Influence of Remote Ischemic Conditioning and Nitrogen Monoxide on Angiogenesis and Microcirculation in a Mouse Ear Burn Model

Abstract

IntroductionRemote ischemic conditioning (RIC) has been shown to improve tissue resilience against ischemia. The aim of this study was to investigate the influence of RIC and its key factor, nitrogen monoxide (NO), on angiogenesis in a burn wound. Materials and methodsA unilateral burn injury on the ear of hairless mice (n = 48) was generated via a hot air jet in a contact-free manner. In four randomized groups, including the control (NoRIC group), RIC alone (RIConly group), RIC plus NO donor (ISDN group), and RIC plus NO synthase inhibitor (L-NAME group), the impact on angiogenesis, vessel diameter, blood flow, edema formation, and leukocyte-endothelial-cell interaction was evaluated over a 12-d period using intravital fluorescence microscopy. ResultsTissue perfusion was significantly improved by RIC (Day 3: ISDN group showed 182% and RIConly group showed 200% of baseline [BL], P < 0.001), while angiogenesis was not improved by RIC (nonperfused area on Day 12: mean 52% of BL in all groups, P >0.05). The application of ISDN did not further enhance the positive effect of RIC, whereas the application of L-NAME neutralized the effect of RIC. The most pronounced edema formation was observed in the RIConly group (mean 145% of BL, P ≤0.001), while the NoRIC group showed the least edema formation (Day 12: 117% of BL). ConclusionsRIC led to increased tissue perfusion, which did not result in improved angiogenesis, which may have been due to increased edema formation after RIC performance. The results of the present study do not support the establishment of a causal therapy strategy for burn wounds, including RIC.