Department of Surgery, University of Pittsburgh, Pittsburgh, USA.
Sci Rep. 2017 Jul 26;7(1):6622. doi: 10.1038/s41598-017-05497-5.
Animal models of sepsis exhibit considerable variability in the temporal development of the physiologic response, which reduces the power of studies, particularly if interventions are tested at arbitrary time points. We developed a biotelemetry-based model of cecal ligation and puncture (CLP) that standardizes the testing of time-sensitive therapies to specific criteria of physiologic deterioration. In this study we seek to further define the variability in physiologic response to CLP sepsis and conduct a cost analysis detailing the potential for reducing animal usage. We have further characterized the variability in physiologic response after CLP in mice and determined peaks in the temporal distribution of points of physiologic decline. Testing therapies at physiologic thresholds reduces the variability found in historical fixed time-based models. Though initial cost is higher with biotelemetry, this is eventually offset by the significantly reduced number of mice needed to conduct physiologically relevant sepsis experiments.
动物脓毒症模型在生理反应的时间发展上表现出相当大的可变性,这降低了研究的效力,特别是如果干预措施在任意时间点进行测试。我们开发了一种基于生物遥测的盲肠结扎和穿刺 (CLP) 模型,该模型将对时间敏感的治疗方法的测试标准化为特定的生理恶化标准。在这项研究中,我们旨在进一步定义 CLP 脓毒症引起的生理反应的可变性,并进行成本分析,详细说明减少动物使用的潜力。我们进一步描述了 CLP 后小鼠生理反应的可变性,并确定了生理下降点的时间分布峰值。在生理阈值下测试治疗方法可减少在基于历史固定时间的模型中发现的变异性。虽然生物遥测的初始成本较高,但这最终会被进行具有生理相关性的脓毒症实验所需的小鼠数量显著减少所抵消。