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. **