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，导致皮肤灌流不足、终末器官衰竭和肢体损伤。这种损害很普遍。 在近50%患有PAD和SVD的糖尿病患者群体中。无数的研究描述了这些困难 糖尿病患者血管病变的诊断，要么是由于获得成本高昂的经皮穿刺术的机会有限 血氧饱和度(TcPO2)，使用踝臂指数(ABI)评估肢体血流缺乏准确性，或肾脏的高风险 使用侵入性血管造影术造成的损害。提议的努力通过提供一种简单、 价格低廉、有效的设备是临床广泛使用的理想设备，用于检测和跟踪PAD和SVD的过程。这个 临床采用拟议技术的预期社会经济影响包括改善患者质量 通过延缓或预防使人衰弱的疾病的发展和降低病人护理费用来延长生命。我们的 诊断系统使用硫化氢(H2S)，一种新描述的内皮衍生血管扩张剂，它随着 血管内皮损伤和功能障碍的发病。重要的是，硫化氢的正常产生对内皮细胞是必不可少的 功能，促进肌肉缺血的恢复，减轻心肌和肾梗死造成的损害。 这项名为经皮动脉气体传递器传感器(TAG™)的技术采用了一种创新的气相检测器，该检测器 非侵入性地测量皮肤释放的痕量硫化氢水平，作为皮肤血管健康的衡量标准。在一次 NHLBI资助的第二阶段SBIR研究工作，在人体受试者中进行了TAG™测量，以评估局部 健康人、无症状T2D患者和有症状的T2D患者的血管和微血管健康状况 接受下肢血管重建术的威胁肢体的伤口。研究发现，标签™信号与 与动脉粥样硬化和心血管危险评分、ASCVD以及HgbA1C和低密度脂蛋白/高密度脂蛋白比率(即 糖尿病的生物标志物)。研究结果还显示，糖尿病患者体内过氧化氢的生物利用度降低。 糖尿病患者四肢(腿)皮肤的TAG™读数可以评估皮肤微血管疾病的严重程度。 拟议的CRP临床前研究旨在邀请更多的临床医生来测试TAG™方法学与其他 测量血管健康，并增加每个队列的大小，为统计评估提供适当的动力。 通过满足我们的特定目标成功地完成了CRP工作，预计将导致IIB期临床研究。

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, leading to inadequate skin perfusion, end-organ failure, and limb damage. This damage is prevalent in the diabetic patient population where nearly 50% suffers from PAD and SVD. Numerous studies describe the difficulties of diagnosing vascular disease in diabetic patients, either due to limited access to the cost-prohibitive Transcutaneous Oximetry (TcPO2), lack of accuracy in limb blood flow evaluation using Ankle Brachial Index (ABI), or the high risk of kidney damage with the use of invasive angiography. The proposed effort addresses this unmet need by offering a simple, inexpensive, and effective device ideal for widespread clinical use to detect and follow the course of PAD and SVD. The expected socioeconomic impacts of clinical adoption of the proposed technology include improvement in patient quality of life by delaying or preventing the development of debilitating disease and a decrease in patient care costs. Our diagnostic system utilizes hydrogen sulfide (H2S), a newly described endothelium-derived vasodilator, that decreases with the onset of endothelial damage and dysfunction. Importantly, normal production of H2S is essential for endothelial function, for improving recovery from muscle ischemia, and to mitigate damage from myocardial and kidney infarction. The technology, Transdermal Arterial Gasotransmitter Sensor (TAGS™), employs an innovative gas-phase detector which noninvasively measures trace levels of H2S emitted from the skin as a measure of vascular health in the skin. During a NHLBI-funded Phase II SBIR research effort, TAGS™ measurements were carried out in human subjects to assess local vascular and microvascular health in healthy individuals, asymptomatic T2D patients, and symptomatic T2D patients with limb-threatening wounds undergoing lower-extremity revascularization surgery. It was found that TAGS™ signals correlate inversely with atherosclerotic and cardiovascular risk score, ASCVD, and with HgbA1C and LDL/HDL ratio (i.e., the biomarkers of diabetes). The results also reveal that PAD in diabetes decreases the bioavailability of H2S in the lower extremity (leg) skin of patients with diabetes so that TAGS™ readings can assess the severity of skin microvascular disease. The proposed CRP pre-clinical study is intended to engage more clinicians to test the TAGS™ methodology against other measures of vascular health and to increase the size of each cohort to provide appropriate power for statistical evaluation. Successful completion of the CRP effort by meeting our Specific Aims is expected to lead to Phase IIB clinical studies.