Sample records for ischemic cardiomyopathy induced

  1. Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

    PubMed

    Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

    2018-08-15

    Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Statins reduce appropriate implantable cardioverter-defibrillator shocks in ischemic cardiomyopathy with no benefit in nonischemic cardiomyopathy.

    PubMed

    Contractor, Tahmeed; Beri, Abhimanyu; Gardiner, Joseph; Ardhanari, Sivakumar; Thakur, Ranjan

    2012-11-01

    Statins have been hypothesized to decrease ventricular arrhythmias through a direct antiarrhythmic effect. Clinical studies have demonstrated a clear reduction only in populations with underlying ischemic heart disease. This study was designed to compare the effect of statins on appropriate shocks between ischemic and nonischemic cardiomyopathy. Patients with an ejection fraction 35% or less who received an implantable cardioverter-defibrillator and had follow-up for at least 1 month were included. The ischemic and nonischemic groups were divided into statin treatment and control subgroups and the occurrence of appropriate shocks was compared. The frequency of shocks was analyzed using negative binomial models to account for overdispersion of the "count" data (number of appropriate shocks) and an adjusted intensity rate ratio was calculated for statin use. A total of 676 patients were included, of which statins were used by 65% (329 of 506) of the ischemic and 42% (72 of 170) of the nonischemic groups. Occurrence of appropriate shocks was significantly reduced with statins in ischemic (13.4% vs 20.9%; relative risk 0.64, P = 0.028), but not in the patients with nonischemic cardiomyopathy. Similarly, although use of statins lowered the intensity rate of appropriate shocks in ischemic patients (intensity rate ratio, 0.23; 95% confidence interval, 0.12-0.47), no such benefit was noted in the nonischemic group (intensity rate ratio, 1.27; 95% confidence interval, 0.37-4.40). In conclusion, statins reduced the occurrence and frequency of appropriate shocks for ventricular arrhythmias in ischemic but not in nonischemic cardiomyopathy. Larger, randomized controlled trials are needed to confirm these findings.

  3. Non-ischemic diabetic cardiomyopathy may initially exhibit a transient subclinical phase of hyperdynamic myocardial performance.

    PubMed

    Hensel, Kai O

    2016-09-01

    Cardiovascular complications are the key cause for mortality in diabetes mellitus. Besides ischemia-related cardiac malfunction there is growing evidence for non-ischemic diabetes-associated heart failure in both type 1 and type 2 diabetes mellitus. The underlying pathophysiology of non-ischemic diabetic cardiomyopathy (NIDC) is poorly understood and data on myocardial mechanics in early stages of the disease are rare. However, several studies in both human and experimental animal settings have reported prima facie unexplained features indicating myocardial hyperdynamics early in the course of the disease. The new hypothesis is that - other than previously thought - NIDC may be non-linear and initially feature an asymptomatic subclinical phase of myocardial hypercontractility that precedes the long-term development of diabetes-associated cardiac dysfunction and ultimately heart failure. Diabetes-induced metabolic imbalances may lead to a paradoxic inotropic increase and inefficient myocardial mechanics that finally result in a gradual deterioration of myocardial performance. In conclusion, diabetic patients should be screened regularly and early in the course of the disease utilizing ultra-sensitive myocardial deformation imaging in order to identify patients at risk for diabetes-associated heart failure. Moreover, hyperdynamic myocardial deformation might help distinguish non-ischemic from ischemic diabetic cardiomyopathy. Further studies are needed to illuminate the underlying pathophysiological mechanisms, the exact spatiotemporal evolvement of diabetic cardiomyopathy and its long-term relation to clinical outcome parameters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The effect of ICD programming on inappropriate and appropriate ICD Therapies in ischemic and nonischemic cardiomyopathy: the MADIT-RIT trial.

    PubMed

    Sedláček, Kamil; Ruwald, Anne-Christine; Kutyifa, Valentina; McNitt, Scott; Thomsen, Poul Erik Bloch; Klein, Helmut; Stockburger, Martin; Wichterle, Dan; Merkely, Bela; DE LA Concha, Joaquin Fernandez; Swissa, Moshe; Zareba, Wojciech; Moss, Arthur J; Kautzner, Josef; Ruwald, Martin H

    2015-04-01

    The MADIT-RIT trial demonstrated reduction of inappropriate and appropriate ICD therapies and mortality by high-rate cut-off and 60-second-delayed VT therapy ICD programming in patients with a primary prophylactic ICD indication. The aim of this analysis was to study effects of MADIT-RIT ICD programming in patients with ischemic and nonischemic cardiomyopathy. First and total occurrences of both inappropriate and appropriate ICD therapies were analyzed by multivariate Cox models in 791 (53%) patients with ischemic and 707 (47%) patients with nonischemic cardiomyopathy. Patients with ischemic and nonischemic cardiomyopathy had similar incidence of first inappropriate (9% and 11%, P = 0.21) and first appropriate ICD therapy (11.6% and 14.1%, P = 0.15). Patients with ischemic cardiomyopathy had higher mortality rate (6.1% vs. 3.3%, P = 0.01). MADIT-RIT high-rate cut-off (arm B) and delayed VT therapy ICD programming (arm C) compared with conventional (arm A) ICD programming were associated with a significant risk reduction of first inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy (HR range 0.11-0.34, P < 0.001 for all comparisons). Occurrence of total inappropriate and appropriate ICD therapies was significantly reduced by high-rate cut-off ICD programming and delayed VT therapy ICD programming in both ischemic and nonischemic cardiomyopathy patients. High-rate cut-off and delayed VT therapy ICD programming are associated with significant reduction in first and total inappropriate and appropriate ICD therapy in patients with ischemic and nonischemic cardiomyopathy. © 2014 Wiley Periodicals, Inc.

  5. Neuregulin-1/erbB-activation improves cardiac function and survival in models of ischemic, dilated, and viral cardiomyopathy.

    PubMed

    Liu, Xifu; Gu, Xinhua; Li, Zhaoming; Li, Xinyan; Li, Hui; Chang, Jianjie; Chen, Ping; Jin, Jing; Xi, Bing; Chen, Denghong; Lai, Donna; Graham, Robert M; Zhou, Mingdong

    2006-10-03

    We evaluated the therapeutic potential of a recombinant 61-residue neuregulin-1 (beta2a isoform) receptor-active peptide (rhNRG-1) in multiple animal models of heart disease. Activation of the erbB family of receptor tyrosine kinases by rhNRG-1 could provide a treatment option for heart failure, because neuregulin-stimulated erbB2/erbB4 heterodimerization is not only critical for myocardium formation in early heart development but prevents severe dysfunction of the adult heart and premature death. Disabled erbB-signaling is also implicated in the transition from compensatory hypertrophy to failure, whereas erbB receptor-activation promotes myocardial cell growth and survival and protects against anthracycline-induced cardiomyopathy. rhNRG-1 was administered IV to animal models of ischemic, dilated, and viral cardiomyopathy, and cardiac function and survival were evaluated. Short-term intravenous administration of rhNRG-1 to normal dogs and rats did not alter hemodynamics or cardiac contractility. In contrast, rhNRG-1 improved cardiac performance, attenuated pathological changes, and prolonged survival in rodent models of ischemic, dilated, and viral cardiomyopathy, with the survival benefits in the ischemic model being additive to those of angiotensin-converting enzyme inhibitor therapy. In addition, despite continued pacing, rhNRG-1 produced global improvements in cardiac function in a canine model of pacing-induced heart failure. These beneficial effects make rhNRG-1 promising as a broad-spectrum therapeutic for the treatment of heart failure due to a variety of common cardiac diseases.

  6. Establishment of a Novel Murine Model of Ischemic Cardiomyopathy with Multiple Diffuse Coronary Lesions

    PubMed Central

    Nakaoka, Hajime; Nakagawa-Toyama, Yumiko; Nishida, Makoto; Okada, Takeshi; Kawase, Ryota; Yamashita, Taiji; Yuasa-Kawase, Miyako; Nakatani, Kazuhiro; Masuda, Daisaku; Ohama, Tohru; Sonobe, Takashi; Shirai, Mikiyasu; Komuro, Issei; Yamashita, Shizuya

    2013-01-01

    Objectives Atherosclerotic lesions of the coronary arteries are the pathological basis for myocardial infarction and ischemic cardiomyopathy. Progression of heart failure after myocardial infarction is associated with cardiac remodeling, which has been studied by means of coronary ligation in mice. However, this ligation model requires excellent techniques. Recently, a new murine model, HypoE mouse was reported to exhibit atherogenic Paigen diet-induced coronary atherosclerosis and myocardial infarction; however, the HypoE mice died too early to make possible investigation of cardiac remodeling. Therefore, we aimed to modify the HypoE mouse model to establish a novel model for ischemic cardiomyopathy caused by atherosclerotic lesions, which the ligation model does not exhibit. Methods and Results In our study, the sustained Paigen diet for the HypoE mice was shortened to 7 or 10 days, allowing the mice to survive longer. The 7-day Paigen diet intervention starting when the mice were 8 weeks old was adequate to permit the mice to survive myocardial infarction. Our murine model, called the “modified HypoE mouse”, was maintained until 8 weeks, with a median survival period of 36 days, after the dietary intervention (male, n = 222). Echocardiography demonstrated that the fractional shortening 2 weeks after the Paigen diet (n = 14) significantly decreased compared with that just before the Paigen diet (n = 6) (31.4±11.9% vs. 54.4±2.6%, respectively, P<0.01). Coronary angiography revealed multiple diffuse lesions. Cardiac remodeling and fibrosis were identified by serial analyses of cardiac morphological features and mRNA expression levels in tissue factors such as MMP-2, MMP-9, TIMP-1, collagen-1, and TGF-β. Conclusion Modified HypoE mice are a suitable model for ischemic cardiomyopathy with multiple diffuse lesions and may be considered as a novel and convenient model for investigations of cardiac remodeling on a highly atherogenic background. PMID

  7. Cardiac magnetic resonance imaging and computed tomography in ischemic cardiomyopathy: an update*

    PubMed Central

    Assunção, Fernanda Boldrini; de Oliveira, Diogo Costa Leandro; Souza, Vitor Frauches; Nacif, Marcelo Souto

    2016-01-01

    Ischemic cardiomyopathy is one of the major health problems worldwide, representing a significant part of mortality in the general population nowadays. Cardiac magnetic resonance imaging (CMRI) and cardiac computed tomography (CCT) are noninvasive imaging methods that serve as useful tools in the diagnosis of coronary artery disease and may also help in screening individuals with risk factors for developing this illness. Technological developments of CMRI and CCT have contributed to the rise of several clinical indications of these imaging methods complementarily to other investigation methods, particularly in cases where they are inconclusive. In terms of accuracy, CMRI and CCT are similar to the other imaging methods, with few absolute contraindications and minimal risks of adverse side-effects. This fact strengthens these methods as powerful and safe tools in the management of patients. The present study is aimed at describing the role played by CMRI and CCT in the diagnosis of ischemic cardiomyopathies. PMID:26929458

  8. Impact of ethyl pyruvate on Adriamycin-induced cardiomyopathy in rats

    PubMed Central

    Liu, Menglin; Wang, Menglong; Liu, Jianfang; Luo, Zhen; Shi, Lei; Feng, Ying; Li, Li; Xu, Lin; Wan, Jun

    2016-01-01

    Ethyl pyruvate (EP), a derivative of pyruvic acid, is known to have protective effects against ischemic cardiomyopathy and other disorders. However, little is known about its role in Adriamycin (ADR)-induced cardiomyopathy. The present study was designed to investigate the impact of EP on ADR-induced cardiomyopathy in an animal model. Sixty male Sprague-Dawley (SD) rats were divided into four groups: Normal control, EP, ADR and ADR + EP groups (n=15/group). Rats in the ADR and ADR + EP groups were treated with ADR (2.5 mg/kg/week intraperitoneally) for 6 weeks. From the eighth week, rats in the EP and ADR + EP groups received EP via gastric lavage at a dose of 50 mg/kg/day for 30 days. After completing the EP treatment, cardiac function was assessed by echocardiography and then rats were sacrificed. Hearts were harvested for subsequent analysis. Compared with rats in the normal control and EP groups (without ADR treatment), rats in the ADR and ADR + EP groups showed significant impairments in terms of cardiac function, apoptosis, severe oxidative stress and fibrosis in the heart. However, these impairments were alleviated by EP treatment in the ADR + EP group. Upon EP treatment, cardiac function was significantly improved. The levels of oxidative stress, fibrosis and apoptosis in the myocardial tissues were also significantly reduced. These findings indicated that EP treatment attenuated, at least partially, ADR-induced cardiomyopathy in rats. PMID:27882138

  9. Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy.

    PubMed

    Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

    2009-10-09

    Insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGFbeta) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFbeta and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFbeta, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies.

  10. Cardiac insulin-like growth factor-1 and cyclins gene expression in canine models of ischemic or overpacing cardiomyopathy

    PubMed Central

    Mahmoudabady, Maryam; Mathieu, Myrielle; Touihri, Karim; Hadad, Ielham; Da Costa, Agnes Mendes; Naeije, Robert; Mc Entee, Kathleen

    2009-01-01

    Background Insulin-like growth factor-1 (IGF-1), transforming growth factor β (TGFβ) and cyclins are thought to play a role in myocardial hypertrophic response to insults. We investigated these signaling pathways in canine models of ischemic or overpacing-induced cardiomyopathy. Methods Echocardiographic recordings and myocardial sampling for measurements of gene expressions of IGF-1, its receptor (IGF-1R), TGFβ and of cyclins A, B, D1, D2, D3 and E, were obtained in 8 dogs with a healed myocardial infarction, 8 dogs after 7 weeks of overpacing and in 7 healthy control dogs. Results Ischemic cardiomyopathy was characterized by moderate left ventricular systolic dysfunction and eccentric hypertrophy, with increased expressions of IGF-1, IGF-1R and cyclins B, D1, D3 and E. Tachycardiomyopathy was characterized by severe left ventricular systolic dysfunction and dilation with no identifiable hypertrophic response. In the latter model, only IGF-1 was overexpressed while IGF-1R, cyclins B, D1, D3 and E stayed unchanged as compared to controls. The expressions of TGFβ, cyclins A and D2 were comparable in the 3 groups. The expression of IGF-1R was correlated with the thickness of the interventricular septum, in systole and diastole, and to cyclins B, D1, D3 and E expression. Conclusion These results agree with the notion that IGF-1/IGF-1R and cyclins are involved in the hypertrophic response observed in cardiomyopathies. PMID:19818143

  11. Polymorphisms in adenosine receptor genes are associated with infarct size in patients with ischemic cardiomyopathy.

    PubMed

    Tang, Z; Diamond, M A; Chen, J-M; Holly, T A; Bonow, R O; Dasgupta, A; Hyslop, T; Purzycki, A; Wagner, J; McNamara, D M; Kukulski, T; Wos, S; Velazquez, E J; Ardlie, K; Feldman, A M

    2007-10-01

    The goal of this experiment was to identify the presence of genetic variants in the adenosine receptor genes and assess their relationship to infarct size in a population of patients with ischemic cardiomyopathy. Adenosine receptors play an important role in protecting the heart during ischemia and in mediating the effects of ischemic preconditioning. We sequenced DNA samples from 273 individuals with ischemic cardiomyopathy and from 203 normal controls to identify the presence of genetic variants in the adenosine receptor genes. Subsequently, we analyzed the relationship between the identified genetic variants and infarct size, left ventricular size, and left ventricular function. Three variants in the 3'-untranslated region of the A(1)-adenosine gene (nt 1689 C/A, nt 2206 Tdel, nt 2683del36) and an informative polymorphism in the coding region of the A3-adenosine gene (nt 1509 A/C I248L) were associated with changes in infarct size. These results suggest that genetic variants in the adenosine receptor genes may predict the heart's response to ischemia or injury and might also influence an individual's response to adenosine therapy.

  12. Current Indications for Implantable Cardioverter Defibrillators in Non-Ischemic Cardiomyopathies and Channelopathies.

    PubMed

    González-Torrecilla, Esteban; Arenal, Angel; Atienza, Felipe; Datino, Tomás; Bravo, Loreto; Ruiz, Pablo; Ávila, Pablo; Fernández-Avilés, Francisco

    2015-01-01

    Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM), there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions do support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies, ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk evaluation and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.

  13. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder.

    PubMed

    Bispo, Miguel; Valente, Ana; Maldonado, Rosário; Palma, Rui; Glória, Helena; Nóbrega, João; Alexandrino, Paula

    2009-06-21

    Heart failure may lead to subclinical circulatory disturbances and remain an unrecognized cause of ischemic liver injury. We present the case of a previously healthy 40-year-old bodybuilder, referred to our Intensive-Care Unit of Hepatology for treatment of severe acute liver failure, with the suspicion of toxic hepatitis associated with anabolic steroid abuse. Despite the absence of symptoms and signs of congestive heart failure at admission, an anabolic steroid-induced dilated cardiomyopathy with a large thrombus in both ventricles was found to be the underlying cause of the liver injury. Treatment for the initially unrecognized heart failure rapidly restored liver function to normal. To our knowledge, this is the first reported case of severe acute liver failure due to an unrecognized anabolic steroid-induced cardiomyopathy. Awareness of this unique presentation will allow for prompt treatment of this potentially fatal cause of liver failure.

  14. Safety and tolerability of omecamtiv mecarbil during exercise in patients with ischemic cardiomyopathy and angina.

    PubMed

    Greenberg, Barry H; Chou, Willis; Saikali, Khalil G; Escandón, Rafael; Lee, Jacqueline H; Chen, Michael M; Treshkur, Tatyana; Megreladze, Irakli; Wasserman, Scott M; Eisenberg, Paul; Malik, Fady I; Wolff, Andrew A; Shaburishvili, Tamaz

    2015-01-01

    The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in patients with ischemic cardiomyopathy and angina. These patients may have increased vulnerability to prolongation of the systolic ejection time. Omecamtiv mecarbil is a selective cardiac myosin activator that augments cardiac contractility in patients with systolic heart failure through a dose-dependent increase in systolic ejection time. In this double-blind, placebo-controlled study, patients with chronic heart failure were randomized 2:1 to receive omecamtiv mecarbil or placebo in 2 sequential cohorts of escalating doses designed to achieve plasma concentrations previously shown to increase systolic function. Patients underwent 2 symptom-limited exercise treadmill tests (ETTs) at baseline (ETT1 and ETT2) and again before the end of a 20-h infusion of omecamtiv mecarbil (ETT3). The primary pre-defined safety endpoint (i.e., the proportion of patients who stopped ETT3 because of angina at a stage earlier than baseline) was observed in 1 patient receiving placebo and none receiving omecamtiv mecarbil. No dose-dependent differences emerged in the proportion of patients stopping ETT3 for any reason or in the pattern of adverse events. Doses of omecamtiv mecarbil producing plasma concentrations previously shown to increase systolic function were well tolerated during exercise in these study patients with ischemic cardiomyopathy and angina. There was no indication that treatment increased the likelihood of myocardial ischemia in this high-risk population. (Pharmacokinetics [PK] and Tolerability of Intravenous [IV] and Oral CK-1827452 in Patients With Ischemic Cardiomyopathy and Angina; NCT00682565). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  15. Feasibility and safety of catheter ablation of electrical storm in ischemic dilated cardiomyopathy.

    PubMed

    Dello Russo, Antonio; Casella, Michela; Pelargonio, Gemma; Santangeli, Pasquale; Bartoletti, Stefano; Bencardino, Gianluigi; Al-Mohani, Ghaliah; Innocenti, Ester; Di Biase, Luigi; Avella, Andrea; Pappalardo, Augusto; Carbucicchio, Corrado; Bellocci, Fulvio; Fiorentini, Cesare; Natale, Andrea; Tondo, Claudio

    2016-06-01

    Electrical storm is an emergency in 'implantation of a cardioverter defibrillator' carriers with ischemic dilated cardiomyopathy (DCM) and negatively impacts long-term prognosis. We evaluated the feasibility, safety, and effectiveness of radiofrequency catheter ablation (RFCA) in controlling electrical storm and its impact on survival and ventricular tachycardia/fibrillation recurrence. We enrolled 27 consecutive patients (25 men, age 73.1 ± 6.5 years) with ischemic DCM and an indication to RFCA for drug-refractory electrical storm. The immediate outcome was defined as failure or success, depending on whether the patient's clinical ventricular tachycardia could still be induced after RFCA; electrical storm resolution was defined as no sustained ventricular tachycardia/ventricular fibrillation in the next 7 days. Of the 27 patients, 1 died before RFCA; in the remaining 26 patients, a total of 33 RFCAs were performed. In all 26 patients, RFCA was successful, although in 6/26 patients (23.1%), repeated procedures were needed, including epicardial ablation in 3/26 (11.5%). In 23/26 patients (88.5%), electrical storm resolution was achieved. At a follow-up of 16.7 ± 8.1 months, 5/26 patients (19.2%) had died (3 nonsudden cardiac deaths, 2 noncardiac deaths) and 10/26 patients (38.5%) had ventricular tachycardia recurrence; none had electrical storm recurrence. A worse long-term outcome was associated with lower glomerular filtration rate, wider baseline QRS, and presence of atrial fibrillation before electrical storm onset. In patients with ischemic DCM, RFCA is well tolerated, feasible and effective in the acute management of drug-refractory electrical storm. It is associated with a high rate of absence of sustained ventricular tachycardia episodes over the subsequent 7 days. After successful ablation, long-term outcome was mainly predicted by baseline clinical variables.

  16. Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance.

    PubMed

    Lopez, Javier E; Yeo, Khung; Caputo, Gary; Buonocore, Michael; Schaefer, Saul

    2009-11-11

    Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies.

  17. Recovery of methamphetamine associated cardiomyopathy predicted by late gadolinium enhanced cardiovascular magnetic resonance

    PubMed Central

    2009-01-01

    Methamphetamine is known to cause a cardiomyopathy which may be reversible with appropriate medical therapy and cessation of use. Late gadolinium enhancement cardiovascular magnetic resonance (CMR) has been shown to identify fibrosis in ischemic and non-ischemic cardiomyopathies. We present a case of severe methamphetamine-associated cardiomyopathy in which cardiac function recovered after 6 months. Evaluation by CMR using late gadolinium enhancement was notable for an absence of enhancement, suggesting an absence of irreversible myocyte injury and a good prognosis. CMR may be useful to predict recovery in toxin-associated non-ischemic cardiomyopathies. PMID:19906310

  18. Anti-inflammatory and pro-angiogenic effects of beta blockers in a canine model of chronic ischemic cardiomyopathy: comparison between carvedilol and metoprolol

    PubMed Central

    Le, D. Elizabeth; Pascotto, Marco; Leong-Poi, Howard; Sari, Ibrahim; Micari, Antonio; Kaul, Sanjiv

    2013-01-01

    There is controversy regarding the superiority of carvedilol (C) over metoprolol (M) in congestive heart failure. We hypothesized that C is superior to M in chronic ischemic cardiomyopathy because of its better anti-inflammatory and pro-angiogenic effects. In order to test our hypothesis we used a chronic canine model of multivessel ischemic cardiomyopathy where myocardial microcatheters were placed from which interstitial fluid was collected over time to measure leukocyte count and cytokine levels. After development of left ventricular dysfunction, the animals were randomized into four groups: sham (n = 7), placebo (n = 8), M (n = 11), and C (n = 10), and followed for 3 months after treatment initiation. Tissue was examined for immunohistochemistry, oxidative stress, and capillary density. At 3 months both rest and stress wall thickening were better in C compared to the other groups. At the end of 3 months of treatment endsystolic wall stress also decreased the most in C. Similarly resting myocardial blood flow (MBF) improved the most in C as did the stress endocardial/epicardial MBF. Myocardial interstitial fluid showed greater attenuation of leukocytosis with C compared to M, which was associated with less fibrosis and oxidative stress. C also had higher IL-10 level and capillary density. In conclusion, in a chronic canine model of multivessel ischemic cardiomyopathy we found 3 months of C treatment resulted in better resting global and regional function as well as better regional function at stress compared to M. These changes were associated with higher myocardial levels of the anti-inflammatory cytokine IL-10 and less myocardial oxidative stress, leukocytosis, and fibrosis. Capillary density and MBF were almost normalized. Thus in the doses used in this study, C appears to be superior to M in a chronic canine model of ischemic cardiomyopathy from beneficial effects on inflammation and angiogenesis. Further studies are required for comparing additional doses

  19. Stress-induced cardiomyopathy caused by heat stroke.

    PubMed

    Chen, Wei-Ta; Lin, Cheng-Hsin; Hsieh, Ming-Hsiung; Huang, Chun-Yao; Yeh, Jong-Shiuan

    2012-07-01

    Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy. Copyright © 2011. Published by Mosby, Inc.

  20. Takotsubo Cardiomyopathy

    PubMed Central

    Tiyyagura, Satish; Fuster, Valentin

    2008-01-01

    Background Takotsubo cardiomyopathy is a novel, yet well-described, reversible cardiomyopathy triggered by profound psychological or physical stress with a female predominance. Objective This review is designed to increase general clinician awareness about the diagnosis, incidence, pathogenesis, and therapies of this entity. Data Sources A complete search of multiple electronic databases (Pubmed, EMBASE, Science Citation Index) was carried out to identify all full-text, English-language articles published from 1980 to the present date and relevant to this review. Review Methods The following search terms were used: takotsubo cardiomyopathy, stress-induced cardiomyopathy, and left ventricular apical ballooning syndrome. Citation lists from identified articles were subsequently reviewed and pertinent articles were further identified. Results Takotsubo cardiomyopathy is typically characterized by the following: 1) acute onset of ischemic-like chest pain or dyspnea, 2) transient apical and mid-ventricular regional wall-motion abnormality, 3) minor elevation of cardiac biomarkers, 4) dynamic electrocardiographic changes, and 5) the absence of epicardial coronary artery disease. The pathogenesis of the syndrome is unknown but has mostly been associated with acute emotional or physiologic stressors. Dote, Sato, Tateishi, Uchida, Ishihara (J Cardiol. 21(2):203–214, 1991); Desmet, Adriaenssens, Dens (Heart. 89(9):1027–1031, Sep., 2003); Bybee, Kara, Prasad, et al. (Ann Intern Med. 141(11):858–865, Dec 7, 2004); Sharkey, Lesser, Zenovich, et al. (Circulation. 111(4):472–479, Feb 1, 2005) The short and long-term prognosis of these patients is overwhelmingly favorable and often only requires supportive therapy. Conclusion Whether an emotional or physical event precedes one’s symptoms, it is apparent that takotsubo cardiomyopathy case presentations mimic ST-segment elevation myocardial infarction, and thus is an important entity to be recognized by the medical

  1. Diagnostic approaches for diabetic cardiomyopathy and myocardial fibrosis

    PubMed Central

    Maya, Lisandro; Villarreal, Francisco J.

    2009-01-01

    In diabetes mellitus, alterations in cardiac structure/function in the absence of ischemic heart disease, hypertension or other cardiac pathologies is termed diabetic cardiomyopathy. In the United States, the prevalence of diabetes mellitus continues to rise and the disease currently affects about 8% of the general population. Hence, it is imperative the use of appropriate diagnostic strategies for diabetic cardiomyopathy, which may help correctly identify the disease at early stages and implement suitable corrective therapies. Currently, there is no single diagnostic method for the identification of diabetic cardiomyopathy. Diabetic cardiomyopathy is known to induce changes in cardiac structure such as, myocardial hypertrophy, fibrosis and fat droplet deposition. Early changes in cardiac function are typically manifested as abnormal diastolic function that with time leads to loss of contractile function. Echocardiography based methods currently stands as the preferred diagnostic approach for diabetic cardiomyopathy, due to its wide availability and economical use. In addition to conventional techniques, magnetic resonance imaging and spectroscopy along with contrast agents are now leading new approaches in the diagnosis of myocardial fibrosis, and cardiac and hepatic metabolic changes. These strategies can be complemented with serum biomarkers so they can offer a clear picture as to diabetes-induced changes in cardiac structure/function even at very early stages of the disease. This review article intends to provide a summary of experimental and routine tools currently available to diagnose diabetic cardiomyopathy induced changes in cardiac structure/function. These tools can be reliably used in either experimental models of diabetes or for clinical applications. PMID:19595694

  2. Cardiovascular Magnetic Resonance Imaging of Myocardial Infarction, Viability, and Cardiomyopathies

    PubMed Central

    West, Amy M.; Kramer, Christopher M.

    2010-01-01

    Cardiovascular magnetic resonance provides the opportunity for a truly comprehensive evaluation of patients with a history of MI, with regards to characterizing the extent of disease, impact on LV function and degree of viable myocardium. The use of contrast-enhanced CMR for first-pass perfusion and late gadolinium enhancement is a powerful technique for delineating areas of myocardial ischemia and infarction. Using a combination of T2-weighted and contrast-enhanced CMR images, information about the acuity of an infarct can be obtained. There is an extensive amount of literature using contrast-enhanced CMR to predict myocardial functional recovery with revascularization in patients with ischemic cardiomyopathies. In addition, CMR imaging in patients with cardiomyopathies can distinguish between ischemic and non-ischemic etiologies, with the ability to further characterize the underlying pathology for non-ischemic cardiomyopathies. PMID:20197150

  3. Impact of cardiac support device combined with slow-release prostacyclin agonist in a canine ischemic cardiomyopathy model.

    PubMed

    Kubota, Yasuhiko; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Watabe, Hiroshi; Daimon, Takashi; Sakai, Yoshiki; Akita, Toshiaki; Sawa, Yoshiki

    2014-03-01

    The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy. Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control. At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05). The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  4. Carbon monoxide poisoning-induced cardiomyopathy from charcoal at a barbecue restaurant: a case report.

    PubMed

    Kim, Hyun-Jun; Chung, Yun Kyung; Kwak, Kyeong Min; Ahn, Se-Jin; Kim, Yong-Hyun; Ju, Young-Su; Kwon, Young-Jun; Kim, Eun-A

    2015-01-01

    Acute carbon monoxide poisoning has important clinical value because it can cause severe adverse cardiovascular effects and sudden death. Acute carbon monoxide poisoning due to charcoal is well reported worldwide, and increased use of charcoal in the restaurant industry raises concern for an increase in occupational health problems. We present a case of carbon monoxide poisoning induced cardiomyopathy in a 47-year-old restaurant worker. A male patient was brought to the emergency department to syncope and complained of left chest pain. Cardiac angiography and electrocardiography were performed to rule out acute ischemic heart disease, and cardiac markers were checked. After relief of the symptoms and stabilization of the cardiac markers, the patient was discharged without any complications. Electrocardiography was normal, but cardiac angiography showed up to a 40% midsegmental stenosis of the right coronary artery with thrombotic plaque. The level of cardiac markers was elevated at least 5 to 10 times higher than the normal value, and the carboxyhemoglobin concentration was 35% measured at one hour after syncope. Following the diagnosis of acute carbon monoxide poisoning induced cardiomyopathy, the patient's medical history and work exposure history were examined. He was found to have been exposed to burning charcoal constantly during his work hours. Severe exposure to carbon monoxide was evident in the patient because of high carboxyhemoglobin concentration and highly elevated cardiac enzymes. We concluded that this exposure led to subsequent cardiac injury. He was diagnosed with acute carbon monoxide poisoning-induced cardiomyopathy due to an unsafe working environment. According to the results, the risk of exposure to noxious chemicals such as carbon monoxide by workers in the food service industry is potentially high, and workers in this sector should be educated and monitored by the occupational health service to prevent adverse effects.

  5. Chloroquine-induced cardiomyopathy: a reversible cause of heart failure.

    PubMed

    Yogasundaram, Haran; Hung, Whitney; Paterson, Ian D; Sergi, Consolato; Oudit, Gavin Y

    2018-06-01

    Chloroquine (CQ) and hydroxychloroquine (HCQ) are anti-rheumatic medications frequently used in the treatment of connective tissue disorders. We present the case of a 45-year-old woman with CQ-induced cardiomyopathy leading to severe heart failure. Electrocardiographic abnormalities included bifascicular block, while structural disease consisted of severe biventricular and biatrial hypertrophy. Appropriate diagnosis via endomyocardial biopsy led to cessation of CQ and subsequent dramatic improvement in symptoms and structural heart disease. Cardiac toxicity is an under-recognized adverse effect of CQ/HCQ leading to cardiomyopathy with concentric hypertrophy and conduction abnormalities, with the potential for significant morbidity and mortality. Predisposing factors for CQ/HCQ-induced cardiomyopathy have been proposed. CQ/HCQ cardiomyopathy is a phenocopy of Fabry disease, and α-galactosidase A polymorphism may account for some heterogeneity of disease presentation. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

  6. Acromegaly-induced cardiomyopathy with dobutamine-induced outflow tract obstruction.

    PubMed

    Abdelsalam, Mahmoud A; Nippoldt, Todd B; Geske, Jeffrey B

    2016-03-09

    A 50-year-old man with a history of acromegaly was referred for preoperative cardiac evaluation preceding trans-sphenoidal resection of a pituitary macroadenoma. Dobutamine stress echocardiography was negative for myocardial ischaemia. Resting left ventricular (LV) LV ejection fraction (LVEF) was 64% and there was hypertrophy of ventricular septum (18 mm) without resting LV outflow tract obstruction. With 40 µg/kg/min of dobutamine, the LVEF became hyperdynamic at 80%, and there was a maximal instantaneous LV outflow tract gradient of 77 mm Hg. There was no delayed myocardial enhancement on cardiac MRI and the pattern of hypertrophy was concentric. Acromegaly-induced cardiomyopathy can mimic hypertrophic cardiomyopathy in the setting of dobutamine provocation. Because cardiomyopathy is an important cause of mortality in acromegaly, diagnosis and appropriate management are critical to improve survival. 2016 BMJ Publishing Group Ltd.

  7. Chemotherapy induced Takotsubo cardiomyopathy

    PubMed Central

    Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

    2014-01-01

    Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine. PMID:25325068

  8. Chemotherapy induced Takotsubo cardiomyopathy.

    PubMed

    Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

    2014-10-16

    Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine.

  9. Low-dose dobutamine gated-SPECT analysis of left ventricular segmental wall thickening in ischemic cardiomyopathy.

    PubMed

    Candell-Riera, Jaume; Romero-Farina, Guillermo; Milá, Marta; Aguadé-Bruix, Santiago

    2008-10-01

    The objective of this study was to use low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) to evaluate segmental thickening of the left ventricle (LV) and its relationship with changes in ejection fraction (EF) and ventricular volumes in patients with ischemic cardiomyopathy. This prospective multicenter study involved 89 patients with ischemic cardiomyopathy (i.e., EF < or =40%) who underwent LDD gated-SPECT at rest. The LV was divided into 17 segments and systolic thickening was assessed in a total of 1513 segments during LDD infusion. RESULTS; A significant increase in LVEF (33.2% vs. 30.8%; P< .001) was observed during LDD infusion and occurred at the expense of a reduction in end-systolic volume (130.5 mL vs. 136.4 mL; P=.005). The increase in EF was > or =5% in 33.7% of patients, while the EF decreased by > or =5% in 5.6% of patients. With LDD infusion, both an improvement in > or =3 segments with severely decreased baseline thickening (odds ratio [OR] = 18.3; 95% confidence interval [CI], 5.3-63) and an improvement in > or =10 segments with mild-to-moderate alterations in baseline thickening (OR = 4.53; 95% CI, 1.26-16.16) were associated with a > or =5% increase in LVEF. During the assessment of global left ventricular contractile reserve by LDD gated-SPECT, attention should be paid not only to the behavior of segments with severely decreased baseline thickening, which are generally regarded as indicating viability, but also to segments with mild-to-moderate alterations and to those in which thickening decreases.

  10. Primary Prevention of Sudden Death in Patients With Valvular Cardiomyopathy.

    PubMed

    Rodríguez-Mañero, Moisés; Barrio-López, María Teresa; Assi, Emad Abu; Expósito-García, Víctor; Bertomeu-González, Vicente; Sánchez-Gómez, Juan Miguel; González-Torres, Luis; García-Bolao, Ignacio; Gaztañaga, Larraitz; Cabanas-Grandío, Pilar; Iglesias-Bravo, José Antonio; Arce-León, Álvaro; la Huerta, Ana Andrés; Fernández-Armenta, Juan; Peinado, Rafael; Arias, Miguel Angel; Díaz-Infante, Ernesto

    2016-03-01

    Few data exist on the outcomes of valvular cardiomyopathy patients referred for defibrillator implantation for primary prevention. The aim of the present study was to describe the outcomes of this cardiomyopathy subgroup. This multicenter retrospective study included consecutive patients referred for defibrillator implantation to 15 Spanish centers in 2010 and 2011, and to 3 centers after 1 January 2008. Of 1174 patients, 73 (6.2%) had valvular cardiomyopathy. These patients had worse functional class, wider QRS, and a history of atrial fibrillation vs patients with ischemic (n=659; 56.1%) or dilated (n=442; 37.6%) cardiomyopathy. During a follow-up of 38.1 ± 21.3 months, 197 patients (16.7%) died, without significant differences among the groups (19.2% in the valvular cardiomyopathy group, 15.8% in the ischemic cardiomyopathy group, and 17.9% in the dilated cardiomyopathy group; P=.2); 136 died of cardiovascular causes (11.6%), without significant differences among the groups (12.3%, 10.5%, and 13.1%, respectively; P=.1). Although there were no differences in the proportion of appropriate defibrillator interventions (13.7%, 17.9%, and 18.8%; P=.4), there was a difference in inappropriate interventions (8.2%, 7.1%, and 12.0%, respectively; P=.03). All-cause and cardiovascular mortality in patients with valvular cardiomyopathy were similar to those in other patients referred for defibrillator implantation. They also had similar rates of appropriate interventions. These data suggest that defibrillator implantation in this patient group confers a similar benefit to that obtained by patients with ischemic or dilated cardiomyopathy. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Role of cardiac MRI in nonischemic cardiomyopathies.

    PubMed

    Anand, Senthil; Janardhanan, Rajesh

    2016-01-01

    Cardiac magnetic resonance (CMR) with its higher spatial resolution is considered the gold standard for evaluating ventricular mass, volumes, and ejection fraction. CMR can be used for accurate diagnosis of several conditions, especially cardiomyopathies. The purpose of this article is to review the utility of CMR in the diagnosis and management of nonischemic cardiomyopathies. We have reviewed both common and rare types of nonischemic cardiomyopathies in detail and elaborated on the specific CMR findings in each. We believe that CMR is an invaluable tool, not only in differentiating nonischemic from ischemic cardiomyopathy, but also in aiding the accurate diagnosis and management of the subtype of nonischemic cardiomyopathy. CMR should routinely be integrated in the diagnostic workup of various cardiomyopathies. Published by Elsevier B.V.

  12. Long-Term Outcomes of Catheter Ablation of Electrical Storm in Nonischemic Dilated Cardiomyopathy Compared With Ischemic Cardiomyopathy.

    PubMed

    Muser, Daniele; Liang, Jackson J; Pathak, Rajeev K; Magnani, Silvia; Castro, Simon A; Hayashi, Tatsuya; Garcia, Fermin C; Supple, Gregory E; Riley, Michael P; Lin, David; Dixit, Sanjay; Zado, Erica S; Frankel, David S; Callans, David J; Marchlinski, Francis E; Santangeli, Pasquale

    2017-07-01

    The goal of this study was to determine the long-term outcomes of catheter ablation (CA) of electrical storm in patients with nonischemic dilated cardiomyopathy (NIDCM) compared with patients with ischemic cardiomyopathy (ICM). CA of ventricular tachycardia (VT) electrical storm has been shown to improve VT-free survival in patients with ICM. Data on the outcomes of CA of electrical storm in patients with NIDCM are insufficient. The study included 267 consecutive patients with NIDCM (n = 71; ejection fraction 32 ± 14%) and ICM (n = 196; ejection fraction 28 ± 12%). Endo-epicardial CA was performed in 59 (22%) patients. CA was guided by activation and entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. After a median follow-up of 45 (25th to 75th percentile: 9 to 71) months and 1 (25th to 75th percentile: 1 to 8) procedures, 76 (29%) patients died, 25 (9%) underwent heart transplantation, 87 (33%) experienced VT recurrence, and 13 (5%) had recurrence of electrical storm. Overall VT-free survival was 54% at 60 months (48% in NIDCM and 54% in ICM; p = 0.128). Patients with VT recurrence experienced a median of 2 (1 to 10) VT episodes in the 5 (1 to 14) months after the procedure. Death/transplantation-free survival was 62% at 60 months (53% in NIDCM and 64% in ICM; p = 0.067). Persistent inducibility of any VT with cycle length ≥250 ms at programmed stimulation at the end of the procedure was the only independent predictor of VT recurrence. Low ejection fraction, New York Heart Association functional class, and VT recurrence over follow-up independently predicted death/transplantation. CA of electrical storm was similarly effective in patients with NIDCM compared with patients with ICM, with elimination of electrical storm in 95% of cases and achievement of complete VT control at long-term follow-up in most patients. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc

  13. Reversible catecholamine-induced cardiomyopathy due to pheochromocytoma: case report.

    PubMed

    Satendra, Milan; de Jesus, Cláudia; Bordalo e Sá, Armando L; Rosário, Luís; Rocha, José; Bicha Castelo, Henrique; Correia, Maria José; Nunes Diogo, António

    2014-03-01

    Pheochromocytoma is a tumor originating from chromaffin tissue. It commonly presents with symptoms and signs of catecholamine excess, such as hypertension, tachycardia, headache and sweating. Cardiovascular manifestations include catecholamine-induced cardiomyopathy, which may present as severe left ventricular dysfunction and congestive heart failure. We report a case of pheochromocytoma which was diagnosed following investigation of dilated cardiomyopathy. We highlight the dramatic symptomatic improvement and reversal of cardiomyopathy, with recovery of left ventricular function after treatment. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  14. Intravenously Delivered Mesenchymal Stem Cells: Systemic Anti-Inflammatory Effects Improve Left Ventricular Dysfunction in Acute Myocardial Infarction and Ischemic Cardiomyopathy.

    PubMed

    Luger, Dror; Lipinski, Michael J; Westman, Peter C; Glover, David K; Dimastromatteo, Julien; Frias, Juan C; Albelda, M Teresa; Sikora, Sergey; Kharazi, Alex; Vertelov, Grigory; Waksman, Ron; Epstein, Stephen E

    2017-05-12

    Virtually all mesenchymal stem cell (MSC) studies assume that therapeutic effects accrue from local myocardial effects of engrafted MSCs. Because few intravenously administered MSCs engraft in the myocardium, studies have mainly utilized direct myocardial delivery. We adopted a different paradigm. To test whether intravenously administered MSCs reduce left ventricular (LV) dysfunction both post-acute myocardial infarction and in ischemic cardiomyopathy and that these effects are caused, at least partly, by systemic anti-inflammatory activities. Mice underwent 45 minutes of left anterior descending artery occlusion. Human MSCs, grown chronically at 5% O 2 , were administered intravenously. LV function was assessed by serial echocardiography, 2,3,5-triphenyltetrazolium chloride staining determined infarct size, and fluorescence-activated cell sorting assessed cell composition. Fluorescent and radiolabeled MSCs (1×10 6 ) were injected 24 hours post-myocardial infarction and homed to regions of myocardial injury; however, the myocardium contained only a small proportion of total MSCs. Mice received 2×10 6 MSCs or saline intravenously 24 hours post-myocardial infarction (n=16 per group). At day 21, we harvested blood and spleens for fluorescence-activated cell sorting and hearts for 2,3,5-triphenyltetrazolium chloride staining. Adverse LV remodeling and deteriorating LV ejection fraction occurred in control mice with large infarcts (≥25% LV). Intravenous MSCs eliminated the progressive deterioration in LV end-diastolic volume and LV end-systolic volume. MSCs significantly decreased natural killer cells in the heart and spleen and neutrophils in the heart. Specific natural killer cell depletion 24 hours pre-acute myocardial infarction significantly improved infarct size, LV ejection fraction, and adverse LV remodeling, changes associated with decreased neutrophils in the heart. In an ischemic cardiomyopathy model, mice 4 weeks post-myocardial infarction were

  15. Diffuse diseases of the myocardium: MRI-pathologic review of cardiomyopathies with dilatation.

    PubMed

    Giesbrandt, Kirk J; Bolan, Candice W; Shapiro, Brian P; Edwards, William D; Mergo, Patricia J

    2013-03-01

    In this radiologic-pathologic review of the cardiomyopathies, we present the pertinent imaging findings of diffuse myocardial diseases that are associated with ventricular dilatation, including ischemic cardiomyopathy, nonischemic dilated cardiomyopathy, cardiac sarcoidosis, and iron overload cardiomyopathy. Correlation of the key radiologic findings with gross and microscopic pathologic features is presented, to provide the reader with a focused and in-depth review of the pathophysiology underlying each entity and the basis for the corresponding imaging characteristics.

  16. Hypophosphatemia-induced Cardiomyopathy.

    PubMed

    Ariyoshi, Nobuhiro; Nogi, Masayuki; Ando, Akika; Watanabe, Hideaki; Umekawa, Sari

    2016-09-01

    Relatively few studies have been conducted to evaluate the effect of hypophosphatemia on cardiac function. The goal of this review was to determine whether there is an association between hypophosphatemia and cardiac function and to increase awareness of hypophosphatemia-induced cardiomyopathy as a new clinical entity and a reversible cause of heart failure. We searched MEDLINE and PubMed from 1971 until March 2015 for primary studies, which reported the relationship between hypophosphatemia and cardiac function. A total of 837 articles were initially obtained. Of these articles, 826 publications were excluded according to the inclusion and exclusion criteria. In all, 11 articles were included in this review. These articles included 7 case series or case reports, 1 case-control study, 1 pretest versus posttest in a single group and 2 animal studies. In conclusion, the mechanisms of hypophosphatemia in cardiomyopathy have been reported to be a depletion of adenosine triphosphate in myocardial cells and decreased 2,3-diphosphoglycerate in erythrocytes. After correction of hypophosphatemia, left ventricular performance seems to improve in patients with severe hypophosphatemia, but not in those with mild-to-moderate hypophosphatemia. However, analyses of the relationship between cardiac function and hypophosphatemia using clinical end points have not been conducted. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  17. Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

    PubMed

    Yogasundaram, Haran; Putko, Brendan N; Tien, Julia; Paterson, D Ian; Cujec, Bibiana; Ringrose, Jennifer; Oudit, Gavin Y

    2014-12-01

    Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine. Retinal toxicity, neuromyopathy, and cardiac disease are recognized adverse effects of hydroxychloroquine. Immediate withdrawal of hydroxychloroquine is essential if toxicity is suspected because of the early reversibility of cardiomyopathy. In addition to recommended ophthalmological screening, regular screening with 12-lead electrocardiogram and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients. Cardiac magnetic resonance imaging and endomyocardial biopsy are valuable tools to provide prognostic insights and confirm the diagnosis of hydroxychloroquine-induced cardiomyopathy. In conclusion, chronic use of hydroxychloroquine can result in an acquired lysosomal storage disorder, leading to a drug-induced cardiomyopathy characterized by concentric hypertrophy and conduction abnormalities associated with increased adverse clinical outcomes and mortality. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  18. Translational systems pharmacology‐based predictive assessment of drug‐induced cardiomyopathy

    PubMed Central

    Messinis, Dimitris E.; Melas, Ioannis N.; Hur, Junguk; Varshney, Navya; Alexopoulos, Leonidas G.

    2018-01-01

    Drug‐induced cardiomyopathy contributes to drug attrition. We compared two pipelines of predictive modeling: (1) applying elastic net (EN) to differentially expressed genes (DEGs) of drugs; (2) applying integer linear programming (ILP) to construct each drug's signaling pathway starting from its targets to downstream proteins, to transcription factors, and to its DEGs in human cardiomyocytes, and then subjecting the genes/proteins in the drugs' signaling networks to EN regression. We classified 31 drugs with availability of DEGs into 13 toxic and 18 nontoxic drugs based on a clinical cardiomyopathy incidence cutoff of 0.1%. The ILP‐augmented modeling increased prediction accuracy from 79% to 88% (sensitivity: 88%; specificity: 89%) under leave‐one‐out cross validation. The ILP‐constructed signaling networks of drugs were better predictors than DEGs. Per literature, the microRNAs that reportedly regulate expression of our six top predictors are of diagnostic value for natural heart failure or doxorubicin‐induced cardiomyopathy. This translational predictive modeling might uncover potential biomarkers. PMID:29341478

  19. Zumba-induced Takotsubo cardiomyopathy: a case report.

    PubMed

    Chams, Sana; El Sayegh, Skye; Hamdon, Mulham; Kumar, Sarwan; Kulairi, Zain

    2018-06-10

    Takotsubo cardiomyopathy or stress cardiomyopathy is characterized by transient left ventricular apical ballooning in the absence of coronary occlusion. The underlying pathophysiological mechanism is still unclear but possible causes have been proposed mainly catecholamine cardiotoxicity, followed by metabolic disturbance, coronary microvascular impairment, and multivessel epicardial coronary artery vasospasm. Takotsubo cardiomyopathy accounts for 1-2% of patients presenting with acute coronary syndrome with the majority of patients diagnosed with Takotsubo cardiomyopathy being women > 55 years of age. Here, we discuss the case of a 38-year-old woman presenting with typical chest pain, electrocardiography changes and cardiac markers consistent with acute coronary syndrome, who was subsequently diagnosed with Takotsubo cardiomyopathy. A 38-year-old healthy American woman with negative past medical history presented to our Emergency Department with chest pain developing while participating in intense outdoor physical activities (Zumba) at a fundraising event. Our patient had typical substernal chest pain induced with exercise and was relieved by sublingual nitroglycerin in the Emergency Department. The pain started after 2 h of intensive Zumba workout. On review of her history, our patient was noted to be taking spironolactone 125 mg once daily for hirsutism for the past year. Our patient denied any family history of cardiac disease or heart failure. She admitted to being a former occasional smoker and to drinking alcohol socially. She denied any illicit drug use. She works as a social worker, and reported that she does not experience much stress in her life and denied any "one big life-changing event" or any major stressful news. While in the Emergency Department, our patient was hemodynamically stable and an electrocardiography was performed and showed sinus rhythm with no ST elevation/depression but noted T-wave inversion in leads I and aVL, and T wave

  20. Management of severe ischemic cardiomyopathy: left ventricular assist device as destination therapy versus conventional bypass and mitral valve surgery.

    PubMed

    Maltais, Simon; Tchantchaleishvili, Vahtang; Schaff, Hartzell V; Daly, Richard C; Suri, Rakesh M; Dearani, Joseph A; Topilsky, Yan; Stulak, John M; Joyce, Lyle D; Park, Soon J

    2014-04-01

    Patients with severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe ischemic mitral regurgitation have a poor survival with medical therapy alone. Left ventricular assist device as destination therapy is reserved for patients who are too high risk for conventional surgery. We evaluated our outcomes with conventional surgery within this population and the comparative effectiveness of these 2 therapies. We identified patients who underwent conventional surgery or left ventricular assist device as destination therapy for severe ischemic cardiomyopathy (left ventricular ejection fraction <25%) and severe mitral regurgitation. The era for conventional surgery spanned from 1993 to 2009 and from 2007 to 2011 for left ventricular assist device as destination therapy. We compared baseline patient characteristics and outcomes in terms of end-organ function and survival. A total of 88 patients were identified; 55 patients underwent conventional surgery (63%), and 33 patients (37%) received a left ventricular assist device as destination therapy. Patients who received left ventricular assist device as destination therapy had the increased prevalence of renal failure, inotrope dependency, and intra-aortic balloon support. Patients undergoing conventional surgery required longer ventilatory support, and patients receiving a left ventricular assist device required more reoperation for bleeding. Mortality rates were similar between the 2 groups at 30 days (7% in the conventional surgery group vs 3% in the left ventricular assist device as destination therapy group, P = .65) and at 1 year (22% in the conventional surgery group vs 15% in the left ventricular assist device as destination therapy group, P = .58). There was a trend toward improved survival in patients receiving a left ventricular assist device compared with the propensity-matched groups at 1 year (94% vs 71%, P = .171). The operative mortality and early survival after conventional

  1. An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

    PubMed Central

    Talavera, Jesús; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M.

    2015-01-01

    Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality. PMID:26788502

  2. Left ventricular strain distribution in healthy dogs and in dogs with tachycardia-induced dilated cardiomyopathy

    PubMed Central

    2013-01-01

    Background Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. Methods Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. Results In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). Conclusion TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This “reverse” distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology. PMID:24304622

  3. Left ventricular strain distribution in healthy dogs and in dogs with tachycardia-induced dilated cardiomyopathy.

    PubMed

    Kusunose, Kenya; Zhang, Youhua; Mazgalev, Todor N; Thomas, James D; Popović, Zoran B

    2013-12-05

    Recently, left ventricular (LV) strain distribution pattern has been assessed in several cardiac disease states. Tachycardia-induced cardiomyopathy (TIC) is an animal model of non-ischemic cardiomyopathy well characterized in terms of global LV dysfunction but with poor understanding of regional variability in LV function. We hypothesized that TIC induces specific changes in LV strain distribution pattern. Twenty five adult mongrel conscious dogs were trained to lie down calmly for echocardiography. In seven selected dogs, we implanted pacing system for TIC induction under general anesthesia. We measured LV geometry and function, strains, and torsion before and after the development of TIC in awake non-sedated state. In 25 healthy dogs, all three types of normal strain significantly increased from base to apex (p <0.05), while a definite and recognizable twist could be measured due to presence of shear strain. In 7 dogs with TIC, marked changes in LV mechanics occurred throughout the cardiac cycle, resulting in decrease of strain (p <0.001), twist (p <0.05), and negative peak twist rate (p <0.05). Interestingly, the relative decrease of strain due to TIC was more pronounced in the apex (p < 0.001), with the radial strain decreasing the most (p < 0.05). TIC is accompanied by decreased systolic LV strain and twist deformation, as well as loss of early diastolic recoil. In addition, the decrease of strain was more profound in the apex. This "reverse" distribution of LV strain may help us understand LV dysfunction in the presence of nonischemic etiology.

  4. Newborn infant with maternal anti-SSA antibody-induced complete heart block accompanying cardiomyopathy.

    PubMed

    Iida, Midori; Inamura, Noboru; Takeuchi, Makoto

    2006-01-01

    Newborn case of maternal anti-SSA antibody-induced congenital complete heart block (CCHB) accompanying cardiomyopathy is presented. Unexpectedly, she died of ventricular tachycardia, not bradycardia, 6 days after birth. Autopsy revealed left ventricular cardiomyopathy with endocardial fibroelastosis. Thus, when evaluating fetal cardiac performance in cases of maternal anti-SSA antibody-induced CCHB, it is necessary to pay attention to myocardial attributes such as endocardial hyperplasia.

  5. Endogenous Agmatine Induced by Ischemic Preconditioning Regulates Ischemic Tolerance Following Cerebral Ischemia

    PubMed Central

    Kim, Jae Hwan; Kim, Jae Young; Jung, Jin Young; Lee, Yong Woo; Lee, Won Taek; Huh, Seung Kon

    2017-01-01

    Ischemic preconditioning (IP) is one of the most important endogenous mechanisms that protect the cells against ischemia-reperfusion (I/R) injury. However, the exact molecular mechanisms remain unclear. In this study, we showed that changes in the level of agmatine were correlated with ischemic tolerance. Changes in brain edema, infarct volume, level of agmatine, and expression of arginine decarboxylase (ADC) and nitric oxide synthases (NOS; inducible NOS [iNOS] and neural NOS [nNOS]) were analyzed during I/R injury with or without IP in the rat brain. After cerebral ischemia, brain edema and infarct volume were significantly reduced in the IP group. The level of agmatine was increased before and during ischemic injury and remained elevated in the early reperfusion phase in the IP group compared to the experimental control (EC) group. During IP, the level of plasma agmatine was increased in the early phase of IP, but that of liver agmatine was abruptly decreased. However, the level of agmatine was definitely increased in the ipsilateral and contralateral hemisphere of brain during the IP. IP also increased the expression of ADC—the enzyme responsible for the synthesis of endogenous agmatine—before, during, and after ischemic injury. In addition, ischemic injury increased endogenous ADC expression in the EC group. The expression of nNOS was reduced in the I/R injured brain in the IP group. These results suggest that endogenous increased agmatine may be a component of the ischemic tolerance response that is induced by IP. Agmatine may have a pivotal role in endogenous ischemic tolerance. PMID:29302205

  6. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy

    PubMed Central

    Zhang, Xiaoli; Schindler, Thomas H.; Prior, John O.; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng

    2016-01-01

    Purpose The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Methods Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25±10 %) were studied with 13N-ammonia and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to 13N-ammonia activity ratios. Results Rest MBF was reduced in viable (0.42±0.18 ml/min per g) and nonviable regions (0.32±0.09 ml/min per g) relative to remote regions (0.68±0.23 ml/min per g, p<0.001) and to normals (0.63±0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p<0.05) and stress (p<0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p>0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39±0.56 vs 1.70±0.45, p>0.05) but were significantly lower in nonviable regions (1.23±0.43, p<0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40±0.14 vs 0.90±0.20, p<0.001) and in nonviable regions (1.13±0.21, p<0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r=−0.424, p<0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. Conclusion As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes. PMID:23287994

  7. Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics.

    PubMed

    Jiang, Ding-Sheng; Zeng, Hao-Long; Li, Rui; Huo, Bo; Su, Yun-Shu; Fang, Jing; Yang, Qing; Liu, Li-Gang; Hu, Min; Cheng, Cai; Zhu, Xue-Hai; Yi, Xin; Wei, Xiang

    2017-03-03

    There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially.

  8. LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar cardiomyopathy: a study of 3 cases.

    PubMed

    Daniels, Brianne H; McComb, Rodney D; Mobley, Bret C; Gultekin, Sakir Humayun; Lee, Han S; Margeta, Marta

    2013-07-01

    Autophagic vacuolar cardiomyopathy is an underrecognized, but potentially fatal, complication of treatment with chloroquine (CQ) and its derivative hydroxychloroquine (HCQ), which are used as therapy for malaria and common connective tissue disorders. Currently, the diagnosis of autophagic vacuolar cardiomyopathy is established through an endomyocardial biopsy and requires electron microscopy, which is not widely available and has a significant potential for sampling error. Recently, we have reported that immunohistochemistry for autophagic markers LC3 and p62 can replace electron microscopy in the diagnosis of HCQ-induced and colchicine-induced autophagic vacuolar skeletal myopathies. In the current study, we use 3 cases of CQ-induced or HCQ-induced cardiomyopathy and 1 HCQ-treated control case to show that the same two markers can be used to diagnose autophagic vacuolar cardiomyopathies by light microscopy. CQ-induced or HCQ-induced autophagic vacuolar cardiomyopathy is not universally fatal, but successful treatment requires early detection. By lowering the barriers to diagnosis, the application of these immunohistochemical markers will decrease the number of misdiagnosed patients, thus increasing the likelihood of favorable clinical outcomes.

  9. Embryonic Stem Cell Therapy of Heart Failure in Genetic Cardiomyopathy

    PubMed Central

    Yamada, Satsuki; Nelson, Timothy J.; Crespo-Diaz, Ruben J.; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

    2009-01-01

    Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K+ (KATP) channel sub-units. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional KATP channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. PMID:18669912

  10. Allogeneic Cardiospheres Delivered via Percutaneous Transendocardial Injection Increase Viable Myocardium, Decrease Scar Size, and Attenuate Cardiac Dilatation in Porcine Ischemic Cardiomyopathy

    PubMed Central

    Tseliou, Eleni; Cheng, Ke; Luthringer, Daniel J.; Ho, Chak-Sum; Takayama, Kentaro; Minamino, Naoto; Dawkins, James F.; Chowdhury, Supurna; Duong, Doan Trang; Seinfeld, Jeffrey; Middleton, Ryan C.; Dharmakumar, Rohan; Li, Debiao; Marbán, Linda; Makkar, Raj R.; Marbán, Eduardo

    2014-01-01

    Background Epicardial injection of heart-derived cell products is safe and effective post-myocardial infarction (MI), but clinically-translatable transendocardial injection has never been evaluated. We sought to assess the feasibility, safety and efficacy of percutaneous transendocardial injection of heart-derived cells in porcine chronic ischemic cardiomyopathy. Methods and Results We studied a total of 89 minipigs; 63 completed the specified protocols. After NOGA-guided transendocardial injection, we quantified engraftment of escalating doses of allogeneic cardiospheres or cardiosphere-derived cells in minipigs (n = 22) post-MI. Next, a dose-ranging, blinded, randomized, placebo-controlled (“dose optimization”) study of transendocardial injection of the better-engrafting product was performed in infarcted minipigs (n = 16). Finally, the superior product and dose (150 million cardiospheres) were tested in a blinded, randomized, placebo-controlled (“pivotal”) study (n = 22). Contrast-enhanced cardiac MRI revealed that all cardiosphere doses preserved systolic function and attenuated remodeling. The maximum feasible dose (150 million cells) was most effective in reducing scar size, increasing viable myocardium and improving ejection fraction. In the pivotal study, eight weeks post-injection, histopathology demonstrated no excess inflammation, and no myocyte hypertrophy, in treated minipigs versus controls. No alloreactive donor-specific antibodies developed over time. MRI showed reduced scar size, increased viable mass, and attenuation of cardiac dilatation with no effect on ejection fraction in the treated group compared to placebo. Conclusions Dose-optimized injection of allogeneic cardiospheres is safe, decreases scar size, increases viable myocardium, and attenuates cardiac dilatation in porcine chronic ischemic cardiomyopathy. The decreases in scar size, mirrored by increases in viable myocardium, are consistent with therapeutic regeneration

  11. Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach

    PubMed Central

    Challis, B G; Pitfield, D; Mahroof, R M; Jamieson, N; Bhagra, C J; Vuylsteke, A; Pettit, S J; Chatterjee, K C

    2017-01-01

    A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases. Here, we report the case of a 38-year-old lady who presented with an acute Takotsubo or stress cardiomyopathy and catecholamine crisis, caused by an occult left-sided 5 cm PC. The initial presenting crisis manifested with symptoms of severe headache and abdominal pain, triggered by a respiratory tract infection. On admission to hospital, the patient rapidly deteriorated, developing respiratory failure, cardiogenic shock and subsequent cardiovascular collapse due to further exacerbation of the catecholamine crisis caused by a combination of opiates and intravenous corticosteroid. An echocardiogram revealed left ventricular apical hypokinesia and ballooning, with an estimated left ventricular ejection fraction of 10–15%. Herein, we outline the early stabilisation period, preoperative optimisation and intraoperative management, providing anecdotal guidance for the management of this rare life-threatening complication of PC. Learning points: A diagnosis of phaeochromocytoma should be considered in patients presenting with acute cardiomyopathy or cardiogenic shock without a clear ischaemic or valvular aetiology. Catecholamine crisis is a life-threatening medical emergency that requires cross-disciplinary expertise and management to ensure the best clinical outcome. After initial resuscitation, treatment of acute

  12. Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses.

    PubMed

    Li, Yang; Zhang, Haiyan

    2017-08-01

    Ischemic cardiomyopathy (IC) is the major cause of heart failure. Conventional medicine has been proved ineffective with adverse effects. Soybean presents exciting adjunctive therapies and shows protective benefits for IC. However, the molecular mechanisms remain unclear. Isoflavones are the main bioactive components of soybean and may be protective against heart disease. Isoflavones were extracted by using an acidic-ethanol method and analyzed by HPLC. All patients with ischemic stroke were randomly and evenly assigned to two groups: the isoflavone group (80 mg day -1 , n = 100) and control group (80 mg day -1 placebo, n = 100), and the whole period of the experiment was 24 weeks. The effects of soybean isoflavone on brachial flow-mediated dilatation (FMD) were measured. HPLC fractionation shows that isoflavone extracts are mainly composed of 55% genistein, 23% daidzein, and 14% glycitein. Isoflavone therapy reduced more levels of triglyceride and LDL-c in females than in males. FMD was higher in the isoflavone group than in the control group after 24-week therapy (treatment effect 2.0%, 95% CI 0.18-3.0, P = 0.01). The baseline differences were adjusted in FMD and the isoflavone therapies were closely associated with the reduction of FMD impairment at 24 weeks (odds ratio 0.30, 95% CI 0.14-0.85, P = 0.01). The effects of isoflavone on brachial FMD were negatively associated with base FMD (r = -0.65, P < 0.01). Furthermore, isoflavone therapy caused a significant increase in the levels of erythroid-derived 2-like 2 (Nrf2), superoxide dismutase (SOD) and a significant decrease in serum levels of C-reactive protein, 8-isoprostane, malondialdehyde, interleukin-6 and tumor necrosis factor alpha. In contrast, the isoflavones had no effects on the levels of oxidation-related molecules when Nrf2 was silenced. These results suggest that soybean isoflavones ameliorate IC patients by improving their antioxidant capacities via the upregulation of Nrf2.

  13. Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Liu, Qian; Zhang, Qi; Wang, Kai; Wang, Shengchan; Lu, Dasheng; Li, Zhenzhen; Geng, Jie; Fang, Ping; Wang, Ying; Shan, Qijun

    2015-12-01

    Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

  14. Embryonic stem cell therapy of heart failure in genetic cardiomyopathy.

    PubMed

    Yamada, Satsuki; Nelson, Timothy J; Crespo-Diaz, Ruben J; Perez-Terzic, Carmen; Liu, Xiao-Ke; Miki, Takashi; Seino, Susumu; Behfar, Atta; Terzic, Andre

    2008-10-01

    Pathogenic causes underlying nonischemic cardiomyopathies are increasingly being resolved, yet repair therapies for these commonly heritable forms of heart failure are lacking. A case in point is human dilated cardiomyopathy 10 (CMD10; Online Mendelian Inheritance in Man #608569), a progressive organ dysfunction syndrome refractory to conventional therapies and linked to mutations in cardiac ATP-sensitive K(+) (K(ATP)) channel subunits. Embryonic stem cell therapy demonstrates benefit in ischemic heart disease, but the reparative capacity of this allogeneic regenerative cell source has not been tested in inherited cardiomyopathy. Here, in a Kir6.2-knockout model lacking functional K(ATP) channels, we recapitulated under the imposed stress of pressure overload the gene-environment substrate of CMD10. Salient features of the human malignant heart failure phenotype were reproduced, including compromised contractility, ventricular dilatation, and poor survival. Embryonic stem cells were delivered through the epicardial route into the left ventricular wall of cardiomyopathic stressed Kir6.2-null mutants. At 1 month of therapy, transplantation of 200,000 cells per heart achieved teratoma-free reversal of systolic dysfunction and electrical synchronization and halted maladaptive remodeling, thereby preventing end-stage organ failure. Tracked using the lacZ reporter transgene, stem cells engrafted into host heart. Beyond formation of cardiac tissue positive for Kir6.2, transplantation induced cell cycle activation and halved fibrotic zones, normalizing sarcomeric and gap junction organization within remuscularized hearts. Improved systemic function induced by stem cell therapy translated into increased stamina, absence of anasarca, and benefit to overall survivorship. Embryonic stem cells thus achieve functional repair in nonischemic genetic cardiomyopathy, expanding indications to the therapy of heritable heart failure. Disclosure of potential conflicts of interest is

  15. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    PubMed

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

    2013-04-01

    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p < 0.001) and to normals (0.63 ± 0.13 ml/min per g). Dipyridamole raised MBFs in controls, remote, viable, and nonviable regions. MBFs at rest (p < 0.05) and stress (p < 0.05) in viable regions were significantly higher than that in nonviable regions, while MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p < 0.001). Moreover, the FDG and thus glucose extraction was higher in viable than in remote (1.40 ± 0.14 vs 0.90 ± 0.20, p < 0.001) and in nonviable regions (1.13 ± 0.21, p < 0.001). The extraction of FDG in viable regions was independent of rest MBF but correlated inversely with MFRs (r =-0.424, p < 0.05). No correlation between the FDG extraction and MFR was observed in nonviable regions. As in the animal model, decreasing MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  16. [Cardiologic emergencies and natural disaster. Prospective study with Xynthia tempest].

    PubMed

    Trebouet, E; Lipp, D; Dimet, J; Orion, L; Fradin, P

    2011-02-01

    Stress-induced cardiomyopathy and ischemic cardiopathy have been described after natural disasters such as earthquakes. Count stress-induced cardiomyopathies and ischemic cardiopathies just after Xynthia tempest which damaged the Vendean coast on February2010, in order to study epidemiology. Included patients were living in a tempest damaged village, and admitted in Vendee hospital just after or in the week following the tempest, and presenting a suspected acute coronary syndrome or stress-induced cardiomyopathy. Among 3350 inhabitants of the two damaged Vendean towns, we count three acute coronary syndromes, two Tako-Tsubo cardiomyopathies, and one coronary spasm. We count five women and one man, average age is 76. The diagnosis of ischemic cardiopathy and stress-induced cardiomyopathy is over-represented in this tempest damaged population, that have been little described. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  17. Cardiomyopathy and Cerebrovascular Accident Associated with Anabolic-Androgenic Steroid Use.

    ERIC Educational Resources Information Center

    Mochizuki, Ronald M.; Richter, Kenneth J.

    1988-01-01

    A case report is presented of a 32 year-old male bodybuilder who sustained an ischemic cerebrovascular accident and showed signs of cardiomyopathy. Although no cause was found, the man had been taking steroids for 16 years. Harmful effects of steroid use are discussed. (IAH)

  18. Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis

    PubMed Central

    Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu

    2014-01-01

    The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments. PMID:25068019

  19. Distribution of late gadolinium enhancement in various types of cardiomyopathies: Significance in differential diagnosis, clinical features and prognosis.

    PubMed

    Satoh, Hiroshi; Sano, Makoto; Suwa, Kenichiro; Saitoh, Takeji; Nobuhara, Mamoru; Saotome, Masao; Urushida, Tsuyoshi; Katoh, Hideki; Hayashi, Hideharu

    2014-07-26

    The recent development of cardiac magnetic resonance (CMR) techniques has allowed detailed analyses of cardiac function and tissue characterization with high spatial resolution. We review characteristic CMR features in ischemic and non-ischemic cardiomyopathies (ICM and NICM), especially in terms of the location and distribution of late gadolinium enhancement (LGE). CMR in ICM shows segmental wall motion abnormalities or wall thinning in a particular coronary arterial territory, and the subendocardial or transmural LGE. LGE in NICM generally does not correspond to any particular coronary artery distribution and is located mostly in the mid-wall to subepicardial layer. The analysis of LGE distribution is valuable to differentiate NICM with diffusely impaired systolic function, including dilated cardiomyopathy, end-stage hypertrophic cardiomyopathy (HCM), cardiac sarcoidosis, and myocarditis, and those with diffuse left ventricular (LV) hypertrophy including HCM, cardiac amyloidosis and Anderson-Fabry disease. A transient low signal intensity LGE in regions of severe LV dysfunction is a particular feature of stress cardiomyopathy. In arrhythmogenic right ventricular cardiomyopathy/dysplasia, an enhancement of right ventricular (RV) wall with functional and morphological changes of RV becomes apparent. Finally, the analyses of LGE distribution have potentials to predict cardiac outcomes and response to treatments.

  20. Exaggerated cardiovascular effects of cocaine in conscious dogs with pacing-induced dilated cardiomyopathy.

    PubMed

    Mathier, Michael A; Shen, You-Tang; Shannon, Richard P

    2002-12-01

    The aim of this study was to explore the characteristics and mechanisms of the cardiovascular effects of cocaine in dilated cardiomyopathy. We studied the cardiovascular responses to acute intravenous cocaine (1 mg/kg) in 8 conscious, chronically instrumented dogs before and after the development of dilated cardiomyopathy induced by rapid ventricular pacing. To help elucidate the role of altered baroreflex function in mediating the cardiovascular effects of cocaine, we also studied responses in 3 conscious, chronically instrumented dogs that had undergone surgical sinoaortic baroreceptor denervation. Cocaine produced greater increases in heart rate (+57 +/- 8% from 112 +/- 5 beats/min versus +28 +/- 3% from 100 +/- 4 beats/min; P <.01), first derivative of left ventricular pressure (+30 +/- 5% from 1,714 +/- 147 mm Hg/sec versus +15 +/- 3% from 3,032 +/- 199 mm Hg/sec; P <.01), coronary vascular resistance (+28 +/- 5% from 2.3 +/- 0.3 mm Hg/mL/min versus +11 +/- 5% from 2.2 +/- 0.3 mm Hg/mL/min; P <.05) and plasma norepinephrine concentration (+130 +/- 31% from 462 +/- 102 pg/mL versus +86 +/- 32% from 286 +/- 77 pg/mL; P <.05) in dogs with dilated cardiomyopathy as compared to controls. In addition, responses were much more rapid in onset following the development of dilated cardiomyopathy. Chronotropic and inotropic responses to cocaine were similarly rapid and exaggerated in dogs after baroreceptor denervation. Cocaine produces rapid and exaggerated chronotropic, inotropic, and coronary vasoconstrictor responses in conscious dogs with pacing-induced dilated cardiomyopathy. Alterations in arterial baroreflex function may play a role in these observations, which in turn may underlie the clinically observed association between cocaine and heart failure.

  1. Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice.

    PubMed

    Anwar, Md Jamir; Pillai, Krishna K; Khanam, Razia; Akhtar, Mohammad; Vohora, Divya

    2012-06-01

    Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days' pre- and 7 days' post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

  2. Calreticulin Induces Dilated Cardiomyopathy

    PubMed Central

    Lee, Dukgyu; Oka, Tatsujiro; Hunter, Beth; Robinson, Alison; Papp, Sylvia; Nakamura, Kimitoshi; Srisakuldee, Wattamon; Nickel, Barbara E.; Light, Peter E.; Dyck, Jason R. B.; Lopaschuk, Gary D.; Kardami, Elissavet; Opas, Michal; Michalak, Marek

    2013-01-01

    Background Calreticulin, a Ca2+-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart. Methodology/Principal Findings We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca2+ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca2+-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca2+-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin. Conclusions/Significance We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca2+ handling genes, gap junction components and left ventricle remodeling. PMID:23437120

  3. Sickle cell-induced ischemic colitis.

    PubMed

    Stewart, Camille L; Ménard, Geraldine E

    2009-07-01

    Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

  4. Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.

    PubMed

    Lee, Yee-Ki; Lau, Yee-Man; Cai, Zhu-Jun; Lai, Wing-Hon; Wong, Lai-Yung; Tse, Hung-Fat; Ng, Kwong-Man; Siu, Chung-Wah

    2017-07-28

    Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient-specific human induced pluripotent stem cells hold promise to transform precision medicine into real-life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC124 induces translational read-through over the premature stop codon and restores production of the full-length proteins from the affected genes. In this study we generated human induced pluripotent stem cells-derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC124 in LMNA -related cardiomyopathy. We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA -related cardiomyopathy. Interestingly, PTC124 treatment increased the production of full-length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC124 treatment not only reduced nuclear blebbing and electrical stress-induced apoptosis but also improved the excitation-contraction coupling of the affected cardiomyocytes. Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC124 treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. [Myocardial regional thickness in patients with and without cardiomyopathy assessed by cardiac magnetic resonance].

