Fischer L G, Freise H, Hilpert J-H, Wendholt D, Lauer S, Van Aken H, Sielenkämper A W
Department of Anesthesiology and Intensive Care, University of Münster, 48149 Münster, Germany.
Intensive Care Med. 2004 Sep;30(9):1821-8. doi: 10.1007/s00134-004-2351-0. Epub 2004 Jun 15.
This study assessed modulation of hypoxic pulmonary vasoconstriction (HPV) in isolated perfused rat lungs during sepsis induced by cecal ligation and perforation (CLP) at different times and its relationship to nitric oxide synthases (NOS).
Prospective controlled trial in a university research laboratory.
102 male Sprague-Dawley rats.
Groups 1-3 received sham laparotomy 6 h before lung isolation: group 1, only laparotomy; group 2, concurrently L- N6-(1-iminoethyl)-lysine (L-NIL, 3 mg/kg); group 3, concurrently N(Omega)-nitro-L-arginine methylester (L-NAME, 5 mg/kg). Groups 4-6 received CLP 6 h before lung isolation: group 4, only CLP; group 5, concurrently L-NIL; group 6, concurrently L-NAME. The same experiments were carried out with sham and CLP treatment for 24 h (groups 7-12). Exhaled NO from rats' lungs was measured after anesthesia and tracheostomy. After the pulmonary circuit was isolated and perfused, angiotensin II (0.1 microg) was injected into the inflow tract. The lungs were ventilated with the hypoxic mixture (HPV, 3% O2) for 10 min and then again with the normoxic mixture (21% O2) for an equal period. Changes in perfusion pressure were measured. Endothelial (eNOS) and inducible NOS (iNOS) expression of the lungs was determined.
Treatment with L-NAME but not L-NIL increased HPV in sham lungs. HPV was unaltered after CLP 6 h and decreased after CLP 24 h compared to sham. In CLP animals eNOS protein expression was reduced whereas iNOS expression was increased compared to sham animals. Exhaled NO, reflecting NOS activity was twice as high in the CLP 24 h group than in the CLP 6 h group.
In the CLP sepsis model modulation of HPV was time-dependent. In addition, vasoconstriction to hypoxic stimuli was dependent on NOS activity.
本研究评估了在不同时间点盲肠结扎穿孔（CLP）诱导的脓毒症期间，离体灌注大鼠肺脏中缺氧性肺血管收缩（HPV）的调节情况及其与一氧化氮合酶（NOS）的关系。
大学研究实验室中的前瞻性对照试验。
102只雄性Sprague-Dawley大鼠。
第1 - 3组在肺脏分离前6小时接受假手术：第1组，仅行剖腹术；第2组，同时给予L - N6 -（1 - 亚氨基乙基）-赖氨酸（L - NIL，3毫克/千克）；第3组，同时给予N（ω）-硝基 - L -精氨酸甲酯（L - NAME，5毫克/千克）。第4 - 6组在肺脏分离前6小时接受CLP：第4组，仅行CLP；第5组，同时给予L - NIL；第6组，同时给予L - NAME。对假手术和CLP处理24小时的大鼠进行相同实验（第7 - 12组）。麻醉和气管切开后测量大鼠肺脏呼出的一氧化氮。分离并灌注肺循环后，将血管紧张素II（0.1微克）注入流入道。用低氧混合气（HPV，3%氧气）对肺脏通气10分钟，然后再用常氧混合气（21%氧气）通气相同时间。测量灌注压力的变化。测定肺脏内皮型（eNOS）和诱导型NOS（iNOS）的表达。
L - NAME而非L - NIL处理增加了假手术肺脏中的HPV。与假手术相比，CLP 6小时后HPV未改变，CLP 24小时后HPV降低。与假手术动物相比，CLP动物中eNOS蛋白表达降低而iNOS表达增加。反映NOS活性的呼出一氧化氮在CLP 24小时组中是CLP 6小时组的两倍。
在CLP脓毒症模型中，HPV的调节是时间依赖性的。此外，对低氧刺激的血管收缩依赖于NOS活性。
