title: Macromolecular capillary leakage is involved in the onset of anaphylactic hypotension.
abstract: BACKGROUND
  The role of the hypovolemic component secondary to the microcirculatory changes in the onset of inaugural anaphylactic hypotension remains debated. We investigated the microcirculatory permeability in a model of anaphylactic shock using a fluorescence confocal microscopy imaging system.
  
  
  METHODS
  Ovalbumin-sensitized anesthetized Brown Norway rats were randomly allocated into two groups (n = 6/group): control and anaphylaxis, respectively induced by intravenous saline or ovalbumin at time 0 (T0). The mesentery was surgically exposed. Macromolecular fluorescein isothiocyanate-dextran was intravenously injected (T0-5min) allowing in vivo visualization of the mesenteric microvascular network by fluorescence microscopy. After a period of stabilization of the contrast agent concentration, a 5-s movie was recorded to obtain baseline signal intensity. Following T0, 5-s movies were recorded every 30 s for 30 min. Capillary leakage of fluorescein isothiocyanate-dextran was assessed in interstitium and compared between groups. Data are expressed as mean ± SD.
  
  
  RESULTS
  Following anaphylactic shock onset, an early, progressive, and global signal intensity increase over time was detected in the interstitium. Mean index leakage differed between control and anaphylaxis (respectively 20 ± 11 vs. 170 ± 127%; P < 0.0001), starting at 2 min after shock onset and progressively increasing. Index leakage correlated with the drop in arterial blood pressure until T0 + 10 min (r = -0.75, P = 0.0001).
  
  
  CONCLUSIONS
  During anaphylaxis, interstitial capillary leakage occurs within minutes after shock onset. Compared with controls, the mesenteric microcirculation showed at least 8-fold-increased macromolecular capillary leakage. The inflammation-induced microcirculatory changes with subsequent intravascular fluid transfer might be involved in the onset of the inaugural hypotension during anaphylactic shock.
authors.affiliation: Université Paris Descartes Sorbonne Paris Cité, INSERM UMR-S970, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faye
authors.forename: Laure
authors.initials: L
authors.lastname: Fournier
authors.forename: Daniel
authors.initials: D
authors.lastname: Balvay
authors.forename: Rokhaya
authors.initials: R
authors.lastname: Thiam
authors.forename: Gilles
authors.initials: G
authors.lastname: Orliaguet
authors.forename: Olivier
authors.initials: O
authors.lastname: Clément
authors.forename: Pascale
authors.initials: P
authors.lastname: Dewachter
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D007022:Hypotension / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D008297:Male; D010047:Ovalbumin / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D010047:Ovalbumin