Mechanisms of Pronounced and Sustained Cutaneous Vasoconstriction during Cryotherapy

Abstract

Cryotherapy is a common therapeutic technique using ice or cold water to reduce local blood flow. While beneficial, it can be associated with some negative physiological side effects such as pronounced tissue ischemia sustained for hours during a post-treatment rewarming period. Previous findings in our laboratory have indicated that this cutaneous vasoconstriction during cryotherapy is abolished following blockade of Rho Kinase. The Rho Kinase enhances vasoconstriction in part via down regulation of nitric oxide synthase (NOS). PURPOSE: To test the hypothesis that a reduction in nitric oxide (NO) bioavailability is involved in the pronounced and sustained cutaneous vasoconstriction that occurs during a typical cyrotherapy protocol. METHODS: 8 healthy individuals (6 male) participated in this protocol. A cryotherapy unit with a water perfused bladder was used. The bladder was placed on the lateral portion of the calf. Four microdialysis membranes were placed in the skin underneath the bladder. One site was perfused with lactated ringers (CON); neuronal NOS (nNOS) was blocked in another site (NPLA); endothelial NOS (eNOS) was blocked in another site (NLIO); and the last site received non-selective NOS blockade (LNAME). All solutions were dissolved in sterile lactated Ringers. Skin temperature (SkT) and skin vascular conductance (SkVC) was measured at each site. 0 °C water perfused through the cryotherapy bladder for 30 min, followed by passive rewarming (i.e. water shut off) for 1 hr, followed by direct heating with 46 °C water for 10 min. RESULTS: SkT fell from 34°C to 19°C during 30 min of cooling in all sites. SkVC at CON was reduced ~75% after 30 min of cooling and was similar to LNAME, NPLA, and LNIO (78, 75, 77%, reduction respectively; P>0.05). During passive rewarming SkVC remained blunted to a similar degree at all sites (Con: 87±1, LNAME: 85±2, NPLA: 87±2, LNIO: 85±1 % reduction; P>0.05). SkVC during 10 min of active warming was also similar between sites (CON: 62%, LNAME: 65%, NPLA: 67%, and LNIO: 68% reduction; P<0.05) CONCLUSION: The current data suggest that reductions in NO bioavailability do not contribute to pronounced and sustained vasoconstriction during cryotherapy. Supported by the National Institute of Biomedical Imaging and Bioengineering; R01EB015522 (Multi PI: K.R. Diller & R.M. Brothers).