INVESTIGATIONS OF NEW THERAPIES IN SEPTIC SHOCK

感染性休克和相关感染后遗症(例如，多器官系统 失败)是重症监护病房最常见的死亡原因。 败血症导致的死亡可以发生在以前健康的人身上。 年龄组，以及各种常见的临床环境中。一些常见的 易患条件为：早产儿，既往健康 儿童获得性感染(如脑膜炎、肺炎、上呼吸道感染) 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病的老年患者。全部的一半 感染感染性休克的儿童和成人死于该综合征。因此， 感染性休克，影响幼儿和老年人(甚至 那些没有诱因的人)，是一种常见而重要的临床 造成大量死亡的问题，并对 社会。令人惊讶的是，人们对这种疾病的病理生理知之甚少。 疾病。现有数据表明，感染性休克是由高度的 与感染有关的因素(生物体毒力)的复杂相互作用 因子和毒素)和与寄主反应有关的因子(内源 影响和调节炎症反应的分子)。因此， 败血症休克综合征的成功治疗降低了发病率 而死亡将产生于治愈感染和阻断 这些生物体和寄主介体的影响。使用专门培育的小猎犬， 感染性休克的犬模型已经成功地提供了关于 人类疾病的病理生理学和治疗。这一型号， 急性和慢性感染，模拟病程和心血管 在感染性休克的儿童和成人中常见的变化。之前 使用该模型的实验已经确定了特定细菌的作用 (革兰氏阳性和革兰氏阴性)、细菌毒素(内毒素)和宿主 产生感染性休克的介质(肿瘤坏死因子)。因此，犬类模型一直是 在模拟人类疾病和指导治疗方面取得了巨大成功 人类。有几种疗法正在调查中，可能是 对人类败血症休克有效。因为这些疗法有潜在的毒性 可能会恶化患者的病情，必须在动物身上进行测试 模拟人类疾病的模型。犬类模型，它 模拟儿童和成人的心血管变化 感染性休克，非常适合于这些新的临床前试验 治疗。犬类模型允许适当的对照试验来评估 治疗机制和治疗的副作用，这并不总是 在人体研究中是可能的。我们正在评估或计划评估 感染性休克犬模型的以下治疗方法：Lipid X； 血浆置换，布洛芬；抗内毒素单抗；抗 肿瘤坏死因子；己酮茶碱；粒细胞刺激因子； 抗血小板活化因子抗体；抗蛋白C抗体； 白血球上受体的抗体。

Septic shock and related sequelae of infection (e.g., 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 a great financial burden on society. Surprisingly, little is known about the pathophysiology of this disease. Available data indicate that septic shock is caused by a highly complex interaction of factors related to the 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. As these therapies are potentially toxic and might worsen a patient's condition, they must be tested in an animal model that closely simulates the human disease. 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 evaluate 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; Lipid X; Plasmapheresis, Ibuprofen; Monoclonal Antibodies to Endotoxin; Antibody to Tumor Necrosis Factor; Pentoxyphylline; Granulocyte Stimulating Factor; Antibodies to Platelet Activating Factor; Antibodies to Protein C; Antibodies to Receptors on White Blood Cells.