxicity. As outcomes in CKD patients after cardiac arrest are poor, primary and secondary prevention of SCD and cardiac arrest could reduce cardiovascular mortality in patients with CKD. PMID:27174593

  15. 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

  16. 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

  17. [Liver transplant with donated graft after controlled cardiac death. Current situation].

    PubMed

    Abradelo De Usera, Manuel; Jiménez Romero, Carlos; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2013-11-01

    An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review.

  18. Sudden cardiac death while playing Australian Rules football: a retrospective 14 year review.

    PubMed

    Parsons, Sarah; Lynch, Matthew

    2016-06-01

    Australian Rules football is a sport which evolved from Gaelic football and which is played by a large number of predominantly male participants in a number of countries. The highest participation rates are in the southern states of Australia. A retrospective review over a period of 14 years identified 14 cases of sudden cardiac death that occurred in individuals while playing the sport. All were male and ranged in age from 13 to 36 years with a mean and median age of 23 years. A spectrum of cardiac causes was identified including coronary artery atherosclerosis, myocarditis, anomalous coronary artery anatomy, arrhythmogenic right ventricular cardiomyopathy, and healed Kawasaki disease. In 5 cases the heart was morphologically normal raising the possibility of a channelopathy. No traumatic deaths were identified. Some of the individuals had experienced symptoms prior to the fatal episode and the role of pre participation screening in reducing mortality is discussed.

  19. A pilot programme of organ donation after cardiac death in China.

    PubMed

    Huang, Jiefu; Millis, J Michael; Mao, Yilei; Millis, M Andrew; Sang, Xinting; Zhong, Shouxian

    2012-03-01

    China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards. PMID:22078722

  20. Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls

    NASA Technical Reports Server (NTRS)

    Rosenbaum, D. S.; Albrecht, P.; Cohen, R. J.

    1996-01-01

    Sudden cardiac death remains a preeminent public health problem. Despite advances in preventative treatment for patients known to be at risk, to date we have been able to identify, and thus treat, only a small minority of these patients. Therefore, there is a major need to develop noninvasive diagnostic technologies to identify patients at risk. Recent studies have demonstrated that measurement of microvolt-level T wave alternans is a promising technique for the accurate identification of patients at risk for ventricular arrhythmias and sudden cardiac death. In this article, we review the clinical data establishing the relationship between microvolt T wave alternans and susceptibility to ventricular arrhythmias. We also review the methods and technology that have been developed to measure microvolt levels of T wave alternans noninvasively in broad populations of ambulatory patients. In particular, we examine techniques that permit the accurate measurement of T wave alternans during exercise stress testing.

  1. A pilot programme of organ donation after cardiac death in China.

    PubMed

    Huang, Jiefu; Millis, J Michael; Mao, Yilei; Millis, M Andrew; Sang, Xinting; Zhong, Shouxian

    2012-03-01

    China's aims are to develop an ethical and sustainable organ transplantation system for the Chinese people and to be accepted as a responsible member of the international transplantation community. In 2007, China implemented the Regulation on Human Organ Transplantation, which was the first step towards the establishment of a voluntary organ donation system. Although progress has been made, several ethical and legal issues associated with transplantation in China remain, including the use of organs from executed prisoners, organ scarcity, the illegal organ trade, and transplantation tourism. In this Health Policy article we outline the standards used to define cardiac death in China and a legal and procedural framework for an organ donation system based on voluntary donation after cardiac death that adheres to both China's social and cultural principles and international transplantation standards.

  2. [Liver transplant with donated graft after controlled cardiac death. Current situation].

    PubMed

    Abradelo De Usera, Manuel; Jiménez Romero, Carlos; Loinaz Segurola, Carmelo; Moreno González, Enrique

    2013-11-01

    An increasing pressure on the liver transplant waiting list, forces us to explore new sources, in order to expand the donor pool. One of the most interesting and with a promising potential, is donation after cardiac death (DCD). Initially, this activity has developed in Spain by means of the Maastricht type II donation in the uncontrolled setting. For different reasons, donation after controlled cardiac death has been reconsidered in our country. The most outstanding circumstance involved in DCD donation is a potential ischemic stress, that could cause severe liver graft cell damage, resulting in an adverse effect on liver transplant results, in terms of complications and outcomes. The complex and particular issues related to DCD Donation will be discussed in this review. PMID:24021972

  3. Novel approaches to expanding the lung donor pool: donation after cardiac death and ex vivo conditioning.

    PubMed

    Cypel, Marcelo; Yeung, Jonathan C; Keshavjee, Shaf

    2011-06-01

    Two novel approaches have been developed to potentially increase the availability of donor lungs for lung transplantation. In the first approach, lungs from donation after cardiac death (DCD) donors are used to increase the quantity of organ donors. In the second approach, a newly developed normothermic ex vivo lung perfusion (EVLP) technique is used as a means of reassessing the adequacy of lung function from DCD and from high-risk brain death donors prior to transplantation. This EVLP technique can also act as a platform for the delivery of novel therapies to repair injured organs ex vivo. PMID:21511086

  4. Cardiac dysfunction following brain death after severe pediatric traumatic brain injury: A preliminary study of 32 children

    PubMed Central

    Krishnamoorthy, Vijay; Prathep, Sumidtra; Sharma, Deepak; Fujita, Yasuki; Armstead, William; Vavilala, Monica S.

    2015-01-01

    Background: Cardiac dysfunction after brain death has been described in a variety of brain injury paradigms but is not well understood after severe pediatric traumatic brain injury (TBI). Cardiac dysfunction may have implications for organ donation in this patient population. Materials and Methods: We conducted a retrospective cohort study of pediatric patients with severe TBI, both with and without a diagnosis of brain death, who underwent echocardiography during the first 2 weeks after TBI, between the period of 2003–2011. We examined cardiac dysfunction in patients with and without a diagnosis of brain death. Results: In all, 32 (2.3%) of 1,413 severe pediatric TBI patients underwent echocardiogram evaluation. Most patients had head abbreviated injury score 5 (range 2–6) and subdural hematoma (34.4%). Ten patients with TBI had brain death compared with 22 severe TBI patients who did not have brain death. Four (40%) of 10 pediatric TBI patients with brain death had a low ejection fraction (EF) compared with 1 (4.5%) of 22 pediatric TBI patients without brain death who had low EF (OR = 14, P = 0.024). Conclusions: The incidence of cardiac dysfunction is higher among pediatric severe TBI patients with a diagnosis of brain death, as compared to patients without brain death. This finding may have implications for cardiac organ donation from this population and deserves further study. PMID:26157654

  5. Polymorphic Ventricular Tachycardia/Ventricular Fibrillation and Sudden Cardiac Death in the Normal Heart.

    PubMed

    Shah, Ashok J; Hocini, Meleze; Denis, Arnaud; Derval, Nicolas; Sacher, Frederic; Jais, Pierre; Haissaguerre, Michel

    2016-09-01

    Primary electrical diseases manifest with polymorphic ventricular tachycardia (PMVT) and ventricular fibrillation (VF) and along with idiopathic VF contribute to about 10% of sudden cardiac deaths (SCDs) overall. These disorders include long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome, and early repolarization syndrome. This article reviews the clinical electrophysiological management of PMVT/VF in a structurally normal heart affected with these disorders. PMID:27521091

  6. Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure.

    PubMed

    Kasama, Shu; Toyama, Takuji; Kurabayashi, Masahiko

    2016-01-01

    The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.

  7. Pathological characteristics of liver allografts from donation after brain death followed by cardiac death in pigs.

    PubMed

    Ye, Hui; Wang, Dong-Ping; Zhang, Chuan-Zhao; Zhang, Long-Juan; Wang, Hao-Chen; Li, Zhuo-Hui; Chen, Zhen; Zhang, Tao; Cai, Chang-Jie; Ju, Wei-Qiang; Ma, Yi; Guo, Zhi-Yong; He, Xiao-Shun

    2014-10-01

    Donation after brain death followed by circulatory death (DBCD) is a unique practice in China. The aim of this study was to define the pathologic characteristics of DBCD liver allografts in a porcine model. Fifteen male pigs (25-30 kg) were allocated randomly into donation after brain death (DBD), donation after circulatory death (DCD) and DBCD groups. Brain death was induced by augmenting intracranial pressure. Circulatory death was induced by withdrawal of life support in DBCD group and by venous injection of 40 mL 10% potassium chloride in DCD group. The donor livers were perfused in situ and kept in cold storage for 4 h. Liver tissue and common bile duct samples were collected for hematoxylin and eosin staining, TUNEL testing and electron microscopic examination. Spot necrosis was found in hepatic parenchyma of DBD and DBCD groups, while a large area of necrosis was shown in DCD group. The apoptosis rate of hepatocytes in DBD [(0.56±0.30)%] and DBCD [(0.50 ± 0.11)%] groups was much lower than that in DCD group [(3.78±0.33)%] (P<0.05). And there was no significant difference between DBD group and DBCD group (P>0.05)). The structures of bile duct were intact in both DBD and DBCD groups, while the biliary epithelium was totally damaged in DCD group. Under electron microscope, the DBD hepatocytes were characterized by intact cell membrane, well-organized endoplasmic reticulum, mild mitochondria edema and abundant glycogens. Broken cell membrane, mild inflammatory cell infiltration and sinusoidal epithelium edema, as well as reduced glycogen volume, were found in the DBCD hepatocytes. The DCD hepatocytes had more profound cell organelle injury and much less glycogen storage. In conclusion, the preservation injury of DBCD liver allografts is much less severe than that of un-controlled DCD, but more severe than that of DBD liver allografts under electron microscope, which might reflect post-transplant liver function to some extent.

  8. 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

  9. Nonapoptotic cell death in acute kidney injury and transplantation.

    PubMed

    Linkermann, Andreas

    2016-01-01

    Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047

  10. 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...

  11. A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death

    PubMed Central

    Wang, Z; Liu, D; Varin, A; Nicolas, V; Courilleau, D; Mateo, P; Caubere, C; Rouet, P; Gomez, A-M; Vandecasteele, G; Fischmeister, R; Brenner, C

    2016-01-01

    Although cardiac cytosolic cyclic 3′,5′-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3−) and Ca2+, sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca2+ entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na+/Ca2+ exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3− rescued the sensitization of mitochondria to Ca2+-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies. PMID:27100892

  12. 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.

  13. End-of-life and brain death in acute coma and disorders of consciousness.

    PubMed

    Greer, David M; Curiale, Gioacchino G

    2013-04-01

    Consulting neurologists are often asked to evaluate patients in acute nontraumatic coma. The authors review prognostication of functional outcomes, determining brain death, and managing end-of-life care. Prognostication of outcome after cardiac arrest in comatose patients is a frequently encountered scenario with high-stakes implications. However, current guidelines are limited by a failure to address the use of therapeutic hypothermia and thus may lead to overly pessimistic outcome prediction. Pupillary light responses and corneal reflexes remain highly predictive clinical signs of a poor prognosis. Motor responses have a high false-positive rate for predicting a poor outcome, especially in patients treated with therapeutic hypothermia. Ancillary testing with electroencephalography, somatosensory evoked potentials, serum neuron-specific enolase, and neuroimaging is often useful in predicting outcomes. Brain death is a clinical condition of irreversible coma of known cause with absent brainstem reflexes and apnea. An understanding of the value of confirmatory testing and the potential for confounding factors is essential in making a correct diagnosis. As coma carries a high mortality rate, neurologists must be capable of guiding goals of care, discussing end-of-life issues, and understanding organ-procurement procedures. PMID:23888399

  14. Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death.

    PubMed

    Stadelmann, Mathieu; Dornbierer, Monika; Clément, David; Gahl, Brigitta; Dick, Florian; Carrel, Thierry P; Tevaearai, Hendrik T; Longnus, Sarah

    2013-03-01

    Although heart donation after cardiac death (DCD) could greatly improve graft availability, concerns regarding warm ischemic damage typically preclude transplantation. Improving tolerance to warm ischemia may thus open a window of opportunity for DCD hearts. We investigated the hypothesis that, compared with normothermia, mild hypothermia (32° C) initiated after ischemic onset improves cardiac functional recovery upon reperfusion. Isolated, working hearts from adult, male Wistar rats underwent global, no-flow ischemia, and reperfusion (n = 28). After ischemic onset, temperature was maintained at either 37° C for 20 or 30 min or reduced to 32° C for 40, 50, or 60 min. Recovery was measured after 60-min reperfusion. Following normothermic ischemia, recovery of rate-pressure product (RPP; per cent of preischemic value) was almost complete after 20-min ischemia (97 ± 9%), whereas no recovery was detectable after 30-min ischemia. After mildly hypothermic ischemia (32° C), RPP also recovered well after 40 min (86 ± 4%). Markers of metabolism and necrosis were similar in 37° C/20 min and 32° C/40 min groups. Simple reduction in cardiac temperature by a few degrees after the onset of global ischemia dramatically prolongs the interval during which the heart remains resistant to functional deterioration. Preservation of hemodynamic function is associated with improved metabolic recovery and reduced necrosis. The application of mild hypothermia may be a simple first step towards development of clinical protocols for DCD heart recovery.

  15. Implantable Defibrillators for Secondary Prevention of Sudden Cardiac Death in Cardiac Surgery Patients With Perioperative Ventricular Arrhythmias

    PubMed Central

    Nageh, Maged F.; Kim, John J.; Chen, Lie‐Hong; Yao, Janis F.

    2014-01-01

    Background Randomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias. Methods and Results The electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty‐four patients were identified; 93/164 had an ICD for sustained pre‐ or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD‐T), and secondary end points are TM and ICD‐T. During the mean follow up of 49 months, the primary endpoint of TM+ICD‐T and individual end points of TM and ICD‐T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD‐T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias. Conclusion Our data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients. PMID:25146702

  16. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction.

    PubMed

    Gatzoulis, Konstantinos A; Tsiachris, Dimitris; Arsenos, Petros; Tousoulis, Dimitris

    2016-01-26

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death. PMID:26839662

  17. Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction.

    PubMed

    Gatzoulis, Konstantinos A; Tsiachris, Dimitris; Arsenos, Petros; Tousoulis, Dimitris

    2016-01-26

    Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death.

  18. Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.

    PubMed

    Kennedy, Hannah; Haack, Tobias B; Hartill, Verity; Mataković, Lavinija; Baumgartner, E Regula; Potter, Howard; Mackay, Richard; Alston, Charlotte L; O'Sullivan, Siobhan; McFarland, Robert; Connolly, Grainne; Gannon, Caroline; King, Richard; Mead, Scott; Crozier, Ian; Chan, Wandy; Florkowski, Chris M; Sage, Martin; Höfken, Thomas; Alhaddad, Bader; Kremer, Laura S; Kopajtich, Robert; Feichtinger, René G; Sperl, Wolfgang; Rodenburg, Richard J; Minet, Jean Claude; Dobbie, Angus; Strom, Tim M; Meitinger, Thomas; George, Peter M; Johnson, Colin A; Taylor, Robert W; Prokisch, Holger; Doudney, Kit; Mayr, Johannes A

    2016-09-01

    We have used whole-exome sequencing in ten individuals from four unrelated pedigrees to identify biallelic missense mutations in the nuclear-encoded mitochondrial inorganic pyrophosphatase (PPA2) that are associated with mitochondrial disease. These individuals show a range of severity, indicating that PPA2 mutations may cause a spectrum of mitochondrial disease phenotypes. Severe symptoms include seizures, lactic acidosis, cardiac arrhythmia, and death within days of birth. In the index family, presentation was milder and manifested as cardiac fibrosis and an exquisite sensitivity to alcohol, leading to sudden arrhythmic cardiac death in the second decade of life. Comparison of normal and mutant PPA2-containing mitochondria from fibroblasts showed that the activity of inorganic pyrophosphatase was significantly reduced in affected individuals. Recombinant PPA2 enzymes modeling hypomorphic missense mutations had decreased activity that correlated with disease severity. These findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized. PMID:27523597

  19. T-Cell Prolymphocytic Leukemia with Extensive Cardiovascular Infiltrate Leading to Multiple Myocardial Infarctions and Cardiac Death

    PubMed Central

    Cheng, Hong; Feldman, Tatyana; Butt, Yasmeen; Chow, Kar F.; Yang, Xiao Yan; de Vinck, David C.

    2014-01-01

    Lymphocytic neoplasm involving the heart is not common and usually presents with pericardial effusion or focal myocardial infiltration. Myocardial infarctions due to leukemic infiltration of the coronary arteries are rarely reported. We present the case of a 52-year-old Guatemalan man with a one-year history of untreated T-cell prolymphocytic leukemia. He was admitted to our hospital for chemotherapy and evaluation of a pulmonary cavitary lesion by wedge resection. During sedation, the patient experienced acute respiratory failure and hypovolemic shock, from which he could not be resuscitated. Autopsy revealed that leukemic cells extensively infiltrated the aorta, myocardium, and coronary arteries. The lumina of the 3 major coronary artery branches showed 70% to 95% stenosis, with multifocal remote myocardial infarctions. Tumor cells were also detected in the lungs and other organs. The acute cardiorespiratory insufficiency secondary to leukemia—particularly the extensive infiltration of the coronary arteries and myocardium, and the multiple myocardial infarctions—eventually resulted in cardiac death. PMID:25593528

  20. Long-Term Adaptive Servo-Ventilator Treatment Prevents Cardiac Death and Improves Clinical Outcome.

    PubMed

    Imamura, Teruhiko; Kinugawa, Koichiro; Nitta, Daisuke; Komuro, Issei

    2016-01-01

    Adaptive servo-ventilation (ASV) is a recently developed, noninvasive therapeutic tool for the treatment of heart failure (HF). However, the efficacy of ASV therapy in patients with advanced HF remains uncertain, especially as regards its contribution to freedom from cardiac replacement therapy. A total of 85 patients with advanced HF (New York Heart Association [NYHA] class IV 71%, inotrope infusion-dependent 34%) refractory to guideline-directed medical therapy, received ASV therapy, irrespective of sleep-disordered breathing, at our institute between 2008 and 2014. Among these 85 patients, 46 continued ASV therapy for > 1 month (continued group), whereas 39 discontinued the therapy after < 1 month because of intolerance (discontinued group). There were no significant differences in baseline variables between the two groups. Heart rate indicating sympathetic activity, left ventricular (LV) reverse remodeling assessed by LV diastolic diameter, LV ejection fraction, and the grades of mitral and tricuspid regurgitations, HF severity assessed by NYHA class and plasma level of B-type natriuretic peptide, and end-organ dysfunction, improved significantly at 6 months following the initiation of ASV therapy (P < 0.05 for all). All-cause mortality and cardiac death rate were significantly lower during 2-year follow up in the continued group (P < 0.05 for both). In conclusion, ASV is a novel therapeutic tool prior to cardiac replacement therapy in patients with advanced HF and may prolong the period until cardiac replacement therapy becomes necessary. PMID:26742883

  1. Risk Stratification for Sudden Cardiac Death: Current Approaches and Predictive Value

    PubMed Central

    Lopera, Gustavo; Curtis, Anne B.

    2009-01-01

    Sudden cardiac death (SCD) is a serious public health problem; the annual incidence of out-of-hospital cardiac arrest in North America is approximately 166,200. Identifying patients at risk is a difficult proposition. At the present time, left ventricular ejection fraction (LVEF) remains the single most important marker for risk stratification. According to current guidelines, most patients with LVEF <35% could benefit from prophylactic ICD implantation, particularly in the setting of symptomatic heart failure. Current risk stratification strategies fail to identify patients at risk of SCD in larger population groups encompassing a greater number of potential SCD victims. However, the best approach to identifying patients and the value of various risk stratification tools is not entirely clear. The goal of this review is to discuss the problem of SCD and the value of the different risk stratification markers and their potential clinical use either alone or in combination with other risk stratification markers. PMID:20066150

  2. Aborted Sudden Cardiac Death and a Mother with Suspected Metabolic Myopathy

    PubMed Central

    Finsterer, Josef; Stöllberger, Claudia; Keller, Hans

    2014-01-01

    Aborted sudden cardiac death (SCD) has not been reported as initial manifestation of cardiac involvement in metabolic myopathy (MM). A 20-year-old female with a previous history of three syncopes, hyperhidrosis, and recurrent tick bites experienced aborted SCD. Her mother presented with MM, and a history of pituitary adenoma, nephroptosis, arterial hypertension, depression, migraine, goiter, pancreatitis, osteoporosis, hyperhidrosis, multiple muscle ruptures, and hyperlipidemia. After a few days of disorientation and amnesia, the young female recovered completely. Clinical neurological examination was noticeable for partial ophthalmoparesis and mild hyperprolactinemia. She received an implantable cardioverter defibrillator, which did not discharge so far. Recurrent syncopes and aborted SCD may be the initial manifestation of MM with multiple organ involvement. The family history is important in cases with aborted SCD to guide the diagnostic work-up. Phenotypic heterogeneity between the family members may be an indicator of MM. PMID:25187745

  3. Clinical islet isolation and transplantation outcomes with deceased cardiac death donors are similar to neurological determination of death donors.

    PubMed

    Andres, Axel; Kin, Tatsuya; O'Gorman, Doug; Livingstone, Scott; Bigam, David; Kneteman, Norman; Senior, Peter; Shapiro, A M James

    2016-01-01

    In islet transplantation, deceased cardiac death (DCD) donation has been identified as a potential extended source. There are currently no studies comparing outcomes between these categories, and our goal was to compare islet isolation success rates and transplantation outcomes between DCD and neurological determination of death (NDD) donors. Islet isolations from 15 DCD and 418 NDD were performed in our centre between September 2008 and September 2014. Donor variables, islet yields, metabolic function of isolated isled and insulin requirements at 1-month post-transplant were compared. Compared to NDD, pancreata from DCD were more often procured locally and donors required less vasopressive support (P < 0.001 and P = 0.023, respectively), but the other variables were similar between groups. Pre- and postpurification islet yields were similar between NDD and DCD (576 vs. 608 × 10(3) islet equivalent, P = 0.628 and 386 vs. 379, P = 0.881, respectively). The metabolic function was similar between NDD and DCD, as well as the mean decrease in insulin requirement at 1-month post-transplantation (NDD: 64.82%; DCD: 60.17% reduction, P = 0.517). These results support the broader use of DCD pancreata for islet isolation. A much larger DCD islet experience will be required to truly determine noninferiority of both short- and long-term outcomes.

  4. Hypothesis: holiday sudden cardiac death: food and alcohol inhibition of SULT1A enzymes as a precipitant.

    PubMed

    Eagle, Ken

    2012-10-01

    Sudden cardiac death is a significant health issue, causing millions of deaths worldwide annually. Studies have found that the likelihood of such death is higher in winter. Further studies identified that the highest likelihood occurs on Christmas Day and New Years Day, but not the interim period. Thanksgiving, Independence Day and the Islamic holiday Eid Al-Fitr also show significant increases in the rate of cardiac events or death. A number of mechanisms have been proposed, but none have satisfactorily explained the evidence. This article reviews the data supporting the existence of a holiday cardiac death phenomenon, the involvement of catecholamines and the normal modes of human catecholamine deactivation. Further evidence is reviewed that supports a hypothesized mechanism whereby critical SULT1A catecholamine deactivation enzymes can in some patients be inhibited by naturally-occurring phenols and polyphenols in foods and alcohols. If deactivation is inhibited by holiday consumption excesses, holiday stress or excitement could lead to a buildup of catecholamines that can cause fatal arrhythmias. Awareness of this mechanism could reduce deaths, both through doctor/patient education leading to a moderation in consumption and through the potential identification of patients with a predisposition to SULT1A inhibition. This hypothesis also raises parallels between sudden cardiac death in adults and Sudden Infant Death Syndrome (SIDS). The possible involvement of SULT1A inhibition in SIDS is discussed.

  5. Usefulness of combined history, physical examination, electrocardiogram, and limited echocardiogram in screening adolescent athletes for risk for sudden cardiac death.

    PubMed

    Anderson, Jeffrey B; Grenier, Michelle; Edwards, Nicholas M; Madsen, Nicolas L; Czosek, Richard J; Spar, David S; Barnes, Allison; Pratt, Jesse; King, Eileen; Knilans, Timothy K

    2014-12-01

    Sudden cardiac death in the young (SCDY) is the leading cause of death in young athletes during sport. Screening young athletes for high-risk cardiac defects is controversial. The purpose of this study was to assess the utility and feasibility of a comprehensive cardiac screening protocol in an adolescent population. Adolescent athletes were recruited from local schools and/or sports teams. Each subject underwent a history and/or physical examination, an electrocardiography (ECG), and a limited echocardiography (ECHO). The primary outcome measure was identification of cardiac abnormalities associated with an elevated risk for sudden death. We secondarily identified cardiac abnormalities not typically associated with a short-term risk of sudden death. A total of 659 adolescent athletes were evaluated; 64% men. Five subjects had cardiac findings associated with an elevated risk for sudden death: prolonged QTc >500 ms (n = 2) and type I Brugada pattern (n = 1), identified with ECG; dilated cardiomyopathy (n = 1) and significant aortic root dilation; and z-score = +5.5 (n = 1). History and physical examination alone identified 76 (11.5%) subjects with any cardiac findings. ECG identified 76 (11.5%) subjects in which a follow-up ECHO or cardiology visit was recommended. Left ventricular mass was normal by ECHO in all but 1 patient with LVH on ECG. ECHO identified 34 (5.1%) subjects in whom a follow-up ECHO or cardiology visit was recommended. In conclusion, physical examination alone was ineffective in identification of subjects at elevated risk for SCDY. Screening ECHO identified patients with underlying cardiac disease not associated with immediate risk for SCDY. Cost of comprehensive cardiac screening is high.

  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. Comparative effectiveness of donation after cardiac death versus donation after brain death liver transplantation: Recognizing who can benefit.

    PubMed

    Jay, Colleen L; Skaro, Anton I; Ladner, Daniela P; Wang, Edward; Lyuksemburg, Vadim; Chang, Yaojen; Xu, Hongmei; Talakokkla, Sandhya; Parikh, Neehar; Holl, Jane L; Hazen, Gordon B; Abecassis, Michael M

    2012-06-01

    Due to organ scarcity and wait-list mortality, transplantation of donation after cardiac death (DCD) livers has increased. However, the group of patients benefiting from DCD liver transplantation is unknown. We studied the comparative effectiveness of DCD versus donation after brain death (DBD) liver transplantation. A Markov model was constructed to compare undergoing DCD transplantation with remaining on the wait-list until death or DBD liver transplantation. Differences in life years, quality-adjusted life years (QALYs), and costs according to candidate Model for End-Stage Liver Disease (MELD) score were considered. A separate model for hepatocellular carcinoma (HCC) patients with and without MELD exception points was constructed. For patients with a MELD score <15, DCD transplantation resulted in greater costs and reduced effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental cost-effectiveness ratio (ICER) was >$2,000,000/QALY. Patients with MELD scores of 21 to 30 (0.25 QALYs) and >30 (0.83 QALYs) also benefited from DCD transplantation with ICERs of $478,222/QALY and $120,144/QALY, respectively. Sensitivity analyses demonstrated stable results for MELD scores <15 and >20, but the preferred strategy for the MELD 15 to 20 category was uncertain. DCD transplantation was associated with increased costs and reduced survival for HCC patients with exception points but led to improved survival (0.26 QALYs) at a cost of $392,067/QALY for patients without exception points. In conclusion, DCD liver transplantation results in inferior survival for patients with a MELD score <15 and HCC patients receiving MELD exception points, but provides a survival benefit to patients with a MELD score >20 and to HCC patients without MELD exception points.

