title: Beta-adrenoreceptor modulation of metabolic, endocrine and immunologic function during critical illness.
abstract: Acute critical illness is characterized by a hypermetabolic and catabolic response where profound endocrine, metabolic and immunologic changes are initiated and sustained through the activation, in part, of beta-adrenergic receptors. The modulation of beta-adrenergic receptor mediated endocrine, immunological and metabolic control may be beneficial in sepsis through a number of mechanisms. However, the complex interaction between beta-adrenoreceptor-mediated, apparently disparate systems may confer both positive and negative clinical outcomes. Chronic cardiac failure and sepsis/critical illness share several similar endocrine, immunologic and metabolic pathological features. Beneficial beta-adrenergic modulation of various pathophysiological changes has been demonstrated in both experimental and clinical heart failure. Investigations in critical illness rarely take into account the role of beta-adrenoreceptor stimulation in patients with such co-morbidities, who are among the most vulnerable to sepsis. Despite similar phenotypes and possibly common mechanisms, few clinical studies have explored whether beta-adrenoreceptor modulation may confer outcome benefit during critical illness. Recent experimental and observational clinical data illustrate that carefully monitored, patient/subject-specific beta-adrenoreceptor modulation may provide a useful intervention to ameliorate the detrimental effects of hyperacute and/or prolonged beta-adrenergic receptor stimulation. Most notably, human studies demonstrate that (non-specific) beta-adrenoreceptor blockade does not increase inflammation, sepsis, or infectious episodes. Furthermore, hemodynamically tailored beta-1 adrenoreceptor antagonism improves outcome in experimental sepsis through novel cardiac and non-cardiac mechanisms. Understanding the dynamic complexity of beta-adrenergic physiology during critical illness offers further insights into the mechanisms underlying maladaptive metabolic and immunologic changes and potentially novel therapeutic interventions.
authors.affiliation: Department of Medicine, Wolfson Institute for Biomedical Research, Wing 3.2, Cruciform Building, Gower Street, University College London, London WC1E 6BT, UK.
authors.forename: Simon James
authors.initials: SJ
authors.lastname: Barnes
authors.forename: Gareth Lewis
authors.initials: GL
authors.lastname: Ackland
mesh_terms: D000818:Animals; D016638:Critical Illness; D004703:Endocrine System / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000276:immunology / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000276:immunology* / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism*
chemical_list: D011943:Receptors, Adrenergic, beta