INVESTIGATIONS OF NEW THERAPIES IN SEPTIC SHOCK

感染性休克和相关的感染后遗症(如多器官系统 失败)是重症监护病房最常见的死亡原因。死亡人数 由于败血症可发生在所有年龄段的以前健康的人身上 在各种常见的临床环境中使用。一些常见的 易感条件是早产儿，以前健康的儿童 获得性感染(如脑膜炎、肺炎、上呼吸道感染 感染)，患有创伤或癌症的青少年和年轻人，以及老年人 肺炎或胆囊病患者。一半的儿童和 感染感染性休克的成年人死于该综合征。因此，感染性休克， 这对儿童和老年人都有影响(即使是那些没有 易患疾病)，是一种常见而重要的临床问题 造成大量死亡，并给社会带来巨大的经济负担。 令人惊讶的是，人们对这种疾病的病理生理学知之甚少。 感染(生物体毒力因素和毒素)及其相关因素 宿主反应(影响和调节细胞周期的内源分子 炎症反应)。因此，感染性休克的成功治疗 减少发病率和死亡率的综合征将产生于治疗 感染和中断这些有机体和宿主的影响 调解人。利用专门培育的比格犬，感染性休克的犬模型 成功地提供了有关该病的病理生理和治疗方面的信息 人类疾病。这个急性和慢性感染的模型模拟了 儿童和成人常见的病程和心血管改变 感染性休克。使用该模型的先前实验已经建立了 特定细菌(革兰氏阳性和革兰氏阴性)的作用，细菌 毒素(内毒素)和宿主介质(TNF)产生感染性休克。因此， 犬类模型在模拟人类疾病方面非常成功。 并指导人类的治疗。下面有几种治疗方法 可能对人类感染性休克有效的研究。就像这些 治疗方法可能是人类疾病。犬类模型，它模拟了 儿童和成人败血症患者的心血管变化 休克，非常适合这些新疗法的临床前试验。这个 犬类模型允许进行适当的对照试验来评估治疗 治疗的机制和副作用，这在 人体研究。我们正在评估或计划评估以下内容 感染性休克犬模型的治疗：脂类X Z；血浆置换； 布洛芬；抗内毒素单抗；抗肿瘤坏死抗体 因子；己酮茶碱；粒细胞刺激因子；抗体 血小板活化因子；抗蛋白C抗体；抗 白细胞上的受体；持续性动-静脉血液滤过。

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 bacterial (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 human disease. The canine model, which simulates the cardiovascular changes seen in children and adult humans with septic shock, is ideally suited for preclinical 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: Lipid X Z; Plasmapheresis; Ibuprofen; Monoclonal Antibodies to Endotoxin; Antibody to Tumor Necrosis Factor; Pentoxyphylline; Granulocyte Stimulating Factor; Antibodies to Platelet Activation Factor; Antibodies to Protein C; Antibodies to Receptors on White Blood Cells; Continuous A-V Hemofitration.