Understanding What Limits Fish Cardiovascular Performance and Environmental Responses

心肺系统（鳃、心脏、血液、血管）对生存至关重要，因为它确保足够的氧气和营养物质输送到组织，并清除代谢废物。我的研究项目采用综合（从分子到整个动物）的方法来研究鱼类之间的氧气消耗（如新陈代谢和代谢能力）、心脏功能、血管功能/生理和压力（儿茶酚胺和皮质醇水平、受体类型/水平）的差异，以及这如何使它们在具有挑战性的条件下生存。虽然我在了解鱼类心脏功能的可塑性及其与性能/生存的关系方面取得了巨大进展，但这项研究仍有许多重要问题未得到解答，并产生了一些新的假设。我在这份拨款申请中提到了其中一些问题。***鱼类心血管生理学的三个基本问题是：1)什么因素/机制决定了个体之间和物种之间最大心率的差异？2)是什么限制了高温下的心率？3)当温度升高时，是什么机制限制了鱼类增加搏动量（每次搏动泵出多少血）的能力。我将研究所有这些问题。****我实验室最近的研究表明，长时间暴露在低氧（缺氧）环境中的鱼会损害心脏功能，但这些物种每泵入的血液体积可以消耗更多的氧气。因此，我将研究后一种影响是否由于线粒体功能的改变和/或与氧摄取和扩散相关的因素的改变。此外，我将研究心脏的泵送能力降低是否由于心脏肌肉收缩能力有限，以及为什么。****我将对非常小的冠状血管（即微血管，在控制血液流向组织中最重要的血管）以及鳟鱼卵巢和肠道中的类似血管进行大量研究。先前的研究是先前工作的延续，并且至关重要，因为冠状动脉血流量是压力条件下心脏功能的关键。将对鳟鱼的肠道和卵巢血管进行研究，因为这两个血管床的灌注分别对消化和卵的发育很重要，冠状血管的数据可能无法反映温度或各种激素如何影响血管舒动反应，从而影响其他组织的血流。*最后，我将研究免疫相关蛋白（白细胞介素-1）对鳟鱼心脏功能和血管阻力的影响，并确定其中的机制。该分子是感染后疾病相关过程的重要介质。****这项研究将极大地提高我们对鱼类心肺系统如何应对压力源的理解的深度和广度，从而，如果/当它们的生存受到威胁。**

The cardiorespiratory system (gills, heart, blood, blood vessels) is critical to survival because it ensures adequate oxygen and nutrient delivery to the tissues, and removes metabolic wastes. My research program uses an integrative (molecular to whole animal) approach to look at how oxygen consumption (e.g. metabolism and metabolic capacity), heart function, blood vessel function/physiology and stress (catecholamine and cortisol levels, receptor types / levels) differ between fish species and how this allows them to survive under challenging conditions. While I have made tremendous progress in understanding the plasticity of fish cardiac function and its relationship to performance / survival, this research has left many important questions unanswered and generated several new hypotheses. I address a number of these in this grant application. *** Three fundamental questions in fish cardiovascular physiology are: 1) what factors / mechanisms determine between individual and between species differences in maximum heart rate?; 2) what limits heart rate at high temperatures?; and 3) what mechanisms constrain the capacity of fishes to increase stroke volume (how much blood is pumped per beat) as temperatures rise. I will examine all of these questions.**** Recent studies in my lab have shown that fish exposed to low oxygen (hypoxia) for prolonged periods have compromised heart function, but that these species can consume more oxygen per volume of blood pumped. Thus, I will investigate whether this latter effect is due to changes in mitochondrial function and/or alterations in factors related to oxygen uptake and diffusion. Further, I will examine whether the heart's reduced pumping capacity is due to a limited capacity of the heart muscle to contract, and why.**** I will conduct a number of studies on very small coronary vessels (i.e, microvessels, the ones that are most important in controlling blood flow to tissues), and similar vessels in the ovary and intestine of trout. The former studies are a continuation of previous work, and are critical as coronary blood flow is key to cardiac performance under stressful conditions. The studies on trout intestinal and ovarian vessels will be performed because perfusion of these two vascular beds is important for digestion and egg development, respectively, and data on coronary vessels may not reflect how temperature or various hormones affect vasomotor responses, and thus blood flow, in other tissues.*Finally, I will investigate the impact of an immune-related protein (interleukin-1) on cardiac performance and vascular resistance in trout, and determine the mechanisms involved. This molecule is an important mediator of post-infection disease-related processes.**** This research will greatly enhance the depth and breadth of our understanding of how the fish cardiorespiratory system responds to stressors, and thus, if/when their survival is threatened. **