  8. Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.

    PubMed

    Navas de Solis, C

    2016-07-01

    Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes. PMID:27156002

  9. Exercising arrhythmias and sudden cardiac death in horses: Review of the literature and comparative aspects.

    PubMed

    Navas de Solis, C

    2016-07-01

    Arrhythmias are common in equine athletes during and immediately after exercise. Many of these rhythm variations are not clinically relevant. In horses, a link between different exercising arrhythmias and poor performance or between exercising arrhythmias and sudden cardiac death (SCD) is strongly suspected but not fully understood or proven. SCD during races or competitions is rare, but has catastrophic consequences for the safety of the human partner and public perceptions of welfare during equestrian sports. This review summarises current knowledge of equine exercise arrhythmias and their implications in SCD and compares existing principles and recommendations for equine subjects with those for human athletes.

  10. Cardiac asystole following cannabis (marijuana) usage--additional mechanism for sudden death?

    PubMed

    Menahem, Samuel

    2013-12-10

    A 21 year old university student previously operated during infancy for an unobstructed total anomalous pulmonary venous drainage with an excellent result, was noted on a routine follow up 24 h Holter monitor to have multiple pauses related to cardiac asystole, the longest lasting 5.8 s and temporally related to marijuana inhalation. A repeat Holter was normal following a two week cessation of marijuana usage and again when carried out 3 months later. The documented periods of asystole may be a precursor of sudden death seen in addicts even without evidence of ischaemic heart disease. PMID:24200372

  11. Cardiac effects of anabolic steroids: hypertrophy, ischemia and electrical remodelling as potential triggers of sudden death.

    PubMed

    Nascimento, J H M; Medei, E

    2011-05-01

    Anabolic-androgenic steroids (AAS) are synthetic testosterone derivatives developed to maximise anabolic activity and minimise androgenic activity. AAS abuse is widespread among both athletes and non-athletes at fitness centres and is becoming a public health issue. In addition to their atherogenic, thrombogenic and spastic effects, AAS have direct cardiotoxic effects by causing hypertrophy, electrical and structural remodelling, and contractile dysfunction and by increasing the susceptibility to ischemic injuries. All of these factors contribute to an increased risk of ventricular arrhythmias and sudden cardiac death.

  12. The Mikamo lecture. Role of higher nervous activity in sudden cardiac death.

    PubMed

    Lown, B

    1990-06-01

    The brain receives and catalogues myriads of information from within and without the organism. These inputs promote neural integration of bodily function through a multiplicity of cybernetic feedback loops. Higher nervous activity shapes the contours of perceived well-being and determines the course and progress of disease. Behavioral and neural factors play an important role in cardiovascular function and are especially relevant to the problem of sudden cardiac death (SCD). Clinical data attesting to the role of biobehavioral factors in SCD derive from a diversity of sources. It has long been known that bereavement increases the prevalence of cardiac fatality. Business failure rates are strongly related to increased mortality among persons aged 55 and over. Recession in economic activity, with increasing unemployment, is associated with augmented death rates from ischemic heart disease. In extensive surveys conducted among London civil servants, Rose and Marmot found not only the level but the type of employment to be a factor determining coronary heart disease mortality. Blue collar workers had a 3.6 times greater chance of dying from heart disease than an age-matched population in the higher ranks of civil service. A man's employment status was a stronger predictor of risk for dying from coronary heart disease than any of the usual risk factors, such as smoking, blood pressure, height-weight ratio, leisure time activities, glucose tolerance, or plasma cholesterol. Operation of behavioral factors is also suggested by the time of occurrence of sudden death. Among 3,983 men followed for more than 30 years, Rabkin and co-workers observed an excess proportion of fatalities on Mondays. No such pattern was noted for cancer mortality. Not only the day of the week but the time of day appears to be a factor. Muller and co-workers found a significant preponderance in the occurrence of myocardial infarction and sudden death from 6:00 AM to noon. They could not implicate

  13. 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

  14. [Updated ESC guideline: innovations for the treatment of ventricular arrhythmias and recommendations for prevention of sudden cardiac death].

    PubMed

    Eckardt, L; Deneke, T

    2016-09-01

    The 2015 European Society of Cardiology Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death is an update of the former 2006 European/American guidelines. This new consensus document gives a detailed overview on prevention and therapy of ventricular arrhythmias and sudden cardiac death. This includes detailed discussion of channelopathies and various cardiomyopathies. Gaps in evidence are identified and also discussed. DNA analysis and postmortem assessment in sudden cardiac death victims is for the first time part of these new recommendations. In addition, for the first time recommendations on subcutaneous implantable cardioverter-defibrillator (ICD) and the wearable defibrillator are given. The guidelines strengthen the role of ICD therapy in primary and secondary prevention of sudden cardiac death although data used as the basis for these recommendations are 10-15 years old and patients' characteristics including therapeutic options have changed during that time. Systematic reassessment of left ventricular function 6-12 weeks after infarction is also included as a new recommendation. The role of catheter ablation in electrical storm and for those presenting with a first episode of sustained ventricular tachycardia has also been upgraded in the new guidelines. Hopefully, the new guidelines will reach not only cardiologists and help to improve patient care, but also contribute to reducing the high number sudden cardiac deaths in Europe. PMID:27581243

  15. Risk stratification for sudden cardiac death: current status and challenges for the future†

    PubMed Central

    Wellens, Hein J.J.; Schwartz, Peter J.; Lindemans, Fred W.; Buxton, Alfred E.; Goldberger, Jeffrey J.; Hohnloser, Stefan H.; Huikuri, Heikki V.; Kääb, Stefan; La Rovere, Maria Teresa; Malik, Marek; Myerburg, Robert J.; Simoons, Maarten L.; Swedberg, Karl; Tijssen, Jan; Voors, Adriaan A.; Wilde, Arthur A.

    2014-01-01

    Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds. PMID:24801071

  16. Explaining the clinical manifestations of T wave alternans in patients at risk for sudden cardiac death

    PubMed Central

    Cutler, Michael J; Rosenbaum, David S.

    2009-01-01

    The mechanisms underlying sudden cardiac death (SCD) are complex and diverse. Therefore, correct application of any marker to risk stratify patients for appropriate therapy requires knowledge regarding how the marker is reflective of a particular electro-anatomical substrate for arrhythmias. Non-invasive measurement of beat-to-beat alternation of the electrocardiographic T-wave, referred to as T-wave alternans (TWA), is an important marker of risk for sudden cardiac death (SCD). Is this relationship a mere association or is TWA mechanistically linked to SCD? Recent experimental evidence strongly supports a mechanistic relationship between TWA and SCD. This review will consider the underlying mechanisms of TWA derived from experimental studies, as they relate to clinical observations of TWA in humans, addressing the following questions derived from common clinical observations: 1) Where does TWA on the surface ECG come from? 2) Why is controlled heart rate elevation required to elicit TWA? 3) Why is TWA associated with risk for SCD? 4) Why is TWA associated with a broad range of ventricular arrhythmias? and 5) How do commonly used medications affect TWA? PMID:19168395

  17. Basis for Sudden Cardiac Death Prediction by T-Wave Alternans from an Integrative Physiology Perspective

    PubMed Central

    Verrier, Richard L.; Kumar, Kapil; Nearing, Bruce D.

    2009-01-01

    Detection of microvolt levels of T-wave alternans (TWA) has been shown to be useful in identifying individuals at heightened risk for sudden cardiac death. The mechanistic bases for TWA are complex, at the cellular level involving multiple mechanisms, particularly instabilities in membrane voltage (i.e., steep action potential duration restitution slope) and disruptions in intracellular calcium cycling dynamics. The integrative factors influencing TWA at the systemic level are also multifold. We focus on three main variables, namely, heart rate, autonomic nervous system activities, and myocardial ischemia. Clinically, there is growing interest in extending TWA testing to include ambulatory ECG monitoring as well as exercise. The former modality permits assessment of the influence of diverse provocative stimuli of daily life, including circadian factors, mental stress, and sleep-state related disturbances in respiratory and cardiovascular function. Two major emerging concepts in clinical TWA testing are discussed, namely, quantitative analysis of TWA level, to complement the current binary classification scheme, and risk stratification of patients with preserved left ventricular function, the population with the largest absolute number of sudden cardiac deaths. PMID:19251221

  18. Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death

    PubMed Central

    Wagner, Stefan; Maier, Lars S.; Bers, Donald M.

    2015-01-01

    Despite improvements in the therapy of underlying heart disease sudden cardiac death (SCD) is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and/or the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure (HF) with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin dependent protein kinase, and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachy-arrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like HF. PMID:26044250

  19. Validity of the GRACE (Global Registry of Acute Coronary Events) acute coronary syndrome prediction model for six month post‐discharge death in an independent data set

    PubMed Central

    Bradshaw, P J; Ko, D T; Newman, A M; Donovan, L R

    2006-01-01

    Objective To determine the validity of the GRACE (Global Registry of Acute Coronary Events) prediction model for death six months after discharge in all forms of acute coronary syndrome in an independent dataset of a community based cohort of patients with acute myocardial infarction (AMI). Design Independent validation study based on clinical data collected retrospectively for a clinical trial in a community based population and record linkage to administrative databases. Setting Study conducted among patients from the EFFECT (enhanced feedback for effective cardiac treatment) study from Ontario, Canada. Patients Randomly selected men and women hospitalised for AMI between 1999 and 2001. Main outcome measure Discriminatory capacity and calibration of the GRACE prediction model for death within six months of hospital discharge in the contemporaneous EFFECT AMI study population. Results Post‐discharge crude mortality at six months for the EFFECT study patients with AMI was 7.0%. The discriminatory capacity of the GRACE model was good overall (C statistic 0.80) and for patients with ST segment elevation AMI (STEMI) (0.81) and non‐STEMI (0.78). Observed and predicted deaths corresponded well in each stratum of risk at six months, although the risk was underestimated by up to 30% in the higher range of scores among patients with non‐STEMI. Conclusions In an independent validation the GRACE risk model had good discriminatory capacity for predicting post‐discharge death at six months and was generally well calibrated, suggesting that it is suitable for clinical use in general populations. PMID:16387810

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Beatquency domain and machine learning improve prediction of cardiovascular death after acute coronary syndrome

    PubMed Central

    Liu, Yun; Scirica, Benjamin M.; Stultz, Collin M.; Guttag, John V.

    2016-01-01

    Frequency domain measures of heart rate variability (HRV) are associated with adverse events after a myocardial infarction. However, patterns in the traditional frequency domain (measured in Hz, or cycles per second) may capture different cardiac phenomena at different heart rates. An alternative is to consider frequency with respect to heartbeats, or beatquency. We compared the use of frequency and beatquency domains to predict patient risk after an acute coronary syndrome. We then determined whether machine learning could further improve the predictive performance. We first evaluated the use of pre-defined frequency and beatquency bands in a clinical trial dataset (N = 2302) for the HRV risk measure LF/HF (the ratio of low frequency to high frequency power). Relative to frequency, beatquency improved the ability of LF/HF to predict cardiovascular death within one year (Area Under the Curve, or AUC, of 0.730 vs. 0.704, p < 0.001). Next, we used machine learning to learn frequency and beatquency bands with optimal predictive power, which further improved the AUC for beatquency to 0.753 (p < 0.001), but not for frequency. Results in additional validation datasets (N = 2255 and N = 765) were similar. Our results suggest that beatquency and machine learning provide valuable tools in physiological studies of HRV. PMID:27708350

  8. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death.

    PubMed

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.

  9. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death.

    PubMed

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. PMID:27322252

  10. Targeting the Innate Immune Response to Improve Cardiac Graft Recovery after Heart Transplantation: Implications for the Donation after Cardiac Death

    PubMed Central

    Toldo, Stefano; Quader, Mohammed; Salloum, Fadi N.; Mezzaroma, Eleonora; Abbate, Antonio

    2016-01-01

    Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response. PMID:27322252

  11. First experience of liver transplantation with type 2 donation after cardiac death in France.

    PubMed

    Savier, Eric; Dondero, Federica; Vibert, Eric; Eyraud, Daniel; Brisson, Hélène; Riou, Bruno; Fieux, Fabienne; Naili-Kortaia, Salima; Castaing, Denis; Rouby, Jean-Jacques; Langeron, Olivier; Dokmak, Safi; Hannoun, Laurent; Vaillant, Jean-Christophe

    2015-05-01

    Organ donation after unexpected cardiac death [type 2 donation after cardiac death (DCD)] is currently authorized in France and has been since 2006. Following the Spanish experience, a national protocol was established to perform liver transplantation (LT) with type 2 DCD donors. After the declaration of death, abdominal normothermic oxygenated recirculation was used to perfuse and oxygenate the abdominal organs until harvesting and cold storage. Such grafts were proposed to consenting patients < 65 years old with liver cancer and without any hepatic insufficiency. Between 2010 and 2013, 13 LTs were performed in 3 French centers. Six patients had a rapid and uneventful postoperative recovery. However, primary nonfunction occurred in 3 patients, with each requiring urgent retransplantation, and 4 early allograft dysfunctions were observed. One patient developed a nonanastomotic biliary stricture after 3 months, whereas 8 patients showed no sign of ischemic cholangiopathy at their 1-year follow-up. In comparison with a control group of patients receiving grafts from brain-dead donors (n = 41), donor age and cold ischemia time were significantly lower in the type 2 DCD group. Time spent on the national organ wait list tended to be shorter in the type 2 DCD group: 7.5 months [interquartile range (IQR), 4.0-11.0 months] versus 12.0 months (IQR, 6.8-16.7 months; P = 0.08. The 1-year patient survival rates were similar (85% in the type 2 DCD group versus 93% in the control group), but the 1-year graft survival rate was significantly lower in the type 2 DCD group (69% versus 93%; P = 0.03). In conclusion, to treat borderline hepatocellular carcinoma, LT with type 2 DCD donors is possible as long as strict donor selection is observed.

  12. 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

  13. 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.

  14. Multivariate clinical models and quantitative dipyridamole-thallium imaging to predict cardiac morbidity and death after vascular reconstruction

    SciTech Connect

    Lette, J.; Waters, D.; Lassonde, J.; Rene, P.; Picard, M.; Laurendeau, F.; Levy, R.; Cerino, M.; Nattel, S. )

    1991-08-01

    Patients with peripheral vascular disease have a high prevalence of coronary artery disease and are at increased risk for cardiac morbidity and death after vascular reconstruction. The present study was undertaken to assess the value of 18 clinical parameters, of 7 clinical scoring systems, and of quantitative dipyridamole-thallium imaging for predicting the occurrence of postoperative myocardial infarction or cardiac death. Vascular surgery was performed in 125 patients. Thirteen postoperative cardiac events occurred, including 10 cardiac deaths and 3 nonfatal infarctions. Clinical parameters were not useful in predicting postoperative outcome. All 63 patients with normal scan results or fixed perfusion defects underwent surgery uneventfully, whereas 21% (13/62) of patients with reversible defects had a postoperative cardiac complication. By use of quantitative scintigraphic indexes we found that patients with reversible defects could be stratified into intermediate and high-risk subgroups with postoperative event rates of 5% (2/47) and 85% (11/13), respectively, despite intensive postoperative monitoring and antianginal medication. Thus in patients unable to complete a standard exercise stress test, postoperative outcome cannot be predicted clinically, whereas dipyridamole-thallium imaging successfully identified all patients who had a postoperative cardiac event. By use of quantification we found that patients with reversible defects can be stratified into an intermediate risk subgroup that can undergo surgery with minimal complication rate and a high-risk subgroup that requires coronary angiography.

  15. Sudden cardiac death in hemodialysis patients: an in-depth review.

    PubMed

    Green, Darren; Roberts, Paul R; New, David I; Kalra, Philip A

    2011-06-01

    Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain.

  16. Predictive Value of Beat-to-Beat QT Variability Index across the Continuum of Left Ventricular Dysfunction: Competing Risks of Non-cardiac or Cardiovascular Death, and Sudden or Non-Sudden Cardiac Death

    PubMed Central

    Tereshchenko, Larisa G.; Cygankiewicz, Iwona; McNitt, Scott; Vazquez, Rafael; Bayes-Genis, Antoni; Han, Lichy; Sur, Sanjoli; Couderc, Jean-Philippe; Berger, Ronald D.; de Luna, Antoni Bayes; Zareba, Wojciech

    2012-01-01

    Background The goal of this study was to determine the predictive value of beat-to-beat QT variability in heart failure (HF) patients across the continuum of left ventricular dysfunction. Methods and Results Beat-to-beat QT variability index (QTVI), heart rate variance (LogHRV), normalized QT variance (QTVN), and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca (MUSIC) HF study (mean age 63.1±11.7; males 70.6%; LVEF >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance (IDEAL) database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death [hazard ratio (HR) 1.67(95%CI 1.14-2.47), P=0.009] and in particular with non-sudden cardiac death [HR 2.91(1.69-5.01), P<0.001]. Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular [HR 1.57(1.04-2.35), P=0.031], and non-sudden cardiac death in multivariate competing risk model [HR 2.58(1.13-3.78), P=0.001]. No interaction between QTVI and LVEF was found. QTVI predicted neither non-cardiac death (P=0.546) nor SCD (P=0.945). Decreased heart rate variability (HRV) rather than increased QT variability was the reason for increased QTVI in this study. Conclusions Increased QTVI due to depressed HRV predicts cardiovascular mortality and non-sudden cardiac death, but neither SCD nor excracardiac mortality in HF across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from HF patients at risk. PMID:22730411

  17. Forensic Pathological Study of 1656 Cases of Sudden Cardiac Death in Southern China

    PubMed Central

    Wu, Qiuping; Zhang, Liyong; Zheng, Jinxiang; Zhao, Qianhao; Wu, Yeda; Yin, Kun; Huang, Lei; Tang, Shuangbo; Cheng, Jianding

    2016-01-01

    Abstract Sudden cardiac death (SCD) is progressively threatening the lives of young people throughout the world. We conducted a retrospective study of SCD cases identified among sudden death cases based on comprehensive autopsies and pathological examinations in the Center for Medicolegal Expertise of Sun Yat-Sen University to investigate the exact etiological distribution and epidemiological features of SCD. One thousand six hundred fifty-six cases were identified, and SCD accounted for 43.0% of these sudden death cases. The mean age of the SCD cases—where the data of definite ages were accessible—was 38.2 years, and the highest incidence occurred among the 31- to 40-year-old cases (25.6%). The male-to-female ratio among SCD cases was 4.3:1, and this ratio peaked in the 41- to 50-year-old group (7.7:1). The places of death were confirmed in 1411 cases, and predominantly in hospitals (46.3%) and at home (33.8%). SCD occurred throughout the year with a marginally increase in April and May. The major causes of SCD were coronary atherosclerotic disease (CAD, 41.6%), unexplained sudden death (15.1%), and myocarditis (11.8%). Our data indicated that in the age group of younger affected persons (below 35 years old), sudden unexplained death and myocarditis were much more prevalent than CAD. According to anatomical examinations of the CAD-related SCD cases, the proportion of cases with coronary artery stenosis exceeding 75% (grade IV) was 67.2%. Moreover, the percentages of higher grades of coronary atherosclerosis increased with age. Among all branches of the coronary arteries, the left anterior descending branch was the most prone to atherosclerosis; atherosclerosis was present in this branch in 95.4% of the cases with atherosclerosis. Additionally, lesions of multiple branches of the coronary artery were associated with ageing. This is the first study to report the causes of death and basic epidemiological data related to SCD in Southern China. PMID:26844513

  18. Forensic Pathological Study of 1656 Cases of Sudden Cardiac Death in Southern China.

    PubMed

    Wu, Qiuping; Zhang, Liyong; Zheng, Jinxiang; Zhao, Qianhao; Wu, Yeda; Yin, Kun; Huang, Lei; Tang, Shuangbo; Cheng, Jianding

    2016-02-01

    Sudden cardiac death (SCD) is progressively threatening the lives of young people throughout the world. We conducted a retrospective study of SCD cases identified among sudden death cases based on comprehensive autopsies and pathological examinations in the Center for Medicolegal Expertise of Sun Yat-Sen University to investigate the exact etiological distribution and epidemiological features of SCD. One thousand six hundred fifty-six cases were identified, and SCD accounted for 43.0% of these sudden death cases. The mean age of the SCD cases-where the data of definite ages were accessible-was 38.2 years, and the highest incidence occurred among the 31- to 40-year-old cases (25.6%). The male-to-female ratio among SCD cases was 4.3:1, and this ratio peaked in the 41- to 50-year-old group (7.7:1). The places of death were confirmed in 1411 cases, and predominantly in hospitals (46.3%) and at home (33.8%). SCD occurred throughout the year with a marginally increase in April and May. The major causes of SCD were coronary atherosclerotic disease (CAD, 41.6%), unexplained sudden death (15.1%), and myocarditis (11.8%). Our data indicated that in the age group of younger affected persons (below 35 years old), sudden unexplained death and myocarditis were much more prevalent than CAD. According to anatomical examinations of the CAD-related SCD cases, the proportion of cases with coronary artery stenosis exceeding 75% (grade IV) was 67.2%. Moreover, the percentages of higher grades of coronary atherosclerosis increased with age. Among all branches of the coronary arteries, the left anterior descending branch was the most prone to atherosclerosis; atherosclerosis was present in this branch in 95.4% of the cases with atherosclerosis. Additionally, lesions of multiple branches of the coronary artery were associated with ageing. This is the first study to report the causes of death and basic epidemiological data related to SCD in Southern China.

  19. Hypertriglyceridemia-induced acute pancreatitis in pregnancy causing maternal death.

    PubMed

    Jeon, Hae Rin; Kim, Suk Young; Cho, Yoon Jin; Chon, Seung Joo

    2016-03-01

    Acute pancreatitis in pregnancy is rare and occurs in approximately 3 in 10,000 pregnancies. It rarely complicates pregnancy, and can occur during any trimester, however over half (52%) of cases occur during the third trimester and during the post-partum period. Gallstones are the most common cause of acute pancreatitis. On the other hand, acute pancreatitis caused by hypertriglyceridemia due to increase of estrogen during the gestational period is very unusual, but complication carries a higher risk of morbidity and mortality for both the mother and the fetus. We experienced a case of pregnant woman who died of acute exacerbation of hypertriglyceridemia-induced acute pancreatitis at 23 weeks of gestation. We report on progress and management of this case along with literature reviews.

  20. Hypertriglyceridemia-induced acute pancreatitis in pregnancy causing maternal death

    PubMed Central

    Jeon, Hae Rin; Cho, Yoon Jin; Chon, Seung Joo

    2016-01-01

    Acute pancreatitis in pregnancy is rare and occurs in approximately 3 in 10,000 pregnancies. It rarely complicates pregnancy, and can occur during any trimester, however over half (52%) of cases occur during the third trimester and during the post-partum period. Gallstones are the most common cause of acute pancreatitis. On the other hand, acute pancreatitis caused by hypertriglyceridemia due to increase of estrogen during the gestational period is very unusual, but complication carries a higher risk of morbidity and mortality for both the mother and the fetus. We experienced a case of pregnant woman who died of acute exacerbation of hypertriglyceridemia-induced acute pancreatitis at 23 weeks of gestation. We report on progress and management of this case along with literature reviews. PMID:27004207

  1. Effect of early bisoprolol administration on ventricular arrhythmia and cardiac death in patients with non-ST elevation myocardial infarction

    PubMed Central

    Maclean, Edd; Zheng, Sean; Nabeebaccus, Adam; O'Gallagher, Kevin; Stewart, Adrian; Webb, Ian

    2015-01-01

    Objective To investigate the impact of early oral beta blockade in patients presenting with acute non-ST elevation myocardial infarction (NSTEMI). Methods We retrospectively identified 890 consecutive patients presenting with NSTEMI to a single UK centre from 2012 to 2014. Included patients all received standardised antiplatelet therapy plus low-dose oral bisoprolol (1.25–2.5 mg) within 4 h (mean 2.2±1.36; ‘Early Group’) or within 5–24 h (mean 15.4±5.7; ‘Late Group’) of presentation. Patients were followed up for the duration of hospital stay with the incidence of major adverse cardiovascular events (MACE—defined as ventricular arrhythmia, cardiac death or repeat infarction) set as the primary outcome. Multivariate logistic regression models analysed early versus late bisoprolol administration and adjusted for potential confounders. Results 399 patients were included. Of the patient parameters, only the GRACE score was significantly different between the early (n=99, GRACE 164.5±29.6) and late (n=300, GRACE 156.7±31.4) groups (p=0.033). The early group had significantly fewer ventricular arrhythmias (1 vs 20, p=0.034), cardiac deaths (0 vs 13, p=0.044) and consequently MACE (1 vs 27, p=0.005) than the late group. After adjusting for the confounders of pulse, blood pressure, smoking and creatinine, logistic regression analysis identified early bisoprolol administration as protective for ventricular arrhythmia (p=0.038, OR 0.114, CI 0.015 to 0.885) and MACE (p=0.011, OR 0.064, CI 0.008 to 0.527). There was one episode of symptomatic bradycardia in the late group. Conclusions This study suggests that low-dose oral bisoprolol administered to patients with NSTEMI within 4 h of admission may be protective and lead to reduced inpatient MACE. PMID:27326220

  2. Is There a Role for Genetics in the Prevention of Sudden Cardiac Death?

    PubMed

    Faragli, Alessandro; Underwood, Katherine; Priori, Silvia G; Mazzanti, Andrea

    2016-09-01

    The identification of patients at risk for sudden cardiac death (SCD) is fundamental for both acquired cardiovascular diseases (such as coronary artery diseases, CAD) and inherited arrhythmia syndromes (such as the long-QT syndrome, LQTS). Genetics may play a role in both situations, although the potential to exploit this information to reduce the burden of SCD varies among these two groups. Concerning acquired cardiovascular diseases, which affect most of the general population, preliminary data suggest an association between genetics and the risk of dying suddenly. The maximal utility, instead, is reached in inherited arrhythmia syndromes, where the discovery of monogenic diseases such as LQTS tracked the way for the first genotype-phenotype correlations. The aim of this review is to provide a general overview focusing on the current genetic knowledge and on the present and future applicability for prevention in these two populations at risk for SCD. PMID:27279603

  3. Potential approaches to improve the outcomes of donation after cardiac death liver grafts.

    PubMed

    Mahboub, Paria; Bozorgzadeh, Adel; Martins, Paulo N

    2016-06-24

    There is a growing discrepancy between the supply and demand of livers for transplantation resulting in high mortality rates on the waiting list. One of the options to decrease the mortality on the waiting list is to optimize organs with inferior quality that otherwise would be discarded. Livers from donation after cardiac death (DCD) donors are frequently discarded because they are exposed to additional warm ischemia time, and this might lead to primary-non-function, delayed graft function, or severe biliary complications. In order to maximize the usage of DCD livers several new preservation approaches have been proposed. Here, we will review 3 innovative organ preservation methods: (1) different ex vivo perfusion techniques; (2) persufflation with oxygen; and (3) addition of thrombolytic therapy. Improvement of the quality of DCD liver grafts could increase the pool of liver graft's for transplantation, improve the outcomes, and decrease the mortality on the waiting list. PMID:27358776

  4. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-07-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27590646

  5. [New strategies for assessing the risk of sudden cardiac death in hypertrophic cardiomyopathy].

