Saba T M, Blumenstock F A, Shah D M, Landaburu R H, Hrinda M E, Deno D C, Holman J M, Cho E, Dayton C, Cardarelli P M
Am J Med. 1986 Feb;80(2):229-40. doi: 10.1016/0002-9343(86)90014-8.
Plasma fibronectin deficiency has been documented in critically ill surgical, trauma, and burn patients. Human plasma fibronectin was isolated by gelatin-Sepharose affinity chromatography and evaluated with respect to its opsonic activity following pasteurization, its in vivo clearance kinetics, and its short-term influence on cardiovascular hemodynamics in postoperative septic sheep. Six patients with low plasma fibronectin levels were also evaluated with respect to temporal changes of immunoreactive fibronectin and opsonic activity following infusion of fibronectin at a dose calculated to elevate the plasma fibronectin level to 400 micrograms/ml. With utilization of three different in vitro radioisotopic phagocytic assays, i.e., liver slice assay, peritoneal macrophage monolayer assay, and Kupffer cell monolayer assay, retention of opsonic activity by fibronectin following pasteurization was documented. The normal biphasic kinetics associated with plasma clearance of fibronectin were also not altered by pasteurization. In postoperative septic sheep with hemodynamic instability, intravenous infusion of 500 mg of purified human fibronectin initiated no abnormal hemodynamic response. Indeed, as compared with placebo, the infusion of fibronectin into the postoperative septic sheep resulted in a more stable systemic vascular resistance and pulmonary vascular resistance with a higher arterial pressure. It also elevated immunoreactive fibronectin levels (p less than 0.05) and increased opsonic activity (p less than 0.05). Surgical, trauma, and burn patients (ages 18 to 80 years) with low plasma fibronectin levels (160 to 236 micrograms/ml) manifested no disturbance in cardiovascular, respiratory, or hematologic parameters following fibronectin infusion (590 to 988 mg per patient), but did display an early increase of opsonic activity. This standardized, pasteurized, and opsonically active preparation of purified human plasma fibronectin (5.0 mg/ml after reconstitution) has utility for future randomized clinical trials in injured patients with sepsis.
在重症外科、创伤和烧伤患者中已证实存在血浆纤连蛋白缺乏。通过明胶 - 琼脂糖亲和层析法分离人血浆纤连蛋白，并对其在巴氏消毒后的调理活性、体内清除动力学以及对术后脓毒症绵羊心血管血流动力学的短期影响进行评估。还对6名血浆纤连蛋白水平较低的患者进行了评估，观察在输注按计算可将血浆纤连蛋白水平提高至400微克/毫升剂量的纤连蛋白后，免疫反应性纤连蛋白和调理活性的时间变化。利用三种不同的体外放射性同位素吞噬试验，即肝切片试验、腹膜巨噬细胞单层试验和枯否细胞单层试验，记录了巴氏消毒后纤连蛋白调理活性的保留情况。巴氏消毒也未改变与纤连蛋白血浆清除相关的正常双相动力学。在血流动力学不稳定的术后脓毒症绵羊中，静脉输注500毫克纯化的人纤连蛋白未引发异常血流动力学反应。事实上，与安慰剂相比（输注纤连蛋白），术后脓毒症绵羊的全身血管阻力和肺血管阻力更稳定，动脉压更高。它还提高了免疫反应性纤连蛋白水平（p<0.05）并增加了调理活性（p<0.05）。血浆纤连蛋白水平较低（160至236微克/毫升）的外科、创伤和烧伤患者（年龄18至80岁）在输注纤连蛋白（每位患者590至988毫克）后，心血管、呼吸或血液学参数未出现紊乱，但调理活性确实早期增加。这种标准化、巴氏消毒且具有调理活性的纯化人血浆纤连蛋白制剂（复溶后为5.0毫克/毫升）对未来脓毒症受伤患者的随机临床试验具有实用性。
