New model of ventilator-associated pneumonia in immunocompetent rabbits
New model of ventilator-associated pneumonia in immunocompetent rabbits
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DOI：
10.1097/00003246-200210000-00016
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发表时间：
2002-10-01
影响因子：
8.8
通讯作者：
Chavanet, P
中科院分区：
文献类型：
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作者：
Charles, PE;Piroth, L;Chavanet, P
目的：尽管呼吸机相关性肺炎的治疗失败率很高，但到目前为止还没有专门设计用于抗菌评价的动物模型。本研究首次描述了呼吸机相关性肺炎的兔模型。设计：前瞻性、随机实验研究。设置：动物研究实验室。受试者：雄性新西兰健康兔（n = 44）。干预措施：经口插管和一小时的机械通气后，呼吸机相关性肺炎组（n = 22）的动物用经校准的产气肠杆菌接种物支气管内感染。非通气性肺炎组（n = 22）由在没有机械通气的情况下接受相同接种物的动物组成。在接种后3、6、12、24或48 h随机处死两组家兔。肺炎评估是基于组织学（宏观和微观评分）和细菌学（细菌计数）的调查结果。主要结果：感染的动物进行机械通气迅速发展为进行性双侧和多灶性肺炎。肺细菌平均浓度（So）为6.48（0.71）log（10）菌落形成单位（cfu）每克组织在48小时，而菌血症发生在大多数情况下。在非通气性肺炎组中，肺炎的细菌计数较轻（3.18 [1.86] log（10）cfu/g; p <0.05），脾培养仍为阴性。此外，显微镜检查显示呼吸机相关性肺炎组的非感染性肺损伤，特别是透明膜填充肺泡腔。值得注意的是，这些功能从来没有观察到在nonventilated pneumonia group.Conclusions：呼吸机相关性肺炎的动物模型中获得免疫功能正常的兔子。组织学和细菌学特征与人类相似。显然，当动物接受机械通气时，肺炎更严重，特别是在全身传播方面。非感染性肺损伤对应于通气诱导的肺损伤可以解释这种差异。该模型强调了机械通气和感染对肺的强烈影响，因为它们在引起肺泡损伤时似乎协同作用。此外，它似乎非常适合测试抗菌效果。
Objective: Despite the high rate of therapeutic failures in ventilator-associated pneumonia, up to now there has been no animal model specifically designed for antimicrobial evaluation. A rabbit model of ventilator-associated pneumonia is described for the first time in this study.Design: Prospective, randomized experimental study.Setting: An animal research laboratory.Subjects: Male New Zealand healthy rabbits (n = 44).Interventions: After oral intubation and an hour of mechanical ventilation, animals in the ventilator-associated pneumonia group (n = 22) were infected intrabronchially with a calibrated inoculum of Enterobacter aerogenes The nonventilated pneumonia group (n = 22) was composed of animals that received the same inoculum in the absence of mechanical ventilation. Rabbits from both groups were randomly killed 3, 6, 12, 24, or 48 hrs after inoculation. Pneumonia evaluation was based on histologic (macroscopic and microscopic score) and bacteriologic (bacterial count) findings.Main results: Infected animals undergoing mechanical ventilation rapidly developed a progressive bilateral and multifocal pneumonia. Lung bacterial mean (So) concentration was 6.48 (0.71) log(10) colony-forming units (cfu) per gram of tissue at 48th hour, whereas bacteremia occurred in most cases. In the nonventilated pneumonia group, pneumonia was less severe in terms of bacterial count (3.18 [1.86] log(10) cfu/g; p < .05), and spleen cultures remained negative. In addition, microscopic examination revealed noninfectious lung injury in the ventilator-associated pneumonia group, especially hyaline membrane filling alveolar spaces. Of note, these features were never observed in the nonventilated pneumonia group.Conclusions: An animal model of ventilator-associated pneumonia was obtained in immunocompetent rabbits. Histopathologic and bacteriologic features were similar to those found in humans. Obviously, pneumonia was more severe when animals underwent mechanical ventilation, especially in terms of systemic spread. Noninfectious lung injury corresponding to ventilation-induced lung injury may explain the difference. This model emphasizes the strong impact of both mechanical ventilation and infection on lung because they seem to act synergistically when causing alveolar damage. Moreover, it seems well suited to testing antimicrobial effectiveness.