    PubMed

    Jaworski, Krzysztof; Możeńska, Olga; Kosior, Dariusz A

    2016-08-01

    Hypertrophic cardiomyopathy (HCM) is characterized by a primarily increased ventricular wall thickness, usually caused by the mutations in genes encoding sarcomere proteins. Thanks to the growing awareness in the medical community as well as advances in diagnostic techniques HCM can be diagnosed at earlier stages than ever before. However, in some cases the first symptom of this disease is a sudden cardiac death (SCD) and diagnosis remains unknown until post-mortem examination. Implantation of a cardioverterdefibrillator (ICD) provides the most effective method of SCD prevention. Nevertheless, due to a number of risks associated with surgery as well as the possession of such devices, predictive factors of serious ventricular arrhythmia in individual patients have been sought for many years. The aim of this review is to present the current strategies of risk assessment and prevention of SCD in patients with HCM. PMID:27591441

  6. Minocycline attenuates microglial response and reduces neuronal death after cardiac arrest and cardiopulmonary resuscitation in mice.

    PubMed

    Wang, Qian-yan; Sun, Peng; Zhang, Qing; Yao, Shang-long

    2015-04-01

    The possible role of minocycline in microglial activation and neuronal death after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in mice was investigated in this study. The mice were given potassium chloride to stop the heart beating for 8 min to achieve CA, and they were subsequently resuscitated with epinephrine and chest compressions. Forty adult C57BL/6 male mice were divided into 4 groups (n=10 each): sham-operated group, CA/CPR group, CA/CPR+minocycline group, and CA/CPR+vehicle group. Animals in the latter two groups were intraperitoneally injected with minocycline (50 mg/kg) or vehicle (normal saline) 30 min after recovery of spontaneous circulation (ROSC). Twenty-four h after CA/CPR, the brains were removed for histological evaluation of the hippocampus. Microglial activation was evaluated by detecting the expression of ionized calcium-binding adapter molecule-1 (Iba1) by immunohistochemistry. Neuronal death was analyzed by hematoxylin and eosin (H&E) staining and the levels of tumor necrosis factor-alpha (TNF-α) in the hippocampus were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that the neuronal death was aggravated, most microglia were activated and TNF-α levels were enhanced in the hippocampus CA1 region of mice subjected to CA/CPR as compared with those in the sham-operated group (P<0.05). Administration with minocycline 30 min after ROSC could significantly decrease the microglial response, TNF-α levels and neuronal death (P<0.05). It was concluded that early administration with minocycline has a strong therapeutic potential for CA/CPR-induced brain injury.

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

    PubMed Central

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

    2013-01-01

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

  8. Sudden death while driving. Role of sinus perinodal degeneration and cardiac neural degeneration and ganglionitis.

    PubMed

    James, T N; Pearce, W N; Givhan, E G

    1980-05-01

    A young business executive was seen to slump over his steering wheel while driving, after which the automobile veered and turned over. Quickly taken unconscious to a nearby emergency room, he was pronounced dead on arrival. Because there was insufficient physical injury found to account for his death, and because atrial fibrillation had been detected for the first time on a routine physical examination 3 months previously, special examination of the cardiac conduction system was performed. A fibroma was present on the right side of the central fibrous body above the His bundle, similar to several fibromas on the mitral valve. Small foci of neuritis were present in the ventricular myocardium and the atrioventricular node. More extensive neural degeneration and ganglionitis were found near the sinus node, which also exhibited an encircling perinodal fibrosis. Ways in which these abnormalities could have caused a fatal electrical instability of the heart are discussed. Careful examination of the cardiac conduction system is warranted in other fatal automobile accidents under similar circumstances.

  9. 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

  10. 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.

  11. 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...

  12. Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases.

    PubMed

    Montisci, Massimo; El Mazloum, Rafi; Cecchetto, Giovanni; Terranova, Claudio; Ferrara, Santo Davide; Thiene, Gaetano; Basso, Cristina

    2012-04-10

    Anabolic androgenic steroids (AAS) are the main class of doping agents and their consumption produces adverse effects involving several organs and systems. Three cases of sudden cardiac death (SCD) and one of death due to congestive heart failure of previously healthy athletes who were AAS users are herein reported. Concentric cardiac hypertrophy with focal fibrosis (one case), dilated cardiomyopathy with patchy myocyte death (two cases) and eosinophilic myocarditis (one case) were observed and most probably relate to the final event. Molecular investigation for viral genomes was positive in one case (Ebstein virus). Our data confirm previous findings, showing that the most typical cardiac abnormality in AAS abusers is left ventricular hypertrophy, associated with fibrosis and myocytolysis. An exceptional cardiovascular substrate was represented by the case with drug induced eosinophilic myocarditis. These features are at risk of ventricular arrhythmias as well as congestive heart failure. The cause-effect relationship between AAS abuse and cardiac death can be established only by a rigorous methodology with the use of standardized protocols, including precise morphological studies of all target organs to search for chronic toxic effects. Laboratory investigations should focus on AAS searching on a wide range of biological matrices to demonstrate type, magnitude and time of exposure.

  13. The mechanism of PDT-induced electrical blockade: the dependence of time-lapse localization of talaporfin sodium on the cell death phenotypes in rat cardiac myocytes

    NASA Astrophysics Data System (ADS)

    Ito, A.; Matsuo, H.; Suenari, T.; Miyoshi, S.; Takatsuki, S.; Ogawa, S.; Arai, T.

    2009-02-01

    We have proposed a new type of atrial fibrillation treatment with the early state photodynamic therapy (PDT), in which the interval time between the photosensitizer injection and irradiation is shorter than that in conventional way. We had demonstrated the acute electrical blockade by the PDT with talaporfin sodium and a red (670 nm) diode laser in ex vivo and in vivo experiment using rat normal myocardial tissue. The previous study of intracellular Ca2+ concentration measurement in rat cardiac myocytes during the PDT indicated that Ca2+ influx induced by the plasma membrane damage might be the main cause of the acute reaction of myocardial tissue. We found that the cell damage of cardiac myocytes triggered by the PDT was mainly influenced by the site where the photosensitizer exists. In this study, we examined the relationship between the sites of talaporfin sodium existing and cell death phenotypes in response to the PDT, in order to clarify the mechanism of the acute electrical blockade induced by the PDT in myocardial tissue. The talaporfin sodium fluorescence was observed after the various incubation times to visualize the time-lapse intracellular photosensitizer localization. The distribution of the photosensitizer was dependent on the incubation time. The change in intracellular Ca2+ concentration during the PDT was examined with a fluorescent Ca2+ indicator by a high-speed Nipkow confocal laser microscope (CSU-X1, Yokogawa Electric Company). We obtained the Ca2+ dynamics during the PDT which can explain the PDT-induced cell death pathways. We concluded that the Ca2+ influx induced by plasma membrane damage is the possible mechanism of the electrical blockade by the early state PDT.

  14. The Use of Donation After Cardiac Death Allografts Does Not Increase Recurrence of Hepatocellular Carcinoma.

    PubMed

    Croome, K P; Lee, D D; Burns, J M; Musto, K; Paz, D; Nguyen, J H; Perry, D K; Harnois, D M; Taner, C B

    2015-10-01

    Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence-free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.

  15. Chronic obstructive pulmonary disease and sudden cardiac death: A systematic review.

    PubMed

    van den Berg, Marten E; Stricker, Bruno H; Brusselle, Guy G; Lahousse, Lies

    2016-10-01

    Both chronic obstructive pulmonary disease (COPD) and sudden cardiac death (SCD) are major health burdens. A number of studies have addressed their interrelationship, but currently no systematic review has been published. Our objective is to give an overview of the literature of the association between COPD and SCD. A search on PubMed with both MeSH headings and free-text keywords was performed. We selected all original articles of studies in humans that assessed COPD on the one hand and SCD, electrocardiographic markers for SCD, ventricular arrhythmias, or asystole on the other. The electronic search yielded 251 articles, from which 27 full publications were selected after careful evaluation of the full-text articles. In these studies, COPD was associated with a prolonged and shortened QT interval. In patients with a myocardial infarction (MI), COPD was associated with an increased risk of ventricular arrhythmias and decreased survival. COPD was a risk factor for SCD both in cardiovascular patient groups and in community-based studies, independent from cardiovascular risk profile. Studies of the potential impact of respiratory treatment on the occurrence of SCD showed conflicting results. In conclusion, cumulating evidence associates COPD with an increased risk of SCD. Asystole and pulseless electric activity could be more common than VT/VF in deaths associated with COPD. Underlying mechanisms explaining this association require further investigation. PMID:27234353

  16. Clinical Outcomes and Quality of Life in Recipients of Livers Donated after Cardiac Death

    PubMed Central

    Parikh, Neehar D.; Skaro, Anton I.; Ladner, Daniela P.; Lyuksemburg, Vadim; Cahan, Joshua G.; Daud, Amna; Butt, Zeeshan

    2015-01-01

    Donation after cardiac death (DCD) has expanded in the last decade in the US; however, DCD liver utilization has flattened in recent years due to poor outcomes. We examined clinical and quality of life (QOL) outcomes of DCD recipients by conducting a retrospective and cross-sectional review of patients from 2003 to 2010. We compared clinical outcomes of DCD recipients (n = 60) to those of donation after brain death (DBD) liver recipients (n = 669) during the same time period. DCD recipients had significantly lower rates of 5-year graft survival (P < 0.001) and a trend toward lower rates of 5-year patient survival (P = 0.064) when compared to the DBD cohort. In order to examine QOL outcomes in our cohorts, we administered the Short Form Liver Disease Quality of Life questionnaire to 30 DCD and 60 DBD recipients. The DCD recipients reported lower generic and liver-specific QOL. We further stratified the DCD cohort by the presence of ischemic cholangiopathy (IC). Patients with IC reported lower QOL when compared to DBD recipients and those DCD recipients without IC (P < 0.05). While the results are consistent with clinical experience, this is the first report of QOL in DCD recipients using standardized measures. These data can be used to guide future comparative effectiveness studies. PMID:25922602

  17. Chronic obstructive pulmonary disease and sudden cardiac death: A systematic review.

    PubMed

    van den Berg, Marten E; Stricker, Bruno H; Brusselle, Guy G; Lahousse, Lies

    2016-10-01

    Both chronic obstructive pulmonary disease (COPD) and sudden cardiac death (SCD) are major health burdens. A number of studies have addressed their interrelationship, but currently no systematic review has been published. Our objective is to give an overview of the literature of the association between COPD and SCD. A search on PubMed with both MeSH headings and free-text keywords was performed. We selected all original articles of studies in humans that assessed COPD on the one hand and SCD, electrocardiographic markers for SCD, ventricular arrhythmias, or asystole on the other. The electronic search yielded 251 articles, from which 27 full publications were selected after careful evaluation of the full-text articles. In these studies, COPD was associated with a prolonged and shortened QT interval. In patients with a myocardial infarction (MI), COPD was associated with an increased risk of ventricular arrhythmias and decreased survival. COPD was a risk factor for SCD both in cardiovascular patient groups and in community-based studies, independent from cardiovascular risk profile. Studies of the potential impact of respiratory treatment on the occurrence of SCD showed conflicting results. In conclusion, cumulating evidence associates COPD with an increased risk of SCD. Asystole and pulseless electric activity could be more common than VT/VF in deaths associated with COPD. Underlying mechanisms explaining this association require further investigation.

  18. Experience With the Wearable Cardioverter-Defibrillator in Patients at High Risk for Sudden Cardiac Death

    PubMed Central

    Günther, Michael; Quick, Silvio; Pfluecke, Christian; Rottstädt, Fabian; Szymkiewicz, Steven J.; Ringquist, Steven; Strasser, Ruth H.; Speiser, Uwe

    2016-01-01

    Background: This study evaluated the wearable cardioverter-defibrillator (WCD) for use and effectiveness in preventing sudden death caused by ventricular tachyarrhythmia or fibrillation. Methods: From April 2010 through October 2013, 6043 German WCD patients (median age, 57 years; male, 78.5%) were recruited from 404 German centers. Deidentified German patient data were used for a retrospective, nonrandomized analysis. Results: Ninety-four patients (1.6%) were treated by the WCD in response to ventricular tachyarrhythmia/fibrillation. The incidence rate was 8.4 (95% confidence interval, 6.8–10.2) per 100 patient-years. Patients with implantable cardioverter-defibrillator explantation had an incidence rate of 19.3 (95% confidence interval, 12.2–29.0) per 100 patient-years. In contrast, an incidence rate of 8.2 (95% confidence interval, 6.4–10.3) was observed in the remaining cardiac diagnosis groups, including dilated cardiomyopathy, myocarditis, and ischemic and nonischemic cardiomyopathies. Among 120 shocked patients, 112 (93%) survived 24 hours after treatment, whereas asystole was observed in 2 patients (0.03%) with 1 resulting death. ConclusionS: This large cohort represents the first nationwide evaluation of WCD use in patients outside the US healthcare system and confirms the overall value of the WCD in German treatment pathways. PMID:27458236

  19. Clinical outcomes and quality of life in recipients of livers donated after cardiac death.

    PubMed

    Parikh, Neehar D; Skaro, Anton I; Ladner, Daniela P; Lyuksemburg, Vadim; Cahan, Joshua G; Daud, Amna; Butt, Zeeshan

    2015-01-01

    Donation after cardiac death (DCD) has expanded in the last decade in the US; however, DCD liver utilization has flattened in recent years due to poor outcomes. We examined clinical and quality of life (QOL) outcomes of DCD recipients by conducting a retrospective and cross-sectional review of patients from 2003 to 2010. We compared clinical outcomes of DCD recipients (n = 60) to those of donation after brain death (DBD) liver recipients (n = 669) during the same time period. DCD recipients had significantly lower rates of 5-year graft survival (P < 0.001) and a trend toward lower rates of 5-year patient survival (P = 0.064) when compared to the DBD cohort. In order to examine QOL outcomes in our cohorts, we administered the Short Form Liver Disease Quality of Life questionnaire to 30 DCD and 60 DBD recipients. The DCD recipients reported lower generic and liver-specific QOL. We further stratified the DCD cohort by the presence of ischemic cholangiopathy (IC). Patients with IC reported lower QOL when compared to DBD recipients and those DCD recipients without IC (P < 0.05). While the results are consistent with clinical experience, this is the first report of QOL in DCD recipients using standardized measures. These data can be used to guide future comparative effectiveness studies.

  20. [Brain death, physiopathology, optimal care and hormonal therapy for cardiac donation].

    PubMed

    Zetina-Tun, Hugo; Lezama-Urtecho, Carlos; Urías-Báez, Rafael; Careaga-Reyna, Guillermo

    2012-01-01

    Heart transplantation goes on leading the standard therapy for the terminal heart failure. The success of this procedure and the post-transplantation survival, meaning during the perioperative time, is variable because of the good performance of the donor graft, due to this situation, the pre-harvesting evaluation is very important. The brain death brought many changes: 1) first of all the "adrenergic storm" with its hemodynamic and cardiac dangerous events; 2) Thyroidal hormones, cortisol, vasopressin, and seric insulin depletion with its metabolic consequences respectively. Since 2002 during the Crystal Consensus started the using of the hormonal therapeutic with triyodothironine, vasopressin and metilprednisolone for improving, meaning those limitrophes ones, the performance donor hearts with brain death, and the goal has been to harvest more donated organs en quality and numbers. This hormonal therapeutic has had great acceptation and is successful; having more harvesting of solids organs: hearts, lungs and kidneys; with more performance and surviving at 1 year post-transplantation and less mortality. Our Hospital began the hormonal therapeutic since January 2011with excellent results. On this basis we can concluded that, hormonal rescue therapy, improves the availability and performance of organs for transplantation.

  1. Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways.

    PubMed

    Cui, Derong; Shang, Hanbing; Zhang, Xiaoli; Jiang, Wei; Jia, Xiaofeng

    2016-01-01

    The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-α (PFT-α) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3-II and DRAM) that generally increase following CA. PFT-α also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA. PMID:27273382

  2. Cardiac arrest triggers hippocampal neuronal death through autophagic and apoptotic pathways

    PubMed Central

    Cui, Derong; Shang, Hanbing; Zhang, Xiaoli; Jiang, Wei; Jia, Xiaofeng

    2016-01-01

    The mechanism of neuronal death induced by ischemic injury remains unknown. We investigated whether autophagy and p53 signaling played a role in the apoptosis of hippocampal neurons following global cerebral ischemia-reperfusion (I/R) injury, in a rat model of 8-min asphyxial cardiac arrest (CA) and resuscitation. Increased autophagosome numbers, expression of lysosomal cathepsin B, cathepsin D, Beclin-1, and microtubule-associated protein light chain 3 (LC3) suggested autophagy in hippocampal cells. The expression of tumor suppressor protein 53 (p53) and its target genes: Bax, p53-upregulated modulator of apoptosis (PUMA), and damage-regulated autophagy modulator (DRAM) were upregulated following CA. The p53-specific inhibitor pifithrin-α (PFT-α) significantly reduced the expression of pro-apoptotic proteins (Bax and PUMA) and autophagic proteins (LC3-II and DRAM) that generally increase following CA. PFT-α also reduced hippocampal neuronal damage following CA. Similarly, 3-methyladenine (3-MA), which inhibits autophagy and bafilomycin A1 (BFA), which inhibits lysosomes, significantly inhibited hippocampal neuronal damage after CA. These results indicate that CA affects both autophagy and apoptosis, partially mediated by p53. Autophagy plays a significant role in hippocampal neuronal death induced by cerebral I/R following asphyxial-CA. PMID:27273382

  3. Current status and recent advances of liver transplantation from donation after cardiac death

    PubMed Central

    Perera, M Thamara PR; Bramhall, Simon R

    2011-01-01

    The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably “prematurely” offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures. PMID:22180833

  4. Physical activity and sudden cardiac death in elders--a Croatian study.

    PubMed

    Duraković, Zijad; Duraković, Marjeta Misigoj; Skavić, Josip; Gojanović, Marija Definis

    2011-03-01

    The paper deals with the sudden cardiac death in elders due to physical activity in Croatia and to compare it to other population groups who practice physical activity. The data are a part of a retrospective study dealing with 59 sudden death due to physical activity in men in Croatia: from January 1, 1988 to December 31, 2008. Fifteen aged 65 to 82 years were recreationally engaged in physical activity: six in swimming, four in tennis, one in driving a bicycle, one in jogging, two in bowling and one died during sexual act. Only one had symptoms of pectoral angina, two suffered from arterial hypertension, and two had congestive heart failure. Eleven were without symptoms before exercise. At forensic autopsy, fourteen had coronary heart disease, seven had critical coronary artery stenosis, three had occluded left descendens anterior coronary artery and four critical coronary stenosis, four had a recent myocardial infarctions, and eleven had myocardial scars due to previous myocardial infarctions. Twelve of them had left ventricular hypertrophy: 15-25 mm. In Croatia, about 7per cent of the entire male population undertake recreational physical activity, while 13 per cent of them are elders. A sudden cardiac death due to recreational physical activity in elders reached 1.71/100 000 yearly, in the entire male population engaged in recreational physical exercise: 0.75/100 000 (p = 0.05730), in the total male population aged 15-40 engaged in sports and recreational physical exercise: 0.57/100.0000 (p = 0.00387), in young athletes: 0.15/100 000 (p = 0.00000). Medical examination of all elderly persons has to be done before starting of recreational physical activity: by clinical examination, searching for risk factors for atherosclerosis, performing ECG at rest, stress ECG, and echocardiography and to repeat the medical examination at least once a year Physical activity should start with a warm-up period and with a gradually increasing load, and usually not to exceed 6

  5. 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.

  6. 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

  7. 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...

  8. Mechanisms of cell death in acute myocardial infarction: pathophysiological implications for treatment

    PubMed Central

    de Zwaan, C.; Daemen, M.J.A.P.; Hermens, W.Th.

    2001-01-01

    The purpose of this review is to draw attention to the growing list of pathophysiological phenomena occurring in blood, the vessel wall and cardiac tissue during myocardial infarction. A further aim is to point to the complexity of factors, contributing to cardiac dysfunction and the implications for therapy, aimed at limiting myocardial cell death. Not all pathophysiological mechanisms have been elucidated yet, indicating the necessity for further research in this area. In addition we describe interventions which have shown promise in animal studies, those which may show promise in humans, and those which are accepted as therapies of choice. PMID:25696691

  9. Tools for risk stratification of sudden cardiac death: A review of the literature in different patient populations

    PubMed Central

    Ragupathi, Loheetha; Pavri, Behzad B.

    2014-01-01

    While various modalities to determine risk of sudden cardiac death (SCD) have been reported in clinical studies, currently reduced left ventricular ejection fraction remains the cornerstone of SCD risk stratification. However, the absolute burden of SCD is greatest amongst populations without known cardiac disease. In this review, we summarize the evidence behind current guidelines for implantable cardioverter defibrillator (ICD) use for the prevention of SCD in patients with ischemic heart disease (IHD). We also evaluate the evidence for risk stratification tools beyond clinical guidelines in the general population, patients with IHD, and patients with other known or suspected medical conditions. PMID:24568833

  10. Anomalous Left Circumflex Coronary Artery Arising from the Right Pulmonary Artery: A Rare Cause of Aborted Sudden Cardiac Death.

    PubMed

    Liu, Bo; Fursevich, Dzmitry; O'Dell, Matthew C; Flores, Miguel; Feranec, Nicholas

    2016-01-01

    We report a case of anomalous origin of the left circumflex coronary artery arising from the right pulmonary artery resulting in stress-induced cardiac arrest. The patient collapsed after running a 5K race and was resuscitated. Subsequent workup revealed the culprit anatomy, which was successfully treated with surgical ligation. To the authors' knowledge, this is only the second case of this variant coronary anomaly resulting in aborted sudden cardiac death, subsequent surgical ligation, and recovery in a healthy young adult and is the first case treated by ligation alone without coronary bypass. PMID:27014533

  11. Sudden cardiac death associated with an extremely rare coronary anomaly of the left and right coronary arteries arising exclusively from the posterior (noncoronary) sinus of valsalva.

    PubMed

    Catanzaro, John N; Makaryus, Amgad N; Catanese, Charles

    2005-11-01

    Congenital anomalies of the coronary arteries are relatively uncommon conditions and have been associated with sudden cardiac death (SCD) in children. Although anomalous coronary artery distribution is widely reported in the literature, no articles to date address the origin of both the right (RCA) and left coronary arteries (LCA) from the posterior (noncoronary) sinus of Valsalva. This is a report of a 16-year-old black male in good health, who collapsed and was unable to be resuscitated after physical exertion while playing basketball. In this patient, postmortem evaluation revealed the LCA and RCA originating exclusively from the posterior (noncoronary) sinus with acute angle takeoff of the LCA which likely lead to ischemia, causing SCD. We discuss the incidence of coronary artery anomalies and the proposed mechanisms that led to SCD in these patients.

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

    PubMed Central

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

    2016-01-01

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

  13. Impact of Denervated Myocardium on Improving Risk Stratification for Sudden Cardiac Death

    PubMed Central

    Cain, Michael E.

    2014-01-01

    Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation (11C-meta-hydroxyephedrine [11C-HED]), perfusion (13N-ammonia), and viability (insulin-stimulated 18F-2-deoxyglucose [18FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium (11C-HED-18FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m2, creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables. PMID:25125727

  14. Impact of denervated myocardium on improving risk stratification for sudden cardiac death.

    PubMed

    Cain, Michael E

    2014-01-01

    Between 184,000 and 462,000 Americans die suddenly each year. Fifty percent to 70% of these deaths are due to ventricular tachycardia/fibrillation (VT/VF). We tested whether hibernating myocardium or myocardial sympathetic denervation identifies patients at high-risk for developing VT/VF independently of ejection fraction (EF). Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia), and viability (insulin-stimulated (18)F-2-deoxyglucose [(18)FDG]) in patients with ischemic cardiomyopathy (EF < 35%) eligible for a primary prevention implantable cardioverter defibrillator (ICD). The primary end-point was sudden cardiac arrest (SCA) defined as arrhythmic death or ICD discharge for VT/VF > 240 bpm. Volumes of total denervated (P = .001) and viable denervated myocardium ((11)C-HED-(18)FDG mismatch, P = .03) predicted SCA, whereas hibernating and infarcted myocardium did not. Multivariate analysis identified four independent predictors of SCA: denervated myocardium > 37.6% of left ventricule (LV), LV end-diastolic volume > 98 mL/m(2), creatinine level > 1.49 mg/dL, and no angiotensin- inhibition therapy. Denervated myocardium had a hazard ratio of 3.5 for SCA (10.3%/year vs. 3.0%/year, p=0.001). Absence of all four factors predicted low risk (44% of cohort; SCA <1%/y) whereas two or more factors identified subjects at high-risk (20% of cohort; SCA 12%/y). Denervated myocardium quantified using PET strongly predicts risk of SCA, and is independent of EF, infarct volume, and other clinical variables.

