Telemetry serves as a valuable tool for measuring cardiovascular parameters in unrestrained, awake animals. Its application has expanded into human medicine, exemplified by the direct measurement of left atrial pressure in heart failure patients¹ and the percutaneous implantation of pressure transducer, such as Cardio MEMS, in the pulmonary artery for patients with pulmonary hypertension² and heart failure.³ This innovation facilitates regular pressure measurements, enabling the early detection of clinical worsening.

In the 1960s, the establishment of telemetric measurements for blood pressure and ECG involved the insertion of devices that were then exteriorized and connected to small amplifiers. The signals were frequency-modulated to allow transmission via FM transmitters placed on the animal’s back. This allowed studies in large animals, ranging from dogs and swine to giraffes roaming in the wild.^4,5

Over the past 2 decades, significant progress has been made in telemetric technology. Devices have evolved to incorporate multiple measurements, including biopotentials, temperature, pressures,^6,7 and blood flow.⁸ Additionally, impedance measurements now allow the assessment of respiratory parameters.⁹ Miniaturization allowed implantation without external leads. The battery size is the main determinant of implant size, with data transmission consuming the most energy.

Communication between implants and antennas is bidirectional, allowing external definition and modification of timing, duration, and frequency of data acquisition. Some implants require direct communication with the acquisition software during data acquisition, while others have internal memory storage for offline data transmission. Implants requiring direct communication with the antenna necessitate strategically located antennas to prevent data loss.

Telemetric measurement of intravascular pressures and biopotentials (electromyography and ECG) have been implemented in studies on autonomic nervous system activity and cardiovascular disease pathogenesis, as well as for monitoring the effects of therapeutic interventions in both large and small animals.^6,7,10–13 The main advantage of telemetry over acute experiments is that measurements of cardiovascular parameters can be repeated over a prolonged period of time (up to several years after implantation⁷), allowing more extensive follow-up, so that measurements can be repeated before and after a therapeutic intervention, reducing variability. Indeed, tail-cuff measurements have been shown to be closely related to measurements via telemetry although some systematic differences in pressure were present.¹⁴ Additionally, as mentioned above, measurements are performed in unrestrained animals, thereby abrogating the cardiodepressive effect of anesthesia on the measurements. Furthermore, once the implant site is healed, animals can be group-housed, which reduces stress and, thereby, animal discomfort. Each implant has its unique code, and, hence, measurements from 2⁹ or more⁷ animals in the same cage can be obtained simultaneously.

It is important to integrate the measured signals with observations of behavior. For example, in large animals, feeding results in excitement and, hence, changes in heart rate and blood pressure,⁹ while measurements repeated over time show consistent diurnal patterns.¹⁴ This should be taken into account when setting up the measurements. Also, changes in group composition were shown to affect behavior and cardiopulmonary function.⁹ Both nonhuman primates and dogs showed signs of stress, such as increased respiration and heart rate when housed solitarily,⁹ but also when exposed to a new cage mate, until the new hierarchy was established. Dogs were also more active when housed with a cage mate.⁹ These observations underscore the importance of an acclimatization period when starting a new experiment but also show that group housing, in accordance with animal welfare guidelines, would be preferred whenever possible.

In small laboratory animals such as mice and rats, radiotelemetry stands out as a widely used and validated method for measuring blood pressure and is crucial for achieving continuous and precise monitoring. Recent recommendations guide its differential use for scientific publications.¹⁵ However, a drawback is the isolation of rodents, which is common during telemetry measurements, leading to potential physical and physiological effects that impact heart rate¹⁶ and blood pressure^17,18 outcomes.

While international animal welfare guidelines^19,20 strongly endorse the social housing of animals in scientific research, a notable discrepancy exists for small animals involved in telemetry studies. Historically, these animals have been individually housed, a practice largely influenced by the persistent limitation of first-generation telemetry systems, which still dominate the market.

