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Beta blockade

Suparna C Clasen, Joyce W Wald
PURPOSE OF REVIEW: We aim to summarize the effect of cancer therapy-related cardiotoxicity on the development of left ventricular (LV) dysfunction. RECENT FINDINGS: We discuss commonly used cancer therapeutics that have the potential for both acute and delayed cardiotoxicity. LV dysfunction from cancer therapies may be found by routine cardiac imaging prior to clinical manifestations of heart failure (HF) and we discuss the current multi-modality approaches for early detection of toxicity with the use of advanced echocardiographic parameters including strain techniques...
March 8, 2018: Current Cardiology Reports
Xingjian Liu, Nikhil Khadtare, Hardek Patel, Ralph Stephani, Jerome Cantor
INTRODUCTION: A number of studies indicate that endothelin-1 (ET-1) may act as an inflammatory cell "gatekeeper," by regulating the influx of neutrophils following pulmonary injury. To further examine the role of ET-1 in modulating lung inflammation, hamsters were treated with an endothelin receptor antagonist (ERA), HJP272, either 1 h prior to intratracheal instillation of amiodarone (AM) or 24 h afterwards. METHODS: In both cases, the extent of lung injury and repair was determined by (1) histopathological changes; (2) neutrophil content in bronchoalveolar lavage fluid (BALF); (3) lung collagen content; (4) tumor necrosis factor receptor 1 expression by BALF macrophages; (5) BALF levels of (a) transforming growth factor beta-1, (b) stromal cell-derived factor 1 (commonly referred to as CXCL12), and (c) platelet-derived growth factor BB; (6) alveolar septal cell apoptosis...
March 7, 2018: Lung
Quan Jin, Chunping Qiao, Jianbin Li, Juan Li, Xiao Xiao
Growth and differentiation factor 11 (GDF11; BMP11) is a circulating cytokine in the transforming growth factor beta (TGF-β) superfamily. Treatment with recombinant GDF11 (rGDF11) protein has previously been shown to reverse skeletal muscle dysfunction in aged mice. However, the actions of GDF11 in skeletal muscle are still not fully understood. Because GDF11 activates the TGF-β-SMAD2/3 pathway, we hypothesized that GDF11 overexpression would inhibit skeletal muscle growth. To test this hypothesis, we generated recombinant adeno-associated virus serotype 9 (AAV9) vectors harboring the gene for either human GDF11 (AAV9-GDF11) or human IgG1 Fc-fused GDF11 propeptide (AAV9-GDF11Pro-Fc-1) to study the effects of GDF11 overexpression or blockade on skeletal muscle growth and function in vivo...
February 2, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Isabel González-Mariscal, Rodrigo A Montoro, Máire E Doyle, Qing-Rong Liu, Michael Rouse, Jennifer F O'Connell, Sara Santa-Cruz Calvo, Susan M Krzysik-Walker, Soumita Ghosh, Olga D Carlson, Elin Lehrmann, Yongqing Zhang, Kevin G Becker, Chee W Chia, Paritosh Ghosh, Josephine M Egan
AIMS/HYPOTHESIS: The cannabinoid 1 receptor (CB1R) regulates insulin sensitivity and glucose metabolism in peripheral tissues. CB1R is expressed on pancreatic beta cells and is coupled to the G protein Gαi, suggesting a negative regulation of endogenous signalling in the beta cell. Deciphering the exact function of CB1R in beta cells has been confounded by the expression of this receptor on multiple tissues involved in regulating metabolism. Thus, in models of global genetic or pharmacological CB1R blockade, it is difficult to distinguish the indirect effects of improved insulin sensitivity in peripheral tissues from the direct effects of inhibiting CB1R in beta cells per se...
March 1, 2018: Diabetologia
Fangyun Tian, Tiecheng Liu, Gang Xu, Duan Li, Talha Ghazi, Trevor Shick, Azeem Sajjad, Michael M Wang, Peter Farrehi, Jimo Borjigin
Sudden cardiac arrest is a leading cause of death in the United States. The neurophysiological mechanism underlying sudden death is not well understood. Previously we have shown that the brain is highly stimulated in dying animals and that asphyxia-induced death could be delayed by blocking the intact brain-heart neuronal connection. These studies suggest that the autonomic nervous system plays an important role in mediating sudden cardiac arrest. In this study, we tested the effectiveness of phentolamine and atenolol, individually or combined, in prolonging functionality of the vital organs in CO2 -mediated asphyxic cardiac arrest model...
