Human respiratory and neurocirculatory plasticity induced by intermittent hypoxia

周期性暴露于低血氧，称为间歇性缺氧（IH），在自然环境中很常见。例如，IH是潜水哺乳动物、飞越高海拔山峰的鹅和冬眠中的松鼠的特征。同样，人类在登山旅行、在高海拔矿井轮班工作以及在睡眠期间暴露于IH，否则正常人可能会出现睡眠呼吸暂停。在我之前的NSERC发现项目中，我展示了IH会导致我们控制呼吸和循环的功能变化。

Periodic exposure to low blood oxygen, termed intermittent hypoxia (IH), is common in the natural environment. For example, IH is a characteristic of diving mammals, geese flying over high-altitude peaks, and in squirrels during winter hibernation. Similarly, humans are exposed to IH during mountain climbing sojourns, shift work in high altitude mines, and during sleep where sleep apnea can develop in otherwise normal people. In my previous NSERC Discovery program, I showed that IH leads to functional changes in how we control our breathing and circulation. My recent progress shows that IH reduces blood flow and the force of blood against the lining of blood vessels. Additionally, we found that IH leads to long-lasting increases in breathing and blood pressure. These findings suggest that IH has a long-lasting effect in how our body controls breathing and our circulation. Specifically, IH increases activity of the body's peripheral chemical receptor, increases oxidative stress, and reduces the production of blood vessel relaxing factors. Consequently, sympathetic neurotransmission may be increased by IH resulting in greater blood vessel constriction. My research program objectives will determine if changes in blood flow patterns, oxidative stress, and blood flow to the body's peripheral chemical receptor can influence breathing and circulation control following IH. I will use novel experimental paradigms and methodological approaches to manipulate blood flow dynamics, oxidative stress, and measure blood flow within the human peripheral chemical receptor. Blood flow dynamics will be manipulated using multiple approaches including localized heating, exercise, and blood flow restriction. Oxidative stress will be reduced using antioxidants. Finally, peripheral chemical receptor blood flow will be measured non-invasively using an innovative contrast ultrasound approach. With each manipulation, I will determine how IH changes the body's control of breathing and circulation. The proposed research program impact contributes to a greater understanding of the human response to a common physiological stress. It will generate new scientific knowledge regarding how blood flow dynamics and oxidative stress change the control of breathing and circulation following IH. Additionally, the proposed research develops an innovative methodology to measure human peripheral chemical receptor blood flow for the first time. This methodology will determine how changes in receptor blood flow influence breathing and circulation control and is likely to generate a novel field of study. I recognize that equity, diversity, and inclusion strengthen the quality, relevance and impact of research. As a result, my HQP training program objectives are designed to include all levels of HQP from a diverse pool of international applicants. My research program trains highly successful HQP to produce leading edge natural sciences and engineering research in Canada.