In 2016, a survey confirmed that individual housing for telemetry assessment remains a prevalent practice among pharmaceutical companies and contract research organizations.²¹ The survey findings revealed that <50% of the respondents socially housed telemetry animals during recordings. It is worth noting that individual housing of rats and mice results in alterations in food intake, visceral fat accumulation, gene expression, and behavior over the long term.²²

In telemetry studies involving small animals, several common reasons for isolating them include (1) the interference of devices transmitting on the same wavelength (ie, not allowing recording from multiple animals within the same cage), (2) the need for animals to recover from implantation surgery, and (3) the use of cage-type monitoring systems that strictly record individual animals.²³ Of course, a simple approach might be to limit the solitary housing to the days that blood pressure is actually measured by telemetry, implying that the animals are housed socially at all other times. However, this becomes less attractive when the telemetry study involves weeks of blood pressure measurement. Under such circumstances, when lacking multitelemetry readers, social housing can be addressed by adding a companion animal. Yet, evidence suggests that this approach might introduce social stress and will lead to cardiovascular, inflammatory, and behavioral alterations.²⁴ A potential additional disadvantage is that females need to be ovariectomized before being used for social housing with males.¹⁶ Alternatively, one might limit this approach to male/male or female/female combinations to avoid unintended reproduction or sterilization procedures. Additionally, special attention should be paid to minimizing social stress factors, such as matching companion age and strain, and avoiding relocation or changes in partners. Regarding blood pressure outcomes, there is no consensus on the effect of group housing and companion approach on blood pressure. One study reported a rise in blood pressure in group-housed spontaneously hypertensive rats.²⁵ Another study showed that social confrontation in Long-Evans rats also increased blood pressure,²⁶ while a decreased blood pressure was reported in normotensive grouped-housed Sprague-Dawley rats.¹⁷ Nevertheless, multihousing is considered default for social animals, with isolation justified based only on sound scientific or veterinary reasons.²³

The emergence of multihousing facilities for small animals might provide a more natural and less stressful environment. A growing number of companies provide implants for recording multiple socially housed small animals, including Data Sciences International, EMKA Technologies, AD Instruments (KAHA Sciences), and TSE Systems (Table).²¹ Obviously, choosing the most suitable telemetry technology depends on the research goals. The Table lists the characteristics of the various options that are currently available. Remarkably, the literature on this approach in rodents is limited, while several concerns must be addressed before implementing multihousing radiotelemetry as a common practice. The cost factor is a significant consideration, as dual-telemetry or multitelemetry technology represents a more advanced and expensive option compared with previous versions. Second, there are serious disadvantages for the animals, given that the dual-frequency transmitters can be twice as large as the traditional probes, while their battery life is shorter. The latter implies more frequent operations to replace the batteries in the case of long-term studies and obviously higher refurbishment costs. Another aspect to address is data accuracy and precision. While telemetry is considered the standard for continuous and direct blood pressure measurement, there is a need to evaluate how the use of multianimal cages affects data accuracy and precision compared with single-animal cage studies. Here, factors such as sample size, blood pressure differences among housing types, number of animals per cage, and differences among dominant/submissive animals must be considered. To the best of our knowledge, none of this has been addressed until today. Additionally, cage arrangement, cage type,²¹ and cage enrichment²⁵ might influence blood pressure, and because these vary greatly among research facilities, this must also be taken into consideration.

Table. Characteristics of Multihousing Telemetry Systems

In conclusion, the exploration of multihousing for small laboratory animals in blood pressure monitoring via radiotelemetry introduces both prospects and challenges. On the one hand, current animal welfare guidelines advocate against housing isolation, and a wide range of companies now provide multitelemetry systems that would enable us to achieve this goal. On the other hand, implementing these new tools requires a critical evaluation of all methodological and technical aspects of this new approach, with a focus on costs, data accuracy, and ethical implications. The transition to multihousing radiotelemetry can only occur once the new approach is standardized and proven to yield results that are as reliable as those obtained with the individual housing approach.

E.O. Cruz-López was supported by the Consejo Nacional de Ciencia y Tecnología (grant 739513, Mexico). D. Merkus was supported by a grant from the German Center for Cardiovascular Research (DZHK81Z0600207) and the Dutch Heart Foundation (2020B008 RECONNEXT).

Disclosures None.

