Cold Injury Prevention and Management in High Altitude Extreme Environments Pharmacological and Therapeutical Interventions

Abstract

Cold injury refers to local or systemic body response that occurs due to massive loss of body heat when the body is exposed to extremely cold temperatures. The current modalities for the prevention and management of cold injury(ies) are very limited due to the paucity of availability of targeted therapeutics. Pathophysiological cascades in cold injury include: (a) desensitization of sensory neurons can be manifest as a result of altered pathophysiological functions viz., Ca2+ imaging, calcitonin gene-related peptide release, expressions of inflammatory mediators (PGE2: prostaglandin E2, NGF: nerve growth factors), (b) inflammatory markers viz.; interleukins (IL-1β, IL-6, and IL-10), tumor necrosis factor-alpha (TNF-α), and CD62E/endothelial-leukocyte adhesion molecule 1 (E-selectin); (c) oxidative stress markers associated with cold injury measured through serum level of protein carbonyl, 4-hydroxy-2-nonenal (4-HNE), superoxide dismutase (SODs), advanced oxidative protein products (AOPP) and nitrotyrosine; (d) endothelial damage: nitric oxide (NO), prostacyclin (PGI2), reactive oxygen species (ROS), Von-Willebrand factor (VWF), CD31/PECAM-1 (platelet/endothelial cell adhesion molecule 1), CD36/SR-B3 (scavenger receptor class B member 3) and tissue-type plasminogen activator (TTPA). In this review paper, we elaborate on the current state-of-the-art pharmacological interventions for cold injury that may be beneficial in developing novel and targeted therapeutics for the prevention, management, and treatment of cold injury.