    PubMed

    de Zan, Macarena; Carrascosa, Patricia; Deviggiano, Alejandro; Capuñay, Carlos; Rodríguez-Granillo, Gastón A

    To explore regional differences in myocardial wall thickness (WT) among the most prevalent cardiomyopathies and in individuals without structural heart disease using cardiac magnetic resonance. Patients older than 18 years referred to cardiac magnetic resonance during the period between January 2014 and September 2014, with a diagnosis of hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, ischemic cardiomyopathy, and myocarditis were retrospectively selected from our database. One hundred twenty patients patients were included. The control group had an average WT of 5.9±1.1mm, with a WT index of 2.9±0.8. Significantly lower mean WT in the apical segments were identified in both the control group (basal 6.7±1.3 vs. mid 6.0±1.3 vs. apical 4.6±1.0mm, P<.0001) and in all evaluated cardiomyopathies (hypertrophic cardiomyopathy: basal 10.5±2.4 vs. mid 10.8±2.7 vs. apical 7.3±3.3mm, P<.0001; idiopathic dilated cardiomyopathy: basal 7.7±1.7 vs. mid 7.6±1.3 vs. apical 5.4±1.3mm, P<.0001; ischemic cardiomyopathy: basal 7.4±1.7 vs. mid 7.5±1.9 vs. apical 5.5±1.8mm, P<.0001; myocarditis: basal 7.1±1.5 vs. mid 6.4±1.1 vs. apical 5.1±0.8, P<.0001). Significant gender differences were also evident regarding the mean WT both in the control group (male 6.5±2.1 vs. female 5.2±1.7mm, P<.0001), as in hypertrophic cardiomyopathy (10.5±5.3 vs. 8.5±5.7mm, P<.0001) and myocarditis (6.6±2.0 vs. 5.2±1.6mm, P<.0001). We found a relatively high prevalence of segments commonly deemed thinned among patients without structural heart disease. We also observed a marked asymmetry and longitudinal gradient in wall thickness both in controls and in the various cardiomyopathies evaluated. Copyright © 2016 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

  6. Acidosis mediates recurrent hypoglycemia-induced increase in ischemic brain injury in treated diabetic rats.

    PubMed

    Rehni, Ashish K; Shukla, Vibha; Perez-Pinzon, Miguel A; Dave, Kunjan R

    2018-03-15

    Cerebral ischemia is a serious possible manifestation of diabetic vascular disease. Recurrent hypoglycemia (RH) enhances ischemic brain injury in insulin-treated diabetic (ITD) rats. In the present study, we determined the role of ischemic acidosis in enhanced ischemic brain damage in RH-exposed ITD rats. Diabetic rats were treated with insulin and mild/moderate RH was induced for 5 days. Three sets of experiments were performed. The first set evaluated the effects of RH exposure on global cerebral ischemia-induced acidosis in ITD rats. The second set evaluated the effect of an alkalizing agent (Tris-(hydroxymethyl)-aminomethane: THAM) on ischemic acidosis-induced brain injury in RH-exposed ITD rats. The third experiment evaluated the effect of the glucose transporter (GLUT) inhibitor on ischemic acidosis-induced brain injury in RH-exposed ITD rats. Hippocampal pH and lactate were measured during ischemia and early reperfusion for all three experiments. Neuronal survival in Cornu Ammonis 1 (CA1) hippocampus served as a measure of ischemic brain injury. Prior RH exposure increases lactate concentration and decreases pH during ischemia and early reperfusion when compared to controls. THAM and GLUT inhibitor treatments attenuated RH-induced increase in ischemic acidosis. GLUT inhibitor treatment reduced the RH-induced increase in lactate levels. Both THAM and GLUT inhibitor treatments significantly decreased ischemic damage in RH-exposed ITD rats. Ischemia causes increased acidosis in RH-exposed ITD rats via a GLUT-sensitive mechanism. Exploring downstream pathways may help understand mechanisms by which prior exposure to RH increases cerebral ischemic damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  7. Activation of p38 MAPK participates in brain ischemic tolerance induced by limb ischemic preconditioning by up-regulating HSP 70.

    PubMed

    Sun, Xiao-Cai; Xian, Xiao-Hui; Li, Wen-Bin; Li, Li; Yan, Cai-Zhen; Li, Qing-Jun; Zhang, Min

    2010-08-01

    This study investigates whether activation of p38 MAPK by the up-regulation of HSP 70 participates in the induction of brain ischemic tolerance by limb ischemic preconditioning (LIP). Western blot and immunohistochemical assays indicated that p38 MAPK activation occurred earlier than HSP 70 induction in the CA1 region of the hippocampus after LIP. P-p38 MAPK expression was up-regulated at 6h and reached its peak 12h after LIP, while HSP 70 expression was not significantly increased until 1 day and peaked 2 days after LIP. Neuropathological evaluation by thionin staining showed that quercetin (4 ml/kg, 50mg/kg, intraperitoneal injection), an inhibitor of HSP 70, blocked the protective effect of LIP against delayed neuronal death that is normally induced by lethal brain ischemic insult, indicating that HSP 70 participates in the induction of brain ischemic tolerance by LIP. Furthermore, SB 203580, an inhibitor of HSP 70, inhibited HSP 70 activation in the CA1 region of the hippocampus induced by LIP either with or without the presence of subsequent brain ischemic insult. Based on the above results, it can be concluded that activation of p38 MAPK participates in the brain ischemic tolerance induced by LIP at least partly by the up-regulation of HSP 70 expression. (c) 2010 Elsevier Inc. All rights reserved.

  8. NecroX-7 prevents oxidative stress-induced cardiomyopathy by inhibition of NADPH oxidase activity in rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Joonghoon; Park, Eok; Ahn, Bong-Hyun

    2012-08-15

    Oxidative stress is one of the causes of cardiomyopathy. In the present study, NecroXs, novel class of mitochondrial ROS/RNS scavengers, were evaluated for cardioprotection in in vitro and in vivo model, and the putative mechanism of the cardioprotection of NecroX-7 was investigated by global gene expression profiling and subsequent biochemical analysis. NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced death of H9C2 rat cardiomyocytes at EC{sub 50} = 0.057 μM. In doxorubicin (DOX)-induced cardiomyopathy in rats, NecroX-7 significantly reduced the plasma levels of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) which were increased by DOX treatment (p < 0.05). Microarray analysis revealed thatmore » 21 genes differentially expressed in tBHP-treated H9C2 cells were involved in ‘Production of reactive oxygen species’ (p = 0.022), and they were resolved by concurrent NecroX-7 treatment. Gene-to-gene networking also identified that NecroX-7 relieved cell death through Ncf1/p47phox and Rac2 modulation. In subsequent biochemical analysis, NecroX-7 inhibited NADPH oxidase (NOX) activity by 53.3% (p < 0.001). These findings demonstrate that NecroX-7, in part, provides substantial protection of cardiomyopathy induced by tBHP or DOX via NOX-mediated cell death. -- Highlights: ► NecroX-7 prevented tert-butyl hydroperoxide-induced in vitro cardiac cell death. ► NecroX-7 ameliorated doxorubicin-induced in vivo cardiomyopathy. ► NecroX-7 prevented oxidative stress and necrosis-enriched transcriptional changes. ► NecroX-7 effectively inhibited NADPH oxidase activation. ► Cardioprotection of Necro-7 was brought on by modulation of NADPH oxidase activity.« less

  9. Vitamin C mitigates oxidative/nitrosative stress and inflammation in doxorubicin-induced cardiomyopathy.

    PubMed

    Akolkar, Gauri; da Silva Dias, Danielle; Ayyappan, Prathapan; Bagchi, Ashim K; Jassal, Davinder S; Salemi, Vera Maria Cury; Irigoyen, Maria Claudia; De Angelis, Katia; Singal, Pawan K

    2017-10-01

    Increase in oxidative/nitrosative stress is one of the mechanisms associated with the development of cardiotoxicity due to doxorubicin (Dox), a potent chemotherapy drug. Previously, we reported mitigation of Dox-induced oxidative/nitrosative stress and apoptosis by vitamin C (Vit C) in isolated cardiomyocytes. In the present in vivo study in rats, we investigated the effect of prophylactic treatment with Vit C on Dox-induced apoptosis, inflammation, oxidative/nitrosative stress, cardiac dysfunction, and Vit C transporter proteins. Dox (cumulative dose: 15 mg/kg) in rats reduced systolic and diastolic cardiac function and caused structural damage. These changes were associated with a myocardial increase in reactive oxygen species, reduction in antioxidant enzyme activities, increased expression of apoptotic proteins, and inflammation. Dox also caused an increase in the expression of proapoptotic proteins Bax, Bnip-3, Bak, and caspase-3. An increase in oxidative/nitrosative stress attributable to Dox was indicated by an increase in superoxide, protein carbonyl formation, lipid peroxidation, nitric oxide (NO), NO synthase (NOS) activity, protein nitrosylation, and inducible NOS protein expression. Dox increased the levels of cardiac proinflammatory cytokines TNF-α, IL-1β, and IL-6, whereas the expression of Vit C transporter proteins (sodium-ascorbate cotransporter 2 and glucose transporter 4) was reduced. Prophylactic and concurrent treatment with Vit C prevented all these changes and improved survival in the Vit C + Dox group. Vit C also improved Dox-mediated systolic and diastolic dysfunctions and structural damage. These results suggest a cardioprotective role of Vit C in Dox-induced cardiomyopathy by reducing oxidative/nitrosative stress, inflammation, and apoptosis, as well as improving Vit C transporter proteins. NEW & NOTEWORTHY This in vivo study provides novel data that vitamin C improves cardiac structure and function in doxorubicin-induced cardiomyopathy

  10. Perioperative management of paraganglioma and catecholamine-induced cardiomyopathy in child- a case report and review of the literature.

    PubMed

    Jia, Xixi; Guo, Xiangyang; Zheng, Qing

    2017-10-17

    Paragangliomas are catecholamine-secreting tumors of the paraganglia. Perioperative mortality of children with paraganglioma is high, but preoperative therapy and anesthetic management of paraganglioma resection are controversial in children. The literatures on catecholamine-induced cardiomyopathy are limited to several case reports,with few reports of studies on children. Here we report the anesthetic management of a child with paraganglioma and catecholamine-induced cardiomyopathy, and the possible perioperative anesthesia problems of the paraganglioma resection are discussed. Preoperative and intraoperative anesthetic management of Pheochromocytomas children should follow the same principles as for adults, The most important aspects are the control of blood pressure liability and maintenance of adequate blood volume. Pheochromocytomas patient may have cardiomoyopathy due to myocardial toxicity of excessive circulating catecholamines level. The perioperative management of catecholamine-induced cardiomyopathy should include lowering sympathetic activation by means of α-and β-adrenergic receptor blocker and diuretics administration in case of volume overload.

  11. Stress Induced Cardiomyopathy Triggered by Acute Myocardial Infarction: A Case Series Challenging the Mayo Clinic Definition.

    PubMed

    Christodoulidis, Georgios; Kundoor, Vishwa; Kaluski, Edo

    2017-08-28

    BACKGROUND Various physical and emotional factors have been previously described as triggers for stress induced cardiomyopathy. However, acute myocardial infarction as a trigger has never been reported. CASE REPORT We describe four patients who presented with an acute myocardial infarction, in whom the initial echocardiography revealed wall motion abnormalities extending beyond the coronary distribution of the infarct artery. Of the four patients identified, the mean age was 59 years; three patients were women and two patients had underlying psychiatric history. Electrocardiogram revealed ST elevation in the anterior leads in three patients; QTc was prolonged in all cases. All patients had ≤ moderately elevated troponin. Single culprit lesion was found uniformly in the proximal or mid left anterior descending artery. Initial echocardiography revealed severely reduced ejection fraction with relative sparing of the basal segments, whereas early repeat echocardiography revealed significant improvement in the left ventricular function in all patients. CONCLUSIONS This is the first case series demonstrating that acute myocardial infarction can trigger stress induced cardiomyopathy. Extensive reversible wall motion abnormalities, beyond the ones expected from angiography, accompanied by modest elevation in troponin and marked QTc prolongation, suggest superimposed stress induced cardiomyopathy.

  12. Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy.

    PubMed

    Kim, Hyun Ah; Rhim, Taiyoun; Lee, Minhyung

    2011-07-18

    Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Azithromycin induced hepatocellular toxicity and hepatic encephalopathy in asymptomatic dilated cardiomyopathy

    PubMed Central

    Das, Bidyut Kumar

    2011-01-01

    Azithromycin is a widely used macrolide derivative and has generally been considered to be a very safe medication. Though gastrointestinal symptoms and reversible hearing loss are common, potentially serious side effects including angioedema and cholestatic jaundice occurred in less than one percent of patients. We report a case of asymptomatic dilated cardiomyopathy with Azithromycin induced severe hepatocellular toxicity and hepatic encephalopathy. PMID:22144789

  14. Left ventricular assist device therapy in patients with restrictive and hypertrophic cardiomyopathy.

    PubMed

    Topilsky, Yan; Pereira, Naveen L; Shah, Dipesh K; Boilson, Barry; Schirger, John A; Kushwaha, Sudhir S; Joyce, Lyle D; Park, Soon J

    2011-05-01

    Left ventricular assist device (LVAD) is being increasingly used in patients with end-stage dilated and ischemic cardiomyopathy. There have been no clinical trials addressing the use of LVAD therapy in patients with end-stage heart failure caused by restrictive (RCM) or hypertrophic cardiomyopathy (HCM). The purpose of this study was therefore to analyze the outcome of LVAD therapy in these patients. Eighty-three patients received continuous axial flow LVAD (Heart mate II, Thoratec, Pleasanton, CA) from February 2007 to May 2010 at our institution. We analyzed the baseline characteristics and surgical and long-term impact of LVAD therapy in 8 patients with RCM or HCM and compared their outcomes with the 75 patients with dilated and ischemic cardiomyopathy. Compared with patients with ischemic or dilated cardiomyopathy, patients with RCM and HCM have significantly smaller left ventricular end-diastolic dimensions (52.5±6 mm versus 68.6±8 mm; P<0.0001) and increased thickness of septal (16 [12, 19] mm versus 10[8.5, 11] mm, P=0.0003) and higher left ventricular ejection fraction (21 [20, 36]% versus 17 [15, 22]%; P=0.0009). We found no difference in early mortality (12.5% versus 9.3%, P=0.57) or length of hospital stay (11 [8, 45] days versus 18.5 [12.2, 27.7] days; P=0.51) between the 2 groups. The right atrial pressure was higher (18 [15, 20] mm Hg versus 12 [9, 15] mm Hg, P=0.03), and pump flow was lower (4.3 [3.8, 4.5] L versus 5.2 [4.7, 5.5] L, P=0.001) after LVAD implantation in patients with RCM and HCM. Central venous catheter related infections were more common in patients with RCM and HCM (87.5% versus 44.5%, P=0.006). There was no difference in the total number of blood units transfused. Median (min, max) follow-up duration after LVAD implantation was 166 [1, 1044] days. The 1-year actuarial survival rate was not different between the 2 groups (87.5% [95% confidence interval, 52.9% to 97.8%] versus 73.2 [95% confidence interval, 60% to 85%]; P=0.77). Our

  15. Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant

    PubMed Central

    Kurklinsky, Andrew K.; Chirila, Razvan

    2015-01-01

    Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion. PMID:26664316

  16. Transient Cardiomyopathy and Quadriplegia Induced by Ephedrine Decongestant.

    PubMed

    Snipelisky, David F; Kurklinsky, Andrew K; Chirila, Razvan

    2015-12-01

    Ephedrine decongestant products are widely used. Common side effects include palpitations, nervousness, and headache. More severe adverse reactions include cardiomyopathy and vasospasm. We report the case of an otherwise healthy 37-year-old woman who presented with acute-onset quadriplegia and heart failure. She had a normal chest radiograph on admission, but developed marked pulmonary edema and bilateral effusions the next day. Echocardiography revealed a left ventricular ejection fraction of 0.18 and no obvious intrinsic pathologic condition such as foramen narrowing on spinal imaging. Laboratory screening was positive for methamphetamines in the urine, and the patient admitted to having used, over the past several weeks, multiple ephedrine-containing products for allergy-symptom relief. She was ultimately diagnosed with an acute catecholamine-induced cardiomyopathy and spinal artery vasospasm consequential to excessive use of decongestants. Her symptoms resolved completely with supportive care and appropriate heart-failure management. An echocardiogram 2 weeks after admission showed improvement of the left ventricular ejection fraction to 0.33. Ten months after the event, the patient was entirely asymptomatic and showed further improvement of her ejection fraction to 0.45. To our knowledge, ours is the first report of spinal artery vasospasm resulting in quadriplegia in a human being after ephedrine ingestion.

  17. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis

    PubMed Central

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P.; De Geest, Bart

    2017-01-01

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher (p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold (p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density (p < 0.001) was decreased, interstitial fibrosis was 1.88-fold (p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold (p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower (p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy. PMID:28718833

  18. Coconut Oil Aggravates Pressure Overload-Induced Cardiomyopathy without Inducing Obesity, Systemic Insulin Resistance, or Cardiac Steatosis.

    PubMed

    Muthuramu, Ilayaraja; Amin, Ruhul; Postnov, Andrey; Mishra, Mudit; Jacobs, Frank; Gheysens, Olivier; Van Veldhoven, Paul P; De Geest, Bart

    2017-07-18

    Studies evaluating the effects of high-saturated fat diets on cardiac function are most often confounded by diet-induced obesity and by systemic insulin resistance. We evaluated whether coconut oil, containing C12:0 and C14:0 as main fatty acids, aggravates pressure overload-induced cardiomyopathy induced by transverse aortic constriction (TAC) in C57BL/6 mice. Mortality rate after TAC was higher ( p < 0.05) in 0.2% cholesterol 10% coconut oil diet-fed mice than in standard chow-fed mice (hazard ratio 2.32, 95% confidence interval 1.16 to 4.64) during eight weeks of follow-up. The effects of coconut oil on cardiac remodeling occurred in the absence of weight gain and of systemic insulin resistance. Wet lung weight was 1.76-fold ( p < 0.01) higher in coconut oil mice than in standard chow mice. Myocardial capillary density ( p < 0.001) was decreased, interstitial fibrosis was 1.88-fold ( p < 0.001) higher, and systolic and diastolic function was worse in coconut oil mice than in standard chow mice. Myocardial glucose uptake was 1.86-fold ( p < 0.001) higher in coconut oil mice and was accompanied by higher myocardial pyruvate dehydrogenase levels and higher acetyl-CoA carboxylase levels. The coconut oil diet increased oxidative stress. Myocardial triglycerides and free fatty acids were lower ( p < 0.05) in coconut oil mice. In conclusion, coconut oil aggravates pressure overload-induced cardiomyopathy.

  19. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.

    PubMed

    Drawnel, Faye M; Boccardo, Stefano; Prummer, Michael; Delobel, Frédéric; Graff, Alexandra; Weber, Michael; Gérard, Régine; Badi, Laura; Kam-Thong, Tony; Bu, Lei; Jiang, Xin; Hoflack, Jean-Christophe; Kiialainen, Anna; Jeworutzki, Elena; Aoyama, Natsuyo; Carlson, Coby; Burcin, Mark; Gromo, Gianni; Boehringer, Markus; Stahlberg, Henning; Hall, Benjamin J; Magnone, Maria Chiara; Kolaja, Kyle; Chien, Kenneth R; Bailly, Jacques; Iacone, Roberto

    2014-11-06

    Diabetic cardiomyopathy is a complication of type 2 diabetes, with known contributions of lifestyle and genetics. We develop environmentally and genetically driven in vitro models of the condition using human-induced-pluripotent-stem-cell-derived cardiomyocytes. First, we mimic diabetic clinical chemistry to induce a phenotypic surrogate of diabetic cardiomyopathy, observing structural and functional disarray. Next, we consider genetic effects by deriving cardiomyocytes from two diabetic patients with variable disease progression. The cardiomyopathic phenotype is recapitulated in the patient-specific cells basally, with a severity dependent on their original clinical status. These models are incorporated into successive levels of a screening platform, identifying drugs that preserve cardiomyocyte phenotype in vitro during diabetic stress. In this work, we present a patient-specific induced pluripotent stem cell (iPSC) model of a complex metabolic condition, showing the power of this technique for discovery and testing of therapeutic strategies for a disease with ever-increasing clinical significance. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Anabolic steroids abuse-induced cardiomyopathy and ischaemic stroke in a young male patient.

    PubMed

    Shamloul, Reham Mohammed; Aborayah, Ahmed Fathy; Hashad, Assem; Abd-Allah, Foad

    2014-02-26

    We report a case of a 37-year-old man presented with acute stroke and hepatorenal impairment which were associated with anabolic-androgenic steroids (AAS) abuse over 2 years. Despite the absence of apparent symptoms and signs of congestive heart failure at presentation, an AAS-induced dilated cardiomyopathy with multiple thrombi in the left ventricle was attributed to be the underlying cause of his condition. Awareness of the complications of AAS led to the prompt treatment of the initially unrecognised dilated cardiomyopathy, and improved the liver and kidney functions. However, the patient was exposed to a second severe ischaemic event, which led to his death. This unique and complex presentation of AAS complications opens for better recognition and treatment of their potentially fatal effects.

  1. Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis.

    PubMed

    Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

    2015-01-06

    Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX's cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may

  2. Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

    PubMed Central

    Hao, Enkui; Mukhopadhyay, Partha; Cao, Zongxian; Erdélyi, Katalin; Holovac, Eileen; Liaudet, Lucas; Lee, Wen-Shin; Haskó, György; Mechoulam, Raphael; Pacher, Pál

    2015-01-01

    Doxorubicin (DOX) is a widely used, potent chemotherapeutic agent; however, its clinical application is limited because of its dose-dependent cardiotoxicity. DOX’s cardiotoxicity involves increased oxidative/nitrative stress, impaired mitochondrial function in cardiomyocytes/endothelial cells and cell death. Cannabidiol (CBD) is a nonpsychotropic constituent of marijuana, which is well tolerated in humans, with antioxidant, antiinflammatory and recently discovered antitumor properties. We aimed to explore the effects of CBD in a well-established mouse model of DOX-induced cardiomyopathy. DOX-induced cardiomyopathy was characterized by increased myocardial injury (elevated serum creatine kinase and lactate dehydrogenase levels), myocardial oxidative and nitrative stress (decreased total glutathione content and glutathione peroxidase 1 activity, increased lipid peroxidation, 3-nitrotyrosine formation and expression of inducible nitric oxide synthase mRNA), myocardial cell death (apoptotic and poly[ADP]-ribose polymerase 1 [PARP]-dependent) and cardiac dysfunction (decline in ejection fraction and left ventricular fractional shortening). DOX also impaired myocardial mitochondrial biogenesis (decreased mitochondrial copy number, mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-alpha, peroxisome proliferator-activated receptor alpha, estrogen-related receptor alpha), reduced mitochondrial function (attenuated complex I and II activities) and decreased myocardial expression of uncoupling protein 2 and 3 and medium-chain acyl-CoA dehydrogenase mRNA. Treatment with CBD markedly improved DOX-induced cardiac dysfunction, oxidative/nitrative stress and cell death. CBD also enhanced the DOX-induced impaired cardiac mitochondrial function and biogenesis. These data suggest that CBD may represent a novel cardioprotective strategy against DOX-induced cardiotoxicity, and the above-described effects on mitochondrial function and biogenesis may

  3. Changes in Implantation Patterns and Therapy Rates of Implantable Cardioverter Defibrillators over Time in Ischemic and Dilated Cardiomyopathy Patients.

    PubMed

    Vandenberk, Bert; Garweg, Christophe; Voros, Gabor; Floré, Vincent; Marynissen, Thomas; Sticherling, Christian; Zabel, Markus; Ector, Joris; Willems, Rik

    2016-08-01

    Clinical guidelines on implantable cardioverter defibrillator (ICD) therapy changed significantly in the last decades with potential inherent effects on therapy efficacy. We aimed to study therapy rates in time and the association between therapies and mortality. All patients receiving an ICD, primary and secondary prevention, were included in a single-center retrospective registry. Information on first appropriate and inappropriate therapies was documented. Dates of implant were divided in P1: 1996-2001, P2: 2002-2008, and P3: 2009-2014. A total of 727 patients, 84.9% male-66.4% ischemic cardiomyopathy (ICM)-56% primary prevention-mean follow-up 5.2 ± 4.1 years, were included. There was a shift from secondary to primary prevention indications, from ischemic to non-ICM, and from single chamber to cardiac resynchronization therapy defibrillator devices. The annual 1- and 3-year appropriate shock (AS) rate declined from 29.4% and 15.1% in P1, over 13.3% and 9.2% in P2 to 7.8% and 5.7% in P3 (log-rank P < 0.001), while inappropriate shock (IAS) rates remained unchanged (log-rank P = 0.635). After multivariate regression analysis a higher age at implant, lower left ventricular ejection fraction, history of stroke, diabetes mellitus, intake of loop diuretics or digitalis, higher creatinine, and longer QTc were independent predictors of mortality. These changes in clinical practice with a shift to primary prevention and rise in non-ICM implants caused a significant decrease in AS incidence, while IAS remained stable. Receiving AS or IAS was not an independent predictor of mortality in our real-life cohort. © 2016 Wiley Periodicals, Inc.

  4. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis.

    PubMed

    Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

    2011-11-01

    Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke.

  5. Cardiorespiratory and cardiovascular interactions in cardiomyopathy patients using joint symbolic dynamic analysis.

    PubMed

    Giraldo, Beatriz F; Rodriguez, Javier; Caminal, Pere; Bayes-Genis, Antonio; Voss, Andreas

    2015-01-01

    Cardiovascular diseases are the first cause of death in developed countries. Using electrocardiographic (ECG), blood pressure (BP) and respiratory flow signals, we obtained parameters for classifying cardiomyopathy patients. 42 patients with ischemic (ICM) and dilated (DCM) cardiomyopathies were studied. The left ventricular ejection fraction (LVEF) was used to stratify patients with low risk (LR: LVEF>35%, 14 patients) and high risk (HR: LVEF≤ 35%, 28 patients) of heart attack. RR, SBP and TTot time series were extracted from the ECG, BP and respiratory flow signals, respectively. The time series were transformed to a binary space and then analyzed using Joint Symbolic Dynamic with a word length of three, characterizing them by the probability of occurrence of the words. Extracted parameters were then reduced using correlation and statistical analysis. Principal component analysis and support vector machines methods were applied to characterize the cardiorespiratory and cardiovascular interactions in ICM and DCM cardiomyopathies, obtaining an accuracy of 85.7%.

  6. Lubiprostone induced ischemic colitis.

    PubMed

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-14

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding.

  7. Lubiprostone induced ischemic colitis

    PubMed Central

    Sherid, Muhammed; Sifuentes, Humberto; Samo, Salih; Deepak, Parakkal; Sridhar, Subbaramiah

    2013-01-01

    Ischemic colitis accounts for 6%-18% of the causes of acute lower gastrointestinal bleeding. It is often multifactorial and more commonly encountered in the elderly. Several medications have been implicated in the development of colonic ischemia. We report a case of a 54-year old woman who presented with a two-hour history of nausea, vomiting, abdominal pain, and bloody stool. The patient had recently used lubiprostone with close temporal relationship between the increase in the dose and her symptoms of rectal bleeding. The radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her condition improved without any serious complications after the cessation of lubiprostone. This is the first reported case of ischemic colitis with a clear relationship with lubiprostone (Naranjo score of 10). Clinical vigilance for ischemic colitis is recommended for patients receiving lubiprostone who are presenting with abdominal pain and rectal bleeding. PMID:23345954

  8. Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

    PubMed

    Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

    2014-01-01

    We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

  9. Geometric differences of the mitral apparatus between ischemic and dilated cardiomyopathy with significant mitral regurgitation: real-time three-dimensional echocardiography study

    NASA Technical Reports Server (NTRS)

    Kwan, Jun; Shiota, Takahiro; Agler, Deborah A.; Popovic, Zoran B.; Qin, Jian Xin; Gillinov, Marc A.; Stewart, William J.; Cosgrove, Delos M.; McCarthy, Patrick M.; Thomas, James D.

    2003-01-01

    BACKGROUND: This study was conducted to elucidate the geometric differences of the mitral apparatus in patients with significant mitral regurgitation caused by ischemic cardiomyopathy (ICM-MR) and by idiopathic dilated cardiomyopathy (DCM-MR) by use of real-time 3D echocardiography (RT3DE). METHODS AND RESULTS: Twenty-six patients with ICM-MR caused by posterior infarction, 18 patients with DCM-MR, and 8 control subjects were studied. With the 3D software, commissure-commissure plane and 3 perpendicular anteroposterior (AP) planes were generated for imaging the medial, central, and lateral sides of the mitral valve (MV) during mid systole. In 3 AP planes, the angles between the annular plane and each leaflet (anterior, Aalpha; posterior, Palpha) were measured. In ICM-MR, Aalpha measured in the medial and central planes was significantly larger than that in the lateral plane (39+/-5 degrees, 34+/-6 degrees, and 27+/-5 degrees, respectively; P<0.01), whereas Palpha showed no significant difference in any of the 3 AP planes (61+/-7 degrees, 57+/-7 degrees, and 56+/-7 degrees, P>0.05). In DCM-MR, both Aalpha (38+/-8 degrees, 37+/-9 degrees, and 36+/-7 degrees, P>0.05) and Palpha (59+/-6 degrees, 58+/-5 degrees, and 57+/-6 degrees, P>0.05) revealed no significant differences in the 3 planes. CONCLUSIONS: The pattern of MV deformation from the medial to the lateral side was asymmetrical in ICM-MR, whereas it was symmetrical in DCM-MR. RT3DE is a helpful tool for differentiating the geometry of the mitral apparatus between these 2 different types of functional mitral regurgitation.

  10. Usefulness of cardiac resynchronization therapy in the management of Doxorubicin-induced cardiomyopathy.

    PubMed

    Ajijola, Olujimi A; Nandigam, K Veena; Chabner, Bruce A; Orencole, Mary; Dec, G William; Ruskin, Jeremy N; Singh, Jagmeet P

    2008-05-01

    Doxorubicin is a widely used antineoplastic agent that may cause irreversible dilated cardiomyopathy. Doxorubicin-induced cardiomyopathy (DIC) can occur several years after exposure and carries a poor prognosis. Although cardiac resynchronization therapy (CRT) is a useful intervention in end-stage heart failure unresponsive to optimal medical therapies, its efficacy in DIC remains unknown. Four consecutive patients receiving CRT for DIC were evaluated before and after CRT. CRT resulted in improvements in the mean left ventricular ejection fraction at 1 month from 21+/-4.7% to 34+/-5% (p=0.03) and at 6 months (to 46+/-7.5%, p=0.01). CRT-induced reverse remodeling was observed, with a mean reduction in left ventricular internal diameter at end-diastole from 54.75+/-3.7 to 52.5+/-1.9 mm at 1 month (p=0.06) and further to 47+/-2.3 mm at 6 months (p=0.03). All patients experienced reductions in heart failure symptoms and improvements in New York Heart Association functional class (p<0.05). The impact of CRT was sustained over a follow-up of 18.5+/-3.5 months. In conclusion, this study suggests that patients with DIC, refractory to optimal pharmacologic therapy and meeting criteria for resynchronization device implantation, may achieve sustained benefit from CRT.

  11. Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis

    PubMed Central

    Rink, Cameron; Christoforidis, Greg; Khanna, Savita; Peterson, Laura; Patel, Yojan; Khanna, Suchin; Abduljalil, Amir; Irfanoglu, Okan; Machiraju, Raghu; Bergdall, Valerie K; Sen, Chandan K

    2011-01-01

    Vitamin E consists of tocopherols and tocotrienols, in which α-tocotrienol is the most potent neuroprotective form that is also effective in protecting against stroke in rodents. As neuroprotective agents alone are insufficient to protect against stroke, we sought to test the effects of tocotrienol on the cerebrovascular circulation during ischemic stroke using a preclinical model that enables fluoroscopy-guided angiography. Mongrel canines (mean weight=26.3±3.2 kg) were supplemented with tocotrienol-enriched (TE) supplement (200 mg b.i.d, n=11) or vehicle placebo (n=9) for 10 weeks before inducing transient middle cerebral artery (MCA) occlusion. Magnetic resonance imaging was performed 1 hour and 24 hours post reperfusion to assess stroke-induced lesion volume. Tocotrienol-enriched supplementation significantly attenuated ischemic stroke-induced lesion volume (P<0.005). Furthermore, TE prevented loss of white matter fiber tract connectivity after stroke as evident by probabilistic tractography. Post hoc analysis of cerebral angiograms during MCA occlusion revealed that TE-supplemented canines had improved cerebrovascular collateral circulation to the ischemic MCA territory (P<0.05). Tocotrienol-enriched supplementation induced arteriogenic tissue inhibitor of metalloprotease 1 and subsequently attenuated the activity of matrix metalloproteinase-2. Outcomes of the current preclinical trial set the stage for a clinical trial testing the effects of TE in patients who have suffered from transient ischemic attack and are therefore at a high risk for stroke. PMID:21673716

  12. Ergotamine-Induced Takotsubo Cardiomyopathy.

    PubMed

    Ozpelit, Ebru; Ozpelit, Mehmet E; Akdeniz, Bahri; Göldeli, Özhan

    2016-01-01

    Takotsubo cardiomyopathy (TC) is a recently increasing diagnosed disease showed by transient apical or mid-apical left ventricular dysfunction. It is known as a disease of postmenopausal women, which is usually triggered by emotional or physical stress. Although the trigger is mostly endogenous, some drugs have also been reported as the cause. Published case reports of TC associated with drug usage consist of sympathomimetic drugs, inotropic agents, thyroid hormone, cocaine, and 5-fluorouracil. We present an unusual case of TC in which the possible trigger is ergotamine toxicity.

  13. Comparative Efficacy of Nebivolol and Metoprolol to Prevent Tachycardia-Induced Cardiomyopathy in a Porcine Model.

    PubMed

    Nazeri, Alireza; Elayda, MacArthur A; Segura, Ana Maria; Stainback, Raymond F; Nathan, Joanna; Lee, Vei-Vei; Bove, Christina; Sampaio, Luiz; Grace, Brian; Massumi, Ali; Razavi, Mehdi

    2016-12-01

    Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model. Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were obtained at baseline and at the end of the study. At the end of week 8, the pigs were euthanized, and complete histopathologic studies were performed. All the pigs developed left ventricular cardiomyopathy but remained hemodynamically stable and survived to the end of the study. The mean left ventricular ejection fraction decreased from baseline by 34%, 20%, and 20% in the nebivolol, metoprolol, and placebo groups, respectively. These changes did not differ significantly among the 3 groups ( P =0.51). Histopathologic analysis revealed mild left ventricular perivascular fibrosis with cardiomyocyte hypertrophy in 14 of the 15 pigs. Both nebivolol and metoprolol failed to prevent cardiomyopathy in our animal model of persistent tachycardia and a high catecholamine state.

  14. Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy

    PubMed Central

    Zhang, Bin; Shen, Qiang; Chen, Yaping; Pan, Ruile; Kuang, Shihuan; Liu, Guiyan; Sun, Guibo; Sun, Xiaobo

    2017-01-01

    Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM. PMID:28287141

  15. Initial clinical experience of real-time three-dimensional echocardiography in patients with ischemic and idiopathic dilated cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Shiota, T.; McCarthy, P. M.; White, R. D.; Qin, J. X.; Greenberg, N. L.; Flamm, S. D.; Wong, J.; Thomas, J. D.

    1999-01-01

    The geometry of the left ventricle in patients with cardiomyopathy is often sub-optimal for 2-dimensional ultrasound when assessing left ventricular (LV) function and localized abnormalities such as a ventricular aneurysm. The aim of this study was to report the initial experience of real-time 3-D echocardiography for evaluating patients with cardiomyopathy. A total of 34 patients were evaluated with the real-time 3D method in the operating room (n = 15) and in the echocardiographic laboratory (n = 19). Thirteen of 28 patients with cardiomyopathy and 6 other subjects with normal LV function were evaluated by both real-time 3-D echocardiography and magnetic resonance imaging (MRI) for obtaining LV volumes and ejection fractions for comparison. There were close relations and agreements for LV volumes (r = 0.98, p <0.0001, mean difference = -15 +/- 81 ml) and ejection fractions (r = 0.97, p <0.0001, mean difference = 0.001 +/- 0.04) between the real-time 3D method and MRI when 3 cardiomyopathy cases with marked LV dilatation (LV end-diastolic volume >450 ml by MRI) were excluded. In these 3 patients, 3D echocardiography significantly underestimated the LV volumes due to difficulties with imaging the entire LV in a 60 degrees x 60 degrees pyramidal volume. The new real-time 3D echocardiography is feasible in patients with cardiomyopathy and may provide a faster and lower cost alternative to MRI for evaluating cardiac function in patients.

  16. Diffuse fibrosis leads to a decrease in unipolar voltage: Validation in a swine model of premature ventricular contraction-induced cardiomyopathy.

    PubMed

    Tanaka, Yasuaki; Rahmutula, Dolkun; Duggirala, Srikant; Nazer, Babak; Fang, Qizhi; Olgin, Jeffrey; Sievers, Richard; Gerstenfeld, Edward P

    2016-02-01

    Frequent premature ventricular contractions (PVCs) may lead to dilated cardiomyopathy. A leftward shift in the unipolar voltage distribution in patients with cardiomyopathy has also been described and attributed to increased fibrosis. We established a swine model of PVC-induced cardiomyopathy and assessed (1) whether an increase in left ventricular fibrosis occurs and (2) whether increased fibrosis leads to a leftward shift in the unipolar voltage distribution. Ten swine underwent implantation of ventricular pacemakers; 6 programmed to deliver a 50% PVC burden and 4 controls without pacing. Voltage maps were acquired at baseline and after 14 weeks of ventricular bigeminy. In the PVC group, left ventricular ejection fraction decreased from 67% ± 7% to 44% ± 15% (P < .05) with no change in controls (71% ± 6% to 73% ± 4%; P = .56). The fifth percentile of the bipolar and unipolar voltage distribution at baseline was 1.63 and 5.36 mV, respectively. In the control group, after 14 weeks of pacing there was no significant change in % bipolar voltage <1.5 mV (pre 1.2% vs post 2.2%; P = .34) or % unipolar voltage <5.5 mV (pre 4.0% vs post 3.5%; P = .20). In the PVC group, there was a significant increase in % unipolar voltage <5.5 mV (5.4% vs 12.6%; P < .01), with a leftward shift in the unipolar voltage distribution. Histologically, % fibrosis was increased in the PVC group (control 1.8% ± 1.3% vs PVC 3.4% ± 2.6%; P < .01). PVC-induced cardiomyopathy in swine leads to an increase in interstitial fibrosis and a leftward shift in the unipolar voltage distribution. These findings are consistent with findings in humans with PVC-induced cardiomyopathy. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  17. Cardiomyopathy Induced by Pulmonary Sequestration in a 50-Year-Old Man

    PubMed Central

    Chatelain, Shaun; Comp, Robert A.; Grace, R. Randal

    2015-01-01

    A 50-year-old black man presented at the emergency department with midsternal, nonradiating chest pressure and chronic dyspnea on exertion. Four years before the current admission, he had been diagnosed with nonischemic cardiomyopathy at another facility. After our complete evaluation, we suspected that his symptoms arose from left-to-left shunting in association with pulmonary sequestration, a congenital malformation. Our preliminary diagnosis of secondary dilated cardiomyopathy was confirmed by normalization of the patient's ventricular size and function after lobectomy. To our knowledge, this patient is the oldest on record to present with cardiomyopathy consequent to pulmonary sequestration. His case is highly unusual because of his age and the rapid resolution of his symptoms after lobectomy. We believe that pulmonary sequestration should be included in the differential diagnosis of dilated cardiomyopathy. PMID:25873803

  18. Sahlgrenska Cardiomyopathy Project

    ClinicalTrials.gov

    2018-05-15

    Dilated Cardiomyopathies; Hypertrophic Cardiomyopathy; Restrictive Cardiomyopathy; Arrhythmogenic Right Ventricular Cardiomyopathy; Myocarditis; Sarcoidosis With Myocarditis; Giant Cell Myocarditis; Amyloidosis; Heart (Manifestation)

  19. Metallothionein as a compensatory component prevents intermittent hypoxia-induced cardiomyopathy in mice

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yin, Xia; Zhou, Shanshan; KCHRI at the Department of Pediatrics, School of Medicine, University of Louisville, Louisville, 40202

    Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (IH) to induce cardiovascular disease, which may be related to oxidative damage. Metallothionein (MT) has been extensively proved to be an endogenous and highly inducible antioxidant protein expressed in the heart. Therefore, we tested the hypotheses that oxidative stress plays a critical role in OSA induced cardiac damage and MT protects the heart from OSA-induced cardiomyopathy. To mimic hypoxia/reoxygenation events that occur in adult OSA patients, mice were exposed to IH for 3 days to 8 weeks. The IH paradigm consisted of alternating cycles of 20.9% O{sub 2}/8% O{sub 2} F{sub I}O{submore » 2} (30 episodes per hour) with 20 s at the nadir F{sub I}O{sub 2} for 12 h a day during daylight. IH significantly increased the ratio of heart weight to tibia length at 4 weeks with a decrease in cardiac function from 4 to 8 weeks. Cardiac oxidative damage and fibrosis were observed after 4 and 8 weeks of IH exposures. Endogenous MT expression was up-regulated in response to 3-day IH, but significantly decreased at 4 and 8 weeks of IH. In support of MT as a major compensatory component, mice with cardiac overexpression of MT gene and mice with global MT gene deletion were completely resistant, and highly sensitive, respectively, to chronic IH induced cardiac effects. These findings suggest that chronic IH induces cardiomyopathy characterized by oxidative stress-mediated cardiac damage and the antioxidant MT protects the heart from such pathological and functional changes. - Highlights: • The effect of intermittent hypoxia (IH) on cardiac metallothionein (MT) • Cardiac MT expression was up-regulated in response to 3-day IH. • Exposure to 4- or 8-week IH downregulated cardiac MT expression. • Overexpression of cardiac MT protects from IH-induced cardiac damage. • Global deletion of MT gene made the heart more sensitive to IH damage.« less

  20. An open-label dose escalation study to evaluate the safety of administration of nonviral stromal cell-derived factor-1 plasmid to treat symptomatic ischemic heart failure.

    PubMed

    Penn, Marc S; Mendelsohn, Farrell O; Schaer, Gary L; Sherman, Warren; Farr, Maryjane; Pastore, Joseph; Rouy, Didier; Clemens, Ruth; Aras, Rahul; Losordo, Douglas W

    2013-03-01

    Preclinical studies indicate that adult stem cells induce tissue repair by activating endogenous stem cells through the stromal cell-derived factor-1:chemokine receptor type 4 axis. JVS-100 is a DNA plasmid encoding human stromal cell-derived factor-1. We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in subjects with ischemic cardiomyopathy to see if JVS-100 improves clinical parameters. Seventeen subjects with ischemic cardiomyopathy, New York Heart Association class III heart failure, with an ejection fraction ≤40% on stable medical therapy, were enrolled to receive 5, 15, or 30 mg of JVS-100 via endomyocardial injection. The primary end points for safety and efficacy were at 1 and 4 months, respectively. The primary safety end point was a major adverse cardiac event. Efficacy end points were change in quality of life, New York Heart Association class, 6-minute walk distance, single photon emission computed tomography, N-terminal pro-brain natruretic peptide, and echocardiography at 4 and 12 months. The primary safety end point was met. At 4 months, all of the cohorts demonstrated improvements in 6-minute walk distance, quality of life, and New York Heart Association class. Subjects in the 15- and 30-mg dose groups exhibited improvements in 6-minute walk distance (15 mg: median [range]: 41 minutes [3-61 minutes]; 30 mg: 31 minutes [22-74 minutes]) and quality of life (15 mg: -16 points [+1 to -32 points]; 30 mg: -24 points [+17 to -38 points]) over baseline. At 12 months, improvements in symptoms were maintained. These data highlight the importance of defining the molecular mechanisms of stem cell-based tissue repair and suggest that overexpression of stromal cell-derived factor-1 via gene therapy is a strategy for improving heart failure symptoms in patients with ischemic cardiomyopathy.

  1. Graft survival after cardiac transplantation for alcohol cardiomyopathy.

    PubMed

    Brinkley, D Marshall; Novak, Eric; Topkara, Veli K; Geltman, Edward M

    2014-08-27

    Alcohol cardiomyopathy (ACM) constitutes up to 40% of patients with non-ischemic dilated cardiomyopathy. Transplant-free survival is worse for patients with ACM versus idiopathic dilated cardiomyopathy (IDCM) with continued exposure. The prognosis for patients with ACM after cardiac transplantation is unknown. We evaluated adults who underwent single-organ, cardiac transplantation from 1994 to 2009 with a diagnosis of ACM (n=134) or IDCM (n=10,243) in the Organ Procurement Transplantation Network registry. Kaplan-Meier curves were generated by cohort for time until graft failure, cardiac allograft vasculopathy, and hospitalization for rejection. A Cox proportional hazards model was created to determine factors associated with each outcome. Patients with ACM were more likely to be males (P<0.0001), minorities (P<0.0001), and smokers (P=0.0310) compared with IDCM. Overall graft survival was lower for the ACM cohort (P=0.0001). After multivariate analysis, ACM was not independently associated with graft survival (HR 1.341, 95% CI 0.944-1.906, P=0.1017). Creatinine, total bilirubin, minority ethnicity, graft under-sizing, life support, diabetes, and donor age were independent predictors of graft failure. There were no significant differences between primary cause of death, vasculopathy, or rejection. There was no association between ACM and graft survival in this large registry study, but poorer overall survival in the ACM cohort was associated with other recipient characteristics.

  2. A left ventricular epicardial to right ventricular endocardial dominant frequency gradient exists in human ventricular fibrillation.

    PubMed

    Torres, Jose Luis; Shah, Bindi K; Greenberg, Richard M; Deger, Florin Titus; Gerstenfeld, Edward P

    2010-10-01

    We hypothesized that in patients with left ventricular dysfunction undergoing implant of a biventricular ICD, the local dominant frequency during early induced ventricular fibrillation would be higher at an epicardial left ventricular position compared to an endocardial right ventricular position. Patients undergoing implant of a biventricular ICD were studied. During ventricular fibrillation induction, bipolar electrograms were recorded from leads at an epicardial left ventricular position and an endocardial right ventricular position. Overlapping 2-s fast Fourier transforms were obtained for 6 s of ventricular fibrillation. The dominant frequency and organizational index were compared. Thirty-four patients (20 men, age 64 ± 11 years) underwent 57 inductions of ventricular fibrillation. Eighteen patients had non-ischemic dilated cardiomyopathy and 16 had ischemic dilated cardiomyopathy. The dominant frequency was higher at a lateral epicardial left ventricular position than an apical endocardial right ventricular position in 18 patients with non-ischemic dilated cardiomyopathy (LV epicardial 5.34 ± 0.37 Hz, RV endocardial 5.09 ± 0.41 Hz, p < 0.001), but not in 16 patients with ischemic dilated cardiomyopathy (LV epicardial 4.99 ± 0.57 Hz, RV epicardial 4.87 ± 0.65 Hz, p = 0.094). In patients with non-ischemic dilated cardiomyopathy, there is a dominant frequency gradient during early ventricular fibrillation induced at ICD testing from the lateral left ventricular epicardium to the apical right ventricular endocardium.

  3. Takotsubo cardiomyopathy post liver transplantation.

    PubMed

    Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

    2016-10-23

    A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

  4. Equivalent cardioprotection induced by ischemic and hypoxic preconditioning.

    PubMed

    Xiang, Xujin; Lin, Haixia; Liu, Jin; Duan, Zeyan

    2013-04-01

    We aimed to compare cardioprotection induced by various hypoxic preconditioning (HPC) and ischemic preconditioning (IPC) protocols. Isolated rat hearts were randomly divided into 7 groups (n = 7 per group) and received 3 or 5 cycles of 3-minute ischemia or hypoxia followed by 3-minute reperfusion (IPC33 or HPC33 or IPC53 or HPC53 group), 3 cycles of 5-minute ischemia or hypoxia followed by 5-minute reperfusion (IPC35 group or HPC35 group), or 30-minute perfusion (ischemic/reperfusion group), respectively. Then all the hearts were subjected to 50-minute ischemia and 120-minute reperfusion. Cardiac function, infarct size, and coronary flow rate (CFR) were evaluated. Recovery of cardiac function and CFR in IPC35, HPC35, and HPC53 groups was significantly improved as compared with I/R group (p < 0.01). There were no significant differences in cardiac function parameters between IPC35 and HPC35 groups. Consistently, infarct size was significantly reduced in IPC35, HPC35, and HPC53 groups compared with ischemic/reperfusion group. Multiple-cycle short duration HPC exerted cardioprotection, which was as powerful as that of IPC. Georg Thieme Verlag KG Stuttgart · New York.

  5. Left Ventricular Thrombus as a Complication of Clozapine-Induced Cardiomyopathy: A Case Report and Brief Literature Review.

    PubMed

    Malik, Shahbaz A; Malik, Sarah; Dowsley, Taylor F; Singh, Balwinder

    2015-01-01

    A 48-year-old male with history of schizoaffective disorder on clozapine presented with chest pain, dyspnea, and new left bundle branch block. He underwent coronary angiography, which revealed no atherosclerosis. The patient's workup was unrevealing for a cause for the cardiomyopathy and thus it was thought that clozapine was the offending agent. The patient was taken off clozapine and started on guideline directed heart failure therapy. During the course of hospitalization, he was also discovered to have a left ventricular (LV) thrombus for which he received anticoagulation. To our knowledge, this is the first case report of clozapine-induced cardiomyopathy complicated by a LV thrombus.

  6. Impact of Shocks on Mortality in Patients with Ischemic or Dilated Cardiomyopathy and Defibrillators Implanted for Primary Prevention

    PubMed Central

    Streitner, Florian; Herrmann, Thomas; Kuschyk, Juergen; Lang, Siegfried; Doesch, Christina; Papavassiliu, Theano; Streitner, Ines; Veltmann, Christian; Haghi, Dariusch; Borggrefe, Martin

    2013-01-01

    Background Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM), the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM) or DCM and defibrillators (ICD) implanted for primary prevention. Methods and Results Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%). During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2%) experienced ≥1 appropriate and 51 out of 561 patients (9.1%) ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects). Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96–2.28, log rank p = 0.072). The effect was significant in ICM patients (HR 1.61, 95% CI 1.00–2.59, log rank p = 0.049) but not in DCM patients (HR 1.03, 95% CI 0.36–2.96, log rank p = 0.96). Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24–3.63, p = 0.005). The effect was driven by ICM patients (HR 2.48, 95% CI 1.41–4.37, p = 0.001), as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083–4.75, p = 0.65). Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns). Conclusion Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within

  7. Impact of shocks on mortality in patients with ischemic or dilated cardiomyopathy and defibrillators implanted for primary prevention.

    PubMed

    Streitner, Florian; Herrmann, Thomas; Kuschyk, Juergen; Lang, Siegfried; Doesch, Christina; Papavassiliu, Theano; Streitner, Ines; Veltmann, Christian; Haghi, Dariusch; Borggrefe, Martin

    2013-01-01

    Emerging interest is seen in the paradox of defibrillator shocks for ventricular tachyarrhythmia and increased mortality risk. Particularly in patients with dilated cardiomyopathy (DCM), the prognostic importance of shocks is unclear. The purpose of this study was to compare the outcome after shocks in patients with ischemic cardiomyopathy (ICM) or DCM and defibrillators (ICD) implanted for primary prevention. Data of 561 patients were analyzed (mean age 68.6±10.6 years, mean left ventricular ejection fraction 28.6±7.3%). During a median follow-up of 49.3 months, occurrence of device therapies and all-cause mortality were recorded. 74 out of 561 patients (13.2%) experienced ≥1 appropriate and 51 out of 561 patients (9.1%) ≥1 inappropriate shock. All-cause mortality was 24.2% (136 out of 561 subjects). Appropriate shock was associated with a trend to higher mortality in the overall patient population (HR 1.48, 95% CI 0.96-2.28, log rank p = 0.072). The effect was significant in ICM patients (HR 1.61, 95% CI 1.00-2.59, log rank p = 0.049) but not in DCM patients (HR 1.03, 95% CI 0.36-2.96, log rank p = 0.96). Appropriate shocks occurring before the median follow-up revealed a much stronger impact on mortality (HR for the overall patient population 2.12, 95% CI 1.24-3.63, p = 0.005). The effect was driven by ICM patients (HR 2.48, 95% CI 1.41-4.37, p = 0.001), as appropriate shocks again did not influence survival of DCM patients (HR 0.63, 95% CI 0.083-4.75, p = 0.65). Appropriate shocks occurring after the median follow-up and inappropriate shocks occurring at any time revealed no impact on survival in any of the groups (p = ns). Appropriate shocks are associated with reduced survival in patients with ICM but not in patients with DCM and ICDs implanted for primary prevention. Furthermore, the negative effect of appropriate shocks on survival in ICM patients is only evident within the first 4 years after device implantation.

  8. Prediction and prognosis of ventricular tachycardia recurrence after catheter ablation with remote magnetic navigation for electrical storm in patients with ischemic cardiomyopathy.

    PubMed

    Jin, Qi; Jacobsen, Peter Karl; Pehrson, Steen; Chen, Xu

    2017-11-01

    Ventricular tachycardia (VT) recurrence after catheter ablation for electrical storm is commonly seen in patients with ischemic cardiomyopathy (ICM). We hypothesized that VT recurrence can be predicted and be related to the all-cause death after VT storm ablation guided by remote magnetic navigation (RMN) in patients with ICM. A total of 54 ICM patients (87% male; mean age, 65 ± 7.1 years) presenting with VT storm undergoing acute ablation using RMN were enrolled. Acute complete ablation success was defined as noninducibility of any sustained monomorphic VT at the end of the procedure. Early VT recurrence was defined as the occurrence of sustained VT within 1 month after the first ablation. After a mean follow-up of 17.1 months, 27 patients (50%) had freedom from VT recurrence. Sustained VT recurred in 12 patients (22%) within 1 month following the first ablation. In univariate analysis, VT recurrence was associated with incomplete procedural success (hazard ratio [HR]: 6.25, 95% confidence interval [CI]: 1.20-32.47, P = 0.029), lack of amiodarone usage before ablation (HR: 4.71, 95% CI: 1.12-19.7, P = 0.034), and a longer procedural time (HR: 1.023, 95% CI: 1.00-1.05, P = 0.05). The mortality of patients with early VT recurrence was higher than that of patients without recurrence (P < 0.01). Inducibility of any VT at the end of procedure for VT storm guided by RMN is the strongest predictor of VT recurrence. ICM patients who have early recurrences after VT storm ablation are at high risk of all-cause death. © 2017 Wiley Periodicals, Inc.

  9. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats

    EPA Science Inventory

    Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loa...

  10. Ischemic conditioning-induced endogenous brain protection: Applications Pre-, Per- or Post-Stroke

    PubMed Central

    Wang, Yuechun; Reis, Cesar; Applegate, Richard; Stier, Gary; Martin, Robert; Zhang, John H.

    2015-01-01

    In the area of brain injury and neurodegenerative diseases, a plethora of experimental and clinical evidence strongly indicates the promise of therapeutically exploiting the endogenous adaptive system at various levels like triggers, mediators and the end-effectors to stimulate and mobilize intrinsic protective capacities against brain injuries. It is believed that ischemic pre- or post-conditioning are actually the strongest known interventions to stimulate the innate neuroprotective mechanism to prevent or reverse neurodegenerative diseases including stoke and traumatic brain injury. Recently, studies showed the effectiveness of ischemic per-conditioning in some organs. Therefore the term ischemic conditioning, including all interventions applied pre-, per- and post- ischemia, which spans therapeutic windows in 3 time periods, has recently been broadly accepted by scientific communities. In addition, it is extensively acknowledged that ischemia-mediated protection not only affects the neurons but also all the components of the neurovascular network (consisting of neurons, glial cells, vascular endothelial cells, pericytes, smooth muscle cells, and venule/veins). The concept of cerebroprotection has been widely used in place of neuroprotection. Intensive studies on the cellular signaling pathways involved in ischemic conditioning have improved the mechanistic understanding of tolerance to cerebral ischemia. This has added impetus to exploration for potential pharmacologic mimetics, which could possibly induce and maximize inherent protective capacities. However, most of these studies were performed in rodents, and the efficacy of these mimetics remains to be evaluated in human patients. Several classical signaling pathways involving apoptosis, inflammation, or oxidation have been elaborated in the past decades. Newly characterized mechanisms are emerging with the advances in biotechnology and conceptual renewal. In this review we are going to focus on those

  11. Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo.

    PubMed

    Wong, Raymond; Abussaud, Ahmed; Leung, Joseph Wh; Xu, Bao-Feng; Li, Fei-Ya; Huang, Sammen; Chen, Nai-Hong; Wang, Guan-Lei; Feng, Zhong-Ping; Sun, Hong-Shuo

    2018-05-01

    Activation of swelling-induced Cl - current (I Cl,swell ) during neonatal hypoxia-ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes chronic neurological morbidity in neonates as well as acute mortality. In this study, we investigated the role of I Cl,swell in hypoxic-ischemic brain injury using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl) oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30% hypotonic solution activated I Cl,swell , which was completely blocked by the application of DCPIB (10 μmol/L). The role of I Cl,swell in neonatal hypoxic-ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic-ischemic brain injury model. Before receiving the ischemic insult, the mouse pups were injected with DCPIB (10 mg/kg, ip). We found that pretreatment with DCPIB significantly reduced the brain damage assessed using TTC staining, Nissl staining and whole brain imaging, and improved the sensorimotor and vestibular recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and cliff avoidance reflex). These results show that DCPIB has neuroprotective effects on neonatal hypoxic-ischemic brain injury, and that the I Cl,swell may serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy.

  12. Relationship of myocardial hibernation, scar, and angiographic collateral flow in ischemic cardiomyopathy with coronary chronic total occlusion.

    PubMed

    Wang, Li; Lu, Min-Jie; Feng, Lei; Wang, Juan; Fang, Wei; He, Zuo-Xiang; Dou, Ke-Fei; Zhao, Shi-Hua; Yang, Min-Fu

    2018-03-07

    The relationship between myocardial viability and angiographic collateral flow is not fully elucidated in ischemic cardiomyopathy (ICM) with coronary artery chronic total occlusion (CTO). We aimed to clarify the relationship between myocardial hibernation, myocardial scar, and angiographic collateral flow in these patients. Seventy-one consecutive ICM patients with 122 CTOs and 652 dysfunctional segments within CTO territories were retrospectively analyzed. Myocardial hibernation (perfusion-metabolism mismatch) and the extent of 18 F-fluorodeoxyglucose (FDG) abnormalities were assessed using 99m Tc-sestamibi and 18 F-FDG imaging. Myocardial scar was evaluated by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging. Collateral flow observed on coronary angiography was assessed using Rentrop classification. In these patients, neither the extent nor frequency of myocardial hibernation or scar was related to the status of collateral flow. Moreover, the matching rate in determining myocardial viability was poor between any 2 imaging indices. The extent of 18 F-FDG abnormalities was linearly related to the extent of LGE rather than myocardial hibernation. Of note, nearly one-third (30.4%) of segments with transmural scar still had hibernating tissue. Hibernation and non-transmural scar had higher sensitivity (63.0% and 66.7%) than collateral flow (37.0%) in predicting global functional improvement. Angiographic collateral cannot accurately predict myocardial viability, and has lower sensitivity in prediction of functional improvement in CTO territories in ICM patients. Hence, assessment of myocardial viability with non-invasive imaging modalities is of importance. Moreover, due to the lack of correlation between myocardial hibernation and scar, these two indices are complementary but not interchangeable.

  13. Role of phosphoinositide 3-kinase in ischemic postconditioning-induced attenuation of cerebral ischemia-evoked behavioral deficits in mice.

    PubMed

    Rehni, Ashish K; Singh, Nirmal

    2007-01-01

    The present study has been designed to pharmacologically investigate the role of phosphoinositide 3-kinase in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion-induced behavioral dysfunction in mice. Bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h was employed in the present study to produce ischemia and reperfusion-induced cerebral injury in mice. Short-term memory was evaluated using the elevated plus maze test. The inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced impaired short-term memory, motor co-ordination and lateral push response. Three episodes of carotid artery occlusion for a period of 10 s and reperfusion of 10 s (ischemic postconditioning) significantly prevented ischemia-reperfusion-induced behavioral deficit measured in terms of loss of short-term memory, motor coordination and lateral push response. Wortmannin (2 mg/kg, iv), a phosphoinositide 3-kinase inhibitor given 10 min before ischemia attenuated the beneficial effects of ischemic postconditioning. It may be concluded that beneficial effects of ischemic postconditioning on global cerebral ischemia and reperfusion-induced behavioral deficits may involve activation of phosphoinositide 3-kinase-linked pathway.

  14. Selenium protein identification and profiling by mass spectrometry: A tool to assess progression of cardiomyopathy in a whale model.

    PubMed

    Bryan, Colleen E; Bossart, Gregory D; Christopher, Steven J; Davis, W Clay; Kilpatrick, Lisa E; McFee, Wayne E; O'Brien, Terrence X

    2017-12-01

    Non-ischemic cardiomyopathy is a leading cause of congestive heart failure and sudden cardiac death in humans and in some cases the etiology of cardiomyopathy can include the downstream effects of an essential element deficiency. Of all mammal species, pygmy sperm whales (Kogia breviceps) present the greatest known prevalence of cardiomyopathy with more than half of examined individuals indicating the presence of cardiomyopathy from gross and histo-pathology. Several factors such as genetics, infectious agents, contaminants, biotoxins, and inappropriate dietary intake (vitamins, selenium, mercury, and pro-oxidants), may contribute to the development of idiopathic cardiomyopathy in K. breviceps. Due to the important role Se can play in antioxidant biochemistry and protein formation, Se protein presence and relative abundance were explored in cardiomyopathy related cases. Selenium proteins were separated and detected by multi-dimension liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS), Se protein identification was performed by liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS), and Se protein profiles were examined in liver (n=30) and heart tissue (n=5) by SEC/UV/ICP-MS detection. Data collected on selenium proteins was evaluated in the context of individual animal trace element concentration, life history, and histological information. Selenium containing protein peak profiles varied in presence and intensity between animals with no pathological findings of cardiomyopathy and animals exhibiting evidence of cardiomyopathy. In particular, one class of proteins, metallothioneins, was found to be associated with Se and was in greater abundance in animals with cardiomyopathy than those with no pathological findings. Profiling Se species with SEC/ICP-MS proved to be a useful tool to identify Se protein pattern differences between heart disease stages in K. breviceps and an approach similar to this may be applied to

  15. [Application of Ischemia Modified Albumin for Acute Ischemic Heart Disease in Forensic Science].

    PubMed

    Wang, P; Zhu, Z L; Zhu, N; Yu, H; Yue, Q; Wang, X L; Feng, C M; Wang, C L; Zhang, G H

    2017-10-01

    To explore the application value and forensic significance of ischemia modified albumin (IMA) in pericardial fluid to diagnose sudden cardiac death. IMA level in pericardial fluid was detected in acute ischemic heart disease group ( n =36), acute myocardial infarction group ( n =6), cardiomyopathy group ( n =4) and control group ( n =15) by albumin cobalt binding method. The levels of IMA were compared among these groups. The best cut-off IMA value was estimated and the sensitivity and specificity of acute myocardial ischemia group was distinguished from control group by receiver operating characteristics (ROC) curve. The IMA level in acute ischemic heart disease group was significantly higher than that of control group ( P <0.05). Compared with acute myocardial infarction group and cardiomyopathy group, the IMA level in acute ischemic heart disease group had no significant difference ( P >0.05). The cut-off value for the identification of acute myocardial ischemia which obtained by ROC analysis was 40.65 U/mL. And the sensitivity and specificity for distinguishing acute ischemia cardiac disease was 60.0% and 80.5%, respectively. The IMA value in pericardial fluid can be a reference marker for the diagnosis of acute myocardial ischemia, which also can provide objective basis for the forensic identification of sudden cardiac death. Copyright© by the Editorial Department of Journal of Forensic Medicine

  16. Pilocarpine-Induced Status Epilepticus in Rats Involves Ischemic and Excitotoxic Mechanisms

    PubMed Central

    Fabene, Paolo Francesco; Merigo, Flavia; Galiè, Mirco; Benati, Donatella; Bernardi, Paolo; Farace, Paolo; Nicolato, Elena; Marzola, Pasquina; Sbarbati, Andrea

    2007-01-01

    The neuron loss characteristic of hippocampal sclerosis in temporal lobe epilepsy patients is thought to be the result of excitotoxic, rather than ischemic, injury. In this study, we assessed changes in vascular structure, gene expression, and the time course of neuronal degeneration in the cerebral cortex during the acute period after onset of pilocarpine-induced status epilepticus (SE). Immediately after 2 hr SE, the subgranular layers of somatosensory cortex exhibited a reduced vascular perfusion indicative of ischemia, whereas the immediately adjacent supragranular layers exhibited increased perfusion. Subgranular layers exhibited necrotic pathology, whereas the supergranular layers were characterized by a delayed (24 h after SE) degeneration apparently via programmed cell death. These results indicate that both excitotoxic and ischemic injuries occur during pilocarpine-induced SE. Both of these degenerative pathways, as well as the widespread and severe brain damage observed, should be considered when animal model-based data are compared to human pathology. PMID:17971868

  17. Total donor ischemic time: relationship to early hemodynamics and intensive care morbidity in pediatric cardiac transplant recipients.

    PubMed

    Rodrigues, Warren; Carr, Michelle; Ridout, Deborah; Carter, Katherine; Hulme, Sara Louise; Simmonds, Jacob; Elliott, Martin; Hoskote, Aparna; Burch, Michael; Brown, Kate L

    2011-11-01

    Single-center studies have failed to link modest increases in total donor ischemic time to mortality after pediatric orthotopic heart transplant. We aimed to investigate whether prolonged total donor ischemic time is linked to pediatric intensive care morbidity after orthotopic heart transplant. Retrospective cohort review. Tertiary pediatric transplant center in the United Kingdom. Ninety-three pediatric orthotopic heart transplants between 2002 and 2006. Total donor ischemic time was investigated for association with early post-orthotopic heart transplant hemodynamics and intensive care unit morbidities. Of 43 males and 50 females with median age 7.2 (interquartile range 2.2, 13.0) yrs, 62 (68%) had dilated cardiomyopathy, 20 (22%) had congenital heart disease, and nine (10%) had restrictive cardiomyopathy. The mean total donor ischemic time was 225.9 (sd 65.6) mins. In the first 24 hrs after orthotopic heart transplant, age-adjusted mean arterial blood pressure increased (p < .001), mean pulmonary arterial pressure fell (p = .012), but central venous pressure (p = .58) and left atrial pressure (p = .20) were unchanged. After adjustment for age, primary diagnosis, pre-orthotopic heart transplant mechanical support, and marginal donor factors, longer total donor ischemic time was significantly associated with lower mean arterial blood pressure (p < .001) in the first 24 hrs after orthotopic heart transplant, longer post-orthotopic heart transplant mechanical ventilation (p = .03), longer post-orthotopic heart transplant stay in the intensive care unit (p = .004), and longer post-orthotopic heart transplant stay in hospital (p = .02). Total donor ischemic time was not related to levels of mean pulmonary arterial pressure (p = .62), left atrial pressure (p = .38), or central venous pressure (p = .76) early after orthotopic heart transplant. Prolonged total donor ischemic time has an adverse effect on the donor organ, contributing to lower mean arterial blood

  18. Cardiomyopathy from 1,1-Difluoroethane Inhalation.

    PubMed

    Kumar, Suwen; Joginpally, Tejaswini; Kim, David; Yadava, Mrinal; Norgais, Konchok; Laird-Fick, Heather S

    2016-10-01

    Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative. His cardiac function improved over time. The exact mechanism of DFE's effects is uncertain but may include catecholamine-induced cardiomyopathy, coronary vasospasm, or direct cellular toxicity.

  19. What's Cardiomyopathy

    MedlinePlus

    ... another over time. According to the pediatric cardiomyopathy survey, dilated cardiomyopathy is the most common (58%), followed ... and are replaced by fatty tissue. In the early stages of the disease, the right side of ...

  20. Adenosine diphosphate-induced platelet-fibrin clot strength: a new thrombelastographic indicator of long-term poststenting ischemic events.

    PubMed

    Gurbel, Paul A; Bliden, Kevin P; Navickas, Irene A; Mahla, Elizabeth; Dichiara, Joseph; Suarez, Thomas A; Antonino, Mark J; Tantry, Udaya S; Cohen, Eli

    2010-08-01

    Poststenting ischemic events occur despite dual-antiplatelet therapy, suggesting that a "one size fits all" antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. We investigated the prognostic utility of the strength of adenosine diphosphate (ADP)-induced (MA(ADP)) and thrombin-induced (MA(THROMBIN)) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTA(ADP)) in 225 serial patients after elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over 3 years. Overall, 59 (26%) first ischemic events occurred. Patients with ischemic events had higher MA(ADP), MA(THROMBIN), and LTA(ADP) (P < .0001 for all comparisons). By receiver operating characteristic curve analysis, MA(ADP) >47 mm had the best predictive value of long-term ischemic events compared with other measurements (P < .0001), with an area under the curve = 0.84 (95% CI 0.78-0.89, P < .0001). The univariate Cox proportional hazards model identified MA(ADP) >47 mm, MA(THROMBIN) >69 mm, and LTA(ADP) >34% as significant independent predictors of first ischemic events at the 3-year time point, with hazard ratios of 10.3 (P < .0001), 3.8 (P < .0001), and 4.8 (P < .0001), respectively. Fifteen bleeding events occurred. Receiver operating characteristic curve and quartile analysis suggests MA(ADP) ischemic events and bleeding. Copyright 2010 Mosby, Inc. All rights reserved.

  1. Long-term outcome of surgical cryoablation for refractory ventricular tachycardia in patients with non-ischemic cardiomyopathy.

    PubMed

    Liang, Jackson J; Betensky, Brian P; Muser, Daniele; Zado, Erica S; Anter, Elad; Desai, Nimesh D; Callans, David J; Deo, Rajat; Frankel, David S; Hutchinson, Mathew D; Lin, David; Riley, Michael P; Schaller, Robert D; Supple, Gregory E; Santangeli, Pasquale; Acker, Michael A; Bavaria, Joseph E; Szeto, Wilson Y; Vallabhajosyula, Prashanth; Marchlinski, Francis E; Dixit, Sanjay

    2018-03-01

    Limited data exist on the long-term outcome of patients (pts) with non-ischemic cardiomyopathy (NICM) and ventricular tachycardia (VT) refractory to conventional therapies undergoing surgical ablation (SA). We aimed to investigate the long-term survival and VT recurrence in NICM pts with VT refractory to radiofrequency catheter ablation (RFCA) who underwent SA. Consecutive pts with NICM and VT refractory to RFCA who underwent SA were included. VT substrate was characterized in the electrophysiology lab and targeted by RFCA. During SA, previous RFCA lesions/scars were identified and targeted with cryoablation (CA; 3 min/lesion; target -150 °C). Follow-up comprised office visits, ICD interrogations and the social security death index. Twenty consecutive patients with NICM who underwent SA (age 53 ± 16 years, 18 males, LVEF 41 ± 20%; dilated CM = 9, arrhythmogenic right ventricular CM = 3, hypertrophic CM = 2, valvular CM = 4, and mixed CM = 2) were studied. Percutaneous mapping/ablation in the electrophysiology lab was performed in 18 and 2 pts had primary SA. During surgery, 4.9 ± 4.0 CA lesions/pt were delivered to the endocardium (2) and epicardium (11) or both (7). VT-free survival was 72.5% at 1 year and over 43 ± 31 months (mos) (range 1-83mos), there was only one arrhythmia-related death. There was a significant reduction in ICD shocks in the 3-mos preceding SA vs. the entire follow-up period (6.6 ± 4.9 vs. 2.3 ± 4.3 shocks/pt, P = 0.001). In select pts with NICM and VT refractory to RFCA, SA guided by pre-operative electrophysiological mapping and ablation may be a therapeutic option. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  2. Ramipril restores PPARβ/δ and PPARγ expressions and reduces cardiac NADPH oxidase but fails to restore cardiac function and accompanied myosin heavy chain ratio shift in severe anthracycline-induced cardiomyopathy in rat.

    PubMed

    Cernecka, Hana; Doka, Gabriel; Srankova, Jasna; Pivackova, Lenka; Malikova, Eva; Galkova, Kristina; Kyselovic, Jan; Krenek, Peter; Klimas, Jan

    2016-11-15

    We hypothesized that peroxisome proliferator-activated receptors (PPARs) might be involved in a complex protective action of ACE inhibitors (ACEi) in anthracyclines-induced cardiomyopathy. For purpose of study, we compared effects of ramipril on cardiac dysfunction, cardiac failure markers and PPAR isoforms in moderate and severe chronic daunorubicin-induced cardiomyopathy. Male Wistar rats were administered with a single intravenous injection of daunorubicin: 5mg/kg (moderate cardiomyopathy), or 15mg/kg (severe cardiomyopathy) or co-administered with daunorubicin and ramipril (1mg/kg/d, orally) or vehicle for 8 weeks. Left ventricular function was measured invasively under anesthesia. Cardiac mRNA levels of heart failure markers (ANP, Myh6, Myh7, Myh7b) and PPARs (alpha, beta/delta and gama) were measured by qRT-PCR. Protein expression of NADPH subunit (gp91phox) was measured by Western blot. Moderate cardiomyopathy exhibited only minor cardiac dysfunction what was corrected by ramipril. In severe cardiomyopathy, hemodynamic dysfunction remained unaltered upon ramipril although it decreased the significantly up-regulated cardiac ANP mRNA expression. Simultaneously, while high-dose daunorubicin significantly decreased PPARbeta/delta and PPARgama mRNA, ramipril normalized these abnormalities. Similarly, ramipril reduced altered levels of oxidative stress-related gp91phox. On the other hand, ramipril was unable to correct both the significantly decreased relative abundance of Myh6 and increased Myh7 mRNA levels, respectively. In conclusion, ramipril had a protective effect on cardiac function exclusively in moderate chronic daunorubicin-induced cardiomyopathy. Although it normalized abnormal PPARs expression and exerted also additional protective effects also in severe cardiomyopathy, it was insufficient to influence impaired cardiac function probably because of a shift in myosin heavy chain isoform content. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A Mouse Model of Cardiomyopathy Induced by Mutations in the Hemochromatosis HFE Gene.

    PubMed

    Djemai, Haidar; Thomasson, Rémi; Trzaskus, Yvan; Mougenot, Nathalie; Meziani, Amira; Toussaint, Jean-François; Noirez, Philippe; Vitiello, Damien

    2017-07-01

    The heart is 1 of the organs most affected by hereditary hemochromatosis (HH). The clinical impact of cardiomyopathy in patients with HH requires a particular diagnosis and less invasive treatments. We developed a model of cardiomyopathy in knockout (KO) mice for the high-Fe (HFE) gene and assessed left ventricular (LV) function and structure from 7-20 months. Male wild-type (WT) heterozygous and KO SV129 mice for the HFE gene were used in this study. Twenty-four mice were used to assess LV function and structure by echocardiography at 7, 14, 18, and 20 months. Evaluations of LV function and structure and myocardial fibrosis were performed at 7 and 20 months. The percent decrease of LV thickness-to-radius ratio between 7 and 20 months was higher in KO mice compared with WT mice (-30.2% ± 5.3% vs -10.5% ± 4.9%; P < 0.01). The LV diameters were higher in old mice compared with young mice (+13% at end-diastole; +33% at end-systole; P < 0.001). The LV ejection fraction values were lower in KO mice compared with WT mice between 7 and 20 months. The highest difference was found at 14 months (60.0% ± 7.6% vs 78.1% ± 3.5%; P < 0.001). Myocardial fibrosis was higher in old KO mice compared with old WT mice (+55%; P < 0.001), and myocardial iron deposition was slightly increased in old KO mice compared with old WT mice (1.31% ± 0.33% vs 0.84% ± 0.22%; P = 0.056). The present mouse model has the potential to allow the determination of underlying mechanisms involved in the cardiomyopathy induced by HFE-related hemochromatosis. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Takotsubo cardiomyopathy: A known unknown foe of asthma.

    PubMed

    Kotsiou, Ourania S; Douras, Alexandros; Makris, Demosthenes; Mpaka, Nikoleta; Gourgoulianis, Konstantinos I

    2017-10-01

    Patients with uncontrolled asthma are at a greater risk of asthma attacks requiring emergency room visits or hospital admissions. Takotsubo cardiomyopathy is potentially a significant complication in a course of status asthmaticus. We describe a 43-year-old female patient who presented with status asthmaticus that was further complicated with takotsubo cardiomyopathy. Recognizing apical ballooning syndrome is challenging in patients with a history of respiratory disease because the symptoms of the last entity may complicate the diagnostic approach. It is difficult to distinguish clinically apical ballooning syndrome from the acute airway exacerbation itself. Both asthma and takotsubo cardiomyopathy share the same clinical presentation with dyspnea and chest tightness. In our patient, the electrocardiographic abnormalities, the rapidly reversible distinctive characteristics of echocardiography, and the modest elevation of serum cardiac biomarkers levels, in combination with the presence of a stress trigger (severe asthma attack), strongly supported the diagnosis of broken heart syndrome. Clinicians should re-evaluate asthma management and be aware of the complications associated with asthma attacks such as stress-induced cardiomyopathy.

  5. Neuroprotective effects of scutellarin against hypoxic-ischemic-induced cerebral injury via augmentation of antioxidant defense capacity.

    PubMed

    Guo, Hong; Hu, Li-Min; Wang, Shao-Xia; Wang, Yu-Lin; Shi, Fang; Li, Hui; Liu, Yang; Kang, Li-Yuan; Gao, Xiu-Mei

    2011-12-31

    An increasing number of studies has indicated that hypoxic-ischemic-induced cerebral injury is partly mediated via oxidative stress. Recent researches have focused on searching for drug and herbal manipulations to protect against hypoxic-ischemic-induced oxidative cell damage. Scutellarin is a flavonoid derived from the Erigeron breviscapus (vant.) and has been reported to exhibit neuroprotective properties. However, its precise mechanism, particularly its antioxidation mechanism, remains elusive. In the present study, we investigated the neuroprotective effects of scutellarin on middle cerebral artery occlusion (MCAO)-induced brain damage in rats, and oxygen-glucose deprivation (OGD)-induced toxicity in primary culture of rat cortical neurons. In vivo, intraperitoneal injections of scutellarin (20 and 60 mg/kg) improved the neurological score and diminished the percentage of brain infarct volume. At the same time, scutellarin significantly increased superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level in ischemic brain tissues, enhancing endogenous antioxidant activity. Moreover, pretreatment of scutellarin (25, 50 and 100 μM) protected neurons against lethal stimuli, decreased the percentage of apoptotic cells and inhibited reactive oxygen species (ROS) generation in OGD-induced primary cortical neurons in vitro. These results suggest that the preventive and therapeutic potential of scutellarin in cerebral injury patients is, at least in part, ascribed to augmentation of cellular antioxidant defense capacity.

