A portable in vivo metabolic and blood analysis system for field and laboratory work

氧气供应减少(即缺氧)对大多数脊椎动物来说是一项艰巨的挑战，是许多临床相关疾病和病理(如心脏病发作、中风、慢性肺病等)的中心组成部分。地球上有许多低氧环境，生活在这些环境中的动物已经进化出独特的适应能力，以应对低氧环境下的生活挑战。不幸的是，我们对耐低氧哺乳动物这些适应的系统控制和进化起源的理解很差。在广泛的系统发育不同的哺乳动物中研究对低氧的生理适应及其潜在的控制对于理解低氧耐受的进化起源至关重要。为了解决这一知识差距，Pamenter实验室研究了哺乳动物耐缺氧的自然进化机制，重点是调节缺氧时通风和新陈代谢的脑干控制中心。关键是，许多耐低氧能力最强的物种无法在商业上获得，必须在野外进行研究，通常是在非常偏远的地方。在这些条件下进行现场工作需要专门的设备。*本RTI应用中要求的设备包括1)高度便携、耐用和自给自足(包括电源和数据存储)的气体检测系统，用于测量整个动物的呼吸系统气体，作为间接但准确的代谢率测量；以及2)同样便携的血液分析仪，能够测量血气特性、酸碱状态和其他代谢物。有了这个系统，帕门特实验室的HQP将能够通过研究稀有和难以接触到的物种来测试关于低氧适应的新假设，这些物种可能具有独特的低氧适应能力，但以前从未被研究过，例如青藏高原和南非平原原产的物种。*所要求的系统代表了便携式代谢研究的最先进水平，适合在清醒和自由行为的动物体内使用，而且与模块化台式系统相比，还提供了相当大的成本节约。更重要的是，该系统经久耐用，便于携带，因此既适用于要求苛刻的现场环境，也适用于经典的大学实验室环境。该系统将由Pamenter博士的业务拨款进行维护和支持，并将立即由他的团队和渥太华大学其他研究小组的HQP每天使用。它对于发展和扩大几个正在进行的国际合作也是至关重要的。在这种设备的支持下，由HQP驱动的研究有望促进我们对哺乳动物适应低氧的机制和进化起源的了解，并为治疗与低氧有关的疾病和病理提供临床策略。

Reduced oxygen availability (i.e., hypoxia) poses a difficult challenge to most vertebrates and is a central component of many clinically-relevant diseases and pathologies (e.g., heart attack, stroke, chronic pulmonary disorders, etc.). There are numerous hypoxic environments on earth and animals that live in these niches have evolved unique adaptations to meet the challenges of life in hypoxia. Unfortunately, our understanding of the systemic control and evolutionary origins of these adaptations in hypoxia-tolerant mammals is poor. Investigating physiological adaptations to hypoxia and their underlying control in a wide range of phylogenetically distinct mammals is critical to understanding the evolutionary origins of hypoxia-tolerance. To address this knowledge gap, the Pamenter laboratory studies naturally-evolved mechanisms of hypoxia-tolerance in mammals, with an emphasis on the brainstem control centers that regulate ventilation and metabolism in hypoxia. Critically, many of the most hypoxia-tolerant species are not commercially available and must be studied in the field, often in very remote locations. Conducting field work under these conditions requires specialized equipment.******The equipment requested in this RTI application comprises 1) a highly portable, durable, and self-contained (including power supply and data storage) gas detection system for the measurement of whole animal respiratory gases as an indirect but accurate measure of metabolic rate, and 2) an equally portable blood analyzer capable of measuring blood-gas properties, acid-base status, and other metabolites. With this system, HQP from the Pamenter laboratory will be able to test novel hypotheses regarding adaptations to hypoxia by studying rare and difficult to reach species that likely have unique adaptations to life in hypoxia but which have never been previously studied, such as those native to the Tibetan plateau and the plains of South Africa. ******The requested system represents the state of the art in portable metabolic investigations suitable for in vivo use in awake and freely behaving animals, and also offers considerable cost-savings relative to modular benchtop systems. More importantly, this system is durable and portable and is therefore suitable for use in both demanding field settings as well as in a classic university laboratory setting. The system will be maintained and supported by the operating grants of Dr. Pamenter and will be used immediately, and on a daily basis, by HQP from his group and other research groups at the University of Ottawa. It will also be critical to the development and expansion of several ongoing international collaborations. HQP-driven research supported by this equipment is expected to advance our knowledge of the mechanisms and evolutionary origins of mammalian adaptation to hypoxia, and also to inform clinical strategies for the treatment of hypoxia-related illnesses and pathologies.**