Sustained cutaneous vasoconstriction during and following cyrotherapy treatment: Role of oxidative stress and Rho kinase

Cryotherapy is a therapeutic technique using ice or cold water applied to the skin to reduce bleeding, inflammation, pain, and swelling following soft tissue trauma and injury. While beneficial, there are some side effects such as pronounced vasoconstriction and tissue ischemia that are sustained for hours post-treatment. This study tested the hypothesis that this vasoconstriction is mediated by 1) the Rho-kinase pathway and/or 2) elevated oxidative stress. 9 subjects were fitted with a commercially available cryotherapy unit with a water perfused bladder on the lateral portion of the right calf. Participants were instrumented with three microdialysis probes underneath the bladder. One site received lactated ringers (control site), one received the Rho-Kinase inhibitor Fasudil, and one received Ascorbic Acid. Skin temperature (Tskin) and cutaneous vascular conductance (CVC) was measured at each site. Subjects had 1 °C water perfused through the bladder for 30 min, followed by passive rewarming for 90 min. Tskin fell from ~ 34 °C to ~ 18.0 °C during active cooling across all sites and this response was similar for all sites (P > 0.05 for all comparisons). During passive rewarming Tskin rose to a similar degree in all sites (P > 0.05 relative to the end of cooling). %CVC was reduced during active cooling in all sites; however, the magnitude of this response was blunted in the Fasudil site relative to control (P < 0.001 for all comparisons) and min 25 and 30 of cooling in the Ascorbic Acid site (P < 0.05). During passive rewarming %CVC at the control and Ascorbic Acid sites did not change such that values were similar to the end of cooling (P > 0.05 for each comparison). %CVC at the Fasudil site remained elevated during passive rewarming such that values were higher compared to the control and Ascorbic Acid sites throughout the 90 min of passive rewarming (P < 0.001 main effect of Fasudil). These findings indicate that the Rho-kinase pathway contributes to pronounced vasoconstriction during cryotherapy as well as the sustained vasoconstriction during the subsequent rewarming period post treatment.