Iontophoresis of treprostinil promotes wound healing in a murine model of scleroderma-related ulcers.

OBJECTIVE: Systemic sclerosis (SSc) is a rare, chronic disease characterized by fibrosis, vascular alterations and digital ulcerations. Few drugs have shown efficacy to enhance wound healing of existing SSc-related ulcers. Local delivery of treprostinil, a prostacyclin analogue, may improve wound healing. The present work aimed first at developing a mouse model of SSc-related ulcerations and second at assessing the effect of iontophoresis of treprostinil on wound healing. METHODS: We used two murine models of SSc: chemically induced with HOCl, and urokinase-type plasminogen activator receptor (uPAR)-deficient. Excisional wounding was performed on the dorsal midline with a biopsy punch. Animals were randomized into three groups: treated with electrostimulation alone, with treprostinil iontophoresis or untreated. We assessed wound healing over time, as well as skin microvascular reactivity, inflammation, microvessel density and collagen distribution, before wounding and after re-epithelialization. RESULTS: uPAR-/- mice, but not HOCl-treated mice, showed impaired wound healing and decreased microvascular reactivity compared with their controls. Treprostinil iontophoresis improved wound healing and microvascular density and decreased inflammation in uPAR-/- mice, while electro-stimulation did not. However, treprostinil had no effect on microvascular reactivity and collagen distribution. CONCLUSION: This study suggests that excisional wounds in uPAR-/- mice are a relevant model of SSc-related ulcers. In addition, treprostinil iontophoresis enhances wound healing in this model. Further work in now needed to show whether this effect translates in humans.

The Effect of a 300 mBar Increase in Barometric Pressure on Digital Microcirculation in Healthy Subjects Exposed to High Altitude: Is the Use of a Portable Hyperbaric Chamber to Treat Frostbite and/or Hypothermia in the Field Indicated? (Flow_Pulse Study).

INTRODUCTION: Hypothermia and frostbite occur when there is a significant decrease in central and peripheral body temperature in individuals exposed to cold windy conditions, often at high altitude or in a mountain environment. Portable hyperbaric chambers increase the barometric pressure and thereby the partial pressure of oxygen inside the chamber, and their use is a well-known treatment for altitude illness. This study aims to show that a portable hyperbaric chamber could also be used to treat hypothermia and frostbite in the field, when rescue or descent is impossible or delayed. METHODS: During a European research program (SOS-MAM, Flow Pulse study) measurements were taken from 27 healthy nonacclimatized voluntary subjects (21 men, 6 women, mean age 41 ± 17) at an altitude of 3800 m (Chamonix Mountain Lab, Aiguille du Midi, France) right before and immediately after spending 1 hour in a portable hyperbaric chamber at 300 mbar. We measured digital cutaneous temperature (Tcut), digital cutaneous blood flow (Fcut), digital tissue oxygenation (TcPO2), blood oxygen saturation (SpO2), heart rate, and core temperature. Air temperature inside the chamber (Tchamb) was measured throughout the whole session. RESULTS: We observed significant increases in Tchamb: 9.3°C compared with the outside temperature, Tcut: +7.5°C (±6.2°C 71%), Fcut: +58PU (±89) (+379%), TcPO2: +18 mmHg (±11.9) (304%), and SpO2: 13%. CONCLUSION: This study shows that a portable hyperbaric chamber can be used to treat frostbite and/or hypothermia in the field at altitude when descent or rescue is impossible or even simply delayed.