Transdermal Detection of Low Concentrations of Hydrogen Sulfide

Abstract

We report here a novel approach to measure circulating hydrogen sulfide (H2S) non‐invasively as a potential way to diagnose and monitor endothelial dysfunction and peripheral artery disease (PAD). PAD is a life‐threatening condition caused by arterial constriction and obstruction of blood flow leading to limb ischemia. Current methods to diagnose and monitor PAD lack sensitivity, result in frequent false‐negatives, and require specialized technicians. Recent studies indicate that decreased H2S production is an underlying cause of PAD. In addition, reduced plasma H2S correlates with endothelial dysfunction in untreated hypertension, diabetes, sleep apnea and other cardiovascular diseases. Conversely, excess H2S is cytotoxic causing irreversible damage to mitochondrial function. Therefore, careful monitoring of plasma H2S levels is essential to diagnose and treat vascular disease and to prevent H2S toxicity. This device was designed to measure H2S at the surface of the skin to test the hypothesis that the diffusion rate (and therefore gas phase concentration) of H2S is directly proportional to the concentration of H2S in the blood. Our results demonstrate that the device is sensitive enough to detect H2S at 10 part per billion (ppb) or lower in gas standards and in the headspace of a 3 nM solution of Na2S (H2S donor). In vitro studies used excised rat skin superfused on the subcutaneous surface with a H2S solution. H2S was detected in a stream of N2 gas flowing through a sealed chamber on the epidermal side both by GC/MS measurement and with the sensor only when the superfusing solution contained an H2S donor demonstrating that H2S diffuses through the skin. The diffusion rate of H2S through excised abdominal skin from a male Sprague‐Dawley rat is approximately 1.42×10−9 μmol/s/cm2/μM. The device also detected increases in H2S on the skin surface in anesthetized rats within seconds of intra‐venous injection of Na2S at doses that caused a fall in arterial pressure, with an estimated average diffusion rate of 4×10−8 μmol/s/cm2/μM. Therefore, this noninvasive, highly‐sensitive and portable device has the potential to transform diagnosis and monitoring of early stage PAD and to monitor H2S biosynthesis or exposure in vivo.