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

Renu Bala Yadav; Arun Kumar Yadav; Dharam Pal Pathak; Rajesh Arora

doi:10.14429/dlsj.9.19450

Renu Bala Yadav DRDO- Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi-110 054, India https://orcid.org/0000-0003-2124-0428
Arun Kumar Yadav Department of Internal Medicine, Army Hospital Research & Referral, Delhi Cantt-110 010, India https://orcid.org/0009-0000-2389-3663
Dharam Pal Pathak Delhi Pharmaceutical Science and Research University, Pushp Vihar, New Delhi-110 017, India https://orcid.org/0000-0001-8022-7632
Rajesh Arora DRDO- Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi-110 054, India https://orcid.org/0000-0001-7307-9221

DOI: https://doi.org/10.14429/dlsj.9.19450

Keywords: High altitude, Cold injury, Pharmacological interventions, Endothelial damages, Oxidative stress, Inflammatory mediators

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 E_2,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.