INVESTIGATIONS OF NEW THERAPIES IN SEPTIC SHOCK

感染性休克和相关的感染后遗症（例如，多器官 是重症监护中最常见的死亡原因 单位败血症导致的死亡可能发生在以前健康的人身上。 个体，在所有年龄组，并在各种常见的临床 设置.一些常见的诱发条件是早产儿， 患有获得性感染的先前健康的儿童（例如， 脑膜炎、肺炎、上呼吸道感染）、青少年和 患有创伤或癌症的年轻人，以及患有 肺炎或胆囊疾病。一半的儿童和成人 感染性休克死于该综合征。因此感染性休克 影响幼儿和老年人（即使是那些没有 诱发疾病），是一种常见的和重要的临床问题， 死亡率很高，给社会造成很大的经济负担。 令人惊讶的是，很少有人知道这种病理生理学 疾病感染（生物体毒力因子和毒素）和因子 与宿主反应相关的内源性分子（影响和 调节炎症反应）。因此，成功治疗 降低发病率和死亡率的败血性休克综合征将 结果是治愈感染和中断这些影响， 生物体和宿主介质。利用专门饲养的比格犬， 脓毒性休克模型成功地提供了关于 病理生理学和人类疾病的治疗。这种模式， 急性和慢性感染模拟过程和心血管 在儿童和成人感染性休克中常见的变化。之前 使用该模型的实验已经确定了特定的 细菌（革兰氏阳性和革兰氏阴性）、细菌毒素 （内毒素）和宿主介质（TNF）以产生脓毒性休克。因此，在本发明中， 犬类模型在模拟人类方面非常成功 疾病和指导人类的治疗。有几种疗法 可能对人类感染性休克有效的药物的 犬模型，该模型模拟了 感染性休克的儿童和成人，非常适合于 这些新疗法的临床前试验。犬科动物模型允许 适当的对照试验，以评估治疗机制， 治疗的不良反应，这在人类中并不总是可能的 问题研究我们正在评估或计划评估以下内容 犬感染性休克模型的治疗：缓激肽拮抗剂; 丹曲林;可溶性肿瘤坏死因子受体; CD 18抗体 受体;布洛芬;肿瘤坏死因子抗体;粒细胞 血小板活化因子;血小板活化因子抗体; 蛋白C抗体;白色血细胞;连续A-V 血液滤过，高密度脂蛋白，血小板活化因子 抑制剂.

Septic shock and related sequelae of infection (eg., multiple organ system failure) are the most common cause of death in intensive care units. Deaths due to sepsis can occur in previously healthy individuals, in all age groups, and in a variety of common clinical settings. Some common predisposing conditions are premature neonates, previously healthy children with acquired infections (e.g., meningitis, pneumonia, upper respiratory infections), teenagers and young adults with trauma or cancer, and elderly patients with pneumonia or gall bladder disease. Half of all children and adults who acquire septic shock die from the syndrome. Thus, septic shock, which affects young children and the elderly alike (even those without predisposing illness), is a common and important clinical problem with substantial mortality and produces great financial burden on society. Surprisingly, little is known about the pathophysiology of this disease infection (organism virulence factors and toxins) and factors related to the host response (endogenous molecules that affect and modulate the inflammatory response). Thus, successful treatment of the septic shock syndrome which reduces morbidity and mortality will result from curing the infection and interrupting the effects of these organism and host mediators. Using purpose-bred beagles, the canine model of septic shock has successfully provided information on the pathophysiology and treatment of the human disease. This model, of acute and chronic infection simulates the course and cardiovascular changes seen routinely in children and adults with septic shock. Prior experiments using the model have established the role of specific bacteria (gram positive and gram negative), bacterial toxins (endotoxin), and host mediators (TNF) to produce septic shock. Thus, the canine model has been highly successful in simulating the human disease and guiding therapy for humans. There are several therapies under investigation that might be effective in human septic shock. The canine model, which simulates the cardiovascular changes seen in children and adult humans with septic shock, is ideally suited for pre-clinical trials of these new therapies. The canine model allows properly controlled trials to evaluated therapeutic mechanisms and adverse effects of therapies, that is not always possible in human studies. We are evaluating or have planned to evaluate the following therapies of septic shock in the canine model: Bradykinin Antagonists; Dantrolene; Soluble Tumor Necrosis Factor Receptor; Antibodies to CD18 receptors; Ibuprofen; Antibody to Tumor Necrosis Factor; Granulocyte Stimulating Factor; Antibodies to Platelet Activation Factor; Antibodies to Protein C; on White Blood Cells; Continuous A-V Hemofiltration, High Density Lipoproteins, Platelet Activating Factor Inhibitor.