Staub N C, Longworth K E, Serikov V, Jerome E H, Elsasser T
Cardiovascular Research Institute, University of California, San Francisco 94143, USA.
J Appl Physiol (1985). 2001 May;90(5):1788-97. doi: 10.1152/jappl.2001.90.5.1788.
Sheep have reactive pulmonary intravascular macrophages, which are essential for the marked pulmonary vascular response to infusions of small quantities of endotoxin. In another species with reactive pulmonary intravascular macrophages, horses, our laboratory found that an intravenous biosafe detergent, tyloxapol, inhibited some systemic and pulmonary responses to endotoxin (Longworth KE, Smith BL, Staub NC, Steffey EP, and Serikov V. Am J Vet Res 57: 1063-1066, 1996). We determined whether the same detergent would inhibit endotoxin responses in awake sheep. In 10 awake, instrumented sheep with chronic lung lymph fistulas, we did a control experiment by intravenously infusing 1 microg/kg Escherichia coli endotoxin. One week later, we gave 40 micromol/kg tyloxapol intravenously 1-4 h before infusing the same dose of endotoxin. In these paired studies, we compared pulmonary hemodynamics, lung lymph dynamics, body temperature, circulating leukocyte concentrations, and circulating tumor necrosis factor for 6 h. In all 10 sheep, tyloxapol blocked 80-90% of the pulmonary responses and 70-90% of the systemic responses. Tyloxapol is safe, inexpensive, easy to use, and effective immediately. It may be a clinically useful approach to contravening many of the effects of endotoxemia, in humans as well as animals.
绵羊具有反应性肺血管内巨噬细胞，这对于对小剂量内毒素输注产生显著的肺血管反应至关重要。在另一种具有反应性肺血管内巨噬细胞的物种——马中，我们实验室发现一种静脉注射用生物安全去污剂泰洛沙泊可抑制对内毒素的一些全身和肺部反应（Longworth KE、Smith BL、Staub NC、Steffey EP和Serikov V.《美国兽医研究杂志》57: 1063 - 1066, 1996）。我们确定了同一种去污剂是否会抑制清醒绵羊对内毒素的反应。在10只清醒的、装有慢性肺淋巴瘘管的绵羊中，我们通过静脉注射1微克/千克大肠杆菌内毒素进行了对照实验。一周后，在输注相同剂量的内毒素前1 - 4小时，我们静脉注射40微摩尔/千克泰洛沙泊。在这些配对研究中，我们比较了6小时内的肺血流动力学、肺淋巴动力学、体温、循环白细胞浓度和循环肿瘤坏死因子。在所有10只绵羊中，泰洛沙泊阻断了80 - 90%的肺部反应和70 - 90%的全身反应。泰洛沙泊安全、便宜、易于使用且起效迅速。它可能是一种在临床上行之有效的方法，可用于对抗内毒素血症在人类和动物中的多种影响。