  6. Heart-Derived Stem Cells in Miniature Swine with Coronary Microembolization: Novel Ischemic Cardiomyopathy Model to Assess the Efficacy of Cell-Based Therapy

    PubMed Central

    Young, Rebeccah F.; Leiker, Merced M.; Suzuki, Takayuki

    2016-01-01

    A major problem in translating stem cell therapeutics is the difficulty of producing stable, long-term severe left ventricular (LV) dysfunction in a large animal model. For that purpose, extensive infarction was created in sinclair miniswine by injecting microspheres (1.5 × 106 microspheres, 45 μm diameter) in LAD. At 2 months after embolization, animals (n = 11) were randomized to receive allogeneic cardiosphere-derived cells derived from atrium (CDCs: 20 × 106, n = 5) or saline (untreated, n = 6). Four weeks after therapy myocardial function, myocyte proliferation (Ki67), mitosis (phosphor-Histone H3; pHH3), apoptosis, infarct size (TTC), myocyte nuclear density, and cell size were evaluated. CDCs injected into infarcted and remodeled remote myocardium (global infusion) increased regional function and global function contrasting no change in untreated animals. CDCs reduced infarct volume and stimulated Ki67 and pHH3 positive myocytes in infarct and remote regions. As a result, myocyte number (nuclear density) increased and myocyte cell diameter decreased in both infarct and remote regions. Coronary microembolization produces stable long-term ischemic cardiomyopathy. Global infusion of CDCs stimulates myocyte regeneration and improves left ventricular ejection fraction. Thus, global infusion of CDCs could become a new therapy to reverse LV dysfunction in patients with asymptomatic heart failure. PMID:27738436

  7. Patient-Specific Induced Pluripotent Stem Cell as a Model for Familial Dilated Cardiomyopathy

    PubMed Central

    Sun, Ning; Yazawa, Masayuki; Liu, Jianwei; Han, Leng; Sanchez-Freire, Veronica; Abilez, Oscar J.; Navarrete, Enrique G.; Hu, Shijun; Wang, Li; Lee, Andrew; Pavlovic, Aleksandra; Lin, Shin; Chen, Rui; Hajjar, Roger J.; Snyder, Michael P.; Dolmetsch, Ricardo E.; Butte, Manish J.; Ashley, Euan A.; Longaker, Michael T.; Robbins, Robert C.; Wu, Joseph C.

    2013-01-01

    Dilated cardiomyopathy (DCM) is the most common cardiomyopathy, characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific models, investigating underlying mechanisms, and optimizing therapy. Here we generated cardiomyocytes (CMs) from iPSCs derived from patients of a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to the control healthy individuals in the same family cohort, DCM iPSC-CMs exhibited altered Ca2+ handling, decreased contractility, and abnormal sarcomeric α-actinin distribution. When stimulated with β-adrenergic agonist, DCM iPSC-CMs showed characteristics of failure such as reduced beating rates, compromised contraction, and significantly more cells with abnormal sarcomeric α-actinin distribution. β-adrenergic blocker treatment and over-expression of sarcoplasmic reticulum Ca2+ ATPase (Serca2a) improved DCM iPSC-CMs function. Our study demonstrated that human DCM iPSC-CMs recapitulated to some extent the disease phenotypes morphologically and functionally, and thus can serve as a useful platform for exploring molecular and cellular mechanisms and optimizing treatment of this particular disease. PMID:22517884

  8. DIGE Proteome Analysis Reveals Suitability of Ischemic Cardiac In Vitro Model for Studying Cellular Response to Acute Ischemia and Regeneration

    PubMed Central

    Haas, Sina; Jahnke, Heinz-Georg; Moerbt, Nora; von Bergen, Martin; Aharinejad, Seyedhossein; Andrukhova, Olena; Robitzki, Andrea A.

    2012-01-01

    Proteomic analysis of myocardial tissue from patient population is suited to yield insights into cellular and molecular mechanisms taking place in cardiovascular diseases. However, it has been limited by small sized biopsies and complicated by high variances between patients. Therefore, there is a high demand for suitable model systems with the capability to simulate ischemic and cardiotoxic effects in vitro, under defined conditions. In this context, we established an in vitro ischemia/reperfusion cardiac disease model based on the contractile HL-1 cell line. To identify pathways involved in the cellular alterations induced by ischemia and thereby defining disease-specific biomarkers and potential target structures for new drug candidates we used fluorescence 2D-difference gel electrophoresis. By comparing spot density changes in ischemic and reperfusion samples we detected several protein spots that were differentially abundant. Using MALDI-TOF/TOF-MS and ESI-MS the proteins were identified and subsequently grouped by functionality. Most prominent were changes in apoptosis signalling, cell structure and energy-metabolism. Alterations were confirmed by analysis of human biopsies from patients with ischemic cardiomyopathy. With the establishment of our in vitro disease model for ischemia injury target identification via proteomic research becomes independent from rare human material and will create new possibilities in cardiac research. PMID:22384053

  9. Adenosine Diphosphate-Induced Platelet-Fibrin Clot Strength: A New Thrombelastographic Indicator of Long-Term Post-Stenting Ischemic Events

    PubMed Central

    Gurbel, Paul A.; Bliden, Kevin P.; Navickas, Irene A.; Mahla, Elizabeth; Dichiara, Joseph; Suarez, Thomas A.; Antonino, Mark J.; Tantry, Udaya S.; Cohen, Eli

    2010-01-01

    Background Post-stenting ischemic events occur despite dual antiplatelet therapy suggesting that a “one size fits all” antithrombotic strategy has significant limitations. Ex vivo platelet function measurements may facilitate risk stratification and personalized antiplatelet therapy. Methods We investigated the prognostic utility of the strength of ADP-induced (MAADP) and thrombin-induced (MATHROMBIN) platelet-fibrin clots measured by thrombelastography and ADP-induced light transmittance aggregation (LTAADP) in 225 serial patients following elective stenting treated with aspirin and clopidogrel. Ischemic and bleeding events were assessed over three-years. Results Overall, 59 (26 %) first ischemic events occurred. Patients with ischemic events had higher MAADP, MATHROMBIN, and LTAADP (p<0.0001 for all comparisons). By receiver operating characteristic curve analysis, MAADP > 47mm had the best predictive value of long-term ischemic events compared to other measurements (p<0.0001) with an area under the curve = 0.84 [95% CI 0.78 – 0.89, p < 0.0001]. The univariate Cox proportional hazards model identified MAADP >47mm, MATHROMBIN >69mm, and LTA ADP >34% as significant independent predictors of first ischemic events at the three-year time point, with hazard ratios of 10.3 (p<0.0001), 3.8 (p<0.0001), and 4.8 (p<0.0001) respectively. Fifteen bleeding events occurred. Receiver operator characteristic curve and quartile analysis suggest MAADP ≤ 31 as a predictive value for bleeding. Conclusion This study is the first demonstration of the prognostic utility of MAADP in predicting long term event occurrence following stenting. The quantitative assessment of ADP-stimulated platelet-fibrin clot strength measured by thrombelastography can serve as a future tool in investigations of personalized antiplatelet treatment designed to reduce ischemic events and bleeding. PMID:20691842

  10. Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis.

    PubMed

    Fang, Qilu; Wang, Jingying; Zhang, Yali; Wang, Lintao; Li, Weixin; Han, Jibo; Huang, Weijian; Liang, Guang; Wang, Yi

    2018-01-01

    Obesity causes cardiovascular diseases, including cardiac hypertrophy and remodeling, via chronic tissue inflammation. Myeloid differentiation factor-2 (MD2), a binding protein of lipopolysaccharide, is functionally essential for the activation of proinflammatory pathways in endotoxin-induced acute inflammatory diseases. Here we tested the hypothesis that MD2 plays a central role in obesity-induced cardiomyopathy. Wildtype or MD2 knockout mice were fed with a high fat diet (HFD) or normal diet (Control) for total 16weeks, and MD2 inhibitor L6H21 (20mg/kg) or vehicle (1% CMC-Na) were administered from the beginning of the 9th week. HFD induced significant weight gain and cardiac hypertrophy, with increased cardiac fibrosis and inflammation. L6H21 administration or MD2 knockout attenuated HFD-induced obesity, inflammation and cardiac remodeling. In vitro exposure of H9C2 cells to high lipids induced cell hypertrophy with activated JNK/ERK and NF-κB pathways, which was abolished by pretreatment of MD2 inhibitor L6H21. Our results demonstrate that MD2 is essential to obesity-related cardiac hypertrophy through activating JNK/ERK and NF-κB-dependent cardiac inflammatory pathways. Targeting MD2 would be a therapeutic approach to prevent obesity-induced cardiac injury and remodeling. Copyright © 2017. Published by Elsevier B.V.

  11. Flow-Induced Mitral Leaflet Motion in Hypertrophic Cardiomyopathy

    NASA Astrophysics Data System (ADS)

    Meschini, Valentina; Mittal, Rajat; Verzicco, Roberto

    2017-11-01

    Hypertrophic cardiomyopathy (HCM) is considered the cause of sudden cardiac death in developed countries. Clinically it is found to be related to the thickening of the intra-ventricular septum combined with elongated mitral leaflets. During systole the low pressure, induced by the abnormal velocities in the narrowed aortic channel, can attract one or both the mitral leaflets causing the aortic obstruction and sometimes instantaneous death. In this paper a fluid structure interaction model for the flow in the left ventricle with a native mitral valve is employed to investigate the physio-pathology of HCM. The problem is studied using direct numerical simulations of the Navier-Stokes equations with a two-way coupled structural solver based on interaction potential approach for the structure dynamics. Simulations are performed for two different degrees of hypertrophy, and two values of pumping efficiency. The leaflets dynamics and the ventricle deformation resulting from the echocardiography of patients affected by HCM are well captured by the simulations. Moreover, the procedures of leaflets plication and septum myectomy are simulated in order to get insights into the efficiency and reliability of such surgery.

  12. Association between Latest Activated Sites in the Left Ventricle and Akinetic Segments in Patients with Ischemic Cardiomyopathy.

    PubMed

    Sadeghian, Hakimeh; Kousari, Aliasghar; Majidi, Shahla; Rezvanfard, Mehrnaz; Kazemisaeid, Ali; Moezzi, Seyed Ali; Vasheghani Farahani, Ali; Abdar Esfahani, Morteza; Sahebjam, Mohammad; Zoroufian, Arezoo; Sadeghian, Afsaneh

    2016-07-06

    Background: It is not clear whether the latest activation sites in the left ventricle (LV) are matched with infracted regions in patients with ischemic cardiomyopathy (ICM). We aimed to investigate whether the latest activation sites in the LV are in agreement with the region of akinesia in patients with ICM. Methods: Data were analyzed in 106 patients (age = 60.5 ± 12.1 y, male = 88.7%) with ICM (ejection fraction ≤ 35%) who were refractory to pharmacological therapy and were referred to the echocardiography department for an evaluation of the feasibility of cardiac resynchronization therapy. Wall motion abnormalities, time to peak systolic myocardial velocity (Ts) of 6 basal and 6 mid-portion segments of the LV, and 4 frequently used dyssynchrony indices were measured using 2-dimensional echocardiography and tissue Doppler imaging (TDI). To evaluate the influence of the electrocardiographic pattern, we categorized the patients into 2 groups: patients with QRS ≤ 120 ms and those with QRS >120 ms. Results: A total of 1 272 segments were studied. The latest activation sites (with longest Ts) were most frequently located in the mid-anterior (n = 32, 30.2%) and basal-anterior segments (n = 29, 27.4%), while the most common sites of akinesia were the mid-anteroseptal (n = 65, 61.3%) and mid-septal (n = 51, 48.1%) segments. Generally, no significant concordance was found between the latest activated segments and akinesia either in all the patients or in the QRS groups. Detailed analysis within the segments indicated a good agreement between akinesia and delayed activation in the basal-lateral segment solely in the patients with QRS duration ≤ 120 ms (Φ = 0.707; p value ≤ 0.001). Conclusion: The akinetic segment on 2-dimensional echocardiogram was not matched with the latest activation sites in the LV determined by TDI in patients with ICM.

  13. Association between Latest Activated Sites in the Left Ventricle and Akinetic Segments in Patients with Ischemic Cardiomyopathy

    PubMed Central

    Sadeghian, Hakimeh; Kousari, Aliasghar; Majidi, Shahla; Rezvanfard, Mehrnaz; Kazemisaeid, Ali; Moezzi, Seyed Ali; Vasheghani Farahani, Ali; Abdar Esfahani, Morteza; Sahebjam, Mohammad; Zoroufian, Arezoo; Sadeghian, Afsaneh

    2016-01-01

    Background: It is not clear whether the latest activation sites in the left ventricle (LV) are matched with infracted regions in patients with ischemic cardiomyopathy (ICM). We aimed to investigate whether the latest activation sites in the LV are in agreement with the region of akinesia in patients with ICM. Methods: Data were analyzed in 106 patients (age = 60.5 ± 12.1 y, male = 88.7%) with ICM (ejection fraction ≤ 35%) who were refractory to pharmacological therapy and were referred to the echocardiography department for an evaluation of the feasibility of cardiac resynchronization therapy. Wall motion abnormalities, time to peak systolic myocardial velocity (Ts) of 6 basal and 6 mid-portion segments of the LV, and 4 frequently used dyssynchrony indices were measured using 2-dimensional echocardiography and tissue Doppler imaging (TDI). To evaluate the influence of the electrocardiographic pattern, we categorized the patients into 2 groups: patients with QRS ≤ 120 ms and those with QRS >120 ms. Results: A total of 1 272 segments were studied. The latest activation sites (with longest Ts) were most frequently located in the mid-anterior (n = 32, 30.2%) and basal-anterior segments (n = 29, 27.4%), while the most common sites of akinesia were the mid-anteroseptal (n = 65, 61.3%) and mid-septal (n = 51, 48.1%) segments. Generally, no significant concordance was found between the latest activated segments and akinesia either in all the patients or in the QRS groups. Detailed analysis within the segments indicated a good agreement between akinesia and delayed activation in the basal-lateral segment solely in the patients with QRS duration ≤ 120 ms (Φ = 0.707; p value ≤ 0.001). Conclusion: The akinetic segment on 2-dimensional echocardiogram was not matched with the latest activation sites in the LV determined by TDI in patients with ICM. PMID:27956911

  14. Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy.

    PubMed

    Bajraktari, Gani; Miccoli, Mario; Buralli, Simona; Fontanive, Paolo; Elezi, Shpend; Metelli, Maria Rita; Baggiani, Angelo; Dini, Frank Lloyd

    2012-10-01

    Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients. Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction ≤ 40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150 ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25 ± 17 months. Median value of MMP-9 was 714 ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5 ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure ≥ 35 mm Hg, N-terminal protype-B natriuretic peptide>1742 pg/ml, and glomerular filtration rate<60 ml/min/1.73 m(2). Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan-Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001). MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients. Copyright © 2012. Published by Elsevier B.V.

  15. Takotsubo cardiomyopathy complicated with acute pericarditis and cardiogenic shock.

    PubMed Central

    Guevara, Rodolfo; Aguinaga-Meza, Melina; Hazin, Moustafa Imran; Hazin, Ribhi; McCord, James

    2007-01-01

    Takotsubo cardiomyopathy (TC) is a relatively uncommon stress-induced cardiomyopathy that accounts for 2.2% of all acute myocardial infarctions. It occurs most commonly in postmenopausal women between the ages of 55-70. The most common complications that have been described are cardiogenic shock and left ventricular outflow tract obstruction, stroke and apical thrombus formation. There have been multiple prior case reports of TC; however, our case is the first to report acute pericarditis as one of its complications. Images Figure 1 Figure 2 PMID:17393953

  16. Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1/AMPK pathway.

    PubMed

    Zhang, Zhiguo; Wang, Shudong; Zhou, Shanshan; Yan, Xiaoqing; Wang, Yonggang; Chen, Jing; Mellen, Nicholas; Kong, Maiying; Gu, Junlian; Tan, Yi; Zheng, Yang; Cai, Lu

    2014-12-01

    Type 2 diabetes mellitus (T2DM)-induced cardiomyopathy is associated with cardiac oxidative stress, inflammation, and remodeling. Sulforaphane (SFN), an isothiocyanate naturally presenting in widely consumed vegetables, particularly broccoli, plays an important role in cardiac protection from diabetes. We investigated the effect of SFN on T2DM-induced cardiac lipid accumulation and subsequent cardiomyopathy. Male C57BL/6J mice were fed a high-fat diet for 3months to induce insulin resistance, followed by a treatment with 100mg/kg body-weight streptozotocin to induce hyperglycemia; we referred to it as the T2DM mouse model. Other age-matched mice were fed a normal diet as control. T2DM and control mice were treated with or without 4-month SFN at 0.5mg/kg daily five days a week. At the study's end, cardiac function was assessed. SFN treatment significantly attenuated cardiac remodeling and dysfunction induced by T2DM. SFN treatment also significantly inhibited cardiac lipid accumulation, measured by Oil Red O staining, and improved cardiac inflammation oxidative stress and fibrosis, shown by down-regulating diabetes-induced PAI-1, TNF-α, CTGF, TGF-β, 3-NT, and 4-HNE expression. Elevated 4-HNE resulted in the increase of 4-HNE-LKB1 adducts that should inhibit LKB1 and subsequent AMPK activity. SFN upregulated the expression of Nrf2 and its downstream genes, NQO1 and HO-1, decreased 4-HNE-LKB1 adducts and then reversed diabetes-induced inhibition of LKB1/AMPK and its downstream targets, including sirtuin 1, PGC-1α, phosphorylated acetyl-CoA carboxylase, carnitine palmitoyl transferase-1, ULK1, and light chain-3 II. These results suggest that SFN treatment to T2DM mice may attenuate the cardiac oxidative stress-induced inhibition of LKB1/AMPK signaling pathway, thereby preventing T2DM-induced lipotoxicity and cardiomyopathy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice.

    PubMed

    Zhang, Zhihao; Zhang, Duoduo; Dou, Mengmeng; Li, Zhubo; Zhang, Jie; Zhao, Xiaoyan

    2016-12-01

    Dendrobium officinale Kimura et Migo (Dendrobium catenatum Lindley), a prized traditional Chinese Medicine, has been used in China and Southeast Asian countries for centuries. The present study was aimed to investigate the effects and the possible mechanisms of the Dendrobium officinale extracts (DOE) on diabetic cardiomyopathy in mice. The diabetic model was induced by intraperitoneal injection of streptozotocin at the dose of 50mg/kg body weight for 5 consecutive days. After 8 weeks treatment of DOE, mice were sacrificed, blood sample and heart tissues were collected. Our results showed that Streptozotocin-induced diabetic model was effectively achieved and serum CK and LDH levels were significantly increased in mice with diabetic cardiomyopathy. Pretreatment with DOE decreased the heart-to-body weight ratio (HW/BW) and showed an evident hypoglycemic effect. DOE pretreatment significantly decreased CK, LDH, TC and TG levels, limited the production of MDA and increased the activities of T-SOD. The histological analysis of Oil red O staining and Sirius red staining showed an obvious amelioration of cardiac injury, inhibition of cardiac lipid accumulation and deposition of collagen when pretreatment with DOE. In addition, Western blot detection and analysis showed that DOE down-regulated the expression of TGF-β, collegan-1, fibronectin, NF-κB, TNF-α and IL-1β. In conclusion, our study suggested that DOE possesses the cardioprotective potential against diabetic cardiomyopathy, which may be due to the inhibition of oxidative stress, cardiac lipid accumulation, pro-inflammatory cytokines and cardiac fibrosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. TIGAR contributes to ischemic tolerance induced by cerebral preconditioning through scavenging of reactive oxygen species and inhibition of apoptosis

    PubMed Central

    Zhou, Jun-Hao; Zhang, Tong-Tong; Song, Dan-Dan; Xia, Yun-Fei; Qin, Zheng-Hong; Sheng, Rui

    2016-01-01

    Previous study showed that TIGAR (TP53-induced glycolysis and apoptosis regulator) protected ischemic brain injury via enhancing pentose phosphate pathway (PPP) flux and preserving mitochondria function. This study was aimed to study the role of TIGAR in cerebral preconditioning. The ischemic preconditioning (IPC) and isoflurane preconditioning (ISO) models were established in primary cultured cortical neurons and in mice. Both IPC and ISO increased TIGAR expression in cortical neurons. Preconditioning might upregulate TIGAR through SP1 transcription factor. Lentivirus mediated knockdown of TIGAR significantly abolished the ischemic tolerance induced by IPC and ISO. ISO also increased TIGAR in mouse cortex and hippocampus and alleviated subsequent brain ischemia-reperfusion injury, while the ischemic tolerance induced by ISO was eliminated with TIGAR knockdown in mouse brain. ISO increased the production of NADPH and glutathione (GSH), and scavenged reactive oxygen species (ROS), while TIGAR knockdown decreased GSH and NADPH production and increased the level of ROS. Supplementation of ROS scavenger NAC and PPP product NADPH effectively rescue the neuronal injury caused by TIGAR deficiency. Notably, TIGAR knockdown inhibited ISO-induced anti-apoptotic effects in cortical neurons. These results suggest that TIGAR participates in the cerebral preconditioning through reduction of ROS and subsequent cell apoptosis. PMID:27256465

  19. Apigenin alleviates STZ-induced diabetic cardiomyopathy.

    PubMed

    Liu, Huang-Jun; Fan, Yun-Lin; Liao, Hai-Han; Liu, Yuan; Chen, Si; Ma, Zhen-Guo; Zhang, Ning; Yang, Zheng; Deng, Wei; Tang, Qi-Zhu

    2017-04-01

    Apigenin is an important component of fruits and vegetables in human daily diets. Several cellular and animal models have been performed to demonstrate its anti-oxidant and anti-inflammatory bioactivities. However, the cardioprotective effects of apigenin in diabetic cardiomyopathy (DCM) remain unclear. In this study, we intended to explore the roles of apigenin in cardiac remodeling of DCM. Male C57BL/6 J mice were treated with streptozotocin (STZ, 50 mg/kg) for 5 consecutive days to induce DCM. The echocardiography and catheter-based measurements of hemodynamic parameters were performed to evaluate the cardiac function. Paraffin slices of harvested hearts were prepared for histological pathological analysis and TUNEL assay. Oxidative assay kits were used to detect Glutathione Peroxidase (GPx), Lipid Peroxidation Malondialdehyde (MDA), and Superoxide Dismutase (SOD). Western blot and real-time PCR were used for accessing the expressions of protein and mRNA. Diabetes mellitus exacerbated the cardiac dysfunction, fibrosis, and overaccumulation of 4-hydroxynonenal accompanying with down-regulation of Bcl2, GPx, and SOD, up-regulation of MDA, cleaved caspase3, and pro-apoptotic protein Bax, and contribution to the translocation of NF-κB. All these pathological changes could be effectively blunted by treatment of apigenin in vivo. Finally, H9c2 treated with high glucose or apigenin was used for further investigation of these effects in vitro; what is more, we also compared the effects between apigenin and Resveratrol in in vitro experiments. Our experiments have demonstrated that apigenin may be a potential drug for diabetic patients suffering from DCM.

  20. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

    PubMed

    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

  1. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy.

    PubMed

    Lin, Bo; Li, Yang; Han, Lu; Kaplan, Aaron D; Ao, Ying; Kalra, Spandan; Bett, Glenna C L; Rasmusson, Randall L; Denning, Chris; Yang, Lei

    2015-05-01

    Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and is characterized by progressive weakness in skeletal and cardiac muscles. Currently, dilated cardiomyopathy due to cardiac muscle loss is one of the major causes of lethality in late-stage DMD patients. To study the molecular mechanisms underlying dilated cardiomyopathy in DMD heart, we generated cardiomyocytes (CMs) from DMD and healthy control induced pluripotent stem cells (iPSCs). DMD iPSC-derived CMs (iPSC-CMs) displayed dystrophin deficiency, as well as the elevated levels of resting Ca(2+), mitochondrial damage and cell apoptosis. Additionally, we found an activated mitochondria-mediated signaling network underlying the enhanced apoptosis in DMD iPSC-CMs. Furthermore, when we treated DMD iPSC-CMs with the membrane sealant Poloxamer 188, it significantly decreased the resting cytosolic Ca(2+) level, repressed caspase-3 (CASP3) activation and consequently suppressed apoptosis in DMD iPSC-CMs. Taken together, using DMD patient-derived iPSC-CMs, we established an in vitro model that manifests the major phenotypes of dilated cardiomyopathy in DMD patients, and uncovered a potential new disease mechanism. Our model could be used for the mechanistic study of human muscular dystrophy, as well as future preclinical testing of novel therapeutic compounds for dilated cardiomyopathy in DMD patients. © 2015. Published by The Company of Biologists Ltd.

  2. Novel MRI-derived quantitative biomarker for cardiac function applied to classifying ischemic cardiomyopathy within a Bayesian rule learning framework

    NASA Astrophysics Data System (ADS)

    Menon, Prahlad G.; Morris, Lailonny; Staines, Mara; Lima, Joao; Lee, Daniel C.; Gopalakrishnan, Vanathi

    2014-03-01

    Characterization of regional left ventricular (LV) function may have application in prognosticating timely response and informing choice therapy in patients with ischemic cardiomyopathy. The purpose of this study is to characterize LV function through a systematic analysis of 4D (3D + time) endocardial motion over the cardiac cycle in an effort to define objective, clinically useful metrics of pathological remodeling and declining cardiac performance, using standard cardiac MRI data for two distinct patient cohorts accessed from CardiacAtlas.org: a) MESA - a cohort of asymptomatic patients; and b) DETERMINE - a cohort of symptomatic patients with a history of ischemic heart disease (IHD) or myocardial infarction. The LV endocardium was segmented and a signed phase-to-phase Hausdorff distance (HD) was computed at 3D uniformly spaced points tracked on segmented endocardial surface contours, over the cardiac cycle. An LV-averaged index of phase-to-phase endocardial displacement (P2PD) time-histories was computed at each tracked point, using the HD computed between consecutive cardiac phases. Average and standard deviation in P2PD over the cardiac cycle was used to prepare characteristic curves for the asymptomatic and IHD cohort. A novel biomarker of RMS error between mean patient-specific characteristic P2PD over the cardiac cycle for each individual patient and the cumulative P2PD characteristic of a cohort of asymptomatic patients was established as the RMS-P2PD marker. The novel RMS-P2PD marker was tested as a cardiac function based feature for automatic patient classification using a Bayesian Rule Learning (BRL) framework. The RMS-P2PD biomarker indices were significantly different for the symptomatic patient and asymptomatic control cohorts (p<0.001). BRL accurately classified 83.8% of patients correctly from the patient and control populations, with leave-one-out cross validation, using standard indices of LV ejection fraction (LV-EF) and LV end-systolic volume

  3. Effect of amiodarone-induced hyperthyroidism on left ventricular outflow obstruction after septal myectomy for hypertrophic cardiomyopathy.

    PubMed

    Pokorney, Sean D; Stone, Neil J; Passman, Rod; Oyer, David; Rigolin, Vera H; Bonow, Robert O

    2010-12-01

    Patients with obstructive hypertrophic cardiomyopathy who undergo septal myectomy are at risk for developing postoperative atrial fibrillation. Amiodarone is effective in treating this arrhythmia but is associated with multiple adverse effects, often with delayed onset. A novel case is described of a patient who developed type 2 amiodarone-induced hyperthyroidism that presented as recurrence of outflow obstruction after septal myectomy. The patient's symptoms and echocardiographic findings of outflow obstruction resolved substantially with the treatment of the amiodarone-induced hyperthyroidism. Amiodarone-induced hyperthyroidism of delayed onset can be a subtle diagnosis, requiring a high index of suspicion. In conclusion, recognition of this diagnosis in patients with recurrence of outflow obstruction by symptoms and cardiac imaging after septal myectomy may avoid unnecessary repeat surgical intervention. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Takotsubo Cardiomyopathy Resulting in Cardiac Arrest in a Patient Undergoing Liver Transplantation.

    PubMed

    Can, M Güner; Özer, A; İyigün, M; Gökay, B Vural; Emiroğlu, R

    2017-12-01

    Cardiac complications during and after liver transplantation are a common cause of death. Although considered to be uncommon, takotsubo cardiomyopathy, which is characterized by reversible left ventricular akinesis without coronary artery obstruction, is becoming increasingly reported. Herein we have presented a case of reversible stress-induced takotsubo cardiomyopathy resulting in cardiac arrest in a patient undergoing liver transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke.

    PubMed

    Kim, Joonki; Kang, Sung-Wook; Mallilankaraman, Karthik; Baik, Sang-Ha; Lim, James C; Balaganapathy, Priyanka; She, David T; Lok, Ker-Zhing; Fann, David Y; Thambiayah, Uma; Tang, Sung-Chun; Stranahan, Alexis M; Dheen, S Thameem; Gelderblom, Mathias; Seet, Raymond C; Karamyan, Vardan T; Vemuganti, Raghu; Sobey, Christopher G; Mattson, Mark P; Jo, Dong-Gyu; Arumugam, Thiruma V

    2018-05-01

    Genetic changes due to dietary intervention in the form of either calorie restriction (CR) or intermittent fasting (IF) are not reported in detail until now. However, it is well established that both CR and IF extend the lifespan and protect against neurodegenerative diseases and stroke. The current research aims were first to describe the transcriptomic changes in brains of IF mice and, second, to determine whether IF induces extensive transcriptomic changes following ischemic stroke to protect the brain from injury. Mice were randomly assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing. The cerebral transcriptome of mice in AL group exhibited robust, sustained up-regulation of detrimental genetic pathways under ischemic stroke, but activation of these pathways was suppressed in IF16 group. Interestingly, the cerebral transcriptome of AL mice was largely unchanged during the 1 h of ischemia, whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways involved in neuroplasticity and down-regulation of protein synthesis. Our data provide a genetic molecular framework for understanding how IF protects brain cells against damage caused by ischemic stroke, and reveal cellular signaling and bioenergetic pathways to target in the development of clinical interventions.

  6. FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs

    PubMed Central

    Nakayoshi, Takaharu; Sasaki, Ken-ichiro; Kajimoto, Hidemi; Koiwaya, Hiroshi; Ohtsuka, Masanori; Ueno, Takafumi; Chibana, Hidetoshi; Itaya, Naoki; Sasaki, Masahiro; Yokoyama, Shinji; Fukumoto, Yoshihiro; Imaizumi, Tsutomu

    2014-01-01

    The effects of therapeutic angiogenesis by intramuscular injection of early pro-angiogenic cells (EPCs) to ischemic limbs are unsatisfactory. Oxidative stress in the ischemic limbs may accelerate apoptosis of injected EPCs, leading to less neovascularization. Forkhead transcription factor 4 (FOXO4) was reported to play a pivotal role in apoptosis signaling of EPCs in response to oxidative stress. Accordingly, we assessed whether FOXO4-knockdown EPCs (FOXO4KD-EPCs) could suppress the oxidative stress-induced apoptosis and augment the neovascularization capacity in ischemic limbs. We transfected small interfering RNA targeted against FOXO4 of human EPCs to generate FOXO4KD-EPCs and confirmed a successful knockdown. FOXO4KD-EPCs gained resistance to apoptosis in response to hydrogen peroxide in vitro. Oxidative stress stained by dihydroethidium was stronger for the immunodeficient rat ischemic limb tissue than for the rat non-ischemic one. Although the number of apoptotic EPCs injected into the rat ischemic limb was greater than that of apoptotic EPCs injected into the rat non-ischemic limb, FOXO4KD-EPCs injected into the rat ischemic limb brought less apoptosis and more neovascularization than EPCs. Taken together, the use of FOXO4KD-EPCs with resistance to oxidative stress-induced apoptosis may be a new strategy to augment the effects of therapeutic angiogenesis by intramuscular injection of EPCs. PMID:24663349

  7. Tailoring therapy for ischemic cardiomyopathy: is Laplace's law enough?

    PubMed

    Adhyapak, Srilakshmi M; Parachuri, V Rao

    2017-09-01

    The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure. Despite several interventions, both pharmaceutical and device based for the treatment of ensuing heart failure, the incidence is increasing in large proportions. Newer molecules like sacubitril show more promise. Despite these novel therapies, several patients relentlessly progress to a stage of advanced heart failure. The use of left-ventricular-assist devices has variable clinical benefit, with some patients progressing to heart transplantation.

  8. Mitochondria as key targets of cardioprotection in cardiac ischemic disease: role of thyroid hormone triiodothyronine.

    PubMed

    Forini, Francesca; Nicolini, Giuseppina; Iervasi, Giorgio

    2015-03-19

    Ischemic heart disease is the major cause of mortality and morbidity worldwide. Early reperfusion after acute myocardial ischemia has reduced short-term mortality, but it is also responsible for additional myocardial damage, which in the long run favors adverse cardiac remodeling and heart failure evolution. A growing body of experimental and clinical evidence show that the mitochondrion is an essential end effector of ischemia/ reperfusion injury and a major trigger of cell death in the acute ischemic phase (up to 48-72 h after the insult), the subacute phase (from 72 h to 7-10 days) and chronic stage (from 10-14 days to one month after the insult). As such, in recent years scientific efforts have focused on mitochondria as a target for cardioprotective strategies in ischemic heart disease and cardiomyopathy. The present review discusses recent advances in this field, with special emphasis on the emerging role of the biologically active thyroid hormone triiodothyronine (T3).

  9. Takotsubo cardiomyopathy associated with thyrotoxicosis: a case report and review of the literature.

    PubMed

    Eliades, Myrto; El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D

    2014-02-01

    Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity.

  10. Takotsubo Cardiomyopathy Associated with Thyrotoxicosis: A Case Report and Review of the Literature

    PubMed Central

    El-Maouche, Diala; Choudhary, Chitra; Zinsmeister, Bruce; Burman, Kenneth D.

    2014-01-01

    Background: Takotsubo or stress-induced cardiomyopathy is a form of reversible cardiomyopathy commonly associated with emotional or physical stress. Thyrotoxicosis has been identified as a rare cause of Takotsubo cardiomyopathy, with only 12 cases reported in the literature. Here, we report a case of thyroid storm presenting with Takotsubo cardiomyopathy in the setting of Graves' disease. Patient Findings: A 71-year-old woman presented with abdominal pain, vomiting, confusion, and history of weight loss. She was initially diagnosed and treated for diabetic ketoacidosis at another hospital and was transferred to our hospital one day after initial presentation because of concern for acute coronary syndrome. A diagnosis of Takotsubo cardiomyopathy was made on the basis of cardiac catheterization. At that time, she was diagnosed and treated for thyroid storm. Follow-up 7 weeks later revealed improvement of her cardiac function and near-normalization of thyroid hormone levels. Summary: In this patient, who presented with symptoms of heart failure, acute coronary syndrome was initially considered, but the diagnosis of Takotsubo cardiomyopathy associated with thyroid storm was ultimately made based on cardiac catheterization and laboratory investigation. Conclusions: Thyrotoxicosis is associated with adverse disturbances in the cardiovascular system. Takotsubo cardiomyopathy could be a presenting manifestation of thyroid storm, perhaps related to excess catecholamine levels or sensitivity. PMID:23560557

  11. The cardiokine story unfolds: ischemic stress-induced protein secretion in the heart.

    PubMed

    Doroudgar, Shirin; Glembotski, Christopher C

    2011-04-01

    Intercellular communication depends on many factors, including proteins released via the classical or non-classical secretory pathways, many of which must be properly folded to be functional. Owing to their adverse effects on the secretion machinery, stresses such as ischemia can impair the folding of secreted proteins. Paradoxically, cells rely on secreted proteins to mount a response designed to resist stress-induced damage. This review examines this paradox using proteins secreted from the heart, cardiokines, as examples, and focuses on how the ischemic heart maintains or even increases the release of select cardiokines that regulate important cellular processes in the heart, including excitation-contraction coupling, hypertrophic growth, myocardial remodeling and stem cell function, in ways that moderate ischemic damage and enhance cardiac repair. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Arrhythmia-induced cardiomyopathies: the riddle of the chicken and the egg still unanswered?

    PubMed

    Simantirakis, Emmanuel N; Koutalas, Emmanuel P; Vardas, Panos E

    2012-04-01

    The hypothesis testing of inappropriate fast, irregular, or asynchronous myocardial contraction provoking cardiomyopathy has been the primary focus of numerous research efforts, especially during the last few decades. Rapid ventricular rates resulting from supraventricular arrhythmias and atrial fibrillation (AF), irregularity of heart rhythm-basic element of AF-and asynchrony, as a consequence of right ventricular pacing, bundle branch block, or frequent premature ventricular complexes, have been established as primary causes of arrhythmia-induced cardiomyopathy. The main pathophysiological pathways involved have been clarified, including neurohumoral activation, energy stores depletion, and abnormalities in stress and strain. Unfortunately, from a clinical point of view, patients usually seek medical advice only when symptoms develop, while the causative arrhythmia may be present for months or years, resulting in myocardial remodelling, diastolic, and systolic dysfunction. In some cases, making a definite diagnosis may become a strenuous exercise for the treating physician, as the arrhythmia may not be present and, additionally, therapy must be applied for the diagnosis to be confirmed retrospectively. The diagnostic process is also hardened due to the fact that strict diagnosing criteria are still a matter of discrepancy. Therapy options include pharmaceutical agents trials, catheter-based therapies and, in the context of chronic ventricular pacing, resynchronization. For the majority of patients, partial or complete recovery is expected, although they have to be followed up thoroughly due to the risk of recurrence. Large, randomized controlled trials are more than necessary to optimize patients' stratification and therapeutic strategy choices.

  13. Sickle cell anemia mice develop a unique cardiomyopathy with restrictive physiology

    PubMed Central

    Bakeer, Nihal; James, Jeanne; Roy, Swarnava; Wansapura, Janaka; Shanmukhappa, Shiva Kumar; Lorenz, John N.; Osinska, Hanna; Backer, Kurt; Huby, Anne-Cecile; Shrestha, Archana; Niss, Omar; Fleck, Robert; Quinn, Charles T.; Taylor, Michael D.; Purevjav, Enkhsaikhan; Aronow, Bruce J.; Towbin, Jeffrey A.; Malik, Punam

    2016-01-01

    Cardiopulmonary complications are the leading cause of mortality in sickle cell anemia (SCA). Elevated tricuspid regurgitant jet velocity, pulmonary hypertension, diastolic, and autonomic dysfunction have all been described, but a unifying pathophysiology and mechanism explaining the poor prognosis and propensity to sudden death has been elusive. Herein, SCA mice underwent a longitudinal comprehensive cardiac analysis, combining state-of-the-art cardiac imaging with electrocardiography, histopathology, and molecular analysis to determine the basis of cardiac dysfunction. We show that in SCA mice, anemia-induced hyperdynamic physiology was gradually superimposed with restrictive physiology, characterized by progressive left atrial enlargement and diastolic dysfunction with preserved systolic function. This phenomenon was absent in WT mice with experimentally induced chronic anemia of similar degree and duration. Restrictive physiology was associated with microscopic cardiomyocyte loss and secondary fibrosis detectable as increased extracellular volume by cardiac-MRI. Ultrastructural mitochondrial changes were consistent with severe chronic hypoxia/ischemia and sarcomere diastolic-length was shortened. Transcriptome analysis revealed up-regulation of genes involving angiogenesis, extracellular-matrix, circadian-rhythm, oxidative stress, and hypoxia, whereas ion-channel transport and cardiac conduction were down-regulated. Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were noted in SCA mice before sudden death. Sudden cardiac death is common in humans with restrictive cardiomyopathies and long QT syndromes. Our findings may thus provide a unifying cardiac pathophysiology that explains the reported cardiac abnormalities and sudden death seen in humans with SCA. PMID:27503873

  14. Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

    PubMed Central

    Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano

    2015-01-01

    The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762

  15. Protective effect of remote ischemic per-conditioning in the ischemia and reperfusion-induce renal injury in rats.

    PubMed

    Yamaki, Vitor Nagai; Gonçalves, Thiago Barbosa; Coelho, João Vitor Baia; Pontes, Ruy Victor Simões; Costa, Felipe Lobato da Silva; Brito, Marcus Vinicius Henriques

    2012-12-01

    To evaluate the protective effect of remote ischemic per-conditioning in ischemia and reperfusion-induced renal injury. Fifteen rats (Rattus norvegicus) were randomized into three groups (n = 5): Group Normality (GN), Control Ischemia and Reperfusion (GIR) and Group remote ischemic per-conditioning (GPER). With the exception of the GN group, all others underwent renal ischemia for 30 minutes. In group GPER we performed the ischemic remote per-conditioning, consisting of three cycles of ischemia and reperfusion applied every five minutes during the ischemic period, to the left hindlimb of the rats by means of a tourniquet. To quantify the lesions we measured serum levels of creatinine and urea, as well as analyzed renal histopathology. The GPER group presented with better levels of urea (83.74 ± 14.58%) and creatinine (0.72 ± 26.14%) when compared to GIR group, approaching the GN group. Histopathologically, the lower levels of medullary congestion and hydropic degeneration were found in group GPER. The remote ischemic per-conditioning had a significant protective effect on renal ischemia and reperfusion.

  16. Hypocalcemic rachitic cardiomyopathy in infants

    PubMed Central

    Elidrissy, Abdelwahab T.H.; Munawarah, Medinah; Alharbi, Khalid M.

    2012-01-01

    Hypocalcemic cardiomyopathy in infants is characterized by heart failure in a previously normal infant with hypocalcemia without organic cardiac lesion. Vitamin D deficiency rickets is increasing in Middle East. In a six month study 136 cases of rickets were diagnosed in the main Children’s Hospital in Almadinah but none of them showed evidence of cardiomyopathy. Concerned of missing this serious complication of rickets we searched pub med and present this review article. Results 61 cases of hypocalcemic cardiomyopathy were reported as case reports with two series of 16 and 15 cases from London and Delhi, respectively. The major features of these cases: the age ranged from one month to 15 months with a mean age of 5 months. All presented with heart failure and hypocalcemia. There was a minor feature of rickets in a few of the cases. All had high alkaline phosphatase. Echocardiology evidence of cardiomyopathy was found in all. Most of them responded to calcium, vitamin D and cardiotonic and diuretics. Discussion We concentrated on pathogenesis of this hypocalcemic cardiomyopathy and reviewed the literature. The evidence available supports that the most likely cause of cardiomyopathy is hypocalcemia. Hypovitamin D also contributes but hyperparathyroidism might have a protective role as we did not detect any evidence of cardiomyopathy with hyperparathyroidism and florid features of rickets. Conclusion We need to look out for cardiomyopathy among infants with hypocalcemia. For prevention maternal supplementation during pregnancy and lactation with up to 2000 units of vitamin D and 400 units for their infants. PMID:24174842

  17. Real-time three-dimensional echocardiographic study of left ventricular function after infarct exclusion surgery for ischemic cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Qin, J. X.; Shiota, T.; McCarthy, P. M.; Firstenberg, M. S.; Greenberg, N. L.; Tsujino, H.; Bauer, F.; Travaglini, A.; Hoercher, K. J.; Buda, T.; hide

    2000-01-01

    BACKGROUND: Infarct exclusion (IE) surgery, a technique of left ventricular (LV) reconstruction for dyskinetic or akinetic LV segments in patients with ischemic cardiomyopathy, requires accurate volume quantification to determine the impact of surgery due to complicated geometric changes. METHODS AND RESULTS: Thirty patients who underwent IE (mean age 61+/-8 years, 73% men) had epicardial real-time 3-dimensional echocardiographic (RT3DE) studies performed before and after IE. RT3DE follow-up was performed transthoracically 42+/-67 days after surgery in 22 patients. Repeated measures ANOVA was used to compare the values before and after IE surgery and at follow-up. Significant decreases in LV end-diastolic (EDVI) and end-systolic (ESVI) volume indices were apparent immediately after IE and in follow-up (EDVI 99+/-40, 67+/-26, and 71+/-31 mL/m(2), respectively; ESVI 72+/-37, 40+/-21, and 42+/-22 mL/m(2), respectively; P:<0.05). LV ejection fraction increased significantly and remained higher (0.29+/-0.11, 0.43+/-0.13, and 0.42+/-0.09, respectively, P:<0.05). Forward stroke volume in 16 patients with preoperative mitral regurgitation significantly improved after IE and in follow-up (22+/-12, 53+/-24, and 58+/-21 mL, respectively, P:<0.005). New York Heart Association functional class at an average 285+/-144 days of clinical follow-up significantly improved from 3.0+/-0.8 to 1.8+/-0.8 (P:<0.0001). Smaller end-diastolic and end-systolic volumes measured with RT3DE immediately after IE were closely related to improvement in New York Heart Association functional class at clinical follow-up (Spearman's rho=0.58 and 0.60, respectively). CONCLUSIONS: RT3DE can be used to quantitatively assess changes in LV volume and function after complicated LV reconstruction. Decreased LV volume and increased ejection fraction imply a reduction in LV wall stress after IE surgery and are predictive of symptomatic improvement.

  18. Peripartum Cardiomyopathy Treatment with Dopamine Agonist and Subsequent Pregnancy with a Satisfactory Outcome.

    PubMed

    Melo, Maria Adélia Medeiros E; Carvalho, Jordão Sousa; Feitosa, Francisco Edson de Lucena; Araujo Júnior, Edward; Peixoto, Alberto Borges; Costa Carvalho, Francisco Herlânio; Carvalho, Regina Coeli Marques

    2016-06-01

    Pathophysiological mechanisms of peripartum cardiomyopathy are not yet completely defined, although there is a strong association with various factors that are already known, including pre-eclampsia. Peripartum cardiomyopathy treatment follows the same recommendations as heart failure with systolic dysfunction. Clinical and experimental studies suggest that products of prolactin degradation can induce this cardiomyopathy. The pharmacological suppression of prolactin production by D2 dopamine receptor agonists bromocriptine and cabergoline has demonstrated satisfactory results in the therapeutic response to the treatment. Here we present a case of an adolescent patient in her first gestation with peripartum cardiomyopathy that evolved to the normalized left ventricular function after cabergoline administration, which was used as an adjuvant in cardiac dysfunction treatment. Subsequently, despite a short interval between pregnancies, the patient exhibited satisfactory progress throughout the entire gestation or puerperium in a new pregnancy without any cardiac alterations. Dopamine agonists that are orally used and are affordable in most tertiary centers, particularly in developing countries, should be considered when treating peripartum cardiomyopathy cases. Thieme Publicações Ltda Rio de Janeiro, Brazil.

  19. EMMPRIN and its ligand cyclophilin A as novel diagnostic markers in inflammatory cardiomyopathy.

    PubMed

    Seizer, Peter; Geisler, Tobias; Bigalke, Boris; Schneider, Martin; Klingel, Karin; Kandolf, Reinhard; Stellos, Konstantinos; Schreieck, Jürgen; Gawaz, Meinrad; May, Andreas E

    2013-03-10

    During inflammatory cardiomyopathy matrix metalloproteinases are crucially involved in cardiac remodeling. The aim of the present study was to investigate whether the "extracellular matrix metalloproteinase inducer" EMMPRIN (CD147) and its ligand Cyclophilin A (CyPA) are upregulated in inflammatory cardiomyopathy and may serve as diagnostic markers. Therefore, a series of 102 human endomyocardial biopsies were analyzed for the expression of EMMPRIN and CyPA and correlated with histological and immunohistological findings. Endomyocardial biopsies were stained for EMMPRIN and CyPA in addition to standard histology (HE, Trichrom) and immunohistological stainings (MHC-II, CD68, CD3). 39 (38.2%) biopsies met the immunohistological criteria of an inflammatory cardiomyopathy. EMMPRIN, which was predominantly expressed on cardiomyocytes, was slightly (but significantly) upregulated in non inflammatory cardiomyopathies compared to normal histopathological findings and highly upregulated in inflammatory cardiomyopathy compared to both non inflammatory cardiomyopathy and normal histopathology. In contrast, CyPA reveals no enhanced expression in non inflammatory cardiomyopathies and a highly enhanced expression in inflammatory cardiomyopathy, where it is closely associated with leucocytes infiltrates. We found a strong correlation between both EMMPRIN and CyPA with the expression of MHC-II molecules (correlation coefficient 0.475 and 0.527, p<0.05). Moreover, we found a correlation for both EMMPRIN and CyPA with CD68 (correlation coefficient 0.393 and 0.387, p<0.05) and CD3 (correlation coefficient 0.360 and 0.235, p<0.05). EMMPRIN is enhanced in both inflammatory and non inflammatory cardiomyopathies and can serve as a marker of myocardial remodeling. CyPA may represent a novel and specific marker for cardiac inflammation. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  20. Major role of the PI3K/Akt pathway in ischemic tolerance induced by sublethal oxygen-glucose deprivation in cortical neurons in vitro.

    PubMed

    Bhuiyan, Mohammad Iqbal Hossain; Jung, Seo Yun; Kim, Hyoung Ja; Lee, Yong Sup; Jin, Changbae

    2011-06-01

    Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. Ischemic tolerance was simulated by preconditioning of the neurons with sublethal 1-h OGD imposed 12 h before lethal 3-h OGD. The time-course studies of relative phosphorylation and expression levels of ERK1/2, JNK and p38 MAPK showed lack of their involvement in ischemic tolerance. However, there were significant increases in Akt phosphorylation levels during the reperfusion period following preconditioned lethal OGD. In addition, Bcl-2 associated death promoter (Bad) and GSK-3β were also found to be inactivated during that reperfusion period. Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.

  1. Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies.

    PubMed

    Voulgari, Christina; Papadogiannis, Dimitrios; Tentolouris, Nicholas

    2010-10-21

    Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.

  2. Genetics Home Reference: familial restrictive cardiomyopathy

    MedlinePlus

    ... the United States and in Europe, restrictive cardiomyopathy accounts for less than five percent of all cardiomyopathies. The proportion of restrictive cardiomyopathy that runs in families is not known. Related Information What information about a genetic condition can statistics ...

  3. Effects of oxymatrine on sympathoexcitatory reflex induced by myocardial ischemic signaling mediated by P2X₃ receptors in rat SCG and DRG.

    PubMed

    Li, Guilin; Liu, Shuangmei; Yang, Yang; Xie, Jinyan; Liu, Jun; Kong, Fanjun; Tu, Guihua; Wu, Raoping; Li, Guodong; Liang, Shangdong

    2011-04-05

    Sympathoexcitatory reflex is characterized by an increase in blood pressure and sympathetic nerve activity. P2X₃ receptors in SCG neurons are involved in increasing sympathoexcitatory reflex after myocardial ischemic (MI) injury. The present study is aimed to explore the effects of oxymatrine (Oxy) on the transmission of myocardial ischemic signaling mediated by P2X₃ receptors in rat superior cervical ganglia (SCG) and cervical dorsal root ganglia (DRG) in the sympathoexcitatory reflex after myocardial ischemic injury. In this study, the expression levels of P2X₃ immunoreactivity, mRNA and protein were analyzed in SCG and DRG neurons by immunohistochemistry, in situ hybridization and Western blotting. The results show that the myocardial ischemic injury induces the increase of the systolic blood pressure and heart rate and upregulates the expression of P2X₃ receptors in SCG and DRG neurons. Upregulated expression of P2X₃ receptors in SCG and DRG neurons subsequently leads to the aggravated sympathoexcitatory reflex. Oxymatrine reduces the systolic blood pressure and heart rate in myocardial ischemic rats. After myocardial ischemic rats are treated with oxymatrine, the expression levels of P2X₃ immunoreactivity, mRNA and protein are lower than those in myocardial ischemic rats. Oxymatrine may decrease the expression of P2X₃ receptor and depress the aggravated sympathoexcitatory reflex induced by the nociceptive transmission of myocardial ischemic injury via P2X₃ receptors of rat SCG and DRG neurons. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Nitric oxide, PKC-ε, and connexin43 are crucial for ischemic preconditioning-induced chemical gap junction uncoupling.

    PubMed

    Rong, Bing; Xie, Fei; Sun, Tao; Hao, Li; Lin, Ming-Jie; Zhong, Jing-Quan

    2016-10-25

    Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-ε (PKC-ε) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-ε levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-ε translocation inhibitory peptide (PKC-ε-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-ε, but not PKC-δ, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-ε translocation, Cx43 phosphorylation, and chemical GJ uncoupling.

  5. Autoantibodies in dilated cardiomyopathy induce vascular endothelial growth factor expression in cardiomyocytes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saygili, Erol, E-mail: erol.saygili@med.uni-duesseldorf.de; Noor-Ebad, Fawad; Schröder, Jörg W.

    2015-09-11

    Background: Autoantibodies have been identified as major predisposing factors for dilated cardiomyopathy (DCM). Patients with DCM show elevated serum levels of vascular endothelial growth factor (VEGF) whose source is unknown. Besides its well-investigated effects on angiogenesis, evidence is present that VEGF signaling is additionally involved in fibroblast proliferation and cardiomyocyte hypertrophy, hence in cardiac remodeling. Whether autoimmune effects in DCM impact cardiac VEGF signaling needs to be elucidated. Methods: Five DCM patients were treated by the immunoadsorption (IA) therapy on five consecutive days. The eluents from the IA columns were collected and prepared for cell culture. Cardiomyocytes from neonatal ratsmore » (NRCM) were incubated with increasing DCM-immunoglobulin-G (IgG) concentrations for 48 h. Polyclonal IgG (Venimmun N), which was used to restore IgG plasma levels in DCM patients after the IA therapy was additionally used for control cell culture purposes. Results: Elevated serum levels of VEGF decreased significantly after IA (Serum VEGF (ng/ml); DCM pre-IA: 45 ± 9.1 vs. DCM post–IA: 29 ± 6.7; P < 0.05). In cell culture, pretreatment of NRCM by DCM-IgG induced VEGF expression in a time and dose dependent manner. Biologically active VEGF that was secreted by NRCM significantly increased BNP mRNA levels in control cardiomyocytes and induced cell-proliferation of cultured cardiac fibroblast (Fibroblast proliferation; NRCM medium/HC-IgG: 1 ± 0.0 vs. NRCM medium/DCM-IgG 100 ng/ml: 5.6 ± 0.9; P < 0.05). Conclusion: The present study extends the knowledge about the possible link between autoimmune signaling in DCM and VEGF induction. Whether this observation plays a considerable role in cardiac remodeling during DCM development needs to be further elucidated. - Highlights: • Mechanisms of remodeling in dilated cardiomyopathy (DCM) are not fully understood. • Autoantibodies have been identified as major predisposing

  6. Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy.

    PubMed

    O'Neal, Wesley T; Griffin, William F; Kent, Susan D; Faiz, Filza; Hodges, Jonathan; Vuncannon, Jackson; Virag, Jitka A I

    2014-01-01

    EphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy.

  7. Deletion of the EphA2 receptor exacerbates myocardial injury and the progression of ischemic cardiomyopathy

    PubMed Central

    O'Neal, Wesley T.; Griffin, William F.; Kent, Susan D.; Faiz, Filza; Hodges, Jonathan; Vuncannon, Jackson; Virag, Jitka A. I.

    2014-01-01

    EphrinA1-EphA-receptor signaling is protective during myocardial infarction (MI). The EphA2-receptor (EphA2-R) potentially mediates cardiomyocyte survival. To determine the role of the EphA2-R in acute non-reperfused myocardial injury in vivo, infarct size, inflammatory cell density, NF-κB, p-AKT/Akt, and MMP-2 protein levels, and changes in ephrinA1/EphA2-R gene expression profile were assessed 4 days post-MI in B6129 wild-type (WT) and EphA2-R-mutant (EphA2-R-M) mice lacking a functional EphA2-R. Fibrosis, capillary density, morphometry of left ventricular chamber and infarct dimensions, and cardiac function also were measured 4 weeks post-MI to determine the extent of ventricular remodeling. EphA2-R-M infarct size and area of residual necrosis were 31.7% and 113% greater than WT hearts, respectively. Neutrophil and macrophage infiltration were increased by 46% and 84% in EphA2-R-M hearts compared with WT, respectively. NF-κB protein expression was 1.9-fold greater in EphA2-R-M hearts at baseline and 56% less NF-κB after infarction compared with WT. EphA6 gene expression was 2.5-fold higher at baseline and increased 9.8-fold 4 days post-MI in EphA2-R-M hearts compared with WT. EphrinA1 gene expression in EphA2-R-M hearts was unchanged at baseline and decreased by 42% 4 days post-MI compared with WT hearts. EphA2-R-M hearts had 66.7% less expression of total Akt protein and 59% less p-Akt protein than WT hearts post-MI. EphA2-R-M hearts 4 weeks post-MI had increased chamber dilation and interstitial fibrosis and decreased MMP-2 expression and capillary density compared with WT. In conclusion, the EphA2-R is necessary to appropriately modulate the inflammatory response and severity of early injury during acute MI, thereby influencing the progression of ischemic cardiomyopathy. PMID:24795639

  8. Gene Editing and Gene-Based Therapeutics for Cardiomyopathies.

    PubMed

    Ohiri, Joyce C; McNally, Elizabeth M

    2018-04-01

    With an increasing understanding of genetic defects leading to cardiomyopathy, focus is shifting to correcting these underlying genetic defects. One approach involves treating mutant RNA through antisense oligonucleotides; the first drug has received regulatory approval to treat specific mutations associated with Duchenne muscular dystrophy. Gene editing is being evaluated in the preclinical setting. For inherited cardiomyopathies, genetic correction strategies require tight specificity for the mutant allele. Gene-editing methods are being tested to create deletions that may be useful to restore protein expression by through the bypass of mutations that restore protein production. Site-specific gene editing, which is required to correct many point mutations, is a less efficient process than inducing deletions. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Neuronal SIRT1 (Silent Information Regulator 2 Homologue 1) Regulates Glycolysis and Mediates Resveratrol-Induced Ischemic Tolerance.

    PubMed

    Koronowski, Kevin B; Khoury, Nathalie; Saul, Isabel; Loris, Zachary B; Cohan, Charles H; Stradecki-Cohan, Holly M; Dave, Kunjan R; Young, Juan I; Perez-Pinzon, Miguel A

    2017-11-01

    Resveratrol, at least in part via SIRT1 (silent information regulator 2 homologue 1) activation, protects against cerebral ischemia when administered 2 days before injury. However, it remains unclear if SIRT1 activation must occur, and in which brain cell types, for the induction of neuroprotection. We hypothesized that neuronal SIRT1 is essential for resveratrol-induced ischemic tolerance and sought to characterize the metabolic pathways regulated by neuronal Sirt1 at the cellular level in the brain. We assessed infarct size and functional outcome after transient 60 minute middle cerebral artery occlusion in control and inducible, neuronal-specific SIRT1 knockout mice. Nontargeted primary metabolomics analysis identified putative SIRT1-regulated pathways in brain. Glycolytic function was evaluated in acute brain slices from adult mice and primary neuronal-enriched cultures under ischemic penumbra-like conditions. Resveratrol-induced neuroprotection from stroke was lost in neuronal Sirt1 knockout mice. Metabolomics analysis revealed alterations in glucose metabolism on deletion of neuronal Sirt1 , accompanied by transcriptional changes in glucose metabolism machinery. Furthermore, glycolytic ATP production was impaired in acute brain slices from neuronal Sirt1 knockout mice. Conversely, resveratrol increased glycolytic rate in a SIRT1-dependent manner and under ischemic penumbra-like conditions in vitro. Our data demonstrate that resveratrol requires neuronal SIRT1 to elicit ischemic tolerance and identify a novel role for SIRT1 in the regulation of glycolytic function in brain. Identification of robust neuroprotective mechanisms that underlie ischemia tolerance and the metabolic adaptations mediated by SIRT1 in brain are crucial for the translation of therapies in cerebral ischemia and other neurological disorders. © 2017 American Heart Association, Inc.

  10. Cardiac Magnetic Resonance Imaging in Ischemic Heart Disease

    PubMed Central

    Florian, A.; Jurcut, R.; Ginghina, C.; Bogaert, J.

    2011-01-01

    Cardiac magnetic resonance imaging (MRI) has emerged as a prime player in the clinical and preclinical detection of ischemic heart disease (IHD) as well in the prognosis assessment by offering a comprehensive approach for all spectrums of coronary artery disease (CAD) patients. The aim of this review is to provide the reader a state–of–the art on how the newest cardiac MRI techniques can be used to study IHD patients. In patients with suspected/stable CAD, functional and perfusion imaging both at rest and during vasodilatatory stress (adenosine, dypiridamole)/dobutamine stress can accurately depict ischemic myocardium secondary to significant coronary artery stenosis. In patients with acute MI, MRI is a robust tool for differentiating and sizing the jeopardized and the infarcted myocardium by using a combination of functional, edema, perfusion and Gd contrast imaging. Moreover, important prognostic factors like myocardial salvage, the presence of microvascular obstruction (MVO), post reperfusion myocardial hemorrhage, RV involvement and infarct related complications can be assessed in the same examination. In patients with chronic ischemic cardiomyopathy, the role of the MRI extends from diagnosis by means of Gadolinium contrast scar imaging to therapy and prognosis by functional assessment and viability testing with rest and dobutamine stress imaging. In all the circumstances mentioned, MRI derived information has been proven valuable in every day clinical decision making and prognosis assessment. Thus, MRI is becoming more and more an accepted alternative to other imaging modalities both in the acute and chronic setting. PMID:22514564

  11. Inherited cardiomyopathies and sports participation.

    PubMed

    Zorzi, A; Pelliccia, A; Corrado, D

    2018-03-01

    Competitive sports activity is associated with an increased risk of sudden cardiovascular death in adolescents and young adults with inherited cardiomyopathies. Many young subjects aspire to continue competitive sport after a diagnosis of cardiomyopathy and the clinician is frequently confronted with the problem of eligibility and the request of designing specific exercise programs. Since inherited cardiomyopathies are the leading cause of sudden cardiovascular death during sports performance, a conservative approach implying disqualification of affected athletes from most competitive athletic disciplines is recommended by all the available international guidelines. On the other hand, we know that the health benefits of practicing recreational sports activity can overcome the potential arrhythmic risk in these patients, provided that the type and level of exercise are tailored on the basis of the specific risk profile of the underlying cardiomyopathy. This article will review the available evidence on the sports-related risk of sudden cardiac death and the recommendations regarding eligibility of individuals affected by inherited cardiomyopathies for sports activities.

  12. Cirrhotic cardiomyopathy

    PubMed Central

    Ruiz-del-Árbol, Luis; Serradilla, Regina

    2015-01-01

    During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to a failure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the follow-up progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function. PMID:26556983

  13. Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism.

    PubMed

    Sarullo, Filippo M; Americo, Luigi; Accardo, Salvatore; Cicero, Sergio; Schicchi, Rossella; Schirò, Maria; Castello, Antonio

    2009-03-01

    A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism.

  14. Psoriasis and dilated cardiomyopathy: coincidence or associated diseases?

    PubMed

    Eliakim-Raz, Noa; Shuvy, Mony; Lotan, Chaim; Planer, David

    2008-01-01

    Psoriasis is a common immune-mediated disease which affects 1-3% of the population. The etiology of psoriasis is unknown. Idiopathic dilated cardiomyopathy is probably the end result of a variety of toxic, metabolic or infectious agents. During a computerized search for cardiomyopathy among all patients hospitalized with psoriasis in the Hadassah University Hospital since 1980 we found an increased prevalence of cardiomyopathy, and specifically dilated cardiomyopathy. We present 4 patients who suffer from both conditions. In accordance with previous data, an association between preexisting psoriasis and dilated cardiomyopathy is suggested. We suggest that the genetic risk factors of dilated cardiomyopathy are shared by psoriasis, and more specifically psoriatic arthritis. Alternatively, the immune reaction that is triggered in dilated cardiomyopathy leading to the progression of the disease might be enhanced in patients with psoriasis or psoriatic arthritis. Chronic inflammation and persistent secretion of proinflammatory cytokines may be considered a potential pathway, triggering the initiation and progression of dilated cardiomyopathy in psoriatic patients. Further investigation of the genetic and immune risk factors involved in dilated cardiomyopathy and in psoriasis may lead to a better understanding of the pathogenesis and treatment of dilated cardiomyopathy. Copyright 2008 S. Karger AG, Basel.

  15. The peptide NDP-MSH induces phenotype changes in the heart that resemble ischemic preconditioning.

    PubMed

    Catania, Anna; Lonati, Caterina; Sordi, Andrea; Leonardi, Patrizia; Carlin, Andrea; Gatti, Stefano

    2010-01-01

    alpha-Melanocyte-stimulating hormone (alpha-MSH) is a pro-opiomelanocortin (POMC)-derived peptide that exerts multiple protective effects on host cells. Previous investigations showed that treatment with alpha-MSH or synthetic melanocortin agonists reduces heart damage in reperfusion injury and transplantation. The aim of this preclinical research was to determine whether melanocortin treatment induces preconditioning-like cardioprotection. In particular, the plan was to assess whether melanocortin administration causes phenotype changes similar to those induced by repetitive ischemic events. The idea was conceived because both ischemic preconditioning and melanocortin signaling largely depend on cAMP response element binding protein (CREB) phosphorylation. Rats received single i.v. injections of 750microg/kg of the alpha-MSH analogue Nle(4),DPhe(7)-alpha-MSH (NDP-MSH) or saline and were sacrificed at 0.5, 1, 3, or 5h. Western blot analysis showed that rat hearts expressed melanocortin 1 receptor (MC1R) protein. Treatment with NDP-MSH was associated with early and marked increase in interleukin 6 (IL-6) mRNA. This was followed by signal transducer and activator of transcription 3 (STAT3) phosphorylation and induction of suppressor of cytokine signaling 3 (SOCS3). There were no changes in expression of other cytokines of the IL-6 family. Expression of IL-10, IL-1beta, and TNF-alpha was likewise unaltered. In hearts of rats treated with NDP-MSH there was increased expression of the orphan nuclear receptor Nur77. The data indicate that NDP-MSH induces phenotype changes that closely resemble ischemic preconditioning and likely contribute to its established protection against reperfusion injury. In addition, the increased expression of Nur77 and SOCS3 could be part of a broader anti-inflammatory effect.

  16. Genetics Home Reference: X-linked dilated cardiomyopathy

    MedlinePlus

    ... Twitter Home Health Conditions X-linked dilated cardiomyopathy X-linked dilated cardiomyopathy Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description X-linked dilated cardiomyopathy is a form of heart ...

  17. Nitric oxide, PKC-ε, and connexin43 are crucial for ischemic preconditioning-induced chemical gap junction uncoupling

    PubMed Central

    Sun, Tao; Hao, Li; Lin, Ming-Jie; Zhong, Jing-Quan

    2016-01-01

    Ischemic preconditioning (IPC) maintains connexin43 (Cx43) phosphorylation and reduces chemical gap junction (GJ) coupling in cardiomyocytes to protect against ischemic damage. However, the signal transduction pathways underlying these effects are not fully understood. Here, we investigated whether nitric oxide (NO) and protein kinase C-ε (PKC-ε) contribute to IPC-induced cardioprotection by maintaining Cx43 phosphorylation and inhibiting chemical GJ coupling. IPC reduced ischemia-induced myocardial infarction and increased cardiomyocyte survival; phosphorylated Cx43, eNOS, and PKC-ε levels; and chemical GJ uncoupling. Administration of the NO donor SNAP mimicked the effects of IPC both in vivo and in vitro, maintaining Cx43 phosphorylation, promoting chemical GJ uncoupling, and reducing myocardial infarction. Preincubation with the NO synthase inhibitor L-NAME or PKC-ε translocation inhibitory peptide (PKC-ε-TIP) abolished these effects of IPC. Additionally, by inducing NO production, IPC induced translocation of PKC-ε, but not PKC-δ, from the cytosolic to the membrane fraction in primary cardiac myocytes. IPC-induced cardioprotection thus involves increased NO production, PKC-ε translocation, Cx43 phosphorylation, and chemical GJ uncoupling. PMID:27655723

  18. Cortical spreading depression preconditioning mediates neuroprotection against ischemic stroke by inducing AMP-activated protein kinase-dependent autophagy in a rat cerebral ischemic/reperfusion injury model.

    PubMed

    Shen, Pingping; Hou, Shuai; Zhu, Mingqin; Zhao, Mingming; Ouyang, Yibing; Feng, Jiachun

    2017-03-01

    Cortical spreading depression (CSD), based on its similarities with peri-infarct depolarization, is an ideal model for investigating transformation from the ischemic penumbra to infarct core. However, the underlying mechanisms remain unclear. To our knowledge, this is the first study to use a middle cerebral artery occlusion ischemic-reperfusion (I/R) injury model to determine whether AMP-activated protein kinase (AMPK)-dependent autophagy contributes to the neuroprotection of CSD preconditioning in rat cortex. In this study, we topically applied a pledget soaked in 1 mol/L KCl solution on rat cortex for 2 h to elicite CSD or 1 mol/L NaCl solution as a control. The results demonstrated that CSD preconditioning significantly decreased the infarct volume, neurological deficits and neuronal apoptosis in the cortical penumbra of middle cerebral artery occlusion rats, which was inhibited by the autophagy inhibitor 3-methyladenine (3-MA, 200 nmol). Furthermore, CSD increased the protein levels of the autophagy markers LC3-II, Beclin-1 and the p-AMPK (Thr 172 )/AMPK ratio at 12 h and decreased P62 and p-P70S6K (Thr 389 ). Moreover, the AMPK inhibitor Compound C (20 mg/kg) down-regulated the LC3-II, p-AMPK (Thr 172 )/AMPK and ULK1 levels, up-regulated the P62 and p-P70S6K (Thr 389 ) levels induced by CSD. The neuroprotection of CSD is likely a result of AMPK-mediated autophagy activity and autophagy-induced neuronal cells apoptosis inhibition. These novel findings support a central role for AMPK and autophagy in CSD-induced ischemic tolerance. AMPK-mediated autophagy may represent a new target for stroke. © 2016 International Society for Neurochemistry.

  19. Intramyocardial VEGF-B167 gene delivery delays the progression towards congestive failure in dogs with pacing-induced dilated cardiomyopathy.

    PubMed

    Pepe, Martino; Mamdani, Mohammed; Zentilin, Lorena; Csiszar, Anna; Qanud, Khaled; Zacchigna, Serena; Ungvari, Zoltan; Puligadda, Uday; Moimas, Silvia; Xu, Xiaobin; Edwards, John G; Hintze, Thomas H; Giacca, Mauro; Recchia, Fabio A

    2010-06-25

    Vascular endothelial growth factor (VEGF)-B selectively binds VEGF receptor (VEGFR)-1, a receptor that does not mediate angiogenesis, and is emerging as a major cytoprotective factor. To test the hypothesis that VEGF-B exerts non-angiogenesis-related cardioprotective effects in nonischemic dilated cardiomyopathy. AAV-9-carried VEGF-B(167) cDNA (10(12) genome copies) was injected into the myocardium of chronically instrumented dogs developing tachypacing-induced dilated cardiomyopathy. After 4 weeks of pacing, green fluorescent protein-transduced dogs (AAV-control, n=8) were in overt congestive heart failure, whereas the VEGF-B-transduced (AAV-VEGF-B, n=8) were still in a well-compensated state, with physiological arterial Po(2). Left ventricular (LV) end-diastolic pressure in AAV-VEGF-B and AAV-control was, respectively, 15.0+/-1.5 versus 26.7+/-1.8 mm Hg and LV regional fractional shortening was 9.4+/-1.6% versus 3.0+/-0.6% (all P<0.05). VEGF-B prevented LV wall thinning but did not induce cardiac hypertrophy and did not affect the density of alpha-smooth muscle actin-positive microvessels, whereas it normalized TUNEL-positive cardiomyocytes and caspase-9 and -3 activation. Consistently, activated Akt, a major negative regulator of apoptosis, was superphysiological in AAV-VEGF-B, whereas the proapoptotic intracellular mediators glycogen synthase kinase (GSK)-3beta and FoxO3a (Akt targets) were activated in AAV-control, but not in AAV-VEGF-B. Cardiac VEGFR-1 expression was reduced 4-fold in all paced dogs, suggesting that exogenous VEGF-B(167) exerted a compensatory receptor stimulation. The cytoprotective effects of VEGF-B(167) were further elucidated in cultured rat neonatal cardiomyocytes exposed to 10(-8) mol/L angiotensin II: VEGF-B(167) prevented oxidative stress, loss of mitochondrial membrane potential, and, consequently, apoptosis. We determined a novel, angiogenesis-unrelated cardioprotective effect of VEGF-B(167) in nonischemic dilated cardiomyopathy

  20. Cardiomyopathy

    MedlinePlus

    ... to grow in the heart and other organs (sarcoidosis) A disorder that causes the buildup of abnormal ... to grow in the heart and other organs (sarcoidosis), or connective tissue disorders Complications Cardiomyopathy can lead ...

  1. Biventricular Takotsubo cardiomyopathy in Graves hyperthyroidism.

    PubMed

    Perkins, Matthew J; Schachter, David T

    2014-03-01

    Graves hyperthyroidism is commonly seen in clinical practice and Takotsubo stress cardiomyopathy is an increasingly recognized cardiac complication of physical or emotional stress. We report the rare case of a patient with Graves hyperthyroidism that was complicated by severe biventricular takotsubo cardiomyopathy, which was demonstrated on heart catheterization. After appropriate pharmacologic treatment of her hyperthyroidism, she had complete resolution of her cardiomyopathy.

  2. Protection of retinal function by sulforaphane following retinal ischemic injury.

    PubMed

    Ambrecht, Lindsay A; Perlman, Jay I; McDonnell, James F; Zhai, Yougang; Qiao, Liang; Bu, Ping

    2015-09-01

    Sulforaphane, a precursor of glucosinolate in cruciferous vegetables such as broccoli and cauliflower, has been shown to protect brain ischemic injury. In this study, we examined the effect of systemic administration of sulforaphane on retinal ischemic reperfusion injury. Intraocular pressure was elevated in two groups of C57BL/6 mice (n = 8 per group) for 45 min to induce retinal ischemic reperfusion injury. Following retinal ischemic reperfusion injury, vehicle (1% DMSO saline) or sulforaphane (25 mg/kg/day) was administered intraperitoneally daily for 5 days. Scotopic electroretinography (ERG) was used to quantify retinal function prior to and one-week after retinal ischemic insult. Retinal morphology was examined one week after ischemic insult. Following ischemic reperfusion injury, ERG a- and b-wave amplitudes were significantly reduced in the control mice. Sulforaphane treatment significantly attenuated ischemic-induced loss of retinal function as compared to vehicle treated mice. In vehicle treated mice, ischemic reperfusion injury produced marked thinning of the inner retinal layers, but the thinning of the inner retinal layers appeared significantly less with sulforaphane treatment. Thus, sulforaphane may be beneficial in the treatment of retinal disorders with ischemic reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Alcoholic cardiomyopathy: Pathophysiologic insights

    PubMed Central

    Piano, Mariann R.; Phillips, Shane A.

    2014-01-01

    Alcoholic cardiomyopathy is a specific heart muscle disease found in individuals with a history of long-term heavy alcohol consumption. Alcoholic cardiomyopathy is associated with a number of adverse histological, cellular, and structural changes within the myocardium. Several mechanisms are implicated in mediating the adverse effects of ethanol, including the generation of oxidative stress, apoptotic cell death, impaired mitochondrial bioenergetics/stress, derangements in fatty acid metabolism and transport, and accelerated protein catabolism. In this review, we discuss the evidence for such mechanisms and present the potential importance of drinking patterns, genetic susceptibility, nutritional factors, race, and sex. The purpose of this review is to provide a mechanistic paradigm for future research in the area of alcoholic cardiomyopathy. PMID:24671642

  4. Infectious agents and inflammation in donated hearts and dilated cardiomyopathies related to cardiovascular diseases, Chagas' heart disease, primary and secondary dilated cardiomyopathies.

