Lo S K, Garcia-Szabo R R, Malik A B
Department of Physiology, Albany Medical College of Union University, New York 12208.
Am J Physiol. 1990 Jul;259(1 Pt 2):H149-55. doi: 10.1152/ajpheart.1990.259.1.H149.
We examined the role of leukocytes in the pathogenesis of lung vascular injury induced by thrombin in awake sheep prepared with the lung lymph fistulas. Thrombin (80 U/kg) infusion in control sheep (n = 6) increased pulmonary arterial pressure (Ppa) twofold and pulmonary vascular resistance (PVR) three-fold for the 5-h experimental period. Thrombin also increased pulmonary vascular permeability to protein as assessed by decrease in the reflection coefficient (sigma) from 0.70 +/- 0.03 to 0.61 +/- 0.01. Thrombin caused similar initial pulmonary hemodynamic changes in sheep rendered neutropenic (n = 7; 2% neutrophil count of controls) by treatment with hydroxyurea; however, both Ppa and PVR returned toward base-line values within 120 min postthrombin challenge. The increases in pulmonary lymph flow and transvascular protein clearance also recovered rapidly beginning at 60 min after challenge with thrombin in neutropenic sheep. Neutropenia prevented the increase in lung vascular permeability as the sigma value of 0.71 +/- 0.02 was similar to the control value. Leukocytes isolated from control donor sheep were infused intra-arterially into recipient neutropenic sheep (n = 4) to assess the effects of neutrophil repletion on the pulmonary vascular responses. Thrombin (80 U/kg) challenge infused at 1-3 h after infusion of leukocytes increased lung lymph flow twofold and transvascular protein clearance fourfold and produced increases in Ppa and PVR comparable with the control group. The increases in these parameters were sustained for the 5-h experiment duration. The data indicate the essential pathogenetic role of neutrophils in mediating the thrombin-induced increase in lung vascular permeability.
我们在制备了肺淋巴瘘的清醒绵羊中，研究了白细胞在凝血酶诱导的肺血管损伤发病机制中的作用。在对照绵羊（n = 6）中输注凝血酶（80 U/kg），在5小时的实验期间，肺动脉压（Ppa）增加了两倍，肺血管阻力（PVR）增加了三倍。凝血酶还增加了肺血管对蛋白质的通透性，反射系数（sigma）从0.70±0.03降至0.61±0.01即表明了这一点。用羟基脲治疗使绵羊中性粒细胞减少（n = 7；中性粒细胞计数为对照组的2%）后，凝血酶引起了类似的初始肺血流动力学变化；然而，在凝血酶激发后120分钟内，Ppa和PVR均恢复到基线值。在中性粒细胞减少的绵羊中，凝血酶激发后60分钟开始，肺淋巴流量和跨血管蛋白清除率的增加也迅速恢复。中性粒细胞减少可防止肺血管通透性增加，因为sigma值为0.71±0.02与对照值相似。将从对照供体绵羊分离的白细胞经动脉内注入受体中性粒细胞减少的绵羊（n = 4），以评估中性粒细胞补充对肺血管反应的影响。在输注白细胞后1 - 3小时给予凝血酶（80 U/kg）激发，使肺淋巴流量增加了两倍，跨血管蛋白清除率增加了四倍，并使Ppa和PVR增加，与对照组相当。在5小时的实验期间，这些参数的增加持续存在。数据表明中性粒细胞在介导凝血酶诱导的肺血管通透性增加中起关键的致病作用。
