Testing an Automatic Drug Delivery System in a Rat Sepsis Model

在大鼠脓毒症模型中测试自动给药系统

• 批准号: 9154086
• 负责人: Peter Eichacker
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9154086
• 关键词: American; Animal Model; Animals; Blood; Blood Pressure; Blood Pressure Monitors; Caring; Chest; Clinical; Dose; Drug Delivery Systems; Escherichia coli; Hour; Individual; Infusion procedures; International; Laboratories; Measurement; Measures; Modeling; Norepinephrine; Normal saline; Nurses; Outcome; Patients; Protocols documentation; Rattus; Regimen; Sepsis; Shock; Societies; Survivors; System; Testing; Vasoconstrictor Agents; Work; base; hemodynamics; improved; instrument; research study; symposium

Developing animal models that simulate conditions encountered clinically is important when testing new therapies. In this regard, animal models of sepsis should include the same types of standard hemodynamic support patients receive. Such standard therapy would include vasopressors titrated to mean arterial blood. Providing this type of therapy however is very labor intensive since vasopressors are typically titrated every 10 to 15 minutes by a nurse at the bedside. However, because titrated vasopressors are such an integral part of sepsis care clinically, our laboratory has now adapted an automated drug delivery system (ADDS) (Harvard Instruments, Cambridge, MA) for possible application in a rat sepsis model ASP CCM 1108. This system administers differing doses of vasopressor (0, low or high dose) based on continuously monitored blood pressure and can perform individual measurements and treatments in up to 12 animals simultaneously. The purpose of the present protocol is to determine whether administration of a three dose norepinephrine (NE) regimen titrated with the ADDS improves outcome in animals challenged with intratracheal (IT) E. coli and treated with a 24 hour normal saline (NS) infusion previously shown to increase survival in the model. From that prior study, in animals receiving NS, MAP (mean+se) was lower in nonsurvivors compared to survivors (91.0 +/- 2.9, n=15 vs. 107.0 +/- 1.9, n=9; measured at 12 and 24 hours after challenge). Experiments performed thus far for this protocol have demonstrated that administration of NE with the ADDS is capable of reliably and consistently increasing blood pressure in animals developing shock related to challenge with intra-bronchial E. coli. The doses of NE necessary to produce these changes are significantly less than the doses administered with a much less sensitive fixed infusion system. Studies continue to determine how the ADDS can be employed to improve survival in this model. Work from this study was presented in the International Conference of the American Thoracic Society 2013.

在测试新疗法时，开发模拟临床条件的动物模型非常重要。在这方面，脓毒症的动物模型应包括患者接受的相同类型的标准血流动力学支持。这样的标准治疗将包括滴定至平均动脉血的血管加压药。 然而，提供这种类型的治疗是非常劳动密集型的，因为血管加压药通常由护士在床边每10至15分钟滴定一次。 然而，由于滴定的血管加压药是临床脓毒症治疗的一个组成部分，我们的实验室现在已经采用了自动给药系统（ADDS）（哈佛仪器，剑桥，MA），用于大鼠脓毒症模型ASP CCM 1108的可能应用。该系统根据连续监测的血压给予不同剂量的血管加压药（0、低或高剂量），并可同时对多达12只动物进行单独测量和治疗。 本方案的目的是确定ADDS滴定的三剂量去甲肾上腺素（NE）方案给药是否改善了用肠内（IT）E激发的动物的结局。大肠杆菌，并用24小时生理盐水（NS）输注处理，先前显示在模型中增加存活。根据先前的研究，在接受NS的动物中，与存活动物相比，非存活动物的MAP（平均值+se）较低（91.0 +/- 2.9，n=15 vs. 107.0 +/- 1.9，n=9;在攻毒后12和24小时测量）。 到目前为止，针对该方案进行的实验已经证明，在发生与支气管内E.杆菌产生这些变化所需的NE剂量显著低于使用灵敏度低得多的固定输注系统所给予的剂量。研究继续确定如何使用ADDS来提高该模型的生存率。 这项研究的工作在2013年美国胸科学会国际会议上发表。