    PubMed

    Mangini, Sandrigo; Higuchi, Maria de Lourdes; Kawakami, Joyce Tiyeko; Reis, Marcia Martins; Ikegami, Renata Nishiyama; Palomino, Suely Aparecida Pinheiro; Pomerantzeff, Pablo Maria Alberto; Fiorelli, Alfredo Inácio; Marcondes-Braga, Fabiana Goulart; Bacal, Fernando; Ferreira, Sílvia Moreira Ayub; Issa, Victor Sarli; Souza, Germano Emílio Conceição; Chizzola, Paulo Roberto; Bocchi, Edimar Alcides

    2015-01-15

    Clinical and experimental conflicting data have questioned the relationship between infectious agents, inflammation and dilated cardiomyopathy (DCM). The aim of this study was to determine the frequency of infectious agents and inflammation in endomyocardial biopsy (EMB) specimens from patients with idiopathic DCM, explanted hearts from different etiologies, including Chagas' disease, compared to donated hearts. From 2008 to 2011, myocardial samples from 29 heart donors and 55 patients with DCMs from different etiologies were studied (32 idiopathic, 9 chagasic, 6 ischemic and 8 other specific etiologies). Inflammation was investigated by immunohistochemistry and infectious agents by immunohistochemistry, molecular biology, in situ hybridization and electron microscopy. There were no differences regarding the presence of macrophages, expression of HLA class II and ICAM-I in donors and DCM. Inflammation in Chagas' disease was predominant. By immunohistochemistry, in donors, there was a higher expression of antigens of enterovirus and Borrelia, hepatitis B and C in DCMs. By molecular biology, in all groups, the positivity was elevated to microorganisms, including co-infections, with a higher positivity to adenovirus and HHV6 in donors towards DCMs. This study was the first to demonstrate the presence of virus in the heart tissue of chagasic DCM. The presence of inflammation and infectious agents is frequent in donated hearts, in the myocardium of patients with idiopathic DCM, myocardial dysfunction related to cardiovascular diseases, and primary and secondary cardiomyopathies, including Chagas' disease. The role of co-infection in Chagas' heart disease physiopathology deserves to be investigated in future studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Cardiogenic shock with basal transient left ventricular ballooning (Takotsubo-like cardiomyopathy) as first presentation of pheochromocytoma.

    PubMed

    Di Palma, Gisella; Daniele, Gian P; Antonini-Canterin, Francesco; Piazza, Rita; Nicolosi, Gian L

    2010-07-01

    Pheochromocytoma is a rare tumor that produces a distant effect by secretion of catecholamines. This tumor usually presents with hypertension and palpitations but it may also cause cardiogenic shock because of catecholamine-induced myocardial dysfunction. We describe a rare case of Takotsubo-like cardiomyopathy as first manifestation of pheochromocytoma with an unusual onset characterized by severe hypotension and transient basal left ventricular ballooning ('inverted' Takotsubo-like cardiomyopathy).

  6. Is There a Role for Genes in Exercise-Induced Atrial Cardiomyopathy?

    PubMed

    Fatkin, Diane; Cox, Charles D; Huttner, Inken G; Martinac, Boris

    2018-04-09

    In endurance athletes, prolonged high intensity exercise participation can have deleterious effects on the myocardium with subsequent structural and electrical remodelling. In a subset of athletes, there is a predilection for atrial involvement and the risk of atrial fibrillation (AF) is increased. The mechanisms underpinning exercise-induced atrial cardiomyopathy have yet to be fully elucidated and the contribution of an individual's genetic makeup is unknown. Some athletes may have rare genetic variants that are sufficient to cause AF irrespective of exercise exposure. In AF-causing variant carriers, the additional haemodynamic stress of exercise on atrial structure and function might accelerate or increase the severity of disease. Variants in genes that lack known links to AF may indirectly promote an arrhythmogenic substrate by affecting threshold levels for exercise-induced myocardial damage and remodelling responses, or by effects on AF-associated co-morbidities, sinus node function, and autonomic nervous system tone. Given the exquisite stress-sensitivity of the atria, mechanosensitive ion channels could plausibly have a key role in mediating exercise effects on atrial structure and function. Knowing an athlete's profile of genetic variants may be useful for AF risk stratification and have implications for clinical management. Pre-participation genetic testing may influence sports choices and facilitate AF prevention. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  7. [Ischemic cholangiopathy induced by extended burns].

    PubMed

    Cohen, Laurence; Angot, Emilie; Goria, Odile; Koning, Edith; François, Arnaud; Sabourin, Jean-Christophe

    2013-04-01

    Ischemic cholangiopathy is a recently described entity occurring mainly after hepatic grafts. Very few cases after intensive care unit (ICU) for extended burn injury were reported. We report the case of a 73-year-old woman consulting in an hepatology unit, for a jaundice appearing during a hospitalisation in an intensive care unit and increasing from her leaving from ICU, where she was treated for an extended burn injury. She had no pre-existing biological features of biliary disease. Biological tests were normal. Magnetic resonance imaging acquisitions of biliary tracts pointed out severe stenosing lesions of diffuse cholangiopathy concerning intrahepatic biliary tract, mainly peri-hilar. Biopsie from the liver confirmed the diagnosis, showing a biliary cirrhosis with bile infarcts. This case is the fourth case of ischemic cholangiopathy after extended burn injury, concerning a patient without a prior history of hepatic or biliary illness and appearing after hospitalisation in intensive care unit. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. Electrocardiogram and Imaging: An Integrated Approach to Arrhythmogenic Cardiomyopathies.

    PubMed

    Savino, Ketty; Bagliani, Giuseppe; Crusco, Federico; Padeletti, Margherita; Lombardi, Massimo

    2018-06-01

    Cardiovascular imaging has radically changed the management of patients with arrhythmogenic cardiomyopathies. This article focuses on the role of echocardiography and MRI in the diagnosis of these structural diseases. Cardiomyopathies with hypertrophic pattern (hypertrophic cardiomyopathy, restrictive cardiomyopathies, amyloidosis, Anderson-Fabry disease, and sarcoidosis), cardiomyopathies with dilated pattern, inflammatory cardiac diseases, and right ventricular arrhythmogenic cardiomyopathy are analyzed. Finally, anatomic predictors of arrhythmias and sudden cardiac death are discussed. Each paragraph is attended by clinical cases that are discussed on the electrocardiogram, after integrated with the anatomic, functional, and hemodynamic modifications of cardiovascular imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Alcoholic cardiomyopathy

    PubMed Central

    Guzzo-Merello, Gonzalo; Cobo-Marcos, Marta; Gallego-Delgado, Maria; Garcia-Pavia, Pablo

    2014-01-01

    Alcohol is the most frequently consumed toxic substance in the world. Low to moderate daily intake of alcohol has been shown to have beneficial effects on the cardiovascular system. In contrast, exposure to high levels of alcohol for a long period could lead to progressive cardiac dysfunction and heart failure. Cardiac dysfunction associated with chronic and excessive alcohol intake is a specific cardiac disease known as alcoholic cardiomyopathy (ACM). In spite of its clinical importance, data on ACM and how alcohol damages the heart are limited. In this review, we evaluate available evidence linking excessive alcohol consumption with heart failure and dilated cardiomyopathy. Additionally, we discuss the clinical presentation, prognosis and treatment of ACM. PMID:25228956

  10. GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in Neuronal Cultures and Animal Models of Ischemic Stroke

    PubMed Central

    Chuang, De-Maw; Wang, Zhifei; Chiu, Chi-Tso

    2011-01-01

    The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3) directly or indirectly by enhancing serine phosphorylation of both α and β isoforms. Lithium robustly protected primary brain neurons from glutamate-induced excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or silencing/inhibiting GSK-3α and/or β isoforms. Lithium rapidly activated Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt inactivation. Lithium also up-regulated Bcl-2 and suppressed glutamate-induced p53 and Bax. Induction of brain-derived neurotrophic factor (BDNF) was required for lithium’s neuroprotection to occur. BDNF promoter IV was activated by GSK-3 inhibition using lithium or other drugs, or through gene silencing/inactivation of either isoform. Further, lithium’s neuroprotective effects were associated with inhibition of NMDA receptor-mediated calcium influx and down-stream signaling. In rodent ischemic models, post-insult treatment with lithium decreased infarct volume, ameliorated neurological deficits, and improved functional recovery. Up-regulation of heat-shock protein 70 and Bcl-2 as well as down-regulation of p53 likely contributed to lithium’s protective effects. Delayed treatment with lithium improved functional MRI responses, which was accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors, matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor were induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells (MSCs) by up-regulation of MMP-9 through GSK-3β inhibition. Notably, transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration to the injured brain regions and improved the neurological performance. Several other GSK-3 inhibitors have also been reported to be beneficial in rodent ischemic models. Together, GSK-3 inhibition is a rational strategy to combat ischemic stroke and other excitotoxicity-related brain

  11. The Natural History of Nonobstructive Hypertrophic Cardiomyopathy.

    PubMed

    Hebl, Virginia B; Miranda, William R; Ong, Kevin C; Hodge, David O; Bos, J Martijn; Gentile, Federico; Klarich, Kyle W; Nishimura, Rick A; Ackerman, Michael J; Gersh, Bernard J; Ommen, Steve R; Geske, Jeffrey B

    2016-03-01

    To describe the survival of a large nonobstructive hypertrophic cardiomyopathy (NO-HCM) cohort and to identify risk factors for increased mortality in this population. Patients were identified from the Mayo Clinic HCM database from January 1, 1975, through November 30, 2006, for this retrospective observational study. Patients with resting or provocable left ventricular outflow tract gradients were excluded. Echocardiographic, clinical, and genetic data were compared between subgroups, and survival data were compared with expected population rates. A total of 706 patients with NO-HCM were identified. During median follow-up of 5 years (mean, 7 years), there were 208 deaths. Overall survival was no different than expected compared with age- and sex-matched white US population mortality rates (P=.77). Independent predictors of death were age at diagnosis, "burned out" HCM, and history of transient ischemic attack or stroke; use of an implantable cardioverter defibrillator (ICD) was inversely related to death. After exclusion of patients with an ICD, there was no difference in survival compared with age- and sex- matched individuals (P=.39); age, previous transient ischemic attack/stroke, and burned out HCM were predictors of death. In this cohort, patients with NO-HCM had similar survival rates as age- and sex-matched white US population mortality rates. Although use of an ICD was inversely related to death, no differences in overall survival were seen after those patients were excluded. Burned out HCM was independently associated with an increased risk of death, identifying a subset of patients who may benefit from more aggressive therapies. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  12. Identification of new biophysical markers for pathological ventricular remodelling in tachycardia-induced dilated cardiomyopathy.

    PubMed

    Benitez-Amaro, Aleyda; Samouillan, Valerie; Jorge, Esther; Dandurand, Jany; Nasarre, Laura; de Gonzalo-Calvo, David; Bornachea, Olga; Amoros-Figueras, Gerard; Lacabanne, Colette; Vilades, David; Leta, Ruben; Carreras, Francesc; Gallardo, Alberto; Lerma, Enrique; Cinca, Juan; Guerra, Jose M; Llorente-Cortés, Vicenta

    2018-06-19

    Our aim was to identify biophysical biomarkers of ventricular remodelling in tachycardia-induced dilated cardiomyopathy (DCM). Our study includes healthy controls (N = 7) and DCM pigs (N = 10). Molecular analysis showed global myocardial metabolic abnormalities, some of them related to myocardial hibernation in failing hearts, supporting the translationality of our model to study cardiac remodelling in dilated cardiomyopathy. Histological analysis showed unorganized and agglomerated collagen accumulation in the dilated ventricles and a higher percentage of fibrosis in the right (RV) than in the left (LV) ventricle (P = .016). The Fourier Transform Infrared Spectroscopy (FTIR) 1st and 2nd indicators, which are markers of the myofiber/collagen ratio, were reduced in dilated hearts, with the 1st indicator reduced by 45% and 53% in the RV and LV, respectively, and the 2nd indicator reduced by 25% in the RV. The 3rd FTIR indicator, a marker of the carbohydrate/lipid ratio, was up-regulated in the right and left dilated ventricles but to a greater extent in the RV (2.60-fold vs 1.61-fold, P = .049). Differential scanning calorimetry (DSC) showed a depression of the freezable water melting point in DCM ventricles - indicating structural changes in the tissue architecture - and lower protein stability. Our results suggest that the 1st, 2nd and 3rd FTIR indicators are useful markers of cardiac remodelling. Moreover, the 2nd and 3rd FITR indicators, which are altered to a greater extent in the right ventricle, are associated with greater fibrosis. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress.

    PubMed

    Das, Subhash K; Patel, Vaibhav B; Basu, Ratnadeep; Wang, Wang; DesAulniers, Jessica; Kassiri, Zamaneh; Oudit, Gavin Y

    2017-01-23

    Sex-related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron-overload cardiomyopathy is poorly understood. Male and female wild-type and hemojuvelin-null mice were injected and fed with a high-iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron-overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron-overloaded mice based on echocardiographic and invasive pressure-volume analyses. Female mice demonstrated a marked suppression of iron-mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron-overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron-induced upregulation of ferritin, decreased myocardial SERCA2a levels, and increased NCX1 levels. 17β-Estradiol therapy rescued the iron-overload cardiomyopathy in male wild-type mice. The responses in wild-type and hemojuvelin-null female mice were remarkably similar, highlighting a conserved mechanism of sex-dependent protection from iron-overload-mediated cardiac injury. Male and female mice respond differently to iron-overload-mediated effects on heart structure and function, and females are markedly protected from iron-overload cardiomyopathy. Ovariectomy in female mice exacerbated iron-induced myocardial injury and precipitated severe cardiac dysfunction during iron-overload conditions, whereas 17β-estradiol therapy was protective in male iron-overloaded mice.

  14. Nicotinamide attenuates the ischemic brain injury-induced decrease of Akt activation and Bad phosphorylation.

    PubMed

    Koh, Phil-Ok

    2011-07-08

    Nicotinamide protects cortical neuronal cells against cerebral ischemic injury through activation of various cytoprotective mechanisms. Here, this study confirmed the neuroprotective effects of nicotinamide in focal cerebral ischemic injury and investigated whether nicotinamide modulates a crucial survival pathway, Akt and its downstream targets. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2h after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. Nicotinamide significantly reduced the infarct volume in the cerebral cortex. Potential activation was measured by phosphorylation of PDK1 at Ser(241), Akt at Ser(473), and Bad at Ser(136) using Western blot analysis. Nicotinamide prevented the injury-induced decrease of pPDK1, pAkt, and pBad levels. 14-3-3 levels were not different between vehicle- and nicotinamide-treated animals. However, pBad and 14-3-3 interaction levels decreased during MCAO, but were maintained in the presence of nicotinamide, compared to levels in control animals. These findings suggest that nicotinamide attenuates cell death due to focal cerebral ischemic injury and that neuroprotective effects are mediated through the Akt signaling pathway, thus enhancing neuronal survival. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. High validity of cardiomyopathy diagnoses in western Sweden (1989-2009).

    PubMed

    Basic, Carmen; Rosengren, Annika; Lindström, Sandra; Schaufelberger, Maria

    2018-04-01

    Hospital discharges with a diagnosis of cardiomyopathy have more than doubled in Sweden since 1987. We validated the cardiomyopathy diagnoses over this time period to investigate that the increase was real and not a result of improved recognition of the diagnosis and better diagnostic methods. Every fifth year from 1989 to 2009, records for all patients with a cardiomyopathy diagnosis were identified by searching the local registers in three hospitals in Västra Götaland, Sweden. The diagnoses were validated according to criteria defined by the European Society of Cardiology from 2008. The population comprised 611 cases with cardiomyopathy diagnoses [mean age 58.9 (SD 15.5) years, 68.2% male], divided into three major groups: dilated, hypertrophic, and other cardiomyopathies. Hypertrophic cardiomyopathy and hypertrophic obstructive cardiomyopathy were analysed as a group. Cardiomyopathies for which there were few cases, such as restrictive, arrhythmogenic right ventricular, left ventricular non-compaction, takotsubo, and peripartum cardiomyopathies, were analysed together and defined as 'other cardiomyopathies'. Relevant co-morbidities were registered. The use of echocardiography was 99.7%, of which 94.6% was complete echocardiography reports. The accuracy rates of the diagnoses dilated cardiomyopathy, hypertrophic cardiomyopathy, and other cardiomyopathies were 85.5%, 87.5%, and 100%, respectively, with no differences between the three hospitals or years studied; nor did the prevalence of co-morbidities differ. The accuracy rate of the cardiomyopathy diagnoses from in-hospital records from >600 patients in western Sweden during a 20 year period was 86.6%, with no significant trend over time, strengthening epidemiological findings that this is likely due to an actual increase in cardiomyopathy diagnoses rather than changes in coding practices. The use of echocardiography was high, and there was no significant difference in co-morbidities during the study period

  16. [Ischemic brain injury and hepatocyte growth factor].

    PubMed

    Takeo, Satoshi; Takagi, Norio; Takagi, Keiko

    2007-11-01

    Cerebral ischemia causes an irreversible and neurodegenerative disorder that may lead to progressive dementia and global cognitive deterioration. Since the overall process of ischemic brain injuries is extremely complex, treatment with endogenous multifunctional factors would be better choices for preventing complicated ischemic brain injuries. Hepatocyte growth factor, HGF, is a multifunctional cytokine originally identified and purified as a potent mitogen for hepatocyte. The activation of the c-Met/HGF receptor evokes diverse cellular responses, including mitogenic, morphogenic, angiogenic and anti-apoptotic activities in various types of cell. Previous studies showed that HGF and c-Met were expressed in various brain regions under normal conditions and that HGF enhanced the survival of hippocampal and cortical neurons during the aging of cells in culture. The protective effects of HGF on in vivo ischemic brain injuries and their mechanisms have not fully understood. To elucidate therapeutic potencies of HGF for ischemic brain injuries, we examined effects of HGF on ischemia-induced learning and memory dysfunction, neuronal cell death and endothelial cell damage by using the 4-vessel occlusion model and the microsphere embolism model in rats. Our findings suggested that treatment with HGF was capable of protecting hippocampal neurons against ischemia-induced cell death through the prevention of apoptosis-inducing factor translocation to the nucleus. Furthermore, we demonstrated that HGF had the ability to prevent tissue degeneration and improved learning and memory function after cerebral embolism, possibly through prevention of cerebral vessel injuries. As HGF has a potent cerebroprotective effect, it could be a prospective agent for the therapy against complicated ischemic brain diseases.

  17. Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography

    PubMed Central

    Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

    2007-01-01

    Background Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. Case Presentation A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Conclusion Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three

  18. Efficacy of chordal cutting in alleviating ischemic mitral regurgitation: insights from 3-dimensional echocardiography.

    PubMed

    Sai-Sudhakar, Chittoor B; Vandse, Rashmi; Armen, Todd A; Bickle, Katherine M; Nathan, Nadia S

    2007-09-25

    Ischemic mitral regurgitation often complicates severe ischemic heart disease and adversely affects the prognosis in these patients. There is wide variation in the clinical spectrum of ischemic mitral regurgitation due to varying location and chronicity of ischemia and anomalies in annular and ventricular remodeling. As a result, there is lack of consensus in treating these patients. Treatment has to be individualized for each patient. Most of the available surgical options do not consistently correct this condition in all the patients. Chordal cutting is one of the newer surgical approaches in which cutting a limited number of critically positioned basal chordae have found success by relieving the leaflet tethering and thereby improving the coaptation of leaflets. Three-dimensional echocardiography is a potentially valuable tool in identifying the specific pattern of tethering and thus the suitability of this procedure in a given clinical scenario. A 66-year-old man with cardiomyopathy and ischemic mitral regurgitation presented to us with the features of congestive heart failure. The three-dimensional echocardiography revealed severe mitral regurgitation associated with the tethering of the lateral (P1) and medial (P3) scallops of the posterior leaflet of the mitral valve due to secondary chordal attachments. The ejection fraction was only 15% with severe global systolic and diastolic dysfunction. Mitral regurgitation was successfully corrected with mitral annuloplasty and resection of the secondary chordae tethering the medial and lateral scallops of the posterior leaflet of the mitral valve. Cutting the second order chordae along with mitral annuloplasty could be a novel method to remedy Ischemic mitral regurgitation by relieving the tethering of the valve leaflets. The preoperative three-dimensional echocardiography should be considered in all patients with Ischemic mitral regurgitation to assess the complex three-dimensional interactions between the mitral

  19. Treatment of Chagas Cardiomyopathy

    PubMed Central

    Botoni, Fernando A.; Ribeiro, Antonio Luiz P.; Marinho, Carolina Coimbra; Lima, Marcia Maria Oliveira; Nunes, Maria do Carmo Pereira; Rocha, Manoel Otávio C.

    2013-01-01

    Chagas' disease (ChD), caused by the protozoa Trypanosoma cruzi (T. cruzi), was discovered and described by the Brazilian physician Carlos Chagas in 1909. After a century of original description, trypanosomiasis still brings much misery to humanity and is classified as a neglected tropical disease prevalent in underdeveloped countries, particularly in South America. It is an increasing worldwide problem due to the number of cases in endemic areas and the migration of infected subjects to more developed regions, mainly North America and Europe. Despite its importance, chronic chagas cardiomyopathy (CCC) pathophysiology is yet poorly understood, and independently of its social, clinical, and epidemiological importance, the therapeutic approach of CCC is still transposed from the knowledge acquired from other cardiomyopathies. Therefore, the objective of this review is to describe the treatment of Chagas cardiomyopathy with emphasis on its peculiarities. PMID:24350293

  20. Effects of long-term post-ischemic treadmill exercise on gliosis in the aged gerbil hippocampus induced by transient cerebral ischemia

    PubMed Central

    Ahn, Ji Hyeon; Shin, Myoung Cheol; Park, Joon Ha; Kim, In Hye; Cho, Jeong-Hwi; Lee, Tae-Kyeong; Lee, Jae-Chul; Chen, Bai Hui; Shin, Bich Na; Tae, Hyun-Jin; Park, Jinseu; Choi, Soo Young; Lee, Yun Lyul; Kim, Dae Won; Kim, Yang Hee; Won, Moo-Ho; Cho, Jun Hwi

    2017-01-01

    Therapeutic exercise is an integral component of the rehabilitation of patients who have suffered a stroke. The objective of the present study was to use immunohistochemistry to investigate the effects of post-ischemic exercise on neuronal damage or death and gliosis in the aged gerbil hippocampus following transient cerebral ischemia. Aged gerbils (male; age, 22–24 months) underwent ischemia and were subjected to treadmill exercise for 1 or 4 weeks. Neuronal death was detected in the stratum pyramidale of the hippocampal CA1 region and in the polymorphic layer of the dentate gyrus using cresyl violet and Fluoro-Jade B histofluorescence staining. No significant difference in neuronal death was identified following 1 or 4 weeks of post-ischemic treadmill exercise. However, post-ischemic treadmill exercise affected gliosis (the activation of astrocytes and microglia). Glial fibrillary acidic protein-immunoreactive astrocytes and ionized calcium binding adaptor molecule 1-immunoreactive microglia were activated in the CA1 and polymorphic layer of the dentate gyrus of the group without treadmill exercise. Conversely, 4 weeks of treadmill exercise significantly alleviated ischemia-induced astrocyte and microglial activation; however, 1 week of treadmill exercise did not alleviate gliosis. These findings suggest that long-term post-ischemic treadmill exercise following transient cerebral ischemia does not influence neuronal protection; however, it may effectively alleviate transient cerebral ischemia-induced astrocyte and microglial activation in the aged hippocampus. PMID:28440411

  1. Ferulic acid prevents cerebral ischemic injury-induced reduction of hippocalcin expression.

    PubMed

    Koh, Phil-Ok

    2013-07-01

    Intracellular calcium overload is a critical pathophysiological factor in ischemic injury. Hippocalcin is a neuronal calcium sensor protein that buffers intracellular calcium levels and protects cells from apoptotic stimuli. Ferulic acid exerts a neuroprotective effect in cerebral ischemia through its anti-oxidant and anti-inflammation activity. This study investigated whether ferulic acid contributes to hippocalcin expression during cerebral ischemia and glutamate exposure-induced neuronal cell death. Rats were immediately treated with vehicle or ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO and followed by assessment of cerebral infarct. Ferulic acid reduced MCAO-induced infarct regions. A proteomics approach elucidated a decrease in hippocalcin in MCAO-operated animals, ferulic acid attenuates the injury-induced decrease in hippocalcin expression. Reverse transcription-polymerase chain reaction and Western blot analyses confirmed that ferulic acid prevents the injury-induced decrease in hippocalcin. In cultured HT22 hippocampal cells, glutamate exposure increased the intracellular Ca(2+) levels, whereas ferulic acid attenuated this increase. Moreover, ferulic acid attenuated the glutamate toxicity-induced decrease in hippocalcin expression. These findings can suggest the possibility that ferulic acid exerts a neuroprotective effect through modulating hippocalcine expression and regulating intracellular calcium levels. Copyright © 2013 Wiley Periodicals, Inc.

  2. Genetics Home Reference: familial hypertrophic cardiomyopathy

    MedlinePlus

    ... Savithri GR, Kumar MS, Narasimhan C, Nallari P. Molecular genetics of familial hypertrophic cardiomyopathy (FHC). J Hum Genet. ... 5(11):747. Citation on PubMed Kimura A. Molecular genetics and pathogenesis of cardiomyopathy. J Hum Genet. 2016 ...

  3. Non-Compact Cardiomyopathy or Ventricular Non-Compact Syndrome?

    PubMed Central

    2014-01-01

    Ventricular myocardial non-compaction has been recognized and defined as a genetic cardiomyopathy by American Heart Association since 2006. The argument on the nomenclature and pathogenesis of this kind of ventricular myocardial non-compaction characterized by regional ventricular wall thickening and deep trabecular recesses often complicated with chronic heart failure, arrhythmia and thromboembolism and usually overlap the genetics and phenotypes of other kind of genetic or mixed cardiomyopathy still exist. The proper classification and correct nomenclature of the non-compact ventricles will contribute to the precisely and completely understanding of etiology and its related patho-physiological mechanism for a better risk stratification and more personalized therapy of the disease individually. All of the genetic heterogeneity and phenotypical overlap and the variety in histopathological, electromechanical and clinical presentation indicates that some of the cardiomyopathies might just be the different consequence of myocardial development variations related to gene mutation and phenotype of one or group genes induced by the interacted and disturbed process of gene modulation at different links of gene function expression and some other etiologies. This review aims to establish a new concept of "ventricular non-compaction syndrome" based on the demonstration of the current findings of etiology, epidemiology, histopathology and echocardiography related to the disorder of ventricular myocardial compaction and myocardial electromechanical function development. PMID:25580189

  4. Takotsubo Cardiomyopathy in the Setting of Tension Pneumothorax.

    PubMed

    Gale, Michael; Loarte, Pablo; Mirrer, Brooks; Mallet, Thierry; Salciccioli, Louis; Petrie, Alison; Cohen, Ronny

    2015-01-01

    Background. Takotsubo cardiomyopathy is defined as a transient left ventricular dysfunction, usually accompanied by electrocardiographic changes. The literature documents only two other cases of Takotsubo cardiomyopathy in the latter setting. Methods. A 78-year-old female presented to the ED with severe shortness of breath, hypertension, and tachycardia. On physical exam, heart sounds (S1 and S2) were regular and wheezing was noticed bilaterally. We found laboratory results with a WBC of 20.0 (103/μL), troponin of 16.52 ng/mL, CK-mb of 70.6%, and BNP of 177 pg/mL. The patient was intubated for acute hypoxemic respiratory failure. A chest X-ray revealed a large left-sided tension pneumothorax. Initial echocardiogram showed apical ballooning with a LVEF of 10-15%. A cardiac angiography revealed normal coronary arteries with no coronary disease. After supportive treatment, the patient's condition improved with a subsequent echocardiogram showing a LVEF of 60%. Conclusion. The patient was found to have Takotsubo cardiomyopathy in the setting of a tension pneumothorax. The exact mechanisms of ventricular dysfunction have not been clarified. However, multivessel coronary spasm or catecholamine cardiotoxicity has been suggested to have a causative role. We suggest that, in our patient, left ventricular dysfunction was induced by the latter mechanism related to the stress associated with acute pneumothorax.

  5. X-linked cardiomyopathy is heterogeneous

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilson, M.J.; Sillence, D.O.; Mulley, J.C.

    Two major loci of X-linked cardiomyopathy have been mapped by linkage analysis. The gene for X-linked dilated cardiomyopathy (XLCM) is mapped to the dystrophin locus at Xp21, while Barth syndrome has been localised to distal Xq28. XLCM usually presents in juvenile males with no skeletal disease but decreased dystrophin in cardiac muscle. Barth syndrome most often presents in infants and is characterized by skeletal myopathy, short stature and neutropenia in association with cardiomyopathy of variable severity. Prior to carrier or prenatal diagnosis in a family, delineation of the cardiomyopathy locus involved is essential. We report the linkage mapping of amore » large kindred in which several male infants have died with hypertrophic cardiomyopathy. There is a family history of unexplained death of infant males less than 6 months old over 4 generations. Features of Barth syndrome such as short stature, skeletal myopathy and neutropenia have not been observed. Genotyping at 10 marker loci in Xq28 has revealed significant pairwise lod scores with the cardiomyopathy phenotype at DXS52 (Z=2.21 at {theta}=0.0), at markers p26 and p39 near DXS15 (Z=2.30 at {theta}=0.0) and at F8C (Z=2.24 at {theta}=0.0). A recombinant detected with DXS296 defines the proximal limit to the localization. No recombinants were detected at any of the loci distal to DXS296. The most distal marker in Xq28, DXS1108, is within 500 kb of the telomere. As the gene in this family is localized to Xq28, it is possible that this disorder is an allelic variant at the Barth syndrome locus.« less

  6. A multicenter, randomized trial on neuroprotection with remote ischemic per-conditioning during acute ischemic stroke: the REmote iSchemic Conditioning in acUtE BRAin INfarction study protocol.

    PubMed

    Pico, Fernando; Rosso, Charlotte; Meseguer, Elena; Chadenat, Marie-Laure; Cattenoy, Amina; Aegerter, Philippe; Deltour, Sandrine; Yeung, Jennifer; Hosseini, Hassan; Lambert, Yves; Smadja, Didier; Samson, Yves; Amarenco, Pierre

    2016-10-01

    Rationale Remote ischemic per-conditioning-causing transient limb ischemia to induce ischemic tolerance in other organs-reduces final infarct size in animal stroke models. Aim To evaluate whether remote ischemic per-conditioning during acute ischemic stroke (<6 h) reduces brain infarct size at 24 h. Methods and design This study is being performed in five French hospitals using a prospective randomized open blinded end-point design. Adults with magnetic resonance imaging confirmed ischemic stroke within 6 h of symptom onset and clinical deficit of 5-25 according to National Institutes of Health Stroke Scale will be randomized 1:1 to remote ischemic per-conditioning or control (stratified by center and intravenous fibrinolysis use). Remote ischemic per-conditioning will consist of four cycles of electronic tourniquet inflation (5 min) and deflation (5 min) to a thigh within 6 h of symptom onset. Magnetic resonance imaging is repeated 24 h after stroke onset. Sample size estimates For a difference of 15 cm 3 in brain infarct growth between groups, 200 patients will be included for 5% significance and 80% power. Study outcomes The primary outcome will be the difference in brain infarct growth from baseline to 24 h in the intervention versus control groups (by diffusion-weighted image magnetic resonance imaging). Secondary outcomes include: National Institutes of Health Stroke Scale score absolute difference between baseline and 24 h, three-month modified Rankin score and daily living activities, mortality, and tolerance and side effects of remote ischemic per-conditioning. Discussion The only remote ischemic per-conditioning trial in humans with stroke did not show remote ischemic per-conditioning to be effective. REmote iSchemic Conditioning in acUtE BRAin INfarction, which has important design differences, should provide more information on the use of this intervention in patients with acute ischemic stroke.

  7. Hyaluronan Synthase 3 Variant and Anthracycline-Related Cardiomyopathy: A Report From the Children's Oncology Group

    PubMed Central

    Wang, Xuexia; Liu, Wei; Sun, Can-Lan; Armenian, Saro H.; Hakonarson, Hakon; Hageman, Lindsey; Ding, Yan; Landier, Wendy; Blanco, Javier G.; Chen, Lu; Quiñones, Adolfo; Ferguson, Daniel; Winick, Naomi; Ginsberg, Jill P.; Keller, Frank; Neglia, Joseph P.; Desai, Sunil; Sklar, Charles A.; Castellino, Sharon M.; Cherrick, Irene; Dreyer, ZoAnn E.; Hudson, Melissa M.; Robison, Leslie L.; Yasui, Yutaka; Relling, Mary V.; Bhatia, Smita

    2014-01-01

    Purpose The strong dose-dependent association between anthracyclines and cardiomyopathy is further exacerbated by the co-occurrence of cardiovascular risk factors (diabetes and hypertension). The high morbidity associated with cardiomyopathy necessitates an understanding of the underlying pathogenesis so that targeted interventions can be developed. Patients and Methods By using a two-stage design, we investigated host susceptibility to anthracycline-related cardiomyopathy by using the ITMAT/Broad CARe cardiovascular single nucleotide polymorphism (SNP) array to profile common SNPs in 2,100 genes considered relevant to de novo cardiovascular disease. Results By using a matched case-control design (93 cases, 194 controls), we identified a common SNP, rs2232228, in the hyaluronan synthase 3 (HAS3) gene that exerts a modifying effect on anthracycline dose-dependent cardiomyopathy risk (P = 5.3 × 10−7). Among individuals with rs2232228 GG genotype, cardiomyopathy was infrequent and not dose related. However, in individuals exposed to high-dose (> 250 mg/m2) anthracyclines, the rs2232228 AA genotype conferred an 8.9-fold (95% CI, 2.1- to 37.5-fold; P = .003) increased cardiomyopathy risk compared with the GG genotype. This gene-environment interaction was successfully replicated in an independent set of 76 patients with anthracycline-related cardiomyopathy. Relative HAS3 mRNA levels measured in healthy hearts tended to be lower among individuals with AA compared with GA genotypes (P = .09). Conclusion Hyaluronan (HA) produced by HAS3 is a ubiquitous component of the extracellular matrix and plays an active role in tissue remodeling. In addition, HA is known to reduce reactive oxygen species (ROS) –induced cardiac injury. The high cardiomyopathy risk associated with AA genotype could be due to inadequate remodeling and/or inadequate protection of the heart from ROS-mediated injury on high anthracycline exposure. PMID:24470002

  8. Ischemic Brain Injury Leads to Brain Edema via Hyperthermia-Induced TRPV4 Activation.

    PubMed

    Hoshi, Yutaka; Okabe, Kohki; Shibasaki, Koji; Funatsu, Takashi; Matsuki, Norio; Ikegaya, Yuji; Koyama, Ryuta

    2018-06-20

    Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain largely unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which male mouse brain slices were treated with oxygen-glucose deprivation (OGD) to mimic ischemia. We continuously measured the cross-sectional area of the brain slice for 150 min under macroscopic microscopy, finding that OGD induces swelling of brain slices. OGD-induced swelling was prevented by pharmacologically blocking or genetically knocking out the transient receptor potential vanilloid 4 (TRPV4), a member of the thermosensitive TRP channel family. Because TRPV4 is activated at around body temperature and its activation is enhanced by heating, we next elevated the temperature of the perfusate in the recording chamber, finding that hyperthermia induces swelling via TRPV4 activation. Furthermore, using the temperature-dependent fluorescence lifetime of a fluorescent-thermosensitive probe, we confirmed that OGD treatment increases the temperature of brain slices through the activation of glutamate receptors. Finally, we found that brain edema following traumatic brain injury was suppressed in TRPV4-deficient male mice in vivo Thus, our study proposes a novel mechanism: hyperthermia activates TRPV4 and induces brain edema after ischemia. SIGNIFICANCE STATEMENT Brain edema is characterized by an increase in net brain water content, which results in an increase in brain volume. Although brain edema is associated with a high fatality rate, the cellular and molecular processes of edema remain unclear. Here, we developed an in vitro model of ischemic stroke-induced edema in which mouse brain slices were treated with oxygen-glucose deprivation. Using this system, we showed that the increase in brain temperature and the following activation of the

  9. Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance

    PubMed Central

    Lehotský, Ján; Tothová, Barbara; Kovalská, Maria; Dobrota, Dušan; Beňová, Anna; Kalenská, Dagmar; Kaplán, Peter

    2016-01-01

    Homocysteine (Hcy) is a toxic, sulfur-containing intermediate of methionine metabolism. Hyperhomocysteinemia (hHcy), as a consequence of impaired Hcy metabolism or defects in crucial co-factors that participate in its recycling, is assumed as an independent human stroke risk factor. Neural cells are sensitive to prolonged hHcy treatment, because Hcy cannot be metabolized either by the transsulfuration pathway or by the folate/vitamin B12 independent remethylation pathway. Its detrimental effect after ischemia-induced damage includes accumulation of reactive oxygen species (ROS) and posttranslational modifications of proteins via homocysteinylation and thiolation. Ischemic preconditioning (IPC) is an adaptive response of the CNS to sub-lethal ischemia, which elevates tissues tolerance to subsequent ischemia. The main focus of this review is on the recent data on homocysteine metabolism and mechanisms of its neurotoxicity. In this context, the review documents an increased oxidative stress and functional modification of enzymes involved in redox balance in experimentally induced hyperhomocysteinemia. It also gives an interpretation whether hyperhomocysteinemia alone or in combination with IPC affects the ischemia-induced neurodegenerative changes as well as intracellular signaling. Studies document that hHcy alone significantly increased Fluoro-Jade C- and TUNEL-positive cell neurodegeneration in the rat hippocampus as well as in the cortex. IPC, even if combined with hHcy, could still preserve the neuronal tissue from the lethal ischemic effects. This review also describes the changes in the mitogen-activated protein kinase (MAPK) protein pathways following ischemic injury and IPC. These studies provide evidence for the interplay and tight integration between ERK and p38 MAPK signaling mechanisms in response to the hHcy and also in association of hHcy with ischemia/IPC challenge in the rat brain. Further investigations of the protective factors leading to ischemic

  10. Grb-2–associated binder 1 (Gab1) regulates postnatal ischemic and VEGF-induced angiogenesis through the protein kinase A–endothelial NOS pathway

    PubMed Central

    Xiong, Yan; Huo, Yingqing; Han, Jingyan; Yang, Xiao; Zhang, Rongli; Zhu, De-Sheng; Klein-Heßling, Stefan; Zhang, Xiaoyu; Han, Xiaofan; Li, Yanli; Shen, Bin; He, Yulong; Shibuya, Masabumi; Feng, Gen-Sheng; Luo, Jincai

    2011-01-01

    The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely understood. Herein we show that Grb-2–associated binder 1 (Gab1) plays a critical role in ischemic and VEGF-induced angiogenesis. Endothelium-specific Gab1 KO (EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF expression. Matrigel plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control mice. The vessels and endothelial cells (ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by VEGF. Biochemical analyses revealed a substantial reduction of endothelial NOS (eNOS) activation in Gab1-deficient vessels and ECs following VEGF stimulation. Interestingly, the phosphorylation of Akt, an enzyme known to promote VEGF-induced eNOS activation, was increased in Gab1-deficient vessels and ECs whereas protein kinase A (PKA) activity was significantly decreased. Introduction of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ECs. Reexpression of WT or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and eNOS. Taken together, these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation, which is dependent on PKA. Of note, this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation, suggesting considerable potential in treatment of human ischemic diseases. PMID:21282639

  11. [Intravenous nitroglycerin infusion suppresses exercise-induced arrhythmia in patients with ischemic cardiopathy: indications for chronic treatment ].

    PubMed

    Bonetti, F; Margonato, A; Mailhac, A; Vicedomini, G; Cianflone, D; Scarpazza, P; Chierchia, S L

    1990-05-01

    In patients with ischemic heart disease and arrhythmias, selection of antiarrhythmic treatment is often difficult as it is hard to separate "primary" from ischemic arrhythmias. We studied 20 patients with ischemic heart disease, who developed ventricular arrhythmias consistently during exercise test. Exercise test was performed twice during infusion of placebo and then during intravenous administration of nitroglycerin, titrated to reduce systolic blood pressure by 10 mmHg. Exercise duration was 7.8 +/- 1.7 and 7.9 +/- 1.5 min, in the 2 placebo tests (NS). Angina developed in 5 patients and ischemic ST changes in 10. With nitroglycerin exercise duration increased to 8.4 +/- 20 min (p less than 0.05), diagnostic ST segment depression was observed in 2 patients and only 1 had angina. In all 20 patients, ventricular arrhythmias were consistently present during both tests on placebo, that were markedly reduced by nitroglycerin. In fact, ventricular ectopic beats were 455 (mean 35.8 +/- 16.8) and 418 (mean 34.4 +/- 11.1) in the 2 exercise tests with placebo, and 11 during nitroglycerin infusion (mean 0.6 +/- 0.1; p less than 0.001). Couplets were 28 and 29 during placebo (NS) and 0 during nitroglycerin (p less than 0.001). Ventricular tachycardia was present in 6 and 8 patients during placebo but in none during nitroglycerin (p less than 0.001). Reduction of exercise-induced arrhythmias was maintained during chronic treatment with oral vasodilators. Prevention of exercise-related arrhythmias by nitroglycerin infusion appears a good indicator of their ischemic origin and may provide valuable information for long-term profilaxis with oral vasodilators, then avoiding the use of antiarrhythmic agents and their potential side effects.

  12. Restrictive cardiomyopathy

    MedlinePlus

    ... People with restrictive cardiomyopathy may be heart transplant candidates. The outlook depends on the cause of the ... www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. ...

  13. Dilated cardiomyopathy

    MedlinePlus

    ... other causes of dilated cardiomyopathy, including: Alcohol or cocaine abuse Diabetes, thyroid disease, or hepatitis Medicines that ... how much salt (sodium) you get in your diet. Most people who have heart failure need to ...

  14. Importance of mitral valve repair associated with left ventricular reconstruction for patients with ischemic cardiomyopathy: a real-time three-dimensional echocardiographic study

    NASA Technical Reports Server (NTRS)

    Qin, Jian Xin; Shiota, Takahiro; McCarthy, Patrick M.; Asher, Craig R.; Hail, Melanie; Agler, Deborah A.; Popovic, Zoran B.; Greenberg, Neil L.; Smedira, Nicholas G.; Starling, Randall C.; hide

    2003-01-01

    BACKGROUND: Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE). METHODS AND RESULTS: Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up. CONCLUSIONS: Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.

  15. TARGETED DELETION OF INDUCIBLE HEAT SHOCK PROTEIN 70 ABROGATES THE LATE INFARCT-SPARING EFFECT OF MYOCARDIAL ISCHEMIC PRECONDITIONING

    EPA Science Inventory

    Abstract submitted for 82nd annual meeting of the American Association for Thoracic Surgery, May 4-8, 2002 in Washington D.C.

    Targeted Deletion of Inducible Heat Shock Protein 70 Abrogates the Late Infarct-Sparing Effect of Myocardial Ischemic Preconditioning

    Craig...

  16. High validity of cardiomyopathy diagnoses in western Sweden (1989–2009)

    PubMed Central

    Rosengren, Annika; Lindström, Sandra; Schaufelberger, Maria

    2017-01-01

    Abstract Aim Hospital discharges with a diagnosis of cardiomyopathy have more than doubled in Sweden since 1987. We validated the cardiomyopathy diagnoses over this time period to investigate that the increase was real and not a result of improved recognition of the diagnosis and better diagnostic methods. Methods and results Every fifth year from 1989 to 2009, records for all patients with a cardiomyopathy diagnosis were identified by searching the local registers in three hospitals in Västra Götaland, Sweden. The diagnoses were validated according to criteria defined by the European Society of Cardiology from 2008. The population comprised 611 cases with cardiomyopathy diagnoses [mean age 58.9 (SD 15.5) years, 68.2% male], divided into three major groups: dilated, hypertrophic, and other cardiomyopathies. Hypertrophic cardiomyopathy and hypertrophic obstructive cardiomyopathy were analysed as a group. Cardiomyopathies for which there were few cases, such as restrictive, arrhythmogenic right ventricular, left ventricular non‐compaction, takotsubo, and peripartum cardiomyopathies, were analysed together and defined as ‘other cardiomyopathies’. Relevant co‐morbidities were registered. The use of echocardiography was 99.7%, of which 94.6% was complete echocardiography reports. The accuracy rates of the diagnoses dilated cardiomyopathy, hypertrophic cardiomyopathy, and other cardiomyopathies were 85.5%, 87.5%, and 100%, respectively, with no differences between the three hospitals or years studied; nor did the prevalence of co‐morbidities differ. Conclusions The accuracy rate of the cardiomyopathy diagnoses from in‐hospital records from >600 patients in western Sweden during a 20 year period was 86.6%, with no significant trend over time, strengthening epidemiological findings that this is likely due to an actual increase in cardiomyopathy diagnoses rather than changes in coding practices. The use of echocardiography was high, and there was no

  17. Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells

    PubMed Central

    Han, Lu; Li, Yang; Tchao, Jason; Kaplan, Aaron D.; Lin, Bo; Li, You; Mich-Basso, Jocelyn; Lis, Agnieszka; Hassan, Narmeen; London, Barry; Bett, Glenna C.L.; Tobita, Kimimasa; Rasmusson, Randall L.; Yang, Lei

    2014-01-01

    Aims Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies. Methods and results To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for ‘Cell Proliferation’ was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments. Conclusion Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases. PMID:25209314

  18. Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

    PubMed Central

    MacFarlane, Elena Gallo; Takimoto, Eiki; Chaudhary, Rahul; Nagpal, Varun; Rainer, Peter P.; Bindman, Julia G.; Gerber, Elizabeth E.; Bedja, Djahida; Schiefer, Christopher; Miller, Karen L.; Zhu, Guangshuo; Myers, Loretha; Amat-Alarcon, Nuria; Lee, Dong I.; Koitabashi, Norimichi; Judge, Daniel P.; Dietz, Harry C.

    2017-01-01

    Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-β ligands, with increased TGF-β signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment. Informatively, TGF-β, angiotensin II type 1 receptor (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK inhibitor, respectively) prevents load-induced cardiac decompensation in MFS mice, despite persistent PO. In situ analyses revealed an unanticipated axis of activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-β ligand expression that culminates in both autocrine and paracrine overdrive of TGF-β signaling. The full compensation seen in wild-type mice exposed to mild PO correlates with enhanced deposition of extracellular fibrillin-1. Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation. PMID:28768908

  19. Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice.

    PubMed

    Rouf, Rosanne; MacFarlane, Elena Gallo; Takimoto, Eiki; Chaudhary, Rahul; Nagpal, Varun; Rainer, Peter P; Bindman, Julia G; Gerber, Elizabeth E; Bedja, Djahida; Schiefer, Christopher; Miller, Karen L; Zhu, Guangshuo; Myers, Loretha; Amat-Alarcon, Nuria; Lee, Dong I; Koitabashi, Norimichi; Judge, Daniel P; Kass, David A; Dietz, Harry C

    2017-08-03

    Among children with the most severe presentation of Marfan syndrome (MFS), an inherited disorder of connective tissue caused by a deficiency of extracellular fibrillin-1, heart failure is the leading cause of death. Here, we show that, while MFS mice (Fbn1C1039G/+ mice) typically have normal cardiac function, pressure overload (PO) induces an acute and severe dilated cardiomyopathy in association with fibrosis and myocyte enlargement. Failing MFS hearts show high expression of TGF-β ligands, with increased TGF-β signaling in both nonmyocytes and myocytes; pathologic ERK activation is restricted to the nonmyocyte compartment. Informatively, TGF-β, angiotensin II type 1 receptor (AT1R), or ERK antagonism (with neutralizing antibody, losartan, or MEK inhibitor, respectively) prevents load-induced cardiac decompensation in MFS mice, despite persistent PO. In situ analyses revealed an unanticipated axis of activation in nonmyocytes, with AT1R-dependent ERK activation driving TGF-β ligand expression that culminates in both autocrine and paracrine overdrive of TGF-β signaling. The full compensation seen in wild-type mice exposed to mild PO correlates with enhanced deposition of extracellular fibrillin-1. Taken together, these data suggest that fibrillin-1 contributes to cardiac reserve in the face of hemodynamic stress, critically implicate nonmyocytes in disease pathogenesis, and validate ERK as a therapeutic target in MFS-related cardiac decompensation.

  20. Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

    PubMed

    Shimauchi, Tsukasa; Yamaura, Ken; Sugibe, Sayaka; Hoka, Sumio

    2014-09-01

    A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy. Copyright © 2014. Published by Elsevier B.V.

  1. Scar Homogenization Versus Limited-Substrate Ablation in Patients With Nonischemic Cardiomyopathy and Ventricular Tachycardia.

    PubMed

    Gökoğlan, Yalçın; Mohanty, Sanghamitra; Gianni, Carola; Santangeli, Pasquale; Trivedi, Chintan; Güneş, Mahmut F; Bai, Rong; Al-Ahmad, Amin; Gallinghouse, G Joseph; Horton, Rodney; Hranitzky, Patrick M; Sanchez, Javier E; Beheiry, Salwa; Hongo, Richard; Lakkireddy, Dhanunjaya; Reddy, Madhu; Schweikert, Robert A; Dello Russo, Antonio; Casella, Michela; Tondo, Claudio; Burkhardt, J David; Themistoclakis, Sakis; Di Biase, Luigi; Natale, Andrea

    2016-11-01

    Scar homogenization improves long-term ventricular arrhythmia-free survival compared with standard limited-substrate ablation in patients with post-infarction ventricular tachycardia (VT). Whether such benefit extends to patients with nonischemic cardiomyopathy and scar-related VT is unclear. The aim of this study was to assess the long-term efficacy of an endoepicardial scar homogenization approach compared with standard ablation in this population. Consecutive patients with dilated nonischemic cardiomyopathy (n = 93), scar-related VTs, and evidence of low-voltage regions on the basis of pre-defined criteria on electroanatomic mapping (i.e., bipolar voltage <1.5 mV) underwent either standard VT ablation (group 1 [n = 57]) or endoepicardial ablation of all abnormal potentials within the electroanatomic scar (group 2 [n = 36]). Acute procedural success was defined as noninducibility of any VT at the end of the procedure; long-term success was defined as freedom from any ventricular arrhythmia at follow-up. Acute procedural success rates were 69.4% and 42.1% after scar homogenization and standard ablation, respectively (p = 0.01). During a mean follow-up period of 14 ± 2 months, single-procedure success rates were 63.9% after scar homogenization and 38.6% after standard ablation (p = 0.031). After multivariate analysis, scar homogenization and left ventricular ejection fraction were predictors of long-term success. During follow-up, the rehospitalization rate was significantly lower in the scar homogenization group (p = 0.035). In patients with dilated nonischemic cardiomyopathy, scar-related VT, and evidence of low-voltage regions on electroanatomic mapping, endoepicardial homogenization of the scar significantly increased freedom from any recurrent ventricular arrhythmia compared with a standard limited-substrate ablation. However, the success rate with this approach appeared to be lower than previously reported with ischemic cardiomyopathy, presumably

  2. Hypertrophic cardiomyopathy.

    PubMed

    Santos Mateo, Juan José; Sabater Molina, María; Gimeno Blanes, Juan Ramón

    2018-06-08

    Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy.

    PubMed

    Lopes, Rosana; Solter, Philip F; Sisson, D David; Oyama, Mark A; Prosek, Robert

    2006-06-01

    To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM). Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM. Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by >or= 2-fold between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. Within narrow pH gradients of control canine heart mitochondrial samples, a total of 1,528 protein spots were revealed. Forty subunits of heart mitochondrial proteins that differ significantly from control tissues were altered in tissue specimens from dogs with naturally occurring and induced forms of DCM. The most affected heart mitochondrial proteins in both groups were those of oxidative phosphorylation (55%). Upregulation of manganese superoxide dismutase was suggestive of heart oxidative injury in tissue specimens from dogs with both forms of DCM. Evidence of apoptosis was associated with overexpression of the heart mitochondrial voltage-dependent anion channel-2 protein and endonuclease G in tissue specimens from dogs with induced DCM. Alterations of heart mitochondrial proteins related to oxidative phosphorylation dysfunction were more prevalent in tissue specimens from dogs with induced or naturally occurring DCM, compared with those of control dogs.

  4. Involvement of adenosine and standardization of aqueous extract of garlic (Allium sativum Linn.) on cardioprotective and cardiodepressant properties in ischemic preconditioning and myocardial ischemia-reperfusion induced cardiac injury

    PubMed Central

    Sharma, Ashish Kumar; Munajjam, Arshee; Vaishnav, Bhawna; Sharma, Richa; Sharma, Ashok; Kishore, Kunal; Sharma, Akash; Sharma, Divya; Kumari, Rita; Tiwari, Ashish; Singh, Santosh Kumar; Gaur, Samir; Jatav, Vijay Singh; Srinivasan, Barthu Parthi; Agarwal, Shyam Sunder

    2012-01-01

    The present study investigated the effect of garlic (Allium sativum Linn.) aqueous extracts on ischemic preconditioning and ischemia-reperfusion induced cardiac injury, as well as adenosine involvement in ischemic preconditioning and garlic extract induced cardioprotection. A model of ischemia-reperfusion injury was established using Langendorff apparatus. Aqueous extract of garlic dose was standardized (0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.03%, 0.01%), and the 0.05% dose was found to be the most effective. Higher doses (more than 0.05%) were highly toxic, causing arrhythmia and cardiodepression, whereas the lower doses were ineffective. Garlic exaggerated the cardioprotective effect of ischemic preconditioning. The cardioprotective effect of ischemic preconditioning and garlic cardioprotection was significantly attenuated by theophylline (1,000 µmol/L) and 8-SPT (10 mg/kg, i.p.) and expressed by increased myocardial infarct size, increased LDH level, and reduced nitrite and adenosine levels. These findings suggest that adenosine is involved in the pharmacological and molecular mechanism of garlic induced cardioprotection and mediated by the modulation of nitric oxide. PMID:23554727

  5. Dabigatran Etexilate Reduces Thrombin-Induced Inflammation and Thrombus Formation in Experimental Ischemic Stroke.

    PubMed

    Dittmeier, Melanie; Wassmuth, Kathrin; Schuhmann, Michael K; Kraft, Peter; Kleinschnitz, Christoph; Fluri, Felix

    2016-01-01

    Dabigatran etexilate (DE), a direct-acting, oral inhibitor of thrombin, significantly reduces the risk of stroke compared with traditional anticoagulants, without increasing the risk of major bleeding. However, studies on the fate of cerebral tissue after ischemic stroke in patients receiving DE are sparse and the role of dabigatran-mediated reduction of thrombin in this context has not yet been investigated. Here, we investigated whether pretreatment with DE reduces thrombin-mediated pro-inflammatory mechanisms and leakage of the blood-brain barrier (BBB) following ischemic stroke in rats. Male Wistar rats received DE (15 mg/kg) or a vehicle solution 1 hour before transient middle cerebral artery occlusion (tMCAO) for 90 minutes. Infarct volume, neurologic outcome and intracranial hemorrhage (ICH) were determined after tMCAO. Thrombin generation was indirectly assessed by measuring thrombin/antithrombin III complex. Microvascular patency was evaluated histologically. Cytokine expression and immunoreactivity of cluster of differentiation (CD) 68 were examined to characterize inflammatory processes after pretreatment with DE. BBB integrity was examined by quantifying brain edema. Rats given DE revealed a significant reduction in infarct size without an increase in ICH and significant recovery of neurologic deficits compared to controls. Administration of DE decreased thrombin generation and thrombus formation, dampened the CD68-immunoreactivity and attenuated pro-inflammatory cytokine expression in the cerebral parenchyma ipsilateral to the ischemic lesion. BBB permeability was unaltered following treatment with DE. In summary, prophylactic anticoagulation with DE improves stroke outcome by reducing thrombin-induced inflammation and thrombus formation without increasing the rate of ICH.

  6. Genetics Home Reference: arrhythmogenic right ventricular cardiomyopathy

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions ARVC Arrhythmogenic right ventricular cardiomyopathy Printable PDF Open All Close All ... to view the expand/collapse boxes. Description Arrhythmogenic right ventricular cardiomyopathy ( ARVC ) is a form of heart ...

  7. Recurrent Takotsubo Cardiomyopathy Related to Recurrent Thyrotoxicosis.

    PubMed

    Patel, Keval; Griffing, George T; Hauptman, Paul J; Stolker, Joshua M

    2016-04-01

    Takotsubo cardiomyopathy, or transient left ventricular apical ballooning syndrome, is characterized by acute left ventricular dysfunction caused by transient wall-motion abnormalities of the left ventricular apex and mid ventricle in the absence of obstructive coronary artery disease. Recurrent episodes are rare but have been reported, and several cases of takotsubo cardiomyopathy have been described in the presence of hyperthyroidism. We report the case of a 55-year-old woman who had recurrent takotsubo cardiomyopathy, documented by repeat coronary angiography and evaluations of left ventricular function, in the presence of recurrent hyperthyroidism related to Graves disease. After both episodes, the patient's left ventricular function returned to normal when her thyroid function normalized. These findings suggest a possible role of thyroid-hormone excess in the pathophysiology of some patients who have takotsubo cardiomyopathy.

  8. Diabetic Cardiomyopathy: Bench to Bedside

    PubMed Central

    Schilling, Joel D.; Mann, Douglas L.

    2012-01-01

    The study of diabetic cardiomyopathy (diabetic CM) is an area of significant interest given the strong association between diabetes and the risk of heart failure. Many unanswered questions remain regarding the clinical definition and pathogenesis of this metabolic cardiomyopathy. This article reviews the current understanding of diabetic CM with a particular emphasis on the unresolved issues that have limited translation of scientific discovery to patient bedside. PMID:22999244

  9. Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage.

    PubMed

    Lorin, Charlotte; Vögeli, Isabelle; Niggli, Ernst

    2015-04-01

    Duchenne muscular dystrophy (DMD), a degenerative pathology of skeletal muscle, also induces cardiac failure and arrhythmias due to a mutation leading to the lack of the protein dystrophin. In cardiac cells, the subsarcolemmal localization of dystrophin is thought to protect the membrane from mechanical stress. The absence of dystrophin results in an elevated stress-induced Ca2+ influx due to the inadequate functioning of several proteins, such as stretch-activated channels (SACs). Our aim was to investigate whether transient receptor potential vanilloid channels type 2 (TRPV2) form subunits of the dysregulated SACs in cardiac dystrophy. We defined the role of TRPV2 channels in the abnormal Ca2+ influx of cardiomyocytes isolated from dystrophic mdx mice, an established animal model for DMD. In dystrophic cells, western blotting showed that TRPV2 was two-fold overexpressed. While normally localized intracellularly, in myocytes from mdx mice TRPV2 channels were translocated to the sarcolemma and were prominent along the T-tubules, as indicated by immunocytochemistry. Membrane localization was confirmed by biotinylation assays. Furthermore, in mdx myocytes pharmacological modulators suggested an abnormal activity of TRPV2, which has a unique pharmacological profile among TRP channels. Confocal imaging showed that these compounds protected the cells from stress-induced abnormal Ca2+ signals. The involvement of TRPV2 in these signals was confirmed by specific pore-blocking antibodies and by small-interfering RNA ablation of TRPV2. Together, these results establish the involvement of TRPV2 in a stretch-activated calcium influx pathway in dystrophic cardiomyopathy, contributing to the defective cellular Ca2+ handling in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  10. CARDIOMYOPATHY AND WORSENED ISCHEMIC HEART FAILURE IN SM22-α CRE-MEDIATED NEUROPILIN-1 NULL MICE: DYSREGULATION OF PGC1α AND MITOCHONDRIAL HOMEOSTASIS

    PubMed Central

    Wang, Ying; Cao, Ying; Yamada, Satsuki; Thirunavukkarasu, Mahesh; Nin, Veronica; Joshi, Mandip; Rishi, Muhammed T.; Bhattacharya, Santanu; Camacho-Pereira, Juliana; Sharma, Anil K.; Shameer, Khader; Kocher, Jean-Pierre A.; Sanchez, Juan A; Wang, Enfeng; Hoeppner, Luke H.; Dutta, Shamit K.; Leof1, Edward B.; Shah, Vijay; Claffey, Kevin P.; Chini, Eduardo; Simons, Michael; Terzic, Andre; Maulik, Nilanjana; Mukhopadhyay, Debabrata

    2015-01-01

    Objective Neuropilin-1 (NRP-1) is a multi-domain membrane receptor involved in angiogenesis and development of neuronal circuits, however, the role of NRP-1 in cardiovascular pathophysiology remains elusive. Approach and Results In this study, we first observed that deletion of NRP-1 induced peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) in cardiomyocytes (CMs) and vascular smooth muscle cells (VSMCs), which was accompanied by dysregulated cardiac mitochondrial accumulation and induction of cardiac hypertrophy- and stress-related markers. To investigate the role of NRP-1 in vivo, we generated mice lacking Nrp-1 in CMs and VSMCs (SM22-α-Nrp-1 KO), which exhibited decreased survival rates, developed cardiomyopathy and aggravated ischemia-induced heart failure. Mechanistically, we found that NRP-1 specifically controls PGC1α and PPARγ in CMs through crosstalk with Notch1 and Smad2 signaling pathways respectively. Moreover, SM22-α-Nrp-1 KO mice exhibited impaired physical activities and altered metabolite levels in serum, liver, and adipose tissues, as demonstrated by global metabolic profiling analysis. Conclusions Our findings provide new insights into the cardio-protective role of NRP-1 and its influence on global metabolism. PMID:25882068

  11. Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy

    EPA Science Inventory

    Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were...

  12. Inducible Glutamate Oxaloacetate Transaminase as a Therapeutic Target Against Ischemic Stroke

    PubMed Central

    Khanna, Savita; Briggs, Zachary

    2015-01-01

    Abstract Significance: Glutamate serves multi-faceted (patho)physiological functions in the central nervous system as the most abundant excitatory neurotransmitter and under pathological conditions as a potent neurotoxin. Regarding the latter, elevated extracellular glutamate is known to play a central role in ischemic stroke brain injury. Recent Advances: Glutamate oxaloacetate transaminase (GOT) has emerged as a new therapeutic target in protecting against ischemic stroke injury. Oxygen-sensitive induction of GOT expression and activity during ischemic stroke lowers glutamate levels at the stroke site while sustaining adenosine triphosphate levels in brain. The energy demands of the brain are among the highest of all organs underscoring the need to quickly mobilize alternative carbon skeletons for metabolism in the absence of glucose during ischemic stroke. Recent work builds on the important observation of Hans Krebs that GOT-mediated metabolism of glutamate generates tri-carboxylic acid (TCA) cycle intermediates in brain tissue. Taken together, outcomes suggest GOT may enable the transformative switch of otherwise excitotoxic glutamate into life-sustaining TCA cycle intermediates during ischemic stroke. Critical Issues: Neuroprotective strategies that focus solely on blocking mechanisms of glutamate-mediated excitotoxicity have historically failed in clinical trials. That GOT can enable glutamate to assume the role of a survival factor represents a paradigm shift necessary to develop the overall significance of glutamate in stroke biology. Future Directions: Ongoing efforts are focused to develop the therapeutic significance of GOT in stroke-affected brain. Small molecules that target induction of GOT expression and activity in the ischemic penumbra are the focus of ongoing studies. Antioxid. Redox Signal. 22, 175–186. PMID:25343301

  13. Clinical and Mechanistic Insights into the Genetics of Cardiomyopathy

    PubMed Central

    Burke, Michael A.; Cook, Stuart A.; Seidman, Jonathan G.; Seidman, Christine E.

    2018-01-01

    Over the last quarter-century, there has been tremendous progress in genetics research that has defined molecular causes for cardiomyopathies. More than a thousand mutations have been identified in many genes with varying ontologies, therein indicating the diverse molecules and pathways that cause hypertrophic, dilated, restrictive, and arrhythmogenic cardiomyopathies. Translation of this research to the clinic via genetic testing can precisely group affected patients according to molecular etiology, and identify individuals without evidence of disease who are at high risk for developing cardiomyopathy. These advances provide insights into the earliest manifestations of cardiomyopathy and help to define the molecular pathophysiological basis for cardiac remodeling. Although these efforts remain incomplete, new genomic technologies and analytic strategies provide unparalleled opportunities to fully explore the genetic architecture of cardiomyopathies. Such data hold the promise that mutation-specific pathophysiology will uncover novel therapeutic targets, and herald the beginning of precision therapy for cardiomyopathy patients. PMID:28007147

  14. Children's Cardiomyopathy Foundation

    MedlinePlus

    ... search for cures while improving diagnosis, treatment, and quality of life for children affected by cardiomyopathy. CCF actively works with federal agencies, medical societies, voluntary health organizations, ...

  15. P-Wave Indices and Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis.

    PubMed

    He, Jinli; Tse, Gary; Korantzopoulos, Panagiotis; Letsas, Konstantinos P; Ali-Hasan-Al-Saegh, Sadeq; Kamel, Hooman; Li, Guangping; Lip, Gregory Y H; Liu, Tong

    2017-08-01

    Atrial cardiomyopathy is associated with an increased risk of ischemic stroke. P-wave terminal force in lead V 1 , P-wave duration, and maximum P-wave area are electrocardiographic parameters that have been used to assess left atrial abnormalities related to developing atrial fibrillation. The aim of this systematic review and meta-analysis was to examine their values for predicting ischemic stroke risk. PubMed and EMBASE databases were searched until December 2016 for studies that evaluated the association between P-wave indices and stroke risk. Both fixed- and random-effects models were used to calculate the overall effect estimates. Ten studies examining P-wave terminal force in lead V 1 , P-wave duration, and maximum P-wave area were included. P-wave terminal force in lead V 1 was found to be an independent predictor of stroke as both a continuous variable (odds ratio [OR] per 1 SD change, 1.18; 95% confidence interval [CI], 1.12-1.25; P <0.0001) and categorical variable (OR, 1.59; 95% CI, 1.10-2.28; P =0.01). P-wave duration was a significant predictor of incident ischemic stroke when analyzed as a categorical variable (OR, 1.86; 95% CI, 1.37-2.52; P <0.0001) but not when analyzed as a continuous variable (OR, 1.05; 95% CI, 0.98-1.13; P =0.15). Maximum P-wave area also predicted the risk of incident ischemic stroke (OR per 1 SD change, 1.10; 95% CI, 1.04-1.17). P-wave terminal force in lead V 1 , P-wave duration, and maximum P-wave area are useful electrocardiographic markers that can be used to stratify the risk of incident ischemic stroke. © 2017 American Heart Association, Inc.

  16. Cardiomyopathy in becker muscular dystrophy: Overview.

    PubMed

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

  17. Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy.

    PubMed

    Sciatti, Edoardo; Vizzardi, Enrico; Bonadei, Ivano; Fabbricatore, Davide; Prati, Francesco; Pagnoni, Mattia; Metra, Marco

    2018-05-13

    Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), since it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by non-ischemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up. 202 patients affected by non-ischemic DCM underwent an outpatient examination by echocardiography and blood pressure check at the brachial artery, in order to calculate aortic elastic properties (i.e., compliance, distensibility, stiffness index, Peterson's elastic modulus, M-mode strain). ROC curves, Kaplan-Meier curves and multivariable Cox regressions (correcting for age, LV ejection fraction (LVEF), atrial fibrillation, cardiac resynchronization therapy (CRT)) were run to assess the predictive ability of aortic elastic properties against the three endpoints. Mean follow-up was 9.83±2.80 years. 24.8% of patients died, while 34.7% were rehospitalized for HF cause and 44.6% experienced the combined endpoint. LVEF did not correlate with aortic elastic properties. ROC curves and Kaplan-Meier curves were elaborated. Aortic stiffness did not predict death in our cohort. Otherwise, all aortic elastic properties predicted HF rehospitalization and combined death or HF rehospitalization, after correcting for age, LVEF, atrial fibrillation, CRT. Elastic properties of the ascending aorta measured by echocardiography in patients with non-ischemic DCM predict long-term HF rehospitalization and combined death or HF rehospitalization, also after correcting for the confounding factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Macrophage Colony-Stimulating Factor Improves Cardiac Function after Ischemic Injury by Inducing Vascular Endothelial Growth Factor Production and Survival of Cardiomyocytes

    PubMed Central

    Okazaki, Tatsuma; Ebihara, Satoru; Asada, Masanori; Yamanda, Shinsuke; Saijo, Yoshifumi; Shiraishi, Yasuyuki; Ebihara, Takae; Niu, Kaijun; Mei, He; Arai, Hiroyuki; Yambe, Tomoyuki

    2007-01-01

    Macrophage colony-stimulating factor (M-CSF), known as a hematopoietic growth factor, induces vascular endothelial growth factor (VEGF) production from skeletal muscles. However, the effects of M-CSF on cardiomyocytes have not been reported. Here, we show M-CSF increases VEGF production from cardiomyocytes, protects cardiomyocytes and myotubes from cell death, and improves cardiac function after ischemic injury. In mice, M-CSF increased VEGF production in hearts and in freshly isolated cardiomyocytes, which showed M-CSF receptor expression. In rat cell line H9c2 cardiomyocytes and myotubes, M-CSF induced VEGF production via the Akt signaling pathway, and M-CSF pretreatment protected these cells from H2O2-induced cell death. M-CSF activated Akt and extracellular signal-regulated kinase signaling pathways and up-regulated downstream anti-apoptotic Bcl-xL expression in these cells. Using goats as a large animal model of myocardial infarction, we found that M-CSF treatment after the onset of myocardial infarction by permanent coronary artery ligation promoted angiogenesis in ischemic hearts but did not reduce the infarct area. M-CSF pretreatment of the goat myocardial infarction model by coronary artery occlusion-reperfusion improved cardiac function, as assessed by hemodynamic parameters and echocardiography. These results suggest M-CSF might be a novel therapeutic agent for ischemic heart disease. PMID:17717142

  19. High Frequency QRS ECG Accurately Detects Cardiomyopathy

    NASA Technical Reports Server (NTRS)

    Schlegel, Todd T.; Arenare, Brian; Poulin, Gregory; Moser, Daniel R.; Delgado, Reynolds

    2005-01-01

    High frequency (HF, 150-250 Hz) analysis over the entire QRS interval of the ECG is more sensitive than conventional ECG for detecting myocardial ischemia. However, the accuracy of HF QRS ECG for detecting cardiomyopathy is unknown. We obtained simultaneous resting conventional and HF QRS 12-lead ECGs in 66 patients with cardiomyopathy (EF = 23.2 plus or minus 6.l%, mean plus or minus SD) and in 66 age- and gender-matched healthy controls using PC-based ECG software recently developed at NASA. The single most accurate ECG parameter for detecting cardiomyopathy was an HF QRS morphological score that takes into consideration the total number and severity of reduced amplitude zones (RAZs) present plus the clustering of RAZs together in contiguous leads. This RAZ score had an area under the receiver operator curve (ROC) of 0.91, and was 88% sensitive, 82% specific and 85% accurate for identifying cardiomyopathy at optimum score cut-off of 140 points. Although conventional ECG parameters such as the QRS and QTc intervals were also significantly longer in patients than controls (P less than 0.001, BBBs excluded), these conventional parameters were less accurate (area under the ROC = 0.77 and 0.77, respectively) than HF QRS morphological parameters for identifying underlying cardiomyopathy. The total amplitude of the HF QRS complexes, as measured by summed root mean square voltages (RMSVs), also differed between patients and controls (33.8 plus or minus 11.5 vs. 41.5 plus or minus 13.6 mV, respectively, P less than 0.003), but this parameter was even less accurate in distinguishing the two groups (area under ROC = 0.67) than the HF QRS morphologic and conventional ECG parameters. Diagnostic accuracy was optimal (86%) when the RAZ score from the HF QRS ECG and the QTc interval from the conventional ECG were used simultaneously with cut-offs of greater than or equal to 40 points and greater than or equal to 445 ms, respectively. In conclusion 12-lead HF QRS ECG employing

  20. Cardiomyopathy in captive African hedgehogs (Atelerix albiventris).

    PubMed

    Raymond, J T; Garner, M M

    2000-09-01

    From 1994 to 1999, 16 captive African hedgehogs (Atelerix albiventris), from among 42 necropsy cases, were diagnosed with cardiomyopathy. The incidence of cardiomyopathy in this study population was 38%. Fourteen of 16 hedgehogs with cardiomyopathy were males and all hedgehogs were adult (>1 year old). Nine hedgehogs exhibited 1 or more of the following clinical signs before death: heart murmur, lethargy, icterus, moist rales, anorexia, dyspnea, dehydration, and weight loss. The remaining 7 hedgehogs died without premonitory clinical signs. Gross findings were cardiomegaly (6 cases), hepatomegaly (5 cases), pulmonary edema (5 cases), pulmonary congestion (4 cases), hydrothorax (3 cases), pulmonary infarct (1 case), renal infarcts (1 case), ascites (1 case), and 5 cases showed no changes. Histologic lesions were found mainly within the left ventricular myocardium and consisted primarily of myodegeneration, myonecrosis, atrophy, hypertrophy, and disarray of myofibers. All hedgehogs with cardiomyopathy had myocardial fibrosis, myocardial edema, or both. Other common histopathologic findings were acute and chronic passive congestion of the lungs, acute passive congestion of the liver, renal tubular necrosis, vascular thrombosis, splenic extramedullary hematopoiesis, and hepatic lipidosis. This is the first report of cardiomyopathy in African hedgehogs.

  1. Cardiomyopathy in becker muscular dystrophy: Overview

    PubMed Central

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-01-01

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  2. Effect and mechanism of Qishen Yiqi Pills on adriamycin- induced cardiomyopathy in mice.

    PubMed

    Tong, Jia-Yi; Xu, Yan-Juan; Bian, Ye-Ping; Shen, Xiang-Bo; Yan, Lei; Zhu, Xin-Yi

    2013-09-01

    To study the effect and probable mechanism of Qishen Yiqi Pills on adriamycin (ADR)-induced cardiomyopathy in mice. Sixty-four mice were randomly divided into (1) the ADR group: saline (1 mL/100 g) administered every day by intragavage, ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks; (2) the ADR + Qishen Yiqi Pills I group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the beginning of the third week Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (3) the ADR + Qishen Yiqi Pills II group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the same time Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (4) the control group: saline (1 mL/100 g) administered every day by intragavage, saline (1 mL·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks. Six weeks later, cardiac function, myocardial pathology, and expression of Bcl-2 and Bax were evaluated. 1. The left ventricular diastolic diameter and the left ventricular systolic diameter were significantly increased (P < 0.05) and the left ventricular ejection fraction was significantly decreased (P < 0.05) in the ADR group, and the cardiac function of both the ADR + Qishen Yiqi Pills I group and the ADR + Qishen Yiqi Pills II group improved. 2. Myocardial morphologic observation showed that the myocardial fibers were disordered, there was cell edema, and gap widening in the ADR group. The degree of myocardial cell injury was reduced in the ADR + Qishen Yiqi Pills I group and ADR + Qishen Yiqi Pills II group compared with the ADR group. 3. The expression of Bax in the ADR group was significantly up-regulated, and the expression of Bcl-2 was significantly downregulated in the ADR group compared with the ADR + Qishen Yiqi Pills

  3. Feline cardiomyopathy.

    PubMed

    Liu, S K; Tilley, L P; Lord, P F

    1975-01-01

    Cardiology was diagnosed by means of clinical, radiographic, electrocardiographic phonocardiographic, angiocardiographic, and pathological findings in 271 or 3,745 cats necropsied from January 1962 to April 1974. The affected cats can be divided into three groups on the basis of the gross and microscopic pathological lesions: 1)endocarditis and myocarditis in 20 young cats; 2)endomyocardial fibrosis and left ventricular hypertrophy in 182 cats; and 3)myocardial degeneration and biventricular dilatation in 69 cats. Of 271 affected cats, thromboembolus was observed in the aorta, and in the carotid, femoral, iliac, renal, pulmonary, and hepatic arteries in 104 instances. The important aspects of cardiomyopathy in cats appears to be the reduced diastolic compliance of the thick left ventricle, resulting in poor fillin. Resistance to ventricular inflow raises the diastolic pressure and causes compensatory left atrial enlargement. A pathogenesis for the onset of clinical signs at any stages as the cause of the heart disease is postulated on the basis of stress causing tachycardia and poor left ventricular filling. Acute left-sided failure with pulmonary edema may be precipitated. Approximately one-fourth of the cats have enlargement of all cardiac chambers, typical of congestive cardiomyopathy. On the basis of the close similarily to cardiomyopathy in man, the cat could serve as a suitable animal model for a conservation of time and effort in the attack against this disorder. There is a need for coordinated research programs for utilizing the multiple avenues of approach such as: epidemiological, clinical, biochemical, pathological, ultrastructural, virological, and immunological.

  4. Psychiatric Illness in Takotsubo (Stress) Cardiomyopathy: A Review.

    PubMed

    Nayeri, Arash; Rafla-Yuan, Eric; Krishnan, Srikanth; Ziaeian, Boback; Cadeiras, Martin; McPherson, John A; Wells, Quinn S

    Takotsubo cardiomyopathy (TC), also known as stress-induced cardiomyopathy, has been increasingly described in relation to psychiatric illness. We performed a literature review to identify the key findings related to psychiatric illness in TC that may be relevant to the practice of mental health and other health care providers. The association of psychiatric illness with TC in addition to the spectrum of psychiatric illness found in TC, the role of exacerbation or treatment of psychiatric illness in triggering TC, different modes of presentation, prognostic implications, and long-term management of psychiatric illness in TC are discussed. Additionally, we review the limitations of the pre-existing literature and suggest areas of future research. There is a strong association between pre-existing psychiatric illness, particularly anxiety and mood spectrum disorders, and TC. Acute exacerbation of psychiatric illness, rapid uptitration or overdose of certain psychotropic agents, and electroconvulsive therapy may trigger TC. Further studies are needed to better evaluate the prognostic significance and long-term management of psychiatric illness in TC. Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.

