Transdermal H2S Sensing Device for Monitoring Peripheral Artery Disease

项目摘要/摘要 拟议的努力解决了对外周动脉疾病(PAD)早期诊断的未得到满足的需求。PAD是一种 影响着800多万美国人的血管循环障碍，其中大多数人并不知道 存在、风险和威胁。PAD主要由斑块引起的动脉粥样硬化引起，在某些情况下 由血管炎症、狭窄和四肢损伤引起。这是一个虚弱的，被低估的， 许多疾病的并发症治疗不足且知之甚少，包括糖尿病、睡眠呼吸暂停和 代谢综合征。患有PAD的患者心脏病发作或中风的可能性是其他患者的3到6倍 无PAD的患者。患有PAD的人功能受损，包括那些没有症状的人，以及 随着时间的推移，下肢功能显著下降，通常会导致严重的肢体缺血 (CLI)、心脏病发作和中风。PAD在早期阶段很难检测到，需要昂贵的设备和 训练有素的技术人员进行诊断，经常不被发现，直到发生不可逆转的组织损伤。 这突显了对一种简单、廉价的筛查方法的需求，这种方法可以用于常规筛查 有患PAD的风险，包括吸烟者、糖尿病患者和血浆胆固醇升高的患者。最近的观察结果 表明动脉闭塞可降低血浆硫化氢水平，维持适当的硫化氢水平可 有益于预防动脉粥样硬化，促进肌肉缺血的恢复，减轻损伤 死于心肌梗塞。目前精确测量血浆硫化氢的方法很少，而且都需要 专门的设备，训练有素的技术人员，没有一个是非侵入性的。在拟议的研究中，我们打算 论证了开发创新的非侵入性血液硫化氢测量设备的可行性，并 基于硫化氢分子的气相电催化的协议。在这项STTR第一阶段研究中，Exhalix将 与新墨西哥大学医学院合作，在 将静脉注射H_2S的雄性SD大鼠血浆中的H_2S水平与 此诊断方法的读数用于验证。血浆样本将从静脉系统采集，用于 在基于高效液相的检测中进行分析，以确定仪器的阈值、灵敏度和重复性 读数。我们预计这些研究将持续大约12个月，并在可行性方面取得成功 预计演示将导致第二阶段的工作，开发先进的原型和人类 学习。

Project Summary/Abstract The proposed effort addresses an unmet need for early diagnosis of peripheral artery disease (PAD). PAD is a disorder of vascular circulation that affects more than 8 million Americans, most of whom are unaware of its existence, risks, and threats. PAD is caused primarily by plaque-induced atherosclerosis and in some instances by blood vessel inflammation, stenosis, and injury to the limbs. It is a debilitating, underdiagnosed, undertreated, and poorly understood complication in many diseases including diabetes, sleep apnea and metabolic syndrome. Patients with PAD are 3 to 6 times more likely to have a heart attack or stroke than are patients without PAD. People with PAD have impaired function, including those who are asymptomatic, and experience a significant decline in lower-extremity functioning over time, often leading to critical limb ischemia (CLI), heart attack, and stroke. PAD is difficult to detect in the early stages, requires expensive equipment and trained technicians to diagnose and frequently goes undetected until irreversible tissue damage has occurred. This highlights the need for a simple, inexpensive screening method that can be used to routinely screen those at risk for PAD, including smokers, diabetics and patients with elevated plasma cholesterol. Recent observations indicate that plasma H2S levels are lowered by arterial occlusions and maintaining an adequate level of H2S can be beneficial for preventing atherosclerosis, improving recovery from muscle ischemia and in mitigating damage from myocardial infarction. There are currently few methods to accurately measure plasma H2S and all require specialized equipment, trained technicians and none is non-invasive. In, the proposed study, we intend to demonstrate the feasibility in development of an innovative non-invasive blood H2S measurement device and protocols based on gas-phase electrocatalysis of H2S molecules. In this STTR Phase I study, Exhalix will collaborate with the University of New Mexico, School of Medicine, to perform laboratory animal studies in which the plasma levels of intravenously administered H2S in male Sprague-Dawley rats will be compared to the readings from this diagnostic approach for validation. Plasma samples will be collected from venous lines for analysis in the HPLC-based assays, to determine the threshold, sensitivity and reproducability of the instrument readings. We anticipate that these studies will last approximately 12 months, and success in feasibility demonstration is expected to lead to a Phase II effort for development of an advanced prototype and human studies.