Academic Journal

Molecular Mechanisms Linking Autonomic Dysfunction and Impaired Cardiac Contractility in Critical Illness

التفاصيل البيبلوغرافية
العنوان: Molecular Mechanisms Linking Autonomic Dysfunction and Impaired Cardiac Contractility in Critical Illness
المؤلفون: Ackland, GL, Whittle, J, Toner, A, Machhada, A, Del Arroyo, AG, Sciuso, A, Jenkins, N, Dyson, A, Struthers, R, Sneyd, JR, Minto, G, Singer, M, Shah, AM, Gourine, AV
المصدر: Critical Care Medicine , 44 (8) e614-e624. (2016)
بيانات النشر: LIPPINCOTT WILLIAMS & WILKINS
سنة النشر: 2016
المجموعة: University College London: UCL Discovery
مصطلحات موضوعية: Science & Technology, Life Sciences & Biomedicine, Critical Care Medicine, General & Internal Medicine, autonomic dysfunction, cardiac contractility, G-protein-coupled receptor, G-protein-coupled receptor kinase, multiple organ dysfunction syndrome, sepsis, Randomized Controlled-trial, Coupled Receptor Kinases, Blood Mononuclear-cells, Heart-rate-variability, Beta-arrestins, Sinoaortic Denervation, Nervous-system, Severe Sepsis, Rate Recovery, Septic Shock
الوصف: OBJECTIVES: Molecular mechanisms linking autonomic dysfunction with poorer clinical outcomes in critical illness remain unclear. We hypothesized that baroreflex dysfunction alone is sufficient to cause cardiac impairment through neurohormonal activation of (nicotinamide adenine dinucleotide phosphate oxidase dependent) oxidative stress resulting in increased expression of G-protein–coupled receptor kinase 2, a key negative regulator of cardiac function. DESIGN: Laboratory/clinical investigations. SETTING: University laboratory/medical centers. SUBJECTS: Adult rats; wild-type/nicotinamide adenine dinucleotide phosphate oxidase subunit-2–deficient mice; elective surgical patients. INTERVENTIONS: Cardiac performance was assessed by transthoracic echocardiography following experimental baroreflex dysfunction (sino-aortic denervation) in rats and mice. Immunoblots assessed G-protein–coupled receptor recycling proteins expression in rodent cardiomyocytes and patient mononuclear leukocytes. In surgical patients, heart rate recovery after cardiopulmonary exercise testing, time/frequency measures of parasympathetic variables were related to the presence/absence of baroreflex dysfunction (defined by spontaneous baroreflex sensitivity of <6 ms mm Hg–1). The associations of baroreflex dysfunction with intraoperative cardiac function and outcomes were assessed. MEASUREMENTS AND MAIN RESULTS: Experimental baroreflex dysfunction in rats and mice resulted in impaired cardiac contractility and upregulation of G-protein–coupled receptor kinase 2 expression. In mice, genetic deficiency of gp91 nicotinamide adenine dinucleotide phosphate oxidase subunit-2 prevented upregulation of G-protein–coupled receptor kinase 2 expression in conditions of baroreflex dysfunction and preserved cardiac function. Baroreflex dysfunction was present in 81 of 249 patients (32.5%) and was characterized by lower parasympathetic tone and increased G-protein–coupled receptor kinase 2 expression in mononuclear leukocytes. Baroreflex dysfunction in ...
نوع الوثيقة: article in journal/newspaper
وصف الملف: text
اللغة: English
Relation: https://discovery.ucl.ac.uk/id/eprint/1489590/1/Ackland%20Molecular%20Mechanisms%20Linking%20Autonomic%20Dysfunction%20and%20Impaired%20Cardiac%20Contractility%20in%20Critical%20Illness%20AAM.pdf; https://discovery.ucl.ac.uk/id/eprint/1489590/
الاتاحة: https://discovery.ucl.ac.uk/id/eprint/1489590/1/Ackland%20Molecular%20Mechanisms%20Linking%20Autonomic%20Dysfunction%20and%20Impaired%20Cardiac%20Contractility%20in%20Critical%20Illness%20AAM.pdf
https://discovery.ucl.ac.uk/id/eprint/1489590/
Rights: open
رقم الانضمام: edsbas.DC4EA91
قاعدة البيانات: BASE