  5. Takotsubo cardiomyopathy: an overlooked cause of chest pain

    PubMed Central

    Tomazelli, Bruno; Furieri, Natassia Prates; Coelho, Renato Alves; de Lima, Camila Fiorese

    2014-01-01

    Takotsubo cardiomyopathy (TTC), also known as apical ballooning syndrome, broken heart syndrome, or stress-induced cardiomyopathy, is defined as a transient disturbance of the left ventricle, which is quite often associated with electrocardiographic abnormalities that may mimic acute myocardial infarction. The syndrome is also characterized by a mild alteration of cardiac biomarkers in absence of coronary blood flow obstruction on the coronariography. Clinical presentation is often manifested by angina, dyspnea, syncope, and arrhythmias. Peculiarly, the left ventricle takes the form of “tako-tsubo” (a Japanese word for “octopus trap”) on the imaging workup. The authors report the case of a post-menopausal, hypertensive, dyslipidemic and type-II diabetic woman admitted at the emergency service with acute chest pain post physical exertion. Electrocardiogram showed signs of ischemia and myocardial necrosis markers were mildly increased. Echocardiography and ventriculography showed apical and mid-ventricular akinesia, with mild atherosclerotic coronary lesions. Thus diagnostic workup and the outcome followed the diagnostic criteria for TTC. The authors called attention to the potential of overlooking this diagnosis, since this syndrome is still not widely recognized. PMID:28580329

  6. Chagas cardiomyopathy is associated with higher incidence of stroke: a meta-analysis of observational studies.

    PubMed

    Cardoso, Rhanderson N; Macedo, Francisco Yuri B; Garcia, Melissa Nolan; Garcia, Daniel C; Benjo, Alexandre M; Aguilar, David; Jneid, Hani; Bozkurt, Biykem

    2014-12-01

    Chagas disease (CD) has been associated with an elevated risk of stroke, but current data are conflicting and prospective controlled studies are lacking. We performed a systematic review and meta-analysis examining the association between stroke and CD. Pubmed, Embase, Cochrane Central, Latin American database, and unpublished data were searched with the use of the following terms: ("Chagas" OR "American trypanosomiasis") AND ("dilated" OR "ischemic" OR "idiopathic" OR "nonChagasic" OR "stroke" OR "cerebrovascular"). We included studies that reported prevalence or incidence of stroke in a CD group compared with a non-CD control group. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed with the use of a random-effects model. A total of 8 studies and 4,158 patients were included, of whom 1,528 (36.7%) had CD. Risk of stroke was elevated in the group of patients with CD (OR 2.10, 95% CI 1.17-3.78). Similar results were observed in a subanalysis of cardiomyopathy patients (OR 1.74, 95% CI 1.02-3.00) and in sensitivity analysis with removal of each individual study. Furthermore, exclusion of studies at higher risk for bias also yielded consistent results (OR 1.70, 95% CI 1.06-2.71). Subanalysis restricted to studies that included patients with the indeterminate form found no significant difference in the stroke prevalence between CD and non-CD patients (OR 3.10, 95% CI 0.89-10.77). CD is significantly associated with cerebrovascular events, particularly among patients with cardiomyopathy. These findings underline the need for prospective controlled studies in patients with Chagas cardiomyopathy to ascertain the prognostic significance of cerebrovascular events and to evaluate the role of therapeutic anticoagulation in primary prevention. Published by Elsevier Inc.

  7. Ferulic Acid Attenuates the Injury-Induced Decrease of Protein Phosphatase 2A Subunit B in Ischemic Brain Injury

    PubMed Central

    Koh, Phil-Ok

    2013-01-01

    Background Ferulic acid provides a neuroprotective effect during cerebral ischemia through its anti-oxidant function. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that contributes broadly to normal brain function. This study investigated whether ferulic acid regulates PP2A subunit B in a middle cerebral artery occlusion (MCAO) animal model and glutamate toxicity-induced neuronal cell death. Methodology/Principal Findings MCAO was surgically induced to yield permanent cerebral ischemic injury in rats. The rats were treated with either vehicle or ferulic acid (100 mg/kg, i.v.) immediately after MCAO, and cerebral cortex tissues were collected 24 h after MCAO. A proteomics approach, RT-PCR, and Western blot analyses performed to identification of PP2A subunit B expression levels. Ferulic acid significantly reduced the MCAO-induced infarct volume of the cerebral cortex. A proteomics approach elucidated the reduction of PP2A subunit B in MCAO-induced animals, and ferulic acid treatment prevented the injury-induced reduction in PP2A subunit B levels. RT-PCR and Western blot analyses also showed that ferulic acid treatment attenuates the injury-induced decrease in PP2A subunit B levels. Moreover, the number of PP2A subunit B-positive cells was reduced in MCAO-induced animals, and ferulic acid prevented these decreases. In cultured neuronal cells, ferulic acid treatment protected cells against glutamate toxicity and prevented the glutamate-induced decrease in PP2A subunit B. Conclusions/Significance These results suggest that the maintenance of PP2A subunit B by ferulic acid in ischemic brain injury plays an important role for the neuroprotective function of ferulic acid. PMID:23349830

  8. Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy.

    PubMed

    Mancuso, Frederico José Neves; Moisés, Valdir Ambrósio; Almeida, Dirceu Rodrigues; Poyares, Dalva; Storti, Luciana Julio; Oliveira, Wércules Antonio; Brito, Flavio Souza; Paola, Angelo Amato Vincenzo de; Carvalho, Antonio Carlos Camargo; Campos, Orlando

    2015-07-01

    Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure. We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM). Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e' wave, E/e' ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson's coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables. Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e' ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e' ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase. The LAV is independently determined by LV filling pressures (E/e' ratio) and mitral regurgitation in DCM.

  9. [Cellular and molecular biology of ischemic retina].

    PubMed

    Honda, Y

    1996-12-01

    We introduce our studies on the retinal ischemia in light of both pre- and post-Noell viewpoints. For several years now, we have employed in vivo intraretinal microelectrodes for this field of experiments. This series of studies on the cat eye revealed that the sensory retina as well as the retinal pigment epithelium is severely damaged after only a ten-minute stoppage of blood flow. This phenomenon in usually masked in the routine electroretinogram, a mass electrical response of the retina monitored from the ocular surface. Our studies, employing cultured amacrine cells from embryonic rat eyes, revealed that ischemic changes in neural cells are induced by an increase in extracellular glutamate. Among the glutamate analogs, N-methyl-D-aspartate (NMDA) is responsive to this change. An influx of calcium through NMDA receptor channels activates nitric oxide synthase (NOS), inducing intracellular nitric oxide (NO) in selected amacrine cells. Nitric oxide reacts with free radicals in the cell and induces peroxinitrite, which is toxic. This cascade triggered by ischemia is interrupted by extracellular zinc, magnesium, hemoglobin, nitroprusside, s-nitrosocysteine, and some NMDA antagonists. In terms of clinical application, there is a possibility that dihydroxyphenylalanine (DOPA), superoxide dismutase (SOD), and catalase (CAT), as well as vitamins B6 and B12, are important candidates for administration before an ischemic attack for prevention of damage to the retinal neurons. Gene expression of NOS, interleukin (IL)-1, IL-6, tumor necrosing factor (TNF), and transforming growth factor (TGF)-beta in the ischemic retina was investigated in order to discover reaction substances common to ischemic change and inflammation.

  10. Delayed Post-ischemic Conditioning Significantly Improves the Outcome after Retinal Ischemia

    PubMed Central

    Dreixler, John C.; Poston, Jacqueline N.; Shaikh, Afzhal R.; Alexander, Michael; Tupper, Kelsey Y.; Marcet, Marcus M.; Bernaudin, Myriam; Roth, Steven

    2011-01-01

    In previous studies, it was shown that post-conditioning, a transient period of brief ischemia following prolonged severe ischemia in the retina, could provide significant improvement in post-ischemic recovery, attenuation of cell loss, and decreased apoptosis. These studies showed that post-conditioning effectively prevented damage after retinal ischemia when it was instituted early (within one hour) in the post-ischemic period. While post-ischemic conditioning holds high promise of clinical translation, patients often present late after the onset of retinal ischemia and therefore immediate application of this anti-ischemic maneuver is generally not feasible. In this study, we examined the hypothesis that application of a post-conditioning stimulus at 24 h or greater following the end of prolonged ischemia would decrease the extent of ischemic injury. Ischemia was induced in rat retina in vivo. Recovery after ischemia followed by 5 minutes of post-conditioning brief ischemia 24 or 48 h after prolonged ischemia was assessed functionally (electroretinography) and histologically at 7 days after ischemia and post-conditioning or sham post-conditioning. We found that the brief ischemic stimulus applied 24, but not 48 h after prolonged ischemia significantly improved functional recovery and decreased histological damage induced by prolonged ischemia. We conclude that within a defined time window, delayed post-ischemic conditioning ameliorated post-ischemic injury in rats. Compared to earlier studies, the present work demonstrates for the first time the novel ability of a significantly delayed ischemic stimulus to provide robust neuroprotection in the retina following ischemia. PMID:21501608

  11. Systemic autoimmunity induced by the TLR7/8 agonist Resiquimod causes myocarditis and dilated cardiomyopathy in a new mouse model of autoimmune heart disease

    PubMed Central

    Hasham, Muneer G.; Baxan, Nicoleta; Stuckey, Daniel J.; Branca, Jane; Perkins, Bryant; Dent, Oliver; Duffy, Ted; Hameed, Tolani S.; Stella, Sarah E.; Bellahcene, Mohammed; Schneider, Michael D.; Harding, Sian E.; Rosenthal, Nadia

    2017-01-01

    ABSTRACT Systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) show significant heart involvement and cardiovascular morbidity, which can be due to systemically increased levels of inflammation or direct autoreactivity targeting cardiac tissue. Despite high clinical relevance, cardiac damage secondary to systemic autoimmunity lacks inducible rodent models. Here, we characterise immune-mediated cardiac tissue damage in a new model of SLE induced by topical application of the Toll-like receptor 7/8 (TLR7/8) agonist Resiquimod. We observe a cardiac phenotype reminiscent of autoimmune-mediated dilated cardiomyopathy, and identify auto-antibodies as major contributors to cardiac tissue damage. Resiquimod-induced heart disease is a highly relevant mouse model for mechanistic and therapeutic studies aiming to protect the heart during autoimmunity. PMID:28250051

  12. Cardiomyopathies in Noonan syndrome and the other RASopathies

    PubMed Central

    Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco

    2015-01-01

    Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID:26380542

  13. Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon.

    PubMed

    Zhang, Zong-Ming; Lin, Xiang-Chun; Ma, Li; Jin, An-Qin; Lin, Fang-Cai; Liu, Zhuo; Liu, Li-Min; Zhang, Chong; Zhang, Na; Huo, Li-Juan; Jiang, Xue-Liang; Kang, Feng; Qin, Hong-Jun; Li, Qiu-Yang; Yu, Hong-Wei; Deng, Hai; Zhu, Ming-Wen; Liu, Zi-Xu; Wan, Bai-Jiang; Yang, Hai-Yan; Liao, Jia-Hong; Luo, Xu; Li, You-Wei; Wei, Wen-Ping; Song, Meng-Meng; Zhao, Yue; Shi, Xue-Ying; Lu, Zhao-Hui

    2017-06-07

    A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids.

  14. Takotsubo (Stress) Cardiomyopathy

    MedlinePlus

    ... the American Heart Association Cardiology Patient Page Takotsubo (Stress) Cardiomyopathy Scott W. Sharkey , John R. Lesser , Barry ... heart contraction has returned to normal. Importance of Stress In 85% of cases, takotsubo is triggered by ...

  15. Update on Myocarditis and Inflammatory Cardiomyopathy: Reemergence of Endomyocardial Biopsy.

    PubMed

    Dominguez, Fernando; Kühl, Uwe; Pieske, Burkert; Garcia-Pavia, Pablo; Tschöpe, Carsten

    2016-02-01

    Myocarditis is defined as an inflammatory disease of the heart muscle and is an important cause of acute heart failure, sudden death, and dilated cardiomyopathy. Viruses account for most cases of myocarditis or inflammatory cardiomyopathy, which could induce an immune response causing inflammation even when the pathogen has been cleared. Other etiologic agents responsible for myocarditis include drugs, toxic substances, or autoimmune conditions. In the last few years, advances in noninvasive techniques such as cardiac magnetic resonance have been very useful in supporting diagnosis of myocarditis, but toxic, infectious-inflammatory, infiltrative, or autoimmune processes occur at a cellular level and only endomyocardial biopsy can establish the nature of the etiological agent. Furthermore, after the generalization of immunohistochemical and viral genome detection techniques, endomyocardial biopsy provides a definitive etiological diagnosis that can lead to specific treatments such as antiviral or immunosuppressive therapy. Endomyocardial biopsy is not commonly performed for the diagnosis of myocarditis due to safety reasons, but both right- and left endomyocardial biopsies have very low complication rates when performed by experienced operators. This document provides a state-of-the-art review of myocarditis and inflammatory cardiomyopathy, with special focus on the role of endomyocardial biopsy to establish specific treatments. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  16. Heart transplantation for Chagas cardiomyopathy.

    PubMed

    Ramalho, Ana Rita; Prieto, David; Antunes, Pedro; Franco, Fátima; Antunes, Manuel J

    2017-11-01

    Chagas disease is an endemic disease in Latin America that is increasingly found in non-endemic areas all over the world due to the flow of migrants from Central and South America. We present the case of a Brazilian immigrant in Portugal who underwent orthotopic heart transplantation for end-stage Chagas cardiomyopathy. Immunosuppressive therapy included prednisone, mycophenolate mofetil and tacrolimus. Twelve months after the procedure she is asymptomatic, with good graft function, and with no evidence of complications such as graft rejection, opportunistic infections, neoplasms or reactivation of Trypanosoma cruzi infection. By reporting the first case in Portugal of heart transplantation for Chagas cardiomyopathy, we aim to increase awareness of Chagas disease as an emerging global problem and of Chagas cardiomyopathy as a serious complication for which heart transplantation is a valuable therapeutic option. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Left Atrial Volume Determinants in Patients with Non-Ischemic Dilated Cardiomyopathy

    PubMed Central

    Mancuso, Frederico José Neves; Moisés, Valdir Ambrósio; Almeida, Dirceu Rodrigues; Poyares, Dalva; Storti, Luciana Julio; Oliveira, Wércules Antonio; Brito, Flavio Souza; de Paola, Angelo Amato Vincenzo; Carvalho, Antonio Carlos Camargo; Campos, Orlando

    2015-01-01

    Background Left atrial volume (LAV) is a predictor of prognosis in patients with heart failure. Objective We aimed to evaluate the determinants of LAV in patients with dilated cardiomyopathy (DCM). Methods Ninety patients with DCM and left ventricular (LV) ejection fraction ≤ 0.50 were included. LAV was measured with real-time three-dimensional echocardiography (eco3D). The variables evaluated were heart rate, systolic blood pressure, LV end-diastolic volume and end-systolic volume and ejection fraction (eco3D), mitral inflow E wave, tissue Doppler e´ wave, E/e´ ratio, intraventricular dyssynchrony, 3D dyssynchrony index and mitral regurgitation vena contracta. Pearson´s coefficient was used to identify the correlation of the LAV with the assessed variables. A multiple linear regression model was developed that included LAV as the dependent variable and the variables correlated with it as the predictive variables. Results Mean age was 52 ± 11 years-old, LV ejection fraction: 31.5 ± 8.0% (16-50%) and LAV: 39.2±15.7 ml/m2. The variables that correlated with the LAV were LV end-diastolic volume (r = 0.38; p < 0.01), LV end-systolic volume (r = 0.43; p < 0.001), LV ejection fraction (r = -0.36; p < 0.01), E wave (r = 0.50; p < 0.01), E/e´ ratio (r = 0.51; p < 0.01) and mitral regurgitation (r = 0.53; p < 0.01). A multivariate analysis identified the E/e´ ratio (p = 0.02) and mitral regurgitation (p = 0.02) as the only independent variables associated with LAV increase. Conclusion The LAV is independently determined by LV filling pressures (E/e´ ratio) and mitral regurgitation in DCM. PMID:25993483

  18. A predictive model for canine dilated cardiomyopathy-a meta-analysis of Doberman Pinscher data.

    PubMed

    Simpson, Siobhan; Edwards, Jennifer; Emes, Richard D; Cobb, Malcolm A; Mongan, Nigel P; Rutland, Catrin S

    2015-01-01

    Dilated cardiomyopathy is a prevalent and often fatal disease in humans and dogs. Indeed dilated cardiomyopathy is the third most common form of cardiac disease in humans, reported to affect approximately 36 individuals per 100,000 individuals. In dogs, dilated cardiomyopathy is the second most common cardiac disease and is most prevalent in the Irish Wolfhound, Doberman Pinscher and Newfoundland breeds. Dilated cardiomyopathy is characterised by ventricular chamber enlargement and systolic dysfunction which often leads to congestive heart failure. Although multiple human loci have been implicated in the pathogenesis of dilated cardiomyopathy, the identified variants are typically associated with rare monogenic forms of dilated cardiomyopathy. The potential for multigenic interactions contributing to human dilated cardiomyopathy remains poorly understood. Consistent with this, several known human dilated cardiomyopathy loci have been excluded as common causes of canine dilated cardiomyopathy, although canine dilated cardiomyopathy resembles the human disease functionally. This suggests additional genetic factors contribute to the dilated cardiomyopathy phenotype.This study represents a meta-analysis of available canine dilated cardiomyopathy genetic datasets with the goal of determining potential multigenic interactions relating the sex chromosome genotype (XX vs. XY) with known dilated cardiomyopathy associated loci on chromosome 5 and the PDK4 gene in the incidence and progression of dilated cardiomyopathy. The results show an interaction between known canine dilated cardiomyopathy loci and an unknown X-linked locus. Our study is the first to test a multigenic contribution to dilated cardiomyopathy and suggest a genetic basis for the known sex-disparity in dilated cardiomyopathy outcomes.

  19. Non compaction cardiomyopathy: Review of a controversial entity.

    PubMed

    Lorca, Rebeca; Rozado, José; Martín, María

    2018-05-11

    Non-compaction cardiomyopathy is a heterogeneous and complex entity concerning which there are still many doubts to be resolved. While the American Heart Association includes it among genetic cardiomyopathies, the European Society of Cardiology treats it as an unclassified cardiomyopathy. It may present in a sporadic or familial form, isolated or associated with other heart diseases, affecting only the left ventricle or both and can sometimes appear as a mixed phenotype in patients with other cardiomyopathies. Different forms of clinical presentation are also associated with its different morphological manifestations, and even non-compaction of the left ventricle may be triggered by other physiological or pathological processes. The purpose of this review is an update of this entity and its controversies. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. HSP70.1 AND -70.3 ARE REQUIRED FOR LATE-PHASE PROTECTION INDUCED BY ISCHEMIC PRECONDITIONING OF MOUSE HEARTS

    EPA Science Inventory

    Heat-Shock Proteins 70.1 and 70.3 Are Required for Late-phase Protection
    Induced by Ischemic Preconditioning of the Mouse Heart
    Craig R. Hampton 1 , Akira Shimamoto 1 , Christine L. Rothnie 1 , Jeaneatte Griscavage-Ennis 1 ,
    Albert Chong 1 , David J. Dix 2 , Edward D. Ve...

  1. Intrathecal baclofen withdrawal: A rare cause of reversible cardiomyopathy.

    PubMed

    Awuor, Stephen O; Kitei, Paul M; Nawaz, Yassir; Ahnert, Amy M

    2016-03-01

    Baclofen is commonly used to treat spasticity of central etiology. Unfortunately, a potentially lethal withdrawal syndrome can complicate its use. This is especially true when the drug is administered intrathecally. There are very few cases of baclofen withdrawal leading to reversible cardiomyopathy described in the literature. The authors present a patient with a history of chronic intrathecal baclofen use who, in the setting of acute baclofen withdrawal, develops laboratory, electrocardiogram, and echocardiogram abnormalities consistent with cardiomyopathy. Upon reinstitution of intrathecal baclofen, the cardiomyopathy and associated abnormalities quickly resolve. Although rare, it is crucial to be aware of this reversible cardiomyopathy to ensure its prompt diagnosis and treatment.

  2. Involvement of glycogen synthase kinase-3β in liver ischemic conditioning induced cardioprotection against myocardial ischemia and reperfusion injury in rats

    PubMed Central

    Yang, Shuai; Abbott, Geoffrey W.; Gao, Wei Dong; Liu, Jin; Luo, Chaozhi

    2017-01-01

    Remote ischemic conditioning has been convincingly shown to render the myocardium resistant to a subsequent more severe sustained episode of ischemia. Compared with other organs, little is known regarding the effect of transient liver ischemic conditioning. We proposed the existence of cardioprotection induced by remote liver conditioning. Male Sprague-Dawley rats were divided into sham-operated control (no further hepatic intervention) and remote liver ischemic conditioning groups. For liver ischemic conditioning, three cycles of 5 min of liver ischemia-reperfusion stimuli were conducted before-(liver preconditioning), post-myocardial ischemia (liver postconditioning), or in combination of both (liver preconditioning + liver postconditioning). Rats were exposed to 45 min of left anterior descending coronary artery occlusion, followed by 3 h of reperfusion thereafter. ECG and hemodynamics were measured throughout the experiment. The coronary artery was reoccluded at the end of reperfusion for infarct size determination. Blood samples were taken for serum lactate dehydrogenase and creatine kinase-MB test. Heart tissues were taken for apoptosis measurements and Western blotting. Our data demonstrate that liver ischemic preconditioning, postconditioning, or a combination of both, offered strong cardioprotection, as evidenced by reduction in infarct size and cardiac tissue damage, recovery of cardiac function, and inhibition of apoptosis after ischemia-reperfusion. Moreover, liver ischemic conditioning increased cardiac (not hepatic) glycogen synthase kinase-3β (GSK-3β) phosphorylation. Accordingly, inhibition of GSK-3β mimicked the cardioprotective action of liver conditioning. These results demonstrate that remote liver ischemic conditioning protected the heart against ischemia and reperfusion injury via GSK-3β-dependent cell-survival signaling pathway. NEW & NOTEWORTHY Remote ischemic conditioning protects hearts against ischemia and reperfusion (I/R) injury

  3. Development of porcine model of chronic tachycardia-induced cardiomyopathy.

    PubMed

    Paslawska, Urszula; Gajek, Jacek; Kiczak, Liliana; Noszczyk-Nowak, Agnieszka; Skrzypczak, Piotr; Bania, Jacek; Tomaszek, Alicja; Zacharski, Maciej; Sambor, Izabela; Dziegiel, Piotr; Zysko, Dorota; Banasiak, Waldemar; Jankowska, Ewa A; Ponikowski, Piotr

    2011-11-17

    There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    DTIC Science & Technology

    2015-12-01

    Amelioration of hyperbilirubinemia in Gunn rats after transplantation of human induced pluripotent stem cell -derived hepatocytes. Stem Cell Reports 2015...use of differentiated pluripotent stem cells as replacement therapy in treating disease. Science 2014; 345:1247391. 12. Nishikawa T, Bell A, Brooks...Award Number: W81XWH-11-1-0803 TITLE: Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy PRINCIPAL INVESTIGATOR

  5. Tapioca Cardiomyopathy: Curse of Cassava Endomyocardial Fibrosis

    PubMed Central

    Anandan, Prem Krishna; Shukkarbhai, Patel Jigarkumar; George, Jimmy; Bhatt, Prabhavathi; Manjunath, Cholenahally Nanjappa

    2015-01-01

    Tropical endomyocardial fibrosis is a rare entity in the present era. Restrictive cardiomyopathy due to tapioca consumption is very rare, although it has been reported in India, especially in state of Kerala. We report a rare case of restrictive cardiomyopathy secondary to tapioca consumption in a 20-year-old male patient. PMID:28197237

  6. Takotsubo cardiomyopathy in a patient with Addison disease.

    PubMed

    Punnam, Sujeeth Reddy; Gourineni, Nandu; Gupta, Vishal

    2010-10-08

    Transient left ventricular apical ballooning syndrome, also known as Takotsubo Cardiomyopathy (Broken Heart Syndrome) is increasingly being reported in the medical literature. Its clinical picture resembles of an acute coronary syndrome with transient apical dyskinesia and normal coronary arteries. We report here a case of Takotsubo cardiomyopathy in a patient with Addison disease with reversible cardiomyopathy. To the best of our knowledge there has been only one other reported case of this syndrome with Addison disease but with a different outcome. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

  7. Xylometazoline abuse induced ischemic stroke in a young adult.

    PubMed

    Leupold, Daniela; Wartenberg, Katja E

    2011-01-01

    substance abuse is an important cause of ischemic stroke in the young. This includes over-the-counter dietary supplements and cough and cold remedies, which were reported to be an independent risk factor for hemorrhagic stroke. this article describes a young male patient with acute ischemic infarctions in the posterior inferior cerebellar and posterior cerebral artery territories bilaterally, the right cerebral peduncle, the left pontine tegmentum, and lateral pons following abuse of xylometazoline-containing nasal decongestant for 10 years. this is the first report in the literature of posterior circulation strokes because of chronic xylometazoline abuse. We hope to contribute to increase knowledge and awareness of the public about these serious complications of cough-and-cold remedies as well as dietary supplements containing sympathomimetics.

  8. BAG3 myofibrillar myopathy presenting with cardiomyopathy.

    PubMed

    Konersman, Chamindra G; Bordini, Brett J; Scharer, Gunter; Lawlor, Michael W; Zangwill, Steven; Southern, James F; Amos, Louella; Geddes, Gabrielle C; Kliegman, Robert; Collins, Michael P

    2015-05-01

    Myofibrillar myopathies (MFMs) are a heterogeneous group of neuromuscular disorders distinguished by the pathological hallmark of myofibrillar dissolution. Most patients present in adulthood, but mutations in several genes including BCL2-associated athanogene 3 (BAG3) cause predominantly childhood-onset disease. BAG3-related MFM is particularly severe, featuring weakness, cardiomyopathy, neuropathy, and early lethality. While prior cases reported either neuromuscular weakness or concurrent weakness and cardiomyopathy at onset, we describe the first case in which cardiomyopathy and cardiac transplantation (age eight) preceded neuromuscular weakness by several years (age 12). The phenotype comprised distal weakness and severe sensorimotor neuropathy. Nerve biopsy was primarily axonal with secondary demyelinating/remyelinating changes without "giant axons." Muscle biopsy showed extensive neuropathic changes that made myopathic changes difficult to interpret. Similar to previous cases, a p.Pro209Leu mutation in exon 3 of BAG3 was found. This case underlines the importance of evaluating for MFMs in patients with combined neuromuscular weakness and cardiomyopathy. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The Role of CMR in Cardiomyopathies

    PubMed Central

    Kramer, Christopher M.

    2015-01-01

    Cardiac magnetic resonance imaging (CMR) has made major inroads in the new millenium in the diagnosis and assessment of prognosis for patients with cardiomyopathies. Imaging of left and right ventricular structure and function and tissue characterization with late gadolinium enhancement (LGE) as well as T1 and T2 mapping enable accurate diagnosis of the underlying etiology. In the setting of coronary artery disease, either transmurality of LGE or contractile reserve in response to dobutamine can assess the likelihood of recovery of function after revascularization. The presence of scar reduces the likelihood of response to medical therapy and to cardiac resynchronization therapy in heart failure. The presence and extent of LGE relate to overall cardiovascular outcome in cardiomyopathies. An emerging major role for CMR in cardiomyopathies is to identify myocardial scar for diagnostic and prognostic purposes. PMID:26033902

  10. Sevoflurane postconditioning against cerebral ischemic neuronal injury is abolished in diet-induced obesity: role of brain mitochondrial KATP channels.

    PubMed

    Yang, Zecheng; Chen, Yunbo; Zhang, Yan; Jiang, Yi; Fang, Xuedong; Xu, Jingwei

    2014-03-01

    Obesity is associated with increased infarct volumes and adverse outcomes following ischemic stroke. However, its effect on anesthetic postconditioning‑induced neuroprotection has not been investigated. The present study examined the effect of sevoflurane postconditioning on focal ischemic brain injury in diet‑induced obesity. Sprague‑Dawley rats were fed a high‑fat diet (HF; 45% kcal as fat) for 12 weeks to develop obesity syndrome. Rats fed a low‑fat diet (LF; 10% kcal as fat) served as controls. The HF or LF‑fed rats were subjected to focal cerebral ischemia for 60 min, followed by 24 h of reperfusion. Postconditioning was performed by exposure to sevoflurane for 15 min immediately at the onset of reperfusion. The involvement of the mitochondrial KATP (mitoKATP) channel was analyzed by the administration of a selective inhibitor of 5‑hydroxydecanoate (5‑HD) prior to sevoflurane postconditioning or by administration of diazoxide (DZX), a mitoKATP channel opener, instead of sevoflurane. The cerebral infarct volume, neurological score and motor coordination were evaluated 24 h after reperfusion. The HF‑fed rats had larger infarct volumes, and lower neurological scores than the LF‑fed rats and also failed to respond to neuroprotection by sevoflurane or DZX. By contrast, sevoflurane and DZX reduced the infarct volumes and improved the neurological scores and motor coordination in the LF‑fed rats. Pretreatment with 5‑HD inhibited sevoflurane‑induced neuroprotection in the LF‑fed rats, whereas it had no effect in the HF‑fed rats. Molecular studies demonstrated that the expression of Kir6.2, a significant mitoKATP channel component, was reduced in the brains of the HF‑fed rats compared with the LF‑fed rats. The results of this study indicate that diet‑induced obesity eliminates the ability of anesthetic sevoflurane postconditioning to protect the brain against cerebral ischemic neuronal injury, most likely due to an impaired brain

  11. Stress cardiomyopathy syndrome: a contemporary review.

    PubMed

    Kapoor, Divya; Bybee, Kevin A

    2009-12-01

    Stress cardiomyopathy (SC) syndrome represents a reversible form of cardiomyopathy that commonly presents proximate to an acute emotional or physiologic stressor. The clinical presentation is similar to an acute coronary syndrome in the absence of obstructive coronary artery disease to explain the unusual distribution of associated transient wall motion abnormalities. Postmenopausal women seem particularly prone to SC for unclear reasons. The pathophysiology of the syndrome is unknown but may involve pathologic sympathetic myocardial stimulation.

  12. Preventive mechanisms of agmatine against ischemic acute kidney injury in rats.

    PubMed

    Sugiura, Takahiro; Kobuchi, Shuhei; Tsutsui, Hidenobu; Takaoka, Masanori; Fujii, Toshihide; Hayashi, Kentaro; Matsumura, Yasuo

    2009-01-28

    The excitation of renal sympathetic nervous system plays an important role in the development of ischemic acute kidney injury in rats. Recently, we found that agmatine, an adrenaline alpha(2)/imidazoline I(1)-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the enhanced renal sympathetic nerve activity during renal ischemia and by decreasing the renal venous norepinephrine overflow after reperfusion. In the present study, we investigated preventive mechanisms of agmatine against ischemic acute kidney injury in rats. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after the contralateral nephrectomy. Pretreatment with efaroxan (30 mumol/kg, i.v.), an alpha(2)/I(1)-receptor antagonist, abolished the suppressive effects of agmatine on the enhanced renal sympathetic nerve activity during renal ischemia and on the elevated norepinephrine overflow after reperfusion, and eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal dysfunction and histological damage. On the other hand, pretreatment with yohimbine (6 mumol/kg, i.v.), an alpha(2)-receptor antagonist, eliminated the preventing effects of agmatine on the ischemia/reperfusion-induced renal injury and norepinephrine overflow, without affecting the lowering effect of agmatine on renal sympathetic nerve activity. These results indicate that agmatine prevents the ischemic renal injury by sympathoinhibitory effect probably via I(1) receptors in central nervous system and by suppressing the norepinephrine overflow through alpha(2) or I(1) receptors on sympathetic nerve endings.

  13. [A reversible cause of dilated cardiomyopathy: hypocalcemia].

    PubMed

    Benzarouel, D; Hasni, K; Ashab, H; El Hattaoui, M

    2014-04-01

    Hypocalcemia is very rare reversible cause of dilated cardiomyopathy (DCMP) witch can concern one or both ventricules. We here presented two cases of DCMP that caused by hypocalcemia and recovered totally after oral calcium and vitamin D supplementation. CASE PRESENTATION 1: A 29-year-old Caucasian female was admitted in our hospital due to congestive heart failure with dyspnea (NYHA class IV) and generalized edema for 2days. She had a history of total thyroidectomy one year a go. She had taken synthyroid as a daily medication associated to calcium supplementation and vitamin D because of hypoparathyroidism. Patient was not compliant to treatment. Trans thoracic echocardiography (TTE) showed a dilated left ventricule (LV) with global hypokinesia with 28% of left ventricule ejection and moderate mitral regurgitation. Laboratory test showed a severe hypocalcemia. After correction of hypocalcemia, there was a clear clinical improvement and four months later a total recovery was found. CASE PRESENTATION 2: A 44-year-old Caucasian male was referred to the hospital for rebel congestive heart failure with dyspnea and edema of lower limbs despite optimal treatment. Patient had no medical past history. TEE showed dilated cardiomyopathy with severe alteration of left ventricule systolic function (25%). Biological tests showed a hypocalcemia and primary hypoparathyroidism. An improvement of symptoms after correction of metabolic disorder was found. LV gradually recovered its performance. Patients outcome in end stage heart failure is different from the classical outcomes in patients with hypocalcemia induced heart disease. DCMP induced by hypocalcemia should be considered in patients with heart failure associated with medical conditions leading to hypocalcemia. It requires a specific treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Ischemic Strokes (Clots)

    MedlinePlus

    ... Month Infographic Stroke Hero F.A.S.T. Quiz Ischemic Strokes (Clots) Updated:May 21,2018 Ischemic stroke accounts for about 87 percent of all cases. View a detailed animation of ischemic stroke . Ischemic strokes occur as a result of an ...

  15. Ischemic or toxic injury: A challenging diagnosis and treatment of drug-induced stenosis of the sigmoid colon

    PubMed Central

    Zhang, Zong-Ming; Lin, Xiang-Chun; Ma, Li; Jin, An-Qin; Lin, Fang-Cai; Liu, Zhuo; Liu, Li-Min; Zhang, Chong; Zhang, Na; Huo, Li-Juan; Jiang, Xue-Liang; Kang, Feng; Qin, Hong-Jun; Li, Qiu-Yang; Yu, Hong-Wei; Deng, Hai; Zhu, Ming-Wen; Liu, Zi-Xu; Wan, Bai-Jiang; Yang, Hai-Yan; Liao, Jia-Hong; Luo, Xu; Li, You-Wei; Wei, Wen-Ping; Song, Meng-Meng; Zhao, Yue; Shi, Xue-Ying; Lu, Zhao-Hui

    2017-01-01

    A 48-year-old woman was admitted with 15-mo history of abdominal pain, diarrhea and hematochezia, and 5-mo history of defecation difficulty. She had been successively admitted to nine hospitals, with an initial diagnosis of inflammatory bowel disease with stenotic sigmoid colon. Findings from computed tomography virtual colonoscopy, radiography with meglumine diatrizoate, endoscopic balloon dilatation, metallic stent implantation and later overall colonoscopy, coupled with the newfound knowledge of compound Qingdai pill-taking, led to a subsequent diagnosis of ischemic or toxic bowel disease with sigmoid colon stenosis. The patient was successfully treated by laparoscopic sigmoid colectomy, and postoperative pathological examination revealed ischemic or toxic injury of the sigmoid colon, providing a final diagnosis of drug-induced sigmoid colon stenosis. This case highlights that adequate awareness of drug-induced colon stenosis has a decisive role in avoiding misdiagnosis and mistreatment. The diagnostic and therapeutic experiences learnt from this case suggest that endoscopic balloon expansion and colonic metallic stent implantation as bridge treatments were demonstrated as crucial for the differential diagnosis of benign colonic stenosis. Skillful surgical technique and appropriate perioperative management helped to ensure the safety of our patient in subsequent surgery after long-term use of glucocorticoids. PMID:28638234

  16. Sleep-Disordered Breathing in Hypertrophic Cardiomyopathy

    PubMed Central

    Somers, Virend K.

    2014-01-01

    Sleep-disordered breathing (SDB) may be a treatable risk factor in patients with hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy. Evidence suggests a high prevalence of SDB in HCM. We summarize the pathophysiology of SDB as it relates to hypertension, coronary artery disease, atrial fibrillation, and sudden cardiac death in patients with HCM. The implications regarding the care of patients with HCM and SDB are discussed as well as the knowledge deficits needing further exploration. PMID:25010966

  17. MELAS syndrome, cardiomyopathy, rhabdomyolysis, and autism associated with the A3260G mitochondrial DNA mutation.

    PubMed

    Connolly, Barbara S; Feigenbaum, Annette S J; Robinson, Brian H; Dipchand, Anne I; Simon, David K; Tarnopolsky, Mark A

    2010-11-12

    The A to G transition mutation at position 3260 of the mitochondrial genome is usually associated with cardiomyopathy and myopathy. One Japanese kindred reported the phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome) in association with the A3260G mtDNA mutation. We describe the first Caucasian cases of MELAS syndrome associated with the A3260G mutation. Furthermore, this mutation was associated with exercise-induced rhabdomyolysis, hearing loss, seizures, cardiomyopathy, and autism in the large kindred. We conclude that the A3260G mtDNA mutation is associated with wide phenotypic heterogeneity with MELAS and other "classical" mitochondrial phenotypes being manifestations. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

    PubMed

    Charron, Philippe; Elliott, Perry M; Gimeno, Juan R; Caforio, Alida L P; Kaski, Juan Pablo; Tavazzi, Luigi; Tendera, Michal; Maupain, Carole; Laroche, Cécile; Rubis, Pawel; Jurcut, Ruxandra; Calò, Leonardo; Heliö, Tiina M; Sinagra, Gianfranco; Zdravkovic, Marija; Kavoliuniene, Aušra; Felix, Stephan B; Grzybowski, Jacek; Losi, Maria-Angela; Asselbergs, Folkert W; García-Pinilla, José Manuel; Salazar-Mendiguchia, Joel; Mizia-Stec, Katarzyna; Maggioni, Aldo P

    2018-05-21

    The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

  19. MR Imaging in Hypertrophic Cardiomyopathy: From Magnet to Bedside.

    PubMed

    Bogaert, Jan; Olivotto, Iacopo

    2014-11-01

    Hypertrophic cardiomyopathy ( HCM hypertrophic cardiomyopathy ), the most common genetically transmitted cardiac disorder, has been the focus of extensive research over the past 50 years. HCM hypertrophic cardiomyopathy is a multifaceted disease with highly heterogeneous genetic background, phenotypic expression, clinical presentation, and long-term outcome. Though most patients have an indolent course with a life expectancy comparable to that of the general population, early diagnosis and accurate risk profiling are essential to identify the sizeable subset at increased risk of sudden cardiac death or disease progression and heart failure-related complications, requiring aggressive management options. Imaging has a central role in the diagnosis and prognostic assessment of HCM hypertrophic cardiomyopathy patients, as well as screening of potentially affected family members. In this context, magnetic resonance (MR) imaging has recently emerged as an ideal complement to transthoracic echocardiography. Its multiparametric approach, fusing spatial, contrast, and temporal resolution, provides the clinician with detailed characterization of the HCM hypertrophic cardiomyopathy phenotype and assessment of its functional consequences including causes and site of dynamic obstruction, presence and extent of myocardial perfusion abnormalities, and fibrosis. Moreover, MR is key in differentiating HCM hypertrophic cardiomyopathy from "phenocopies"-that is, hearts with similar morphology but profoundly different etiology, such as amyloid or Anderson-Fabry disease. Long term, the incremental information provided by MR is relevant to planning of septal reduction therapies, identification of the early stages of end-stage progression, and stratification of arrhythmic risk. The aim of this review is to depict the increasingly important role of MR imaging in relation to the complexity of HCM hypertrophic cardiomyopathy , highlighting its role in clinical decision making.

  20. A case of reversible dilated cardiomyopathy after alpha-interferon therapy in a patient with renal cell carcinoma.

    PubMed

    Kuwata, Akiko; Ohashi, Masuo; Sugiyama, Masaya; Ueda, Ryuzo; Dohi, Yasuaki

    2002-12-01

    A 47-year-old man with renal cell carcinoma underwent nephrectomy, and postoperative chemotherapy was performed with recombinant alpha-interferon. Five years later, he experienced dyspnea during physical exertion. An echocardiogram revealed dilatation and systolic dysfunction of the left ventricle, and thallium-201 myocardial scintigraphy showed diffuse heterogeneous perfusion. We diagnosed congestive heart failure because of cardiomyopathy induced by alpha-interferon therapy. Withdrawal of interferon therapy and the combination of an angiotensin-converting enzyme inhibitor, diuretics, and digitalis improved left ventricular systolic function. Furthermore, myocardial scintigraphy using [123I] beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) or [123 I]metaiodobenzylguanidine (123I-MIBG) revealed normal perfusion after the improvement of congestive heart failure. This is a rare case of interferon-induced cardiomyopathy that resulted in normal myocardial images in 123I-BMIPP and 123I-MIBG scintigrams after withdrawal of interferon therapy.

  1. Infant with cardiomyopathy: When to suspect inborn errors of metabolism?

    PubMed Central

    Byers, Stephanie L; Ficicioglu, Can

    2014-01-01

    Inborn errors of metabolism are identified in 5%-26% of infants and children with cardiomyopathy. Although fatty acid oxidation disorders, lysosomal and glycogen storage disorders and organic acidurias are well-known to be associated with cardiomyopathies, emerging reports suggest that mitochondrial dysfunction and congenital disorders of glycosylation may also account for a proportion of cardiomyopathies. This review article clarifies when primary care physicians and cardiologists should suspect inborn errors of metabolism in a patient with cardiomyopathy, and refer the patient to a metabolic specialist for a further metabolic work up, with specific discussions of “red flags” which should prompt additional evaluation. PMID:25429327

  2. Hypertrophic Cardiomyopathy Association

    MedlinePlus

    ... services. Shirt Closeout Sale!!! - Visit our Store to purchase yours today!!! ►►►►►■... Online Shopping Amazon donates 0.5% of the purchase price to Hypertrophic Cardiomyopathy Association. Bookmark the link ...

  3. Targeted delivery of growth factors in ischemic stroke animal models.

    PubMed

    Rhim, Taiyoun; Lee, Minhyung

    2016-01-01

    Ischemic stroke is caused by reduced blood supply and leads to loss of brain function. The reduced oxygen and nutrient supply stimulates various physiological responses, including induction of growth factors. Growth factors prevent neuronal cell death, promote neovascularization, and induce cell growth. However, the concentration of growth factors is not sufficient to recover brain function after the ischemic damage, suggesting that delivery of growth factors into the ischemic brain may be a useful treatment for ischemic stroke. In this review, various approaches for the delivery of growth factors to ischemic brain tissue are discussed, including local and targeting delivery systems. To develop growth factor therapy for ischemic stroke, important considerations should be taken into account. First, growth factors may have possible side effects. Thus, concentration of growth factors should be restricted to the ischemic tissues by local administration or targeted delivery. Second, the duration of growth factor therapy should be optimized. Growth factor proteins may be degraded too fast to have a high enough therapeutic effect. Therefore, delivery systems for controlled release or gene delivery may be useful. Third, the delivery systems to the brain should be optimized according to the delivery route.

  4. Myocardial recovery in peripartum cardiomyopathy: prospective comparison with recent onset cardiomyopathy in men and nonperipartum women.

    PubMed

    Cooper, Leslie T; Mather, Paul J; Alexis, Jeffrey D; Pauly, Daniel F; Torre-Amione, Guillermo; Wittstein, Ilan S; Dec, G William; Zucker, Mark; Narula, Jagat; Kip, Kevin; McNamara, Dennis M

    2012-01-01

    Whether myocardial recovery occurs more frequently in peripartum cardiomyopathy (PPCM) than in recent onset cardiomyopathies in men and nonperipartum women has not been prospectively evaluated. This was examined through an analysis of outcomes in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) registry. IMAC2 enrolled 373 subjects with recent onset nonischemic dilated cardiomyopathy. Left ventricular ejection fraction (LVEF) was assessed at entry and 6 months, and subjects followed for up to 4 years. Myocardial recovery was compared between men (group 1), nonperipartum women (group 2) and subjects with PPCM (group 3). The cohort included 230 subjects in group 1, 104 in group 2, and 39 in group 3. The mean LVEF at baseline in groups 1, 2, and 3 was 0.23 ± 0.08, 0.24 ± 0.08, and 0.27 ± 0.07 (P = .04), and at 6 months was 0.39 ± 0.12, 0.42 ± 0.11, and 0.45 ± 0.14 (P = .007). Subjects in group 3 had a much greater likelihood of achieving an LVEF >0.50 at 6 months than groups 1 or 2 (19 %, 34%, and 48% respectively, P = .002). Prospective evaluation confirms myocardial recovery is greatest in women with PPCM, poorest in men, and intermediate in nonperipartum women. On contemporary therapy, nearly half of women with PPCM normalize cardiac function by 6 months. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. The Migraine-Ischemic Stroke Relation in Young Adults

    PubMed Central

    Pezzini, Alessandro; Del Zotto, Elisabetta; Giossi, Alessia; Volonghi, Irene; Costa, Paolo; Dalla Volta, Giorgio; Padovani, Alessandro

    2011-01-01

    In spite of the strong epidemiologic evidence linking migraine and ischemic stroke in young adults, the mechanisms explaining this association remain poorly understood. The observation that stroke occurs more frequently during the interictal phase of migraine prompts to speculation that an indirect relation between the two diseases might exist. In this regard, four major issues might be considered which may be summarized as follows: (1) the migraine-ischemic stroke relation is influenced by specific risk factors such as patent foramen ovale or endothelial dysfunction and more frequent in particular conditions like spontaneous cervical artery dissection; (2) migraine is associated with an increased prevalence of cardiovascular risk factors; (3) the link is caused by migraine-specific drugs; (4) migraine and ischemic vascular events are linked via a genetic component. In the present paper, we will review epidemiological studies, discuss potential mechanisms of migraine-induced stroke and comorbid ischemic stroke, and pose new research questions. PMID:21197470

  6. Controversies Surrounding Exercise in Genetic Cardiomyopathies.

    PubMed

    Atteya, Gourg; Lampert, Rachel

    2018-04-01

    Exercise and sports are an integral part of daily life for millions of Americans, with 16% of the US population older than age 15 years engaged in sports or exercise activities (Bureau of Labor statistics). The physical and psychological benefits of exercise are well-recognized. However, high-profile cases of athletes dying suddenly on the field, often due to undiagnosed genetic cardiomyopathies, raise questions about the risks and benefits of exercise for those with cardiomyopathy. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. The mitochondrial superoxide dismutase A16V polymorphism in the cardiomyopathy associated with hereditary haemochromatosis.

    PubMed

    Valenti, L; Conte, D; Piperno, A; Dongiovanni, P; Fracanzani, A L; Fraquelli, M; Vergani, A; Gianni, C; Carmagnola, L; Fargion, S

    2004-12-01

    The A16V mitochondrial targeting sequence polymorphism influences the antioxidant activity of MnSOD, an enzyme involved in neutralising iron induced oxidative stress. Patients with hereditary haemochromatosis develop parenchymal iron overload, which may lead to cirrhosis, diabetes, hypogonadism, and heart disease. The objective of this study was to determine in patients with haemochromatosis whether the presence of the Val MnSOD allele, associated with reduced enzymatic activity, affects tissue damage, and in particular heart disease, as MnSOD knockout mice develop lethal cardiomyopathy. We studied 217 consecutive unrelated probands with haemochromatosis, and 212 healthy controls. MnSOD polymorphism was evaluated by restriction analysis. The frequency distribution of the polymorphism did not differ between patients and controls. Patients carrying the Val allele had higher prevalence of cardiomyopathy (A/A 4%, A/V 11%, V/V 30%, p = 0.0006) but not of cirrhosis, diabetes, or hypogonadism, independently of age, sex, alcohol misuse, diabetes, and iron overload (odds ratio 10.1 for V/V, p = 0.006). The frequency of the Val allele was higher in patients with cardiomyopathy (0.67 v 0.45, p = 0.003). The association was significant in both C282Y+/+ (p = 0.02), and in non-C282Y+/+ patients (p = 0.003), and for both dilated (p = 0.01) and non-dilated stage (p = 0.04) cardiomyopathy, but not for ischaemic heart disease. In patients with hereditary haemochromatosis, the MnSOD genotype affects the risk of cardiomyopathy related to iron overload and possibly to other known and unknown risk factors and could represent an iron toxicity modifier gene.

  8. IGF-1 Prevents Diastolic and Systolic Dysfunction Associated with Cardiomyopathy and Preserves Adrenergic Sensitivity

    PubMed Central

    Roof, Steve R.; Boslett, James; Russell, Duncan; del Rio, Carlos; Alecusan, Joe; Zweier, Jay L.; Ziolo, Mark T.; Hamlin, Robert; Mohler, Peter J.; Curran, Jerry

    2015-01-01

    Aims Insulin-like growth factor 1 (IGF-1)-dependent signaling promotes exercise-induced physiological cardiac hypertrophy. However, the in vivo therapeutic potential of IGF-1 for heart disease is not well established. Here we test the potential therapeutic benefits of IGF-1 on cardiac function using an in vivo model of chronic catecholamine-induced cardiomyopathy. Methods Rats were perfused with isoproterenol via osmotic pump (1 mg/kg/day) and treated with 2 mg/kg IGF-1 (2 mg/kg/day, 6 days a week) for 2 or 4 weeks. Echocardiography, ECG, and blood pressure were assessed. In vivo pressure-volume loop studies were conducted at 4 weeks. Heart sections were analyzed for fibrosis and apoptosis, and relevant biochemical signaling cascades were assessed. Results After 4 weeks, diastolic function (EDPVR, EDP, tau, E/A ratio), systolic function (PRSW, ESPVR, dP/dtmax), and structural remodeling (LV chamber diameter, wall thickness) were all adversely affected in isoproterenol-treated rats. All these detrimental effects were attenuated in rats treated with Iso+IGF-1. Isoproterenol-dependent effects on BP were attenuated by IGF-1 treatment. Adrenergic sensitivity was blunted in isoproterenol-treated rats but was preserved by IGF-1 treatment. Immunoblots indicate that cardioprotective p110α signaling and activated Akt are selectively upregulated in Iso+IGF-1 treated hearts. Expression of iNOS was significantly increased in both the Iso and Iso+IGF-1 groups, however tetrahydrobiopterin (BH4) levels were decreased in the Iso group and maintained by IGF-1 treatment. Conclusion IGF-1 treatment attenuates diastolic and systolic dysfunction associated with chronic catecholamine-induced cardiomyopathy while preserving adrenergic sensitivity and promoting BH4 production. These data support the potential use of IGF-1 therapy for clinical applications for cardiomyopathies. PMID:26399932

  9. Genetic basis of arrhythmogenic cardiomyopathy.

    PubMed

    Karmouch, Jennifer; Protonotarios, Alexandros; Syrris, Petros

    2018-05-01

    To date 16 genes have been associated with arrhythmogenic cardiomyopathy (ACM). Mutations in these genes can lead to a broad spectrum of phenotypic expression ranging from disease affecting predominantly the right or left ventricle, to biventricular subtypes. Understanding the genetic causes of ACM is important in diagnosis and management of the disorder. This review summarizes recent advances in molecular genetics and discusses the application of next-generation sequencing technology in genetic testing in ACM. Use of next-generation sequencing methods has resulted in the identification of novel causative variants and genes for ACM. The involvement of filamin C in ACM demonstrates the genetic overlap between ACM and other types of cardiomyopathy. Putative pathogenic variants have been detected in cadherin 2 gene, a protein involved in cell adhesion. Large genomic rearrangements in desmosome genes have been systematically investigated in a cohort of ACM patients. Recent studies have identified novel causes of ACM providing new insights into the genetic spectrum of the disease and highlighting an overlapping phenotype between ACM and dilated cardiomyopathy. Next-generation sequencing is a useful tool for research and genetic diagnostic screening but interpretation of identified sequence variants requires caution and should be performed in specialized centres.

  10. Determinants of Thyrotoxic Cardiomyopathy Recovery

    PubMed Central

    Oliveros-Ruiz, Lucia; Vallejo, Maite; Diez Canseco, L. Fernando; Cárdenas, Manuel; Hermosillo, J. Antonio G.

    2013-01-01

    The purpose was to evaluate the effect of the disease duration prior to treatment, thyroid hormones level, or both on the reversibility of dilated cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with a 6 months follow-up was carried on. One hundred and seventy patients with hyperthyroidism were referred to the cardiologist, and 127 had a 6 months followup after antithyroid treatment and were evaluated by echocardiography. Dilated cardiomyopathy reversibility criteria were established according to echocardiographic parameters. Complete reversibility existed when all parameters were met, partial reversibility when LVEF was ≥55% plus two or three other parameters, and no reversibility when LVEF was ≤55% regardless of other parameters. The results showed that echocardiography parameters related to the regression of myocardial mass were associated with a disease duration shorter than 10.38 months. This was the main predictive variable for reversal of dilated cardiomyopathy, followed by β-blocker treatment, and the last predictive variable was the serum level of free triiodothyronine. This study showed that the effect on the myocardium related to thyrotoxicosis was associated with the disease duration before treatment. PMID:24106705

  11. Redox signaling in remote ischemic preconditioning-induced cardioprotection: Evidences and mechanisms.

    PubMed

    Singh, Lovedeep; Randhawa, Puneet Kaur; Singh, Nirmal; Jaggi, Amteshwar Singh

    2017-08-15

    Reactive oxygen species are the reactive molecules that are derived from molecular oxygen and play an important role as redox signaling molecules to confer cardioprotection. Various scientists have demonstrated the key role of redox signaling in cardioprotection by showing a transient increase in their levels during remote ischemic preconditioning (RIPC) phase. The transient increase in reactive oxygen species levels during remote preconditioning phase may take place either through activation of K ATP channels or through increased nitric oxide (NO) production. A transient increase in reactive oxygen species during preconditioning may also increase the expression of heat shock proteins (HSP), the level of antioxidant enzymes and decrease the expression of inflammatory genes (Egr-1) during ischemia-reperfusion phase to confer cardioprotection. The present review describes the role of redox signaling in RIPC-induced cardioprotective effect with possible mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Causes of Pediatric Cardiomyopathy

    MedlinePlus

    ... pediatric cardiomyopathy. Mutations are defects in the DNA spiral, the protein structure of many genes. The abnormalities ... in the future there will be a clinical method to identify carriers of the gene within affected ...

  13. The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

    PubMed

    Ramos-Araque, Maria E; Rodriguez, Cristina; Vecino, Rebeca; Cortijo Garcia, Elisa; de Lera Alfonso, Mercedes; Sanchez Barba, Mercedes; Colàs-Campàs, Laura; Purroy, Francisco; Arenillas, Juan F; Almeida, Angeles; Delgado-Esteban, Maria

    2018-04-23

    Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

  14. Novel protective role of the circadian nuclear receptor retinoic acid-related orphan receptor-α in diabetic cardiomyopathy.

    PubMed

    Zhao, Yichao; Xu, Longwei; Ding, Song; Lin, Nan; Ji, Qingqi; Gao, Lingchen; Su, Yuanyuan; He, Ben; Pu, Jun

    2017-04-01

    Diabetic cardiomyopathy is a major complication that significantly contributes to morbidity and mortality in diabetics with few therapies. Moreover, antidiabetic drugs reported inconsistent or even adverse cardiovascular effects, suggesting that it is important to exploit novel therapeutic targets against diabetic cardiomyopathy. Here, we observed that the nuclear melatonin receptor, the retinoic acid-related orphan receptor-α (RORα), was downregulated in diabetic hearts. By utilizing a mouse line with RORα disruption, we demonstrated that RORα deficiency led to significantly augmented diastolic dysfunction and cardiac remodeling induced by diabetes. Microscopic and molecular analyses further indicated that the detrimental effects of RORα deficiency were associated with aggravated myocardial apoptosis, autophagy dysfunction, and oxidative stress by disrupting antioxidant gene expression. By contrast, restoration of cardiac RORα levels in transgenic mice significantly improved cardiac functional and structural parameters at 8 weeks after diabetes induction. Consistent with genetic manipulation, pharmacological activation of RORα by melatonin and SR1078 (a synthetic agonist) showed beneficial effects against diabetic cardiomyopathy, while the RORα inhibitor SR3335 significantly exacerbated cardiac impairments in diabetic mice. Collectively, these findings suggest that cardiac-targeted manipulation of nuclear melatonin receptor RORα may hold promise for delaying diabetic cardiomyopathy development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Fatal arrhythmogenic right ventricular cardiomyopathy in 2 related subadult chimpanzees (Pan troglodytes).

    PubMed

    Tong, L J; Flach, E J; Sheppard, M N; Pocknell, A; Banerjee, A A; Boswood, A; Bouts, T; Routh, A; Feltrer, Y

    2014-07-01

    Cardiovascular disease is increasingly recognized as an important cause of morbidity and mortality in captive chimpanzees (Pan troglodytes). This report records 2 cases of sudden cardiac death in closely related subadult captive chimpanzees with marked replacement fibrosis and adipocyte infiltration of the myocardium, which resemble specific atypical forms of the familial human disease arrhythmogenic right ventricular cardiomyopathy. Changes were consistent with left-dominant and biventricular subtypes, which are both phenotypic variants found within human families with familial arrhythmogenic right ventricular cardiomyopathy. Previously reported fibrosing cardiomyopathies in chimpanzees were characterized by nonspecific interstitial fibrosis, in contrast to the replacement fibrofatty infiltration with predilection for the outer myocardium seen in these 2 cases. To the authors' knowledge, this case report is the first to describe cardiomyopathy resembling arrhythmogenic right ventricular cardiomyopathy in nonhuman primates and the first to describe left-dominant arrhythmogenic cardiomyopathy-type lesions in an animal. © The Author(s) 2013.

  16. Conditioned Medium Derived from Neural Progenitor Cells Induces Long-term Post-ischemic Neuroprotection, Sustained Neurological Recovery, Neurogenesis, and Angiogenesis.

    PubMed

    Doeppner, Thorsten R; Traut, Viktorija; Heidenreich, Alexander; Kaltwasser, Britta; Bosche, Bert; Bähr, Mathias; Hermann, Dirk M

    2017-03-01

    Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity-promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia and intravenously applied conditioned medium (CM) derived from subventricular zone NPCs. CM dose-dependently reduced infarct volume and brain leukocyte infiltration after 48 h when delivered up to 12 h after focal cerebral ischemia. Neuroprotection persisted in the post-acute stroke phase yielding enhanced neurological recovery that lasted throughout the 28-day observation period. Increased Bcl-2, phosphorylated Akt and phosphorylated STAT-3 abundance, and reduced caspase-3 activity and Bax abundance were noted in ischemic brains of CM-treated mice at 48 h post-stroke, indicative of enhanced cell survival signaling. Long-term neuroprotection was associated with increased brain glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) concentrations at 28 days resulting in increased neurogenesis and angiogenesis. The observation that NPC-derived CM induces sustained neuroprotection and neurological recovery suggests that cell transplantation may be dispensable when secreted factors are instead administered.

  17. Takotsubo cardiomyopathy after treatment of pulmonary arterial hypertension

    PubMed Central

    Cork, David P.; Mehrotra, Amit K.; Gomberg-Maitland, Mardi

    2012-01-01

    Pulmonary arterial hypertension is a fatal disease. Intravenous prostanoids are often utilized for long-term management of patients. The therapy requires a significant commitment and change in lifestyle for both the patient and family. Takotsubo cardiomyopathy, transient apical ballooning syndrome, has been reported in association with emotional and physical stress. This case report describes a patient with pulmonary arterial hypertension who developed Takotsubo cardiomyopathy after treatment initiation with intravenous treprostinil. Over time, the syndrome resolved and the patient had return of normal left ventricular function. Takotsubo cardiomyopathy should be recognized as a potential, rare complication of therapy initiation due to the severity of the illness and the emotional stress of the disease. PMID:23130109

  18. Animal Models of Congenital Cardiomyopathies Associated With Mutations in Z-Line Proteins.

    PubMed

    Bang, Marie-Louise

    2017-01-01

    The cardiac Z-line at the boundary between sarcomeres is a multiprotein complex connecting the contractile apparatus with the cytoskeleton and the extracellular matrix. The Z-line is important for efficient force generation and transmission as well as the maintenance of structural stability and integrity. Furthermore, it is a nodal point for intracellular signaling, in particular mechanosensing and mechanotransduction. Mutations in various genes encoding Z-line proteins have been associated with different cardiomyopathies, including dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and left ventricular noncompaction, and mutations even within the same gene can cause widely different pathologies. Animal models have contributed to a great advancement in the understanding of the physiological function of Z-line proteins and the pathways leading from mutations in Z-line proteins to cardiomyopathy, although genotype-phenotype prediction remains a great challenge. This review presents an overview of the currently available animal models for Z-line and Z-line associated proteins involved in human cardiomyopathies with special emphasis on knock-in and transgenic mouse models recapitulating the clinical phenotypes of human cardiomyopathy patients carrying mutations in Z-line proteins. Pros and cons of mouse models will be discussed and a future outlook will be given. J. Cell. Physiol. 232: 38-52, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Deletion of interleukin-6 alleviated interstitial fibrosis in streptozotocin-induced diabetic cardiomyopathy of mice through affecting TGFβ1 and miR-29 pathways.

    PubMed

    Zhang, Yang; Wang, Jing-Hao; Zhang, Yi-Yuan; Wang, Ying-Zhe; Wang, Jin; Zhao, Yue; Jin, Xue-Xin; Xue, Gen-Long; Li, Peng-Hui; Sun, Yi-Lin; Huang, Qi-He; Song, Xiao-Tong; Zhang, Zhi-Ren; Gao, Xu; Yang, Bao-Feng; Du, Zhi-Min; Pan, Zhen-Wei

    2016-03-14

    Interleukin 6 (IL-6) has been shown to be an important regulator of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-6 in the development of diabetic cardiomyopathy and the underlying mechanisms. Cardiac function of IL-6 knockout mice was significantly improved and interstitial fibrosis was apparently alleviated in comparison with wildtype (WT) diabetic mice induced by streptozotocin (STZ). Treatment with IL-6 significantly promoted the proliferation and collagen production of cultured cardiac fibroblasts (CFs). High glucose treatment increased collagen production, which were mitigated in CFs from IL-6 KO mice. Moreover, IL-6 knockout alleviated the up-regulation of TGFβ1 in diabetic hearts of mice and cultured CFs treated with high glucose or IL-6. Furthermore, the expression of miR-29 reduced upon IL-6 treatment, while increased in IL-6 KO hearts. Overexpression of miR-29 blocked the pro-fibrotic effects of IL-6 on cultured CFs. In summary, deletion of IL-6 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The mechanism involves the regulation of IL-6 on TGFβ1 and miR-29 pathway. This study indicates the therapeutic potential of IL-6 suppression on diabetic cardiomyopathy disease associated with fibrosis.

  20. Dilated cardiomyopathy and sinoatrial dysfunction in an Estrela mountain dog.

    PubMed

    Lobo, Luis; Pinheiro-Vieira, António; Gomes, João L; Canada, Nuno; Ribeiro, Lenio; Costa, Paulo D; Oliveira, Pedro; Bussadori, Claudio

    2012-01-01

    A 1 yr old male Estrela mountain dog was evaluated as a part of a screening program for dilated cardiomyopathy. The dog came from a family with a history of dilated cardiomyopathy but was asymptomatic. Occult dilated cardiomyopathy and sino-atrial dysfunction were diagnosed based on echocardiography and electrocardiography. These two disorders may be associated given that related dogs have been diagnosed with the same disorders. The dog has remained asymptomatic for 4 years following initial evaluation.

  1. Ischemic colitis induced by the newly reformulated multicomponent weight-loss supplement Hydroxycut®

    PubMed Central

    Sherid, Muhammed; Samo, Salih; Sulaiman, Samian; Gaziano, Joseph H

    2013-01-01

    Ischemic colitis accounts for 6%-18% of causes of acute lower gastrointestinal bleeding. It is more often multifactorial and more common in elderly. Drugs are considered important causative agents of this disease with different mechanisms. In this paper, we describe a 37-year-old otherwise healthy female presented with sudden onset diffuse abdominal pain and bloody stool. Radiologic, colonoscopic and histopathologic findings were all consistent with ischemic colitis. Her only suspected factor was hydroxycut which she had been taking for a period of 1 mo prior to her presentation. Her condition improved uneventfully after cessation of hydroxycut, bowel rest, intravenous hydration, and antibiotics. This is a first case of ischemic colitis with clear relationship with hydroxycut use (Naranjo score of 7). Our case demonstrates the importance of questioning patients regarding the usage of dietary supplements; especially since many patients consider them safe and do not disclose their use voluntarily to their physicians. Hydroxycut has to be considered as a potential trigger for otherwise unexplained ischemic colitis. PMID:23596542

  2. NGS testing for cardiomyopathy: Utility of adding RASopathy-associated genes.

    PubMed

    Ceyhan-Birsoy, Ozge; Miatkowski, Maya M; Hynes, Elizabeth; Funke, Birgit H; Mason-Suares, Heather

    2018-04-25

    RASopathies include a group of syndromes caused by pathogenic germline variants in RAS-MAPK pathway genes and typically present with facial dysmorphology, cardiovascular disease, and musculoskeletal anomalies. Recently, variants in RASopathy-associated genes have been reported in individuals with apparently nonsyndromic cardiomyopathy, suggesting that subtle features may be overlooked. To determine the utility and burden of adding RASopathy-associated genes to cardiomyopathy panels, we tested 11 RASopathy-associated genes by next-generation sequencing (NGS), including NGS-based copy number variant assessment, in 1,111 individuals referred for genetic testing for hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). Disease-causing variants were identified in 0.6% (four of 692) of individuals with HCM, including three missense variants in the PTPN11, SOS1, and BRAF genes. Overall, 36 variants of uncertain significance (VUSs) were identified, averaging ∼3VUSs/100 cases. This study demonstrates that adding a subset of the RASopathy-associated genes to cardiomyopathy panels will increase clinical diagnoses without significantly increasing the number of VUSs/case. © 2018 Wiley Periodicals, Inc.

  3. Genetic advances in sarcomeric cardiomyopathies: state of the art

    PubMed Central

    Ho, Carolyn Y.; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y.; Pinto, Yigal

    2015-01-01

    Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. PMID:25634555

  4. Myocardial regeneration in adriamycin cardiomyopathy by nuclear expression of GLP1 using ultrasound targeted microbubble destruction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Shuyuan; Chen, Jiaxi; Huang, Pintong

    Recently GLP-1 was found to have cardioprotective effects independent of those attributable to tight glycemic control. Methods and results: We employed ultrasound targeted microbubble destruction (UTMD) to deliver piggybac transposon plasmids encoding the GLP-1 gene with a nuclear localizing signal to rat hearts with adriamycin cardiomyopathy. After a single UTMD treatment, overexpression of transgenic GLP-1 was found in nuclei of rat heart cells with evidence that transfected cardiac cells had undergone proliferation. UTMD-GLP-1 gene therapy restored LV mass, fractional shortening index, and LV posterior wall diameter to nearly normal. Nuclear overexpression of GLP-1 by inducing phosphorylation of FoxO1-S256 and translocationmore » of FoxO1 from the nucleus to the cytoplasm significantly inactivated FoxO1 and activated the expression of cyclin D1 in nuclei of cardiac muscle cells. Reversal of adriamycin cardiomyopathy appeared to be mediated by dedifferentiation and proliferation of nuclear FoxO1-positive cardiac muscle cells with evidence of embryonic stem cell markers (OCT4, Nanog, SOX2 and c-kit), cardiac early differentiation markers (NKX2.5 and ISL-1) and cellular proliferation markers (BrdU and PHH3) after UTMD with GLP-1 gene therapy. Conclusions: Intranuclear myocardial delivery of the GLP-1gene can reverse established adriamycin cardiomyopathy by stimulating myocardial regeneration. - Highlights: • The activation of nuclear FoxO1 in cardiac muscle cells associated with adriamycin cardiomyopathy. • Myocardial nuclear GLP-1 stimulates myocardial regeneration and reverses adriamycin cardiomyopathy. • The process of myocardial regeneration associated with dedifferentiation and proliferation.« less

  5. Radon inhalation protects against transient global cerebral ischemic injury in gerbils.

    PubMed

    Kataoka, Takahiro; Etani, Reo; Takata, Yuji; Nishiyama, Yuichi; Kawabe, Atsushi; Kumashiro, Masayuki; Taguchi, Takehito; Yamaoka, Kiyonori

    2014-10-01

    Although brain disorders are not the main indication for radon therapy, our previous study suggested that radon inhalation therapy might mitigate brain disorders. In this study, we assessed whether radon inhalation protects against transient global cerebral ischemic injury in gerbils. Gerbils were treated with inhaled radon at a concentration of 2,000 Bq/m(3) for 24 h. After radon inhalation, transient global cerebral ischemia was induced by bilateral occlusion of the common carotid artery. Results showed that transient global cerebral ischemia induced neuronal damage in hippocampal CA1, and the number of damaged neurons was significantly increased compared with control. However, radon treatment inhibited ischemic damage. Superoxide dismutase (SOD) activity in the radon-treated gerbil brain was significantly higher than that in sham-operated gerbils. These findings suggested that radon inhalation activates antioxidative function, especially SOD, thereby inhibiting transient global cerebral ischemic injury in gerbils.

  6. Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways

    PubMed Central

    Twu, Cheryl; Liu, Nancy Q.; Popik, Waldemar; Bukrinsky, Michael; Sayre, James; Roberts, Jaclyn; Rania, Shammas; Bramhandam, Vishnu; Roos, Kenneth P.; MacLellan, W. Robb; Fiala, Milan

    2002-01-01

    We investigated 18 AIDS hearts (5 with and 13 without cardiomyopathy) by using immunocytochemistry and computerized image analysis regarding the roles of HIV-1 proteins and tumor necrosis factor ligands in HIV cardiomyopathy (HIVCM). HIVCM and cardiomyocyte apoptosis were significantly related to each other and to the expression by inflammatory cells of gp120 and tumor necrosis factor-α. In HIVCM heart, active caspase 9, a component of the mitochondrion-controlled apoptotic pathway, and the elements of the death receptor-mediated pathway, tumor necrosis factor-α and Fas ligand, were expressed strongly on macrophages and weakly on cardiomyocytes. HIVCM showed significantly greater macrophage infiltration and cardiomyocyte apoptosis rate compared with non-HIVCM. HIV-1 entered cultured neonatal rat ventricular myocytes by macropinocytosis but did not replicate. HIV-1- or gp120-induced apoptosis of rat myocytes through a mitochondrion-controlled pathway, which was inhibited by heparin, AOP-RANTES, or pertussis toxin, suggesting that cardiomyocyte apoptosis is induced by signaling through chemokine receptors. In conclusion, in patients with HIVCM, cardiomyocytes die through both mitochondrion- and death receptor-controlled apoptotic pathways. PMID:12379743

  7. Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways.

    PubMed

    Twu, Cheryl; Liu, Nancy Q; Popik, Waldemar; Bukrinsky, Michael; Sayre, James; Roberts, Jaclyn; Rania, Shammas; Bramhandam, Vishnu; Roos, Kenneth P; MacLellan, W Robb; Fiala, Milan

    2002-10-29

    We investigated 18 AIDS hearts (5 with and 13 without cardiomyopathy) by using immunocytochemistry and computerized image analysis regarding the roles of HIV-1 proteins and tumor necrosis factor ligands in HIV cardiomyopathy (HIVCM). HIVCM and cardiomyocyte apoptosis were significantly related to each other and to the expression by inflammatory cells of gp120 and tumor necrosis factor-alpha. In HIVCM heart, active caspase 9, a component of the mitochondrion-controlled apoptotic pathway, and the elements of the death receptor-mediated pathway, tumor necrosis factor-alpha and Fas ligand, were expressed strongly on macrophages and weakly on cardiomyocytes. HIVCM showed significantly greater macrophage infiltration and cardiomyocyte apoptosis rate compared with non-HIVCM. HIV-1 entered cultured neonatal rat ventricular myocytes by macropinocytosis but did not replicate. HIV-1- or gp120-induced apoptosis of rat myocytes through a mitochondrion-controlled pathway, which was inhibited by heparin, AOP-RANTES, or pertussis toxin, suggesting that cardiomyocyte apoptosis is induced by signaling through chemokine receptors. In conclusion, in patients with HIVCM, cardiomyocytes die through both mitochondrion- and death receptor-controlled apoptotic pathways.

  8. Neuroprotective Effect of a New Synthetic Aspirin-decursinol Adduct in Experimental Animal Models of Ischemic Stroke

    PubMed Central

    Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

    2013-01-01

    Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants. PMID:24073226

  9. Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

    PubMed

    Yan, Bing Chun; Park, Joon Ha; Shin, Bich Na; Ahn, Ji Hyeon; Kim, In Hye; Lee, Jae-Chul; Yoo, Ki-Yeon; Hwang, In Koo; Choi, Jung Hoon; Park, Jeong Ho; Lee, Yun Lyul; Suh, Hong-Won; Jun, Jong-Gab; Kwon, Young-Guen; Kim, Young-Myeong; Kwon, Seung-Hae; Her, Song; Kim, Jin Su; Hyun, Byung-Hwa; Kim, Chul-Kyu; Cho, Jun Hwi; Lee, Choong Hyun; Won, Moo-Ho

    2013-01-01

    Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.

  10. Prooxidant Mechanisms in Iron Overload Cardiomyopathy

    PubMed Central

    Cheng, Ching-Feng; Lian, Wei-Shiung

    2013-01-01

    Iron overload cardiomyopathy (IOC), defined as the presence of systolic or diastolic cardiac dysfunction secondary to increased deposition of iron, is emerging as an important cause of heart failure due to the increased incidence of this disorder seen in thalassemic patients and in patients of primary hemochromatosis. At present, although palliative treatment by regular iron chelation was recommended; whereas IOC is still the major cause for mortality in patient with chronic heart failure induced by iron-overloading. Because iron is a prooxidant and the associated mechanism seen in iron-overload heart is still unclear; therefore, we intend to delineate the multiple signaling pathways involved in IOC. These pathways may include organelles such as calcium channels, mitochondria; paracrine effects from both macrophages and fibroblast, and novel mediators such as thromboxane A2 and adiponectin; with increased oxidative stress and inflammation found commonly in these signaling pathways. With further understanding on these complex and inter-related molecular mechanisms, we can propose potential therapeutic strategies to ameliorate the cardiac toxicity induced by iron-overloading. PMID:24350287

  11. Investigation of Reperfusion Injury and Ischemic Preconditioning in Microsurgry

    PubMed Central

    Wang, Wei Zhong

    2008-01-01

    Ischemia/reperfusion (I/R) is inevitable in many vascular and musculoskeletal traumas, diseases, free tissue transfers, and during time-consuming reconstructive surgeries in the extremities. Salvage of a prolonged ischemic extremity or flap still remains a challenge for the microvascular surgeon. One of the common complications after microsurgery is I/R-induced tissue death or I/R injury. Twenty years after the discovery, ischemic preconditioning (IPC) has emerged as a powerful method for attenuating I/R injury in a variety of organs or tissues. However, its therapeutic expectations still need to be fulfilled. In this article, the author reviews some important experimental evidences of I/R injury as well as preconditioning-induced protection in the fields relevant to microsurgery. PMID:18946882

  12. Is Internet use associated with anxiety in patients with and at risk for cardiomyopathy?

    PubMed

    Minto, Clara; Bauce, Barbara; Calore, Chiara; Rigato, Ilaria; Folino, Franco; Soriani, Nicola; Hochdorn, Alexander; Iliceto, Sabino; Gregori, Dario

    2015-07-01

    The aim of the study was to determine the relation between online health information seeking behavior and anxiety level among a sample of patients with manifested cardiomyopathy or at risk for cardiomyopathy. The research is a cross-sectional study conducted among 104 patients with cardiomyopathy diagnosis and patients at risk for cardiomyopathy. Patients completed 3 different questionnaires: Use of Internet Health Information questionnaire about the use of Internet, Short Form SF-12 items questionnaire on quality of life, and State-Trait Anxiety Inventory measuring general anxiety levels. Forty-eight patients had a diagnosis of primary or secondary cardiomyopathy, and 56 patients, with conditions predisposing to cardiomyopathy. Eighty-five percent of the considered population is surfing the Internet to obtain nonspecific information about health in general, and the 65% use it to look specifically for heart disease. For both groups of patients with cardiomyopathy and at risk for cardiomyopathy, online health information seeking behavior is associated with substantially lower state anxiety levels (P = .041). Web use, as a source of health information, has been shown to be associated with anxiety reduction in patients with or at risk for cardiomyopathy, suggesting that Internet technology can be a useful instrument due to its informational power and its potentially therapeutic value. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Secondary Coronary Artery Vasospasm Promotes Cardiomyopathy Progression

    PubMed Central

    Wheeler, Matthew T.; Korcarz, Claudia E.; Collins, Keith A.; Lapidos, Karen A.; Hack, Andrew A.; Lyons, Matthew R.; Zarnegar, Sara; Earley, Judy U.; Lang, Roberto M.; McNally, Elizabeth M.

