Evgenov O V, Hevroy O, Bremnes K E, Bjertnaes L J
Department of Anesthesiology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway.
Am J Respir Crit Care Med. 2000 Aug;162(2 Pt 1):465-70. doi: 10.1164/ajrccm.162.2.9907100.
It has been suggested that enhanced generation of nitric oxide by inducible nitric oxide synthase (iNOS) may contribute to acute lung injury. We hypothesized that aminoguanidine (AG), a proposed selective inhibitor of iNOS, would alter pulmonary hemodynamics, fluid filtration, and gas exchange after endotoxin in chronically instrumented awake sheep. Eighteen sheep were randomly assigned to receive either AG (10 mg/kg + 1 mg/kg/h), or NaCl 0.9% intravenously for 4 h, beginning 2 h after injection of Escherichia coli endotoxin (1 microgram/kg). After endotoxin, pulmonary artery pressure (Ppa), capillary pressure (Pc), and vascular resistance index (PVRI) rose concomitantly with six-fold increments in lung lymph flow (Q L) and protein clearance (CL). Extravascular lung water (EVLW) doubled, as assessed with the thermal dye dilution technique; Pa(O(2)) decreased, AaPO(2) and venous admixture (Q S/Q T) increased. After AG, Q L and CL increased further by approximately 30%, whereas EVLW remained unchanged, despite an additional increase in Pc. Ppa, PVRI, and systemic vascular resistance index rose, whereas cardiac index and pulmonary blood volume index declined. In addition, Pa(O(2)) rose, and AaPO(2) and Q S/Q T decreased. We conclude that in endotoxemic sheep, AG improves gas exchange and increases Q L and CL, whereas EVLW remains unchanged in spite of enhanced Pc. Apparently, increased lymphatic drainage prevents EVLW from rising after AG.
有人提出，诱导型一氧化氮合酶（iNOS）产生一氧化氮增加可能导致急性肺损伤。我们假设氨基胍（AG），一种推测的iNOS选择性抑制剂，会改变长期植入仪器的清醒绵羊内毒素血症后的肺血流动力学、液体滤过和气体交换。18只绵羊随机分为两组，一组静脉注射AG（10mg/kg + 1mg/kg/h），另一组静脉注射0.9%氯化钠溶液，持续4小时，在注射大肠杆菌内毒素（1μg/kg）后2小时开始给药。内毒素血症后，肺动脉压（Ppa）、毛细血管压（Pc）和血管阻力指数（PVRI）升高，同时肺淋巴流量（QL）和蛋白清除率（CL）增加了6倍。用热染料稀释技术评估，血管外肺水（EVLW）增加了一倍；动脉血氧分压（Pa（O₂））降低，肺泡-动脉血氧分压差（AaPO₂）和静脉血掺杂（QS/QT）增加。给予AG后，QL和CL进一步增加约30%，而尽管Pc进一步升高，但EVLW保持不变。Ppa、PVRI和全身血管阻力指数升高，而心指数和肺血容量指数下降。此外，Pa（O₂）升高，AaPO₂和QS/QT降低。我们得出结论，在内毒素血症绵羊中，AG改善气体交换，增加QL和CL，尽管Pc升高，但EVLW保持不变。显然，淋巴引流增加可防止AG给药后EVLW升高。
