Lhuillier F, Robert M-O, Crova P, Goudable J, Arnal F, Cespuglio R, Annat G, Viale J-P
Département d'Anesthésie-Réanimation, Hôpital de la Croix Rousse, 103 Grande Rue de la Croix-Rousse, 69317 Lyon Cedex 04, France.
Br J Anaesth. 2006 Aug;97(2):137-46. doi: 10.1093/bja/ael097. Epub 2006 Apr 13.
Direct evidence of nitric oxide (NO) involvement in the regulation of hepatic microcirculation is not yet available under physiological conditions nor in haemorrhagic shock.
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).
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.
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.
在生理条件下以及失血性休克状态下，一氧化氮（NO）参与肝微循环调节的直接证据尚不明确。
采用激光多普勒血流仪测量肝灌注指数，并将一根对NO敏感的特定电极插入麻醉兔的肝实质。在中度低血容量（平均动脉压为50 mmHg且肝灌注无改变；失血17.7（4.2）ml [均值（标准差）]）或失血性休克（平均动脉压为20 mmHg，伴有肝灌注受损和乳酸酸中毒；失血56.0（6.8）ml）期间，对肝自动调节功能进行60分钟的研究，随后快速输注所失血液。使用非特异性抑制剂N - 硝基 - L - 精氨酸对硝基苯胺（NAPNA）评估一氧化氮合酶的参与情况。
在自动调节组中，平均动脉压下降[30.0（4.0）mmHg]并未改变肝灌注指数，而肝内NO浓度升高并达到一个平台期[125（10）%；与基线相比；P < 0.05]。给予一氧化氮合酶抑制剂后，该NO浓度降至零。失血性休克导致肝灌注指数迅速下降[60（7）%；与基线相比；P < 0.05]，随后NO浓度立即持续升高[250（50）%；与基线相比；P < 0.05]。在失血性休克前输注NO抑制剂可使NO浓度降至零，肝灌注降至基线的60（8）%（P < 0.05）。平均动脉压同时升高。在这些动物中，出血期间NO浓度仍持续升高，肝灌注略有增加。在除NAPNA + 失血性休克组之外的所有组中，输血可使各项指标恢复至基线值。
NO在自动调节过程中对肝微循环起生理作用。其产生依赖于酶。相反，失血性休克导致肝内NO迅速增加，这至少部分是不依赖于酶的。