    2004-01-01

    Genetic defects in the plasma membrane-associated sarcoglycan complex produce cardiomyopathy characterized by focal degeneration. The infarct-like pattern of cardiac degeneration has led to the hypothesis that coronary artery vasospasm underlies cardiomyopathy in this disorder. We evaluated the coronary vasculature of γ-sarcoglycan mutant mice and found microvascular filling defects consistent with arterial vasospasm. However, the vascular smooth muscle sarcoglycan complex was intact in the coronary arteries of γ-sarcoglycan hearts with perturbation of the sarcoglycan complex only within the adjacent myocytes. Thus, in this model, coronary artery vasospasm derives from a vascular smooth muscle-cell extrinsic process. To reduce this secondary vasospasm, we treated γ-sarcoglycan-deficient mice with the calcium channel antagonist verapamil. Verapamil treatment eliminated evidence of vasospasm and ameliorated histological and functional evidence of cardiomyopathic progression. Echocardiography of verapamil-treated, γ-sarcoglycan-null mice showed an improvement in left ventricular fractional shortening (44.3 ± 13.3% treated versus 37.4 ± 15.3% untreated), maximal velocity at the aortic outflow tract (114.9 ± 27.9 cm/second versus 92.8 ± 22.7 cm/second), and cardiac index (1.06 ± 0.30 ml/minute/g versus 0.67 ± 0.16 ml/minute/g, P < 0.05). These data indicate that secondary vasospasm contributes to the development of cardiomyopathy and is an important therapeutic target to limit cardiomyopathy progression. PMID:14982859

  14. Chagasic cardiomyopathy and Pompe disease: case report

    PubMed Central

    de Morais, Rafael OB; Chaves-Markman, Ândrea V; Miranda, Anna PP; Amorim, Ingrid G; Cavalcanti, Maria da GA de M; Markman, Manuel; Markman-Filho, Brivaldo

    2018-01-01

    Background: Pompe disease is a lysosomal storage disease with an autosomal recessive inheritance characterized by an insufficient activity of the acid alpha-glucosidase enzyme. The incidence varies from 1:40000 to 1:200000 live births and cardiac involvement in adults is rare. Chagas disease is an infection caused by the protozoan Trypanosoma cruzi, in which one-third of the cases progress to the chronic form, and may lead to cardiac involvement, usually from the fifth decade of life onwards. We report a case of a patient with Chagas and Pompe diseases who had early cardiac involvement and rapid evolution to heart failure. Case report: A 43-year-old male patient with a history of ischemic stroke at 28 years with gait ataxia sequelae. A few years after the episode, he experienced gait impairment and difficulty climbing stairs, attributed to stroke. A family screening for Pompe disease was carried out years later, and thus the diagnosis was made. As for Chagas disease, the investigation was performed because the patient lives in an endemic area. The cardiovascular physical examination did not show significant changes. The electrocardiogram showed sinus rhythm with left bundle branch block and first-degree atrioventricular block; the transthoracic echocardiogram demonstrated left ventricular systolic dysfunction; the Holter monitoring showed several episodes of ventricular tachycardia. The patient is undergoing optimized treatment for heart failure and enzyme replacement therapy for Pompe disease. Conclusion: Cardiomyopathy with early onset and with rapid evolution suggests overlap of the two diseases. PMID:29755837

  15. [Usefullness of Beta-blocker for Hemodynamic Changes Induced by Uterotonic Drug in a Patient with Hypertrophic Obstructive Cardiomyopathy Undergoing Elective Cesarean Section].

    PubMed

    Tsukano, Yuri; Sugita, Michiko; Ikuta, Yoshihiro; Yamamoto, Tatsuo

    2015-06-01

    Combined spinal-epidural anesthesia (CSEA) was given to a 27-year-old woman with hypertrophic obstructive cardiomyopathy (HOCM) for a selective cesarean section. After the injection of uterotonic drug via uterine muscle and a vein after delivery, the patient developed dyspnea, tachycardia, ST-change on elecrocardiogram and hypotension. It is important in HOCM patients to control heart rate and left ventricular contractile force. We started to infuse beta-blocker (landiolol, 10 μg x kg(-1) x min(-1)) and improved these symptoms of the patient. This case demonstrates that CSEA is safe for HOCM patients and beta-blocker is effective to improve hemodynamic changes induced by uterotonic drug in these patients.

  16. Genetic advances in sarcomeric cardiomyopathies: state of the art.

    PubMed

    Ho, Carolyn Y; Charron, Philippe; Richard, Pascale; Girolami, Francesca; Van Spaendonck-Zwarts, Karin Y; Pinto, Yigal

    2015-04-01

    Genetic studies in the 1980s and 1990s led to landmark discoveries that sarcomere mutations cause both hypertrophic and dilated cardiomyopathies. Sarcomere mutations also likely play a role in more complex phenotypes and overlap cardiomyopathies with features of hypertrophy, dilation, diastolic abnormalities, and non-compaction. Identification of the genetic cause of these important conditions provides unique opportunities to interrogate and characterize disease pathogenesis and pathophysiology, starting from the molecular level and expanding from there. With such insights, there is potential for clinical translation that may transform management of patients and families with inherited cardiomyopathies. If key pathways for disease development can be identified, they could potentially serve as targets for novel disease-modifying or disease-preventing therapies. By utilizing gene-based diagnostic testing, we can identify at-risk individuals prior to the onset of clinical disease, allowing for disease-modifying therapy to be initiated early in life, at a time that such treatment may be most successful. In this section, we review the current application of genetics in clinical management, focusing on hypertrophic cardiomyopathy as a paradigm; discuss state-of-the-art genetic testing technology; review emerging knowledge of gene expression in sarcomeric cardiomyopathies; and discuss both the prospects, as well as the challenges, of bringing genetics to medicine. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  17. Hypertrophic Cardiomyopathy: Clinical Update.

    PubMed

    Geske, Jeffrey B; Ommen, Steve R; Gersh, Bernard J

    2018-05-01

    Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy, manifesting as left ventricular hypertrophy in the absence of a secondary cause. The genetic underpinnings of HCM arise largely from mutations of sarcomeric proteins; however, the specific underlying mutation often remains undetermined. Patient presentation is phenotypically diverse, ranging from asymptomatic to heart failure or sudden cardiac death. Left ventricular hypertrophy and abnormal ventricular configuration result in dynamic left ventricular outflow obstruction in most patients. The goal of therapeutic interventions is largely to reduce dynamic obstruction, with treatment modalities spanning lifestyle modifications, pharmacotherapies, and septal reduction therapies. A small subset of patients with HCM will experience sudden cardiac death, and risk stratification remains a clinical challenge. This paper presents a clinical update for diagnosis, family screening, clinical imaging, risk stratification, and management of symptoms in patients with HCM. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  18. Activin-A, transforming growth factor-beta, and myostatin signaling pathway in experimental dilated cardiomyopathy.

    PubMed

    Mahmoudabady, Maryam; Mathieu, Myrielle; Dewachter, Laurence; Hadad, Ielham; Ray, Lynn; Jespers, Pascale; Brimioulle, Serge; Naeije, Robert; McEntee, Kathleen

    2008-10-01

    The pathogenic mechanisms of dilated cardiomyopathy are still uncertain. A number of cytokines and growth factors participate in the remodeling process of the disease. We investigated the cardiac myostatin, transforming growth factor (TGF)beta, and activin-A/Smad growth inhibitory signaling pathway in experimental dilated cardiomyopathy. Transvenous endomyocardial biopsies of the interventricular septum were taken weekly in 15 beagle dogs during the development of heart failure (HF) induced by rapid pacing over a period of 7 weeks. Genes involved in the myostatin-TGFbeta-activin-A/Smad signaling pathway and the cardiac hypertrophic process were quantified by real-time quantitative polymerase chain reaction. Left ventricular volume, function, and mass were evaluated by echocardiography. Overpacing was associated with increased left ventricular volumes and decreased ejection fraction, whereas the left ventricular mass remained unchanged. TGFbeta was increased in moderate HF. Activin-A mRNA expression was 4-fold higher in overt congestive HF than at baseline. A 2-fold decrease of activin type II receptors and activin receptor interacting protein 2 gene expressions were observed, as well as a transient decrease of follistatin. Activin type I receptors, activin receptor interacting protein 1, follistatin-related gene, and myostatin remained unchanged. The inhibitory Smad 7, a negative feedback loop regulator of the Smad pathway, was overexpressed in severe HF. Gene expression of the cyclin-dependent kinase inhibitor p21, a direct target gene of the Smad pathway, was 8-fold up-regulated in HF, whereas cyclin D1 was down-regulated. We conclude that tachycardia-induced dilated cardiomyopathy is characterized by gene overexpression of the TGFbeta-activin-A/Smad signaling pathway and their target gene p21 and by the absence of ventricular hypertrophy.

  19. Brain ischemic preconditioning protects against ischemic injury and preserves the blood-brain barrier via oxidative signaling and Nrf2 activation.

    PubMed

    Yang, Tuo; Sun, Yang; Mao, Leilei; Zhang, Meijuan; Li, Qianqian; Zhang, Lili; Shi, Yejie; Leak, Rehana K; Chen, Jun; Zhang, Feng

    2018-05-06

    Brain ischemic preconditioning (IPC) with mild ischemic episodes is well known to protect the brain against subsequent ischemic challenges. However, the underlying mechanisms are poorly understood. Here we demonstrate the critical role of the master redox transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), in IPC-mediated neuroprotection and blood-brain barrier (BBB) preservation. We report that IPC causes generation of endogenous lipid electrophiles, including 4-hydroxy-2-nonenal (4-HNE), which release Nrf2 from inhibition by Keap1 (via Keap1-C288) and inhibition by glycogen synthase kinase 3β (via GSK3β-C199). Nrf2 then induces expression of its target genes, including a new target, cadherin 5, a key component of adherens junctions of the BBB. These effects culminate in mitigation of BBB leakage and of neurological deficits after stroke. Collectively, these studies are the first to demonstrate that IPC protects the BBB against ischemic injury by generation of endogenous electrophiles and activation of the Nrf2 pathway through inhibition of Keap1- and GSK3β-dependent Nrf2 degradation. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  20. MicroRNA-146a is a therapeutic target and biomarker for peripartum cardiomyopathy

    PubMed Central

    Halkein, Julie; Tabruyn, Sebastien P.; Ricke-Hoch, Melanie; Haghikia, Arash; Nguyen, Ngoc-Quynh-Nhu; Scherr, Michaela; Castermans, Karolien; Malvaux, Ludovic; Lambert, Vincent; Thiry, Marc; Sliwa, Karen; Noel, Agnes; Martial, Joseph A.; Hilfiker-Kleiner, Denise; Struman, Ingrid

    2013-01-01

    Peripartum cardiomyopathy (PPCM) is a life-threatening pregnancy-associated cardiomyopathy in previously healthy women. Although PPCM is driven in part by the 16-kDa N-terminal prolactin fragment (16K PRL), the underlying molecular mechanisms are poorly understood. We found that 16K PRL induced microRNA-146a (miR-146a) expression in ECs, which attenuated angiogenesis through downregulation of NRAS. 16K PRL stimulated the release of miR-146a–loaded exosomes from ECs. The exosomes were absorbed by cardiomyocytes, increasing miR-146a levels, which resulted in a subsequent decrease in metabolic activity and decreased expression of Erbb4, Notch1, and Irak1. Mice with cardiomyocyte-restricted Stat3 knockout (CKO mice) exhibited a PPCM-like phenotype and displayed increased cardiac miR-146a expression with coincident downregulation of Erbb4, Nras, Notch1, and Irak1. Blocking miR-146a with locked nucleic acids or antago-miRs attenuated PPCM in CKO mice without interrupting full-length prolactin signaling, as indicated by normal nursing activities. Finally, miR-146a was elevated in the plasma and hearts of PPCM patients, but not in patients with dilated cardiomyopathy. These results demonstrate that miR-146a is a downstream-mediator of 16K PRL that could potentially serve as a biomarker and therapeutic target for PPCM. PMID:23619365

  1. [Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart].

    PubMed

    Peng, Long-yun; Ma, Hong; He, Jian-gui; Gao, Xiu-ren; Zhang, Yan; He, Xiao-hong; Zhai, Yuan-sheng; Zhang, Xue-jiao

    2006-08-01

    To explore the effects of ischemic postconditioning on ischemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning. Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3beta (Ser9). Following groups were studied (n = 12 each group): IR, 30 min ischemia (I)/60 min Reperfusion (R); Post: 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; Post Wort: 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin (10(-7) mol/L) followed by 60 min R; Wort: 30 min ischemia, wortmannin (10(-7) mol/L) followed by 60 min R. Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) induced by ischemic postconditioning, but only partly abolished the cardioprotection of ischemic postconditioning. Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The cardioprotective effects of ischemic postconditioning were partly mediated through PI3K/Akt/GSK-3beta signaling pathway.

  2. Novel Phenotype-Genotype Correlations of Restrictive Cardiomyopathy With Myosin-Binding Protein C (MYBPC3) Gene Mutations Tested by Next-Generation Sequencing.

    PubMed

    Wu, Wei; Lu, Chao-Xia; Wang, Yi-Ning; Liu, Fang; Chen, Wei; Liu, Yong-Tai; Han, Ye-Chen; Cao, Jian; Zhang, Shu-Yang; Zhang, Xue

    2015-07-10

    MYBPC3 dysfunctions have been proven to induce dilated cardiomyopathy, hypertrophic cardiomyopathy, and/or left ventricular noncompaction; however, the genotype-phenotype correlation between MYBPC3 and restrictive cardiomyopathy (RCM) has not been established. The newly developed next-generation sequencing method is capable of broad genomic DNA sequencing with high throughput and can help explore novel correlations between genetic variants and cardiomyopathies. A proband from a multigenerational family with 3 live patients and 1 unrelated patient with clinical diagnoses of RCM underwent a next-generation sequencing workflow based on a custom AmpliSeq panel, including 64 candidate pathogenic genes for cardiomyopathies, on the Ion Personal Genome Machine high-throughput sequencing benchtop instrument. The selected panel contained a total of 64 genes that were reportedly associated with inherited cardiomyopathies. All patients fulfilled strict criteria for RCM with clinical characteristics, echocardiography, and/or cardiac magnetic resonance findings. The multigenerational family with 3 adult RCM patients carried an identical nonsense MYBPC3 mutation, and the unrelated patient carried a missense mutation in the MYBPC3 gene. All of these results were confirmed by the Sanger sequencing method. This study demonstrated that MYBPC3 gene mutations, revealed by next-generation sequencing, were associated with familial and sporadic RCM patients. It is suggested that the next-generation sequencing platform with a selected panel provides a highly efficient approach for molecular diagnosis of hereditary and idiopathic RCM and helps build new genotype-phenotype correlations. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  3. A distinct subgroup of cardiomyopathy patients characterized by transcriptionally active cardiotropic erythrovirus and altered cardiac gene expression.

    PubMed

    Kuhl, U; Lassner, D; Dorner, A; Rohde, M; Escher, F; Seeberg, B; Hertel, E; Tschope, C; Skurk, C; Gross, U M; Schultheiss, H-P; Poller, W

    2013-09-01

    Recent studies have detected erythrovirus genomes in the hearts of cardiomyopathy and cardiac transplant patients. Assessment of the functional status of viruses may provide clinically important information beyond detection of the viral genomes. Here, we report transcriptional activation of cardiotropic erythrovirus to be associated with strongly altered myocardial gene expression in a distinct subgroup of cardiomyopathy patients. Endomyocardial biopsies (EMBs) from 415 consecutive cardiac erythrovirus (B19V)-positive patients with clinically suspected cardiomyopathy were screened for virus-encoded VP1/VP2 mRNA indicating transcriptional activation of the virus, and correlated with cardiac host gene expression patterns in transcriptionally active versus latent infections, and in virus-free control hearts. Transcriptional activity was detected in baseline biopsies of only 66/415 patients (15.9 %) harbouring erythrovirus. At the molecular level, significant differences between cardiac B19V-positive patients with transcriptionally active versus latent virus were revealed by expression profiling of EMBs. Importantly, latent B19V infection was indistinguishable from controls. Genes involved encode proteins of antiviral immune response, B19V receptor complex, and mitochondrial energy metabolism. Thus, functional mapping of erythrovirus allows definition of a subgroup of B19V-infected cardiomyopathy patients characterized by virus-encoded VP1/VP2 transcripts and anomalous host myocardial transcriptomes. Cardiac B19V reactivation from latency, as reported here for the first time, is a key factor required for erythrovirus to induce altered cardiac gene expression in a subgroup of cardiomyopathy patients. Virus genome detection is insufficient to assess pathogenic potential, but additional transcriptional mapping should be incorporated into future pathogenetic and therapeutic studies both in cardiology and transplantation medicine.

  4. An update on canine cardiomyopathies - is it all in the genes?

    PubMed

    Dutton, E; López-Alvarez, J

    2018-04-17

    Dilated cardiomyopathy is the second most common cardiac disease in dogs and causes considerable morbidity and mortality. Primary dilated cardiomyopathy is suspected to be familial, and genetic loci have been associated with the disease in a number of breeds. Because it is an adult-onset disease, usually with late onset, testing breeding dogs and bitches before breeding for a genetic mutation that could lead to dilated cardiomyopathy would be helpful to prevent disease. There is growing evidence that the genetic basis may be multigenic rather than monogenic in the majority of studied breeds. This review article describes the known genetic aspects of canine dilated cardiomyopathy and the implications of genetic tests on heart testing and the future of veterinary cardiology. © 2018 British Small Animal Veterinary Association.

  5. Identifying the Etiology: A Systematic Approach Using Delayed Enhancement Cardiovascular Magnetic Resonance

    PubMed Central

    Senthilkumar, Annamalai; Majmudar, Maulik D.; Shenoy, Chetan; Kim, Han W.; Kim, Raymond J.

    2009-01-01

    SYNOPSIS In patients with heart failure, treatment and survival are directly related to the etiology. Clinically, as a practical first step, patients are classified as having either ischemic or nonischemic cardiomyopathy and this delineation is usually based on the presence or absence of epicardial coronary artery disease. However, this approach does not account for patients with nonischemic cardiomyopathy who also have coronary artery disease, which may be either incidental or partly contributing to myocardial dysfunction (mixed cardiomyopathy). By allowing direct assessment of the myocardium, delayed enhancement cardiovascular magnetic resonance (DE-CMR) may aid in addressing these conundrums. In this article we explore how DE-CMR may be helpful in identifying ischemic and nonischemic myopathic processes and detail a systematic approach using this technique to determine the etiology of cardiomyopathy. PMID:19564013

  6. Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

    PubMed

    Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

    At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

  7. Amphetamine-associated ischemic stroke: clinical presentation and proposed pathogenesis.

    PubMed

    De Silva, Deidre Anne; Wong, Meng Cheong; Lee, Moi Pin; Chen, Christopher Li-Hsian; Chang, Hui Meng

    2007-01-01

    We report a young lady with acute left middle cerebral artery infarction after acute intake of amphetamine. This is the first case report of amphetamine-induced ischemic stroke with serial angiography and transcranial color-coded Doppler studies. The temporal sequence of stenosis of at least 3 weeks with subsequent complete resolution by 3 months and a "beaded" appearance on angiography support vasculitis or vasospasm as the pathogenesis of ischemic stroke in this patient. The presence of microembolic signals supports acute thrombosis at the site of vasculitis/vasospasm with distal embolism.

  8. Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) trial.

    PubMed

    Rassi, Anis; Marin, José Antonio; Rassi, Anis

    2017-03-01

    Chagas cardiomyopathy is the most frequent and most severe manifestation of chronic Chagas disease, and is one of the leading causes of morbidity and death in Latin America. Although the pathogenesis of Chagas cardiomyopathy is incompletely understood, it may involve several mechanisms, including parasite-dependent myocardial damage, immune-mediated myocardial injury (induced by the parasite itself and by self-antigens), and microvascular and neurogenic disturbances. In the past three decades, a consensus has emerged that parasite persistence is crucial to the development and progression of Chagas cardiomyopathy. In this context, antiparasitic treatment in the chronic phase of Chagas disease could prevent complications related to the disease. However, according to the results of the BENEFIT trial, benznidazole seems to have no benefit for arresting disease progression in patients with chronic Chagas cardiomyopathy. In this review, we give an update on the main pathogenic mechanisms of Chagas disease, and re-examine and discuss the results of the BENEFIT trial, together with its limitations and implications.

  9. Role of high-resolution image integration to visualize left phrenic nerve and coronary arteries during epicardial ventricular tachycardia ablation.

    PubMed

    Yamashita, Seigo; Sacher, Frédéric; Mahida, Saagar; Berte, Benjamin; Lim, Han S; Komatsu, Yuki; Amraoui, Sana; Denis, Arnaud; Derval, Nicolas; Laurent, François; Montaudon, Michel; Hocini, Mélèze; Haïssaguerre, Michel; Jaïs, Pierre; Cochet, Hubert

    2015-04-01

    Epicardial ventricular tachycardia (VT) ablation is associated with risks of coronary artery (CA) and phrenic nerve (PN) injury. We investigated the role of multidetector computed tomography in visualizing CA and PN during VT ablation. Ninety-five consecutive patients (86 men; age, 57 ± 15) with VT underwent cardiac multidetector computed tomography. The PN detection rate and anatomic variability were analyzed. In 49 patients undergoing epicardial mapping, real-time multidetector computed tomographic integration was used to display CAs/PN locations in 3-dimensional mapping systems. Elimination of local abnormal ventricular activities (LAVAs) was used as ablation end point. The distribution of CAs/PN with respect to LAVA was analyzed and compared between VT etiologies. Multidetector computed tomography detected PN in 81 patients (85%). Epicardial LAVAs were observed in 44 of 49 patients (15 ischemic cardiomyopathy, 15 nonischemic cardiomyopathy, and 14 arrhythmogenic right ventricular cardiomyopathy) with a mean of 35 ± 37 LAVA points/patient. LAVAs were located within 1 cm from CAs and PN in 35 (80%) and 18 (37%) patients, respectively. The prevalence of LAVA adjacent to CAs was higher in nonischemic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy than in ischemic cardiomyopathy (100% versus 86% versus 53%; P < 0.01). The prevalence of LAVAs adjacent to PN was higher in nonischemic cardiomyopathy than in ischemic cardiomyopathy (93% versus 27%; P < 0.001). Epicardial ablation was performed in 37 patients (76%). Epicardial LAVAs could not be eliminated because of the proximity to CAs or PN in 8 patients (18%). The epicardial electrophysiological VT substrate is often close to CAs and PN in patients with nonischemic cardiomyopathy. High-resolution image integration is potentially useful to minimize risks of PN and CA injury during epicardial VT ablation. © 2015 American Heart Association, Inc.

  10. Analysis of selected genes associated with cardiomyopathy by next-generation sequencing.

    PubMed

    Szabadosova, Viktoria; Boronova, Iveta; Ferenc, Peter; Tothova, Iveta; Bernasovska, Jarmila; Zigova, Michaela; Kmec, Jan; Bernasovsky, Ivan

    2018-02-01

    As the leading cause of congestive heart failure, cardiomyopathy represents a heterogenous group of heart muscle disorders. Despite considerable progress being made in the genetic diagnosis of cardiomyopathy by detection of the mutations in the most prevalent cardiomyopathy genes, the cause remains unsolved in many patients. High-throughput mutation screening in the disease genes for cardiomyopathy is now possible because of using target enrichment followed by next-generation sequencing. The aim of the study was to analyze a panel of genes associated with dilated or hypertrophic cardiomyopathy based on previously published results in order to identify the subjects at risk. The method of next-generation sequencing by IlluminaHiSeq 2500 platform was used to detect sequence variants in 16 individuals diagnosed with dilated or hypertrophic cardiomyopathy. Detected variants were filtered and the functional impact of amino acid changes was predicted by computational programs. DNA samples of the 16 patients were analyzed by whole exome sequencing. We identified six nonsynonymous variants that were shown to be pathogenic in all used prediction softwares: rs3744998 (EPG5), rs11551768 (MGME1), rs148374985 (MURC), rs78461695 (PLEC), rs17158558 (RET) and rs2295190 (SYNE1). Two of the analyzed sequence variants had minor allele frequency (MAF)<0.01: rs148374985 (MURC), rs34580776 (MYBPC3). Our data support the potential role of the detected variants in pathogenesis of dilated or hypertrophic cardiomyopathy; however, the possibility that these variants might not be true disease-causing variants but are susceptibility alleles that require additional mutations or injury to cause the clinical phenotype of disease must be considered. © 2017 Wiley Periodicals, Inc.

  11. Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

    PubMed

    Tatlisumak, Turgut; Putaala, Jukka; Innilä, Markus; Enzinger, Christian; Metso, Tiina M; Curtze, Sami; von Sarnowski, Bettina; Amaral-Silva, Alexandre; Jungehulsing, Gerhard Jan; Tanislav, Christian; Thijs, Vincent; Rolfs, Arndt; Norrving, Bo; Fazekas, Franz; Suomalainen, Anu; Kolodny, Edwin H

    2016-02-01

    Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

  12. Usefulness of colonoscopy in ischemic colitis.

    PubMed

    Lozano-Maya, M; Ponferrada-Díaz, A; González-Asanza, C; Nogales-Rincón, O; Senent-Sánchez, C; Pérez-de-Ayala, V; Jiménez-Aleixandre, P; Cos-Arregui, E; Menchén-Fernández-Pacheco, P

    2010-07-01

    the ischemic colitis is intestinal the most frequent cause of ischemia. With this work we determine the demographic and clinical characteristics, and the usefulness of the colonoscopy in the patients with ischemic colitis diagnosed in our centre in relation to a change of therapeutic attitude. retrospective study in which were selected 112 patients diagnosed with ischemic colitis by colonoscopy and biopsy, in a period of five years. It was analyzed: age, sex, reason for examination, factors of cardiovascular risk, endoscopic degree of ischemia, change in the therapeutic attitude, treatment and outcome. the average age was of 73.64 + or - 12.10 years with an equal incidence in women (50.9%) and the men (49.1%). The associated factors were the HTA (61.1%), tobacco (37.2%) and antecedents of cardiovascular episode (52.2%). The most frequent reason for colonoscopy was rectorrhagia (53.6%) followed of the abdominal pain (30.4%), being urgent the 65.3%. Colonoscopy allowed a change in the therapeutic attitude in the 50 increasing in the urgent one to the 65.75%. Global mortality was of 27.67%. The serious ischemic colitis (25%) was more frequent in men (64.3%) in urgent indication (85.71%) and attends with high mortality (53.57%). Surgical treatment in the 57.14% was made with a good evolution in the 50%, whereas the patients with mild or moderate ischemic colitis had a better prognosis (favourable evolution in 80.95%) with smaller requirement of the surgical treatment (4.76%), p < 0.05. the colitis ischemic are more frequent in the older age. The most frequent symptoms are the rectorrhagia and the abdominal pain. The colonoscopy is a useful technique to evaluate the gravity and it induces a change of attitude according to the result of the same one. The evidence of a serious colitis supposed an increase of the necessity of surgery and worse prognosis.

  13. Prevention of the collapse of pial collaterals by remote ischemic perconditioning during acute ischemic stroke.

    PubMed

    Ma, Junqiang; Ma, Yonglie; Dong, Bin; Bandet, Mischa V; Shuaib, Ashfaq; Winship, Ian R

    2017-08-01

    Collateral circulation is a key variable determining prognosis and response to recanalization therapy during acute ischemic stroke. Remote ischemic perconditioning (RIPerC) involves inducing peripheral ischemia (typically in the limbs) during stroke and may reduce perfusion deficits and brain damage due to cerebral ischemia. In this study, we directly investigated pial collateral flow augmentation due to RIPerC during distal middle cerebral artery occlusion (MCAo) in rats. Blood flow through pial collaterals between the anterior cerebral artery (ACA) and the MCA was assessed in male Sprague Dawley rats using in vivo laser speckle contrast imaging (LSCI) and two photon laser scanning microscopy (TPLSM) during distal MCAo. LSCI and TPLSM revealed that RIPerC augmented collateral flow into distal MCA segments. Notably, while control rats exhibited an initial dilation followed by a progressive narrowing of pial arterioles 60 to 150-min post-MCAo (constricting to 80-90% of post-MCAo peak diameter), this constriction was prevented or reversed by RIPerC (such that vessel diameters increased to 105-110% of post-MCAo, pre-RIPerC diameter). RIPerC significantly reduced early ischemic damage measured 6 h after stroke onset. Thus, prevention of collateral collapse via RIPerC is neuroprotective and may facilitate other protective or recanalization therapies by improving blood flow in penumbral tissue.

  14. The Loss of Myocardial Benefit following Ischemic Preconditioning Is Associated with Dysregulation of Iron Homeostasis in Diet-Induced Diabetes

    PubMed Central

    Berenshtein, Eduard; Eliashar, Ron; Chevion, Mordechai

    2016-01-01

    Whether the diabetic heart benefits from ischemic preconditioning (IPC), similar to the non-diabetic heart, is a subject of controversy. We recently proposed new roles for iron and ferritin in IPC-protection in Type 1-like streptozotocin-induced diabetic rat heart. Here, we investigated iron homeostasis in Cohen diabetic sensitive rat (CDs) that develop hyperglycemia when fed on a high-sucrose/low-copper diet (HSD), but maintain normoglycemia on regular-diet (RD). Control Cohen-resistant rats (CDr) maintain normoglycemia on either diet. The IPC procedure improved the post-ischemic recovery of normoglycemic hearts (CDr-RD, CDr-HSD and CDs-RD). CDs-HSD hearts failed to show IPC-associated protection. The recovery of these CDs-HSD hearts following I/R (without prior IPC) was better than their RD controls. During IPC ferritin levels increased in normoglycemic hearts, and its level was maintained nearly constant during the subsequent prolonged ischemia, but decayed to its baseline level during the reperfusion phase. In CDs-HSD hearts the baseline levels of ferritin and ferritin-saturation with iron were notably higher than in the controls, and remained unchanged during the entire experiment. This unique and abnormal pattern of post-ischemic recovery of CDs-HSD hearts is associated with marked changes in myocardial iron homeostasis, and suggests that iron and iron-proteins play a causative role/s in the etiology of diabetes-associated cardiovascular disorders. PMID:27458721

  15. European Cardiomyopathy Pilot Registry: EURObservational Research Programme of the European Society of Cardiology.

    PubMed

    Elliott, Perry; Charron, Philippe; Blanes, Juan Ramon Gimeno; Tavazzi, Luigi; Tendera, Michal; Konté, Marème; Laroche, Cécile; Maggioni, Aldo P

    2016-01-07

    Cardiomyopathies are a heterogeneous group of disorders associated with premature death due to ventricular arrhythmia or heart failure. The purpose of this study was to examine the characteristics of patients enrolled in the pilot phase of the EURObservational Research Programme (EORP) cardiomyopathy registry. Between 1 December 2012 and 30 November 2013, four cardiomyopathy phenotypes were studied: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). Twenty-seven centres in 12 countries participated; 1115 patients were enrolled. The commonest cardiomyopathy was HCM (n = 681), followed by DCM (n = 346), ARVC (n = 59), and RCM (n = 29); 423 patients (46.4% of those reported) had familial disease; and 56 (5.0%) had rare disease phenocopies. Median age at enrolment and diagnosis was 54 [interquartile range (IQR), 42-64] and 46 years (IQR, 32-58), respectively; fewer patients with ARVC and more with RCM were diagnosed in the upper age quartile (P < 0.0001). There was a male predominance for all cardiomyopathies except RCM (P = 0.0023). Most patients were in New York Heart Association functional class I (n = 813) at enrolment; 139 (12.5%) reported syncope, most frequently in ARVC (P = 0.0009). Five hundred and seven (45.5%) patients underwent cardiac magnetic resonance imaging, 117 (10.6%) endomyocardial biopsy, and 462 (41.4%) genetic testing with a causative mutation reported in 236 individuals (51.1%). 1026 patients (92.0%) were receiving drug therapy; 316 (28.3%) had received an implantable cardioverter defibrillator (highest proportion in ARVC, P < 0.0001). This pilot study shows that services for patients with cardiomyopathy are complex, requiring access to a large range of invasive and non-invasive investigations and involvement of multidisciplinary teams. Treatment regimens are equally multifaceted and show that patients are likely to need long-term follow

  16. Echocardiography Differences Between Athlete's Heart Hearth and Hypertrophic Cardiomyopathy.

    PubMed

    Kreso, Amir; Barakovic, Fahir; Medjedovic, Senad; Halilbasic, Amila; Klepic, Muhamed

    2015-10-01

    Among long term athletes there is always present hypertrophy of the left ventricle walls as well as increased cardiac mass. These changes are the result of the heart muscle adaptation to load during the years of training, which should not be considered as pathology. In people suffering from hypertrophic cardiomyopathy (HCM), there is also present hypertrophy of the left ventricle walls and increased mass of the heart, but these changes are the result of pathological changes in the heart caused by a genetic predisposition for the development HCM of. Differences between myocardial hypertrophy in athletes and HCM are not clearly differentiated and there are always dilemmas between pathological and physiological hypertrophy. The goal of the study is to determine and compare the echocardiographic cardiac parameters of longtime athletes to patients with hypertrophic cardiomyopathy. The study included 60 subjects divided into two groups: active athletes and people with hypertrophic cardiomyopathy. Mean values of IVSd recorded in GB is IVSd=17.5 mm (n=20, 95% CI, 16.00-19.00 mm), while a significantly smaller mean value is recorded in GA, IVSd=10.0 mm (n=40, 95% CI, 9.00-11.00 mm). The mean value of the left ventricle in diastole (LVDd) recorded in the GA is LVDd=51 mm (n=40; 95% CI, 48.00 to 52.00 mm), while in the group with hypertrophic cardiomyopathy (GB) mean LVDd value is 42 mm (n=20; 95% CI, 40.00 to 48.00 mm). The mean value of the rear wall of the left ventricle (LVPWd) recorded in the GA is LVDd=10 mm (n=40; 95% CI, 9.00-10.00 mm) while in the group with hypertrophic cardiomyopathy (GB) mean LVDd is 14 mm (n=20; 95% CI, 12.00 to 16.00 mm). The mean of the left ventricle during systole (LVSD) observed in GA is LVSD=34 mm (n=40; 95% CI, 32.00 to 36.00 mm), while in the group with hypertrophic cardiomyopathy (GB) mean LVSD is 28 mm (n=20; 95% CI, 24.00 to 28.83 mm). The mean ejection fraction (EF%) observed in GA is EF=60% (n=40; 95% CI, 56.41 to 63.00%), while in

  17. Left Ventricular Noncompaction Cardiomyopathy and Recurrent Polymorphic Ventricular Tachycardia: A Case Report and Literature Review.

    PubMed

    Akinseye, Oluwaseun A; Ibebuogu, Uzoma N; Jha, Sunil K

    2017-01-01

    Noncompaction cardiomyopathy is a rare phenotype of cardiomyopathy associated with severe cardiac arrhythmia and thromboembolic complications. A 55-year-old woman presented with frank pulmonary edema and received a diagnosis of noncompaction cardiomyopathy. Left ventricular noncompaction cardiomyopathy is increasingly being diagnosed because of advances in imaging modalities. It is important to differentiate this new phenotype of cardiomyopathy from others because its diagnosis, management, and prognosis differ. We reviewed the literature and summarized the diagnostic criteria, associated complications, initial and long-term management, and the recommendation for family screening.

  18. Ischemic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Ischemic stroke is the most common type. It is usually ... are at risk for having a more serious stroke. Symptoms of stroke are Sudden numbness or weakness ...

  19. [Improvement and the mechanism of cardiac function by knockdown of ADAM10 in adriamycin-induced cardiomyopathy rats].

    PubMed

    Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei

    2018-01-01

    Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.

  20. Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

    PubMed Central

    Afzal, Muhammad Z.; Reiter, Melanie; Gastonguay, Courtney; McGivern, Jered V.; Guan, Xuan; Ge, Zhi-Dong; Mack, David L.; Childers, Martin K.; Ebert, Allison D.; Strande, Jennifer L.

    2016-01-01

    Background Dystrophin-deficient cardiomyopathy is a growing clinical problem without targeted treatments. We investigated whether nicorandil promotes cardioprotection in human dystrophin-deficient induced pluripotent stem cell (iPSC)-derived cardiomyocytes and the muscular dystrophy mdx mouse heart. Methods and Results Dystrophin-deficient iPSC-derived cardiomyocytes had decreased levels of endothelial nitric oxide synthase and neuronal nitric oxide synthase. The dystrophin-deficient cardiomyocytes had increased cell injury and death after 2 hours of stress and recovery. This was associated with increased levels of reactive oxygen species and dissipation of the mitochondrial membrane potential. Nicorandil pretreatment was able to abolish these stress-induced changes through a mechanism that involved the nitric oxide–cyclic guanosine monophosphate pathway and mitochondrial adenosine triphosphate-sensitive potassium channels. The increased reactive oxygen species levels in the dystrophin-deficient cardiomyocytes were associated with diminished expression of select antioxidant genes and increased activity of xanthine oxidase. Furthermore, nicorandil was found to improve the restoration of cardiac function after ischemia and reperfusion in the isolated mdx mouse heart. Conclusion Nicorandil protects against stress-induced cell death in dystrophin-deficient cardiomyocytes and preserves cardiac function in the mdx mouse heart subjected to ischemia and reperfusion injury. This suggests a potential therapeutic role for nicorandil in dystrophin-deficient cardiomyopathy. PMID:26940570

  1. Opposite effects of catalase and MnSOD ectopic expression on stress induced defects and mortality in the desmin deficient cardiomyopathy model.

    PubMed

    Rapti, Kleopatra; Diokmetzidou, Antigoni; Kloukina, Ismini; Milner, Derek J; Varela, Aimilia; Davos, Constantinos H; Capetanaki, Yassemi

    2017-09-01

    Oxidative stress has been linked strongly to cell death and cardiac remodeling processes, all hallmarks of heart failure. Mice deficient for desmin (des-/-), the major muscle specific intermediate filament protein, develop dilated cardiomyopathy and heart failure characterized by mitochondrial defects and cardiomyocyte death. The cellular and biochemical alterations in the hearts of these mice strongly suggest that oxidative stress is one of the mechanisms contributing to the pathogenesis of the phenotype. Recently, we showed that indeed the desmin deficient cardiomyocytes are under increased oxidative stress. In order to verify these findings in vivo, we generated transgenic animals overexpressing SOD2 (MnSOD) and/or catalase in the heart and crossed them with des-/- mice, thus allowing us to evaluate the contribution of oxidative injury in inherited cardiomyopathies, as well as the therapeutic potential of antioxidant strategies. Moderate MnSOD and/or catalase overexpression in des-/- hearts leads to a marked decrease in intracellular reactive oxygen species (ROS), ameliorates mitochondrial and other ultrastructural defects, minimizes myocardial degeneration and leads to a significant improvement of cardiac function. Importantly, catalase overexpression increased the 50% survival rate of des-/- mice in an obligatory exercise to 100%. In contrast, MnSOD overexpression enhanced the lethality of des-/- mice, underscoring the importance of a fine balanced cellular redox status. Overall, the present study supports the contribution of oxidative stress in the development of des-/- cardiomyopathy and points to a well-considered antioxidant treatment as therapeutic for cardiomyopathies. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. A Matched Cohort Study of Patients With End-Stage Heart Failure from Anthracycline-Induced Cardiomyopathy Requiring Advanced Cardiac Support.

    PubMed

    Thomas, Garry R; McDonald, Michael A; Day, Jennifer; Ross, Heather J; Delgado, Diego H; Billia, Filio; Butany, Jagdish W; Rao, Vivek; Amir, Eitan; Bedard, Philippe L; Thavendiranathan, Paaladinesh

    2016-11-15

    Anthracycline-induced cardiomyopathy (AIC) may progress to end-stage heart failure requiring mechanical circulatory support or orthotopic heart transplantation (OHT). Previous studies have described important clinical differences between AIC and nonischemic cardiomyopathy (NIC) cohorts requiring these advanced interventions. Therefore, we sought to extend this literature by comparing echocardiographic parameters, treatment strategies, and the prognosis between matched patients from these cohorts. This is a retrospective matched cohort study. All patients who received a ventricular assist device or OHT at a large Canadian center were reviewed (n = 421; 1988 to 2015) and subjects with clinical and pathologic evidence of AIC were included (n = 17, 4.0%). A comparison cohort with idiopathic NIC from the same database, matched 3:1 for age, gender, ethnicity, and year of heart failure onset was selected. The Mann-Whitney rank-sum and Fisher's exact tests were used for comparisons. Patients with AIC were predominantly women (70.6%) with heart failure diagnosed at age 40.2 ± 15.8 and 8.3 ± 8.9 years after anthracycline treatment. Compared with NIC, no differences were seen in co-morbidities, echocardiographic measures, the proportion of patients receiving a defibrillator, ventricular assist device, or OHT, the incidence of graft failure, and all-cause mortality. In contrast to other studies, AIC was not associated with a higher incidence of right ventricular dysfunction. A greater proportion of patients with AIC developed cancer (recurrence or new primary) post-OHT (21.4% vs 2.3%, p = 0.042). In conclusion, we demonstrate that when matched cohorts of patients with end-stage heart failure secondary to AIC and idiopathic NIC are compared, they are similar with respect to co-morbidities, degree of ventricular dysfunction, and advanced therapeutics used. The prognosis with OHT is also similar. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Correlation between right ventricular T1 mapping and right ventricular dysfunction in non-ischemic cardiomyopathy.

    PubMed

    Jellis, Christine L; Yingchoncharoen, Teerapat; Gai, Neville; Kusunose, Kenya; Popović, Zoran B; Flamm, Scott; Kwon, Deborah

    2018-01-01

    Right ventricular (RV) fibrosis is increasingly recognized as the underlying pathological substrate in a variety of clinical conditions. We sought to employ cardiac magnetic resonance (CMR) techniques of strain imaging and longitudinal relaxation time (T 1 ) mapping to better examine the relationship between RV function and structure. Our aim was to initially evaluate the feasibility of these techniques to evaluate the right ventricle. We then sought to explore the relationship between RV function and underlying fibrosis, along with examining the evolution of RV remodeling according to the amount of baseline fibrosis. Echocardiography was performed in 102 subjects with non-ischemic cardiomyopathy. Right ventricular parameters were assessed including: fractional area change (FAC) and longitudinal strain. The same cohort underwent CMR. Post-contrast T 1 mapping was performed as a marker of fibrosis with a Look-Locker technique using inversion recovery imaging. Mid-ventricular post-contrast T 1 values of the RV free wall, RV septum and lateral LV were calculated using prototype analysis software. Biventricular volumetric data including ejection fraction was measured by CMR using a cine short axis stack. CMR strain analysis was also performed to assess 2D RV longitudinal and radial strain. Simultaneous biochemical and anthropometric data were recorded. Subjects were followed over a median time of 29 months (IQR 20-37 months) with echocardiography to evaluate temporal change in RV FAC according to baseline post-contrast T 1 values. Longitudinal data analysis was performed to adjust for patient loss during follow-up. Subjects (62% men, 51 ± 15 years) had mild to moderately impaired global RV systolic function (RVEF = 39 ± 15%; RVEDV = 187 ± 69 ml; RVESV = 119 ± 68 ml) and moderate left ventricular dysfunction at baseline (LVEF 30 ± 17%). Good correlation was observed between mean LV and RV post-contrast T 1 values (r = 0.652, p

  4. [The relationship between ischemic preconditioning-induced infarction size limitation and duration of test myocardial ischemia].

    PubMed

    Blokhin, I O; Galagudza, M M; Vlasov, T D; Nifontov, E M; Petrishchev, N N

    2008-07-01

    Traditionally infarction size reduction by ischemic preconditioning is estimated in duration of test ischemia. This approach limits the understanding of real antiischemic efficacy of ischemic preconditioning. Present study was performed in the in vivo rat model of regional myocardial ischemia-reperfusion and showed that protective effect afforded by ischemic preconditioning progressively decreased with prolongation of test ischemia. There were no statistically significant differences in infarction size between control and preconditioned animals when the duration of test ischemia was increased up to 1 hour. Preconditioning ensured maximal infarction-limiting effect in duration of test ischemia varying from 20 to 40 minutes.

  5. Role of left ventricular twist mechanics in cardiomyopathies, dance of the helices

    PubMed Central

    Kauer, Floris; Geleijnse, Marcel Leonard; van Dalen, Bastiaan Martijn

    2015-01-01

    Left ventricular twist is an essential part of left ventricular function. Nevertheless, knowledge is limited in “the cardiology community” as it comes to twist mechanics. Fortunately the development of speckle tracking echocardiography, allowing accurate, reproducible and rapid bedside assessment of left ventricular twist, has boosted the interest in this important mechanical aspect of left ventricular deformation. Although the fundamental physiological role of left ventricular twist is undisputable, the clinical relevance of assessment of left ventricular twist in cardiomyopathies still needs to be established. The fact remains; analysis of left ventricular twist mechanics has already provided substantial pathophysiological understanding on a comprehensive variety of cardiomyopathies. It has become clear that increased left ventricular twist in for example hypertrophic cardiomyopathy may be an early sign of subendocardial (microvascular) dysfunction. Furthermore, decreased left ventricular twist may be caused by left ventricular dilatation or an extensive myocardial scar. Finally, the detection of left ventricular rigid body rotation in noncompaction cardiomyopathy may provide an indispensible method to objectively confirm this difficult diagnosis. All this endorses the value of left ventricular twist in the field of cardiomyopathies and may further encourage the implementation of left ventricular twist parameters in the “diagnostic toolbox” for cardiomyopathies. PMID:26322187

  6. Dystrophic Cardiomyopathy: Complex Pathobiological Processes to Generate Clinical Phenotype

    PubMed Central

    Tsuda, Takeshi; Fitzgerald, Kristi K.

    2017-01-01

    Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and X-linked dilated cardiomyopathy (XL-DCM) consist of a unique clinical entity, the dystrophinopathies, which are due to variable mutations in the dystrophin gene. Dilated cardiomyopathy (DCM) is a common complication of dystrophinopathies, but the onset, progression, and severity of heart disease differ among these subgroups. Extensive molecular genetic studies have been conducted to assess genotype-phenotype correlation in DMD, BMD, and XL-DCM to understand the underlying mechanisms of these diseases, but the results are not always conclusive, suggesting the involvement of complex multi-layers of pathological processes that generate the final clinical phenotype. Dystrophin protein is a part of dystrophin-glycoprotein complex (DGC) that is localized in skeletal muscles, myocardium, smooth muscles, and neuronal tissues. Diversity of cardiac phenotype in dystrophinopathies suggests multiple layers of pathogenetic mechanisms in forming dystrophic cardiomyopathy. In this review article, we review the complex molecular interactions involving the pathogenesis of dystrophic cardiomyopathy, including primary gene mutations and loss of structural integrity, secondary cellular responses, and certain epigenetic and other factors that modulate gene expressions. Involvement of epigenetic gene regulation appears to lead to specific cardiac phenotypes in dystrophic hearts. PMID:29367543

  7. MELAS syndrome and cardiomyopathy: linking mitochondrial function to heart failure pathogenesis.

    PubMed

    Hsu, Ying-Han R; Yogasundaram, Haran; Parajuli, Nirmal; Valtuille, Lucas; Sergi, Consolato; Oudit, Gavin Y

    2016-01-01

    Heart failure remains an important clinical burden, and mitochondrial dysfunction plays a key role in its pathogenesis. The heart has a high metabolic demand, and mitochondrial function is a key determinant of myocardial performance. In mitochondrial disorders, hypertrophic remodeling is the early pattern of cardiomyopathy with progression to dilated cardiomyopathy, conduction defects and ventricular pre-excitation occurring in a significant proportion of patients. Cardiac dysfunction occurs in approximately a third of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome, a stereotypical example of a mitochondrial disorder leading to a cardiomyopathy. We performed unique comparative ultrastructural and gene expression in a MELAS heart compared with non-failing controls. Our results showed a remarkable increase in mitochondrial inclusions and increased abnormal mitochondria in MELAS cardiomyopathy coupled with variable sarcomere thickening, heterogeneous distribution of affected cardiomyocytes and a greater elevation in the expression of disease markers. Investigation and management of patients with mitochondrial cardiomyopathy should follow the well-described contemporary heart failure clinical practice guidelines and include an important role of medical and device therapies. Directed metabolic therapy is lacking, but current research strategies are dedicated toward improving mitochondrial function in patients with mitochondrial disorders.

  8. Clinical Presentation and Natural History of Hypertrophic Cardiomyopathy in RASopathies.

    PubMed

    Calcagni, Giulio; Adorisio, Rachele; Martinelli, Simone; Grutter, Giorgia; Baban, Anwar; Versacci, Paolo; Digilio, Maria Cristina; Drago, Fabrizio; Gelb, Bruce D; Tartaglia, Marco; Marino, Bruno

    2018-04-01

    RASopathies are a heterogeneous group of genetic syndromes characterized by mutations in genes that regulate cellular processes, including proliferation, differentiation, survival, migration, and metabolism. Excluding congenital heart defects, hypertrophic cardiomyopathy is the most frequent cardiovascular defect in patients affected by RASopathies. A worse outcome (in terms of surgical risk and/or mortality) has been described in a specific subset of Rasopathy patients with early onset, severe hypertrophic cardiomyopathy presenting with heart failure. New short-term therapy with a mammalian target of rapamycin inhibitor has recently been used to prevent heart failure in these patients with a severe form of hypertrophic cardiomyopathy. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Intermittent fasting attenuates inflammasome activity in ischemic stroke.

    PubMed

    Fann, David Yang-Wei; Santro, Tomislav; Manzanero, Silvia; Widiapradja, Alexander; Cheng, Yi-Lin; Lee, Seung-Yoon; Chunduri, Prasad; Jo, Dong-Gyu; Stranahan, Alexis M; Mattson, Mark P; Arumugam, Thiruma V

    2014-07-01

    Recent findings have revealed a novel inflammatory mechanism that contributes to tissue injury in cerebral ischemia mediated by multi-protein complexes termed inflammasomes. Intermittent fasting (IF) can decrease the levels of pro-inflammatory cytokines in the periphery and brain. Here we investigated the impact of IF (16h of food deprivation daily) for 4months on NLRP1 and NLRP3 inflammasome activities following cerebral ischemia. Ischemic stroke was induced in C57BL/6J mice by middle cerebral artery occlusion, followed by reperfusion (I/R). IF decreased the activation of NF-κB and MAPK signaling pathways, the expression of NLRP1 and NLRP3 inflammasome proteins, and both IL-1β and IL-18 in the ischemic brain tissue. These findings demonstrate that IF can attenuate the inflammatory response and tissue damage following ischemic stroke by a mechanism involving suppression of NLRP1 and NLRP3 inflammasome activity. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation

    PubMed Central

    Lynch, Thomas L.; Sivaguru, Mayandi; Velayutham, Murugesan; Cardounel, Arturo J.; Michels, Michelle; Barefield, David; Govindan, Suresh; dos Remedios, Cristobal; van der Velden, Jolanda; Sadayappan, Sakthivel

    2015-01-01

    Cardiomyopathies can result from mutations in genes encoding sarcomere proteins including MYBPC3, which encodes cardiac myosin binding protein-C (cMyBP-C). However, whether oxidative stress is augmented due to contractile dysfunction and cardiomyocyte damage in MYBPC3-mutated cardiomyopathies has not been elucidated. To determine whether oxidative stress markers were elevated in MYBPC3-mutated cardiomyopathies, a previously characterized 3-month-old mouse model of dilated cardiomyopathy (DCM) expressing a homozygous MYBPC3 mutation (cMyBP-C(t/t)) was used, compared to wild-type (WT) mice. Echocardiography confirmed decreased percentage of fractional shortening in DCM versus WT hearts. Histopathological analysis indicated a significant increase in myocardial disarray and fibrosis while the second harmonic generation imaging revealed disorganized sarcomeric structure and myocyte damage in DCM hearts when compared to WT hearts. Intriguingly, DCM mouse heart homogenates had decreased glutathione (GSH/GSSG) ratio and increased protein carbonyl and lipid malondialdehyde content compared to WT heart homogenates, consistent with elevated oxidative stress. Importantly, a similar result was observed in human cardiomyopathy heart homogenate samples. These results were further supported by reduced signals for mitochondrial semiquinone radicals and Fe-S clusters in DCM mouse hearts measured using electron paramagnetic resonance spectroscopy. In conclusion, we demonstrate elevated oxidative stress in MYPBC3-mutated DCM mice, which may exacerbate the development of heart failure. PMID:26508994

  11. The association of methamphetamine use and cardiomyopathy in young patients.

    PubMed

    Yeo, Khung-Keong; Wijetunga, Mevan; Ito, Hiroki; Efird, Jimmy T; Tay, Kevin; Seto, Todd B; Alimineti, Kavitha; Kimata, Chieko; Schatz, Irwin J

    2007-02-01

    Methamphetamine is the most widespread illegally used stimulant in the United States. Previously published case reports and series suggest a potential association between methamphetamine exposure and cardiomyopathy. The objective of this study is to demonstrate an association between methamphetamine use and cardiomyopathy. Case-control study based on chart review of discharges from a tertiary care medical center from January 2001 to June 2004. Patients were < or =45 years old. Cases included patients with a discharge diagnosis of either cardiomyopathy or heart failure. Controls included hospitalized patients who had an echocardiographic assessment of left ventricular function with ejection fraction > or =55% and no wall motion abnormalities. One hundred and seven cases and 114 controls were identified. Both groups had similar gender distribution, length of hospital stay, rates of health insurance, prevalence of coronary artery disease, diabetes mellitus, hypertension, cigarette smoking, alcohol abuse, and marijuana and cocaine use. Cases were older than controls (mean age: 38 vs 35 years; P=.008), had higher body mass index (BMI) (mean BMI: 37 vs 30 kg/m2; P<.001), and higher prevalence of renal failure (13% vs 4.4%; P=.03). Methamphetamine users had a 3.7-fold increased odds ratio [95% confidence interval, 1.8-7.8] for cardiomyopathy, adjusting for age, body mass index, and renal failure. Methamphetamine use was associated with cardiomyopathy in young patients.

  12. [Acute brain expansion during emergency neck clipping surgery for cerebral aneurysms in a patient with dilated cardiomyopathy].

    PubMed

    Nakao, M; Kawaguchi, R; Nakatani, K; Niinai, H; Takezaki, T; Hanaki, C

    1996-06-01

    A 61-year-old male with coma and undiagnosed dilated cardiomyopathy received emergency cerebral aneurysm surgery. Anesthesia was induced with thiamylal, fentanyl and vecuronium and maintained with 66% N2O and 1.0% isoflurane. Five hundred ml of 20% mannitol was infused in 30 min. At the end of the infusion, hypotension occurred. Immediately after the injection of ephedrine, acute brain swelling was observed. The operation was switched to external decompression. Post-operative echocardiography revealed the presence of dilated cardiomyopathy (DCM). The ejection fraction was 34%. Two weeks later, the second operation was scheduled. The anesthesia was induced with fentanyl, midazolam and vecuronium and maintained with N2O and 0.7% isoflurane. Nitroglycerine, lidocaine, PGE1, dopamine and dobutamine were infused throughout the operation. Five hundred ml of 20% mannitol was infused in 60 min. There were no considerable hemodynamic changes and no episode of brain expansion during operation. We conclude that the rapid infusion of mannitol can trigger acute cardiac failure and brain edema in patients with DCM.

  13. Trastuzumab-induced cardiomyopathy.

    PubMed

    Guglin, Maya; Cutro, Raymond; Mishkin, Joseph D

    2008-06-01

    Trastuzumab is a recombinant humanized monoclonal antibody used for the treatment of advanced breast cancer. It improves survival and increases response to chemotherapy. The major side effect of trastuzumab is cardiotoxicity manifesting as a reduction in left ventricular systolic function, either asymptomatic or with signs and symptoms of heart failure. Although reversible in most cases, cardiotoxicity frequently results in the discontinuation of trastuzumab. The objective of this review is to summarize facts about trastuzumab-induced cardiotoxicity and to highlight the areas of future investigations. We searched PubMed for trials involving trastuzumab used as an adjuvant therapy for breast cancer, including the metastatic breast cancer setting, and focused on cardiotoxicity.

  14. Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy.

    PubMed

    Lopes, Rosana; Solter, Philip F; Sisson, D David; Oyama, Mark A; Prosek, Robert

    2006-06-01

    To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM). Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing. Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis. Protein spots that increased or decreased in density by 2-fold or greater between groups were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or quadrupole selecting, quadrupole collision cell, time-of-flight mass spectrometry. A total of 22 altered mitochondrial proteins were identified in complexes I to V. Ten and 12 were found in complex I and complexes II to V, respectively. Five were mitochondrial encoded, and 17 were nuclear encoded. Most altered mitochondrial proteins in tissue specimens from dogs with naturally occurring DCM were associated with complexes I and V, whereas in tissue specimens from dogs subjected to rapid ventricular pacing, complexes I and IV were more affected. In the experimentally induced form of DCM, only nuclear-encoded subunits were changed in complex I. In both disease groups, the 22-kd subunit was downregulated. Natural and induced forms of DCM resulted in altered mitochondrial protein expression in complexes I to V. However, subcellular differences between the experimental and naturally occurring forms of DCM may exist.

  15. Ischemic Colitis

    PubMed Central

    Montessori, Gino; Liepa, Egils V.

    1970-01-01

    Twenty cases of ischemic colitis are reviewed; 19 were obtained from autopsy files and the diagnosis in one was made from a surgical specimen. The majority of the patients were elderly with generalized arteriosclerosis. In approximately two-thirds of the patients the ischemic colitis was precipitated by preceding trauma, operation or congestive heart failure. Clinically, ischemic colitis is characterized by abdominal pain, distension and bleeding per rectum. Perforation of large bowel may occur. The lesions tend to be localized around the splenic flexure and junction of the descending and sigmoid colon, and in cases following aortic graft surgery the rectum is involved. Microscopically, there is necrosis, hemorrhage and ulceration. In less severe cases the mucosa only is affected. Cases with perforation show necrosis of all layers. It is considered that ischemic colitis is comparatively frequent and should be distinguished from other inflammatory conditions of the colon. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9 PMID:5308923

  16. Anti-oxidant effect of bergamot polyphenolic fraction counteracts doxorubicin-induced cardiomyopathy: Role of autophagy and c-kitposCD45negCD31neg cardiac stem cell activation.

    PubMed

    Carresi, Cristina; Musolino, Vincenzo; Gliozzi, Micaela; Maiuolo, Jessica; Mollace, Rocco; Nucera, Saverio; Maretta, Alessia; Sergi, Domenico; Muscoli, Saverio; Gratteri, Santo; Palma, Ernesto; Bosco, Francesca; Giancotta, Caterina; Muscoli, Carolina; Marino, Fabiola; Aquila, Iolanda; Torella, Daniele; Romeo, Franco; Mollace, Vincenzo

    2018-04-12

    Doxorubicin (DOXO) is one of the most widely used antineoplastic drugs. Despite its highly beneficial effects against several malignancies, the clinical use of DOXO is often associated to cardiomyopathy that leads to congestive heart failure. Here we investigated the antioxidant and cardioprotective effects of a polyphenol-rich fraction of citrus bergamot (BPF), in DOXO-induced cardiac damage in rats. Moreover, we evaluated the effect of BPF on cardiomyocyte survival and resident endogenous cardiac stem/progenitor cell (eCSC) activation. Adult male Wistar rats were i.p. injected with saline (serving as controls, CTRL, n = 10), BPF (20 mg/kg daily for 14 consecutive days, n = 10), DOXO (6 doses of 2,5 mg/Kg from day 1 to day 14, n = 10), and DOXO + BPF (n = 10). Animals were then sacrificed 7 days later (i.e., at 21 days). DOXO administration reduced cardiac function at 21 days, an adverse effect significantly attenuated in animals receiving DOXO + BPF. No changes were detected in rats receiving just saline or BPF alone. The cardioprotective effect of BPF on DOXO acute toxicity was also associated with a significant antioxidant effect coupled with protective autophagy restoration, and attenuation of cardiomyocyte apoptosis and reactive hypertrophy. Finally, treatment of rats with BPF prevented eCSCs attrition by DOXO which was followed by a limited but significant increase of newly-formed BrdU + cardiomyocytes. In conclusion, BPF reduces DOXO-induced cardiotoxicity by counteracting reactive oxygen species (ROS) overproduction, thereby restoring protective autophagy and attenuating cardiomyocyte apoptosis and pathologic remodeling. This beneficial effects on the early toxicity of DOXO is associated with enhanced CSCs survival and regenerative potential. Overall these data point to a potential clinical role by diet supplementation with polyphenol-rich fraction of citrus bergamot in counteracting antracycline-induced cardiomyopathy

  17. Transient ischemic attack

    MedlinePlus

    ... artery surgery - discharge Stroke - discharge Taking warfarin (Coumadin) Images Endarterectomy Transient Ischemic attack (TIA) References Biller J, Ruland S, Schneck MJ. Ischemic cerebrovascular disease. In Daroff ...

  18. Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review

    PubMed Central

    Shekhar, Shashank; Liu, Ruen; Travis, Olivia K; Roman, Richard J; Fan, Fan

    2017-01-01

    Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function. PMID:29333537

  19. Reverse remodeling and the mechanism of mitral regurgitation improvement in patients with dilated cardiomyopathy.

    PubMed

    Kuperstein, Rafael; Blechman, Ido; Ben Zekry, Sagit; Klempfner, Robert; Freimark, Dov; Arad, Michael

    2015-01-01

    Functional mitral regurgitation (MR) is a common finding in dilated cardiomyopathy. Left ventricular (LV) reverse remodeling with LV size reduction and improvement in LV function is a well recognized phenomenon. We aimed to evaluate the impact of LV remodeling on the mechanism leading to functional MR. Among 188 patients with non-ischemic dilated cardiomyopathy, 10 patients significantly improved their LV function, reduced LV size and MR severity during follow-up (RRMR). A comparison was made between their baseline and follow-up echocardiographic examinations and to a matched-control group of patients who did not improve (no RRMR). LV and left atrium (LA) dimensions and volumes, LV mass (LVM), LV ejection fraction (LVEF) (Simpsons), sphericity index (SI), mitral valve tenting area (TA) coaptation distance (CD), effective regurgitant orifice (ERO), and regurgitant volume were calculated. Multivariable analysis was performed in order to evaluate which echocardiographic parameters related to MR improvement in reverse remodeling. LV and LA dimensions and volumes, LVM, SI, TA, CD, ERO and right ventricle, in the RRMR group significantly decreased at follow-up (p < 0.04 for all). When compared to no RRMR, despite a similar ERO (0.2 ± 0.05 vs. 0.2 ± 0.08, p = 0.13) and a larger regurgitant volume (38 ± 9 vs. 29 ± 8 mL, p = 0.05) and despite similar clinical characteristics and medical treatment we found significantly higher LVEF, smaller LV dimensions and volumes, smaller LVM and SI in the RRMR group (p < 0.05 for all). On multivariable analysis the SI was the sole predictor of RRMR (p = 0.04, OR = 0.76, CI 0.58-0.99). Reverse remodeling characterized by improvement in LV function, reduction in LV size and an associated reduction in MR severity is related to LV SI at baseline.

  20. High prevalence of myocardial monoclonal antimyosin antibody uptake in patients with chronic idiopathic dilated cardiomyopathy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Obrador, D.; Ballester, M.; Carrio, I.

    1989-05-01

    Monoclonal antimyosin antibody studies were undertaken to assess the presence of myocardial uptake in patients with chronic idiopathic dilated cardiomyopathy. Three groups were studied: 17 patients with chronic (greater than 12 months) idiopathic dilated cardiomyopathy, 12 patients with a large, poorly contracting left ventricle not due to dilated cardiomyopathy (control patients) and 8 normal individuals. The patients in the cardiomyopathy and control groups showed a similar degree of clinical and functional impairment. Imaging was undertaken 48 h after antimyosin injection. The heart/lung ratio of antimyosin uptake was used to assess the results. The mean ratio in the cardiomyopathy group wasmore » 1.83 +/- 0.36 (range 1.40 to 2.80), a value significantly higher than that obtained in the control patients without cardiomyopathy (mean 1.46 +/- 0.04, range 1.38 to 1.50) or normal subjects (mean 1.46 +/- 0.13, range 1.31 to 1.6) (p less than 0.01). No difference in the ratio was noted between the normal subjects and control patients. Abnormal antimyosin uptake was seen in 12 (70%) of the 17 patients with cardiomyopathy and in only 1 (8%) of the 12 control patients. Positive monoclonal antimyosin antibody studies are highly prevalent in chronic idiopathic dilated cardiomyopathy.« less

  1. Cell models of arrhythmogenic cardiomyopathy: advances and opportunities

    PubMed Central

    Stadiotti, Ilaria; Perrucci, Gianluca L.; Tondo, Claudio; Pompilio, Giulio

    2017-01-01

    ABSTRACT Arrhythmogenic cardiomyopathy is a rare genetic disease that is mostly inherited as an autosomal dominant trait. It is associated predominantly with mutations in desmosomal genes and is characterized by the replacement of the ventricular myocardium with fibrous fatty deposits, arrhythmias and a high risk of sudden death. In vitro studies have contributed to our understanding of the pathogenic mechanisms underlying this disease, including its genetic determinants, as well as its cellular, signaling and molecular defects. Here, we review what is currently known about the pathogenesis of arrhythmogenic cardiomyopathy and focus on the in vitro models that have advanced our understanding of the disease. Finally, we assess the potential of established and innovative cell platforms for elucidating unknown aspects of this disease, and for screening new potential therapeutic agents. This appraisal of in vitro models of arrhythmogenic cardiomyopathy highlights the discoveries made about this disease and the uses of these models for future basic and therapeutic research. PMID:28679668

  2. Diabetic Cardiomyopathy and Metabolic Remodeling of the Heart

    PubMed Central

    Battiprolu, Pavan K.; Lopez-Crisosto, Camila; Wang, Zhao V.; Nemchenko, Andriy; Lavandero, Sergio; Hill, Joseph A.

    2012-01-01

    The incidence and prevalence of diabetes mellitus are each increasing rapidly in societies around the globe. The majority of patients with diabetes succumb ultimately to heart disease, much of which stems from atherosclerotic disease and hypertension. However, the diabetic milieu is itself intrinsically noxious to the heart, and cardiomyopathy can develop independent of elevated blood pressure or coronary artery disease. This process, termed diabetic cardiomyopathy, is characterized by significant changes in the physiology, structure, and mechanical function of the heart. Presently, therapy for patients with diabetes focuses largely on glucose control, and attention to the heart commences with the onset of symptoms. When the latter develops, standard therapy for heart failure is applied. However, recent studies highlight that specific elements of the pathogenesis of diabetic heart disease are unique, raising the prospect of diabetes-specific therapeutic intervention. Here, we review recently unveiled insights into the pathogenesis of diabetic cardiomyopathy and associated metabolic remodeling with an eye toward identifying novel targets with therapeutic potential. PMID:23123443

  3. Novel inhibitor candidates of TRPV2 prevent damage of dystrophic myocytes and ameliorate against dilated cardiomyopathy in a hamster model.

    PubMed

    Iwata, Yuko; Katayama, Yoshimi; Okuno, Yasushi; Wakabayashi, Shigeo

    2018-03-06

    Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a principal candidate for abnormal Ca 2+ -entry pathways, which is a potential target for therapy of muscular dystrophy and cardiomyopathy. Here, an in silico drug screening and the following cell-based screening to measure the TRPV2 activation were carried out in HEK293 cells expressing TRPV2 using lead compounds (tranilast or SKF96365) and off-patent drug stocks. We identified 4 chemical compounds containing amino-benzoyl groups and 1 compound (lumin) containing an ethylquinolinium group as candidate TRPV2 inhibitors. Three of these compounds inhibited Ca 2+ entry through both mouse and human TRPV2, with IC 50 of less than 10 μM, but had no apparent effect on other members of TRP family such as TRPV1 and TRPC1. Particularly, lumin inhibited agonist-induced TRPV2 channel activity at a low dose. These compounds inhibited abnormally increased Ca 2+ influx and prevented stretch-induced skeletal muscle damage in cultured myocytes from dystrophic hamsters (J2N-k). Further, they ameliorated cardiac dysfunction, and prevented disease progression in vivo in the same J2N-k hamsters developing dilated cardiomyopathy as well as muscular dystrophy. The identified compounds described here are available as experimental tools and represent potential treatments for patients with cardiomyopathy and muscular dystrophy.

  4. Novel inhibitor candidates of TRPV2 prevent damage of dystrophic myocytes and ameliorate against dilated cardiomyopathy in a hamster model

    PubMed Central

    Iwata, Yuko; Katayama, Yoshimi; Okuno, Yasushi; Wakabayashi, Shigeo

    2018-01-01

    Transient receptor potential cation channel, subfamily V, member 2 (TRPV2) is a principal candidate for abnormal Ca2+-entry pathways, which is a potential target for therapy of muscular dystrophy and cardiomyopathy. Here, an in silico drug screening and the following cell-based screening to measure the TRPV2 activation were carried out in HEK293 cells expressing TRPV2 using lead compounds (tranilast or SKF96365) and off-patent drug stocks. We identified 4 chemical compounds containing amino-benzoyl groups and 1 compound (lumin) containing an ethylquinolinium group as candidate TRPV2 inhibitors. Three of these compounds inhibited Ca2+ entry through both mouse and human TRPV2, with IC50 of less than 10 μM, but had no apparent effect on other members of TRP family such as TRPV1 and TRPC1. Particularly, lumin inhibited agonist-induced TRPV2 channel activity at a low dose. These compounds inhibited abnormally increased Ca2+ influx and prevented stretch-induced skeletal muscle damage in cultured myocytes from dystrophic hamsters (J2N-k). Further, they ameliorated cardiac dysfunction, and prevented disease progression in vivo in the same J2N-k hamsters developing dilated cardiomyopathy as well as muscular dystrophy. The identified compounds described here are available as experimental tools and represent potential treatments for patients with cardiomyopathy and muscular dystrophy. PMID:29581825

  5. Targeted Analysis of Whole Genome Sequence Data to Diagnose Genetic Cardiomyopathy

    DOE PAGES

    Golbus, Jessica R.; Puckelwartz, Megan J.; Dellefave-Castillo, Lisa; ...

