Cesarovic Nikola, Jirkof Paulin, Rettich Andreas, Arras Margarete
Division of Surgical Research, University Hospital Zurich.
J Vis Exp. 2011 Nov 21(57):3260. doi: 10.3791/3260.
The laboratory mouse is the animal species of choice for most biomedical research, in both the academic sphere and the pharmaceutical industry. Mice are a manageable size and relatively easy to house. These factors, together with the availability of a wealth of spontaneous and experimentally induced mutants, make laboratory mice ideally suited to a wide variety of research areas. In cardiovascular, pharmacological and toxicological research, accurate measurement of parameters relating to the circulatory system of laboratory animals is often required. Determination of heart rate, heart rate variability, and duration of PQ and QT intervals are based on electrocardiogram (ECG) recordings. However, obtaining reliable ECG curves as well as physiological data such as core body temperature in mice can be difficult using conventional measurement techniques, which require connecting sensors and lead wires to a restrained, tethered, or even anaesthetized animal. Data obtained in this fashion must be interpreted with caution, as it is well known that restraining and anesthesia can have a major artifactual influence on physiological parameters. Radiotelemetry enables data to be collected from conscious and untethered animals. Measurements can be conducted even in freely moving animals, and without requiring the investigator to be in the proximity of the animal. Thus, known sources of artifacts are avoided, and accurate and reliable measurements are assured. This methodology also reduces interanimal variability, thus reducing the number of animals used, rendering this technology the most humane method of monitoring physiological parameters in laboratory animals. Constant advancements in data acquisition technology and implant miniaturization mean that it is now possible to record physiological parameters and locomotor activity continuously and in realtime over longer periods such as hours, days or even weeks. Here, we describe a surgical technique for implantation of a commercially available telemetry transmitter used for continuous measurements of core body temperature, locomotor activity and biopotential (i.e. onelead ECG), from which heart rate, heart rate variability, and PQ and QT intervals can be established in freeroaming, untethered mice. We also present pre-operative procedures and protocols for post-operative intensive care and pain treatment that improve recovery, well-being and survival rates in implanted mice.
在学术领域和制药行业,实验小鼠是大多数生物医学研究首选的动物物种。小鼠体型易于管理,饲养相对容易。这些因素,再加上有大量自发和实验诱导的突变体,使得实验小鼠非常适合广泛的研究领域。在心血管、药理学和毒理学研究中,通常需要准确测量与实验动物循环系统相关的参数。心率、心率变异性以及PQ和QT间期的测定基于心电图(ECG)记录。然而,使用传统测量技术很难在小鼠身上获得可靠的ECG曲线以及诸如核心体温等生理数据,因为传统技术需要将传感器和导线连接到受限制、被束缚甚至麻醉的动物身上。以这种方式获得的数据必须谨慎解读,因为众所周知,限制和麻醉会对生理参数产生重大的人为影响。无线电遥测技术能够从清醒且未被束缚的动物身上收集数据。甚至可以在自由活动的动物身上进行测量,而且不需要研究人员靠近动物。因此,避免了已知的人为因素来源,确保了准确可靠的测量。这种方法还减少了动物个体之间的差异,从而减少了所用动物的数量,使这项技术成为监测实验动物生理参数最人道的方法。数据采集技术和植入设备小型化的不断进步意味着现在有可能在数小时、数天甚至数周等较长时间内连续实时记录生理参数和运动活动。在这里,我们描述一种手术技术,用于植入一种商用遥测发射器,该发射器用于连续测量核心体温、运动活动和生物电位(即单导联ECG),由此可以在自由活动、未被束缚的小鼠身上确定心率、心率变异性以及PQ和QT间期。我们还介绍了术前程序以及术后重症监护和疼痛治疗的方案,这些方案可提高植入小鼠的恢复情况、健康状况和存活率。