  15. Prevention of sudden cardiac death in the young and in athletes: dream or reality?

    PubMed

    Thiene, Gaetano; Carturan, Elisa; Corrado, Domenico; Basso, Cristina

    2010-01-01

    Cardiovascular diseases account for 40% of all deaths in the Western countries, and nearly two thirds of them occur suddenly. Young people (<35 years) are not spared from sudden death (SD) with a rate of 1/100,000 per year. Effort is a trigger with a threefold risk in athletes vs. nonathletes, and sports disqualification is by itself life-saving in people with underlying concealed cardiovascular diseases. Several culprits of cardiac SD may be identified at postmortem and atherosclerotic coronary artery disease is the leading cause (25% of SD cases in the young), mostly consisting of a single obstructive plaque with fibrocellular intimal proliferation. However, the spectrum of cardiovascular substrates is wide and include also congenital diseases of the coronary arteries (mainly anomalous origin), myocardium (arrhythmogenic and hypertrophic cardiomyopathies, myocarditis), valves (aortic stenosis and mitral valve prolapse), and conduction system (ventricular preexcitation, accelerated atrioventricular conduction and block). In up to 20% of cases, the heart is grossly and histologically normal at autopsy (unexplained SD or "mors sine materia"), and inherited ion channel diseases have been implicated (long and short QT syndromes, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia). Targets to treat and prevent SD in the young consist of the following: (a) avoid triggers like effort or emotion, (b) inhibit the onset of arrhythmias with drugs or ablation, (c) switch off arrhythmias with defibrillator, and (d) hinder the recurrence of the disease with genetic counseling and/or therapy. In vivo detection of cardiomyopathies is nowadays feasible by electrocardiogram and/or echocardiography, which resulted in a sharp decline of SD in the athletes in Italy, thanks to obligatory preparticipation screening for sport activity. Genetic screening could play a pivotal role in early detection of asymptomatic mutation carriers of cardiovascular diseases at risk

  16. Incidence of sudden cardiac death in athletes: a state-of-the-art review.

    PubMed

    Harmon, Kimberly G; Drezner, Jonathan A; Wilson, Mathew G; Sharma, Sanjay

    2014-08-01

    Sudden cardiac death (SCD) is the leading medical cause of death in athletes; however, the precise incidence is unknown. The objectives of this review were to examine studies on the rate of SCD in athletes, assess the methodological strengths and weaknesses used to arrive at estimates, compare studies in athletes with estimates in similar populations and arrive at an approximation of the incidence of SCD based on the best available evidence. A comprehensive literature search was performed in PubMed using key terms related to SCD in athletes. Articles were reviewed for relevance and included if they contained information on the incidence of SCD in athletes or young persons up to the age of 40. The reference list from each manuscript was reviewed for additional relevant articles. The methods for case identification were examined, as well as the inclusion and exclusion criteria and the precision of the population denominator studied. Thirteen studies were found investigating the rate of SCD in athletes who ranged in age from 9 to 40. An additional 15 incidence studies were located examining the rate of SCD in other populations under the age of 40. Rates of SCD varied from 1:917,000 to 1:3000. Studies with higher methodological quality consistently yielded incidence rates in the range of 1:40,000 to 1:80,000. Some athlete subgroups, specifically men, African-American/black athletes and basketball players, appear to be at higher risk. The incidence of SCD in athletes is likely higher than traditional estimates which may impact the development of more effective prevention strategies.

  17. [The morphological changes in the myocardial tissue after sudden cardiac death from alcoholic cardiomyopathy].

    PubMed

    Sokolova, O V

    2016-01-01

    This paper was designed to report the results of the retrospective analysis of the protocols of 180 forensic medical autopsy sections stored in the archives of Sankt-Petersburg Bureau of Forensic Medical Expertise and the data of the histological studies of myocardial tissues obtained after sudden cardiac death from alcoholic cardiomyopathy. The study revealed the following most pathognomonic histological criteria for alcoholic heart lesions: the alternation of hypertrophic and atrophic cardiomyocytes in the state of severe parenchymatous degeneration, pronounced mesenchymal fatty dystrophy in combination with pathological changes of the vascular walls (vascular wall plasmatization), sub-endothelial accumulation of the PAS-positive tissue compounds, microcirculatory disorders in the form of erythrocyte stasis with the manifestations of the blood "sludge" phenomenon, and precapillary fibrosis. The signs of severe parenchymatous and stromal vascular dystrophy of the myocardial histohematic barrier (HHB) are supposed to reflect the toxic effects of ethanol and its metabolites that are directly involved in the mechanisms underlying the disturbances of intracellular metabolism and dyscirculatory events leading to the development of heart muscle hypoxia.

  18. The Gordon Wilson Lecture: Neurohormonal Signaling Pathways That Link Cardiac Growth and Death

    PubMed Central

    Dorn, Gerald W.

    2007-01-01

    Far from being a simple muscular pump, the heart senses changes in hemodynamic forces and neurohormonal signaling, and responds by elaborating autocrine and paracrine factors that self-regulate cardiomyocyte contraction, growth, and programmed death. Interference with the afferent or efferent arms of this stress-response mechanism, as with inhibition of the β-adrenergic or renin/angiotensin systems, is a mainstay of pharmacological therapy for heart failure. However, despite striking group-mean effects showing mortality benefits of neurohormonal antagonists, inter-individual variability in the therapeutic response to these agents suggests a pharmacogenomic interaction, where common sequence variations of genes that regulate neurohormonal signaling modify the individual response to treatment. Furthermore, there is increasing evidence that, depending upon physiological milieu, conventional neurohormone receptor-ligand pairs can activate non-traditional signaling pathways, with pathological consequences. Recently, studies that integrate the findings from human gene polymorphism discovery, recombinant gene variant expression in cell and animal models, and outcome or risk analysis of polymorphisms in human disease have provided additional understanding into adaptive and maladaptive events that are the consequence of the cardiac stress-response sequence. PMID:18528498

  19. Minimising cold ischaemic time is essential in cardiac death donor-associated liver transplantation

    PubMed Central

    Karp, Seth J; Johnson, Scott; Evenson, Amy; Curry, Michael P; Manning, Diarmuid; Malik, Raza; Lake-Bakaar, Gerond; Lai, Michelle; Hanto, Douglas

    2011-01-01

    Background An important issue in the transplantation of livers procured from cardiac death donors (CDDs) concerns why some centres report equivalent outcomes and others report inferior outcomes in transplantations using CDD organs compared with standard criteria donor (SCD) organs. Resolving this discrepancy may increase the number of usable organs. Objectives This study aimed to test whether differences in cold ischaemic time (CIT) are critical during CDD organ transplantation and whether such differences might explain the disparate outcomes. Methods Results of CDD liver transplants in our own centre were compared retrospectively with results in a matched cohort of SCD liver recipients. Endpoints of primary non-function (PNF) and ischaemic cholangiopathy (IC) were used because these outcomes are clearly associated with CDD organ use. Results In 22 CDD organ transplants, CIT was a strong predictor of PNF or IC (P = 0.021). Minimising CIT in CDD organ transplants produced outcomes similar to those in a matched SCD organ transplant cohort at our centre and in SCD organ transplant results nationally (1- and 3-year graft and patient survival rates: 90.9% and 73.3% vs. 77.6% and 69.2% in CDD and SCD grafts, respectively. A review of the published literature demonstrated that centres with higher CITs tend to have higher rates of PNF or IC (correlation coefficient: 0.41). Conclusions These findings suggest that a targeted effort to minimise CIT might improve outcomes and allow the safer use of CDD organs. PMID:21609374

  20. 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

  1. 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

  2. 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.

  3. Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases.

    PubMed

    Hertz, Christin Loeth; Christiansen, Sofie Lindgren; Larsen, Maiken Kudahl; Dahl, Morten; Ferrero-Miliani, Laura; Weeke, Peter Ejvin; Pedersen, Oluf; Hansen, Torben; Grarup, Niels; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Banner, Jytte; Morling, Niels

    2016-06-01

    Sudden infant death syndrome (SIDS) is the most frequent manner of post-perinatal death among infants. One of the suggested causes of the syndrome is inherited cardiac diseases, mainly channelopathies, that can trigger arrhythmias and sudden death. The purpose of this study was to investigate cases of sudden unexpected death in infancy (SUDI) for potential causative variants in 100 cardiac-associated genes. We investigated 47 SUDI cases of which 38 had previously been screened for variants in RYR2, KCNQ1, KCNH2 and SCN5A. Using the Haloplex Target Enrichment System (Agilent) and next-generation sequencing (NGS), the coding regions of 100 genes associated with inherited channelopathies and cardiomyopathies were captured and sequenced on the Illumina MiSeq platform. Sixteen (34%) of the SUDI cases had variants with likely functional effects, based on conservation, computational prediction and allele frequency, in one or more of the genes screened. The possible effects of the variants were not verified with family or functional studies. Eight (17%) of the SUDI cases had variants in genes affecting ion channel functions. The remaining eight cases had variants in genes associated with cardiomyopathies. In total, one third of the SUDI victims in a forensic setting had variants with likely functional effect that presumably contributed to the cause of death. The results support the assumption that channelopathies are important causes of SUDI. Thus, analysis of genes associated with cardiac diseases in SUDI victims is important in the forensic setting and a valuable supplement to the clinical investigation in all cases of sudden death.

  4. Genetic investigations of sudden unexpected deaths in infancy using next-generation sequencing of 100 genes associated with cardiac diseases.

    PubMed

    Hertz, Christin Loeth; Christiansen, Sofie Lindgren; Larsen, Maiken Kudahl; Dahl, Morten; Ferrero-Miliani, Laura; Weeke, Peter Ejvin; Pedersen, Oluf; Hansen, Torben; Grarup, Niels; Ottesen, Gyda Lolk; Frank-Hansen, Rune; Banner, Jytte; Morling, Niels

    2016-06-01

    Sudden infant death syndrome (SIDS) is the most frequent manner of post-perinatal death among infants. One of the suggested causes of the syndrome is inherited cardiac diseases, mainly channelopathies, that can trigger arrhythmias and sudden death. The purpose of this study was to investigate cases of sudden unexpected death in infancy (SUDI) for potential causative variants in 100 cardiac-associated genes. We investigated 47 SUDI cases of which 38 had previously been screened for variants in RYR2, KCNQ1, KCNH2 and SCN5A. Using the Haloplex Target Enrichment System (Agilent) and next-generation sequencing (NGS), the coding regions of 100 genes associated with inherited channelopathies and cardiomyopathies were captured and sequenced on the Illumina MiSeq platform. Sixteen (34%) of the SUDI cases had variants with likely functional effects, based on conservation, computational prediction and allele frequency, in one or more of the genes screened. The possible effects of the variants were not verified with family or functional studies. Eight (17%) of the SUDI cases had variants in genes affecting ion channel functions. The remaining eight cases had variants in genes associated with cardiomyopathies. In total, one third of the SUDI victims in a forensic setting had variants with likely functional effect that presumably contributed to the cause of death. The results support the assumption that channelopathies are important causes of SUDI. Thus, analysis of genes associated with cardiac diseases in SUDI victims is important in the forensic setting and a valuable supplement to the clinical investigation in all cases of sudden death. PMID:26350513

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. The factors affecting early death after the initial therapy of acute myeloid leukemia

    PubMed Central

    Malkan, Umit Yavuz; Gunes, Gursel; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Etgul, Sezgin; Aslan, Tuncay; Yayar, Okan; Aydin, Seda; Demiroglu, Haluk; Ozcebe, Osman Ilhami; Sayinalp, Nilgun; Goker, Hakan; Aksu, Salih; Buyukasik, Yahya

    2015-01-01

    There are some improvements in management of acute myeloid leukemia (AML). However, induction-induced deaths still remain as a major problem. The aim of this study is to assess clinical parameters affecting early death in patients with AML. 199 AML patients, who were treated with intensive, non-intensive or supportive treatment between 2002 and 2014 in Hacettepe Hematology Department, were analyzed retrospectively. In our study early death rate for elderly was found to be lower than previous reports whereas it was similar for those who were under age of 60. Better ECOG performance (ECOG performance score 0 and 1) and non-intensive treatment associated with lower early death rates, however APL-type disease associated with higher early death rates. ECOG performance score at diagnosis was found to be the most related independent factor with higher rate of early death in 15 days after treatment (P<0.001). Therefore we decided to understand the factors which were related with ECOG. WBC count at diagnosis was found to be the only related parameter with ECOG performance score. Leucocyte count at diagnosis appears like to have an indirect effect on early death in AML patients. It maybe suggested that in recent years there is an improvement in early death rates of elderly AML patients. The currently reported findings require prospective validation and would encourage the incorporation of other next generation genomics for the prediction of early death and overall risk status of AML. PMID:26885243

  11. 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

  12. Remote Liver Ischemic Preconditioning Protects against Sudden Cardiac Death via an ERK/GSK-3β-Dependent Mechanism

    PubMed Central

    Hu, Zhaoyang; Hu, Sheng; Yang, Shuai; Chen, Mou; Zhang, Ping; Liu, Jin; Abbott, Geoffrey W.

    2016-01-01

    Background Preconditioning stimuli conducted in remote organs can protect the heart against subsequent ischemic injury, but effects on arrhythmogenesis and sudden cardiac death (SCD) are unclear. Here, we investigated the effect of remote liver ischemia preconditioning (RLIPC) on ischemia/reperfusion (I/R)-induced cardiac arrhythmia and sudden cardiac death (SCD) in vivo, and determined the potential role of ERK/GSK-3βsignaling. Methods/Results Male Sprague Dawley rats were randomized to sham-operated, control, or RLIPC groups. RLIPC was induced by alternating four 5-minute cycles of liver ischemia with 5-minute intermittent reperfusions. To investigate I/R-induced arrhythmogenesis, hearts in each group were subsequently subjected to 5-minute left main coronary artery ligation followed by 20-minute reperfusion. RLIPC reduced post-I/R ventricular arrhythmias, and decreased the incidence of SCD >threefold. RLIPC increased phosphorylation of cardiac ERK1/2, and GSK-3β Ser9 but not Tyr216 post-I/R injury. Inhibition of either GSK-3β (with SB216763) or ERK1/2 (with U0126) abolished RLIPC-induced antiarrhythmic activity and GSK-3β Ser9 and ERK1/2 phosphorylation, leaving GSK-3β Tyr216 phosphorylation unchanged. Conclusions RLIPC exerts a powerful antiarrhythmic effect and reduces predisposition to post-IR SCD. The underlying mechanism of RLIPC cardioprotection against I/R-induced early arrhythmogenesis may involve ERK1/2/GSK-3β Ser9-dependent pathways. PMID:27768739

  13. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

    PubMed

    Lee, Sun-Hyo; Park, Samel; Lee, Jung-Won; Hwang, Il-Woong; Moon, Hyung-Jun; Kim, Ki-Hwan; Park, Su-Yeon; Gil, Hyo-Wook; Hong, Sae-Yong

    2016-07-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

  14. 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.

  15. 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.

  16. 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

  17. Resveratrol protects ROS-induced cell death by activating AMPK in H9c2 cardiac muscle cells

    PubMed Central

    Hwang, Jin-Taek; Kwon, Dae Young; Park, Ock Jin

    2007-01-01

    Resveratrol, one of polyphenols derived from red wine, has been shown to protect against cell death, possibly through the association with several signaling pathways. Currently numerous studies indicate that cardiovascular diseases are linked to the release of intracellular reactive oxygen species (ROS) often generated in states such as ischemia/reperfusion injury. In the present study, we investigated whether resveratrol has the capability to control intracellular survival signaling cascades involving AMP-activated kinase (AMPK) in the inhibitory process of cardiac injury. We hypothesized that resveratrol may exert a protective effect on damage to heart muscle through modulating of the AMPK signaling pathway. We mimicked ischemic conditions by inducing cell death with H2O2 in H9c2 muscle cells. In this experiment, resveratrol induced strong activation of AMPK and inhibited the occurrence of cell death caused by treatment with H2O2. Under the same conditions, inhibition of AMPK using dominant negative AMPK constructs dramatically abolished the effect of resveratrol on cell survival in H2O2-treated cardiac muscle cells. These results indicate that resveratrol-induced cell survival is mediated by AMPK in H9c2 cells and may exert a novel therapeutic effect on oxidative stress induced in cardiac disorders. PMID:18850225

  18. 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

  19. 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

  20. Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

    PubMed

    Lee, David D; Singh, Amandeep; Burns, Justin M; Perry, Dana K; Nguyen, Justin H; Taner, C Burcin

    2014-12-01

    Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. PMID:25179581

  1. 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.

  2. 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

  3. A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death.

    PubMed

    Huttner, Inken G; Trivedi, Gunjan; Jacoby, Arie; Mann, Stefan A; Vandenberg, Jamie I; Fatkin, Diane

    2013-08-01

    The recent exponential increase in human genetic studies due to the advances of next generation sequencing has generated unprecedented numbers of new gene variants. Determining which of these are causative of human disease is a major challenge. In-vitro studies and murine models have been used to study inherited cardiac arrhythmias but have several limitations. Zebrafish models provide an attractive alternative for modeling human heart disease due to similarities in cardiac electrophysiology and contraction, together with ease of genetic manipulation, external development and optical transparency. Although zebrafish cardiac mutants and morphants have been widely used to study loss and knockdown of zebrafish gene function, the phenotypic effects of human dominant-negative gene mutations expressed in transgenic zebrafish have not been evaluated. The aim of this study was to generate and characterize a transgenic zebrafish arrhythmia model harboring the pathogenic human cardiac sodium channel mutation SCN5A-D1275N, that has been robustly associated with a range of cardiac phenotypes, including conduction disease, sinus node dysfunction, atrial and ventricular arrhythmias, and dilated cardiomyopathy in humans and in mice. Stable transgenic fish with cardiac expression of human SCN5A were generated using Tol2-mediated transgenesis and cardiac phenotypes were analyzed using video microscopy and ECG. Here we show that transgenic zebrafish expressing the SCN5A-D1275N mutation, but not wild-type SCN5A, exhibit bradycardia, conduction-system abnormalities and premature death. We furthermore show that SCN5A-WT, and to a lesser degree SCN5A-D1275N, are able to compensate the loss of endogenous zebrafish cardiac sodium channels, indicating that the basic pathways, through which SCN5A acts, are conserved in teleosts. This proof-of-principle study suggests that zebrafish may be highly useful in vivo models to differentiate functional from benign human genetic variants in cardiac

  4. Radiation Therapy and Cardiac Death in Long-Term Survivors of Esophageal Cancer: An Analysis of the Surveillance, Epidemiology, and End Result Database

    PubMed Central

    Gharzai, Laila; Verma, Vivek; Denniston, Kyle A.; Bhirud, Abhijeet R.; Bennion, Nathan R.; Lin, Chi

    2016-01-01

    Objective Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. Methods 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973–2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Results Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255–367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03–1.47, HR 1.961, 95% CI 1.466–2.624). Lower esophageal subsite (33–40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Conclusions Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death

  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. Cardiac glycoside-induced cell death and Rho/Rho kinase pathway: Implication of different regulation in cancer cell lines.

    PubMed

    Özdemir, Aysun; Şimay, Yaprak Dilber; İbişoğlu, Burçin; Yaren, Biljana; Bülbül, Döne; Ark, Mustafa

    2016-05-01

    Previously, we demonstrated that the Rho/ROCK pathway is involved in ouabain-induced apoptosis in HUVEC. In the current work, we investigated whether the Rho/ROCK pathway is functional during cardiac glycosides-induced cytotoxic effects in cancer cell lines, as well as in non-tumor cells. For that purpose, we evaluated the role of ROCK activation in bleb formation and cell migration over upstream and downstream effectors in addition to ROCK cleavage after cardiac glycosides treatment. All three cardiac glycosides (ouabain, digoxin and bufalin) induced cell death in HeLa and HepG2 cells and increased the formation of blebbing in HeLa cells. In contrast to our previous study, ROCK inhibitor Y27632 did not prevent bleb formation. Observation of ROCK II cleavage after ouabain, digoxin and oxaliplatin treatments in HeLa and/or HepG2 cells suggested that cleavage is independent of cell type and cell death induction. While inhibiting cleavage of ROCK II by the caspase inhibitors z-VAD-fmk, z-VDVAD-fmk and z-DEVD-fmk, evaluation of caspase 2 siRNA ineffectiveness on this truncation indicated that caspase-dependent ROCK II cleavage is differentially regulated in cancer cell lines. In HeLa cells, ouabain induced the activation of ROCK, although it did not induce phosphorylation of ERM, an upstream effector. While Y27632 inhibited the migration of HeLa cells, 10nM ouabain had no effect on cell migration. In conclusion, these findings indicate that the Rho/ROCK pathway is regulated differently in cancer cell lines compared to normal cells during cardiac glycosides-induced cell death. PMID:27017918

  8. Immediate multivessel revascularization may increase cardiac death and myocardial infarction in patients with ST-elevation myocardial infarction and multivessel coronary artery disease: data analysis from real world practice

    PubMed Central

    Chung, Woo-Young; Seo, Jae-Bin; Choi, Dong-Hyun; Cho, Young-Seok; Lee, Joo Myung; Suh, Jung-Won; Youn, Tae-Jin; Chae, In-Ho; Choi, Dong-Ju

    2016-01-01

    Background/Aims: The best revascularization strategy for patients with both acute ST-elevation myocardial infarction (STEMI) and multivessel coronary disease (MVD) is still debatable. We aimed to compare the outcomes of multivessel revascularization (MVR) with those of culprit-only revascularization (COR). Methods: A cohort of 215 consecutive patients who had received primary angioplasty for STEMI and MVD were divided into two groups according to whether angioplasty had been also performed for a stenotic nonculprit artery. The primary endpoint was one-year major adverse cardiac events defined as a composite of cardiac death, recurrent myocardial infarction, or any repeat revascularization. Results: One-year major adverse cardiac events were not significantly different between MVR (n = 107) and COR (n = 108) groups. However, the one-year composite hard endpoint of cardiac death or recurrent myocardial infarction was notably increased in the MVR group compared to the COR group (20.0% vs. 8.9%, p = 0.024). In subgroup analysis, the hard endpoint was significantly more frequent in the immediate than in the staged MVR subgroup (26.6% vs. 9.8%, p = 0.036). The propensity score-matched cohorts confirmed these findings. Conclusions: In patients with STEMI and MVD, MVR, especially immediate MVR with primary percutaneous intervention, was not beneficial and led to worse outcomes. Therefore, we conclude that COR or staged MVR would be better strategies for patients with STEMI and MVD. PMID:27048252

  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. Sensitization of acute lymphoblastic leukemia cells for LCL161-induced cell death by targeting redox homeostasis.

    PubMed

    Haß, Christina; Belz, Katharina; Schoeneberger, Hannah; Fulda, Simone

    2016-04-01

    Disturbed redox homeostasis with both elevated reactive oxygen species (ROS) levels and antioxidant defense mechanisms has been reported in acute lymphoblastic leukemia (ALL). We therefore hypothesized that inhibition of pathways responsible for ROS detoxification renders ALL cells more susceptible for cell death. Here, we report that pharmacological inhibitors of key pathways for the elimination of ROS, i.e. Erastin, buthionine sulfoximine (BSO) and Auranofin, sensitize ALL cells for cell death upon treatment with the Smac mimetic LCL161 that antagonizes Inhibitor of Apoptosis (IAP) proteins. Erastin, BSO or Auranofin significantly increase LCL161-induced cell death and also act in concert with LCL161 to profoundly suppress long-term clonogenic survival in several ALL cell lines. Erastin or BSO cooperates with LCL161 to stimulate ROS production and lipid peroxidation prior to cell death. ROS production and lipid peroxidation are required for this cotreatment-induced cell death, since ROS scavengers or pharmacological inhibition of lipid peroxidation provides significant protection against cell death. These results emphasize that inhibition of antioxidant defense mechanisms can serve as a potent approach to prime ALL cells for LCL161-induced cell death.

  11. Pathophysiological role of different tubular epithelial cell death modes in acute kidney injury

    PubMed Central

    Sancho-Martínez, Sandra M.; López-Novoa, José M.; López-Hernández, Francisco J.

    2015-01-01

    The histological substrate of many forms of intrinsic acute kidney injury (AKI) has been classically attributed to tubular necrosis. However, more recent studies indicate that necrosis is not the main form of cell death in AKI and that other forms such as apoptosis, regulated necrosis (i.e. necroptosis and parthanatos), autophagic cell death and mitotic catastrophe, also participate in AKI and that their contribution depends on the cause and stage of AKI. Herein, we briefly summarize the main characteristics of the major types of cell death and we also critically review the existing evidence on the occurrence of different types of cell death reported in the most common experimental models of AKI and human specimens. We also discuss the pathophysiological mechanisms linking tubule epithelial cell death with reduced glomerular filtration, azotaemia and hydroelectrolytic imbalance. For instance, special relevance is given to the analysis of the inflammatory component of some forms of cell death over that of others, as an important and differential pathophysiological determinant. Finally, known molecular mechanisms and signalling pathways involved in each cell death type pose appropriate targets to specifically prevent or reverse AKI, provided that further knowledge of their participation and repercussion in each AKI syndrome is progressively increased in the near future. PMID:26413280

  12. An approach to predict Sudden Cardiac Death (SCD) using time domain and bispectrum features from HRV signal.

    PubMed

    Houshyarifar, Vahid; Chehel Amirani, Mehdi

    2016-08-12

    In this paper we present a method to predict Sudden Cardiac Arrest (SCA) with higher order spectral (HOS) and linear (Time) features extracted from heart rate variability (HRV) signal. Predicting the occurrence of SCA is important in order to avoid the probability of Sudden Cardiac Death (SCD). This work is a challenge to predict five minutes before SCA onset. The method consists of four steps: pre-processing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In second step, bispectrum features of HRV signal and time-domain features are obtained. Six features are extracted from bispectrum and two features from time-domain. In the next step, these features are reduced to one feature by the linear discriminant analysis (LDA) technique. Finally, KNN and support vector machine-based classifiers are used to classify the HRV signals. We used two database named, MIT/BIH Sudden Cardiac Death (SCD) Database and Physiobank Normal Sinus Rhythm (NSR). In this work we achieved prediction of SCD occurrence for six minutes before the SCA with the accuracy over 91%. PMID:27567781

  13. [Death].

    PubMed

    Ribas, Jordi Domingo

    2003-12-01

    Intercultural factors are essential for reflection. In this article, the authors deals with a more direct vision on the special edition about Grief and Mourning, about the topic which lies in the depths of all of our consciences: death and the question what lies beyond death? The author provides us elements to reflect about concepts, some accepted in various cases, rejected in others, but always polemical, which help us to penetrate farther into the real mystery of life: death and what follows death.

  14. 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

  15. 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

  16. Usefulness of cardiac meta-iodobenzylguanidine imaging to identify patients with chronic heart failure and left ventricular ejection fraction <35% at low risk for sudden cardiac death.