For Sources of Funding and Disclosures, see page 949.

The opinions expressed in this article are not necessarily those of the editors nor the American Heart Association.

遥测是测量不受约束、清醒的动物心血管参数的宝贵工具。其应用已扩展到人类医学，例如直接测量心力衰竭患者的左心房压力^{1以及在肺动脉高压2}和心力衰竭患者的肺动脉中经皮植入压力传感器（例如 Cardio MEMS） 。 ³这项创新有助于定期进行压力测量，从而能够及早发现临床恶化情况。

在 20 世纪 60 年代，血压和心电图遥测测量的建立涉及插入设备，然后将这些设备外部化并连接到小型放大器。这些信号经过调频，可以通过放置在动物背上的调频发射器进行传输。这使得对大型动物的研究成为可能，从狗、猪到野外的长颈鹿。^4,5

在过去的二十年里，遥测技术取得了重大进展。设备已经发展到包含多种测量值，包括生物电势、温度、压力、^6,7和血流。⁸此外，阻抗测量现在可以评估呼吸参数。⁹小型化允许无需外部引线即可植入。电池尺寸是植入物尺寸的主要决定因素，其中数据传输消耗的能量最多。

植入物和天线之间的通信是双向的，允许外部定义和修改数据采集的时间、持续时间和频率。一些植入物需要在数据采集过程中与采集软件直接通信，而另一些植入物则具有用于离线数据传输的内部存储器。需要与天线直接通信的植入物需要战略性地定位天线以防止数据丢失。

血管内压力和生物电势（肌电图和心电图）的遥测测量已应用于自主神经系统活动和心血管疾病发病机制的研究，以及监测大型和小型动物治疗干预的效果。^6,7,10–13遥测相对于急性实验的主要优点是，心血管参数的测量可以在很长一段时间内重复测量（植入后长达几年⁷），允许更广泛的随访，以便测量可以在治疗干预之前和之后重复，以减少变异性。事实上，尾套测量已被证明与遥测测量密切相关，尽管存在一些系统的压力差异。¹⁴此外，如上所述，测量是在不受约束的动物中进行的，从而消除了麻醉对测量的心脏抑制作用。此外，一旦植入部位愈合，动物就可以被集中饲养，从而减少压力，从而减少动物的不适。每个植入物都有其独特的代码，因此可以同时获得同一笼子中2 ⁹或更多^{7 只动物的测量结果。}

将测量到的信号与行为观察相结合非常重要。例如，在大型动物中，进食会导致兴奋，从而导致心率和血压发生变化，⁹而随着时间的推移重复测量显示出一致的昼夜模式。¹⁴设置测量时应考虑到这一点。此外，群体组成的变化被证明会影响行为和心肺功能。⁹非人类灵长类动物和狗都表现出压力迹象，例如单独饲养时呼吸频率和心率增加，⁹以及暴露于新的笼中伙伴时，直到新的等级制度建立为止。当狗与笼中伙伴一起饲养时，它们也会更加活跃。⁹这些观察结果强调了开始新实验时适应期的重要性，但也表明，只要有可能，根据动物福利准则，集体饲养将是首选。

在小鼠和大鼠等小型实验动物中，无线电遥测技术是一种广泛使用且经过验证的血压测量方法，对于实现连续和精确的监测至关重要。最近的建议指导其在科学出版物中的不同用途。¹⁵然而，一个缺点是啮齿动物的隔离，这在遥测测量期间很常见，导致潜在的物理和生理效应，影响心率¹⁶和血压^17,18结果。

虽然国际动物福利准则^19,20强烈支持科学研究中动物的社会住房，但对于参与遥测研究的小动物存在显着差异。从历史上看，这些动物一直被单独饲养，这种做法很大程度上受到第一代遥测系统持续存在的限制的影响，而该系统仍然在市场上占据主导地位。

2016 年的一项调查证实，为遥测评估提供个人住房仍然是制药公司和合同研究组织的普遍做法。²¹调查结果显示，<50% 的受访者在录音期间社会饲养遥测动物。值得注意的是，从长远来看，大鼠和小鼠的单独饲养会导致食物摄入、内脏脂肪积累、基因表达和行为的改变。²²

在涉及小动物的遥测研究中，隔离它们的几个常见原因包括（1）以相同波长传输的设备的干扰（即不允许对同一笼子内的多个动物进行记录），（2）动物需要恢复（3）使用严格记录个体动物的笼式监测系统。²³当然，一个简单的方法可能是将单独饲养限制在通过遥测实际测量血压的日子，这意味着动物在其他时间都被社会饲养。然而，当遥测研究涉及数周的血压测量时，这就变得不那么有吸引力了。在这种情况下，当缺乏多遥测读取器时，可以通过添加伴侣动物来解决社会住房问题。然而，有证据表明，这种方法可能会带来社会压力，并导致心血管、炎症和行为改变。²⁴另一个潜在的缺点是，女性在与男性一起入住社会住房之前需要切除卵巢。¹⁶或者，人们可能会将这种方法限制为男性/男性或女性/女性组合，以避免意外的繁殖或绝育程序。此外，应特别注意尽量减少社会压力因素，例如匹配伴侣年龄和压力，并避免搬迁或更换伴侣。关于血压结果，对于集体住宿和陪伴方式对血压的影响尚未达成共识。一项研究报告称，群养的自发性高血压大鼠的血压会升高。²⁵另一项研究表明，Long-Evans 大鼠的社会对抗也会导致血压升高，²⁶而据报道，血压正常、群养的 Sprague-Dawley 大鼠的血压会降低。¹⁷尽管如此，多住所被认为是社会动物的默认选择，只有基于合理的科学或兽医原因，隔离才是合理的。²³

小动物多住所设施的出现可能会提供一个更自然、压力更小的环境。越来越多的公司提供用于记录多种社会饲养小动物的植入物，包括 Data Sciences International、EMKA Technologies、AD Instruments (KAHA Sciences) 和 TSE Systems（表）。²¹显然，选择最合适的遥测技术取决于研究目标。该表列出了当前可用的各种选项的特征。值得注意的是，关于啮齿类动物这种方法的文献有限，而在将多房屋无线电遥测作为常见做法之前必须解决几个问题。成本因素是一个重要的考虑因素，因为与以前的版本相比，双遥测或多遥测技术代表了更先进和更昂贵的选择。其次，由于双频发射器的体积是传统探头的两倍，而且电池寿命较短，因此对动物来说存在严重的缺点。后者意味着在长期研究的情况下需要更频繁地更换电池，并且翻新成本明显更高。需要解决的另一个方面是数据准确性和精度。虽然遥测被认为是连续和直接血压测量的标准，但与单动物笼研究相比，需要评估多动物笼的使用如何影响数据的准确性和精确度。在这里，必须考虑诸如样本量、不同饲养类型之间的血压差异、每个笼子的动物数量以及优势/顺从动物之间的差异等因素。据我们所知，直到今天这些问题都还没有得到解决。此外，笼子布置、笼子类型²¹和笼子富集度²⁵可能会影响血压，并且由于这些在研究设施之间差异很大，因此也必须考虑到这一点。

桌子。多外壳遥测系统的特点

总之，通过无线电遥测技术对小型实验动物进行血压监测的多舍环境的探索既带来了前景，也带来了挑战。一方面，当前的动物福利准则主张反对住房隔离，并且许多公司现在提供多重遥测系统，使我们能够实现这一目标。另一方面，实施这些新工具需要对这种新方法的所有方法和技术方面进行严格评估，重点关注成本、数据准确性和道德影响。只有当新方法标准化并被证明能够产生与单独住房方法获得的结果一样可靠的结果时，才能向多住房无线电遥测技术过渡。

EO Cruz-López 得到了 Consejo Nacional de Ciencia y Tecnología 的支持（拨款 739513，墨西哥）。 D. Merkus 得到了德国心血管研究中心 (DZHK81Z0600207) 和荷兰心脏基金会 (2020B008 RECONNEXT) 的资助。

披露无。

有关资金来源和披露信息，请参阅第 949 页。

本文表达的观点不一定代表编辑或美国心脏协会的观点。