2018: Frontiers in Physiology
Kei Iizuka, Tomohiro Nishinaka, Noritsugu Naito, Daichi Akiyama, Yoshiaki Takewa, Kenji Yamazaki, Eisuke Tatsumi
Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48 ± 2 kg) underwent centrifugal type LVAD, EVAHEART, implantation...
February 20, 2018: Journal of Artificial Organs: the Official Journal of the Japanese Society for Artificial Organs
Kyunghwa Baek, Jiho Kang, Jinu Lee, Min Kim, Jeong-Hwa Baek
We aimed to clarify the key factor determining the effect of beta blocker attenuating high fat diet- induced obesity and bone loss. Six-week-old C57BL/6 male mice were assigned to groups reflecting different relative onset of obesity and beta blocker administration, different diet (control vs. high fat), and treatment (vehicle vs. beta blocker: propranolol). Mice in Group 1 were fed a control diet (CON) or high fat diet (HIGH) with vehicle or propranolol for 12 weeks. Mice in Group 2 were fed a CON or HIGH without pharmaceutical treatment for the first 12 weeks, followed by another 12 weeks of treatment with vehicle or propranolol...
February 19, 2018: Calcified Tissue International
Mercedes N Munkonda, Shareef Akbari, Chloe Landry, Suzy Sun, Fengxia Xiao, Maddison Turner, Chet E Holterman, Rania Nasrallah, Richard L Hébert, Christopher R J Kennedy, Dylan Burger
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses...
2018: Journal of Extracellular Vesicles
Elizabeth do Espirito Santo Cestário, Letícia Aparecida Barufi Fernandes, Luiz Tadeu Giollo-Júnior, Jéssica Rodrigues Roma Uyemura, Camila Suemi Sato Matarucco, Manoel Idelfonso Paz Landim, Luciana Neves Cosenso-Martin, Lúcia Helena Bonalume Tácito, Heitor Moreno, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo
BACKGROUND: Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney...
February 12, 2018: Trials
Hanho Shin, Ji Hye Han, Juhwan Yoon, Hyo Jung Sim, Tae Joo Park, Siyoung Yang, Eun Kyung Lee, Rohit N Kulkarni, Josephine M Egan, Wook Kim
Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating β-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse β-cell lines and human islets. In addition, silencing CB1R in mouse β cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in β cells lacking insulin receptor...
February 12, 2018: Journal of Cellular and Molecular Medicine
Christie L Glau, Thomas W Conlon, Adam S Himebauch, Nadir Yehya, Scott L Weiss, Robert A Berg, Akira Nishisaki
OBJECTIVES: Diaphragm atrophy is associated with delayed weaning from mechanical ventilation and increased mortality in critically ill adults. We sought to test for the presence of diaphragm atrophy in children with acute respiratory failure. DESIGN: Prospective, observational study. SETTING: Single-center tertiary noncardiac PICU in a children's hospital. PATIENTS: Invasively ventilated children with acute respiratory failure...
February 5, 2018: Pediatric Critical Care Medicine
Kathleen M Kokolus, Ying Zhang, Jeffrey M Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A Repasky, Joseph J Drabick, Todd D Schell
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers...
2018: Oncoimmunology
Harald A Bergan, Per S Halvorsen, Andreas Espinoza, Viesturs Kerans, Helge Skulstad, Erik Fosse, Jan F Bugge
Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated...
February 2, 2018: Therapeutic Hypothermia and Temperature Management
Gabriel Camargo-Silva, Larissa Córdova Turones, Kellen Rosa da Cruz, Karina Pereira Gomes, Michelle Mendanha Mendonça, Allancer Nunes, Itamar Guedes de Jesus, Diego Basile Colugnati, Aline Priscila Pansani, Roger Luis Henschel Pobbe, Robson Santos, Marco Antônio Peliky Fontes, Silvia Guatimosim, Carlos Henrique de Castro, Danielle Ianzer, Reginaldo Nassar Ferreira, Carlos Henrique Xavier
Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress. AIMS: In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats. MAIN METHODS AND KEY FINDINGS: Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade...
