Nitric oxide and liver microcirculation during autoregulation and haemorrhagic shock in rabbit model.
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.
Lhuillier
F
F
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
Robert
M-O
MO
Crova
P
P
Goudable
J
J
Arnal
F
F
Cespuglio
R
R
Annat
G
G
Viale
J-P
JP
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*
D000813:Anilides; D002245:Carbon Dioxide; D009569:Nitric Oxide; C080840:N(G)-nitroarginine-4-nitroanilide; D001120:Arginine; D019001:Nitric Oxide Synthase; D010100:Oxygen