title: Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model.
abstract: BACKGROUND
  Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock.
  
  
  METHODS
  A laser Doppler flowmetry was used to measure liver perfusion index and a specific NO-sensitive electrode was inserted into liver parenchyma of anaesthetized rabbits. Hepatic autoregulation during moderate hypovolaemia {mean arterial pressure at 50 mm Hg without liver perfusion alteration; blood withdrawal 17.7 (4.2) ml [mean (SD)]} or haemorrhagic shock [mean arterial pressure at 20 mm Hg associated with liver perfusion impairment and lactic acidosis; blood withdrawal 56.0 (6.8) ml] were investigated over 60 min and were followed by a rapid infusion of the shed blood. Involvement of NO synthases was evaluated using a non-specific inhibitor, NAPNA (Nomega-nitro-L-arginine P-nitro-anilide).
  
  
  RESULTS
  In the autoregulation group, a decrease [30.0 (4.0) mm Hg] of mean arterial pressure did not alter liver perfusion index, whereas the liver NO concentration increased and reached a plateau [125 (10)%; compared with baseline; P<0.05]. This NO concentration was reduced to zero by the administration of NO synthase inhibitor. Haemorrhagic shock led to a rapid decrease in liver perfusion index [60 (7)%; compared with baseline; P<0.05] before an immediate and continuous increase in NO concentration [250 (50)%; compared with baseline; P<0.05]. Infusion of NO inhibitor before haemorrhagic shock reduced the NO concentration to zero and hepatic perfusion by 60 (8)% (P<0.05) of the baseline. Mean arterial pressure increased simultaneously. In these animals, during haemorrhage, a continuous increase in NO concentration still occurred and liver perfusion slightly increased. In all groups but NAPNA+haemorrhagic shock, blood replacement induced recovery of baseline values.
  
  
  CONCLUSIONS
  NO plays a physiological role in the liver microcirculation during autoregulation. Its production is enzyme-dependent. Conversely, haemorrhagic shock induces a rapid increase in hepatic NO that is at least partially enzyme-independent.
authors.affiliation: Département d'Anesthésie-Réanimation, Hôpital de la Croix Rousse, 103 Grande Rue de la Croix-Rousse, 69317 Lyon Cedex 04, France. franck.lhuillier@chu-lyon.fr
authors.forename: F
authors.initials: F
authors.lastname: Lhuillier
authors.forename: M-O
authors.initials: MO
authors.lastname: Robert
authors.forename: P
authors.initials: P
authors.lastname: Crova
authors.forename: J
authors.initials: J
authors.lastname: Goudable
authors.forename: F
authors.initials: F
authors.lastname: Arnal
authors.forename: R
authors.initials: R
authors.lastname: Cespuglio
authors.forename: G
authors.initials: G
authors.lastname: Annat
authors.forename: J-P
authors.initials: JP
authors.lastname: Viale
mesh_terms: D000813:Anilides / Q000008:administration & dosage; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives; D001794:Blood Pressure / Q000502:physiology; D002245:Carbon Dioxide / Q000502:physiology; D004195:Disease Models, Animal; D006499:Hepatic Artery / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D007262:Infusions, Intravenous; D008099:Liver / Q000098:blood supply* / Q000502:physiology; D008833:Microcirculation; D023421:Models, Animal; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010100:Oxygen / Q000502:physiology; D011817:Rabbits; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D000813:Anilides; D002245:Carbon Dioxide; D009569:Nitric Oxide; C080840:N(G)-nitroarginine-4-nitroanilide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen