Effects of chronic use of thickened liquids in a rat model of aging

摘要 吞咽障碍在老年人中非常普遍，包括那些患有与年龄有关的疾病的人。 增稠液体经常用于治疗吞咽障碍，并且已经显示出 立即减少气道侵入的机会。然而，增稠的液体已经与 有害的健康影响，如脱水、尿路感染和生活质量下降。尽管他们 常见的临床用途，增稠液体的长期功效，以及它们对吞咽运动学的影响， 全身水合作用和潜在的生物学尚不清楚。鉴于人口的迅速增长， 65岁以上的人，估计到2051年将达到21亿，了解吞咽困难的疗效至关重要 干预措施。该提案的总体目标是为生物学的基础知识做出贡献。 功能性吞咽变化的潜在机制是对一种经常使用但研究不足的， 老年人群吞咽困难管理的干预措施。这项拟议中的研究将使用一只老龄大鼠 模型，以询问使用增稠液体如何影响吞咽运动学，全身水合作用， 潜在的生物学。我们有三个具体的目标，每个目标都有一个独特的假设。目标1将测试 假设长期使用增稠的液体质地降低了推注速度，降低了 吞咽肌肉，并破坏正常的吞咽-吞咽事件顺序。目标2将检验假设 增稠的液体会导致液体摄入量减少和全身脱水， 因粘度和年龄而加剧。目标3将检验这样一个假设，即在没有稀薄液体的情况下， 液体，将减缓吞咽运动，动态改变肌肉收缩特性，包括减少 舌头的力量和增加收缩时间在一个年龄依赖性的方式。在音乐会上，快速的比例- 收缩IIb型肌球蛋白重链（MyHC）同种型在舌头将减少，导致增加 收缩较慢的亚型的比例，如IIa型和I型。这项研究意义重大， 这将是第一个在衰老动物模型中研究增稠液体对全身水合作用的影响 沿着潜在的肌肉生物学、运动学和生理学，以及与临床相关的 吞咽功能的结果测量。从这项工作中获得的知识将导致假设的测试， 对于必须平衡患者误吸风险和后续风险的临床决策至关重要的临床研究 医疗并发症，防止增稠液体对患者整体的潜在有害影响 医疗状况和生活质量。

Abstract Swallowing disorders are highly prevalent in elderly people, including those with age-related diseases. Thickened liquids are frequently used in the treatment of swallowing disorders and have been shown to immediately reduce the chance of airway invasion. However, thickened liquids have been associated with deleterious health effects such as dehydration, urinary tract infection, and reduced quality of life. Despite their common clinical use, the long-term efficacy of thickened liquids, and their effect on swallowing kinematics, systemic hydration, and underlying biology, is not well understood. Given the rapidly increasing population of persons over 65, estimated to reach 2.1 billion by 2051, it is critical to understand the efficacy of dysphagia interventions. The overarching goal of this proposal is to contribute foundational knowledge of biological mechanisms underlying functional swallowing changes in response to a frequently used, but understudied, intervention for dysphagia management in the aging population. The proposed study will use an aging rat model to interrogate how use of thickened liquids affects swallowing kinematics, systemic hydration, and underlying biology over time. We have 3 specific aims, each with a unique hypothesis. Aim 1 will test the hypothesis that chronic use of thickened liquid textures reduces bolus speed, reduces coordination of swallowing muscles, and disrupts normal respiratory-swallow event sequencing. Aim 2 will test the hypothesis that thickened liquids result in reduced volume of fluid intake and systemic dehydration, which will be exacerbated by viscosity and age. Aim 3 will test the hypothesis that thickened liquids, in the absence of thin liquid, will slow swallowing movements, dynamically altering muscle contractile properties to include reduced tongue forces and increased contraction times in an age-dependent manner. In concert, the proportion of fast- contracting type IIb myosin heavy chain (MyHC) isoforms in the tongue will be reduced, causing an increased proportion of slower-contracting isoforms, such as type IIa and type I. This research is highly significant in that it will be the first in an aging animal model to examine the effects of thickened liquids on systemic hydration along with underlying muscle biology, kinematics, and physiology, and the relationship to clinically relevant outcome measures of swallow function. Knowledge gained from this work will lead to hypotheses for testing in clinical studies that are crucial for clinical decisions that must balance patient risk of aspiration and subsequent medical complications, against the impact of potential deleterious effects of thickened liquids on patient overall medical status and quality of life.