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，因为它确保向组织输送足够的氧气和营养，并清除代谢废物。我的研究计划使用综合（分子到整个动物）的方法来研究耗氧量（例如代谢和代谢能力），心脏功能，血管功能/生理学和压力（儿茶酚胺和皮质醇水平，受体类型/水平）在鱼类之间的差异以及如何使它们在具有挑战性的条件下生存。虽然我在理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，但这项研究仍然留下了许多重要的问题没有答案，并产生了几个新的假设。我在这份拨款申请中提到了其中的一些问题。*** 鱼类心血管生理学中的三个基本问题是：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)在高温下是什么限制了心率？以及3）当温度升高时，什么机制限制了鱼类增加每搏输出量（每搏泵出多少血液）的能力。我会回答所有这些问题 *。 我的实验室最近的研究表明，长时间暴露在低氧（缺氧）环境中的鱼类会损害心脏功能，但这些物种每泵出的血液体积会消耗更多的氧气。因此，我将研究后一种效应是否是由于线粒体功能的变化和/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是由于心肌收缩能力有限，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方面最重要的血管）以及鳟鱼卵巢和肠道中的类似血管进行一些研究。以前的研究是以前工作的延续，并且是至关重要的，因为冠状动脉血流是压力条件下心脏性能的关键。对鳟鱼肠道和卵巢血管的研究将进行，因为这两个血管床的灌注分别对消化和卵子发育很重要，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，并确定所涉及的机制。这种分子是感染后疾病相关过程的重要介质。* 这项研究将大大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，因此，如果/当它们的生存受到威胁时。**

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. **