    PubMed

    Kawai, Tsutomu; Yamada, Takahisa; Tamaki, Shunsuke; Morita, Takashi; Furukawa, Yoshio; Iwasaki, Yusuke; Kawasaki, Masato; Kikuchi, Atsushi; Kondo, Takumi; Takahashi, Satoshi; Ishimi, Masashi; Hakui, Hideyuki; Ozaki, Tatsuhisa; Sato, Yoshihiro; Seo, Masahiro; Sakata, Yasushi; Fukunami, Masatake

    2015-06-01

    Patients with chronic heart failure (CHF) at risk of sudden cardiac death (SCD) are often treated with implantable cardiac defibrillators (ICDs). However, current criteria for device use that is based largely on left ventricular ejection fraction (LVEF) lead to many patients receiving ICDs that never deliver therapy. It is of clinical significance to identify patients who do not require ICDs. Although cardiac I-123 meta-iodobenzylguanidine (MIBG) imaging provides prognostic information about CHF, whether it can identify patients with CHF who do not require an ICD remains unclear. We studied 81 patients with CHF and LVEF <35%, assessed by cardiac MIBG imaging at enrollment. The heart-to-mediastinal ratio (H/M) in delayed images and washout rates were divided into 6 grades from 0 to 5, according to the degree of deviation from control values. The study patients were classified into 3 groups: low (1 to 4), intermediate (5 to 7), and high (8 to 10), according to the MIBG scores defined as the sum of the H/M and washout rate scores. Sixteen patients died of SCD during a follow-up period. Patients with low MIBG score had a significantly lower risk of SCD than those with intermediate and high scores (low [n = 19], 0%; intermediate [n = 37], 19%; high [n = 25], 36%; p = 0.001). The positive predictive value of low MIBG score for identifying patients without SCD was 100%. In conclusion, the MIBG score can identify patients with CHF and LVEF <35% who have low risk of developing SCD. PMID:25851796

  17. 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

  18. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports.

    PubMed

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

    2016-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  20. 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.

  1. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

    PubMed Central

    2016-01-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3-, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID:27366016

  2. The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication.

    PubMed

    Lee, Sun-Hyo; Park, Samel; Lee, Jung-Won; Hwang, Il-Woong; Moon, Hyung-Jun; Kim, Ki-Hwan; Park, Su-Yeon; Gil, Hyo-Wook; Hong, Sae-Yong

    2016-07-01

    Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na(+), K(+), Cl(-) HCO3 (-), Ca(++)), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication. PMID:27366016

  3. 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.

  4. 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

  5. Acute poisonings and sudden deaths in Crete: a five-year review (1991-1996).

    PubMed

    Christakis-Hampsas, M; Tutudakis, M; Tsatsakis, A M; Assithianakis, P; Alegakis, A; Katonis, P G; Michalodimitrakis, E N

    1998-08-01

    Fatal and non-fatal acute poisonings and other sudden deaths examined in the Toxicology Laboratory of University Hospital of Iraklion, Crete, from 1991 to 1996 mainly involved the abuse of drugs (heroin, flunitrazepam and other psychoactive substances), accidental poisonings or suicide attempts with pesticides (carbamates, organophosphates, paraquat), other chemicals (cyanide salts, paint thinner, chlorine), traffic accidents, drownings and violent deaths (gunshots). Many of the cases were related to poisonous gases or volatiles (carbon monoxide, methylbromide). Fatalities due to alcohol and methylene-dioxy-ethyl amphetamine were also examined. Amphetamine and alcohol-related deaths due to drowning were more recent. A significant number of cases were related to the accidental ingestion of alcohol, drugs or suicide attempts by children. Some of the cases were treated successfully in various Cretan hospitals, while others had fatal outcomes due to late hospital admission. PMID:9682411

  6. [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

  7. Reduction of cardiac cell death after helium postconditioning in rats: transcriptional analysis of cell death and survival pathways.

    PubMed

    Oei, Gezina T M L; Heger, Michal; van Golen, Rowan F; Alles, Lindy K; Flick, Moritz; van der Wal, Allard C; van Gulik, Thomas M; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2015-01-20

    Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways.

  8. Reduction of Cardiac Cell Death after Helium Postconditioning in Rats: Transcriptional Analysis of Cell Death and Survival Pathways

    PubMed Central

    Oei, Gezina TML; Heger, Michal; van Golen, Rowan F; Alles, Lindy K; Flick, Moritz; van der Wal, Allard C; van Gulik, Thomas M; Hollmann, Markus W; Preckel, Benedikt; Weber, Nina C

    2014-01-01

    Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways. PMID:25171109

  9. Sudden cardiac death in the soccer field: a retrospective study in young soccer players from 2000 to 2013.

    PubMed

    Davogustto, Giovanni; Higgins, John

    2014-11-01

    Soccer is the most popular sport in the world, with over 200 million active players. Sudden cardiac death (SCD) represents the most striking as well as the most common cause of death in the soccer field. Underlying cardiovascular pathologies predispose to life threatening ventricular arrhythmias and SCD in soccer players. Up to thousands to hundred thousands players might have an underlying condition that predisposes them for SCD. After several media striking SCD events in soccer players the Fédération Internationale de Football Association (FIFA) has made screening recommendations that are more thorough than the ones recommended for the American Heart Association and the European Society of Cardiology. We present a retrospective search through Internet databases that resulted in 54 soccer players with SCD events from 2000 until 2013. In this article, we will describe and discuss the conditions of those cases of SCD in order to provide more knowledge of the factors that may precipitate SCD in young soccer players.

  10. [How to increase availability of grafts in lung transplantion: ex vivo lung reconditioning - cardiac death donors - high emergency list].

    PubMed

    Souilamas, R; Souilamas, J; Saueressig, M; Pison, C; Briot, R

    2010-02-01

    Lung transplantation has become an established treatment for end-stage pulmonary failure refractory to medical management. However, the scarcity of lung grafts and the growing number of candidates has led to an increase in deaths among patients on waiting lists. Despite improvements in donor management, organ preservation, and the use of marginal and cardiac death donors, only about 20% of candidate lungs are currently being transplanted. A new ex vivo "reconditioning" technique is opening up new perspectives. Indeed, a significant number of rejected lungs can now be retrieved and transplanted with acceptable results. Given the longer storage times provided by this technique, transplantation can be programmed, with better surgical efficiency. A new mobile organ-care machine is currently under evaluation. In near future, a pilot laboratory will be created and dedicated to ex vivo reconditionning of all lung grafts before transplantation and grafts will be sent to lung transplant centers after immunologic cross-matching.

  11. [How to increase availability of grafts in lung transplantion: ex vivo lung reconditioning - cardiac death donors - high emergency list].

    PubMed

    Souilamas, R; Souilamas, J; Saueressig, M; Pison, C; Briot, R

    2010-02-01

    Lung transplantation has become an established treatment for end-stage pulmonary failure refractory to medical management. However, the scarcity of lung grafts and the growing number of candidates has led to an increase in deaths among patients on waiting lists. Despite improvements in donor management, organ preservation, and the use of marginal and cardiac death donors, only about 20% of candidate lungs are currently being transplanted. A new ex vivo "reconditioning" technique is opening up new perspectives. Indeed, a significant number of rejected lungs can now be retrieved and transplanted with acceptable results. Given the longer storage times provided by this technique, transplantation can be programmed, with better surgical efficiency. A new mobile organ-care machine is currently under evaluation. In near future, a pilot laboratory will be created and dedicated to ex vivo reconditionning of all lung grafts before transplantation and grafts will be sent to lung transplant centers after immunologic cross-matching. PMID:21353972

  12. 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: ...

  13. QT prolongation and sudden cardiac death in patients with alcoholic liver disease

    SciTech Connect

    Day, C.P.; James, O.F.W. . Dept. of Medicine); Butler, T.J. . Dept. of Medical Statistics); Campbell, R.W.F. . Dept. of Academic Cardiology)

    1993-06-05

    Cardiovascular death is the most important cause of mortality in alcoholics, yet alcohol may protect against ischemic heart disease. This could be explained if deaths were a consequence of alcohol-related arrhythmias rather than of coronary atheroma. In many conditions, abnormalities of the QT interval are markers of arrhythmia and for risk of sudden death. The authors examined the relation between QT intervals and mortality in patients with alcoholic liver disease.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. The phenoptosis problem: what is causing the death of an organism? Lessons from acute kidney injury.

    PubMed

    Zorov, D B; Plotnikov, E Y; Jankauskas, S S; Isaev, N K; Silachev, D N; Zorova, L D; Pevzner, I B; Pulkova, N V; Zorov, S D; Morosanova, M A

    2012-07-01

    Programmed execution of various cells and intracellular structures is hypothesized to be not the only example of elimination of biological systems - the general mechanism can also involve programmed execution of organs and organisms. Modern rating of programmed cell death mechanisms includes 13 mechanistic types. As for some types, the mechanism of actuation and manifestation of cell execution has been basically elucidated, while the causes and intermediate steps of the process of fatal failure of organs and organisms remain unknown. The analysis of deaths resulting from a sudden heart arrest or multiple organ failure and other acute and chronic pathologies leads to the conclusion of a special role of mitochondria and oxidative stress activating the immune system. Possible mechanisms of mitochondria-mediated induction of the signaling cascades involved in organ failure and death of the organism are discussed. These mechanisms include generation of reactive oxygen species and damage-associated molecular patterns in mitochondria. Some examples of renal failure-induced deaths are presented with mechanisms and settings determined by some hypothetical super system rather than by the kidneys themselves. This system plays the key role in the process of physiological senescence and termination of an organism. The facts presented suggest that it is the immune system involved in mitochondrial signaling that can act as the system responsible for the organism's death. PMID:22817538

  4. 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.

  5. Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells.

    PubMed

    Kothari, Anisha; Hittelman, Walter N; Chambers, Timothy C

    2016-06-15

    Microtubule-targeting agents (MTA), such as the taxanes and vinca alkaloids, are used to treat a variety of cancers due to their ability to perturb microtubule dynamics. In cell culture, MTAs exert their anticancer effects primarily by causing mitotic arrest and cell death. However, accumulating indirect evidence suggests that MTAs may exert their cytotoxicity in human tumors by interfering with interphase microtubules. In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with <2N DNA content, suggesting a mixed response. Therefore, we separated ALL cells into distinct phases of the cell cycle by centrifugal elutriation, labeled cells with 5-ethynyl-2'-deoxyuridine (EdU), and then treated each population with vincristine. Cells isolated during G1 underwent cell death without evidence of EdU uptake, indicating that the cytotoxic effects of vincristine took place during G1 Conversely, cells isolated during S or G2-M phases underwent death following mitotic arrest. Thus, vincristine induces distinct death programs in primary ALL cells depending on cell-cycle phase, and cells in G1 are particularly susceptible to perturbation of interphase microtubules. Primary ALL cells may therefore provide a powerful model system in which to study the multimodal mechanisms underlying MTA-induced cell death. Cancer Res; 76(12); 3553-61. ©2016 AACR. PMID:27197148

  6. Cell Cycle-Dependent Mechanisms Underlie Vincristine-Induced Death of Primary Acute Lymphoblastic Leukemia Cells.

    PubMed

    Kothari, Anisha; Hittelman, Walter N; Chambers, Timothy C

    2016-06-15

    Microtubule-targeting agents (MTA), such as the taxanes and vinca alkaloids, are used to treat a variety of cancers due to their ability to perturb microtubule dynamics. In cell culture, MTAs exert their anticancer effects primarily by causing mitotic arrest and cell death. However, accumulating indirect evidence suggests that MTAs may exert their cytotoxicity in human tumors by interfering with interphase microtubules. In this study, we sought to develop and characterize an experimental system in which to test the hypothesis that MTAs induce cell death during interphase. Primary adult acute lymphoblastic leukemia (ALL) cells treated with vincristine only weakly exhibited colocalization between mitotic and apoptotic markers and major characteristics of mitotic death, such as an increase in cells with 4N DNA content before the appearance of cells with <2N DNA content, suggesting a mixed response. Therefore, we separated ALL cells into distinct phases of the cell cycle by centrifugal elutriation, labeled cells with 5-ethynyl-2'-deoxyuridine (EdU), and then treated each population with vincristine. Cells isolated during G1 underwent cell death without evidence of EdU uptake, indicating that the cytotoxic effects of vincristine took place during G1 Conversely, cells isolated during S or G2-M phases underwent death following mitotic arrest. Thus, vincristine induces distinct death programs in primary ALL cells depending on cell-cycle phase, and cells in G1 are particularly susceptible to perturbation of interphase microtubules. Primary ALL cells may therefore provide a powerful model system in which to study the multimodal mechanisms underlying MTA-induced cell death. Cancer Res; 76(12); 3553-61. ©2016 AACR.

  7. 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.

  8. 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

  9. One in Five Maternal Deaths in Bangladesh Associated with Acute Jaundice: Results from a National Maternal Mortality Survey.

    PubMed

    Shah, Rupal; Nahar, Quamrun; Gurley, Emily S

    2016-03-01

    We estimated the proportion of maternal deaths in Bangladesh associated with acute onset of jaundice. We used verbal autopsy data from a nationally representative maternal mortality survey to calculate the proportion of maternal deaths associated with jaundice and compared it to previously published estimates. Of all maternal deaths between 2008 and 2010, 23% were associated with jaundice, compared with 19% from 1998 to 2001. Approximately one of five maternal deaths was preceded by jaundice, unchanged in 10 years. Our findings highlight the need to better understand the etiology of these maternal deaths in Bangladesh.

  10. Nonischemic Left Ventricular Scar as a Substrate of Life-Threatening Ventricular Arrhythmias and Sudden Cardiac Death in Competitive Athletes

    PubMed Central

    Zorzi, Alessandro; Perazzolo Marra, Martina; Rigato, Ilaria; De Lazzari, Manuel; Susana, Angela; Niero, Alice; Pilichou, Kalliopi; Migliore, Federico; Rizzo, Stefania; Giorgi, Benedetta; De Conti, Giorgio; Sarto, Patrizio; Serratosa, Luis; Patrizi, Giampiero; De Maria, Elia; Pelliccia, Antonio; Basso, Cristina; Schiavon, Maurizio; Bauce, Barbara; Iliceto, Sabino; Thiene, Gaetano

    2016-01-01

    Background— The clinical profile and arrhythmic outcome of competitive athletes with isolated nonischemic left ventricular (LV) scar as evidenced by contrast-enhanced cardiac magnetic resonance remain to be elucidated. Methods and Results— We compared 35 athletes (80% men, age: 14–48 years) with ventricular arrhythmias and isolated LV subepicardial/midmyocardial late gadolinium enhancement (LGE) on contrast-enhanced cardiac magnetic resonance (group A) with 38 athletes with ventricular arrhythmias and no LGE (group B) and 40 healthy control athletes (group C). A stria LGE pattern with subepicardial/midmyocardial distribution, mostly involving the lateral LV wall, was found in 27 (77%) of group A versus 0 controls (group C; P<0.001), whereas a spotty pattern of LGE localized at the junction of the right ventricle to the septum was respectively observed in 11 (31%) versus 10 (25%; P=0.52). All athletes with stria pattern showed ventricular arrhythmias with a predominant right bundle branch block morphology, 13 of 27 (48%) showed ECG repolarization abnormalities, and 5 of 27 (19%) showed echocardiographic hypokinesis of the lateral LV wall. The majority of athletes with no or spotty LGE pattern had ventricular arrhythmias with a predominant left bundle branch block morphology and no ECG or echocardiographic abnormalities. During a follow-up of 38±25 months, 6 of 27 (22%) athletes with stria pattern experienced malignant arrhythmic events such as appropriate implantable cardiac defibrillator shock (n=4), sustained ventricular tachycardia (n=1), or sudden death (n=1), compared with none of athletes with no or LGE spotty pattern and controls. Conclusions— Isolated nonischemic LV LGE with a stria pattern may be associated with life-threatening arrhythmias and sudden death in the athlete. Because of its subepicardial/midmyocardial location, LV scar is often not detected by echocardiography. PMID:27390211

  11. Degree Of Diminution In Vagal-Cardiac Activity Predicts Sudden Death In Familial Dysautonomia When Resting Tachycardia Is Absent

    NASA Technical Reports Server (NTRS)

    Schlegel, T. T.; Marthol, H.; Bucchner, S.; Tutaj, M.; Berlin, D.; Axelrod, F. B.; Hilz, M. J.

    2004-01-01

    Patients with familial dysautonomia (FD) have an increased risk of sudden death, but sensitive and specific predictors of sudden death in FD are lacking. Methods. We recorded 10-min resting high-fidelity 12-lead ECGs in 14 FD patients and in 14 age/gender-matched healthy subjects and studied 25+ different heart rate variability (HRV) indices for their ability to predict sudden death in the FD patients. Indices studied included those from 4 "nonlinear" HRV techniques (detrended fluctuation analysis, approximate entropy, correlation dimension, and PoincarC analyses). The predictive value of PR, QRS, QTc and JTc intervals, QT dispersion (QTd), beat-to-beat QT and PR interval variability indices (QTVI and PRVI) and 12- lead high frequency QRS ECG (150-250 Hz) were also studied. FD patients and controls (C) differed (Pless than 0.0l) with respect to 20+ of the HRV indices (FD less than C) and with respect to QTVI and PRVI (FDBC) and HF QRS- related root mean squared voltages (FDBC) and reduced amplitude zone counts (FD less than C). They differed less with respect to PR intervals (FD less than C) and JTc intervals (FD greater than C) (P less than 0.05 for both) and did not differ at all with respect to QRS and QTc intervals and to QTd. Within 12 months after study, 2 of the 14 patients succumbed to sudden cardiac arrest. The best predictor of sudden death was the degree of diminution in HRV vagal-cardiac (parasympathetic) parameters such as RMSSD, the SDl of Poincare plots, and HF spectral power. Excluding the two FD patients who had resting tachycardia (HR greater than 100, which confounds traditional HRV analyses), the following criteria were independently 100% sensitive and 100% specific for predicting sudden death in the remaining 12 FD patients during spontaneous breathing: RMSSD less than 13 ms and/or PoincarC SD1 less than 9 ms. In FD patients without supine tachycardia, the degree of diminution in parasympathetic HRV parameters (by high-fidelity ECG) predicts

  12. Hypertrophic cardiomyopathy and sudden cardiac death due to physical exercise in Croatia in a 27-year period.

    PubMed

    Duraković, Zijad; Duraković, Marjeta Misigoj; Skavić, Josip

    2011-12-01

    The paper deals with the sudden cardiac death during physical exercise in males in Croatia. The data are a part of a retrospective study dealing with 69 sudden death due to physical activity in men in Croatia during 27 years: from January 1, 1984 to December 31, 2010. Three of them suddenly died during training and two of them died during recreational physical exercise, probably because of malignant ventricular arrhythmia due to hyperthrophic cardiomyopathy. One had an obstructive form of hypertrophic cardiomyopathy with i.v. septum of 40 mm and four had a non-obstructive forms of hyperthrophic cardiomyopathy with left ventricular wall of 18-20-22-25 mm. First athlete was a short trails runner, aged 24, with no any previous physical discomforts, who suddenly collapsed and died during training. The second athlete was a soccer player aged 18, with no any previous physical discomfort, who suddenly collapsed and died during training. The third aged 15, was a school boy, basketball player, with no any previous physical discomfort, who collapsed and died during training. Two aged 25 and 34, were with no physical discomfort during exercise and died suddenly during recreational soccer games. A sudden cardiac death due to physical exercise in young athletes in Croatia suffered of hyperthropic cardiomyopathy reached 0.06/100 000 yearly (p = 0.00000) in 27 years, in teenagers 0.26/100 000 (p = 0.00226), in teenagers suffered of hypertrophic cardiomyopathy reached 0.10/100 000 (p = 0.00000), in all young athletes suffered of other heart diseases reached 0.19/100 000 (p = 0.00005), and in the total male population aged 15 or more, engaged in sports and recreational physical exercise: 0.71/100.0000 (p = 0.00001).

  13. 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

  14. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review

    PubMed Central

    Doust, Jenny A; Pietrzak, Eva; Dobson, Annette; Glasziou, Paul

    2005-01-01

    Objective To assess how well B-type natriuretic peptide (BNP) predicts prognosis in patients with heart failure. Design Systematic review of studies assessing BNP for prognosis in patients with heart failure or asymptomatic patients. Data sources Electronic searches of Medline and Embase from January 1994 to March 2004 and reference lists of included studies. Study selection and data extraction We included all studies that estimated the relation between BNP measurement and the risk of death, cardiac death, sudden death, or cardiovascular event in patients with heart failure or asymptomatic patients, including initial values and changes in values in response to treatment. Multivariable models that included both BNP and left ventricular ejection fraction as predictors were used to compare the prognostic value of each variable. Two reviewers independently selected studies and extracted data. Data synthesis 19 studies used BNP to estimate the relative risk of death or cardiovascular events in heart failure patients and five studies in asymptomatic patients. In heart failure patients, each 100 pg/ml increase was associated with a 35% increase in the relative risk of death. BNP was used in 35 multivariable models of prognosis. In nine of the models, it was the only variable to reach significance—that is, other variables contained no prognostic information beyond that of BNP. Even allowing for the scale of the variables, it seems to be a strong indicator of risk. Conclusion Although systematic reviews of prognostic studies have inherent difficulties, including the possibility of publication bias, the results of the studies in this review show that BNP is a strong prognostic indicator for both asymptomatic patients and for patients with heart failure at all stages of disease. PMID:15774989

  15. Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2011-03-01

    The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed.

  16. [Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death].

    PubMed

    Zamarrón-de Lucas, Ester; García-Fernández, Eugenia; Carpio, Carlos; Alcolea, Sergio; Martínez-Abad, Yolanda; Álvarez-Sala, Rodolfo

    2016-06-17

    The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome.

  17. [Massive cardiac lipomatosis, an autopsy finding in a patient with sudden death].

    PubMed

    Zamarrón-de Lucas, Ester; García-Fernández, Eugenia; Carpio, Carlos; Alcolea, Sergio; Martínez-Abad, Yolanda; Álvarez-Sala, Rodolfo

    2016-06-17

    The fat replacement of myocardial cells is a degenerative process that usually affects the right ventricle and is found in 50% of the elderly. The problem arises when this degeneration occurs to a massive degree, a differential diagnosis with other pathologies being necessary. We present the case of a patient who died suddenly and a massive cardiac lipomatosis was found on autopsy, as the only explanation of the outcome. PMID:27143526

  18. 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

  19. 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

  20. 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

  1. 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

  2. Cardiomyocyte death: mechanisms and translational implications.

    PubMed

    Chiong, M; Wang, Z V; Pedrozo, Z; Cao, D J; Troncoso, R; Ibacache, M; Criollo, A; Nemchenko, A; Hill, J A; Lavandero, S

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications. PMID:22190003

  3. Cardiomyocyte death: mechanisms and translational implications

    PubMed Central

    Chiong, M; Wang, Z V; Pedrozo, Z; Cao, D J; Troncoso, R; Ibacache, M; Criollo, A; Nemchenko, A; Hill, J A; Lavandero, S

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although treatments have improved, development of novel therapies for patients with CVD remains a major research goal. Apoptosis, necrosis, and autophagy occur in cardiac myocytes, and both gradual and acute cell death are hallmarks of cardiac pathology, including heart failure, myocardial infarction, and ischemia/reperfusion. Pharmacological and genetic inhibition of autophagy, apoptosis, or necrosis diminishes infarct size and improves cardiac function in these disorders. Here, we review recent progress in the fields of autophagy, apoptosis, and necrosis. In addition, we highlight the involvement of these mechanisms in cardiac pathology and discuss potential translational implications. PMID:22190003

  4. Clinical Cosmobiology - Sudden Cardiac Death and Daily / Monthly Geomagnetic, Cosmic Ray and Solar Activity - the Baku Study (2003-2005)

    NASA Astrophysics Data System (ADS)

    Stoupel, E.; Babayev, E. S.; Mustafa, F. R.; Abramson, E.; Israelevich, P.; Sulkes, J.

    2006-12-01

    Part of results of collaborative studies for revealing an influence of the periodical changes of solar, geomagnetic and cosmic ray activities on the sudden cardiac death (SCD) mortality is described in this paper. The data covering daily and monthly temporal distribution of SCD (788 patients in 36 months in 2003-2005), taken from all of emergency and first medical aid stations of grand Baku area, were analyzed and compared with certain cosmophysical parameters. It was obtained that SCD is higher on the highest and lowest daily levels of geomagnetic activity. Days with SCD are accompanied by higher cosmic ray (neutron) activity. The monthly number of SCD was inversely related to solar and geomagnetic activities while was positively linked with cosmic ray activity level. It was concluded that cosmic ray activity could be considered as one of regulating external/environmental factors in human homeostasis.

  5. Recurrent aborted sudden cardiac death with seizures and rhabdomyolysis due to bulimia-induced hypokalemia: report of one case.

    PubMed

    Finsterer, Josef; Stöllberger, Claudia

    2014-06-01

    Recurrent vomiting due to bulimia associated with abuse of furosemide and laxatives causing severe hypokalemia may result in recurrent aborted sudden cardiac death (SCD) and seizures. We report a 25-year-old female with a history of bulimia associated with abuse of furosemide and laxatives since the age of 15 years, migraine since puberty, renal abscesses at age 20 y, and rhabdomyolysis of unknown cause at age 24 y. She experienced aborted SCD due to severe hypokalemia with symptomatic seizures at 21 and 25 years of age. Bulimia patients additionally taking laxatives or furosemide are at particular risk of SCD and rhabdomyolysis and require periodic determination of electrolytes, potassium substitution, and adequate psychiatric therapy and surveillance.

  6. Preventing Sudden Cardiac Death: Automated External Defibrillators in Ohio High Schools

    PubMed Central

    Lear, Aaron; Hoang, Minh-Ha; Zyzanski, Stephen J.

    2015-01-01

    Context Ohio passed legislation in 2004 for optional public funding of automated external defibrillators (AEDs) in all Ohio high schools. Objective To report occurrences of sudden cardiac arrest in which AEDs were used in Ohio high schools and to evaluate the adherence of Ohio high schools with AEDs to state law and published guidelines on AEDs and emergency action plans (EAPs) in schools. Design Cross-sectional survey. Setting Web-based survey. Patients or Other Participants A total of 264 of 827 schools that were members of the Ohio High School Athletic Association. Main Outcome Measure(s) We surveyed schools on AED use, AED maintenance, and EAPs. Results Twenty-five episodes of AED deployment at 22 schools over an 11-year period were reported; 8 (32%) involved students and 17 (68%) involved adults. The reported survival rate was 60% (n = 15). Most events (n = 20, 80%) in both students and adults occurred at or near athletic facilities. The annual use rate of AEDs was 0.7%. Fifty-three percent (n = 140) of schools reported having an EAP in place for episodes of cardiac arrest. Of the schools with EAPs, 57% (n = 80) reported having rehearsed them. Conclusions Our data supported the placement of AEDs in high schools given the frequency of use for sudden cardiac arrest and the survival rate reported. They also suggested the need for increased awareness of recommendations for EAPs and the need to formulate and practice EAPs. School EAPs should emphasize planning for events in the vicinity of athletic facilities. PMID:26381367

  7. Preparticipation Screening for Sudden Cardiac Death in High School and College Athletes.

    ERIC Educational Resources Information Center

    Braden, David S.; Strong, William B.

