Improving Warfighters' Sustainment and Performance in Extreme Environmental Conditions; Final rept. 8 Jun 2007-7 Feb 2008

摘要

In this project, we have developed and verified experimental rat models capable of reproducing physiological responses to extreme environmental conditions, such as simulated high-altitude hypoxia, acute heat stress, and chronic cold stress, comparable to conditions in military relevant scenarios. The major goal of the project was to experimentally test a drug treatment using a heat-shock protein co-inducer (Arimoclomol ; CytRx, Los Angeles, CA) in these rat models of extreme environmental exposures. We measured parameters of metabolic and tissue integrity of vital organs, and tested motor function and cognitive performance in animals exposed to simulated high-altitude hypoxia, acute heat stress or chronic cold stress, and treated either with the drug or vehicle immediately before the stress exposure. Our results demonstrated that the drug, given immediately to the animals before being exposed to the extreme condition: (1) significantly reduced the stress-induced reduction in both motor function and cognitive performance; (2) reduced stress-induced damage (such as oxidative stress and inflammation, among others) in vital organs (heart, liver, kidneys, and brain); and (3) increased the body's tolerance to these extreme environmental conditions. Based on these preliminary results, we suggest continuation of the research in a form of a larger-scope 3-year project, which would include both experimental and clinical studies, to fine-tune the experimental models and validate the beneficial role of the drug in human population.