Vascular Determinants of Anesthesia-Induced Hypotension at the Extremes of Age

项目概要/摘要 每年，数以亿计的患者接受全身麻醉进行手术。数百万 这些患者在手术期间特别容易受伤，因为他们或者非常年轻（例如， 新生儿和婴儿）或更大（>70岁）。麻醉师的一个关键作用是确保 血液动力学稳定性和充分的器官灌注（例如，防止术中低血压）。当照顾 对于年龄极端的患者，这可能具有挑战性，因为高达80%的新生儿、婴儿和老年人 出现术中低血压。这是一个重大的公共卫生问题，因为术中 低血压已被证明在这一人群中引起显著的发病率和死亡率， 每年都有数百万美元的额外医疗费用。虽然很明显术中 低血压是新生儿、婴儿和老年人的一个重要问题， 术中低血压的风险增加及其后果尚不清楚。 为了解决这个问题，我们建议使用互补的体外和体内方法来提供新的见解 研究年龄极端的患者术中低血压的机制， 频率.这项研究计划的目标是调查血管系统的独特性质， 年龄的极端有助于术中低血压的发展， 全身麻醉药。我们发表的和初步的数据表明，幼年大鼠的肠系膜动脉硬化 与成年人相比，对去甲肾上腺素的收缩能力减弱。相反，大脑中动脉 从幼年大鼠表现出减少僵硬和受损的脑血流自动调节时， 与成年人相比。总之，这些数据提供了我们假设 高龄患者术中低血压风险增加的潜在机制 起源于血管。 在接下来的5年里，我们计划研究血管机制， 年龄的患者术中低血压和由此导致的器官灌注不足的风险增加 全麻通过研究离体肠系膜动脉和脑动脉，我们将确定其生物力学特性， 区分非常年轻和老年人与中年人的细胞机制。 另外，我们将使用体内方法来确定低血压的定义， 器官灌注最后，我们将确定哪种麻醉方案最不可能产生低血压， 以及用于治疗低血压的最佳平衡疗法，在改善血压的同时保持整体- 身体器官灌注这些不同但互补的调查路线将是朝着以下目标迈出的重要一步： 优化高龄患者的围手术期护理。

PROJECT SUMMARY/ABSTRACT Each year, hundreds of millions of patients are exposed to general anesthesia for surgery. Millions of these patients are particularly vulnerable to injury during surgery because they are either very young (e.g., neonates and infants) or older (>70 years of age). One critical role of the anesthesiologist is to ensure hemodynamic stability and adequate organ perfusion (e.g., prevent intraoperative hypotension). When caring for patients at the extremes of age, this can be challenging because up to 80% of neonates, infants, and older adults experience intraoperative hypotension. This represents a significant public health problem as intraoperative hypotension has been shown to cause significant morbidity and mortality in this population and is associated with millions of dollars in additional healthcare costs per year. Though it is clear that intraoperative hypotension is a significant problem in neonates, infants, and older adults, the mechanisms that underlie the increased risk of intraoperative hypotension and its consequences remain unclear. To address this, we propose to use complementary in vitro and in vivo approaches to provide new insights into mechanisms by which patients at extremes of age suffer intraoperative hypotension with increased frequency. The goal of this research program is to investigate how the unique properties of the vasculature at the extremes of age contribute to the development of intraoperative hypotension in the setting of commonly used general anesthetics. Our published and preliminary data show that mesenteric arteries in juvenile rats are stiffer with diminished capacity to constrict to norepinephrine compared to adults. In contrast, middle cerebral arteries from juvenile rats demonstrated reduced stiffness and impaired autoregulation of cerebral blood flow when compared to adults. Taken together, these data provide the foundation upon which we hypothesize that the underlying mechanism of increased risk of intraoperative hypotension in patients at the extremes of age is vascular in origin. Over the next 5 years, we propose to investigate vascular mechanisms by which patients at the extremes of age are at increased risk of intraoperative hypotension and resultant organ hypoperfusion when exposed to general anesthesia. By studying isolated mesenteric and cerebral arteries we will identify biomechanical and cellular mechanisms that differentiate the very young and older adults from adults of intermediate age. Separately, we will use in vivo approaches to identify definitions of hypotension that are determined based upon organ perfusion. Finally, we will determine which anesthetic regimens are least likely to produce hypotension, and which therapies used to treat hypotension best balance improving blood pressure while preserving whole- body organ perfusion. These distinct but complementary lines of inquiry will be an important step towards optimizing perioperative care for those at the extremes of age.