    1988-01-01

    A properly performed screening history and cardiovascular examination can identify most young athletes at risk for sudden death from heart abnormalities. Warning signs and examiner response are discussed as well as appropriate use of echocardiography. Included is a sample preparticipation examination form recommended by the American Academy of…

  8. Lapatinib induces autophagic cell death and differentiation in acute myeloblastic leukemia

    PubMed Central

    Chen, Yu-Jen; Fang, Li-Wen; Su, Wen-Chi; Hsu, Wen-Yi; Yang, Kai-Chien; Huang, Huey-Lan

    2016-01-01

    Lapatinib is an oral-form dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR or ErbB/Her) superfamily members with anticancer activity. In this study, we examined the effects and mechanism of action of lapatinib on several human leukemia cells lines, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and acute lymphoblastic leukemia (ALL) cells. We found that lapatinib inhibited the growth of human AML U937, HL-60, NB4, CML KU812, MEG-01, and ALL Jurkat T cells. Among these leukemia cell lines, lapatinib induced apoptosis in HL-60, NB4, and Jurkat cells, but induced nonapoptotic cell death in U937, K562, and MEG-01 cells. Moreover, lapatinib treatment caused autophagic cell death as shown by positive acridine orange staining, the massive formation of vacuoles as seen by electronic microscopy, and the upregulation of LC3-II, ATG5, and ATG7 in AML U937 cells. Furthermore, autophagy inhibitor 3-methyladenine and knockdown of ATG5, ATG7, and Beclin-1 using short hairpin RNA (shRNA) partially rescued lapatinib-induced cell death. In addition, the induction of phagocytosis and ROS production as well as the upregulation of surface markers CD14 and CD68 was detected in lapatinib-treated U937 cells, suggesting the induction of macrophagic differentiation in AML U937 cells by lapatinib. We also noted the synergistic effects of the use of lapatinib and cytotoxic drugs in U937 leukemia cells. These results indicate that lapatinib may have potential for development as a novel antileukemia agent. PMID:27499639

  9. 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.

  10. 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

  11. Congenital anomalies of coronary arteries: role in the pathogenesis of sudden cardiac death.

    PubMed

    Cheitlin, Melvin D; MacGregor, John

    2009-06-01

    After hypertrophic cardiomyopathy, coronary artery anomalies of origin from the wrong sinus of Valsalva are the second most common cause of sudden death on the athletic field in the USA. Although the right coronary artery arising from the left coronary sinus (ARCA) is four times as common as the left coronary artery arising from the anterior sinus (ALCA), it is the latter that is by far the more common cause of sudden death with or shortly after vigorous physical activity. Of the four types of ALCA, the interarterial type, where the left coronary artery passes anteriorly between the aorta and the right ventricular outflow tract, is the only type that places the patient at risk of sudden death. Another feature of this syndrome is the fact that sudden death occurs associated with or shortly after vigorous exercise and is very unusual after the patient is > 35 years of age. The mechanism by which there is sudden occlusion of the interarterial coronary artery is at present unknown, although there are a number of hypotheses involving the oblique passage of the vessel as it leaves the aorta. Sudden death is probably rare considering the number of people who have these anomalies. Symptoms premonitory to a fatal event such as exertional syncope, chest pain, or palpitations are probably common in patients at risk, and surgical correction is indicated in symptomatic patients at any age. In older asymptomatic patients, surgery is not recommended, since the incidence of sudden death in this age group is extremely small. In asymptomatic young patients, a stress test, preferably with radioisotope myocardial perfusion imaging or stress echocardiogram, should be done and surgical correction performed in those with ischemia provoked in the appropriate myocardial region. Since there is evidence that in patients who have survived a potentially fatal event, it is rare to be able to provoke ischemia with equal or greater exercise than had precipitated the malignant arrhythmia, the

  12. 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.

  13. 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

  14. 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

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

    PubMed Central

    Cedars, Ari M.

    2015-01-01

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

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

    PubMed

    Sodhi, Sandeep S; Cedars, Ari M

    2015-08-01

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

  17. 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

  18. Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

    PubMed

    Woodside, Kenneth J; Goldfarb, David A; Rabets, John C; Sanchez, Edmund Q; Lebovitz, Daniel J; Schulak, James A; Fung, John J; Eghtesad, Bijan

    2015-12-01

    Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.

  19. 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

  20. Risk Factors for Death and Major Morbidity in Guatemalan Children with Acute Bacterial Meningitis

    PubMed Central

    Olson, Daniel; Lamb, Molly M.; Gaensbauer, James T.; Todd, James K.; Halsey, Neal A.; Asturias, Edwin J.

    2015-01-01

    Background Acute bacterial meningitis (ABM) remains a significant cause of pediatric illness and death in low and middle income countries (LMICs). Identifying severity risk factors and predictive scores may guide interventions to reduce poor outcomes. Methods Data from a prospective surveillance study for ABM in children aged 0-59 months admitted to 3 referral hospitals in Guatemala City from 2000-2007 was analyzed. ABM was defined as positive cerebrospinal fluid (CSF) culture; positive latex agglutination; or CSF WBC > 100 cells/mL. Univariate and multivariate analyses of risk factors at hospital admission that predicted major morbidity or death during hospitalization were performed, along with validation of the predictive Herson-Todd (HTS). Results Of 809 children with ABM episodes, 221 (27.3%) survived with major morbidity, and 192 (23.7%) died. Among 383 children with non-missing data, the most significant multivariate predictors for death or major morbidity were seizure (OR 101.5, p<0.001), CSF glucose < 20 mg/dL (OR 5.3, p = 0.0004), symptom duration > 3 days (OR 3.7, p=0.003), and coma (OR 6.3, p=0.004). Of 221 children with a HTS score > 5, 204 (92%) died or suffered major morbidity (OR 10.3, p<0.0001). Conclusion ABM is a cause of considerable morbidity and mortality in Guatemala. Several clinical risk factors and the composite Herson-Todd Score predicted death or major morbidity. These predictors could help clinicians in LMIC guide medical care for ABM, and could contribute to the public health impact assessment in preventing meningitis with vaccines. PMID:26069947

  1. Role of caspase-10 in the death of acute leukemia cells

    PubMed Central

    Guo, Wenjian; Dong, Aishu; Pan, Xiahui; Lin, Xiaoji; Lin, Ying; He, Muqing; Zhu, Baoling; Jin, Liming; Yao, Rongxing

    2016-01-01

    Autophagy can protect cells from stress, but can also induce cancer cell death. Caspase-10 is now considered to be a factor that is associated with autophagy in cancer. The present study therefore investigated whether caspase-10 affects autophagy in acute leukemia cells. The rates of survival vs. apoptosis in acute leukemia HL-60 and Jurkat cells treated with drugs were tested using cell viability assays and flow cytometry, and the levels of caspase-3 and −10 were tested by western blotting. In HL-60 cells that were treated with chemotherapy drugs combined with a caspase-10 inhibitor, the rate of survival decreased significantly compared with HL-60 cells treated with chemotherapy drugs alone. In contrast, the rate of survival of Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor increased significantly compared with Jurkat cells treated with chemotherapy drugs alone. The results of the flow cytometry and western blotting showed that the changes in the survival rate may be caused by a change in the amount of apoptosis occurring in the Jurkat cells treated with chemotherapy drugs combined with the caspase-10 inhibitor. However, in HL-60 cells undergoing this combination treatment, the change in the survival rate was not caused by a change in the rate of apoptosis. When HL-60 cells were treated with the chemotherapy drugs combined with the caspase-10 inhibitor and the autophagy inhibitor 3-methyl adenine, the survival rate increased, whereas the rate of apoptosis did not change. These results show that caspase-10 may be associated with autophagy in acute myeloid leukemia cells, but not in acute lymphatic leukemia cells. PMID:27446483

  2. Autophagy plays an important role in Sunitinib-mediated cell death in H9c2 cardiac muscle cells

    SciTech Connect

    Zhao Yuqin; Xue Tao; Yang Xiaochun; Zhu Hong; Ding Xiaofei; Lou Liming; Lu Wei; Yang Bo; He Qiaojun

    2010-10-01

    Sunitinib, which is a multitargeted tyrosine-kinase inhibitor, exhibits antiangiogenic and antitumor activity, and extends survival of patients with metastatic renal-cell carcinoma (mRCC) and gastrointestinal stromal tumors (GIST). This molecule has also been reported to be associated with cardiotoxicity at a high frequency, but the mechanism is still unknown. In the present study, we observed that Sunitinib showed high anti-proliferative effect on H9c2 cardiac muscle cells measured by PI staining and the MTT assay. But apoptotic markers (PARP cleavage, caspase 3 cleavage and chromatin condensation) were uniformly negative in H9c2 cells after Sunitinib treatment for 48 h, indicating that another cell death pathway may be involved in Sunitinib-induced cardiotoxicity. Here we found Sunitinib dramatically increased autophagic flux in H9c2 cells. Acidic vesicle fluorescence and high expression of LC3-II in H9c2 cells identified autophagy as a Sunitinib-induced process that might be associated with cytotoxicity. Furthermore, knocking down Beclin 1 by RNA-interference to block autophagy in H9c2 cells revealed that the death rate was decreased when treated with Sunitinib in comparison to control cells. These results confirmed that autophagy plays an important role in Sunitinib-mediated H9c2 cells cytotoxicity. Taken together, the data presented here strongly suggest that autophagy is associated with Sunitinib-induced cardiotoxicity, and that inhibition of autophagy constitutes a viable strategy for reducing Sunitinib-induced cardiomyocyte death thereby alleviating Sunitinib cardiotoxicity.

  3. Functional characterization of CaVα2δ mutations associated with sudden cardiac death.

    PubMed

    Bourdin, Benoîte; Shakeri, Behzad; Tétreault, Marie-Philippe; Sauvé, Rémy; Lesage, Sylvie; Parent, Lucie

    2015-01-30

    L-type Ca(2+) channels play a critical role in cardiac rhythmicity. These ion channels are oligomeric complexes formed by the pore-forming CaVα1 with the auxiliary CaVβ and CaVα2δ subunits. CaVα2δ increases the peak current density and improves the voltage-dependent activation gating of CaV1.2 channels without increasing the surface expression of the CaVα1 subunit. The functional impact of genetic variants of CACNA2D1 (the gene encoding for CaVα2δ), associated with shorter repolarization QT intervals (the time interval between the Q and the T waves on the cardiac electrocardiogram), was investigated after recombinant expression of the full complement of L-type CaV1.2 subunits in human embryonic kidney 293 cells. By performing side-by-side high resolution flow cytometry assays and whole-cell patch clamp recordings, we revealed that the surface density of the CaVα2δ wild-type protein correlates with the peak current density. Furthermore, the cell surface density of CaVα2δ mutants S755T, Q917H, and S956T was not significantly different from the cell surface density of the CaVα2δ wild-type protein expressed under the same conditions. In contrast, the cell surface expression of CaVα2δ D550Y, CaVα2δ S709N, and the double mutant D550Y/Q917H was reduced, respectively, by ≈30-33% for the single mutants and by 60% for the latter. The cell surface density of D550Y/Q917H was more significantly impaired than protein stability, suggesting that surface trafficking of CaVα2δ was disrupted by the double mutation. Co-expression with D550Y/Q917H significantly decreased CaV1.2 currents as compared with results obtained with CaVα2δ wild type. It is concluded that D550Y/Q917H reduced inward Ca(2+) currents through a defect in the cell surface trafficking of CaVα2δ. Altogether, our results provide novel insight in the molecular mechanism underlying the modulation of CaV1.2 currents by CaVα2δ. PMID:25527503

  4. Not without cause: Vibrio parahaemolyticus induces acute autophagy and cell death.

    PubMed

    Burdette, Dara L; Yarbrough, Melanie L; Orth, Kim

    2009-01-01

    Vibrio parahaemolyticus (V. parahaemolyticus) is a gram-negative halophillic bacterium that causes worldwide seafood-borne gastroenteritis. The prevalence of V. parahaemolyticus in the environment and incidence of infection have been linked to rising water temperatures caused by global warming. Among its virulence factors, V. parahaemolyticus harbors two type III secretion systems (T3SS). Recently, we have shown that T3SS1 induces rapid cellular death that initiates with acute autophagy, as measured by LC3 lipidation and accumulation of early autophagosomal vesicles. While not the first characterized pathogen to usurp autophagy, this is the first example of an extracellular pathogen that exploits this pathway for its own benefit. Here we discuss possible roles for the induction of autophagy during infection and discuss how V. parahaemolyticus-induced autophagy provides insight into key regulatory steps that govern the decision between apoptosis and autophagy.

  5. Fulminant Peripartum myocarditis associated with sudden cardiac death: a case report.

    PubMed

    Ciccone, Marco Matteo; Dentamaro, Ilaria; Carbonara, Santa; Ricci, Gabriella; Vestito, Domenico; Marzullo, Andrea; Tunzi, Francesco; Solarino, Biagio

    2016-01-01

    Myocarditis is an inflammatory disease of myocardium, associated with nonischemic necrosis and degeneration of myocytes. Although the clinical course is rapid, myocarditis can lead to dilated cardiomyopathy with chambers dilatation and ventricular dysfunction. The pathophysiology of myocarditis in humans is not completely understood. There are several etiological agents implicated, mainly viral agents. The clinical presentation is extremely various, with nonspecific systemic symptoms until sudden death. The great variability of symptoms makes the diagnosis, therefore, extremely difficult. We report the case of a 40-year-old woman who developed, after childbirth, hyperthermia associated with neck and left arm pain; initially treated with acetaminophen, without any benefit, the young woman, after few days, died suddenly. The autopsy documented the presence of edematous lungs and enlarged and congested liver. The microbiological tests performed 4 days after death were negative. The heart was normal in shape and volume; a section of the left ventricle wall showed subendocardial discromic areas histologically characterized by multifocal perivascular and interstitial inflammatory infiltrates. These infiltrates consisted mainly of neutrophils with eosinophil component associated with myocyte necrosis and hemorrhagic interstitial infiltration.

  6. ECG risk markers for atrial fibrillation and sudden cardiac death in minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised trial

    PubMed Central

    Schlatzer, Christian; Bratton, Daniel J; Craig, Sonja E; Kohler, Malcolm; Stradling, John R

    2016-01-01

    Objective Obstructive sleep apnoea (OSA), atrial fibrillation (AF) and sudden cardiac death (SCD) may occur concomitantly, and are of considerable epidemiological interest, potentially leading to morbidity and mortality. Effective treatment of OSA with continuous positive airway pressure (CPAP) could prevent progression and/or recurrence of AF and factors leading to SCD. Recently, a randomised controlled trial showed a statistically and clinically significant prolongation of measures of cardiac repolarisation after CPAP withdrawal in symptomatic patients with moderate to severe OSA. Whether or not CPAP therapy improves ECG risk markers of AF and SCD in patients with minimally symptomatic OSA as well, is unknown. Methods 3 centres taking part in the MOSAIC (Multicentre Obstructive Sleep Apnoea Interventional Cardiovascular) trial randomisd 303 patients with minimally symptomatic OSA to receive either CPAP or standard care for 6 months. Treatment effects of CPAP on P-wave duration, P-wave dispersion, QT interval, QT dispersion, Tpeak-to-Tend (TpTe) and TpTe/QT ratio were analysed. Results Participants were primarily men (83%). Mean age was 57.8 (7.2) and mean ODI (Oxygen Desaturation Index) at baseline was 13.1/h (12.3). Full 12-lead ECG data was available in 250 patients. Mean (SD) baseline intervals of P-wave duration, P-wave dispersion, QTc interval, QT dispersion, TpTe and TpTe/QT ratio in ms were 87.4 (8.3), 42.3 (11.9), 397.8 (22.7), 43.1 (16.7), 73.5 (13.7) and 0.19 (0.0), respectively. No treatment effect of CPAP on risk markers for AF and SCD was found. Conclusions There seems to be no effect of CPAP on ECG measures of arrhythmia risk in patients with minimally symptomatic OSA. Trial registration number ISRCTN34164388; Post-results. PMID:26983946

  7. A New Insight Into Sudden Cardiac Death in Young People: A Systematic Review of Cases of Takotsubo Cardiomyopathy.

    PubMed

    Wang, Yueyue; Xia, Lei; Shen, Xiaodong; Han, Guoxin; Feng, Dan; Xiao, Hongju; Zhai, Yongzhi; Chen, Xin; Miao, Yuanyuan; Zhao, Chunhong; Wang, Yingchan; Guo, Mingguang; Li, Tanshi; Zhu, Hai Yan

    2015-08-01

    Takotsubo cardiomyopathy (TTC) causes sudden cardiac death and has garnered increased attention worldwide in recent years. However, few studies have clearly classified the risk factors for this disease, including gender, race and morbidity, as well as the physical and mental stressors that can exacerbate the disease, particularly in young patients. To better analyze the characteristics of young TTC patients, we performed a systematic review of reported cases involving young patients.A computer-assisted search was performed using prominent electronic medical information sources to identify literature published between January 1965 and December 2013. Relevant studies containing clinical data of young TTC patients were included.Ninety-six records that included information about 104 cases were ultimately selected for our review. Several of the following results were noted: First, physical stress was more likely to exacerbate TTC than was mental stress in young patients. Second, more female than male TTC patients were noted among both young patients and the general population. Third, ethnicity appears to play no role in the disease, as no significant differences were noted among individuals of different races with respect to clinical characteristics, morbidity or stressors. Fourth, the clinical manifestations of TTC were similar to those of other cardiac diseases, including coronary heart disease. However, TTC may be detected using the combination of echocardiography and ventriculography.Clinicians should consider TTC if young patients present with symptoms similar to those of coronary heart disease so that harmful treatments such as coronary artery stent placement may be avoided. Moreover, the answers to questions regarding the clinical diagnostic criteria, etiology, pathophysiology, and the management of this syndrome in youth remain unclear; therefore, further research is needed. PMID:26266349

  8. Selective BCL-2 Inhibition by ABT-199 Causes On Target Cell Death in Acute Myeloid Leukemia

    PubMed Central

    Pan, Rongqing; Hogdal, Leah J.; Benito, Juliana M; Bucci, Donna; Han, Lina; Borthakur, Gautam; Cortes, Jorge; DeAngelo, Daniel J.; Debose, LaKeisha; Mu, Hong; Döhner, Hartmut; Gaidzik, Verena I.; Galinsky, Ilene; Golfman, Leonard S.; Haferlach, Torsten; Harutyunyan, Karine G.; Hu, Jianhua; Leverson, Joel D; Marcucci, Guido; Müschen, Markus; Newman, Rachel; Park, Eugene; Ruvolo, Peter P.; Ruvolo, Vivian; Ryan, Jeremy; Schindela, Sonja; Zweidler-McKay, Patrick; Stone, Richard M.; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina; Letai, Anthony G.

    2014-01-01

    B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nM, and cell death occurred within 2 h. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia (CLL), a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML. PMID:24346116

  9. Sudden Death Due To Acute Cocaine Toxicity-Excited Delirium in a Body Packer.

    PubMed

    Shields, Lisa B E; Rolf, Cristin M; Hunsaker, John C

    2015-11-01

    Excited delirium denotes a life-threatening medical condition characterized by the acute onset of agitated and violent behavior that often results in a sudden and unexplained death. Cocaine-induced excited delirium refers to fatal cocaine intoxication with the following symptoms occurring sequentially: hyperthermia, delirium with agitation, respiratory arrest, and death. We present a case of cocaine-induced excited delirium in a cocaine "body packer" or a "mule", specifically an individual who attempts to smuggle cocaine within the body. Investigators at the scene initially suspected homicide due to the victim's sharp and blunt force injuries. Three rubber packets containing cocaine were removed from the victim's rectum. Blood toxicological analysis revealed an alcohol concentration of 0.016 g/100 and cocaine >1 mg/L. The forensic pathologist should consider cocaine-induced excited delirium when an individual exhibits aggressive behavior, unexpected strength, and resistance to pain who dies suddenly. Further analysis should be performed during the scene investigation and autopsy for evidence of body packing.

  10. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    PubMed

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice.

  11. Acute pulmonary emphysema in death by hanging: a morphometric digital study.

    PubMed

    Castiglioni, Claudia; Baumann, Pia; Fracasso, Tony

    2016-09-01

    Acute pulmonary emphysema (APE) has been described in cases of mechanical asphyxia such as ligature or manual strangulation but not in cases of hanging. In this study, we wanted to verify by morphometric digital analysis of lung tissue whether APE occurs in death by hanging.We investigated 16 cases of hanging (eight complete, eight incomplete), 10 cases of freshwater drowning (positive control group), and 10 cases of acute external bleeding (negative control group). Tissue sections were obtained from each pulmonary lobe. For each slide, five fields were randomly selected. The area of every alveolar space was measured by image analysis software. The mean alveolar area (MAA) was calculated for each group.In incomplete hanging, MAA was significantly higher than that observed in complete hanging and similar to the one observed in freshwater drowning.APE in cases of incomplete hanging can be considered as a sign of vitality. The high number of conditions that can cause alveolar distension (that were excluded in this study) limits the applicability of this vital sign in the routine forensic practice. PMID:27448112

  12. Arrhythmias and sudden cardiac death in elite athletes. American College of Cardiology, 16th Bethesda Conference.

    PubMed

    Garson, A

    1998-01-01

    With the recent high visibility deaths of Hank Gathers and Reggie Lewis, two nationally recognized elite basketball players due to cardiovascular disease and arrhythmias, our awareness of the most optimal ways to manage athletes with known arrhythmias has become heightened. In making medical decisions we physicians come to rely in large measure on data, in addition to clinical acumen and experience. Unfortunately, we are at a disadvantage with respect to athletes since previously published data on the natural history and outcome of such individuals with known arrhythmias are sparse. Furthermore, the tragedies of Lewis, Gathers, Pete Maravich and others are also poignant reminders that the denominator of this equation is not defined and that we do not really know precisely how many athletes experience important arrhythmias, nor their relation to sports activity. In the decade since the 16th Bethesda Conference, an American College of Cardiology sponsored consensus panel that developed standards and recommendations for the disqualification from competition of athletes with known cardiovascular disease, little new data have been developed to make objective decisions in these areas (including arrhythmias) much easier. Nevertheless, while such decision-making in athletes involves situations that are relatively rare, the consequences of misjudgement are substantial. Unfortunately, to complicate matters, even if the precise likelihood of sudden death for a given athlete with arrhythmias were known, many (if not most) professional and elite college athletes might still regard any risk as acceptable and withdrawal from formal competition as highly unacceptable from a financial and psychological standpoint. In this review, consideration will be given to the state of our medical knowledge in these areas. Many controversies persist with regard to arrhythmias, most notably for the athlete who has Wolff-Parkinson-White, mitral valve prolapse, myocarditis, or complex ventricular

  13. 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

  14. 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...

  15. 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

  16. Effects of Mineralocorticoid Receptor Antagonists on the Risk of Sudden Cardiac Death in Patients With Left Ventricular Systolic Dysfunction

    PubMed Central

    Bapoje, Srinivas R.; Bahia, Amit; Hokanson, John E.; Peterson, Pamela N.; Heidenreich, Paul A.; Lindenfeld, JoAnn; Allen, Larry A.; Masoudi, Frederick A.

    2013-01-01

    Background Sudden cardiac death (SCD) is an important cause of death in patients with left ventricular systolic dysfunction. Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. The objective of this meta-analysis was to assess the impact of MRAs on SCD in patients with left ventricular systolic dysfunction. Methods and Results We systematically searched PubMed, EMBASE, Cochrane, and other databases through March 30, 2012, without language restrictions. We included trials that enrolled patients with left ventricular ejection fraction of ≤45%, randomized subjects to MRAs versus control and reported outcomes on SCD, total and cardiovascular mortality. Eight published trials that enrolled 11875 patients met inclusion criteria. Of these, 6 reported data on SCD and cardiovascular mortality, and 7 reported data on total mortality. No heterogeneity was observed among the trials. Patients treated with MRAs had 23% lower odds of experiencing SCD compared with controls (odds ratio, 0.77; 95% confidence interval, 0.66–0.89; P=0.001). Similar reductions were observed in cardiovascular (0.75; 95% confidence interval, 0.68– 0.84; P<0.001) and total mortality (odds ratio, 0.74; 95% confidence interval, 0.63–0.86; P<0.001). Although publication bias was observed, the results did not change after a trim and fill test, suggesting that the impact of this bias was likely insignificant. Conclusions MRAs reduce the risk of SCD in patients with left ventricular systolic dysfunction. Comparative effectiveness studies of MRAs on SCD in usual care as well as studies evaluating the efficacy of other therapies to prevent SCD in patients receiving optimal MRA therapy are needed to guide clinical decision-making. PMID:23403436

  17. Small molecule-mediated up-regulation of microRNA targeting a key cell death modulator BNIP3 improves cardiac function following ischemic injury

    PubMed Central

    Lee, Se-Yeon; Lee, Seahyoung; Choi, Eunhyun; Ham, Onju; Lee, Chang Youn; Lee, Jiyun; Seo, Hyang-Hee; Cha, Min-Ji; Mun, Bohyun; Lee, Yunmi; Yoon, Cheesoon; Hwang, Ki-Chul

    2016-01-01

    Genetic ablation of BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), an essential regulator of cardiac cell death, is an effective way to prevent cardiac cell death triggered by pathologic conditions. However, currently there exists no known means, such as inhibitors, to down-regulate BNIP3 in mature heart. Here, we report that a small molecule inducer of microRNA-182 (miR-182) suppressed ischemia/reperfusion (I/R)-induced cardiac cell death by down-regulating BNIP3. We first selected miR-182 as a potent BNIP3-targeting miRNA based on miRNA-target prediction databases and empirical data. The subsequent screening of small molecules for inducing miR-182 expression identified Kenpaullone as a hit compound. Both exogenous miR-182 and Kenpaullone significantly suppressed hypoxia-induced cardiomyocyte death in vitro. To investigate the effect of changing substituents of Kenpaullone on miR-182 expression, we synthesized 9 derivatives of Kenpaullone. Among these derivatives, compound 5 showed significantly improved ability to induce miR-182 expression. The results of the in vivo study showed that compound 5 significantly improved heart function following I/R-injury in rats. Our study provides strong evidence that the small molecule-mediated up-regulation of miRNAs is a viable strategy to down-regulate target proteins with no known chemical inhibitor and that compound 5 may have potential to prevent I/R-inflicted cardiac cell death. PMID:27008992

  18. 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

  19. PD98059 Protects Brain against Cells Death Resulting from ROS/ERK Activation in a Cardiac Arrest Rat Model

    PubMed Central

    Nguyen Thi, Phuong Anh; Chen, Meng-Hua; Li, Nuo; Zhuo, Xiao-Jun; Xie, Lu

    2016-01-01

    The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR. PMID:27069530

  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. Usefulness of Electrocardiographic Patterns at Presentation to Predict Long-term Risk of Cardiac Death in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Biagini, Elena; Pazzi, Chiara; Olivotto, Iacopo; Musumeci, Beatrice; Limongelli, Giuseppe; Boriani, Giuseppe; Pacileo, Giuseppe; Mastromarino, Vittoria; Bacchi Reggiani, Maria Letizia; Lorenzini, Massimiliano; Lai, Francesco; Berardini, Alessandra; Mingardi, Francesca; Rosmini, Stefania; Resciniti, Elvira; Borghi, Claudia; Autore, Camillo; Cecchi, Franco; Rapezzi, Claudio

    2016-08-01

    The objective of this study was to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic cardiomyopathy; 1,004 consecutive patients with hypertrophic cardiomyopathy and a recorded standard ECG (64% men, mean age 50 ± 16 years) were evaluated at 4 Italian centers. The study end points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest and major cardiovascular events (including SCD or surrogates and death due to heart failure, cardioembolic stroke, or heart transplantation). Prevalence of baseline electrocardiographic characteristics was: normal ECG 4%, ST-segment depression 56%, pseudonecrosis waves 33%, "pseudo-ST-segment elevation myocardial infarction (STEMI)" pattern 17%, QRS duration ≥120 ms 17%, giant inverted T waves 6%, and low QRS voltages 3%. During a mean follow-up of 7.4 ± 6.8 years, 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.4 to 4.5, p = 0.003), left ventricular ejection fraction <50% (HR 3.5, 95% CI 1.9 to 6.7, p = 0.0001), nonsustained ventricular tachycardia (HR 1.7, 95% CI 1.1 to 2.6, p = 0.027), pseudo-STEMI pattern (HR 2.3, 95% CI 1.4 to 3.8, p = 0.001), QRS duration ≥120 ms (HR 1.8, 95% CI 1.1 to 3.0, p = 0.033), and low QRS voltages (HR 2.3, 95% CI 1.01 to 5.1, p = 0.048). Independent predictors of major cardiovascular events were age (HR 1.02, 95% CI 1.01 to 1.03, p = 0.0001), LV ejection fraction <50% (HR 3.73, 95% CI 2.39 to 5.83, p = 0.0001), pseudo-STEMI pattern (HR 1.66, 95% CI 1.13 to 2.45, p = 0.010), QRS duration ≥120 ms (HR 1.69, 95% CI 1.16 to 2.47, p = 0.007), and prolonged QTc interval (HR 1.68, 95% CI 1.21 to 2.34, p = 0.002). In conclusion, a detailed

  2. End-of-life discontinuation of destination therapy with cardiac and ventilatory support medical devices: physician-assisted death or allowing the patient to die?