January 20, 2018: Life Sciences
Thomas F Whayne, Sibu P Saha
PURPOSE OF REVIEW: Coronary artery event includes acute coronary syndrome (ACS), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery. Following such an event, risk of noncardiac surgery is increased. Of major concern is what can make this surgery safer? RECENT FINDINGS: High functional capacity improves cardiovascular (CV) risk; at least 4.0 metabolic equivalents (METs) on stress test are favorable. Risk scores can suggest need for further evaluation...
January 20, 2018: Current Cardiology Reports
Amir Azarbal, Kevin L Leadholm, Takamaru Ashikaga, Richard J Solomon, Harold L Dauerman
Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is associated with increased mortality. As significant hemodynamic improvement may occur with relief of aortic stenosis, we hypothesized that TAVI patients may demonstrate the opposite phenomena: acute kidney recovery (AKR). We studied the incidence and predictors of AKR in post-TAVI patients. A total of 366 consecutive patients underwent TAVI (January 2012 to January 2017) at a single center. We defined AKR as a 25% improvement in glomerular filtration rate (GFR) at 48 hours after TAVI...
December 13, 2017: American Journal of Cardiology
James T Pearson, Nicola Collie, Regis R Lamberts, Tadakatsu Inagaki, Misa Yoshimoto, Keiji Umetani, Philip Davis, Gerard Wilkins, Pete P Jones, Mikiyasu Shirai, Daryl O Schwenke
Acute myocardial infarction (MI) triggers an adverse increase in cardiac sympathetic nerve activity (SNA). While β-adrenergic receptor (β-AR)-blockers are routinely used for the management of MI, they may also counter β-AR-mediated vasodilation of coronary vessels. We have reported that ghrelin prevents sympathetic activation following MI. Whether ghrelin modulates coronary vascular tone following MI, either through the modulation of SNA, or directly as a vasoactive mediator, has never been addressed.We utilized synchrotron microangiography to image coronary perfusion and vessel internal diameter (ID) in anesthetized Sprague Dawley rats before, and then again 30 mins after induction of an MI (left coronary artery ligation)...
January 9, 2018: Endocrinology
Jiangchun Wu, Ruobing Wang, Dianxu Yang, Wenbin Tang, Zeli Chen, Qinglei Sun, Lin Liu, Rongyu Zang
Retinal ischemia/reperfusion injury (IRI) plays a crucial role in the pathophysiology of various ocular diseases. Our previous study have shown that postconditioning with inhaled hydrogen (H2) (HPC) can protect retinal ganglion cells (RGCs) in a rat model of retinal IRI. Our further study aims to investigate potential mechanisms underlying HPC-induced protection. Retinal IRI was performed on the right eyes of rats and was followed by inhalation of 67% H2 mixed with 33% oxygen immediately after ischemia for 1 h daily for one week...
December 27, 2017: Biochemical and Biophysical Research Communications
Waseem Anani, Michael R Shurin
Myeloid derived suppressor cells (MDSC) represent only a minor fraction of circulating blood cells but play an important role in tumor formation and progression. They are a heterogeneous group of cells that influence the tumor microenvironment by depletion of amino acids, oxidative stress, decreased trafficking of antitumor effector cells, and increased regulatory T and regulatory dendritic cell responses. Investigational treatment strategies targeting MDSCs have attempted to inhibit MDSC development and expansion (stem cell factor blockade, modulate of cell signaling, and target MDSC migration and recruitment), inhibit MDSC function (nitric oxide inhibition and reactive oxygen and nitrogen species inhibition), differentiate MDSCs into more mature cells (Vitamins A and D, all-trans retinoic acid, interleukin-2, toll-like receptor 9 inhibitors, taxanes, beta-glucan particles, tumor-derived exosome inhibition, and very small size proteoliposomes), and destroy MDSCs (cytotoxic agents, ephrin A2 degradation, anti-interleukin 13, and histamine blockers)...
2017: Advances in Experimental Medicine and Biology
Jordan M Reese, Elizabeth S Bruinsma, David G Monroe, Vivian Negron, Vera J Suman, James N Ingle, Matthew P Goetz, John R Hawse
Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation...
November 14, 2017: Oncotarget
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