    2014-09-01

    Background—Cardiomyopathy is highly heritable but genetically diverse. At present, genetic testing for cardiomyopathy uses targeted sequencing to simultaneously assess the coding regions of more than 50 genes. New genes are routinely added to panels to improve the diagnostic yield. With the anticipated $1000 genome, it is expected that genetic testing will shift towards comprehensive genome sequencing accompanied by targeted gene analysis. Therefore, we assessed the reliability of whole genome sequencing and targeted analysis to identify cardiomyopathy variants in 11 subjects with cardiomyopathy. Methods and Results—Whole genome sequencing with an average of 37× coverage was combined with targeted analysis focused onmore » 204 genes linked to cardiomyopathy. Genetic variants were scored using multiple prediction algorithms combined with frequency data from public databases. This pipeline yielded 1-14 potentially pathogenic variants per individual. Variants were further analyzed using clinical criteria and/or segregation analysis. Three of three previously identified primary mutations were detected by this analysis. In six subjects for whom the primary mutation was previously unknown, we identified mutations that segregated with disease, had clinical correlates, and/or had additional pathological correlation to provide evidence for causality. For two subjects with previously known primary mutations, we identified additional variants that may act as modifiers of disease severity. In total, we identified the likely pathological mutation in 9 of 11 (82%) subjects. We conclude that these pilot data demonstrate that ~30-40× coverage whole genome sequencing combined with targeted analysis is feasible and sensitive to identify rare variants in cardiomyopathy-associated genes.« less

  6. Enhanced Skeletal Muscle Expression of EcSOD Mitigates Streptozotocin-Induced Diabetic Cardiomyopathy by Reducing Oxidative Stress and Aberrant Cell Signaling

    PubMed Central

    Call, Jarrod A.; Chain, Kristopher H.; Martin, Kyle S.; Lira, Vitor A.; Okutsu, Mitsuharu; Zhang, Mei; Yan, Zhen

    2015-01-01

    Background Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM). Methods and Results Exercise training promotes EcSOD expression in skeletal muscle and provides protection against DCM; however, it is not known if enhanced EcSOD expression in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle-specific EcSOD transgenic mice (TG) are protected from cardiac hypertrophy, fibrosis and dysfunction under the condition of type-1 diabetes induced by STZ injection. We also show that both exercise training and muscle-specific transgenic expression of EcSOD result in elevated EcSOD protein in the blood and heart without increased transcription in the heart, suggesting enhanced expression of EcSOD from skeletal muscle redistributes to the heart. Importantly, cardiac tissue in TG mice displayed significantly reduced oxidative stress, aberrant cell signaling and inflammatory cytokine expression compared with wild type mice under the same diabetic condition. Conclusions Enhanced expression of EcSOD in skeletal muscle is sufficient to mitigate STZ-induced DCM through attenuation of oxidative stress, aberrant cell signaling and inflammation, suggesting a cross-organ mechanism by which exercise training improves cardiac function in diabetes. PMID:25504759

  7. Ischemic Preconditioning Blunts Muscle Damage Responses Induced by Eccentric Exercise.

    PubMed

    Franz, Alexander; Behringer, Michael; Harmsen, Jan-Frieder; Mayer, Constantin; Krauspe, Rüdiger; Zilkens, Christoph; Schumann, Moritz

    2018-01-01

    Ischemic preconditioning (IPC) is known to reduce muscle damage induced by ischemia and reperfusion injury during surgery. Because of similarities between the pathophysiological formation of ischemia and reperfusion injury and eccentric exercise-induced muscle damage (EIMD), as characterized by an intracellular accumulation of Ca, an increased production of reactive oxygen species, and increased proinflammatory signaling, the purpose of the present study was to investigate whether IPC performed before eccentric exercise may also protect against EIMD. Nineteen healthy men were matched to an eccentric-only (ECC; n = 9) or eccentric proceeded by IPC group (IPC + ECC; n = 10). The exercise protocol consisted of bilateral biceps curls (3 × 10 repetitions at 80% of the concentric one-repetition maximum). In IPC + ECC, IPC was applied bilaterally at the upper arms by a tourniquet (200 mm Hg) immediately before the exercise (3 × 5 min of occlusion, separated by 5 min of reperfusion). Creatine kinase (CK), arm circumference, subjective pain (visual analog scale score), and radial displacement (tensiomyography, maximal radial displacement) were assessed before IPC, preexercise, postexercise, and 20 min, 2 h, 24 h, 48 h, and 72 h postexercise. CK differed from baseline only in ECC at 48 h (P < 0.001) and 72 h (P < 0.001) postexercise. After 24, 48, and 72 h, CK was increased in ECC compared with IPC + ECC (between groups: 24 h, P = 0.004; 48 h, P < 0.001; 72 h, P < 0.001). The visual analog scale score was significantly higher in ECC at 24-72 h postexercise when compared with IPC + ECC (between groups: all P values < 0.001). The maximal radial displacement was decreased on all postexercise days in ECC (all P values < 0.001) but remained statistically unchanged in IPC + ECC (between groups: P < 0.01). These findings indicate that IPC performed before a bout of eccentric exercise of the elbow flexors blunts EIMD and exercise-induced pain while maintaining the contractile

  8. Diabetic cardiomyopathy: Where are we 40 years later?

    PubMed Central

    Sharma, Vijay; McNeill, John H

    2006-01-01

    Diabetic cardiomyopathy is a cardiac disease that arises as a result of the diabetic state, independent of vascular or valvular pathology. It manifests initially as asymptomatic diastolic dysfunction, which progresses to symptomatic heart failure. The compliance of the heart wall is decreased and contractile function is impaired. The pathophysiology is incompletely understood, but appears to be initiated both by hyperglycemia and changes in cardiac metabolism. These changes induce oxidative stress and activate a number of secondary messenger pathways, leading to cardiac hypertrophy, fibrosis and cell death. Alterations in contractile proteins and intracellular ions impair excitation-contraction coupling, while decreased autonomic responsiveness and autonomic neuropathy impair its regulation. Extensive structural abnormalities also occur, which have deleterious mechanical and functional consequences. PMID:16568154

  9. Targets for therapy in sarcomeric cardiomyopathies

    PubMed Central

    Tardiff, Jil C.; Carrier, Lucie; Bers, Donald M.; Poggesi, Corrado; Ferrantini, Cecilia; Coppini, Raffaele; Maier, Lars S.; Ashrafian, Houman; Huke, Sabine; van der Velden, Jolanda

    2015-01-01

    To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use. As perturbations in the heart are stage-specific, proper timing of drug treatment is essential to prevent initiation and progression of cardiac disease in mutation carrier individuals. In this review, we emphasize potential novel therapies which may prevent, delay, or even reverse hypertrophic cardiomyopathy caused by sarcomeric gene mutations. These include corrections of genetic defects, altered sarcomere function, perturbations in intracellular ion homeostasis, and impaired myocardial energetics. PMID:25634554

  10. Far Forward Battlefield Telemedicine: Ultrasonic Guidance in Diagnosis and Emergency Therapeutics

    DTIC Science & Technology

    2008-03-01

    Thomas JD, Garcia MJ. Planimetric assessment of anatomic valve area overestimates effective orifice area in bicuspid aortic stenosis . J Am Soc...Popovic ZB, Khot UN, Novaro GM, Casas F, Greenberg NL, Garcia MJ, Francis GS, Thomas JD. Effects of sodium nitroprusside in aortic stenosis ...aneurysmal ventricles,3 aortic regurgitation,4 hypertrophic cardiomyopathy,5 mitral regurgitation,6 ischemic cardiomyopathy,7 and dilated cardiomyopathy

  11. Nonsurgical reduction of the interventricular septum in patients with hypertrophic cardiomyopathy.

    PubMed

    Shamim, Waqar; Yousufuddin, Mohammed; Wang, Duolao; Henein, Michael; Seggewiss, Hubert; Flather, Marcus; Coats, Andrew J S; Sigwart, Ulrich

    2002-10-24

    In patients with hypertrophic cardiomyopathy and obstruction of the left ventricular outflow tract, nonsurgical reduction of the septum is a treatment option when medical therapy has failed. We investigated the long-term effects of nonsurgical reduction of the septum on functional capacity and electrocardiographic and echocardiographic characteristics. Sixty-four consecutive patients with hypertrophic cardiomyopathy and a mean (+/-SD) age of 48.5+/-17.2 years underwent nonsurgical reduction of the septum by injection of ethanol into the septal perforator branch of the left anterior descending coronary artery. These patients were assessed by exercise testing, electrocardiography, and resting and dobutamine (stress-induced) echocardiography after a mean period of 3.0+/-1.3 years. At follow-up, patients had significant improvements in New York Heart Association class, peak oxygen consumption (from 18.4+/-5.8 to 30.0+/-4.4 ml per kilogram of body weight per minute, P<0.001), and left ventricular outflow tract gradients (resting gradient, from 64+/-36 to 16+/-15 mm Hg; P<0.001; stress-induced gradient, from 132+/-34 to 45+/-19 mm Hg; P<0.001). Procedure-related complications included right bundle-branch block in all patients, complete heart block in 31 patients (48 percent), and significant increases in QRS and corrected QT intervals. Seventeen patients (27 percent) required permanent pacing. R-wave amplitude was significantly decreased (from 32+/-8 to 17+/-7 mV, P<0.001). The dimensions of the left ventricular cavity increased, and the interventricular septal thickness was reduced. Nonsurgical septal reduction leads to sustained improvements in both subjective and objective measures of exercise capacity in association with a persistent reduction in resting and stress-induced left ventricular outflow tract gradients. It is also associated with a high incidence of procedure-related complete heart block, however, often requiring permanent pacing. Copyright 2002

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

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2017-01-01

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

  14. Impact of microRNA-134 on neural cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by targeting HSPA12B.

    PubMed

    Chi, Wenying; Meng, Fanjun; Li, Yan; Li, Peilong; Wang, Guizhi; Cheng, Hong; Han, Song; Li, Junfa

    2014-12-10

    As a newly discovered member of the HSP70 family, heat shock protein A12B (HSPA12B) is involved in brain ischemic injury. According to our previous study, microRNA-134 (miR-134) could target HSPA12B by binding to its 3'-untranslated region (UTR). However, the regulation of miR-134 on HSPA12B and their role in protecting neuronal cells from ischemic injury are unclear. In this study, the miR-134 expression level was manipulated, and the HSPA12B protein levels were also determined in oxygen-glucose deprivation (OGD)-treated primary cultured neuronal cells in vitro and mouse brain after middle cerebral artery occlusion (MCAO)-induced ischemic stroke in vivo. The results showed that miR-134 expression levels increased in primary cultured neuronal cells and mouse brain from 12h to 7 day reoxygenation/reperfusion after 1h OGD or 1h MCAO treatment. miR-134 overexpression promoted neuronal cell death and apoptosis by decreasing HSPA12B protein levels. Conversely, downregulating miR-134 reduced neuronal cell death and apoptosis by enhancing HSPA12B protein levels. Also, HSPA12B siRNA could block miR-134 inhibitor-mediated neuroprotection against OGD-induced neuronal cell injury in vitro. Taken together, miR-134 might influence neuronal cell survival against ischemic injury in primary cultured neuronal cells and mouse brain with ischemic stroke by negatively modulating HSPA12B protein expression in a posttranscriptional manner. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Animal and in silico models for the study of sarcomeric cardiomyopathies

    PubMed Central

    Duncker, Dirk J.; Bakkers, Jeroen; Brundel, Bianca J.; Robbins, Jeff; Tardiff, Jil C.; Carrier, Lucie

    2015-01-01

    Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise ‘knock-in’ models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy. PMID:25600962

  16. Cardiovascular Nursing on Human Genomics: What do cardiovascular nurses need to know about congestive heart failure?

    PubMed Central

    Frazier, Lorraine; Wung, Shu-Fen; Sparks, Elizabeth; Eastwood, Cathy

    2009-01-01

    This paper presents the main causes of heart failure (HF) and an update on the genetics studies on each cause. The review includes a delineation of the etiology and fundamental pathophysiology of HF and provides rational for treatment for the patient and family. Various cardiomyopathies are discussed, includingprimary cardiomyopathies, mixed cardiomyopathies, cardiomyopathies that involve altered cardiac muscle along with generalized multi-organ disorders, and various cardiovascular conditions, such as coronary artery disease (ischemic cardiomyopathy) and hypertension (hypertensive cardiomyopathy).1 A brief review of pharmacogenetics and HF is presented. The application of the genetic components of cardiomyopathy and pharmacogenetics is included to enhance cardiovascular nursing care. PMID:19737164

  17. An unusual ST-segment elevation: apical hypertrophic cardiomyopathy shows the ace up its sleeve.

    PubMed

    de Santis, Francesco; Pergolini, Amedeo; Zampi, Giordano; Pero, Gaetano; Pino, Paolo Giuseppe; Minardi, Giovanni

    2013-01-01

    Apical hypertrophic cardiomyopathy is part of the broad clinical and morphologic spectrum of hypertrophic cardiomyopathy. We report a patient with electrocardiographic abnormalities in whom acute coronary syndrome was excluded and apical hypertrophic cardiomyopathy was demonstrated by careful differential diagnosis. Copyright © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  18. Blockade of N-methyl-D-aspartate Receptors May Protect against Ischemic Damage in the Brain

    NASA Astrophysics Data System (ADS)

    Simon, R. P.; Swan, J. H.; Griffiths, T.; Meldrum, B. S.

    1984-11-01

    In rats ischemia of the forebrain induced by a 30-minute occlusion of the carotid artery, followed by 120 minutes of arterial reperfusion, produced ischemic lesions of selectively vulnerable pyramidal cells in both hippocampi. Focal microinfusion into the dorsal hippocampus of 2-amino-7-phosphonoheptanoic acid, an antagonist of excitation at the N-methyl-d-asparate-preferring receptor, before ischemia was induced protected against the development of ischemic damage. It is proposed that excitatory neurotransmission plays an important role in selective neuronal loss due to cerebral ischemia.

  19. Takotsubo cardiomyopathy associated with Miller-Fisher syndrome.

    PubMed

    Gill, Dalvir; Liu, Kan

    2017-07-01

    51-year-old female who presented with progressive paresthesia, numbness of the lower extremities, double vision, and trouble walking. Physical exam was remarkable for areflexia, and ptosis. Her initial EKG showed nonspecific ST segment changes and her Troponin T was elevated to 0.41ng/mL which peaked at 0.66ng/mL. Echocardiogram showed a depressed left ventricular ejection fraction to 35% with severely hypokinetic anterior wall and left ventricular apex was severely hypokinetic. EMG nerve conduction study showed severely decreased conduction velocity and prolonged distal latency in all nerves consistent with demyelinating disease. She was treated with 5days of intravenous immunoglobulin therapy to which she showed significant improvement in strength in her lower extremities. Echocardiogram repeated 4days later showing an improved left ventricular ejection fraction of 55% and no left ventricular wall motion abnormalities. Takotsubo cardiomyopathy is a rare complication of Miller-Fisher syndrome and literature review did not reveal any cases. Miller-Fisher syndrome is an autoimmune process that affects the peripheral nervous system causing autonomic dysfunction which may involve the heart. Due to significant autonomic dysfunction in Miller-Fisher syndrome, it could lead to arrhythmias, blood pressure changes, acute coronary syndrome and myocarditis, Takotsubo cardiomyopathy can be difficult to distinguish. The treatment of Takotsubo cardiomyopathy is supportive with beta-blockers and angiotensin-converting enzyme inhibitors are recommended until left ventricle ejection fraction improvement. Takotsubo cardiomyopathy is a rare complication during the acute phase of Miller-Fisher syndrome and must be distinguished from autonomic dysfunction as both diagnoses have different approaches to treatment. Published by Elsevier Inc.

  20. GSK-3β inhibitor TWS119 attenuates rtPA-induced hemorrhagic transformation and activates the Wnt/β-catenin signaling pathway after acute ischemic stroke in rats.

    PubMed

    Wang, Wei; Li, Mingchang; Wang, Yuefei; Li, Qian; Deng, Gang; Wan, Jieru; Yang, Qingwu; Chen, Qianxue; Wang, Jian

    2016-12-01

    Hemorrhagic transformation (HT) is a devastating complication for patients with acute ischemic stroke who are treated with tissue plasminogen activator (tPA). It is associated with high morbidity and mortality, but no effective treatments are currently available to reduce HT risk. Therefore, methods to prevent HT are urgently needed. In this study, we used TWS119, an inhibitor of glycogen synthase kinase 3β (GSK-3β), to evaluate the role of the Wnt/β-catenin signaling pathway in recombinant tPA (rtPA)-induced HT. Sprague-Dawley rats were subjected to a middle cerebral artery occlusion (MCAO) model of ischemic stroke and then were administered rtPA, rtPA combined with TWS119, or vehicle at 4 h. The animals were sacrificed 24 h after infarct induction. Rats treated with rtPA showed evident HT, had more severe neurologic deficit, brain edema, and blood-brain barrier breakdown, and had larger infarction volume than did the vehicle group. Rats treated with TWS119 had significantly improved outcomes compared with those of rats treated with rtPA alone. In addition, Western blot analysis showed that TWS119 increased the protein expression of β-catenin, claudin-3, and ZO-1 while suppressing the expression of GSK-3β. These results suggest that TWS119 reduces rtPA-induced HT and attenuates blood-brain barrier disruption, possibly through activation of the Wnt/β-catenin signaling pathway. This study provides a potential therapeutic strategy to prevent tPA-induced HT after acute ischemic stroke.

  1. Restrictive Cardiomyopathy Associated With Long-Term Use of Hydroxychloroquine for Systemic Lupus Erythematosus.

    PubMed

    Sabato, Leah A; Mendes, Lisa A; Cox, Zachary L

    2017-10-01

    Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient's cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy.

  2. Determination of multidirectional myocardial deformations in cats with hypertrophic cardiomyopathy by using two-dimensional speckle-tracking echocardiography.

    PubMed

    Suzuki, Ryohei; Mochizuki, Yohei; Yoshimatsu, Hiroki; Teshima, Takahiro; Matsumoto, Hirotaka; Koyama, Hidekazu

    2017-12-01

    Objectives Hypertrophic cardiomyopathy, a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of myocardial deformation with two-dimensional speckle-tracking echocardiography in cats with various stages of hypertrophic cardiomyopathy has not yet been reported. This study was designed to measure quantitatively multidirectional myocardial deformations of cats with hypertrophic cardiomyopathy. Methods Thirty-two client-owned cats with hypertrophic cardiomyopathy and 14 healthy cats serving as controls were enrolled and underwent assessment of myocardial deformation (peak systolic strain and strain rate) in the longitudinal, radial and circumferential directions. Results Longitudinal and radial deformations were reduced in cats with hypertrophic cardiomyopathy, despite normal systolic function determined by conventional echocardiography. Cats with severely symptomatic hypertrophic cardiomyopathy also had lower peak systolic circumferential strain, in addition to longitudinal and radial strain. Conclusions and relevance Longitudinal and radial deformation may be helpful in the diagnosis of hypertrophic cardiomyopathy. Additionally, the lower circumferential deformation in cats with severe hypertrophic cardiomyopathy may contribute to clinical findings of decompensation, and seems to be related to severe cardiac clinical signs. Indices of multidirectional myocardial deformations by two-dimensional speckle-tracking echocardiography may be useful markers and help to distinguish between cats with hypertrophic cardiomyopathy and healthy cats. Additionally, they may provide more detailed assessment of contractile function in cats with hypertrophic cardiomyopathy.

  3. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy.

    PubMed

    Das, Subhash K; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B; Hajjar, Roger J; Dyck, Jason R B; Kassiri, Zamaneh; Oudit, Gavin Y

    2015-12-07

    Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca(2+) homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca(2+) homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload.

  4. Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy

    PubMed Central

    Das, Subhash K.; Wang, Wang; Zhabyeyev, Pavel; Basu, Ratnadeep; McLean, Brent; Fan, Dong; Parajuli, Nirmal; DesAulniers, Jessica; Patel, Vaibhav B.; Hajjar, Roger J.; Dyck, Jason R. B.; Kassiri, Zamaneh; Oudit, Gavin Y.

    2015-01-01

    Iron-overload cardiomyopathy is a prevalent cause of heart failure on a world-wide basis and is a major cause of mortality and morbidity in patients with secondary iron-overload and genetic hemochromatosis. We investigated the therapeutic effects of resveratrol in acquired and genetic models of iron-overload cardiomyopathy. Murine iron-overload models showed cardiac iron-overload, increased oxidative stress, altered Ca2+ homeostasis and myocardial fibrosis resulting in heart disease. Iron-overload increased nuclear and acetylated levels of FOXO1 with corresponding inverse changes in SIRT1 levels in the heart corrected by resveratrol therapy. Resveratrol, reduced the pathological remodeling and improved cardiac function in murine models of acquired and genetic iron-overload at varying stages of iron-overload. Echocardiography and hemodynamic analysis revealed a complete normalization of iron-overload mediated diastolic and systolic dysfunction in response to resveratrol therapy. Myocardial SERCA2a levels were reduced in iron-overloaded hearts and resveratrol therapy restored SERCA2a levels and corrected altered Ca2+ homeostasis. Iron-mediated pro-oxidant and pro-fibrotic effects in human and murine cardiomyocytes and cardiofibroblasts were suppressed by resveratrol which correlated with reduction in iron-induced myocardial oxidative stress and myocardial fibrosis. Resveratrol represents a clinically and economically feasible therapeutic intervention to reduce the global burden from iron-overload cardiomyopathy at early and chronic stages of iron-overload. PMID:26638758

  5. Efficient attenuation of Friedreich's ataxia (FRDA) cardiomyopathy by modulation of iron homeostasis-human induced pluripotent stem cell (hiPSC) as a drug screening platform for FRDA.

    PubMed

    Lee, Yee-Ki; Lau, Yee-Man; Ng, Kwong-Man; Lai, Wing-Hon; Ho, Shu-Leong; Tse, Hung-Fat; Siu, Chung-Wah; Ho, Philip Wing-Lok

    2016-01-15

    Friedreich's ataxia (FRDA), a recessive neurodegenerative disorder commonly associated with hypertrophic cardiomyopathy, is caused by silencing of the frataxin (FXN) gene encoding the mitochondrial protein involved in iron-sulfur cluster biosynthesis. Application of our previously established FRDA human induced pluripotent stem cell (hiPSC) derived cardiomyocytes model as a platform to assess the efficacy of treatment with either the antioxidant coenzyme Q10 analog, idebenone (IDE) or the iron chelator, deferiprone (DFP), which are both under clinical trial. DFP was able to more significantly suppress synthesis of reactive oxygen species (ROS) than IDE at the dosages of 25 μM and 10nM respectively which agreed with the reduced rate of intracellular accumulation of iron by DFP treatment from 25 to 50 μM. With regard to cardiac electrical-contraction (EC) coupling function, decay velocity of calcium handling kinetics in FRDA-hiPSC-cardiomyocytes was significantly improved by DFP treatment but not by IDE. Further mechanistic studies revealed that DFP also modulated iron induced mitochondrial stress as reflected by mitochondria network disorganization and decline level of respiratory chain protein, succinate dehydrogenase (CxII) and cytochrome c oxidase (COXIV). In addition, iron-response protein (IRP-1) regulatory loop was overridden by DFP as reflected by resumed level of ferritin (FTH) back to basal level and the attenuated transferrin receptor (TSFR) mRNA level suppression thereby reducing further iron uptake. DFP modulated iron homeostasis in FRDA-hiPSC-cardiomyocytes and effectively relieved stress-stimulation related to cardiomyopathy. The resuming of redox condition led to the significantly improved cardiac prime events, cardiac electrical-coupling during contraction. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. Changing outcomes after heart transplantation in patients with amyloid cardiomyopathy.

    PubMed

    Davis, Margot K; Lee, Peter H U; Witteles, Ronald M

    2015-05-01

    Amyloid cardiomyopathy (ACM) is associated with a poor prognosis. Previous reports have suggested unfavorable post-heart transplant (HT) survival in this population compared with other HT recipients. Data from the United Network for Organ Sharing (UNOS) registry were used to study outcomes among ACM patients undergoing HT in the modern era (Era 2, 2008 to 2013) as compared with the historical era (Era 1, 1987 to 2007). One hundred eighty-eight ACM patients underwent primary single-organ HT. Ninety-seven patients (51.6%) were transplanted in Era 1 and 91 (48.4%) in Era 2. ACM patients undergoing HT in Era 2 were older (p < 0.0001), had higher body mass index (p = 0.008) and longer ischemic times (p = 0.02), and were more likely to be African-American (p < 0.0001), UNOS Status 1A (p < 0.0001), male (p = 0.01) and highly sensitized (p < 0.0001) compared with those in Era 1. Compared with patients with other etiologies of restrictive cardiomyopathy (RCM; n = 339 in Era 1, n = 164 in Era 2), adjusted hazard ratios (HRs) for post-HT mortality of ACM were 2.08 (p < 0.0001) in Era 1 and 1.22 (p = not statistically significant) in Era 2. Adjusted HRs for mortality of ACM vs all other diagnoses (n = 36,334 in Era 1, n = 9,225 in Era 2) were 1.84 (p < 0.0001) in Era 1 and 1.38 (p = NS) in Era 2. Although post-HT survival did not change with time among non-ACM RCM patients, post-HT mortality was lower in Era 2 compared with Era 1 among ACM patients (HR 0.49, p = 0.03). Although historically associated with inferior survival, post-HT outcomes in ACM patients in the modern era are now approaching those of non-ACM patients. Changes in patients' demographics suggest that this may be related to improved patient selection, including an increased proportion of patients with transthyretin ACM. HT should be considered for appropriate candidates with ACM. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. Histopathology of motor cortex in an experimental focal ischemic stroke in mouse model.

    PubMed

    de Oliveira, Juçara Loli; Crispin, Pedro di Tárique Barreto; Duarte, Elisa Cristiana Winkelmann; Marloch, Gilberto Domingos; Gargioni, Rogério; Trentin, Andréa Gonçalves; Alvarez-Silva, Marcio

    2014-05-01

    Experimental ischemia results in cortical brain lesion followed by ischemic stroke. In this study, focal cerebral ischemia was induced in mice by occlusion of the middle cerebral artery. We studied cortical layers I, II/III, V and VI in the caudal forelimb area (CFA) and medial agranular cortex (AGm) from control and C57BL/6 mice induced with ischemic stroke. Based on our analysis of CFA and AGm motor cortex, significant differences were observed in the numbers of neurons, astrocytes and microglia in the superficial II/III and deep V cortical layers. Cellular changes were more prominent in layer V of the CFA with nuclear pyknosis, chromatin fragmentation, necrosis and degeneration, as well as, morphological evidence of apoptosis, mainly in neurons. As result, the CFA was more severely impaired than the AGm in this focal cerebral ischemic model, as evidenced by the proliferation of astrocytes, potentially resulting in neuroinflammation by microglia-like cells. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Normotensive cardiomyopathy and malignant hypertension in phaeochromocytoma

    PubMed Central

    Shapiro, L. M.; Trethowan, N.; Singh, S. P.

    1982-01-01

    A patient with two different presentations of phaeochromocytoma is described. She initially presented with normal blood pressure and heart failure following a prolonged feverish prodrome. A provisional diagnosis of myocarditis or early congestive cardiomyopathy was made and she improved with digoxin and diuretics. Eighteen months later, after a period of normotension free from heart failure, she developed malignant hypertension with recurrence of heart failure. A phaeochromocytoma was surgically removed, with return to normal of blood pressure and cardiac status. It would seem that the initial presentation of the phaeochromocytoma was a catecholamine-induced myocarditis without hypertension and this resolved with the subsequent development of malignant hypertension. The possible mechanisms responsible for this are discussed and it is concluded that phaeochromocytoma should be considered in patients who have heart failure and persistent features of myocarditis. PMID:7100023

  9. Changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy using UPLC/Q-TOF/MS analysis.

    PubMed

    Dong, Shifen; Zhang, Rong; Liang, Yaoyue; Shi, Jiachen; Li, Jiajia; Shang, Fei; Mao, Xuezhou; Sun, Jianning

    2017-01-01

    Diabetic cardiomyopathy (DCM) is a serious cardiac dysfunction induced by changes in the structure and contractility of the myocardium that are initiated in part by alterations in energy substrates. The underlying mechanisms of DCM are still under controversial. The observation of lipids, especially lipidomics profiling, can provide an insight into the know the biomarkers of DCM. The aim of our research was to detect changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy. Diabetic cardiomyopathy was induced by feeding a high-sucrose/fat diet (HSFD) for 28 weeks and streptozotocin (30 mg/kg, intraperitoneally). The ultra-high-performance liquid chromatography (UPLC) coupled to quadruple time-of flight (QTOF) mass spectrometer was used to acquire and analyze the lipidomics profiling of myocardial tissue. Meanwhile, parameters of cardiac function were collected using cardiac catheterization, and the cardiac index was calculated, and fasting blood glucose and lipid levels were measured by an ultraviolet spectrophotometric method. We detected 3023 positive ion peaks and 300 negative ion peaks. Levels of phosphatidylcholine (PC) (22:6/18:2), PC (22:6/18:1), PC (20:4/16:1), PC (16:1/18:3), phosphatidylethanolamine (PE) (20:4/18:2), and PE (20:4/16:0) were down-regulated, and PC (20:2/18:2), PC (18:0/16:0), and PC (20:4/18:0) were up-regulated in DCM model rats, when compared with control rats. Cardiac functions signed as values of left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure and maximal decreasing velocity of left ventricular pressure were injured by 21-44%, and the cardiac index was increased by 25%, and fasting blood glucose and lipids were increased by 34-368%. Meanwhile, the cardiac lipid-related biomarkers have significant correlation with changes of cardiac function and cardiac index. UPLC/Q-TOF/MS analysis data suggested changes of some potential lipid biomarkers in the development of

  10. Transient Ischemic Attack

    MedlinePlus Videos and Cool Tools

    Transient Ischemic Attack TIA , or transient ischemic attack, is a "mini stroke" that occurs when a blood ... The only difference between a stroke and TIA is that with TIA the blockage is transient (temporary). ...

  11. Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

    PubMed

    Santangeli, Pasquale; Zado, Erica S; Supple, Gregory E; Haqqani, Haris M; Garcia, Fermin C; Tschabrunn, Cory M; Callans, David J; Lin, David; Dixit, Sanjay; Hutchinson, Mathew D; Riley, Michael P; Marchlinski, Francis E

    2015-12-01

    Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO-EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56±44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on β-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs. © 2015 American Heart Association, Inc.

  12. Optical-resolution photoacoustic microscopy of ischemic stroke

    NASA Astrophysics Data System (ADS)

    Hu, Song; Gonzales, Ernie; Soetikno, Brian; Gong, Enhao; Yan, Ping; Maslov, Konstantin; Lee, Jin-Moo; Wang, Lihong V.

    2011-03-01

    A major obstacle in understanding the mechanism of ischemic stroke is the lack of a tool to noninvasively or minimally invasively monitor cerebral hemodynamics longitudinally. Here, we applied optical-resolution photoacoustic microscopy (OR-PAM) to longitudinally study ischemic stroke induced brain injury in a mouse model with transient middle cerebral artery occlusion (MCAO). OR-PAM showed that, during MCAO, the average hemoglobin oxygen saturation (sO2) values of feeder arteries and draining veins within the stroke core region dropped ~10% and ~34%, respectively. After reperfusion, arterial sO2 recovered back to the baseline; however, the venous sO2 increased above the baseline value by ~7%. Thereafter, venous sO2 values were close to the arterial sO2 values, suggesting eventual brain tissue infarction.

  13. Cardiovascular magnetic resonance in the evaluation of hypertrophic and infiltrative cardiomyopathies.

    PubMed

    O'Hanlon, Rory; Pennell, Dudley J

    2009-07-01

    There is often considerable phenotypic overlap in hypertrophic and infiltrative cardiomyopathies. This overlap creates difficulties, when using routine imaging modalities, in arriving at a conclusive diagnosis. Cardiovascular magnetic resonance (CMR) can make diagnosis easier and more certain. Used with gadolinium contrast agent for tissue characterization, CMR offers a superior field of view and temporal resolution, enabling clinicians to make more confident assessments of etiology. CMR may also be a useful modality for stratifying risk and monitoring treatment responses over time in patients with hypertrophic or infiltrative cardiomyopathies. This article highlights the role of CMR in the assessment and, if relevant, the risk stratification of hypertrophic and infiltrative cardiomyopathies.

  14. Renal Hypoxia and Dysoxia After Reperfusion of the Ischemic Kidney

    PubMed Central

    Legrand, Matthieu; Mik, Egbert G; Johannes, Tanja; Payen, Didier; Ince, Can

    2008-01-01

    Ischemia is the most common cause of acute renal failure. Ischemic-induced renal tissue hypoxia is thought to be a major component in the development of acute renal failure in promoting the initial tubular damage. Renal oxygenation originates from a balance between oxygen supply and consumption. Recent investigations have provided new insights into alterations in oxygenation pathways in the ischemic kidney. These findings have identified a central role of microvascular dysfunction related to an imbalance between vasoconstrictors and vasodilators, endothelial damage and endothelium–leukocyte interactions, leading to decreased renal oxygen supply. Reduced microcirculatory oxygen supply may be associated with altered cellular oxygen consumption (dysoxia), because of mitochondrial dysfunction and activity of alternative oxygen-consuming pathways. Alterations in oxygen utilization and/or supply might therefore contribute to the occurrence of organ dysfunction. This view places oxygen pathways’ alterations as a potential central player in the pathogenesis of acute kidney injury. Both in regulation of oxygen supply and consumption, nitric oxide seems to play a pivotal role. Furthermore, recent studies suggest that, following acute ischemic renal injury, persistent tissue hypoxia contributes to the development of chronic renal dysfunction. Adaptative mechanisms to renal hypoxia may be ineffective in more severe cases and lead to the development of chronic renal failure following ischemia-reperfusion. This paper is aimed at reviewing the current insights into oxygen transport pathways, from oxygen supply to oxygen consumption in the kidney and from the adaptation mechanisms to renal hypoxia. Their role in the development of ischemia-induced renal damage and ischemic acute renal failure are discussed. PMID:18488066

  15. Sex and Gender Differences in Myocarditis and Dilated Cardiomyopathy

    PubMed Central

    Fairweather, DeLisa; Cooper, Leslie T; Blauwet, Lori A

    2014-01-01

    Heart failure due to nonischemic dilated cardiomyopathy (DCM) contributes significantly to the global burden of cardiovascular disease. Myocarditis is in turn a major cause of acute dilated cardiomyopathy in both men and women. However, recent clinical and experimental evidence suggests that the pathogenesis and prognosis of DCM differ between the sexes. This seminar provides a contemporary perspective on the immune mediators of myocarditis, including interdependent elements of the innate and adaptive immune response. The heart's acute response to injury is influenced by sex hormones that appear to determine the subsequent risk of chronic DCM. Preliminary data suggest additional genetic variations may account for some of the differences in epidemiology, left ventricular recovery and survival between men and women. We highlight the gaps in our knowledge regarding the management of women with acute DCM and discuss emerging therapies, including bromocriptine for the treatment of peripartum cardiomyopathy. PMID:23158412

  16. Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.

    PubMed

    Brito, Dulce; Miltenberger-Miltenyi, Gabriel; Vale Pereira, Sónia; Silva, Doroteia; Diogo, António Nunes; Madeira, Hugo

    2012-09-01

    Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown. Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients. Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease. Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling. Copyright © 2011 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  17. [Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy].

    PubMed

    Liu, X H; Ding, W W; Han, L; Liu, X R; Xiao, Y Y; Yang, J; Mo, Y

    2017-10-02

    Objective: To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy. Method: Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database. Result: Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy. Conclusion: Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

  18. Non-Invasive Monitoring of CNS MHC-I Molecules in Ischemic Stroke Mice.

    PubMed

    Xia, Jing; Zhang, Ying; Zhao, Huanhuan; Wang, Jie; Gao, Xueren; Chen, Jinpeng; Fu, Bo; Shen, Yuqing; Miao, Fengqin; Zhang, Jianqiong; Teng, Gaojun

    2017-01-01

    Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. The expression of major histocompatibility complex class I (MHC-I) molecules in the central nervous system, which are silenced under normal physiological conditions, have been reported to be induced by injury stimulation. The purpose of this study was to determine whether MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke and to assess whether a high-affinity peptide specific for MHC-I molecules could be applied in the near-infrared imaging of cerebral ischemic mice. Quantitative real-time PCR and Western blotting were used to detect the expression of MHC-I molecules in two mouse models of cerebral ischemic stroke and an in vitro model of ischemia. The NetMHC 4.0 server was used to screen a high-affinity peptide specific for mouse MHC-I molecules. The Rosetta program was used to identify the specificity and affinity of the screened peptide (histocompatibility-2 binding peptide, H2BP). The results demonstrated that MHC-I molecules could serve as molecular targets for the acute phase of ischemic stroke. Cy5.5-H2BP molecular probes could be applied in the near-infrared imaging of cerebral ischemic mice. Research on the expression of MHC-I molecules in the acute phase after ischemia and MHC-I-targeted imaging may not only be helpful for understanding the mechanism of ischemic and hypoxic brain injury and repair but also has potential application value in the imaging of ischemic stroke.

  19. Prolonged Delirium Secondary to Hypoxic-ischemic Encephalopathy Following Cardiac Arrest

    PubMed Central

    Yogaratnam, Jegan; Jacob, Rajesh; Naik, Sandeep; Magadi, Harish

    2013-01-01

    Hypoxic-ischemic brain injury encompasses a complex constellation of pathophysiological and cellular brain injury induced by hypoxia, ischemia, cytotoxicity, or combinations of these mechanisms and can result in poor outcomes including significant changes in personality and cognitive impairments in memory, cognition, and attention. We report a case of a male patient with normal premorbid functioning who developed prolonged delirium following hypoxic-ischemic brain insults subsequent to cardiac arrest. The case highlights the importance of adopting a multidisciplinary treatment approach involving the coordinated care of medical and nursing teams to optimise management of patients suffering from such a debilitating organic brain syndrome. PMID:23678354

  20. I(f) current inhibitor ivabradine in patients with idiopathic dilated cardiomyopathy: Impact on the exercise tolerance and quality of life.

    PubMed

    Abdel-Salam, Zainab; Rayan, Mona; Saleh, Ayman; Abdel-Barr, Mohamed G; Hussain, Mohamed; Nammas, Wail

    2015-01-01

    Evidence supported a beneficial effect of ivabradine on clinical outcome of patients with systolic heart failure, and a sinus heart rate (HR) ≥ 70 bpm. We explored the effect of ivabradine, vs. placebo, added to evidence-based treatment on exercise tolerance and quality of life in patients with idiopathic dilated cardiomyopathy. We enrolled 43 consecutive patients with dilated cardiomyopathy of no apparent cause, a left ventricular ejection fraction (LVEF) < 40%, New York Heart Association class ≥ II, sinus HR ≥ 70 bpm, and background evidence-based anti-failure medications. Ischemic heart disease was ruled out. Patients were randomized (1:1) to receive ivabradine or placebo. Ivabradine was titrated up gradually till 7.5 mg twice daily, or a HR < 60 bpm, and continued for 3 months. Symptom-limited exercise tolerance test was performed, and quality of life was assessed by the Minnesota Living With Heart Failure Questionnaire at 0, and 3 months. Forty-three patients were randomized to ivabradine (n = 20), or placebo (n = 23). Mean age was 50.8 ± 14.5 years (53.5% males). Mean HR was 85 ± 12 bpm, and mean LVEF was 32 ± 6%. Mean dose of carvedilol was 31.2% of the target dose. Baseline HR, blood pressure, exercise tolerance, Minnesota questionnaire score, and left ventricular systolic function were comparable between the two groups (p > 0.05 for all). At 3 months, mean dose of ivabradine was 6.8 mg bid. Ivabradine-treated patients had a lower HR, and improved left ventricular dimensions and systolic function, versus placebo-treated ones (p < 0.05 for all). HR dropped by a mean of 14 bpm in the ivabradine group, corrected for placebo. Both exercise tolerance, and Minnesota questionnaire score were better in the ivabradine group (p < 0.05 both). Ivabradine was well-tolerated. In symptomatic patients with idiopathic dilated cardiomyopathy, the addition of ivabradine, vs. placebo, to evidence-based treatment, reduced HR, and improved functional capacity, at short

  1. Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6 (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1 Signaling

    PubMed Central

    Chen, Zhidan; Li, Yang; Wang, Ying; Qian, Juying; Ma, Hong; Wang, Xiang; Jiang, Guoliang; Liu, Ming; An, Yanpeng; Ma, Leilei; Kang, Le; Jia, Jianguo; Yang, Chunjie; Zhang, Guoping; Chen, Ying; Gao, Wei; Fu, Mingqiang; Huang, Zheyong; Tang, Huiru; Zhu, Yichun; Ge, Junbo; Gong, Hui; Zou, Yunzeng

    2018-01-01

    Low density lipoprotein receptor-related protein 6 (LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. Methods: We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot. Tamoxifen-inducible cardiac-specific LRP6 knockout mouse was constructed. Hemodynamic and echocardiographic analyses were performed to these mice. Results: Cardiac LRP6 expression was dramatically decreased in patients with end-stage dilated cardiomyopathy (DCM) compared to control group. Tamoxifen-inducible cardiac-specific LRP6 knockout mice developed acute heart failure and mitochondrial dysfunction with reduced survival. Proteomic analysis suggests the fatty acid metabolism disorder involving peroxisome proliferator-activated receptors (PPARs) signaling in the LRP6 deficient heart. Accumulation of mitochondrial targeting to autophagosomes and lipid droplet were observed in LRP6 deletion hearts. Further analysis revealed cardiac LRP6 deletion suppressed autophagic degradation and fatty acid utilization, coinciding with activation of dynamin-related protein 1 (Drp1) and downregulation of nuclear TFEB (Transcription factor EB). Injection of Mdivi-1, a Drp1 inhibitor, not only promoted nuclear translocation of TFEB, but also partially rescued autophagic degradation, improved PPARs signaling, and attenuated cardiac dysfunction induced by cardiac specific LRP6 deletion. Conclusions: Cardiac LRP6 deficiency greatly suppressed autophagic degradation and fatty acid utilization, and subsequently leads to lethal dilated cardiomyopathy and cardiac dysfunction through activation of Drp1 signaling. It suggests that heart failure progression may be attenuated by therapeutic modulation of LRP6 expression. PMID:29344294

  2. Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

    PubMed

    Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

    2016-09-15

    Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy.

    PubMed

    Trojan, Meghan K Borden; Biederman, Robert W

    2017-07-01

    Healthcare professionals are faced with challenging decisions regarding patient evaluation and management on a daily basis. Once a diagnosis is made, additional challenges include how to proceed with the management. Here, we present an eighty-two-year-old female who was incidentally diagnosed with the apical variant of hypertrophic cardiomyopathy on a transthoracic echocardiogram. She was found to have newly diagnosed atrial fibrillation, but was otherwise asymptomatic from a cardiomyopathy standpoint. No specific guidelines exist for this patient population. Therefore, how does one proceed with the management of an asymptomatic patient with the apical variant of hypertrophic cardiomyopathy? © 2017, Wiley Periodicals, Inc.

  4. Targeted Expression of Catalase to Mitochondria Protects Against Ischemic Myopathy in High-Fat Diet–Fed Mice

    PubMed Central

    Ryan, Terence E.; Schmidt, Cameron A.; Green, Thomas D.; Spangenburg, Espen E.; Neufer, P. Darrell

    2016-01-01

    Patients with type 2 diabetes respond poorly to treatments for peripheral arterial disease (PAD) and are more likely to present with the most severe manifestation of the disease, critical limb ischemia. The underlying mechanisms linking type 2 diabetes and the severity of PAD manifestation are not well understood. We sought to test whether diet-induced mitochondrial dysfunction and oxidative stress would increase the susceptibility of the peripheral limb to hindlimb ischemia (HLI). Six weeks of high-fat diet (HFD) in C57BL/6 mice was insufficient to alter skeletal muscle mitochondrial content and respiratory function or the size of ischemic lesion after HLI, despite reducing blood flow. However, 16 weeks of HFD similarly decreased ischemic limb blood flow, but also exacerbated limb tissue necrosis, increased the myopathic lesion size, reduced muscle regeneration, attenuated muscle function, and exacerbated ischemic mitochondrial dysfunction. Mechanistically, mitochondrial-targeted overexpression of catalase prevented the HFD-induced ischemic limb necrosis, myopathy, and mitochondrial dysfunction, despite no improvement in limb blood flow. These findings demonstrate that skeletal muscle mitochondria are a critical pathological link between type 2 diabetes and PAD. Furthermore, therapeutically targeting mitochondria and oxidant burden is an effective strategy to alleviate tissue loss and ischemic myopathy during PAD. PMID:27284110

  5. National experience with long-term use of the wearable cardioverter defibrillator in patients with cardiomyopathy.

    PubMed

    Lamichhane, Madhab; Gardiner, Joseph C; Bianco, Nicole R; Szymkiewicz, Steven J; Thakur, Ranjan K

    2017-01-01

    The wearable cardioverter defibrillator (WCD) is generally used for short periods of sudden cardiac death (SCD) risk; circumstances may occasionally result in prolonged use (over 1 year). The aim of this study was to determine the benefits and risks of prolonged use in patients with systolic heart failure (HF). ZOLL's post-market US database included adult patients (≥18 years) with ischemic and/or non-ischemic cardiomyopathy (ICM, NICM) and at least 1 year of use. Cox-regression was used to identify factors associated with survival with WCD use, and reasons for stopping use were entered as time-dependent factors. Among 220 patients, age (mean ± SD) 55.4 ± 14.8 years, WCD use 451.4 ± 289.9 days, and 67.3 % were male and their left ventricle ejection fraction (EF) averaged 20.9 ± 7.2 %. Eighty-nine (40.5 %) were continuing WCD use at the last follow-up. Thirty-six (16.4 %) and 56 (25.5 %) patients discontinued WCD use because of EF recovery and implantable cardioverter (ICD) implantation, respectively. Nine patients (4.1 %) received appropriate shock therapy for 13 episodes of sustained ventricular tachyarrhythmia with 12 (92.3 %) successful shocks. One patient died of refractory ventricular fibrillation. One patient died from sinus bradycardia transitioning to asystole. Eight patients (3.6 %) had nine episodes of non-fatal inappropriate shocks. Long-term use of the WCD is safe and effective. Recovery of EF was seen in significant number of patients even after 1 year of WCD use.

  6. Agonist of inward rectifier K+ channels enhances the protection of ischemic postconditioning in isolated rat hearts.

    PubMed

    Liao, Z; Feng, Z; Long, C

    2014-07-01

    Selective inhibition of inward rectifier K + channels could abolish the protection mediated by ischemic preconditioning, but the roles of these channels in ischemic postconditioning have not been well characterized. Our study aims to evaluate the effect of inward rectifier K + channels on the protection induced by ischemic postconditioning. Langendorff-perfused rat hearts (n=8 per group) were split into four groups: postconditioning hearts (IPO group); ischemic postconditioning with BaCl 2 hearts (PB group); ischemic postconditioning with zacopride hearts (PZ group); and without ischemic postconditioning (CON group). After suffering 30 minutes of global ischemia, groups IPO, PB and PZ went through 10 seconds of ischemic postconditioning with three different perfusates: respectively, Krebs-Henseleit buffer (IPO group); 20 μmol/L BaCl 2 (antagonist of the channel, PB group); 1 μmol/L zacopride (agonist of the channel, PZ group). At the end of reperfusion, the myocardial performance was better preserved in the PZ group than the other three groups. The PB group showed no significant differences from the CON group. Our study has shown that the I K1 channel agonist zacopride is associated with the enhancement of ischemic postconditioning. © The Author(s) 2014.

  7. Exogenous Gene Transmission of Isocitrate Dehydrogenase 2 Mimics Ischemic Preconditioning Protection.

    PubMed

    Kolb, Alexander L; Corridon, Peter R; Zhang, Shijun; Xu, Weimin; Witzmann, Frank A; Collett, Jason A; Rhodes, George J; Winfree, Seth; Bready, Devin; Pfeffenberger, Zechariah J; Pomerantz, Jeremy M; Hato, Takashi; Nagami, Glenn T; Molitoris, Bruce A; Basile, David P; Atkinson, Simon J; Bacallao, Robert L

    2018-04-01

    Ischemic preconditioning confers organ-wide protection against subsequent ischemic stress. A substantial body of evidence underscores the importance of mitochondria adaptation as a critical component of cell protection from ischemia. To identify changes in mitochondria protein expression in response to ischemic preconditioning, we isolated mitochondria from ischemic preconditioned kidneys and sham-treated kidneys as a basis for comparison. The proteomic screen identified highly upregulated proteins, including NADP+-dependent isocitrate dehydrogenase 2 (IDH2), and we confirmed the ability of this protein to confer cellular protection from injury in murine S3 proximal tubule cells subjected to hypoxia. To further evaluate the role of IDH2 in cell protection, we performed detailed analysis of the effects of Idh2 gene delivery on kidney susceptibility to ischemia-reperfusion injury. Gene delivery of IDH2 before injury attenuated the injury-induced rise in serum creatinine ( P <0.05) observed in controls and increased the mitochondria membrane potential ( P <0.05), maximal respiratory capacity ( P <0.05), and intracellular ATP levels ( P <0.05) above those in controls. This communication shows that gene delivery of Idh2 can confer organ-wide protection against subsequent ischemia-reperfusion injury and mimics ischemic preconditioning. Copyright © 2018 by the American Society of Nephrology.

  8. Dilated Cardiomyopathy: Genetic Determinants and Mechanisms.

    PubMed

    McNally, Elizabeth M; Mestroni, Luisa

    2017-09-15

    Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subtypes. Moreover, cascade genetic testing in family members can identify those who are at risk or with early stage disease, offering the opportunity for early intervention. This review will address diagnosis and management of DCM, including the role of genetic evaluation. We will also overview distinct genetic pathways linked to DCM and their pathogenetic mechanisms. Historically, cardiac morphology has been used to classify cardiomyopathy subtypes. Determining genetic variants is emerging as an additional adjunct to help further refine subtypes of DCM, especially where arrhythmia risk is increased, and ultimately contribute to clinical management. © 2017 American Heart Association, Inc.

  9. Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats.

    PubMed

    Liang, Zhongshu; Leo, Sunnar; Wen, Helin; Ouyang, Mao; Jiang, Weihong; Yang, Kan

    2015-05-13

    Triptolide treatment leads to an improvement in Diabetic Cardiomyopathy (DCM) in streptozotocin-induced diabetic rat model. DCM is characterized by abnormal cardiac energy metabolism. We hypothesized that triptolide ameliorated cardiac metabolic abnormalities in DCM. We proposed (31)P nuclear magnetic resonance ((31)P NMR) spectrometry method for assessing cardiac energy metabolism in vivo and evaluating the effect of triptolide treatment in DCM rats. Six weeks triptolide treatment was conducted on streptozotocin-induced diabetic rats with dose of 100, 200 or 400 μg/kg/day respectively. Sex- and age-matched non-diabetic rats were used as control group. Cardiac chamber dimension and function were determined with echocardiography. Whole heart preparations were perfused with Krebs-Henseleit buffer and (31)P NMR spectroscopy was performed. Cardiac p38 Mitogen Activating Protein Kinase (MAPK) was measured using real time PCR and western blot analysis. In diabetic rats, cardiac mass index was significantly higher, where as cardiac EF was lower than control group. (31)P NMR spectroscopy showed that ATP and pCr concentrations in diabetic groups were also remarkably lower than control group. Compared to non-treated diabetic rats, triptolide-treated diabetic groups showed remarkable lower cardiac mass index and higher EF, ATP, pCr concentrations, and P38 MAPK expressions. Best improvement was seen in group treated with Triptolide with dose 200 μg/kg/day. (31)P NMR spectroscopy enables assessment of cardiac energy metabolism in whole heart preparations. It detects energy metabolic abnormalities in DCM hearts. Triptolide therapy improves cardiac function and increases cardiac energy metabolism at least partly through upregulation of MAPK signaling transduction.

  10. Divergent effects of adrenaline in human induced pluripotent stem cell-derived cardiomyocytes obtained from hypertrophic cardiomyopathy

    PubMed Central

    Prajapati, Chandra

    2018-01-01

    ABSTRACT Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disease that affects the heart muscle with diverse clinical outcomes. HCM can cause sudden cardiac death (SCD) during or immediately after mild to rigorous physical activity in young patients. However, the mechanism causing SCD as a result of exercise remains unknown, but exercise-induced ventricular arrhythmias are thought to be responsible for this fatal consequence. To understand the disease mechanism behind HCM in a better way, we generated patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from HCM patients carrying either the MYBPC3-Gln1061X or TPM1-Asp175Asn mutation. We extensively investigated the effects of low to high concentrations of adrenaline on action potential characteristics, and the occurrence of arrhythmias in the presence of various concentrations of adrenaline and in wash-out condition. We classified and quantified different types of arrhythmias observed in hiPSC-CMs, and found that the occurrence of arrhythmias was dependent on concentrations of adrenaline and positions of mutations in genes causing HCM. In addition, we observed ventricular tachycardia types of arrhythmias in hiPSC-CMs carrying the TPM1-Asp175Asn mutation. We additionally examined the antiarrhythmic potency of bisoprolol in HCM-specific hiPSC-CMs. However, bisoprolol could not reduce the occurrence of arrhythmias during administration or during the wash-out condition of adrenaline in HCM-specific hiPSC-CMs. Our study demonstrates hiPSC-CMs as a promising tool for studying HCM. The experimental design used in this study could be suitable and beneficial for studying other components and drugs related to cardiac disease in general. PMID:29361520

  11. iPSC-derived cardiomyocytes reveal abnormal TGFβ signaling in left ventricular non-compaction cardiomyopathy

    PubMed Central

    Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D.; Shukla, Praveen; Abilez, Oscar J.; Churko, Jared M.; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M.; Snyder, Michael P.; Bernstein, Daniel; Wu, Joseph C.

    2016-01-01

    Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC. PMID:27642787

  12. Prevalence of dilated cardiomyopathy in Doberman Pinschers in various age groups.

    PubMed

    Wess, G; Schulze, A; Butz, V; Simak, J; Killich, M; Keller, L J M; Maeurer, J; Hartmann, K

    2010-01-01

    Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Seven hundred and seventy-five examinations in 412 Doberman Pinschers. Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24-hour ECG (Holter) examination. A cut-off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.

  13. Acute myocardial infarction and stress cardiomyopathy following the Christchurch earthquakes.

    PubMed

    Chan, Christina; Elliott, John; Troughton, Richard; Frampton, Christopher; Smyth, David; Crozier, Ian; Bridgman, Paul

    2013-01-01

    Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36 am on 4 September 2010, magnitude 7.1 and at 12:51 pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region's only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations. Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others. There was a significant increase in overall admissions (p<0.003), ST elevation myocardial infarction (p<0.016), and non cardiac chest pain (p<0.022) in the first 2 weeks following the early morning September earthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6-6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44-2.62). Statistical analysis showed this to be a significant difference between the earthquakes (p<0.05). The early morning September earthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events.

  14. Pharmacokinetic Study of Piracetam in Focal Cerebral Ischemic Rats.

    PubMed

    Paliwal, Pankaj; Dash, Debabrata; Krishnamurthy, Sairam

    2018-04-01

    Cerebral ischemia affects hepatic enzymes and brain permeability extensively. Piracetam was investigated up to phase III of clinical trials and there is lack of data on brain penetration in cerebral ischemic condition. Thus, knowledge of the pharmacokinetics and brain penetration of piracetam during ischemic condition would aid to improve pharmacotherapeutics in ischemic stroke. Focal cerebral ischemia was induced by middle cerebral artery occlusion for 2 h in male Wistar rats followed by reperfusion. After 24 h of middle cerebral artery occlusion or 22 h of reperfusion, piracetam was administered for pharmacokinetic, brain penetration, and pharmacological experiments. In pharmacokinetic study, blood samples were collected at different time points after 200-mg/kg (oral) and 75-mg/kg (intravenous) administration of piracetam through right external jugular vein cannulation. In brain penetration study, the cerebrospinal fluid, systemic blood, portal blood, and brain samples were collected at pre-designated time points after 200-mg/kg oral administration of piracetam. In a separate experiment, the pharmacological effect of the single oral dose of piracetam in middle cerebral artery occlusion was assessed at a dose of 200 mg/kg. All the pharmacokinetic parameters of piracetam including area under curve (AUC 0-24 ), maximum plasma concentration (C max ), time to reach the maximum plasma concentration (t max ), elimination half-life (t 1/2 ), volume of distribution (V z ), total body clearance, mean residence time, and bioavailability were found to be similar in ischemic stroke condition except for brain penetration. Piracetam exposure (AUC 0-2 ) in brain and CSF were found to be 2.4- and 3.1-fold higher, respectively, in ischemic stroke compared to control rats. Piracetam significantly reduced infarct volume by 35.77% caused by middle cerebral artery occlusion. There was no change in the pharmacokinetic parameters of piracetam in the ischemic stroke model except for

  15. Hypertrophic Cardiomyopathy Associated with Mid-cavity Obstruction and High Left Intraventricular Pressure

    PubMed Central

    A. Bejiqi, Ramush; J. Retkoceri, Ragip; Sh. Bejiqi, Hana

    2011-01-01

    We report a case of a child, with a rare form of the idiopathic hypertrophic cardiomyopathy, associated with mid-cavity obstruction and high intraventricular peak pressure. Cardiomyopathy, diagnosed antenataly, was followed postnataly and, despite of a lot echocardiographic findings - the growing, development and clinical signs are minimal. PMID:23407799

  16. Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

    PubMed Central

    Lara-Celador, I.; Goñi-de-Cerio, F.; Alvarez, Antonia; Hilario, Enrique

    2013-01-01

    One of the most important causes of brain injury in the neonatal period is a perinatal hypoxic-ischemic event. This devastating condition can lead to long-term neurological deficits or even death. After hypoxic-ischemic brain injury, a variety of specific cellular mechanisms are set in motion, triggering cell damage and finally producing cell death. Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury. After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury, various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes. Among them, the endocannabinoid system emerges as a natural system of neuroprotection. The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury, acting as a natural neuroprotectant. The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury, and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury. PMID:25206720

  17. Clinical Outcomes for Peripartum Cardiomyopathy in North America

    PubMed Central

    McNamara, Dennis M.; Elkayam, Uri; Alharethi, Rami; Damp, Julie; Hsich, Eileen; Ewald, Gregory; Modi, Kalgi; Alexis, Jeffrey D.; Ramani, Gautam V.; Semigran, Marc J.; Haythe, Jennifer; Markham, David W.; Marek, Josef; Gorcsan, John; Wu, Wen-Chi; Lin, Yan; Halder, Indrani; Pisarcik, Jessica; Cooper, Leslie T.; Fett, James D.

    2017-01-01

    BACKGROUND Peripartum cardiomyopathy (PPCM) remains a major cause of maternal morbidity and mortality. OBJECTIVES This study sought to prospectively evaluate recovery of the left ventricular ejection fraction (LVEF) and clinical outcomes in the multicenter IPAC (Investigations of Pregnancy Associated Cardiomyopathy) study. METHODS We enrolled and followed 100 women with PPCM through 1 year post-partum. The LVEF was assessed by echocardiography at baseline and at 2, 6, and 12 months post-partum. Survival free from major cardiovascular events (death, transplantation, or left ventricular [LV] assist device) was determined. Predictors of outcome, particularly race, parameters of LV dysfunction (LVEF), and remodeling (left ventricular end-diastolic diameter [LVEDD]) at presentation, were assessed by univariate and multivariate analyses. RESULTS The cohort was 30% black, 65% white, 5% other; the mean patient age was 30 ± 6 years; and 88% were receiving beta-blockers and 81% angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The LVEF at study entry was 0.35 ± 0.10, 0.51 ± 0.11 at 6 months, and 0.53 ± 0.10 at 12 months. By 1 year, 13% had experienced major events or had persistent severe cardiomyopathy with an LVEF <0.35, and 72% achieved an LVEF ≥0.50. An initial LVEF <0.30 (p = 0.001), an LVEDD ≥6.0 cm (p < 0.001), black race (p = 0.001), and presentation after 6 weeks postpartum (p = 0.02) were associated with a lower LVEF at 12 months. No subjects with both a baseline LVEF <0.30 and an LVEDD ≥6.0 cm recovered by 1 year post-partum, whereas 91% with both a baseline LVEF ≥0.30 and an LVEDD <6.0 cm recovered (p < 0.00001). CONCLUSIONS In a prospective cohort with PPCM, most women recovered; however, 13% had major events or persistent severe cardiomyopathy. Black women had more LV dysfunction at presentation and at 6 and 12 months post-partum. Severe LV dysfunction and greater remodeling at study entry were associated with less recovery

  18. Mitral stenosis and hypertrophic obstructive cardiomyopathy: An unusual combination.

    PubMed

    Hong, Joonhwa; Schaff, Hartzell V; Ommen, Steve R; Abel, Martin D; Dearani, Joseph A; Nishimura, Rick A

    2016-04-01

    Systolic anterior motion of mitral valve (MV) leaflets is a main pathophysiologic feature of left ventricular outflow tract (LVOT) obstruction in hypertrophic obstructive cardiomyopathy. Thus, restricted leaflet motion that occurs with MV stenosis might be expected to minimize outflow tract obstruction related to systolic anterior motion. From January 1993 through February 2015, we performed MV replacement and septal myectomy in 12 patients with mitral stenosis and hypertrophic obstructive cardiomyopathy at Mayo Clinic Hospital in Rochester, Minn. Preoperative data, echocardiographic images, operative records, and postoperative outcomes were reviewed. Mean (standard deviation) age was 70 (7.6) years. Preoperative mean (standard deviation) maximal LVOT pressure gradient was 75.0 (35.0) mm Hg; MV gradient was 13.7 (2.8) mm Hg. From echocardiographic images, 4 mechanisms of outflow tract obstruction were identified: systolic anterior motion without severe limitation in MV leaflet excursion, severe limitation in MV leaflet mobility with systolic anterior motion at the tip of the MV anterior leaflet, septal encroachment toward the LVOT, and MV displacement toward the LVOT by calcification. Mitral valve replacement and extended septal myectomy relieved outflow gradients in all patients, with no death or serious morbidity. Patients with mitral stenosis and hypertrophic obstructive cardiomyopathy have multiple LVOT obstruction mechanisms, and MV replacement may not be adequate treatment. We favor septal myectomy and MV replacement in this complex subset of hypertrophic obstructive cardiomyopathy. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  19. Migraine prophylaxis, ischemic depolarizations and stroke outcomes in mice

    PubMed Central

    Eikermann-Haerter, Katharina; Lee, Jeong Hyun; Yalcin, Nilufer; Yu, Esther Sori; Daneshmand, Ali; Wei, Ying; Zheng, Yi; Can, Anil; Sengul, Buse; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Ayata, Cenk

    2014-01-01

    Background and Purpose Migraine with aura is an established stroke risk factor, and excitatory mechanisms such as spreading depression are implicated in the pathogenesis of both migraine and stroke. Spontaneous spreading depression waves originate within the peri-infarct tissue and exacerbate the metabolic mismatch during focal cerebral ischemia. Genetically enhanced spreading depression susceptibility facilitates anoxic depolarizations and peri-infarct spreading depressions and accelerates infarct growth, suggesting that susceptibility to spreading depression is a critical determinant of vulnerability to ischemic injury. Because chronic treatment with migraine prophylactic drugs suppresses spreading depression susceptibility, we tested whether migraine prophylaxis can also suppress ischemic depolarizations and improve stroke outcome. Methods We measured the cortical susceptibility to spreading depression and ischemic depolarizations, and determined tissue and neurological outcome after middle cerebral artery occlusion in wild type and familial hemiplegic migraine type 1 knock-in mice treated with vehicle, topiramate or lamotrigine daily for 7 weeks or as a single dose shortly before testing. Results Chronic treatment with topiramate or lamotrigine reduces the susceptibility to KCl- or electrical stimulation-induced spreading depressions as well as ischemic depolarizations in both wild-type and familial hemiplegic migraine type 1 mutant mice. Consequently, both tissue and neurological outcomes are improved. Notably, treatment with a single dose of either drug is ineffective. Conclusions These data underscore the importance of hyperexcitability as a mechanism for increased stroke risk in migraineurs, and suggest that migraine prophylaxis may not only prevent migraine attacks but also protect migraineurs against ischemic injury. PMID:25424478

  20. Neovascularization of Ischemic Myocardium by Newly Isolated Tannins Prevents Cardiomyocyte Apoptosis and Improves Cardiac Function

    PubMed Central

    Gu, Xuemei; Cheng, Lei; Chueng, Winghong L; Yao, Xinsheng; Liu, Hongwei; Qi, Guoqing; Li, Ming

    2006-01-01

    During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases. PMID:17380192

  1. Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

    NASA Astrophysics Data System (ADS)

    Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

    2016-04-01

    Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

  2. Alcohol septal ablation in obstructive acromegalic hypertrophic cardiomyopathy - a first case report.

    PubMed

    Viveiros Monteiro, André; Fiarresga, António; Cacela, Duarte; de Sousa, Lídia; Ramos, Ruben; Galrinho, Ana; Branco, Luísa; Cruz Ferreira, Rui

    2016-09-01

    Acromegaly is a rare disease, mostly caused by a growth hormone (GH)-secreting benign pituitary tumor, with an increased production of GH and insulin-like growth factor 1 (IGF-1). Cardiovascular complications are common and are associated with cardiomyocyte apoptosis and concentric cardiac hypertrophy. Suppression of GH and IGF-1 appears to improve cardiac function only in the short term, with little or no decrease in left ventricular mass or improvement in cardiac function after prolonged treatment. Alcohol septal ablation (ASA) has emerged as a minimally invasive alternative to septal myectomy, with significant improvement in symptoms, gradients and left ventricular remodeling. In this report, we describe the case of a 73-year-old woman with acromegaly due to a pituitary adenoma diagnosed and treated surgically at the age of 38 but with recurrence and reoperation at the age of 50. She was referred to our cardiology department due to a three-month history of progressively worsening exercise-induced dyspnea and orthopnea under optimal medical therapy. Echocardiography and magnetic resonance imaging revealed severe basal hypertrophy of the interventricular septum (19 mm), dynamic left ventricular outflow tract obstruction with a gradient of 70 mmHg at rest and 120 mmHg with Valsalva maneuver, and systolic anterior movement (SAM). Genetic testing excluded the most frequent forms of familial hypertrophic cardiomyopathy. ASA was performed with injection of 2 cc of alcohol in the first septal branch of the left coronary artery, without complications. At one-year reassessment, significant clinical and echocardiographic improvement was noted, with disappearance of SAM. To our knowledge, there have been no previously reported cases of ASA in hypertrophic cardiomyopathy due to acromegaly. We report a case of successful ASA in acromegalic cardiomyopathy. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Role of decoy molecules in neuronal ischemic preconditioning

    PubMed Central

    Panneerselvam, Mathivadhani; Patel, Piyush M.; Roth, David M.; Kidd, Michael W.; Chin-Lee, Blake; Head, Brian P.; Niesman, Ingrid R.; Inoue, Satoki; Patel, Hemal H.; Davis, Daniel P.

    2011-01-01

    Decoy receptors bind with TNF related apoptosis inducing ligands (TRAIL) but do not contain the cytoplasmic domains necessary to transduce apoptotic signals. We hypothesized that decoy receptors may confer neuronal protection against lethal ischemia after ischemic preconditioning (IPC). Mixed cortical neurons were exposed to IPC one day prior to TRAIL treatment or lethal ischemia. IPC increased decoy receptor but reduced death receptor expression compared to lethal ischemia. IPC-induced increase in decoy receptor expression was reduced by prior treatment with CAPE, a nuclear factor-kappa B inhibitor (NFκB). Expression of decoy molecules, dependent on NFκB, may mediate neuronal survival induced by IPC. PMID:21315738

  4. Risk factors and outcomes of sepsis-induced myocardial dysfunction and stress-induced cardiomyopathy in sepsis or septic shock

    PubMed Central

    Jeong, Han Saem; Lee, Tae Hyub; Bang, Cho Hee; Kim, Jong-Ho; Hong, Soon Jun

    2018-01-01

    Abstract While both sepsis-induced myocardial dysfunction (SIMD) and stress-induced cardiomyopathy (SICMP) are common in patients with sepsis, the pathogenesis of the 2 diseases is different, and they require different treatment strategies. Thus, we aimed to investigate risk factors and outcomes between the 2 diseases. This retrospective study enrolled patients diagnosed with sepsis or septic shock, admitted to intensive care unit via emergency department in Korea University Anam Hospital, and who underwent transthoracic echocardiography within the first 24 hours of admission. In all, 25 patients with SIMD and 27 patients with SICMP were enrolled. Chronic obstructive pulmonary disease and a history of heart failure (HF) were more prevalent in both the SIMD and SICMP groups than in the control group. In the SIMD and SICMP groups, levels of inflammatory cytokines were similar. Serum troponin level was significantly elevated in the SICMP and SIMD group compared to the control group. N-terminal pro-brain natriuretic peptide (NT pro-BNP) level was significantly elevated in the SIMD group compared to the SICMP group or control group. The in-hospital mortality rate in the SIMD and SICMP group was about 40%, showing increased trends compared with the control group. The in-hospital mortality rate was significantly increased in SIMD group with EF<30% than in SICMP group with EF<30%. In multiple logistic regression analysis, a past history of diabetes mellitus (DM) and HF was significantly associated with the incidence of SIMD. Younger age, elevated levels of NT pro-BNP, and positive result of blood culture also showed significant odds ratio regard to the occurrence of SIMD. However, only elevated lactate and troponin level were positively associated with the incidence of SICMP. The SIMD and SICMP had different risk factors. The risk factors of SIMD were younger age, history of DM, history of HF, elevated NT pro-BNP, and positive result of blood culture. The elevated levels

  5. Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke.

    PubMed

    Chen, Bin; Wang, Guoxiang; Li, Weiwei; Liu, Weilin; Lin, Ruhui; Tao, Jing; Jiang, Min; Chen, Lidian; Wang, Yun

    2017-02-15

    Ischemic stroke, the second leading cause of death worldwide, leads to excessive glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and massive influx of calcium (Ca 2+ ), which may activate calpain and caspase-3, resulting in cellular damage and death. Memantine is an uncompetitive NMDAR antagonist with low-affinity/fast off-rate. We investigated the potential mechanisms through which memantine protects against ischemic stroke in vitro and in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to establish an experimental model of ischemic stroke. The neuroprotective effects of memantine on ischemic rats were evaluated by neurological deficit scores and infarct volumes. The activities of calpain and caspase-3, and expression levels of microtubule-associated protein-2 (MAP2) and postsynaptic density-95 (PSD95) were determined by Western blotting. Additionally, Nissl staining and immunostaining were performed to examine brain damage, cell apoptosis, and neuronal loss induced by ischemia. Our results show that memantine could significantly prevent ischemic stroke-induced neurological deficits and brain infarct, and reduce ATP depletion-induced neuronal death. Moreover, memantine markedly suppressed the activation of the calpain-caspase-3 pathway and cell apoptosis, and consequently, attenuated brain damage and neuronal loss in MCAO rats. These results provide a molecular basis for the role of memantine in reducing neuronal apoptosis and preventing neuronal damage, suggesting that memantine may be a promising therapy for stroke patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The characteristics of stress cardiomyopathy in an ethnically heterogeneous population.

    PubMed

    Nascimento, Francisco O; Santana, Orlando; Perez-Caminero, Margarita; Benjo, Alexandre M

    2011-01-01

    Stress cardiomyopathy is a cardiac syndrome that is characterized by transient left ventricular systolic dysfunction in the absence of obstructive coronary artery disease. Its epidemiology has been described in homogeneous Asian, Caucasian and Black populations, but its characteristics in heterogeneous populations are poorly understood. Our aim was to assess the characteristics of stress cardiomyopathy in a heterogeneous population that included a large percentage of Hispanics. We reviewed 59 consecutive cases of stress cardiomyopathy that were confirmed by coronary angiography and were in agreement with the Mayo Clinic diagnostic criteria. The mean age of the patients was 74 years (range, 39-91 years), and 37 patients were female (62.7%). Twenty-nine patients (49.2%) were Latino/Hispanic, 26 (44%) were Caucasian, 3 (5%) were Asian, and 1 patient (1.7%) was Black. The most common chief symptom was dyspnea, followed by chest pain and an absence of symptoms in 54.2, 28.8, and 18.6% of the patients, respectively. The primary EKG abnormalities consisted of a T wave inversion, an ST segment elevation, and ST segment depression in 69.5%, 25.4%, and 15.3% of the patients, respectively. The stressor event was identified in 90% of the cases. In 32 cases (54%), the stressor event was physical stress or a medical illness, and in 21 cases (35.6%), the stressor event was emotional stress. The in-hospital mortality rate was 8.5%. In our heterogeneous study population, stress cardiomyopathy presented with a 3:2 female-to-male ratio, and dyspnea was the most common chief complaint. Stress cardiomyopathy exhibited a T wave inversion as the primary EKG abnormality. These findings differ from previous cases that have been reported, and further studies are needed.

  7. Early administration of trimetazidine may prevent or ameliorate diabetic cardiomyopathy.

    PubMed

    Wenmeng, Wang; Qizhu, Tang

    2011-02-01

    Diabetic cardiomyopathy is a type of cardiac dysfunction resulting from diabetes, independent of vascular or valvular pathology. It clinically manifests initially as asymptomatic diastolic dysfunction and then progresses to symptomatic heart failure. Two major contributors to the development of diabetic cardiomyopathy, which are unique to diabetes, are hyperglycemia and diabetes-related alterations in myocardial metabolism. Diabetes mellitus is characterized by reduced glucose and lactate metabolism and enhanced fatty acid metabolism, which are the early consequences of the disease. Studies on the effect of intensive glucose control on heart failure events in patients with diabetes have been conducted with neutral results. However, no study on the effect of metabolic modulators on the prevention of heart failure has been reported. Trimetazidine, a 3-ketoacyl coenzyme A thiolase (3-KAT) inhibitor, shifts cardiac energy metabolism from free fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-KAT, and is used clinically as an effective antianginal agent. Studies have shown that trimetazidine improves heart function in patients with idiopathic cardiomyopathy and in diabetic patients with cardiac ischemia or heart failure. In addition to being effective, trimetazidine has only mild side effects. Therefore, instead of routine administration of trimetazidine for the treatment of diabetic cardiomyopathy, we hypothesize that the early application of trimetazidine may prevent or ameliorate diabetic cardiomyopathy. In addition to life style modifications, ACEI, ARB, and beta-blockers, which have been recommended in the past, trimetazidine should be administered to those patients with impaired glucose tolerance or patients in the early course of diabetes. In this way, we may reduce the prevalence of heart failure and improve the long-term survival of patients with diabetes through early normalization of the myocardial substrate metabolism

  8. Acute Myocardial Infarction and Stress Cardiomyopathy following the Christchurch Earthquakes

    PubMed Central

    Chan, Christina; Elliott, John; Troughton, Richard; Frampton, Christopher; Smyth, David; Crozier, Ian; Bridgman, Paul

    2013-01-01

    Background Christchurch, New Zealand, was struck by 2 major earthquakes at 4:36am on 4 September 2010, magnitude 7.1 and at 12:51pm on 22 February 2011, magnitude 6.3. Both events caused widespread destruction. Christchurch Hospital was the region's only acute care hospital. It remained functional following both earthquakes. We were able to examine the effects of the 2 earthquakes on acute cardiac presentations. Methods Patients admitted under Cardiology in Christchurch Hospital 3 week prior to and 5 weeks following both earthquakes were analysed, with corresponding control periods in September 2009 and February 2010. Patients were categorised based on diagnosis: ST elevation myocardial infarction, Non ST elevation myocardial infarction, stress cardiomyopathy, unstable angina, stable angina, non cardiac chest pain, arrhythmia and others. Results There was a significant increase in overall admissions (p<0.003), ST elevation myocardial infarction (p<0.016), and non cardiac chest pain (p<0.022) in the first 2 weeks following the early morning September earthquake. This pattern was not seen after the early afternoon February earthquake. Instead, there was a very large number of stress cardiomyopathy admissions with 21 cases (95% CI 2.6–6.4) in 4 days. There had been 6 stress cardiomyopathy cases after the first earthquake (95% CI 0.44–2.62). Statistical analysis showed this to be a significant difference between the earthquakes (p<0.05). Conclusion The early morning September earthquake triggered a large increase in ST elevation myocardial infarction and a few stress cardiomyopathy cases. The early afternoon February earthquake caused significantly more stress cardiomyopathy. Two major earthquakes occurring at different times of day differed in their effect on acute cardiac events. PMID:23844213

  9. Natural genetic variation of the cardiac transcriptome in non-diseased donors and patients with dilated cardiomyopathy.

    PubMed

    Heinig, Matthias; Adriaens, Michiel E; Schafer, Sebastian; van Deutekom, Hanneke W M; Lodder, Elisabeth M; Ware, James S; Schneider, Valentin; Felkin, Leanne E; Creemers, Esther E; Meder, Benjamin; Katus, Hugo A; Rühle, Frank; Stoll, Monika; Cambien, François; Villard, Eric; Charron, Philippe; Varro, Andras; Bishopric, Nanette H; George, Alfred L; Dos Remedios, Cristobal; Moreno-Moral, Aida; Pesce, Francesco; Bauerfeind, Anja; Rüschendorf, Franz; Rintisch, Carola; Petretto, Enrico; Barton, Paul J; Cook, Stuart A; Pinto, Yigal M; Bezzina, Connie R; Hubner, Norbert

    2017-09-14

    Genetic variation is an important determinant of RNA transcription and splicing, which in turn contributes to variation in human traits, including cardiovascular diseases. Here we report the first in-depth survey of heart transcriptome variation using RNA-sequencing in 97 patients with dilated cardiomyopathy and 108 non-diseased controls. We reveal extensive differences of gene expression and splicing between dilated cardiomyopathy patients and controls, affecting known as well as novel dilated cardiomyopathy genes. Moreover, we show a widespread effect of genetic variation on the regulation of transcription, isoform usage, and allele-specific expression. Systematic annotation of genome-wide association SNPs identifies 60 functional candidate genes for heart phenotypes, representing 20% of all published heart genome-wide association loci. Focusing on the dilated cardiomyopathy phenotype we found that eQTL variants are also enriched for dilated cardiomyopathy genome-wide association signals in two independent cohorts. RNA transcription, splicing, and allele-specific expression are each important determinants of the dilated cardiomyopathy phenotype and are controlled by genetic factors. Our results represent a powerful resource for the field of cardiovascular genetics.

  10. Expression of Flk-1 and Cyclin D2 mRNA in the Myocardium of Rats with Doxorubicin-Induced Cardiomyopathy and after Treatment with Betulonic Acid Amide.

    PubMed

    Mzhelskaya, M M; Klinnikova, M G; Koldysheva, E V; Lushnikova, E L

    2017-10-01

    The expression of VEGFR2 (Flk-1, according to immunohistochemistry) and of cyclin D2 mRNA (according to real-time PCR) in the myocardium of rats is studied in doxorubicin-induced cardiomyopathy and in response to betulonic acid amide. Doxorubicin alone and in combination with betulonic acid amide causes after 3 days a manifest reduction of cyclin D2 mRNA expression (by 38 and 63%, respectively), while injection of betulonic acid amide alone causes a 23-fold increase of cyclin D2 mRNA expression. An increase of cyclin D2 mRNA expression has been detected in all experimental groups after 14 days of experiment, the most pronounced in response to betulonic acid amide (63 times). The expression of Flk-1 in cardiomyocytes increases significantly in response to both chemical agents starting from day 3 of experiment. These results indicate that doxorubicin and betulonic acid amide induce cytoprotective reactions in the myocardium, first at the intracellular, then at the cellular levels.

  11. Leptin suppresses non-apoptotic cell death in ischemic rat cardiomyocytes by reduction of iPLA{sub 2} activity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Takatani-Nakase, Tomoka, E-mail: nakase@mukogawa-u.ac.jp; Takahashi, Koichi, E-mail: koichi@mukogawa-u.ac.jp

    Caspase-independent, non-apoptotic cell death is an important therapeutic target in myocardial ischemia. Leptin, an adipose-derived hormone, is known to exhibit cytoprotective effects on the ischemic heart, but the mechanisms are poorly understood. In this research, we found that pretreatment of leptin strongly suppressed ischemic-augmented nuclear shrinkage and non-apoptotic cell death on cardiomyocytes. Leptin was also shown to significantly inhibit the activity of iPLA{sub 2}, which is considered to play crucial roles in non-apoptotic cell death, resulting in effective prevention of ischemia-induced myocyte death. These findings provide the first evidence of a protective mechanism of leptin against ischemia-induced non-apoptotic cardiomyocyte death.more » - Highlights: • Myocardial ischemia-model induces in caspase-independent, non-apoptotic cell death. • Leptin strongly inhibits ischemic-augmented non-apoptotic cell death. • Leptin reduces iPLA{sub 2} activity, leading to avoidance of non-apoptotic cell death.« less

  12. Breast Cancer Clinical Trial of Chemotherapy and Trastuzumab: Potential Tool to Identify Cardiac Modifying Variants of Dilated Cardiomyopathy

    PubMed Central

    Serie, Daniel J.; Crook, Julia E.; Necela, Brian M.; Axenfeld, Bianca C.; Dockter, Travis J.; Colon-Otero, Gerardo; Perez, Edith A.; Thompson, E. Aubrey; Norton, Nadine

    2017-01-01

    Doxorubicin and the ERBB2 targeted therapy, trastuzumab, are routinely used in the treatment of HER2+ breast cancer. In mouse models, doxorubicin is known to cause cardiomyopathy and conditional cardiac knock out of Erbb2 results in dilated cardiomyopathy and increased sensitivity to doxorubicin-induced cell death. In humans, these drugs also result in cardiac phenotypes, but severity and reversibility is highly variable. We examined the association of decline in left ventricular ejection fraction (LVEF) at 15,204 single nucleotide polymorphisms (SNPs) spanning 72 cardiomyopathy genes, in 800 breast cancer patients who received doxorubicin and trastuzumab. For 7033 common SNPs (minor allele frequency (MAF) > 0.01) we performed single marker linear regression. For all SNPs, we performed gene-based testing with SNP-set (Sequence) Kernel Association Tests: SKAT, SKAT-O and SKAT-common/rare under rare variant non-burden; rare variant optimized burden and non-burden tests; and a combination of rare and common variants respectively. Single marker analyses identified seven missense variants in OBSCN (p = 0.0045–0.0009, MAF = 0.18–0.50) and two in TTN (both p = 0.04, MAF = 0.22). Gene-based rare variant analyses, SKAT and SKAT-O, performed very similarly (ILK, TCAP, DSC2, VCL, FXN, DSP and KCNQ1, p = 0.042–0.006). Gene-based tests of rare/common variants were significant at the nominal 5% level for OBSCN as well as TCAP, DSC2, VCL, NEXN, KCNJ2 and DMD (p = 0.044–0.008). Our results suggest that rare and common variants in OBSCN, as well as in other genes, could have modifying effects in cardiomyopathy. PMID:29367538

  13. Echocardiographic evaluation of diastolic parameters in dogs with dilated cardiomyopathy.

    PubMed

    Garncarz, M A

    2007-01-01

    Echocardiography is a valuable tool for the evaluation of systolic and diastolic cardiac function. A high correlation between measurements of diastolic mitral inflow parameters analyzed with Doppler echocardiography and invasive methods makes the former valuable. The aim of this study was to ascertain if significant differences occur in diastolic myocardial parameters between dogs with no heart disease and dogs with subclinical or clinical dilated cardiomyopathy. Furthermore the aim of the study was to determine whether heart failure in dilated cardiomypathy is a result of systolic dysfunction alone or both systolic and diastolic dysfunction. Eleven parameters were analyzed: E wave, E-AT, E-DT, E time, A wave, A-AT, A-DT, A time, E+A time, E/A ratio, and IVRT. The study confirmed the value of noninvasive echocardiographic assessment of diastolic function in dogs with dilated cardiomyopathy. Significant differences were found in E wave, E-AT, E time, E/A ratio and IVRT between healthy dogs and dogs with dilated cardiomyopathy. All are characterized by a significant decrease compared to healthy dogs after taking into account age and body weight except for the E/A ratio, which significantly increased in value. There were no significant changes in any of the Doppler parameters for diastolic evaluation in subclinical cases of DCM. Advanced heart failure in dilated cardiomyopathy entails systolic and diastolic dysfunction.

