ROLE OF COMPLEMENT IN ENDOTOXIC SHOCK

对给予亚致死剂量内毒素的正常人的研究表明， 与人类败血症反应相似的心肺反应 令人震惊。这种正常的人体模型已被用于对照研究 阐明感染性休克的病理生理学(N Engl J Med 1989年；321：280)。 感染性休克是一种高度致命的疾病(50%-50%的死亡率)，尽管 抗生素和心血管支持疗法。脓毒症死亡率 休克是由心血管衰竭或多器官系统引起的 失败了。脓毒症是中国最常见的患者死亡原因。 密集的汽车单元。内毒素，细菌外细胞壁的一种成分 革兰氏阴性菌，被释放到循环中的患者 感染性休克，被认为是主要的致病毒素。 在脓毒症期间，宿主细胞释放介质以响应细菌毒素 (内毒素)。这些介质产生特有的心肺功能 败血症和感染性休克的反应。补语系统是一系列 在脓毒症期间激活的宿主介质，可能有益于或 对寄主有害。总的来说，如果补充剂产生有害的影响 在败血症期间，补体的拮抗剂现在可用于人类和 将被考虑用于感染性休克的治疗。 布列塔尼西班牙犬在第三组分中存在遗传缺陷 补体(C3)在Johns的补语研究中已被使用 霍普金斯大学。这些狗基本上不会产生C3(正常的0.003 用酶联免疫吸附试验测定的水平)。他们有正常水平的其他 补充性因素。补体成分激活需要补体C3 C5-C9通过经典途径和替代途径。因此，对 这些动物的内毒素血症将阐明其病理生理作用。 互补性。 该方案建议研究一种亚致死性内毒素的作用。 为缺乏C3的布列塔尼猎犬输液。因为这些动物是 很难繁殖，而且极其稀缺，有少量这样的 值得调查的珍贵动物。为了保护这些动物， 这些狗会受到亚致死剂量的内毒素的挑战 产生类似于人类感染性休克的心血管特征。

Studies of normal humans given a sublethal dose of endotoxin have shown a cardiopulmonary response similar to the response of humans with septic shock. This normal human model has been used in controlled investigations to elucidate the pathophysiology of septic shock (N Engl J Med 1989;321:280). Septic shock is a highly lethal disease (50-50% mortality) despite optimal antibiotic and cardiovascular supportive therapy. Mortality from septic shock is caused by cardiovascular collapse or multiple organ system failure. Sepsis is the most prevalent cause of death of patients in intensive car units. Endotoxin, a component of the outer cell wall of Gram-negative bacterial, is released into the circulation in patients with septic shock and thought to be the major pathogenic toxin. During sepsis host cells release mediators in response to bacterial toxins (endotoxin). These mediators produce the characteristic cardiopulmonary response of sepsis and septic shock. The complement system is a cascade of host mediators that are activated during sepsis and may be beneficial or harmful to the host. If complement produces, on balance, harmful effects during sepsis, antagonists to complement are now available for humans and would be considered for therapy for septic shock. Brittany spaniels that are genetically deficient in the third component of complement (C3) have been used in investigations of complement at Johns Hopkins University. These dogs produce essentially no C3 (0.003% of normal levels as determined by ELISA). They have normal levels of other complement factors. C3 is required for activation of complement components C5-C9 via classical and alternative pathways. Thus, investigation of endotoxemia in these animals would clarify the pathophysiologic role of complement. This protocol proposes investigation of the effect of a sublethal endotoxin infusion on C3 deficient Brittany spaniels. Because these animals are difficult to breed and extremely scarce, there are a small number of these valuable animals for investigation. In order to preserve these animals, the dogs would be challenged with a sublethal dose of endotoxin that produces cardiovascular profile similar to human septic shock.