Transdermal H2S Sensing Device for Monitoring Peripheral Artery Disease

项目摘要/摘要 外周动脉疾病(PAD)和小血管疾病(SVD)是内皮细胞损伤的后果 它排列在所有血管上，导致皮肤灌注量不足以及末端器官和肢体的损伤。它在糖尿病患者中很常见。 近50%的患者患有PAD和SVD。拟议的努力解决了早期未得到满足的需求 高危人群中PAD和SVD的诊断。许多研究描述了诊断动脉疾病的困难。 在糖尿病患者中，包括血管钙化的高风险，这导致ABI高估肢体血流量 部分闭塞的测量和漏诊。尽管皮肤灌流的作用很重要，但很少见 由于缺乏常规筛查方案和要求，在早期阶段检测或甚至测试 昂贵的诊断设备和训练有素的技术人员。这突显了发展 简单、廉价的方案，对有皮肤灌注风险因素的受试者进行常规筛查，及早进行筛查 糖尿病视网膜病变、神经病变、肢体缺血、脑血管疾病、冠状动脉病变的更有效的治疗选择 血管疾病和肾病。创造一种在变化可逆的时间点检测血管疾病的方法将： 1)通过延缓或防止终末器官损害的发展来提高患者的生活质量；以及2)减少患者 护理费用。建议的方案使用硫化氢(H2S)，一种新描述的内皮衍生血管扩张剂， 随着血管内皮细胞疾病的发病而减少，这是大多数PAD和SVD病例的根本原因。此外，正常 硫化氢水平有利于预防内皮功能障碍，促进肌肉缺血的恢复，并在 减轻心肌梗死造成的损害。目前还没有一种非侵入性的方法来准确测量血浆 硫化氢和为数不多的现有技术需要专门的设备和熟练的技术人员。我们提出的技术，即 透皮气体传感器(TAG™)，采用了一种创新的气相检测器，可以非侵入性地测量 血浆中的硫化氢水平。在STTR第一阶段可行性研究中，Exhalix和新墨西哥大学团队开发了和 使用实验室版本的标签进行初步的动物研究，在这些研究中，生理上相关的正常和 在雄性SD大鼠的经皮吸收试验中发现血浆中H_2S水平降低。在建议的SBIR阶段 更新研究，我们打算继续开发先进的标签原型。这些原型将是 在广泛的受试者中进行验证和验证，包括健康和糖尿病动物和人类受试者 在医学院和疾病控制中心与经验丰富的内科科学家的合作下 翻译与临床科学。我们预计，在第二阶段成功开发和验证标签将 导致该技术的IIB期临床研究和商业化。

Project Summary/Abstract Peripheral artery disease (PAD) and small vessel disease (SVD) are the consequences of damage to the endothelial cells that line all vessels, both leading to inadequate skin perfusion and end-organ and limb damage. It is prevalent in diabetic patient population in which nearly 50% suffers from PAD and SVD. The proposed effort addresses an unmet need for early diagnosis of PAD and SVD in this high-risk group. A number of studies describe the difficulties in diagnosing arterial disease in diabetic patients, including the high risk of vascular calcification, which leads to overestimates of limb blood flow by ABI measurements and missed diagnosis of partial occlusions. Despite the important role of skin perfusion, it is seldom detected or even tested for in its early stages due to the lack of routine screening protocols and the requirement for expensive diagnostic equipment and trained technicians. This highlights the significant opportunity for development of a simple, inexpensive protocol to routinely screen subjects with skin perfusion risk factors early enough that would allow more effective treatment options for diabetic retinopathy, neuropathy, limb ischemia, cerebral vascular disease, coronary vascular disease and nephropathy. Creating a way to detect vascular disease at a point where changes are reversible will: 1) improve patient quality of life by delaying or preventing the development of end organ damage; and 2) decrease patient care costs. The proposed protocol utilizes hydrogen sulfide (H2S), a newly described endothelium-derived vasodilator that decreases with the onset of endothelial disease, the underlying cause of most PAD and SVD cases. Furthermore, normal levels of H2S are beneficial for preventing endothelial dysfunction, for improving recovery from muscle ischemia and in mitigating damage from myocardial infarction. There is currently no non-invasive method to accurately measure plasma H2S and the few existing techniques require specialized equipment and skilled technicians. Our proposed technology, the transdermal gasotransmitter sensor (TAGS™), employs an innovative gas-phase detector which noninvasively measures plasma levels of H2S. In the STTR Phase I feasibility study, the Exhalix and University of New Mexico team developed and used a laboratory version of TAGS to perform preliminary animal studies in which physiologically relevant normal and reduced plasma levels of H2S were transdermally detected in male Sprague-Dawley rats. During the proposed SBIR Phase II renewal studies, we intend to continue the development of advanced prototypes of TAGS. These prototypes will be verified and validated across a broad cross-section of subjects, including healthy and diabetic animal and human subjects of both sexes, in collaboration with experienced physician scientists at the School of Medicine and the Center for Translational and Clinical Sciences. We anticipate that successful development and validation of TAGS during Phase II will lead to Phase IIB clinical studies and commercialization of the technology.