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 目的：阐明感染性休克的病理生理学(N Engl J Med； 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。 重症监护室。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)。这些调解人产生的特征是 败血症和感染性休克的心肺反应。补充性系统 是在脓毒症期间被激活的宿主介质的级联，并且可能是 对宿主有利或有害的。如果补体产生，总的来说， 败血症期间的有害影响，现在可以用拮抗剂来补充 对人类来说，并将被考虑用于治疗感染性休克。 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 由EILSA确定的水平)。他们有正常水平的其他 作为演员的补充。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。 这项方案建议对亚致死剂量的 内毒素输注治疗C3缺乏的布列塔尼猎犬。因为这些 动物很难繁殖，而且极其稀缺，有一种很小的 这些可供调查的珍贵动物的数量。为了保存 这些动物，狗会受到亚致死剂量的挑战 产生类似于人类败血症的心血管特征的内毒素 令人震惊。

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 care units. Endotoxin, a component of the outer cell wall of Gram-negative bacteria, is released into the circulation in patients with septic shock and is 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 EILSA). They have normal levels of other complement actors. 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.