    PubMed Central

    2010-01-01

    Background Bioethics and law distinguish between the practices of "physician-assisted death" and "allowing the patient to die." Discussion Advances in biotechnology have allowed medical devices to be used as destination therapy that are designed for the permanent support of cardiac function and/or respiration after irreversible loss of these spontaneous vital functions. For permanent support of cardiac function, single ventricle or biventricular mechanical assist devices and total artificial hearts are implanted in the body. Mechanical ventilators extrinsic to the body are used for permanent support of respiration. Clinical studies have shown that destination therapy with ventricular assist devices improves patient survival compared to medical management, but at the cost of a substantial alteration in end-of-life trajectories. The moral and legal assessment of the appropriateness and permissibility of complying with a patient's request to electively discontinue destination therapy in a life-terminating act in non-futile situations has generated controversy. Some argue that complying with this request is ethically justified because patients have the right to request withdrawal of unwanted treatment and be allowed to die of preexisting disease. Other commentators reject the argument that acceding to an elective request for death by discontinuing destination therapy is 'allowing a patient to die' because of serious flaws in interpreting the intention, causation, and moral responsibility of the ensuing death. Summary Destination therapy with cardiac and/or ventilatory medical devices replaces native physiological functions and successfully treats a preexisting disease. We posit that discontinuing cardiac and/or ventilatory support at the request of a patient or surrogate can be viewed as allowing the patient to die if--and only if--concurrent lethal pathophysiological conditions are present that are unrelated to those functions already supported by medical devices in

  3. 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.

  4. Predictors of hyperkalemia and death in patients with cardiac and renal disease.

    PubMed

    Jain, Nishank; Kotla, Suman; Little, Bertis B; Weideman, Rick A; Brilakis, Emmanouil S; Reilly, Robert F; Banerjee, Subhash

    2012-05-15

    Predictors of hyperkalemia in patients with cardiovascular disease (CVD; defined as patients with hypertension and heart failure) and associated chronic kidney disease (CKD) are not well established. The aim of this study was to ascertain risk factors of hyperkalemia (defined as serum potassium concentration >5.0 mEq/L) and associated all-cause mortality in patients with CVD treated with antihypertensive drugs that impair potassium homeostasis. In a retrospective analysis using a logistic regression model, risk factors for hyperkalemia and all-cause mortality were analyzed in 15,803 patients with CVD treated with antihypertensive drugs. The mean estimated glomerular filtration rate and mean serum potassium concentration were 55.55 ml/min/1.73 m(2) and 4.06 mEq/L, respectively. Hyperkalemia was observed in 24.5% of study patients and 1.7% of total hospital admissions. Compared to patients with normokalemia, those with hyperkalemia had a higher percentage of death (6.25% vs 2.92%, p = 0.0001) and admissions (7.80% vs 5.04%, p = 0.0001). Predictors of hyperkalemia were CKD stage (odds ratio [OR] 2.14, 95% confidence interval [CI] 2.02 to 2.28), diabetes mellitus (OR 1.59, 95% CI 1.47 to 1.72), coronary artery disease (OR 1.32, 95% CI 1.21 to 1.43), and peripheral vascular disease (OR 1.55, 95% CI 1.36 to 1.77). Predictors of all-cause mortality were CKD stage (OR 1.26, 95% CI 1.12 to 1.43), hyperkalemic event (OR 1.56, 95% CI 1.30 to 1.88), age (OR 1.04, 95% CI 1.03 to 1.05), and hospitalization (OR 1.04, 95% CI 1.04 to 1.05). In conclusion, hyperkalemia is encountered frequently in patients with established CVD who are taking antihypertensive drugs and is associated with increases in all-cause mortality and hospitalizations. Advanced CKD, diabetes mellitus, coronary artery disease, and peripheral vascular disease are independent predictors of hyperkalemia.

  5. Resveratrol attenuates acute kidney injury by inhibiting death receptor‑mediated apoptotic pathways in a cisplatin‑induced rat model.

    PubMed

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-10-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti‑inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin‑induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor‑α (TNF‑α), caspase‑8 and Bcl‑2 associated protein X apoptosis regulator (Bax), and decreased expression of anti‑apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl‑2). Administration of resveratrol significantly reversed the cisplatin‑induced alteration in these apoptosis‑associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin‑induced acute kidney injury through inactivation of the death receptor‑mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  6. Resveratrol attenuates acute kidney injury by inhibiting death receptor-mediated apoptotic pathways in a cisplatin-induced rat model

    PubMed Central

    Hao, Qiufa; Xiao, Xiaoyan; Zhen, Junhui; Feng, Jinbo; Song, Chun; Jiang, Bei; Hu, Zhao

    2016-01-01

    Acute kidney injury is a clinical syndrome characterized by a loss of renal function and acute tubular necrosis. Resveratrol exerts a wide range of pharmacological effects based on its anti-inflammatory, antioxidant and cytoprotective properties. The present study aimed to evaluate whether resveratrol attenuates acute kidney injury in a cisplatin-induced rat model and to investigate the potential mechanisms involved. Rats were randomly divided into four treatment groups: Control, cisplatin, resveratrol, and cisplatin plus resveratrol. Rats exposed to cisplatin displayed acute kidney injury, identified by analysis of renal function and histopathological observation. Resveratrol significantly ameliorated the increased serum creatinine, blood urea nitrogen, renal index and histopathological damage induced by cisplatin. Furthermore, compared with untreated control animals, cisplatin lead to significantly increased expression of Fas ligand, tumor necrosis factor-α (TNF-α), caspase-8 and Bcl-2 associated protein X apoptosis regulator (Bax), and decreased expression of anti-apoptosis regulators, BH3 interacting domain death agonist (BID) and B cell lymphoma 2 apoptosis regulator (Bcl-2). Administration of resveratrol significantly reversed the cisplatin-induced alteration in these apoptosis-associated proteins. In conclusion, these findings suggest that resveratrol attenuates cisplatin-induced acute kidney injury through inactivation of the death receptor-mediated apoptotic pathway, and may provide a new therapeutic strategy to ameliorate the process of acute kidney injury. PMID:27600998

  7. 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

  8. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells

    PubMed Central

    Weeks, Robert J.; Ludgate, Jackie L.; LeMée, Gwenn; Morison, Ian M.

    2016-01-01

    Background Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. Methods Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5’-aza-2’-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. Results In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. Conclusions These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. PMID:26985820

  9. Familial Atrial Septal Defect and Sudden Cardiac Death: Identification of a Novel NKX2‐5 Mutation and a Review of the Literature

    PubMed Central

    Ellesøe, Sabrina Gade; Johansen, Morten Munk; Bjerre, Jesper Vandborg; Hjortdal, Vibeke Elisabeth; Brunak, Søren

    2015-01-01

    Abstract Objective Atrial septal defect (ASD) is the second most common congenital heart defect (CHD) and is observed in families as an autosomal dominant trait as well as in nonfamilial CHD. Mutations in the NKX2‐5 gene, located on chromosome 5, are associated with ASD, often combined with conduction disturbances, cardiomyopathies, complex CHD, and sudden cardiac death as well. Here, we show that NKX2‐5 mutations primarily occur in ASD patients with conduction disturbances and heritable ASD. Furthermore, these families are at increased risk of sudden cardiac death. Results We screened 39 probands with familial CHD for mutations in NKX2‐5 and discovered a novel mutation in one family (2.5%) with ASD and atrioventricular block. A review of the literature revealed 59 different NKX2‐5 mutations in 202 patients. Mutations were significantly more common in familial cases compared to nonfamilial cases (P = 7.1 × 10−9). The majority of patients (74%) had ASD with conduction disturbance. Nineteen patients (15%) of 120 with familial ASD and conduction disturbance died from sudden cardiac death of which nine (8%) were confirmed mutation carriers, and 10 were possible carriers. Conclusions NKX2‐5 mutations mainly occur in familial CHD, the signature phenotype is ASD with conduction disturbances and mutation carriers are at increased risk of sudden cardiac death. We suggest that familial ASD patients should be screened for NKX2‐5 mutations and, if they are mutation carriers, implantation of an implantable cardioverter‐defibrillator should be considered in these patients. PMID:26679770

  10. 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.

  11. Utility of a novel risk score for prediction of ventricular tachycardia and cardiac death in chronic Chagas disease - the SEARCH-RIO study

    PubMed Central

    Benchimol-Barbosa, P.R.; Tura, B.R.; Barbosa, E.C.; Kantharia, B.K.

    2013-01-01

    The SEARCH-RIO study prospectively investigated electrocardiogram (ECG)-derived variables in chronic Chagas disease (CCD) as predictors of cardiac death and new onset ventricular tachycardia (VT). Cardiac arrhythmia is a major cause of death in CCD, and electrical markers may play a significant role in risk stratification. One hundred clinically stable outpatients with CCD were enrolled in this study. They initially underwent a 12-lead resting ECG, signal-averaged ECG, and 24-h ambulatory ECG. Abnormal Q-waves, filtered QRS duration, intraventricular electrical transients (IVET), 24-h standard deviation of normal RR intervals (SDNN), and VT were assessed. Echocardiograms assessed left ventricular ejection fraction. Predictors of cardiac death and new onset VT were identified in a Cox proportional hazard model. During a mean follow-up of 95.3 months, 36 patients had adverse events: 22 new onset VT (mean±SD, 18.4±4‰/year) and 20 deaths (26.4±1.8‰/year). In multivariate analysis, only Q-wave (hazard ratio, HR=6.7; P<0.001), VT (HR=5.3; P<0.001), SDNN<100 ms (HR=4.0; P=0.006), and IVET+ (HR=3.0; P=0.04) were independent predictors of the composite endpoint of cardiac death and new onset VT. A prognostic score was developed by weighting points proportional to beta coefficients and summing-up: Q-wave=2; VT=2; SDNN<100 ms=1; IVET+=1. Receiver operating characteristic curve analysis optimized the cutoff value at >1. In 10,000 bootstraps, the C-statistic of this novel score was non-inferior to a previously validated (Rassi) score (0.89±0.03 and 0.80±0.05, respectively; test for non-inferiority: P<0.001). In CCD, surface ECG-derived variables are predictors of cardiac death and new onset VT. PMID:24270912

  12. Prevention and Mitigation of Acute Death of Mice after Abdominal Irradiation by the Antioxidant N-Acetyl-cysteine (NAC)

    PubMed Central

    Jia, Dan; Koonce, Nathan A.; Griffin, Robert J.; Jackson, Cassie; Corry, Peter M.

    2010-01-01

    Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation. PMID:20426657

  13. 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

  14. 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.

  15. 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.

  16. Acute death associated with Citrobacter freundii infection in an African elephant (Loxodonta africana).

    PubMed

    Ortega, Joaquín; Corpa, Juan M; Orden, José A; Blanco, Jorge; Carbonell, María D; Gerique, Amalia C; Latimer, Erin; Hayward, Gary S; Roemmelt, Andreas; Kraemer, Thomas; Romey, Aurore; Kassimi, Labib B; Casares, Miguel

    2015-09-01

    A 21-year-old male African elephant (Loxodonta africana) died suddenly with no previous medical history. Grossly, there were severe multifocal epicardial and endocardial hemorrhages of the atria and ventricles, hydropericardium, multifocal pleural hemorrhages, and severe pulmonary congestion and edema. Histologically, there was fibrinoid vasculitis and thrombosis in the heart and lung and myocardial necrosis. Citrobacter freundii was isolated in abundance in pure culture from liver and heart samples. Low levels of multiples types of elephant endotheliotropic herpesvirus (EEHV-6, EEHV-2B, and EEHV-3A) were detected in spleen samples, but not in heart samples. The levels of EEHV DNA found were much lower than those usually associated with acute EEHV hemorrhagic disease, and many other genomic loci that would normally be found in such cases were evidently below the level of detection. Therefore, these findings are unlikely to indicate lethal EEHV disease. Polymerase chain reaction for encephalomyocarditis virus (EMCV) and toxicology for oleander (Nerium oleander) were negative. Stress, resulting from recent transport, and antimicrobial therapy may have contributed to the death of this animal.

  17. Risk of mortality (including sudden cardiac death) and major cardiovascular events in atypical and typical antipsychotic users: a study with the general practice research database.

    PubMed

    Murray-Thomas, Tarita; Jones, Meghan E; Patel, Deven; Brunner, Elizabeth; Shatapathy, Chetan C; Motsko, Stephen; Van Staa, Tjeerd P

    2013-01-01

    Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64-1.87); cardiac mortality 1.72 (95% CI: 1.42-2.07); SCD primary definition 5.76 (95% CI: 2.90-11.45); SCD secondary definition 2.15 (95% CI: 1.64-2.81); CHD 1.16 (95% CI: 0.94-1.44); and VA 1.16 (95% CI: 1.02-1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80-0.85); cardiac mortality 0.89 (95% CI: 0.82-0.97); and SCD secondary definition 0.76 (95% CI: 0.55-1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

  18. Micromorphological changes in cardiac tissue of drug-related deaths with emphasis on chronic illicit opioid abuse

    PubMed Central

    Seltenhammer, Monika H; Marchart, Katharina; Paula, Pia; Kordina, Nicole; Klupp, Nikolaus; Schneider, Barbara; Fitzl, Christine; Risser, Daniele U

    2013-01-01

    Aims The main intention of this retrospective study was to investigate whether chronic illicit drug abuse, especially the intravenous use of opioids (heroin), could potentially trigger the development of myocardial fibrosis in drug addicts. Design A retrospective case–control study was performed using myocardial tissue samples from both drug-related deaths (DRD) with verifiable opioid abuse and non-drug-related deaths in the same age group. Setting Department of Forensic Medicine, Medical University of Vienna, Austria (1993–94). Participants Myocardial specimens were retrieved from 76 deceased intravenous opioid users and compared to those of 23 deceased non-drug users. Measurements Drug quantification was carried out using the enzyme-multiplied immunoassay technique (EMIT), followed by [gas chromatography–mass spectrometry (GC–MS), MAT 112®], and analysed using the Integrator 3390A by Hewlett Packard® and LABCOM.1 computer (MSS-G.G.). The amount of fibrous connective tissue (FCT) in the myocardium was determined by using the morphometric software LUCIA Net version 1.16.2©, Laboratory Imaging, with NIS Elements 3.0®. Findings Drug analysis revealed that 67.11% were polydrug users and the same proportion was classified as heroin addicts (6-monoacetylmorphine, 6-MAM)—32.89% were users of pure heroin. In 76.32% of DRD cases, codeine was detected. Only 2.63% consumed cocaine. The mean morphine concentrations were 389.03 ng/g in the cerebellum and 275.52 ng/g in the medulla oblongata, respectively. Morphometric analysis exhibited a strong correlation between DRD and myocardial fibrosis. The mean proportion of FCT content in the drug group was 7.6 ± 2.9% (females: 6.30 ± 2.19%; males: 7.91 ± 3.01%) in contrast to 5.2 ± 1.7% (females: 4.45 ± 1.23%; males: 5.50 ± 1.78%) in the control group, indicating a significant difference (P = 0.0012), and a significant difference in the amount of FCT between females and males (P = 0.0383). There was no significant

  19. Radiologic Characterization of Ischemic Cholangiopathy in Donation-After-Cardiac-Death Liver Transplants and Correlation With Clinical Outcomes

    PubMed Central

    Giesbrandt, Kirk J.; Bulatao, Ilynn G.; Keaveny, Andrew P.; Nguyen, Justin H.; Paz-Fumagalli, Ricardo; Taner, C. Burcin

    2016-01-01

    OBJECTIVE The purpose of this study was to define the cholangiographic patterns of ischemic cholangiopathy and clinically silent nonanastomotic biliary strictures in donation-after-cardiac-death (DCD) liver grafts in a large single-institution series. We also examined the correlation of the radiologic findings with laboratory data and clinical outcomes. MATERIALS AND METHODS Data were collected for all DCD liver transplants at one institution from December 1998 to December 2011. Posttransplant cholangiograms were obtained during postoperative weeks 1 and 3 and when clinically indicated. Intrahepatic biliary strictures were classified by anatomic distribution and chronologic development. Radiologic findings were correlated with laboratory data and with 1-, 3-, and 5-year graft and patient survival rates. RESULTS A total of 231 patients received DCD grafts. Cholangiograms were available for 184 of these patients. Postoperative cholangiographic findings were correlated with clinical data and divided into the following three groups: A, normal cholangiographic findings with normal laboratory values; B, radiologic abnormalities and cholangiopathy according to laboratory values; and C, radiologic abnormalities without laboratory abnormalities. Group B had four distinct abnormal cholangiographic patterns that were predictive of graft survival. Group C had mild nonprogressive multifocal stenoses and decreased graft and patient survival rates, although cholangiopathy was not detected in these patients according to laboratory data. CONCLUSION Patterns and severity of nonanastomotic biliary abnormalities in DCD liver transplants can be defined radiologically and correlate with clinical outcomes. Postoperative cholangiography can depict the mild biliary abnormalities that occur in a subclinical manner yet cause a marked decrease in graft and patient survival rates in DCD liver transplants. PMID:26496544

  20. SCD-HeFT: Use of RR Interval Statistics for Long-term Risk Stratification for Arrhythmic Sudden Cardiac Death

    PubMed Central

    Au-yeung, Wan-tai M.; Reinhall, Per; Poole, Jeanne E.; Anderson, Jill; Johnson, George; Fletcher, Ross D.; Moore, Hans J.; Mark, Daniel B.; Lee, Kerry L.; Bardy, Gust H.

    2015-01-01

    Background In the SCD-HeFT a significant fraction of the congestive heart failure (CHF) patients ultimately did not die suddenly from arrhythmic causes. CHF patients will benefit from better tools to identify if ICD therapy is needed. Objective To identify predictor variables from baseline SCD-HeFT patients’ RR intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. Methods Ten predictor variables were extracted from pre-randomization Holter data from 475 patients enrolled in the SCD-HeFT ICD arm using novel and traditional heart rate variability methods. All variables were correlated to SCD using Mann Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. Results α1 and α2 from detrended fluctuation analysis, the ratio of low to high frequency power, the number of PVCs per hour and heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (p<0.001) and survival (log-rank p<0.01). The most powerful multivariate predictor tool using the Cox Proportional Hazards was α2 with a hazard ratio of 0.0465 (95% CI: 0.00528 – 0.409, p<0.01). Conclusion Predictor variables from RR intervals correlate to the occurrences of SCD and distinguish survival among SCD-HeFT ICD patients. We believe SCD prediction models should incorporate Holter based RR interval analysis to refine ICD patient selection especially in removing patients who are unlikely to benefit from ICD therapy. PMID:26096609

  1. Early prognosis of survival or death after a recent stroke by blood levels of acute-phase proteins.

    PubMed

    Ionescu, D A; Haţegan, D; Jipescu, I; Steinbruch, L; Ghiţescu, M

    1991-01-01

    From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.

  2. 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

  3. 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.

  4. Postmortem cardiac troponin T levels in the blood and pericardial fluid. Part 1. Analysis with special regard to traumatic causes of death.

    PubMed

    Zhu, Bao-Li; Ishikawa, Takaki; Michiue, Tomomi; Li, Dong-Ri; Zhao, Dong; Oritani, Shigeki; Kamikodai, Yasunobu; Tsuda, Kohei; Okazaki, Shuji; Maeda, Hitoshi

    2006-03-01

    In forensic pathology, previous studies have suggested the possible application of cardiac troponins in the diagnosis of myocardial infarction. However, there appears to be insufficient practical data on other causes of death. The present study was a comprehensive analysis of the cardiac, peripheral blood and pericardial levels of cardiac troponin T (cTnT) in serial medicolegal autopsy cases (n = 405) with a survival time <24 h and within 48 h postmortem to assess the validity of investigating myocardial damage with special regard to traumatic causes of death. These included blunt and sharp instrument injury (n = 122 and 21, respectively), asphyxiation (n = 35), drowning (n = 27), fire fatalities (n = 94), hyperthermia (n = 13), hypothermia (n = 6), fatal methamphetamine (MA) abuse (n = 12) and carbon monoxide (CO) poisoning (n = 5) in comparison with myocardial infarction (MI, n = 57) and cerebrovascular diseases (n = 13). Cases within 12h postmortem usually showed lower cardiac and pericardial cTnT levels than did those of longer postmortem time of 12-48 h. In the early postmortem period of <12 h, significantly elevated serum cTnT levels were observed for hyperthermia. Thereafter, fatal MA abuse, CO poisoning and MI cases also showed higher levels. However, cTnT remained at lower levels for hypothermia and drowning. The elevation of cTnT was associated with the pathology of advanced myocardial damage involving swelling and liquefactive necrosis. The above-mentioned differences were the smallest for peripheral blood. These findings suggest that elevations in postmortem serum and pericardial cTnT levels depend on the severity of myocardial damage at the time of death and are related to the pathological findings, although postmortem interference should be taken into consideration.

  5. Early Activation of the Kynurenine Pathway Predicts Early Death and Long‐term Outcome in Patients Resuscitated From Out‐of‐Hospital Cardiac Arrest

    PubMed Central

    Ristagno, Giuseppe; Latini, Roberto; Vaahersalo, Jukka; Masson, Serge; Kurola, Jouni; Varpula, Tero; Lucchetti, Jacopo; Fracasso, Claudia; Guiso, Giovanna; Montanelli, Alessandro; Barlera, Simona; Gobbi, Marco; Tiainen, Marjaana; Pettilä, Ville; Skrifvars, Markus B.

