Remmers D, Dwenger A, Grotz M, Seekamp A, Pape H C, Gruner A, Hafemann R, Regel G
Department of Trauma Surgery, Hannover Medical School, Germany.
J Surg Res. 1996 May;62(2):278-83. doi: 10.1006/jsre.1996.0208.
Animal studies have shown that 21-aminosteroids have beneficial effects on cell and organ functions in several acute models of traumatic, hemorrhagic, and septic shock. However, it is not known if the 21-aminosteroid U74389G has any beneficial effect on organ functions in a recently developed chronic sheep model of multiple organ dysfunction after trauma. Furthermore, it is not known whether this drug has any effect on in vivo leukocyte function in this animal model. To study this, anesthetized animals were subjected to hemorrhagic shock (2 hr at a mean arterial blood pressure of 50 mmHg) and femoral reaming at Day 0. The following 5 days, endotoxin (ET; 0.75 micrograms/kg BW) and zymosan-activated plasma (ZAP; 20 ml/animal) were given every 12 hr. During the third phase (Days 6-10), the animals were merely observed. This kind of model resulted in progressive organ dysfunction indicated by increased cardiac output, decreased systemic vascular resistance, an increase of plasma-sorbitoldehydrogenase, impaired bilirubin metabolism, and impaired renal and lung function in nontreated animals. Animals receiving U74389G (3 mg/kg BW) during resuscitation from hemorrhagic shock and each time before ET/ZAP administration showed less severe organ dysfunction. Furthermore, U74389G showed beneficial effects on lung function, although it had no effect on accumulation of leukocytes in the lung or on the chemiluminescence response of isolated leukocytes from bronchoalveolar lavage fluid. These results suggest that U74389G may be a useful therapeutic agent in the prevention of multiple organ dysfunction after hemorrhagic and traumatic shock.
动物研究表明，在创伤性、出血性和感染性休克的几种急性模型中，21-氨基类固醇对细胞和器官功能具有有益作用。然而，尚不清楚21-氨基类固醇U74389G对最近建立的创伤后多器官功能障碍慢性绵羊模型中的器官功能是否有任何有益作用。此外，尚不清楚该药物对该动物模型中的体内白细胞功能是否有任何影响。为了研究这一点，在第0天对麻醉的动物进行出血性休克（平均动脉血压为50 mmHg，持续2小时）和股骨扩髓。在接下来的5天里，每12小时给予内毒素（ET；0.75微克/千克体重）和酵母聚糖激活血浆（ZAP；20毫升/只动物）。在第三阶段（第6 - 10天），仅对动物进行观察。这种模型导致未治疗动物出现进行性器官功能障碍，表现为心输出量增加、全身血管阻力降低、血浆山梨醇脱氢酶升高、胆红素代谢受损以及肾和肺功能受损。在从出血性休克复苏期间以及每次给予ET/ZAP之前接受U74389G（3毫克/千克体重）的动物，其器官功能障碍较轻。此外，U74389G对肺功能显示出有益作用，尽管它对肺中白细胞的积聚或支气管肺泡灌洗液中分离出的白细胞的化学发光反应没有影响。这些结果表明，U74389G可能是预防出血性和创伤性休克后多器官功能障碍的一种有用治疗剂。