  14. Down Syndrome with Complete Atrioventricular Septal Defect, Hypertrophic Cardiomyopathy, and Pulmonary Vein Stenosis.

    PubMed

    Mahadevaiah, Guruprasad; Gupta, Manoj; Ashwath, Ravi

    2015-10-01

    The prevalence of congenital heart disease in infants with Down syndrome is 40%, compared with 0.3% in children who have normal chromosomes. Atrioventricular and ventricular septal defects are often associated with chromosomal aberrations, such as in trisomy 21, whereas hypertrophic cardiomyopathy is chiefly thought to be secondary to specific gene mutations. We found only one reported case of congenital hypertrophic cardiomyopathy and atrioventricular septal defect in an infant with Down syndrome. Here, we report atrioventricular septal defect, hypertrophic cardiomyopathy, and pulmonary vein stenosis in a neonate with Down syndrome-an apparently unique combination. In addition, we discuss the relevant medical literature.

  15. A Case Report of Recurrent Takotsubo Cardiomyopathy in a Patient during Myasthenia Crisis

    PubMed Central

    Battineni, Anusha; Mullaguri, Naresh; Thanki, Shail; Chockalingam, Anand

    2017-01-01

    Introduction Patients with myasthenia crisis can develop Takotsubo stress cardiomyopathy (SC) due to emotional or physical stress and high level of circulating catecholamines. We report a patient who developed recurrent Takotsubo cardiomyopathy during myasthenia crisis. Coexisting autoimmune disorders known to precipitate stress cardiomyopathy like Grave's disease need to be evaluated. Case Report A 69-year-old female with seropositive myasthenia gravis (MG), Grave's disease, and coronary artery disease on monthly infusion of intravenous immunoglobulin (IVIG), prednisone, pyridostigmine, and methimazole presented with shortness of breath and chest pain. Electrocardiogram (ECG) showed ST elevation in anterolateral leads with troponemia. Coronary angiogram was unremarkable for occlusive coronary disease with left ventriculogram showing reduced wall motion with apical and mid left ventricle (LV) hypokinesis suggestive of Takotsubo stress cardiomyopathy. Her symptoms were attributed to MG crisis. Her symptoms, ECG, and echocardiographic findings resolved after five cycles of plasma exchange (PLEX). She had another similar episode one year later during myasthenia crisis with subsequent resolution in 10 days after PLEX. Conclusion Takotsubo cardiomyopathy can be one of the manifestations of myasthenia crisis with or without coexisting Grave's disease. These patients might benefit from meticulous fluid status and cardiac monitoring while administering rescue treatments like IVIG and PLEX. PMID:29201468

  16. Therapeutic targeting of oxidative stress with coenzyme Q10 counteracts exaggerated diabetic cardiomyopathy in a mouse model of diabetes with diminished PI3K(p110α) signaling.

    PubMed

    De Blasio, Miles J; Huynh, Karina; Qin, Chengxue; Rosli, Sarah; Kiriazis, Helen; Ayer, Anita; Cemerlang, Nelly; Stocker, Roland; Du, Xiao-Jun; McMullen, Julie R; Ritchie, Rebecca H

    2015-10-01

    Diabetes-induced cardiac complications include left ventricular (LV) dysfunction and heart failure. We previously demonstrated that LV phosphoinositide 3-kinase p110α (PI3K) protects the heart against diabetic cardiomyopathy, associated with reduced NADPH oxidase expression and activity. Conversely, in dominant negative PI3K(p110α) transgenic mice (dnPI3K), reduced cardiac PI3K signaling exaggerated diabetes-induced cardiomyopathy, associated with upregulated NADPH oxidase. The goal was to examine whether chronic supplementation with the antioxidant coenzyme Q(10) (CoQ(10)) could attenuate LV superoxide and diabetic cardiomyopathy in a setting of impaired PI3K signaling. Diabetes was induced in 6-week-old nontransgenic and dnPI3K male mice via streptozotocin. After 4 weeks of diabetes, CoQ(10) supplementation commenced (10 mg/kg ip, 3 times/week, 8 weeks). At study end (12 weeks of diabetes), markers of LV function, cardiomyocyte hypertrophy, collagen deposition, NADPH oxidase, oxidative stress (3-nitrotyrosine), and concentrations of CoQ(9) and CoQ(10) were determined. LV NADPH oxidase (Nox2 gene expression and activity, and lucigenin-enhanced chemiluminescence), as well as oxidative stress, were increased by diabetes, exaggerated in diabetic dnPI3K mice, and attenuated by CoQ(10). Diabetes-induced LV diastolic dysfunction (prolonged deceleration time, elevated end-diastolic pressure, impaired E/A ratio), cardiomyocyte hypertrophy and fibrosis, expression of atrial natriuretic peptide, connective tissue growth factor, and β-myosin heavy chain were all attenuated by CoQ(10). Chronic CoQ(10) supplementation attenuates aspects of diabetic cardiomyopathy, even in a setting of reduced cardiac PI3K protective signaling. Given that CoQ(10) supplementation has been suggested to have positive outcomes in heart failure patients, chronic CoQ(10) supplementation may be an attractive adjunct therapy for diabetic heart failure. Copyright © 2015 Elsevier Inc. All rights

  17. Induced hypothermia for infants with hypoxic- ischemic encephalopathy using a servo-controlled fan: an exploratory pilot study.

    PubMed

    Horn, Alan; Thompson, Clare; Woods, David; Nel, Alida; Bekker, Adrie; Rhoda, Natasha; Pieper, Clarissa

    2009-06-01

    Several trials suggest that hypothermia is beneficial in selected infants with hypoxic-ischemic encephalopathy. However, the cooling methods used required repeated interventions and were either expensive or reported significant temperature variation. The objective of this pilot study was to describe the use, efficacy, and physiologic impact of an inexpensive servo-controlled cooling fan blowing room-temperature air. A servo-controlled fan was manufactured and used to cool 10 infants with hypoxic-ischemic encephalopathy to a rectal temperature of 33 degrees C to 34 degrees C. The infants were sedated with phenobarbital, but clonidine was administered to some infants if shivering or discomfort occurred. A servo-controlled radiant warmer was used simultaneously with the fan to prevent overcooling. The settings used on the fan and radiant warmer differed slightly between some infants as the technique evolved. A rectal temperature of 34 degrees C was achieved in a median time of 58 minutes. Overcooling did not occur, and the mean temperature during cooling was 33.6 degrees C +/- 0.2 degrees C. Inspired oxygen requirements increased in 6 infants, and 5 infants required inotropic support during cooling, but this was progressively reduced after 1 to 2 days. Dehydration did not occur. Five infants shivered when faster fan speeds were used, but 4 of the 5 infants had hypomagnesemia. Shivering was controlled with clonidine in 4 infants, but 1 infant required morphine. Servo-controlled fan cooling with room-temperature air, combined with servo-controlled radiant warming, was an effective, simple, and safe method of inducing and maintaining rectal temperatures of 33 degrees C to 34 degrees C in sedated infants with hypoxic-ischemic encephalopathy. After induction of hypothermia, a low fan speed facilitated accurate temperature control, and warmer-controlled rewarming at 0.2 degrees C increments every 30 minutes resulted in more appropriate rewarming than when 0.5 degrees C

  18. Histologic characterization of canine dilated cardiomyopathy.

    PubMed

    Tidholm, A; Jönsson, L

    2005-01-01

    Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

  19. The Mutations Associated with Dilated Cardiomyopathy

    PubMed Central

    Parvari, Ruti; Levitas, Aviva

    2012-01-01

    Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM). The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes. PMID:22830024

  20. The mutations associated with dilated cardiomyopathy.

    PubMed

    Parvari, Ruti; Levitas, Aviva

    2012-01-01

    Cardiomyopathy is an important cause of heart failure and a major indication for heart transplantation in children and adults. This paper describes the state of the genetic knowledge of dilated cardiomyopathy (DCM). The identification of the causing mutation is important since presymptomatic interventions of DCM have proven value in preventing morbidity and mortality. Additionally, as in general in genetic studies, the identification of the mutated genes has a direct clinical impact for the families and population involved. Identifying causative mutations immediately amplifies the possibilities for disease prevention through carrier screening and prenatal testing. This often lifts a burden of social isolation from affected families, since healthy family members can be assured of having healthy children. Identification of the mutated genes holds the potential to lead to the understanding of disease etiology, pathophysiology, and therefore potential therapy. This paper presents the genetic variations, or disease-causing mutations, contributing to the pathogenesis of hereditary DCM, and tries to relate these to the functions of the mutated genes.

  1. TIA (Transient Ischemic Attack)

    MedlinePlus

    ... a TIA . The symptoms are similar to an ischemic stroke, but TIA symptoms usually last less than five ... treated for a blockage-related stroke (called an ischemic stroke), between 7 and 40% report experiencing a TIA ...

  2. Hypertrophic Cardiomyopathy: A Vicious Cycle Triggered by Sarcomere Mutations and Secondary Disease Hits.

    PubMed

    Wijnker, Paul J M; Sequeira, Vasco; Kuster, Diederik W D; Velden, Jolanda van der

    2018-04-11

    Hypertrophic cardiomyopathy (HCM) is a cardiac genetic disease characterized by left ventricular hypertrophy, diastolic dysfunction, and myocardial disarray. Disease onset occurs between 20 and 50 years of age, thus affecting patients in the prime of their life. HCM is caused by mutations in sarcomere proteins, the contractile building blocks of the heart. Despite increased knowledge of causal mutations, the exact path from genetic defect leading to cardiomyopathy is complex and involves additional disease hits. Recent Advances: Laboratory-based studies indicate that HCM development not only depends on the primary sarcomere impairment caused by the mutation but also on secondary disease-related alterations in the heart. Here we propose a vicious mutation-induced disease cycle, in which a mutation-induced energy depletion alters cellular metabolism with increased mitochondrial work, which triggers secondary disease modifiers that will worsen disease and ultimately lead to end-stage HCM. Evidence shows excessive cellular reactive oxygen species (ROS) in HCM patients and HCM animal models. Oxidative stress markers are increased in the heart (oxidized proteins, DNA, and lipids) and serum of HCM patients. In addition, increased mitochondrial ROS production and changes in endogenous antioxidants are reported in HCM. Mutant sarcomeric protein may drive excessive levels of cardiac ROS via changes in cardiac efficiency and metabolism, mitochondrial activation and/or dysfunction, impaired protein quality control, and microvascular dysfunction. Interventions restoring metabolism, mitochondrial function, and improved ROS balance may be promising therapeutic approaches. We discuss the effects of current HCM pharmacological therapies and potential future therapies to prevent and reverse HCM. Antioxid. Redox Signal. 00, 000-000.

  3. Use of calcium channel blockers in hypertrophic cardiomyopathy.

    PubMed

    Lorell, B H

    1985-02-22

    Recent studies in patients with either obstructive or nonobstructive hypertrophic cardiomyopathy have suggested that increased resistance to diastolic filling of the stiff left ventricle may be an important mechanism contributing to symptoms. These observations have led to exploration of the effects of calcium channel blockers on systolic and diastolic function in patients with hypertrophic cardiomyopathy. Acute hemodynamic studies using verapamil and nifedipine have shown that these agents tend to cause: (1) a slight fall in systemic arterial pressure and reflex increase in heart rate; (2) a reduction in left ventricular outflow gradient in most but not all patients; and (3) variable effect on left-side heart filling pressures. In contrast to beta-adrenergic blockers, these hemodynamic effects are not associated with depression of systolic function, but appear to be related to improved left ventricular distensibility. Clinical trials have suggested that long-term administration of verapamil in patients with hypertrophic cardiomyopathy promotes improvement in symptomatic status and exercise tolerance in many but not all patients; similar results have been reported in preliminary studies using nifedipine. Potential major adverse effects include depression of sinoatrial activity and atrioventricular conduction with verapamil, and marked hypotension and, rarely, pulmonary edema with both verapamil and nifedipine.

  4. Protective effect of agmatine on ischemia/reperfusion-induced renal injury in rats.

    PubMed

    Sugiura, Takahiro; Tsutsui, Hidenobu; Takaoka, Masanori; Kobuchi, Shuhei; Hayashi, Kentaro; Fujii, Toshihide; Matsumura, Yasuo

    2008-03-01

    Enhanced renal sympathetic nerve activity (RSNA) during ischemic period and the renal venous norepinephrine (NE) overflow after reperfusion play important roles in the development of ischemic/reperfusion (I/R)-induced acute renal failure (ARF) in rats. This study evaluated whether agmatine, which is known to reduce sympathetic nerve activity and NE overflow by electrical stimulation, would prevent the I/R-induced renal dysfunction. Ischemic ARF was induced by clamping the left renal artery and vein for 45 minutes followed by reperfusion 2 weeks after the contralateral nephrectomy. Intravenous (IV) injection of agmatine (100 and 300 micromol/kg) to ischemic ARF rats dose-dependently suppressed the enhanced RSNA and attenuated the I/R-induced renal dysfunction and histological damage. Intracerebroventricular (ICV) injection of agmatine (600 nmol/kg) to ischemic ARF rats suppressed the enhanced RSNA during the ischemic period and attenuated the I/R-induced renal injury. Furthermore, both IV and ICV injection of agmatine significantly suppressed the renal venous NE overflow after the reperfusion. These results indicate that agmatine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppression of the enhanced RSNA during ischemic period and NE overflow from renal sympathetic nerve endings.

  5. Association of caspase-1 polymorphisms with Chagas cardiomyopathy among individuals in Santa Cruz, Bolivia.

    PubMed

    Fu, Katherine Yih-Jia; Zamudio, Roxana; Henderson-Frost, Jo; Almuedo, Alex; Steinberg, Hannah; Clipman, Steven Joseph; Duran, Gustavo; Marcus, Rachel; Crawford, Thomas; Alyesh, Daniel; Colanzi, Rony; Flores, Jorge; Gilman, Robert Hugh; Bern, Caryn

    2017-01-01

    Trypanosoma cruzi (Tc) infection is usually acquired in childhood in endemic areas, leading to Chagas disease, which progresses to Chagas cardiomyopathy in 20-30% of infected individuals over decades. The pathogenesis of Chagas cardiomyopathy involves the host inflammatory response to T. cruzi, in which upstream caspase-1 activation prompts the cascade of inflammatory chemokines/cytokines, cardiac remodeling, and myocardial dysfunction. The aim of the present study was to examine the association of two caspase-1 single nucleotide polymorphisms (SNPs) with cardiomyopathy. We recruited infected (Tc+, n = 149) and uninfected (Tc-, n = 87) participants in a hospital in Santa Cruz, Bolivia. Cardiac status was classified (I, II, III, IV) based on Chagas cardiomyopathy-associated electrocardiogram findings and ejection fractions on echocardiogram. Genotypes were determined using Taqman probes via reverse transcription-polymerase chain reaction of peripheral blood DNA. Genotype frequencies were analyzed according to three inheritance patterns (dominant, recessive, additive) using logistic regression adjusted for age and sex. The AA allele for the caspase-1 SNP rs501192 was more frequent in Tc+ cardiomyopathy (classes II, III, IV) patients compared to those with a normal cardiac status (class I) [odds ratio (OR) = -2.18, p = 0.117]. This trend approached statistical significant considering only Tc+ patients in class I and II (OR = -2.64, p = 0.064). Caspase-1 polymorphisms may play a role in Chagas cardiomyopathy development and could serve as markers to identify individuals at higher risk for priority treatment.

  6. Recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy in Africa.

    PubMed

    Sliwa, Karen; Mayosi, Bongani M

    2013-09-01

    This review addresses recent advances in the epidemiology, pathogenesis and prognosis of acute heart failure and cardiomyopathy based on research conducted in Africa. We searched Medline/PubMed for publications on acute decompensated heart failure and cardiomyopathy in Africa for the past 5 years (ie, 1 January 2008 to 31 December 2012). This was supplemented with personal communications with colleagues from Africa working in the field. A large prospective registry has shown that acute decompensated heart failure is caused by hypertension, cardiomyopathy and rheumatic heart disease in 90% of cases, a pattern that is in contrast with the dominance of coronary artery disease in North America and Europe. Furthermore, acute heart failure is a disease of the young with a mean age of 52 years, occurs equally in men and women, and is associated with high mortality at 6 months (∼18%), which is, however, similar to that observed in non-African heart failure registries, suggesting that heart failure has a dire prognosis globally, regardless of aetiology. The molecular genetics of dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy in Africans is consistent with observations elsewhere in the world; the unique founder effects in the Afrikaner provide an opportunity for the study of genotype-phenotype correlations in large numbers of individuals with cardiomyopathy due to the same mutation. Advances in the understanding of the molecular mechanisms of peripartum cardiomyopathy have led to promising clinical trials of bromocriptine in the treatment of peripartum heart failure. The key challenges of management of heart failure are the urgent need to increase the use of proven treatments by physicians, and the control of hypertension in primary care and at the population level.

  7. Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.

    PubMed

    Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung; Rothwell, Peter M

    2017-06-01

    Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P <0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P <0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78-1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P =0.011) but not intracerebral hemorrhage ( P =0.10) or all-cause mortality ( P =0.16). CS-PVSs were not associated with recurrent stroke ( P =0.57) or mortality ( P =0.072). Prognostic associations were similar in both cohorts. Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. © 2017 The Authors.

  8. Arrhythmogenic ventricular cardiomyopathy: A paradigm shift from right to biventricular disease

    PubMed Central

    Saguner, Ardan M; Brunckhorst, Corinna; Duru, Firat

    2014-01-01

    Arrhythmogenic ventricular cardiomyopathy (AVC) is generally referred to as arrhythmogenic right ventricular (RV) cardiomyopathy/dysplasia and constitutes an inherited cardiomyopathy. Affected patients may succumb to sudden cardiac death (SCD), ventricular tachyarrhythmias (VTA) and heart failure. Genetic studies have identified causative mutations in genes encoding proteins of the intercalated disk that lead to reduced myocardial electro-mechanical stability. The term arrhythmogenic RV cardiomyopathy is somewhat misleading as biventricular involvement or isolated left ventricular (LV) involvement may be present and thus a broader term such as AVC should be preferred. The diagnosis is established on a point score basis according to the revised 2010 task force criteria utilizing imaging modalities, demonstrating fibrous replacement through biopsy, electrocardiographic abnormalities, ventricular arrhythmias and a positive family history including identification of genetic mutations. Although several risk factors for SCD such as previous cardiac arrest, syncope, documented VTA, severe RV/LV dysfunction and young age at manifestation have been identified, risk stratification still needs improvement, especially in asymptomatic family members. Particularly, the role of genetic testing and environmental factors has to be further elucidated. Therapeutic interventions include restriction from physical exercise, beta-blockers, sotalol, amiodarone, implantable cardioverter-defibrillators and catheter ablation. Life-long follow-up is warranted in symptomatic patients, but also asymptomatic carriers of pathogenic mutations. PMID:24772256

  9. Clinical use of cardiac PET/MRI: current state-of-the-art and potential future applications.

    PubMed

    Krumm, Patrick; Mangold, Stefanie; Gatidis, Sergios; Nikolaou, Konstantin; Nensa, Felix; Bamberg, Fabian; la Fougère, Christian

    2018-05-01

    Combined PET/MRI is a novel imaging method integrating the advances of functional and morphological MR imaging with PET applications that include assessment of myocardial viability, perfusion, metabolism of inflammatory tissue and tumors, as well as amyloid deposition imaging. As such, PET/MRI is a promising tool to detect and characterize ischemic and non-ischemic cardiomyopathies. To date, the greatest benefit may be expected for diagnostic evaluation of systemic diseases and cardiac masses that remain unclear in cardiac MRI, as well as for clinical and scientific studies in the setting of ischemic cardiomyopathies. Diagnosis and therapeutic monitoring of cardiac sarcoidosis has the potential of a possible 'killer-application' for combined cardiac PET/MRI. In this article, we review the current evidence and discuss current and potential future applications of cardiac PET/MRI.

  10. [Fiessinger-Leroy-Reiter syndrome with non-obstructive cardiomyopathy treated with methotrexate].

    PubMed

    Blétry, O; De Prost, Y; Scheuble, C; Frank, R; Godeau, P

    1979-07-01

    The case of a 50 year old male with the Fiessinger-Leroy-Reiter syndrome, ankylosing spondylitis and generalised pustular psoriasis is reported. This condition wax complicated by non-obstructive cardiomyopathy, congestive cardiac failure and first-degree atrioventricular block, the site of which was localised by electrophysiological studies (nodal block with an infrahisian conduction defect). After failure of several therapeutic regimes, a spectacular improvement was obtained with Methotrexate associated with a diuretic; the signs of heart failure regressed and the cardiomyopathy stablised. A parallel improvement was seen in the skin, cardiac and articular lesions and has been maintained with an 18 months follow-up. Left ventricular performance was studied by echocardiography. The mechanism of the beneficial effect of Methotrexate is unclear; this therapeutic trial is to be extended to include other cases of primary cardiomyopathy without obstruction.

  11. RESTRICTIVE CARDIOMYOPATHY AND SECONDARY CONGESTIVE HEART FAILURE IN A MCDOWELL'S CARPET PYTHON (MORELIA SPILOTA MCDOWELLI).

    PubMed

    Schilliger, Lionel; Chetboul, Valérie; Damoiseaux, Cécile; Nicolier, Alexandra

    2016-12-01

    Echocardiography is an established and noninvasive diagnostic tool used in herpetologic cardiology. Various cardiac lesions have been previously described in reptiles with the exception of restrictive cardiomyopathy. In this case report, restrictive cardiomyopathy and congestive heart failure associated with left atrial and sinus venosus dilation were diagnosed in a 2-yr-old captive lethargic McDowell's carpet python ( Morelia spilota mcdowelli), based on echocardiographic, Doppler, and histopathologic examinations. This cardiomyopathy was also associated with thrombosis within the sinus venosus.

  12. Takotsubo Cardiomyopathy: Case Series and Literature Review

    PubMed Central

    Cavayero, Chase; Kar, Pran; Kar, Sunny

    2016-01-01

    Although originally considered to be uncommon, Takotsubo cardiomyopathy is becoming increasingly visible, annually comprising an increasing portion of suspected diagnoses of acute coronary syndrome. This condition is characterized by reversible left ventricular akinesis without significant coronary artery obstruction. This case study presents five patients diagnosed with Takotsubo cardiomyopathy, as confirmed by echocardiogram and angiography. All of the patients presented with classic myocardial chest pain and elevated troponins. Following diagnosis, they were treated with supportive measures, particularly angiotensin-converting enzyme inhibitors, and beta-blockers. All patients made a full recovery. Though the mechanism of Takotsubo has not been fully elucidated, hypotheses suggest it may be related to excessive catecholamine levels causing either myocardial stunning or coronary vasospasm. Recognition and understanding of this unusual pathology are essential because it can lead to improved clinical management. PMID:27446769

  13. Vidarabine, an Anti-Herpes Virus Agent, Protects Against the Development of Heart Failure With Relatively Mild Side-Effects on Cardiac Function in a Canine Model of Pacing-Induced Dilated Cardiomyopathy.

    PubMed

    Nakamura, Takashi; Fujita, Takayuki; Kishimura, Megumi; Suita, Kenji; Hidaka, Yuko; Cai, Wenqian; Umemura, Masanari; Yokoyama, Utako; Uechi, Masami; Ishikawa, Yoshihiro

    2016-11-25

    In heart failure patients, chronic hyperactivation of sympathetic signaling is known to exacerbate cardiac dysfunction. In this study, the cardioprotective effect of vidarabine, an anti-herpes virus agent, which we identified as a cardiac adenylyl cyclase inhibitor, in dogs with pacing-induced dilated cardiomyopathy (DCM) was evaluated. In addition, the adverse effects of vidarabine on basal cardiac function was compared to those of the β-blocker, carvedilol.Methods and Results:Vidarabine and carvedilol attenuated the development of pacing-induced systolic dysfunction significantly and with equal effectiveness. Both agents also inhibited the development of cardiac apoptosis and fibrosis and reduced the Na + -Ca 2+ exchanger-1 protein level in the heart. Importantly, carvedilol significantly enlarged the left ventricle and atrium; vidarabine, in contrast, did not. Vidarabine-treated dogs maintained cardiac response to β-AR stimulation better than carvedilol-treated dogs did. Vidarabine may protect against pacing-induced DCM with less suppression of basal cardiac function than carvedilol in a dog model. (Circ J 2016; 80: 2496-2505).

  14. Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis.

    PubMed

    Pelliccia, Antonio; Corrado, Domenico; Bjørnstad, Hans Halvor; Panhuyzen-Goedkoop, Nicole; Urhausen, Axel; Carre, Francois; Anastasakis, Aris; Vanhees, Luc; Arbustini, Eloisa; Priori, Silvia

    2006-12-01

    Several relatively uncommon, but important cardiovascular diseases are associated with increased risk for acute cardiac events during exercise (including sudden death), such as hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC) and myo-pericarditis. Practising cardiologists are frequently asked to advise on exercise programmes and sport participation in young individuals with these cardiovascular diseases. Indeed, many asymptomatic (or mildly symptomatic) patients with cardiomyopathies aspire to a physically active lifestyle to take advantage of the many documented benefits of exercise. While recommendations dictating the participation in competitive sport for athletes with cardiomyopathies and myo-pericarditis have recently been published as a consensus document of the European Society of Cardiology, no European guidelines have addressed the possible participation of patients with cardiomyopathies in recreational and amateur sport activities. The present document is intended to offer a comprehensive overview to practising cardiologists and sport physicians of the recommendations governing safe participation in different types of competitive sport, as well as the participation in a variety of recreational physical activities and amateur sports in individuals with cardiomyopathies and myo-pericarditis. These recommendations, based largely on the experience and insights of the expert panel appointed by the European Society of Cardiology, include the most up-to-date information concerning regular exercise and sports activity in patients with cardiomyopathies and myo-pericarditis.

  15. DOR activation inhibits anoxic/ischemic Na+ influx through Na+ channels via PKC mechanisms in the cortex.

    PubMed

    Chao, Dongman; He, Xiaozhou; Yang, Yilin; Bazzy-Asaad, Alia; Lazarus, Lawrence H; Balboni, Gianfranco; Kim, Dong H; Xia, Ying

    2012-08-01

    Activation of delta-opioid receptors (DOR) is neuroprotective against hypoxic/ischemic injury in the cortex, which is at least partially related to its action against hypoxic/ischemic disruption of ionic homeostasis that triggers neuronal injury. Na(+) influx through TTX-sensitive voltage-gated Na(+) channels may be a main mechanism for hypoxia-induced disruption of K(+) homeostasis, with DOR activation attenuating the disruption of ionic homeostasis by targeting voltage-gated Na(+) channels. In the present study we examined the role of DOR in the regulation of Na(+) influx in anoxia and simulated ischemia (oxygen-glucose deprivation) as well as the effect of DOR activation on the Na(+) influx induced by a Na(+) channel opener without anoxic/ischemic stress and explored a potential PKC mechanism underlying the DOR action. We directly measured extracellular Na(+) activity in mouse cortical slices with Na(+) selective electrodes and found that (1) anoxia-induced Na(+) influx occurred mainly through TTX-sensitive Na(+) channels; (2) DOR activation inhibited the anoxia/ischemia-induced Na(+) influx; (3) veratridine, a Na(+) channel opener, enhanced the anoxia-induced Na(+) influx; this could be attenuated by DOR activation; (4) DOR activation did not reduce the anoxia-induced Na(+) influx in the presence of chelerythrine, a broad-spectrum PKC blocker; and (5) DOR effects were blocked by PKCβII peptide inhibitor, and PKCθ pseudosubstrate inhibitor, respectively. We conclude that DOR activation inhibits anoxia-induced Na(+) influx through Na(+) channels via PKC (especially PKCβII and PKCθ isoforms) dependent mechanisms in the cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation.

    PubMed

    Bai, Yang; Cui, Wenpeng; Xin, Ying; Miao, Xiao; Barati, Michelle T; Zhang, Chi; Chen, Qiang; Tan, Yi; Cui, Taixing; Zheng, Yang; Cai, Lu

    2013-04-01

    This study was to investigate whether sulforaphane (SFN) can prevent diabetic cardiomyopathy. Type 1 diabetes was induced in FVB mice by multiple intraperitoneal injections with low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without SFN at 0.5mg/kg daily in five days of each week for 3 months and then kept until 6 months. At 3 and 6 months of diabetes, blood pressure and cardiac function were assessed. Cardiac fibrosis, inflammation, and oxidative damage were assessed by Western blot, real-time qPCR, and histopathological examination. SFN significantly prevented diabetes-induced high blood pressure and cardiac dysfunction at both 3 and 6 months, and also prevented diabetes-induced cardiac hypertrophy (increased the ratio of heart weight to tibia length and the expression of atrial natriuretic peptide mRNA and protein) and fibrosis (increased the accumulation of collagen and expression of connective tissue growth factor and tissue growth factor-β). SFN also almost completely prevented diabetes-induced cardiac oxidative damage (increased accumulation of 3-nitrotyrosine and 4-hydroxynonenal) and inflammation (increased tumor necrotic factor-α and plasminogen activator inhibitor 1 expression). SFN up-regulated NFE2-related factor 2 (Nrf2) expression and transcription activity that was reflected by increased Nrf2 nuclear accumulation and phosphorylation as well as the mRNA and protein expression of Nrf2 downstream antioxidants. Furthermore, in cultured H9c2 cardiac cells silencing Nrf2 gene with its siRNA abolished the SFN's prevention of high glucose-induced fibrotic response. These results suggest that diabetes-induced cardiomyopathy can be prevented by SFN, which was associated with the up-regulated Nrf2 expression and transcription function. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Minocycline attenuates both OGD-induced HMGB1 release and HMGB1-induced cell death in ischemic neuronal injury in PC12 cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kikuchi, Kiyoshi; Department of Neurosurgery, Omuta City General Hospital, 2-19-1 Takarazaka, Omuta-City, Fukuoka 836-8567; Kawahara, Ko-ichi

    2009-07-24

    High mobility group box-1 (HMGB1), a non-histone DNA-binding protein, is massively released into the extracellular space from neuronal cells after ischemic insult and exacerbates brain tissue damage in rats. Minocycline is a semisynthetic second-generation tetracycline antibiotic which has recently been shown to be a promising neuroprotective agent. In this study, we found that minocycline inhibited HMGB1 release in oxygen-glucose deprivation (OGD)-treated PC12 cells and triggered the activation of p38mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases (ERK1/2). The ERK kinase (MEK)1/2 inhibitor U-0126 and p38MAPK inhibitor SB203580 blocked HMGB1 release in response to OGD. Furthermore, HMGB1 triggered cell death inmore » a dose-dependent fashion. Minocycline significantly rescued HMGB1-induced cell death in a dose-dependent manner. In light of recent observations as well as the good safety profile of minocycline in humans, we propose that minocycline might play a potent neuroprotective role through the inhibition of HMGB1-induced neuronal cell death in cerebral infarction.« less

  18. Experiences of health care in women with Peripartum Cardiomyopathy in Sweden: a qualitative interview study.

    PubMed

    Patel, Harshida; Schaufelberger, Maria; Begley, Cecily; Berg, Marie

    2016-12-08

    Peripartum cardiomyopathy is often associated with severe heart failure occurring towards the end of pregnancy or in the months following birth with debilitating, exhausting and frightening symptoms requiring person-centered care. The aim of this study was to explore women's experiences of health care while being diagnosed with peripartum cardiomyopathy. Qualitative interviews were conducted with 19 women with peripartum cardiomyopathy in Sweden, following consent. Data were analysed using qualitative content analysis. Confirmability was ensured by peer-debriefing, and an audit trail was kept to establish the credibility of the study. The main theme in the experience of health care was, 'Exacerbated Suffering', expressed in three subthemes; 'not being cared about', 'not being cared for' and 'not feeling secure.' The suffering was present in relation to the illness with failing health symptoms, but most of all in relation to not being taken seriously and adequately cared for by healthcare professionals. Women felt they were on an assembly line in midwives' routine work where knowledge about peripartum cardiomyopathy was lacking and they showed distrust and dissatisfaction with care related to negligence and indifference experienced from healthcare professionals. Feelings of being alone and lost were prominent and related to a sense of insecurity, distress and uneasiness. This study shows a knowledge gap of peripartum cardiomyopathy in maternity care personnel. This is alarming as the deprecation of symptoms and missed diagnosis of peripartum cardiomyopathy can lead to life-threatening consequences. To prompt timely diagnosis and avoid unnecessary suffering it is important to listen seriously to, and respect, women's narratives and act on expressions of symptoms of peripartum cardiomyopathy, even those overlapping normal pregnancy symptoms.

  19. Takotsubo cardiomyopathy in a patient with Addison disease: is apical ballooning always reversible?

    PubMed

    Barcin, Cem; Kursaklioglu, Hurkan; Kose, Sedat; Amasyali, Basri; Isik, Ersoy

    2010-01-07

    Takotsubo cardiomyopathy is characterized by acute ventricular dysfunction in the absence of coronary obstruction. Complete improvement of ventricular function is seen in the vast majority of the patients. We describe a 40-year-old woman with Addison disease who experienced Takotsubo cardiomyopathy but with persistent apical dysfunction during 5-month-follow up.

  20. Dilated cardiomyopathy and severe heart failure. An update for pediatricians.

    PubMed

    Caviedes Bottner, Paola; Córdova Fernández, Tamara; Larraín Valenzuela, Marcos; Cruces Romero Presentación de Casos Clínicos, Pablo

    2018-06-01

    Dilated cardiomyopathy is the main cause of heart failure leading to heart transplant. Its prognosis is variable and depends on the etiology, the patient's age at onset, and the severity. The management of dilated cardiomyopathy is aimed at minimizing symptoms and preventing disease progression; it requires a comprehensive screening for comorbidities and the prevention of complications to improve the overall status of these children and mitigate their prognosis. Here we present a review oriented at the multidisciplinary management that pediatricians should consider when seeing these patients. Sociedad Argentina de Pediatría.

  1. Platelet reactivity to adenosine diphosphate and long-term ischemic event occurrence following percutaneous coronary intervention: a potential antiplatelet therapeutic target.

    PubMed

    Gurbel, Paul A; Antonino, Mark J; Bliden, Kevin P; Dichiara, Joseph; Suarez, Thomas A; Singla, Anand; Tantry, Udaya S

    2008-12-01

    Platelets play a central role in the genesis of post-percutaneous coronary intervention (PCI) ischemic events. High post-procedural platelet reactivity to adenosine diphosphate (HPR(ADP)) may be a risk factor for ischemic events after PCI. The study was designed to evaluate a cutpoint of platelet reactivity that is associated with the occurrence of ischemic events after PCI. Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 297 consecutive patients undergoing non-emergent PCI. Patients were prospectively followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Eighty-one patients (27%) suffered ischemic events. Patients with ischemic events had higher 5 microM ADP-induced platelet aggregation (46 +/- 14% vs. 30 +/- 17%, p < 0.001) and 20 microM ADP-induced platelet aggregation (60 +/- 13% vs. 43 +/- 19%, p < 0.001) compared to patients without ischemic events. Using a combined receiver operator curve analysis, cutpoints of >46% aggregation following 5 microM ADP stimulation and >59% aggregation following 20 microM ADP stimulation (HPR(ADP)) were associated with 58 and 54% of ischemic events, respectively. Multivariate Cox regression demonstrated a significant relation between event occurrence and post-procedural HPR(ADP) cutpoints (5 microM ADP, OR=3.9, and 20 microM ADP, OR=3.8, p < 0.001 for both). High post-procedural platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data support a potential therapeutic target for antiplatelet therapy based on the results of an ex vivo platelet function test. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

  2. INCIDENCE OF ABNORMAL POSITRON EMISSION TOMOGRAPHY IN PATIENTS WITH UNEXPLAINED CARDIOMYOPATHY AND VENTRICULAR ARRHYTHMIAS

    PubMed Central

    Tung, Roderick; Bauer, Brenton; Schelbert, Heinrich; Lynch, Joseph; Auerbach, Martin; Gupta, Pawan; Schiepers, Christiaan; Chan, Samantha; Ferris, Julie; Barrio, Martin; Ajijola, Olujimi; Bradfield, Jason; Shivkumar, Kalyanam

    2015-01-01

    Background The incidence of myocardial inflammation in patients with unexplained cardiomyopathy referred for ventricular arrhythmias (VA) is unknown. Objective To report fasting PET scan findings in consecutive patients referred with unexplained cardiomyopathy and VA. Methods 18-FDG PET/CT scans with a >16 hour fasting protocol were prospectively ordered for patients referred for VA and unexplained cardiomyopathy (EF<55%). Patients with focal myocardial FDG uptake were labeled as arrhythmogenic inflammatory cardiomyopathy (AIC) and classified into four groups based on the presence of lymph node uptake (AIC+) and perfusion abnormalities (early vs late stage). Results Over a 3-year period, 103 PET scan were performed with 49% (AIC+=17, AIC=33) exhibiting focal FDG uptake. The mean age was 52±12 years with an EF of 36±16%. Patients with AIC were more likely to have a history of pacemaker (32% vs 6%, p=0.002) compared to those with normal PET. When biopsy was performed, histologic diagnosis revealed non-granulomatous inflammation in 6 patients and sarcoidosis in 18 patients. 90% of patients with AIC/AIC+ were prescribed immunosuppressive therapy and 58% underwent ablation. Correlation between areas of perfusion abnormalities and FDG uptake with electro-anatomic mapping was observed in 79% patients and MRI findings matched in only 33%. Conclusions Nearly 50% of patients referred with unexplained cardiomyopathy and VA demonstrate ongoing focal myocardial inflammation on FDG PET. These data suggests that a significant proportion of patients labeled “idiopathic” may have occult arrhythmogenic inflammatory cardiomyopathy, which may benefit from early detection and immunosuppressive medical therapy. PMID:26272522

  3. Effect of non-invasive remote ischemic preconditioning on intra-renal perfusion in volunteers.

    PubMed

    Robert, René; Vinet, Mathieu; Jamet, Angéline; Coudroy, Rémi

    2017-06-01

    Remote ischemic preconditioning may attenuate renal injury and protect the kidney during subsequent inflammatory or ischemic stress. However, the mechanism of such a protection is not well understood. The aim of this study was to investigate the impact of remote ischemic preconditioning on renal resistivity index (RRI) in nine healthy volunteers. In six volunteers, four cycles of 4-min inflation of a blood pressure cuff were applied to one upper arm, followed by 4-min reperfusion with the cuff deflated. RRI was determined using Doppler echography during each cuff deflated period. Measures were also performed in three volunteers without preconditioning. The median value of RRI significantly decreased progressively from 0.59 [0.53-0.62] before the remote conditioning (baseline) to 0.49 [0.46-0.53] at the end of the experiment (p < 0.001) whereas there was no change in controls. In this study, for the first time, we have clearly shown in a small group of subjects that remote ischemic preconditioning can induce a significantly decrease in RRI through increased intra-renal perfusion.

  4. Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis.

    PubMed

    Varutti, Rosanna; Setti, Tommaso; Ezri, Tiberiu; Nicolosi, Gianluigi; Rellini, Gianluigi; Cassin, Matteo; Leykin, Yigal

    2015-04-01

    The Takotsubo cardiomyopathy is a rare haemodynamic dysfunction, only recently reported perioperatively. While the diagnostic criteria have been established and the outcome is known as favorable, the pathophysiological mechanisms are not entirely understood. Here we present the case of a patient scheduled for laparoscopic hysterectomy and adnexectomy, who early postoperatively developed a Takotsubo cardiomyopathy supposedly triggered by an acute hypertensive crisis due to intraoperative fluid overload.

  5. Autoimmune Myocarditis, Valvulitis, and Cardiomyopathy

    PubMed Central

    Myers, Jennifer M.; Cunningham, Madeleine W.; Fairweather, DeLisa; Huber, Sally A.

    2013-01-01

    Cardiac myosin-induced autoimmune myocarditis (EAM) is a model of inflammatory heart disease initiated by CD4+ T cells (Smith and Allen 1991; Li, Heuser et al. 2004). It is a paradigm of the immune-mediated cardiac damage believed to play a role in the pathogenesis of a subset of postinfectious human cardiomyopathies (Rose, Herskowitz et al. 1993). Myocarditis is induced in susceptible mice by immunization with purified cardiac myosin (Neu, Rose et al. 1987) or specific peptides derived from cardiac myosin (Donermeyer, Beisel et al. 1995; Pummerer, Luze et al. 1996) (see Basic Protocol 1), or by adoptive transfer of myosin-reactive T cells (Smith and Allen 1991) (see Alternate Protocol). Myocarditis has been induced in Lewis rats by immunization with purified rat or porcine cardiac myosin (Kodama, Matsumoto et al. 1990; Li, Heuser et al. 2004) (see Basic Protocol 2) or S2-16 peptide (Li, Heuser et al. 2004), or by adoptive transfer of T cells stimulated by specific peptides derived from cardiac myosin (Wegmann, Zhao et al. 1994). Myocarditis begins 12 to 14 days after the first immunization, and is maximal after 21 days. Other animal models commonly used to study myocarditis development include the pathogen-induced models in which disease is initiated by viral infection. The first murine model of acute viral myocarditis causes sudden death via viral damage to cardiomyocytes (Huber, Gauntt et al. 1998; Horwitz, La Cava et al. 2000; Fong 2003; Fuse, Chan et al. 2005; Fairweather and Rose 2007; Cihakova and Rose 2008) whereas the second model is based on inoculation with heart-passaged coxsackievirus B3 (CVB3) that includes damaged heart proteins (Fairweather, Frisancho-Kiss et al. 2004; Fairweather D 2004; Fairweather and Rose 2007; Cihakova and Rose 2008) In addition to the protocols used to induce EAM in mice and rats, support protocols are included for preparing purified cardiac myosin using mouse or rat heart tissue (see Support Protocol 1), preparing purified

  6. Experience with beta-blockers in long term management of peripartum cardiomyopathy.

    PubMed

    Mohsin, Kiren; Akhtar, Naveed

    2004-01-01

    Peripartum cardiomyopathy (PPCM) is an ominous complication of pregnancy, about which little is known. Although the role of Beta Blockers is well established in heart failure, there is limited data evaluating their use in Peripartum cardiomyopathy. We report the use of Beta-Blockers (metoprolol) in conjunct with standard heart failure therapy in two patients of PPCM with favorable long-term outcome. Our experience, although limited, highlights the significance of use of Beta-Blockers in this rare life threatening condition.

  7. Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke

    PubMed Central

    Lau, Kui-Kai; Li, Linxin; Lovelock, Caroline E.; Zamboni, Giovanna; Chan, Tsz-Tai; Chiang, Man-Fung; Lo, Kin-Ting; Küker, Wilhelm; Mak, Henry Ka-Fung

    2017-01-01

    Background and Purpose— Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. Methods— Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. Results— Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11–20 PVSs: HR, 1.15; 95% confidence interval, 0.78–1.68; >20 PVSs: HR, 1.82; 1.18–2.80; P=0.011) but not intracerebral hemorrhage (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were similar in both cohorts. Conclusions— Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not. PMID:28495831

  8. Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

    PubMed Central

    Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

    2015-01-01

    A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

  9. Protective effects of transduced Tat-DJ-1 protein against oxidative stress and ischemic brain injury.

    PubMed

    Jeong, Hoon Jae; Kim, Dae Won; Kim, Mi Jin; Woo, Su Jung; Kim, Hye Ri; Kim, So Mi; Jo, Hyo Sang; Hwang, Hyun Sook; Kim, Duk Soo; Cho, Sung Woo; Won, Moo Ho; Han, Kyu Hyung; Park, Jin Seu; Eum, Won Sik; Choi, Soo Young

    2012-10-31

    Reactive oxygen species (ROS) contribute to the development of a number of neuronal diseases including ischemia. DJ-1, also known to PARK7, plays an important role in transcriptional regulation, acting as molecular chaperone and antioxidant. In the present study, we investigated whether DJ-1 protein shows a protective effect against oxidative stress-induced neuronal cell death in vitro and in ischemic animal models in vivo. To explore DJ-1 protein's potential role in protecting against ischemic cell death, we constructed cell permeable Tat-DJ-1 fusion proteins. Tat-DJ-1 protein efficiently transduced into neuronal cells in a doseand time-dependent manner. Transduced Tat-DJ-1 protein increased cell survival against hydrogen peroxide (H2O2) toxicity and also reduced intracellular ROS. In addition, Tat-DJ-1 protein inhibited DNA fragmentation induced by H2O2. Furthermore, in animal models, immunohistochemical analysis revealed that Tat-DJ-1 protein prevented neuronal cell death induced by transient forebrain ischemia in the CA1 region of the hippocampus. These results demonstrate that transduced Tat-DJ-1 protein protects against cell death in vitro and in vivo, suggesting that the transduction of Tat-DJ-1 may be useful as a therapeutic agent for ischemic injuries related to oxidative stress.

  10. Muscle Stem Cell Therapy for the Treatment of DMD Associated Cardiomyopathy

    DTIC Science & Technology

    2013-10-01

    Fehrenbacher JW et al. Proinflammatory cytokine effects on mesenchymal stem cell therapy for the ischemic heart. Ann Thorac Surg Sep 2009;88:1036–1043. 45 Payne... mesenchymal stem cells (MSCs) (5). Activation of RhoA-ROCK signaling in cultured MSCs in vitro induces their osteogenesis but Figure 5 Angiogenesis...osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res. 2005;20(10):1858-66. PMCID

  11. Mild and Short-Term Caloric Restriction Prevents Obesity-Induced Cardiomyopathy in Young Zucker Rats without Changing in Metabolites and Fatty Acids Cardiac Profile

    PubMed Central

    Ruiz-Hurtado, Gema; García-Prieto, Concha F.; Pulido-Olmo, Helena; Velasco-Martín, Juan P.; Villa-Valverde, Palmira; Fernández-Valle, María E.; Boscá, Lisardo; Fernández-Velasco, María; Regadera, Javier; Somoza, Beatriz; Fernández-Alfonso, María S.

    2017-01-01

    Caloric restriction (CR) ameliorates cardiac dysfunction associated with obesity. However, most of the studies have been performed under severe CR (30–65% caloric intake decrease) for several months or even years in aged animals. Here, we investigated whether mild (20% food intake reduction) and short-term (2-weeks) CR prevented the obese cardiomyopathy phenotype and improved the metabolic profile of young (14 weeks of age) genetically obese Zucker fa/fa rats. Heart weight (HW) and HW/tibia length ratio was significantly lower in fa/fa rats after 2 weeks of CR than in counterparts fed ad libitum. Invasive pressure measurements showed that systolic blood pressure, maximal rate of positive left ventricle (LV) pressure, LV systolic pressure and LV end-diastolic pressure were all significantly higher in obese fa/fa rats than in lean counterparts, which were prevented by CR. Magnetic resonance imaging revealed that the increase in LV end-systolic volume, stroke volume and LV wall thickness observed in fa/fa rats was significantly lower in animals on CR diet. Histological analysis also revealed that CR blocked the significant increase in cardiomyocyte diameter in obese fa/fa rats. High resolution magic angle spinning magnetic resonance spectroscopy analysis of the LV revealed a global decrease in metabolites such as taurine, creatine and phosphocreatine, glutamate, glutamine and glutathione, in obese fa/fa rats, whereas lactate concentration was increased. By contrast, fatty acid concentrations in LV tissue were significantly elevated in obese fa/fa rats. CR failed to restore the LV metabolomic profile of obese fa/fa rats. In conclusion, mild and short-term CR prevented an obesity-induced cardiomyopathy phenotype in young obese fa/fa rats independently of the cardiac metabolic profile. PMID:28203206

  12. Developments in the management of Chagas cardiomyopathy

    PubMed Central

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2016-01-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising. PMID:26496376

  13. Developments in the management of Chagas cardiomyopathy.

    PubMed

    Tanowitz, Herbert B; Machado, Fabiana S; Spray, David C; Friedman, Joel M; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi; Moraes, Diego N; Garg, Nisha Jain; Nunes, Maria Carmo P; Ribeiro, Antonio Luiz P

    2015-12-01

    Over 100 years have elapsed since the discovery of Chagas disease and there is still much to learn regarding pathogenesis and treatment. Although there are antiparasitic drugs available, such as benznidazole and nifurtimox, they are not totally reliable and often toxic. A recently released negative clinical trial with benznidazole in patients with chronic Chagas cardiomyopathy further reinforces the concerns regarding its effectiveness. New drugs and new delivery systems, including those based on nanotechnology, are being sought. Although vaccine development is still in its infancy, the reality of a therapeutic vaccine remains a challenge. New ECG methods may help to recognize patients prone to developing malignant ventricular arrhythmias. The management of heart failure, stroke and arrhythmias also remains a challenge. Although animal experiments have suggested that stem cell based therapy may be therapeutic in the management of heart failure in Chagas cardiomyopathy, clinical trials have not been promising.

  14. Asn391Thr Mutation of β-Myosin Heavy Chain in a Hypertrophic Cardiomyopathy Family.

    PubMed

    Feng, Xiaotong; He, Tingting; Wang, Ji-Gang; Zhao, Peng

    2018-05-30

    The present study was performed to identify the genetic abnormalities in a family with familial hypertrophic cardiomyopathy.Peripheral blood samples were collected from 22 members of a Chinese family with hypertrophic cardiomyopathy and 307 healthy controls. A total of 26 candidate pathogenic genes were analyzed in the proband using targeted capture sequencing. Identified mutations were analyzed using Sanger sequencing in all family members and healthy controls.A missense mutation (c.1172A>C, p. Asn391Thr) in exon 12 of MYH7 was identified in eight family members, among which six of them were hypertrophic cardiomyopathy carriers. Three carriers presented with cardiac dysfunction. Four members of this pedigree died suddenly, three of whom were diagnosed with hypertrophic cardiomyopathy.From the results of this study, we concluded that the Asn391Thr mutation of MYH7 is a malignant mutation for HCM and that mutation carriers should get effective treatment to prevent sudden death.

  15. Eriodictyol-7-O-glucoside activates Nrf2 and protects against cerebral ischemic injury

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jing, Xu; Ren, Dongmei; Wei, Xinbing

    Stroke is a complex disease that may involve oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2/antioxidant response element (Nrf2/ARE) pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and thus has been considered a potential target for neuroprotection in stroke. The aim of the present study was to determine whether eriodictyol-7-O-glucoside (E7G), a novel Nrf2 activator, can protect against cerebral ischemic injury and to understand the role of the Nrf2/ARE pathway in neuroprotection. In primary cultured astrocytes, E7G increased the nuclear localization of Nrf2 and induced the expression of the Nrf2/ARE-dependentmore » genes. Exposure of astrocytes to E7G provided protection against oxygen and glucose deprivation (OGD)-induced oxidative insult. The protective effect of E7G was abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo administration of E7G in a rat model of focal cerebral ischemia significantly reduced the amount of brain damage and ameliorated neurological deficits. These data demonstrate that activation of Nrf2/ARE signaling by E7G is directly associated with its neuroprotection against oxidative stress-induced ischemic injury and suggest that targeting the Nrf2/ARE pathway may be a promising approach for therapeutic intervention in stroke. - Highlights: • E7G activates Nrf2 in astrocytes. • E7G stimulates expression of Nrf2-mediated cytoprotective proteins in astrocytes. • E7G protects astrocytes against OGD-induced cell death and apoptosis. • The neuroprotective effect of E7G involves the Nrf2/ARE pathway. • E7G protects rats against cerebral ischemic injury.« less

  16. Ventricular assist device implantation in a young patient with non-compaction cardiomyopathy and hereditary spherocytosis.

    PubMed

    Huenges, Katharina; Panholzer, Bernd; Cremer, Jochen; Haneya, Assad

    2018-04-01

    A case of a 15-year-old female patient with acute heart failure due to non-compaction cardiomyopathy and hereditary anaemia (hereditary spherocytic elliptocytosis) requiring ventricular assist device implantation as a bridge to transplantation is presented. The possible effects of mechanical stress on erythrocytes potentially induced by mechanical circulatory support remains unclear, but it may lead to haemolytic crisis in patients suffering from hereditary anaemia. In our case, ventricular assist device therapy was feasible, and haematological complications did not occur within 6 weeks of bridging our patient to heart transplantation.

  17. Congestive cardiomyopathy and endobronchial granulomas as manifestations of Churg-Strauss syndrome.

    PubMed Central

    Alvarez-Sala, R.; Prados, C.; Armada, E.; Del Arco, A.; Villamor, J.

    1995-01-01

    Churg-Strauss syndrome is a systemic vasculitis. Its most frequent complications are heart diseases and asthma. Usually, cardiological manifestations are pericarditis, cardiac failure and myocardial infarction. Endobronchial granulomas identified by bronchoscopy are unusual. We present the case of a man with congestive cardiomyopathy and endobronchial granulomas macroscopically visible at bronchoscopy. After a review of medical literature, we found one case of congestive cardiomyopathy and no cases of endobronchial granulomas observed by bronchoscopy associated with Churg-Strauss syndrome. Images Figure PMID:7644400

  18. Postoperative Takotsubo cardiomyopathy triggered by intraoperative fluid overload and acute hypertensive crisis

    PubMed Central

    Varutti, Rosanna; Setti, Tommaso; Ezri, Tiberiu; Nicolosi, Gianluigi; Rellini, Gianluigi; Cassin, Matteo; Leykin, Yigal

    2015-01-01

    The Takotsubo cardiomyopathy is a rare haemodynamic dysfunction, only recently reported perioperatively. While the diagnostic criteria have been established and the outcome is known as favorable, the pathophysiological mechanisms are not entirely understood. Here we present the case of a patient scheduled for laparoscopic hysterectomy and adnexectomy, who early postoperatively developed a Takotsubo cardiomyopathy supposedly triggered by an acute hypertensive crisis due to intraoperative fluid overload. PMID:28913455

  19. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Magnusson, Lisa U.; Lundqvist, Annika; Asp, Julia

    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to lowmore » concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  20. Long-term survival and regeneration of neuronal and vasculature cells inside the core region after ischemic stroke in adult mice.

    PubMed

    Jiang, Michael Qize; Zhao, Ying-Ying; Cao, Wenyuan; Wei, Zheng Zachory; Gu, Xiaohuan; Wei, Ling; Yu, Shan Ping

    2017-07-01

    Focal cerebral ischemia results in an ischemic core surrounded by the peri-infarct region (penumbra). Most research attention has been focused on penumbra while the pattern of cell fates inside the ischemic core is poorly defined. In the present investigation, we tested the hypothesis that, inside the ischemic core, some neuronal and vascular cells could survive the initial ischemic insult while regenerative niches might exist many days after stroke in the adult brain. Adult mice were subjected to focal cerebral ischemia induced by permanent occlusion of distal branches of the middle cerebral artery (MCA) plus transient ligations of bilateral common carotid artery (CCA). The ischemic insult uniformly reduced the local cerebral blood flow (LCBF) by 90%. Massive cell death occurred due to multiple mechanisms and a significant infarction was cultivated in the ischemic cortex 24 h later. Nevertheless, normal or even higher levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) persistently remained in the core tissue, some NeuN-positive and Glut-1/College IV-positive cells with intact ultrastructural features resided in the core 7-14 days post stroke. BrdU-positive but TUNEL-negative neuronal and endothelial cells were detected in the core where extensive extracellular matrix infrastructure developed. Meanwhile, GFAP-positive astrocytes accumulated in the penumbra and Iba-1-positive microglial/macrophages invaded the core several days after stroke. The long term survival of neuronal and vascular cells inside the ischemic core was also seen after a severe ischemic stroke induced by permanent embolic occlusion of the MCA. We demonstrate that a therapeutic intervention of pharmacological hypothermia could save neurons/endothelial cells inside the core. These data suggest that the ischemic core is an actively regulated brain region with residual and newly formed viable neuronal and vascular cells acutely and chronically after at

  1. Peripartum cardiomyopathy in the Hospital Albert Schweitzer District of Haiti.

    PubMed

    Fett, James D; Carraway, Robert D; Dowell, Duane L; King, Mary Etta; Pierre, Ronald

    2002-05-01

    This report details current epidemiologic information on peripartum cardiomyopathy in 1 district of Haiti and represents the initial report of an ongoing investigation that addresses potential etiologic and prognostic factors. Another goal is to alert the medical community of what appears to be a high-incidence area. A detailed peripartum cardiomyopathy registry has been implemented to include a review of case records from 1994 to 2000 and subsequently to identify new cases from February 1, 2000, to July 1, 2001. The Hospital Albert Schweitzer District of Haiti is a 600-square mile area with approximately 258,000 population served by a hospital, an associated clinic, and outlying health centers. There are approximately 7740 live births annually. This report details epidemiologic information on the HAS District peripartum cardiomyopathy patients including incidence, mortality rate, complications, and prognostic factors. There were 47 confirmed patients (retrospective cohort, 20 patients; prospective cohort, 27 patients), which was approximately 1 case per 400 live births (compared with an incidence of 1 case per 3000 to 4000 live births in the United States). There were 4 deaths (14% of 29 patients with follow-up), and 7 complications (pulmonary embolism, 1 case; hemiplegia, 1 case; subsequent deterioration of heart function, 5 cases). The prognosis for subsequent pregnancy was 4 of 5 cases (80%) of recurrent congestive heart failure. Peripartum cardiomyopathy appears to be relatively common in the Hospital Albert Schweitzer District of Haiti. A core group of patients is identified for ongoing epidemiologic and immunohematologic investigation of risk factors and potential etiologic factors.

  2. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Ching-Chih; Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan; Tumor Center, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival ratemore » between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.« less

  3. A Novel Locus For Dilated Cardiomyopathy Maps to Canine Chromosome 8

    PubMed Central

    Werner, Petra; Raducha, Michael G.; Prociuk, Ulana; Sleeper, Meg M.; Henthorn, Paula S.

    2008-01-01

    Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint LOD scores of 10.8 and 14, respectively. The locus maps to a 3.9 Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure. PMID:18442891

  4. A novel locus for dilated cardiomyopathy maps to canine chromosome 8.

    PubMed

    Werner, Petra; Raducha, Michael G; Prociuk, Ulana; Sleeper, Meg M; Van Winkle, Thomas J; Henthorn, Paula S

    2008-06-01

    Dilated cardiomyopathy (DCM), the most common form of cardiomyopathy, often leads to heart failure and sudden death. While a substantial proportion of DCMs are inherited, mutations responsible for the majority of DCMs remain unidentified. A genome-wide linkage study was performed to identify the locus responsible for an autosomal recessive inherited form of juvenile DCM (JDCM) in Portuguese water dogs using 16 families segregating the disease. Results link the JDCM locus to canine chromosome 8 with two-point and multipoint lod scores of 10.8 and 14, respectively. The locus maps to a 3.9-Mb region, with complete syntenic homology to human chromosome 14, that contains no genes or loci known to be involved in the development of any type of cardiomyopathy. This discovery of a DCM locus with a previously unknown etiology will provide a new gene to examine in human DCM patients and a model for testing therapeutic approaches for heart failure.

  5. Angiotensin II effects on ischemic focal ventricular tachycardia are predominantly mediated through myocardial AT(2) receptor.

    PubMed

    Gopinathannair, Rakesh; Chaudhary, Ashok K; Xing, Dezhi; Ely, Debra; Zheng, Wei; Martins, James B

    2009-11-01

    Ischemic focal ventricular tachycardia (VT) occurs in animals and humans. Angiotensin-converting enzyme inhibitors and receptor blockers reduce sudden death in patients with ischemic heart disease. In our dog model of coronary artery occlusion (CAO), we tested the hypothesis that angiotensin II (AGII) will selectively promote focal VT and that the specific AT(2) blocker PD-123319 (PD), or AT(1) blocker losartan, will affect this VT. Anesthetized dogs (n = 90) underwent CAO, followed by three-dimensional activation mapping of inducible VT. Dogs without VT in 1-3 h after CAO received AGII, and those with VT received either PD or losartan. Focal endocardium excised from ischemic sites was studied in vitro with standard microelectrode. Of 33 dogs with no inducible VT, AGII infusion resulted in sustained VT of only focal Purkinje origin in 13 (39%) compared with 0 of 20 dogs with saline. Of 26 dogs with inducible VT at baseline, given PD, reinduction was blocked in 8 of 10 (P < 0.05) focal VT, but only 1 of 15 with reentry. In contrast, of 11 dogs given losartan, reinduction of either mechanism was not blocked. In vitro triggered activity in Purkinje was blocked by PD in 13 of 19 (P < 0.05), but not by losartan in 8. Also, triggered activity was promoted by AGII, losartan, or the combination in 9 of 12 tissues. AGII promotes only focal, mainly Purkinje ischemic VT. PD, but not losartan, preferentially blocked focal VT, which is likely due to triggered activity due to delayed afterdepolarizations in Purkinje.

  6. Contribution of mammalian target of rapamycin in the pathophysiology of cirrhotic cardiomyopathy.

    PubMed

    Saeedi Saravi, Seyed Soheil; Ghazi-Khansari, Mahmoud; Ejtemaei Mehr, Shahram; Nobakht, Maliheh; Mousavi, Seyyedeh Elaheh; Dehpour, Ahmad Reza

    2016-05-21

    To explore the role of mammalian target of rapamycin (mTOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition. Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon (CCl4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin (2 mg/kg per day). The QTc intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles were isolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-mTOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor (TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-mTOR protein. Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight (P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl4 (P < 0.001), while this prolongation was decreased with rapamycin treatment (P < 0.01). CCl4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-mTOR expression in left ventricles. Phosphorylated-mTOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-mTOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. In this study, we demonstrated a potential role for cardiac mTOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin

  7. Nerve Growth Factor Gene Therapy Using Adeno-Associated Viral Vectors Prevents Cardiomyopathy in Type 1 Diabetic Mice

    PubMed Central

    Meloni, Marco; Descamps, Betty; Caporali, Andrea; Zentilin, Lorena; Floris, Ilaria; Giacca, Mauro; Emanueli, Costanza

    2012-01-01

    Diabetes is a cause of cardiac dysfunction, reduced myocardial perfusion, and ultimately heart failure. Nerve growth factor (NGF) exerts protective effects on the cardiovascular system. This study investigated whether NGF gene transfer can prevent diabetic cardiomyopathy in mice. We worked with mice with streptozotocin-induced type 1 diabetes and with nondiabetic control mice. After having established that diabetes reduces cardiac NGF mRNA expression, we tested NGF gene therapies with adeno-associated viral vectors (AAVs) for the capacity to protect the diabetic mouse heart. To this aim, after 2 weeks of diabetes, cardiac expression of human NGF or β-Gal (control) genes was induced by either intramyocardial injection of AAV serotype 2 (AAV2) or systemic delivery of AAV serotype 9 (AAV9). Nondiabetic mice were given AAV2–β-Gal or AAV9–β-Gal. We found that the diabetic mice receiving NGF gene transfer via either AAV2 or AAV9 were spared the progressive deterioration of cardiac function and left ventricular chamber dilatation observed in β-Gal–injected diabetic mice. Moreover, they were additionally protected from myocardial microvascular rarefaction, hypoperfusion, increased deposition of interstitial fibrosis, and increased apoptosis of endothelial cells and cardiomyocytes, which afflicted the β-Gal–injected diabetic control mice. Our data suggest therapeutic potential of NGF for the prevention of cardiomyopathy in diabetic subjects. PMID:22187379

  8. Retinal ischemic injury rescued by sodium 4-phenylbutyrate in a rat model.

    PubMed

    Jeng, Yung-Yue; Lin, Nien-Ting; Chang, Pen-Heng; Huang, Yuan-Ping; Pang, Victor Fei; Liu, Chen-Hsuan; Lin, Chung-Tien

    2007-03-01

    Retinal ischemia is a common cause of visual impairment for humans and animals. Herein, the neuroprotective effects of phenylbutyrate (PBA) upon retinal ischemic injury were investigated using a rat model. Retinal ganglion cells (RGCs) were retrograde labeled with the fluorescent tracer fluorogold (FG) applied to the superior collicoli of test Sprague-Dawley rats. High intraocular pressure and retinal ischemia were induced seven days subsequent to such FG labeling. A dose of either 100 or 400 mg/kg PBA was administered intraperitoneally to test rats at two time points, namely 30 min prior to the induction of retinal ischemia and 1 h subsequent to the cessation of the procedure inducing retinal ischemia. The test-rat retinas were collected seven days subsequent to the induction of retinal ischemia, and densities of surviving RGCs were estimated by counting FG-labeled RGCs within the retina. Histological analysis revealed that ischemic injury caused the loss of retinal RGCs and a net decrease in retinal thickness. For PBA-treated groups, almost 100% of the RGCs were preserved by a pre-ischemia treatment with PBA (at a dose of either 100 or 400 mg/kg), while post-ischemia treatment of RGCs with PBA did not lead to the preservation of RGCs from ischemic injury by PBA as determined by the counting of whole-mount retinas. Pre-ischemia treatment of RGCs with PBA (at a dose of either 100 or 400 mg/kg) significantly reduced the level of ischemia-associated loss of thickness of the total retina, especially the inner retina, and the inner plexiform layer of retina. Besides, PBA treatment significantly reduced the ischemia-induced loss of cells in the ganglion-cell layer of the retina. Taken together, these results suggest that PBA demonstrates a marked neuroprotective effect upon high intraocular pressure-induced retinal ischemia when the PBA is administered prior to ischemia induction.

  9. THE INVOLVEMENT OF HUMAN MONOGENIC CARDIOMYOPATHY GENES IN EXPERIMENTAL POLYGENIC CARDIAC HYPERTROPHY.

    PubMed

    Prestes, Priscilla R; Marques, Francine Z; Lopez-Campos, Guillermo; Lewandowski, Paul; Delbridge, Lea M D; Charchar, Fadi J; Harrap, Stephen B

    2018-05-18

    Hypertrophic cardiomyopathy thickens heart muscles reducing functionality and increasing risk of cardiac disease and morbidity. Genetic factors are involved, but their contribution is poorly understood. We used the hypertrophic heart rat (HHR), a unique normotensive polygenic model of cardiac hypertrophy and heart failure to investigate the role of genes associated with monogenic human cardiomyopathy. We selected 42 genes involved in monogenic human cardiomyopathies to study: 1) DNA variants, by sequencing the whole-genome of 13-week old HHR and age-matched normal heart rat (NHR), its genetic control strain; 2) mRNA expression, by targeted RNA-sequencing in left ventricles of HHR and NHR at five ages (2-days old, 4-, 13-, 33- and 50-weeks old) compared to human idiopathic dilated data; and 3) microRNA expression, with rat microRNA microarrays in left ventricles of 2-days old HHR and age-matched NHR. We also investigated experimentally validated microRNA-mRNA interactions. Whole-genome sequencing revealed unique variants mostly located in non-coding regions of HHR and NHR. We found 29 genes differentially expressed in at least one age. Genes encoding desmoglein 2 (Dsg2) and transthyretin (Ttr) were significantly differentially expressed at all ages in the HHR, but only Ttr was also differentially expressed in human idiopathic cardiomyopathy. Lastly, only two microRNAs differentially expressed in the HHR were present in our comparison of validated microRNA-mRNA interactions. These two microRNAs interact with five of the genes studied. Our study shows that genes involved in monogenic forms of human cardiomyopathies may also influence polygenic forms of the disease.

  10. Brain-Derived Neurotrophic Factor Promotes Vasculature-Associated Migration of Neuronal Precursors toward the Ischemic Striatum

    PubMed Central

    Grade, Sofia; Weng, Yuan C.; Snapyan, Marina; Kriz, Jasna; Malva, João O.; Saghatelyan, Armen

    2013-01-01

    Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS. PMID:23383048

  11. Laser speckle contrast imaging of collateral blood flow during acute ischemic stroke

    PubMed Central

    Armitage, Glenn A; Todd, Kathryn G; Shuaib, Ashfaq; Winship, Ian R

    2010-01-01

    Collateral vasculature may provide an alternative route for blood flow to reach the ischemic tissue and partially maintain oxygen and nutrient support during ischemic stroke. However, much about the dynamics of stroke-induced collateralization remains unknown. In this study, we used laser speckle contrast imaging to map dynamic changes in collateral blood flow after middle cerebral artery occlusion in rats. We identified extensive anastomatic connections between the anterior and middle cerebral arteries that develop after vessel occlusion and persist for 24 hours. Augmenting blood flow through these persistent yet dynamic anastomatic connections may be an important but relatively unexplored avenue in stroke therapy. PMID:20517321

  12. Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet.

    PubMed

    Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

    2015-03-23

    Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH.

  13. Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet

    PubMed Central

    Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

    2015-01-01

    Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH. PMID:25797953

  14. Hypertrophic Cardiomyopathy in Athletes: Catching a Killer.

    ERIC Educational Resources Information Center

    Maron, Barry J.

    1993-01-01

    A leading cause of sudden death among young athletes, hypertrophic cardiomyopathy (HCM) does not always present cardiac signs and symptoms. Echocardiography offers the most effective means for diagnosis. Some patients require pharmaceutical or surgical intervention. Patients with HCM should not engage in organized competitive sports or…

  15. Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome

    PubMed Central

    Boyden, Lynn M.; Kam, Chen Y.; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G.; Sidbury, Robert; Mathes, Erin F.; Maguiness, Sheilagh M.; Crumrine, Debra A.; Williams, Mary L.; Hu, Ronghua; Lifton, Richard P.; Elias, Peter M.; Green, Kathleen J.; Choate, Keith A.

    2016-01-01

    Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. PMID:26604139

  16. Left dominant arrhythmogenic cardiomyopathy: a morbid association of ventricular arrhythmias and unexplained infero-lateral T-wave inversion.

    PubMed

    Protonotarios, Alexandros; Patrianakos, Alexandros; Spanoudaki, Elpida; Kochiadakis, Georgios; Michalodimitrakis, Emmanouel; Vardas, Panagiotis

    2013-01-01

    Left-dominant arrhythmogenic cardiomyopathy is a subtype of arrhythmogenic right ventricular cardiomyopathy characterized by early predominant left ventricular involvement. Α 34-year-old man presented with palpitations and a history of frequent ventricular extrasystoles of both LBBB and RBBB configuration. Cardiac workup revealed repolarization abnormalities at infero-lateral leads in the absence of diagnostic structural/functional alterations or obstructive coronary artery disease. Six months later he died suddenly. Histopathology was diagnostic for arrhythmogenic right ventricular cardiomyopathy affecting predominantly the left ventricle at subepicardial/midwall myocardial layers. Thus, ventricular arrhythmias accompanied by unexplained infero-lateral T-wave inversion should warn of a possible morbid association underlying left-dominant arrhythmogenic cardiomyopathy. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. [Left atrial function and left atrial appendage flow velocity in hypertrophic cardiomyopathy: comparison of patients with and without paroxysmal atrial fibrillation].

    PubMed

    Akasaka, K; Kawashima, E; Shiokoshi, T; Ishii, Y; Hasebe, N; Kikuchi, K

    1998-07-01

    The involvement of left atrial (LA) appendage flow velocity in reduced left atrial function was investigated in 24 patients with hypertrophic cardiomyopathy, who retained sinus rhythm at the examination. Patients were divided into 11 with a history of paroxysmal atrial fibrillation [PAf(+)] and 13 without such history [PAf(-)]. Transthoracic echocardiography was performed to evaluate LA fractional shortening (LA%FS) and mean velocity of circumferential LA fiber shortening (LAmVcf), as contractile functions of the left atrium at the phase of active atrial contraction. Transesophageal echocardiographic Doppler examination was performed in all patients to measure the LA appendage velocity. In all patients, significant positive correlations were observed between the LA appendage velocity and LA%FS (r = 0.50, p < 0.05) or LAmVcf (r = 0.82, p < 0.001). LAmVcf and LA appendage velocity in patients with paroxysmal fibrillation were significantly lower than in those without (0.84 +/- 0.15 vs 1.28 +/- 0.37 circ/sec, 44 +/- 12 vs 65 +/- 20 cm/sec, both p < 0.01), whereas LA diameter was greater in the former compared to the latter (45 +/- 5 vs 38 +/- 5 mm, p < 0.01). LAmVcf and LA appendage velocity were low in four patients with cerebral infarction or transient cerebral ischemic attack (LAmVcf < 1.0 circ/sec, LA appendage velocity < or = 40 cm/sec). Importantly, all these patients had a history of paroxysmal fibrillation. These results indicate that there is a close relationship between LA appendage velocity and LA contractile function in patients with hypertrophic cardiomyopathy with paroxysmal atrial fibrilation, and these patients have potential risk of cerebral infarction.

  18. [CHANGING OF ISCHEMIC M. SOLEUS TETANIC CONTRACTION PARAMETERS IN RATS WITH CHRONIC ALCOHOL INTOXICATION].

    PubMed

    Melnychuk, O A; Motuziuk, O P; Shvayko, S Ye

    2015-01-01

    This article deals with the changes of isolated ischemic m. soleus tetanus parameters in rats with chronic alcohol intoxication. The experiments were carried out on 15 male Wistar rats that were divided into three groups for 5 animals in each: group I (control) and two groups in which was induced hind limbs acute muscles ischemia: group II - rats without alcoholic intoxication, group III - rats with chronic alcoholic intoxication. Strain measurement muscle mechanical activity were conducted in isometric mode under conditions of direct electrical muscular preparation stimulation. It is proved that ischemic m. soleus tetanic force in rats with chronic alcoholic intoxication in comparison with rats without alcoholic intoxication does not significant changes. But signifycantly increases the reaching tetanus peak time. It is shown that in rats without alcoholic intoxication and with chronic alcoholic intoxication in comparison with intact animals, significantly decreases the duration of ischemic m. soleus stabile force level. It is shoved significant changes of individual muscles contraction time course of ischemic m. soleus tetanus in this rats group in comparison to intact animal. It is shown that these changes influence on successive muscular contraction efficiency of frequency summation in ischemic m. soleus tetanus and their speed-power characteristics.

  19. VKORC1 and CYP2C9 Gene Polymorphisms and Warfarin Management

    ClinicalTrials.gov

    2009-09-02

    Atrial Fibrillation; Cardiac Thrombus; Deep Vein Thrombosis; Pulmonary Embolism; Heart Valve Replacement (Mechanical or Biological With AF); Cardiomyopathy (Ischemic or Dilated); Peripheral Vascular Disease

  20. Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature.

    PubMed

    Kleinschnitz, Christoph; Kraft, Peter; Dreykluft, Angela; Hagedorn, Ina; Göbel, Kerstin; Schuhmann, Michael K; Langhauser, Friederike; Helluy, Xavier; Schwarz, Tobias; Bittner, Stefan; Mayer, Christian T; Brede, Marc; Varallyay, Csanad; Pham, Mirko; Bendszus, Martin; Jakob, Peter; Magnus, Tim; Meuth, Sven G; Iwakura, Yoichiro; Zernecke, Alma; Sparwasser, Tim; Nieswandt, Bernhard; Stoll, Guido; Wiendl, Heinz

    2013-01-24

    We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)-positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke and this protective effect was preserved at later stages of infarct development. The specificity of this detrimental Treg effect was confirmed by adoptive transfer experiments in wild-type mice and in Rag1(-/-) mice lacking lymphocytes. Mechanistically, Tregs induced microvascular dysfunction in vivo by increased interaction with the ischemic brain endothelium via the LFA-1/ICAM-1 pathway and platelets and these findings were confirmed in vitro. Ablation of Tregs reduced microvascular thrombus formation and improved cerebral reperfusion on stroke, as revealed by ultra-high-field magnetic resonance imaging at 17.6 Tesla. In contrast, established immunoregulatory characteristics of Tregs had no functional relevance. We define herein a novel and unexpected role of Tregs in a primary nonimmunologic disease state.