title: Endotoxemia causes central downregulation of sympathetic vasomotor tone in healthy humans.
abstract: Experimental endotoxemia as a model of the initial septic response affects the autonomic nervous system with profound cardiovascular sequelae. Whether the postsynaptic sympathoneural activity to the muscle vascular bed is altered in the early septic phase remains to be determined. The present study aimed to elucidate the early effects of LPS on muscle sympathetic nerve activity (MSNA) and cardiovascular regulation in healthy humans. Young, healthy volunteers randomly received either an LPS bolus (4 ng/kg body wt, n = 11) or placebo (saline; n = 7). Experimental baroreflex assessment (baseline measurements followed by infusion of vasoactive drugs nitroprusside/phenylephrine) was done prior to and 90 min following LPS or placebo challenge. MSNA, heart rate, blood pressure, and blood levels of catecholamines, TNF-alpha and IL-6 were measured sequentially. Endotoxin but not placebo-induced flu-like symptoms and elevated cytokine levels. In contrast to placebo, LPS significantly suppressed MSNA burst frequency 90 min after injection [mean +/- SE: 12.1 +/- 2.9 vs. 27.5 +/- 3.3 burst/min (post- vs. pre-LPS); P < 0.005] but increased heart rate [78.4 +/- 3.1 vs. 60.6 +/- 2.0 beats/min (post- vs. pre-LPS); P < 0.001]. Baseline blood pressure was not altered, but baroreflex testing demonstrated a blunted MSNA response and uncoupling of heart rate modulation to blood pressure changes in the endotoxin group. We conclude that endotoxin challenge in healthy humans has rapid suppressive effects on postsynaptic sympathetic nerve activity to the muscle vascular bed and alters baroreflex function which may contribute to the untoward cardiovascular effects of sepsis.
authors.affiliation: Clinic for Internal Medicine I, Univ. Hospital of Schleswig-Holstein, Campus Luebeck, Ratzeburger Allee 160, 23538 Luebeck, Germany. f.sayk@t-online.de
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Sayk
authors.forename: Alexander
authors.initials: A
authors.lastname: Vietheer
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schaaf
authors.forename: Peter
authors.initials: P
authors.lastname: Wellhoener
authors.forename: Gunther
authors.initials: G
authors.lastname: Weitz
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Christoph
authors.initials: C
authors.lastname: Dodt
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019446:Endotoxemia / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000294:innervation; D010919:Placebos; D011311:Pressoreceptors / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014666:Vasomotor System / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha