title: Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study.
abstract: OBJECTIVE
  Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown.
  
  
  RESULTS
  In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation.
  
  
  CONCLUSIONS
  These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH.
authors.affiliation: Istituto Auxologico Italiano, Milano, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Seravalle
authors.affiliation: Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy Ospedale San Gerardo, Monza, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
authors.affiliation: Ospedale San Gerardo, Monza, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mariani
authors.affiliation: Ospedale San Gerardo, Monza, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Pelloni
authors.affiliation: Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Facchetti
authors.affiliation: Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Dell'Oro
authors.affiliation: Istituto Auxologico Italiano, Milano, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Cuspidi
authors.affiliation: Istituto Auxologico Italiano, Milano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mancia
authors.affiliation: Dipartimento di Scienze della Salute, Università Milano-Bicocca, Milan, Italy IRCCS Multimedica, Sesto San Giovanni, Milano, Italy guido.grassi@unimib.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Grassi
mesh_terms: D000308:Adrenocortical Hyperfunction / Q000503:physiopathology; D000328:Adult; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D005293:Ferritins / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006432:Hemochromatosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D007502:Iron Chelating Agents / Q000627:therapeutic use; D019190:Iron Overload / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation; D013564:Sympathetic Nervous System / Q000502:physiology*; D014168:Transferrin / Q000378:metabolism
chemical_list: D007502:Iron Chelating Agents; D014168:Transferrin; D005293:Ferritins
keywords: Cardiovascular risk; Haemochromatosis; Iron depletion; Iron overload; Serum ferritin; Sympathetic nervous system