    2014-01-01

    Background The kynurenine pathway (KP) is the major route of tryptophan (TRP) catabolism and is activated by inflammation and after cardiac arrest in animals. We hypothesized that the KP activation level correlates with severity of post–cardiac arrest shock, early death, and long‐term outcome. Methods and Results Plasma was obtained from 245 patients enrolled in a prospective multicenter observational study in 21 intensive care units in Finland. Time to return of spontaneous circulation, lowest systolic arterial pressure, and bicarbonate during the first 24 hours were collected. A cerebral performance category of 3 to 5 defined 12‐month poor outcome. Plasma TRP and KP metabolites, kynurenine (KYN), kynurenic acid, 3‐hydroxyanthranilic acid, and the ratio of KYN to TRP were measured by liquid chromatography and mass spectrometry. All KP metabolites at intensive care unit admission were significantly higher in cardiac arrest patients with a nonshockable rhythm compared to those with a shockable rhythm, and kynurenic acid and 3‐hydroxyanthranilic acid correlated with time to return of spontaneous circulation. Patients with higher levels of KYN, KYN to TRP, kynurenic acid, and 3‐hydroxyanthranilic acid had lower 24‐hour systolic arterial pressure and bicarbonate. All KP metabolites and the ratio of KYN to TRP, but not TRP, were significantly higher in patients who died in the intensive care unit in comparison to those who survived. Multivariable logistic regression showed that high kynurenic acid (odds ratio: 1.004; 95% confidence interval: 1.001 to 1.008; P=0.014), and 3‐hydroxyanthranilic acid (odds ratio: 1.011; 95% confidence interval: 1.001 to 1.022; P=0.03) were independently associated with 12‐month poor outcome and significantly improved risk reclassification. Conclusions KP is activated early after cardiac arrest and is associated with severity of post–cardiac arrest shock, early death, and poor long‐term outcome. PMID:25092787

  6. Presumed consent for organ preservation in uncontrolled donation after cardiac death in the United States: a public policy with serious consequences

    PubMed Central

    Verheijde, Joseph L; Rady, Mohamed Y; McGregor, Joan

    2009-01-01

    Organ donation after cessation of circulation and respiration, both controlled and uncontrolled, has been proposed by the Institute of Medicine as a way to increase opportunities for organ procurement. Despite claims to the contrary, both forms of controlled and uncontrolled donation after cardiac death raise significant ethical and legal issues. Identified causes for concern include absence of agreement on criteria for the declaration of death, nonexistence of universal guidelines for duration before stopping resuscitation efforts and techniques, and assumption of presumed intent to donate for the purpose of initiating temporary organ-preservation interventions when no expressed consent to donate is present. From a legal point of view, not having scientifically valid criteria of cessation of circulation and respiration for declaring death could lead to a conclusion that organ procurement itself is the proximate cause of death. Although the revised Uniform Anatomical Gift Act of 2006 provides broad immunity to those involved in organ-procurement activities, courts have yet to provide an opinion on whether persons can be held liable for injuries arising from the determination of death itself. Preserving organs in uncontrolled donation after cardiac death requires the administration of life-support systems such as extracorporeal membrane oxygenation. These life-support systems can lead to return of signs of life that, in turn, have to be deliberately suppressed by the administration of pharmacological agents. Finally, allowing temporary organ-preservation interventions without expressed consent is inherently a violation of the principle of respect for a person's autonomy. Proponents of organ donation from uncontrolled donation after cardiac death, on the other hand, claim that these nonconsensual interventions enhance respect for autonomy by allowing people, through surrogate decision making, to execute their right to donate organs. However, the lack of transparency

  7. 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

  8. 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

  9. Nitric oxide is the key mediator of death induced by fisetin in human acute monocytic leukemia cells.

    PubMed

    Ash, Dipankar; Subramanian, Manikandan; Surolia, Avadhesha; Shaha, Chandrima

    2015-01-01

    Nitric oxide (NO) has been shown to be effective in cancer chemoprevention and therefore drugs that help generate NO would be preferable for combination chemotherapy or solo use. This study shows a new evidence of NO as a mediator of acute leukemia cell death induced by fisetin, a promising chemotherapeutic agent. Fisetin was able to kill THP-1 cells in vivo resulting in tumor shrinkage in the mouse xenograft model. Death induction in vitro was mediated by an increase in NO resulting in double strand DNA breaks and the activation of both the extrinsic and the intrinsic apoptotic pathways. Double strand DNA breaks could be reduced if NO inhibitor was present during fisetin treatment. Fisetin also inhibited the downstream components of the mTORC1 pathway through downregulation of levels of p70 S6 kinase and inducing hypo-phosphorylation of S6 Ri P kinase, eIF4B and eEF2K. NO inhibition restored phosphorylation of downstream effectors of mTORC1 and rescued cells from death. Fisetin induced Ca(2+) entry through L-type Ca(2+) channels and abrogation of Ca(2+) influx reduced caspase activation and cell death. NO increase and increased Ca(2+) were independent phenomenon. It was inferred that apoptotic death of acute monocytic leukemia cells was induced by fisetin through increased generation of NO and elevated Ca(2+) entry activating the caspase dependent apoptotic pathways. Therefore, manipulation of NO production could be viewed as a potential strategy to increase efficacy of chemotherapy in acute monocytic leukemia.

  10. 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

  11. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death.

    PubMed

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5(+) endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. PMID:26857994

  12. Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death

    PubMed Central

    Bouilloux, Fabrice; Thireau, Jérôme; Ventéo, Stéphanie; Farah, Charlotte; Karam, Sarah; Dauvilliers, Yves; Valmier, Jean; Copeland, Neal G; Jenkins, Nancy A; Richard, Sylvain; Marmigère, Frédéric

    2016-01-01

    Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5+ endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. DOI: http://dx.doi.org/10.7554/eLife.11627.001 PMID:26857994

  13. Prognostic factors for death and survival with or without complications in cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency surgery

    PubMed Central

    Siriphuwanun, Visith; Punjasawadwong, Yodying; Lapisatepun, Worawut; Charuluxananan, Somrat; Uerpairojkit, Ketchada

    2014-01-01

    Purpose To determine prognostic factors for death and survival with or without complications in cardiac arrest patients who received cardiopulmonary resuscitation (CPR) within 24 hours of receiving anesthesia for emergency surgery. Patients and methods A retrospective cohort study approved by the Maharaj Nakorn Chiang Mai University Hospital Ethical Committee. Data used were taken from records of 751 cardiac arrest patients who received their first CPR within 24 hours of anesthesia for emergency surgery between January 1, 2003 and October 31, 2011. The reviewed data included patient characteristics, surgical procedures, American Society of Anesthesiologist (ASA) physical status classification, anesthesia information, the timing of cardiac arrest, CPR details, and outcomes at 24 hours after CPR. Univariate and polytomous logistic regression analyses were used to determine prognostic factors associated with the outcome variable. P-values of less than 0.05 were considered statistically significant. Results The outcomes at 24 hours were death (638/751, 85.0%), survival with complications (73/751, 9.7%), and survival without complications (40/751, 5.3%). The prognostic factors associated with death were: age between 13–34 years (OR =3.08, 95% CI =1.03–9.19); ASA physical status three and higher (OR =6.60, 95% CI =2.17–20.13); precardiopulmonary comorbidity (OR =3.28, 95% CI =1.09–9.90); the condition of patients who were on mechanical ventilation prior to receiving anesthesia (OR =4.11, 95% CI =1.17–14.38); surgery in the upper abdominal site (OR =14.64, 95% CI =2.83–75.82); shock prior to cardiac arrest (OR =6.24, 95% CI =2.53–15.36); nonshockable electrocardiography (EKG) rhythm (OR =5.67, 95% CI =1.93–16.62); cardiac arrest occurring in postoperative period (OR =7.35, 95% CI =2.89–18.74); and duration of CPR more than 30 minutes (OR =4.32, 95% CI =1.39–13.45). The prognostic factors associated with survival with complications were being greater

  14. 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.

  15. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants

    PubMed Central

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1+∕+-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca2+ sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady-state and

  16. Molecular and Functional Effects of a Splice Site Mutation in the MYL2 Gene Associated with Cardioskeletal Myopathy and Early Cardiac Death in Infants.

    PubMed

    Zhou, Zhiqun; Huang, Wenrui; Liang, Jingsheng; Szczesna-Cordary, Danuta

    2016-01-01

    The homozygous appearance of the intronic mutation (IVS6-1) in the MYL2 gene encoding for myosin ventricular/slow-twitch skeletal regulatory light chain (RLC) was recently linked to the development of slow skeletal muscle fiber type I hypotrophy and early cardiac death. The IVS6-1 (c403-1G>C) mutation resulted from a cryptic splice site in MYL2 causing a frameshift and replacement of the last 32 codons by 19 different amino acids in the RLC mutant protein. Infants who were IVS6-1(+∕+)-positive died between 4 and 6 months of age due to cardiomyopathy and heart failure. In this report we have investigated the molecular mechanism and functional consequences associated with the IVS6-1 mutation using recombinant human cardiac IVS6-1 and wild-type (WT) RLC proteins. Recombinant proteins were reconstituted into RLC-depleted porcine cardiac muscle preparations and subjected to enzymatic and functional assays. IVS6-1-RLC showed decreased binding to the myosin heavy chain (MHC) compared with WT, and IVS6-1-reconstituted myosin displayed reduced binding to actin in rigor. The IVS6-1 myosin demonstrated a significantly lower Vmax of the actin-activated myosin ATPase activity compared with WT. In stopped-flow experiments, IVS6-1 myosin showed slower kinetics of the ATP induced dissociation of the acto-myosin complex and a significantly reduced slope of the kobs-[MgATP] relationship compared to WT. In skinned porcine cardiac muscles, RLC-depleted and IVS6-1 reconstituted muscle strips displayed a significant decrease in maximal contractile force and a significantly increased Ca(2+) sensitivity, both hallmarks of hypertrophic cardiomyopathy-associated mutations in MYL2. Our results showed that the amino-acid changes in IVS6-1 were sufficient to impose significant conformational alterations in the RLC protein and trigger a series of abnormal protein-protein interactions in the cardiac muscle sarcomere. Notably, the mutation disrupted the RLC-MHC interaction and the steady

  17. 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

  18. 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

  19. 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

  20. 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

  1. The effect of anterograde persufflation on energy charge and hepatocyte function in donation after cardiac death livers unsuitable for transplant.

    PubMed

    Khorsandi, Shirin Elizabeth; Jitraruch, Suttiruk; Fairbanks, Lynette; Cotoi, Corina; Jassem, Wayel; Vilca-Melendez, Hector; Prachalias, Andreas; Dhawan, Anil; Heaton, Nigel; Srinivasan, Parthi

    2014-06-01

    Donation after cardiac death (DCD) livers are considered to be marginal organs for solid organ and cell transplantation. Low energy charge (EC) and low purine quantity within the liver parenchyma has been associated with poor outcome after liver transplantation. The aim of this work was to assess the effect of anterograde persufflation (A-PSF) using an electrochemical concentrator on DCD liver energy status and hepatocyte function. Organs utilized for research were DCD livers considered not suitable for transplant. Each liver was formally split, and the control non-persufflated (non-PSF) section was stored in University of Wisconsin (UW) solution at 4°C. The A-PSF liver section was immersed in UW solution on ice, and A-PSF was performed via the portal vein with 40% oxygen. Tissue samples were taken 2 hours after A-PSF from the A-PSF and control non-PSF liver sections for snap freezing. Purine analysis was performed with photodiode array detection. Hepatocytes were isolated from A-PSF and control non-PSF liver sections using a standard organs utilized for research were DCD livers considered not suitable for transplant collagenase perfusion technique. Hepatocyte function was assessed using mitochondrial dehydrogenase activity {3-[4,5-dimethylthiazol-2-y1]-2,5-diphenyl tetrazolium bromide (MTT)} and the sulforhodamine B (SRB) assay for cell attachment. In DCD livers with <30% steatosis (n = 6), A-PSF increased EC from 0.197 ± 0.025 to 0.23 ± 0.035 (P = 0.04). In DCD livers with >30% steatosis (n = 4), A-PSF had no beneficial effect. After isolation (n=4, <30% steatosis), A-PSF was found to increase MTT from 0.92 ± 0.045 to 1.19 ± 0.55 (P < 0.001) and SRB from 2.53 ± 0.12 to 3.2 ± 0.95 (P < 0.001). In conclusion, A-PSF can improve the EC and function of isolated hepatocytes from DCD livers with <30% steatosis. PMID:24604782

  2. IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction

    PubMed Central

    Tejada, Thor; Tan, Lin; Torres, Rebecca A.; Calvert, John W.; Lambert, Jonathan P.; Zaidi, Madiha; Husain, Murtaza; Berce, Maria D.; Naib, Hussain; Pejler, Gunnar; Abrink, Magnus; Graham, Robert M.; Lefer, David J.; Naqvi, Nawazish; Husain, Ahsan

    2016-01-01

    Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in postischemic heart disease. PMID:27274047

  3. How are European patients at risk of malignant arrhythmias or sudden cardiac death identified and informed about their risk profile: results of the European Heart Rhythm Association survey.

    PubMed

    Proclemer, Alessandro; Bongiorni, Maria Grazia; Dagres, Nikolaos; Sciaraffia, Elena; Todd, Derick; Blomstrom-Lundqvist, Carina

    2015-06-01

    The purpose of this EP wire is to examine clinical practice in the field of screening of patients of risk of ventricular arrhythmias and/or sudden cardiac death (SCD) in European countries. A systematic screening programme existed in the majority of centres and was organized by a multidisciplinary dedicated team or by an activity programme of implantable cardioverter-defibrillator (ICD) or heart failure clinics. In particular, high-risk subgroups of patients with ischaemic and non-ischaemic cardiomyopathy ICD implantation are considered strongly indicated within 90 days of myocardial revascularization or initial diagnosis. Cardiac magnetic resonance imaging appears as an important tool to better characterize the left ventricular arrhythmogenic substrate in patients at risk of SCD.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Is a good death possible in Australian critical and acute settings?: physician experiences with end-of-life care

    PubMed Central

    2014-01-01

    Background In Australia approximately 70% of all deaths are institutionalised but over 15% of deaths occur in intensive care settings where the ability to provide a “good death” is particularly inhibited. Yet, there is a growing trend for death and dying to be managed in the ICU and physicians are increasingly challenged to meet the new expectations of their specialty. This study examined the unexplored interface between specialised Australian palliative and intensive care and the factors influencing a physician’s ability to manage deaths well. Method A qualitative investigation was focused on palliative and critical/acute settings. A thematic analysis was conducted on semi-structured in-depth interviews with 13 specialist physicians. Attention was given to eliciting meanings and experiences in Australian end-of-life care. Results Physicians negotiated multiple influences when managing dying patients and their families in the ICU. The way they understood and experienced end-of-life care practices was affected by cultural, institutional and professional considerations, and personal values and beliefs. Interpersonal and intrapsychic aspects highlighted the emotional and psychological relationship physicians have with patients and others. Many physicians were also unaware of what their cross-disciplinary colleagues could or could not do; poor professional recognition and collaboration, and ineffective care goal transition impaired their ability to assist good deaths. Experience was subject to the efficacy of physicians in negotiating complex bedside dynamics. Conclusions Regardless of specialty, all physicians identified the problematic nature of providing expert palliation in critical and acute settings. Strategies for integrating specialised palliative and intensive care were offered with corresponding directions for future research and clinical development. PMID:25147481

  9. The FIFA medical emergency bag and FIFA 11 steps to prevent sudden cardiac death: setting a global standard and promoting consistent football field emergency care.

    PubMed

    Dvorak, Jiri; Kramer, Efraim B; Schmied, Christian M; Drezner, Jonathan A; Zideman, David; Patricios, Jon; Correia, Luis; Pedrinelli, André; Mandelbaum, Bert

    2013-12-01

    Life-threatening medical emergencies are an infrequent but regular occurrence on the football field. Proper prevention strategies, emergency medical planning and timely access to emergency equipment are required to prevent catastrophic outcomes. In a continuing commitment to player safety during football, this paper presents the FIFA Medical Emergency Bag and FIFA 11 Steps to prevent sudden cardiac death. These recommendations are intended to create a global standard for emergency preparedness and the medical response to serious or catastrophic on-field injuries in football.

  10. 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

  11. The novel marker LTBP2 predicts all-cause and pulmonary death in patients with acute dyspnoea.

    PubMed

    Breidthardt, Tobias; Vanpoucke, Griet; Potocki, Mihael; Mosimann, Tamina; Ziller, Ronny; Thomas, Gregoire; Laroy, Wouter; Moerman, Piet; Socrates, Thenral; Drexler, Beatrice; Mebazaa, Alexandre; Kas, Koen; Mueller, Christian

    2012-11-01

    The risk stratification in patients presenting with acute dyspnoea remains a challenge. We therefore conducted a prospective, observational cohort study enrolling 292 patients presenting to the emergency department with acute dyspnoea. A proteomic approach for antibody-free targeted protein quantification based on high-end MS was used to measure LTBP2 [latent TGF (transforming growth factor)-binding protein 2] levels. Final diagnosis and death during follow-up were adjudicated blinded to LTBP2 levels. AHF (acute heart failure) was the final diagnosis in 54% of patients. In both AHF (P<0.001) and non-AHF (P=0.015) patients, LTBP2 levels at presentation were significantly higher in non-survivors compared with survivors with differences on median levels being 2.2- and 1.5-fold respectively. When assessing the cause of death, LTBP2 levels were significantly higher in patients dying from pulmonary causes (P=0.0005). Overall, LTBP2 powerfully predicted early pulmonary death {AUC (area under the curve), 0.95 [95% CI (confidence interval), 0.91-0.98]}. In ROC (receiver operating characteristic) curve analyses for the prediction of 1-year mortality LTBP2 achieved an AUC of 0.77 (95% CI, 0.71-0.84); comparable with the predictive potential of NT-proBNP [N-terminal pro-B-type natriuruetic peptide; 0.77 (95% CI, 0.72-0.82)]. Importantly, the predictive potential of LTBP2 persisted in patients with AHF as the cause of dypnea (AUC 0.78) and was independent of renal dysfunction (AUC 0.77). In a multivariate Cox regression analysis, LTBP2 was the strongest independent predictor of death [HR (hazard ratio), 3.76 (95% CI, 2.13-6.64); P<0.0001]. In conclusion, plasma levels of LTBP2 present a novel and powerful predictor of all-cause mortality, and particularly pulmonary death. Cause-specific prediction of death would enable targeted prevention, e.g. with pre-emptive antibiotic therapy.

  12. 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

  13. 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

  14. 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

  15. 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

  16. Dextrose containing intravenous fluid impairs outcome and increases death after eight minutes of cardiac arrest and resuscitation in dogs.

    PubMed

    D'Alecy, L G; Lundy, E F; Barton, K J; Zelenock, G B

    1986-09-01

    Use of dextrose in intravenous resuscitation fluids is common practice; however, this study indicates that 5% dextrose solutions, even if administered in physiologic quantities, greatly worsens the outcome of survivable cardiac arrest. Twelve adult male mongrel dogs were premedicated with morphine, anesthetized with halothane, instrumented, intubated, and ventilated. Each dog was first given 500 ml of either lactated Ringer's (LR) (n = 6) or 5% dextrose in LR (D5LR) (n = 6). Halothane was stopped and fibrillation was induced (60 Hz). Blood glucose just before cardiac arrest was 129 mg/dl in the LR dogs and was increased to 335 mg/dl in the D5LR dogs. After eight minutes of arrest, resuscitation, including internal cardiac massage and standard advanced cardiac life support drug protocols (modified for dogs), was begun. When stable cardiac rhythm was obtained, the chest was closed, and LR or D5LR continued until a total of 1L was given. A neurologic score (0 = normal to 100 = dead) was assigned at 1, 2, 6, and 24 hours. The LR group did not differ statistically from the D5LR group in operative time, number of defibrillatory shocks, time to spontaneous ventilation, time to extubation, or drugs required. Resuscitation was successful in all six LR and five of six D5LR group; however, by 2 hours after resuscitation and thereafter, D5LR group had a significantly greater neurologic deficit (p less than 0.05) than did the LR group. By 9 hours, four of six D5LR dogs displayed convulsive activity and died. At 24 hours the D5LR group had a greater (p less than 0.008) neurologic deficit (82 +/- 11) than did the LR group (21 +/- 7), which walked and ate. We conclude that the addition of 5% dextrose to standard intravenous fluids greatly increases the morbidity and mortality associated with cardiac resuscitation. PMID:3738770

  17. A Case of Mushroom Poisoning with Russula subnigricans: Development of Rhabdomyolysis, Acute Kidney Injury, Cardiogenic Shock, and Death

    PubMed Central

    2016-01-01

    Mushroom exposures are increasing worldwide. The incidence and fatality of mushroom poisoning are reported to be increasing. Several new syndromes in mushroom poisoning have been described. Rhabdomyolytic mushroom poisoning is one of new syndromes. Russula subnigricans mushroom can cause delayed-onset rhabdomyolysis with acute kidney injury in the severely poisoned patient. There are few reports on the toxicity of R. subnigricans. This report represents the first record of R. subnigricans poisoning with rhabdomyolysis in Korea, describing a 51-year-old man who suffered from rhabdomyolysis, acute kidney injury, severe hypocalcemia, respiratory failure, ventricular tachycardia, cardiogenic shock, and death. Mushroom poisoning should be considered in the evaluation of rhabdomyolysis of unknown cause. Furthermore, R. subnigricans should be considered in the mushroom poisoning with rhabdomyolysis. PMID:27366018

  18. Cotreatment with Smac mimetics and demethylating agents induces both apoptotic and necroptotic cell death pathways in acute lymphoblastic leukemia cells.

    PubMed

    Gerges, Steve; Rohde, Katharina; Fulda, Simone

    2016-05-28

    Treatment resistance in acute lymphoblastic leukemia (ALL) is often caused by defects in programmed cell death, e.g. by overexpression of Inhibitor of Apoptosis (IAP) proteins. Here, we report that small-molecule Smac mimetics (i.e. BV6, LCL161, birinapant) that neutralize x-linked IAP (XIAP), cellular IAP (cIAP)1 and cIAP2 cooperate with demethylating agents (i.e. 5-azacytidine (5AC) or 5-aza-2'-deoxycytidine (DAC)) to induce cell death in ALL cells. Molecular studies reveal that induction of cell death is preceded by BV6-mediated depletion of cIAP1 protein and involves tumor necrosis factor (TNF)α autocrine/paracrine signaling, since the TNFα-blocking antibody Enbrel significantly reduces BV6/5AC-induced cell death. While BV6/5AC cotreatment induces caspase-3 activation, the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) only partly rescues ALL cells from BV6/5AC-induced cell death. This indicates that BV6/5AC cotreatment engages non-apoptotic cell death upon caspase inhibition. Indeed, genetic silencing of key components of necroptosis such as Receptor-Interacting Protein (RIP)3 or mixed lineage kinase domain-like (MLKL) in parallel with administration of zVAD.fmk provides a significantly better protection against BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. Similarly, concomitant administration of pharmacological inhibitors of necroptosis (i.e. necrostatin-1s, GSK'872, dabrafenib, NSA) together with zVAD.fmk is superior in rescuing cells from BV6/5AC-induced cell death compared to the use of zVAD.fmk alone. These findings demonstrate that in ALL cells BV6/5AC-induced cell death is mediated via both apoptotic and necroptotic pathways. Importantly, BV6/5AC cotreatment triggers necroptosis in ALL cells that are resistant to apoptosis due to caspase inhibition. This opens new perspectives to overcome apoptosis resistance with important implications for the development of new treatment strategies

  19. Early and treatment-related deaths in childhood acute myeloid leukaemia in the Nordic countries: 1984-2003.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2010-12-01

    Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5-15% of patients still die from treatment-related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment-related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-84, -88 and -93 trials. Seventy patients (13%) died before starting treatment or from treatment-related complications. The death rate rose from 11% in NOPHO-AML-84 to 29% in -88, but then fell to 8% in -93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment-related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO-AML-88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed.

  20. Furosemide and Potassium Chloride-induced Alteration in Protein Profile of Left Ventricle and its Associated Risk for Sudden Cardiac Death

    PubMed Central

    Murugan, Ponniah Senthil; Selvam, Govindan Sadasivam

    2014-01-01

    Background: Potassium ion (K+) plays an essential role in maintaining the electrical potential across the plasma membrane of cells. An abnormal serum K+ level is associated with increased risk of ventricular arrhythmia and sudden cardiac death (SCD) and these patients are generally prescribed with furosemide and potassium chloride (KCl). We explored the association between the use of these drugs and the risk of SCD by analyzing biochemical parameters and proteomic changes. Materials and Methods: The rats were administered with furosemide and KCl and their effect was analyzed by studying cardiac and oxidative markers, electrolyte content and histopathology. Two-dimensional gel electrophoresis (2-DE) and electrospray ionization-mass spectrometry were performed to investigate the LV proteomic changes. Results: Furosemide and KCl treatments showed significant effect on physiological and biochemical parameters, and LV histopathology of experimental rats. Proteomic analysis indicated 17 differentially expressed proteins. Among them, eight protein spots were identified using peptide mass fingerprinting. In furosemide-treated group, four proteins were upregulated and two proteins were downregulated when compared to 2-DE proteomic profile of control. While in KCl-treated rats, seven proteins were found downregulated. Conculsion: The present study revealed the differential expression of proteins by furosemide and KCl treatment. Thus, the results suggest that the use of these drugs leads to proteomic alteration, which involve in cardiac conductivity that might increase the risk of SCD. PMID:24748728

  1. Radiation injury and acute death in Armadillidium vulgare (terrestrial isopod, Crustacea) subjected to ionizing radiation. [/sup 137/Cs

    SciTech Connect

    Nakatsuchi, Y.; Egami, N.

    1981-01-01

    From whole- and partial-body irradiation experiments with adult Armadillidium vulgare, the following conclusions were drawn: the LD/sub 50/-30 days for this animal when subjected to ..gamma.. radiation at 25 +- 2/sup 0/C was about 30 kR. Radiosensitivity of the animal changed during the molt cycle. Ionizing radiation increased mortality at ecdysis and during intermolt stages. Anatomical and histological observations indicated that (1) gastrointestinal injury as the major cause of acute death does not apply to this animal because the intestine is not a cell-proliferative organ: (2) the epidermis may be the critical target organ.

  2. [On the importance of a comprehensive study for diagnostics of death from acute ethanol poisoning and coronary heart disease].

    PubMed

    Porodenko, V A; Korkhmazov, V T

    2011-01-01

    Over 30 000 cases of acute poisoning with ethyl alcohol and its surrogates are recorded annually in this country. Differential diagnostics between fatal poisoning and death from coronary heart disease encounters serious difficulties. The authors report a comprehensive forensic chemical, morphometric, and pathomorphological study of the activity of ethanol-oxidizing enzyme systems in the internal organs. The results of histochemical examination provide a basis for the extension of diagnostic potential of the available methods and the enhancement of the objective value of expert reports. PMID:21866846

  3. 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

  4. Programmed cell death of T lymphocytes during acute viral infection: a mechanism for virus-induced immune deficiency.

    PubMed Central

    Razvi, E S; Welsh, R M

    1993-01-01

    Acute viral infections induce immune deficiencies, as shown by unresponsiveness to mitogens and unrelated antigens. T lymphocytes isolated from mice acutely infected with lymphocytic choriomeningitis virus (LCMV) were found in this study to undergo activation-induced apoptosis upon signalling through the T-cell receptor (TcR)-CD3 complex. Kinetic studies demonstrated that this sensitivity to apoptosis directly correlated with the induction of immune deficiency, as measured by impaired proliferation in response to anti-CD3 antibody or to concanavalin A. Cell cycling in interleukin-2 (IL-2) alone stimulated proliferation of LCMV-induced T cells without inducing apoptosis, but preculturing of T cells from acutely infected mice in IL-2 accelerated apoptosis upon subsequent TcR-CD3 cross-linking. T lymphocytes isolated from mice after the acute infection were less responsive to IL-2, but those T cells, presumably memory T cells, responding to IL-2 were primed in each case to die a rapid apoptotic death upon TcR-CD3 cross-linking. These results indicate that virus infection-induced unresponsiveness to T-cell mitogens is due to apoptosis of the activated lymphocytes and suggest that the sensitization of memory cells by IL-2 induced during infection will cause them to die upon antigen recognition, thereby impairing specific responses to nonviral antigens. Images PMID:8371341

  5. 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

  6. 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.

  7. Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis.

    PubMed

    Sun, Wei-Ping; Li, Chun-Lei; Guo, Jin-Cheng; Zhang, Li-Xin; Liu, Ran; Zhang, Hai-Bin; Zhang, Ling

    2016-07-01

    Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63-0.96; P = 0.02; I (2) = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53-1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50-0.89; P = 0.005; I (2) = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57-0.77; P < 0.0001; I (2) = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.

  8. [Periodic Repolarization Dynamics--innovative st