Understanding What Limits Fish Cardiovascular Performance and Environmental Responses

了解鱼类心血管性能和环境反应的限制因素

• 批准号: RGPIN-2016-04481
• 负责人: Gamperl, Anthony
• 金额: $ 4.44万
• 依托单位: Memorial University of Newfoundland
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615090
• 关键词: Understanding; What; Limits; Fish; Cardiovascular

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-1ß) 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.

心肺系统(鳃、心脏、血液、血管)对生存至关重要，因为它确保向组织提供足够的氧气和营养，并清除代谢废物。我的研究项目使用(分子到整个动物)的综合方法来研究不同鱼种之间的耗氧量(例如新陈代谢和代谢能力)、心脏功能、血管功能/生理和应激(儿茶酚胺和皮质醇水平、受体类型/水平)的差异，以及这如何使它们能够在具有挑战性的条件下生存。虽然我在理解鱼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的进展，但这项研究留下了许多重要的问题没有得到回答，并产生了几个新的假说。我在这次拨款申请中解决了其中的一些问题。 鱼类心血管生理学的三个基本问题是：1)是什么因素/机制决定了个体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)随着温度的升高，什么机制限制了鱼类增加每搏输出量(每跳多少血液)的能力。我将研究所有这些问题。 我实验室最近的研究表明，长期暴露在低氧(低氧)环境中的鱼会损害心脏功能，但这些物种每泵出的血液可以消耗更多的氧气。因此，我将调查后一种效应是否源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，我将研究心脏泵血能力降低是否由于心肌收缩能力有限，以及原因。 我将对非常小的冠状血管(即微血管，对控制流向组织的血液最重要的那些)以及鲑鱼卵巢和肠道中类似的血管进行一些研究。以前的研究是先前工作的继续，并且非常关键，因为冠脉血流是应激条件下心脏功能的关键。将进行关于鲑鱼肠道和卵巢血管的研究，因为这两个血管床的灌流分别对消化和卵子发育非常重要，而关于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运动反应，从而影响其他组织的血液流动。 最后，我将研究一种免疫相关蛋白(白介素1)对鲑鱼心脏性能和血管阻力的影响，并确定相关机制。这种分子是感染后疾病相关过程的重要介体。 这项研究将大大提高我们对鱼类心肺系统如何应对应激源的理解的深度和广度，从而了解它们的生存是否/何时受到威胁。