Hyperbaric oxygen mechanisms of protection in sepsis

Beth Israel Deaconess Medical Center, Boston MA

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Abstract

DESCRIPTION (provided by applicant): Sepsis is a significant cause of morbidity and mortality due to limited therapeutic interventions currently available. Hyperbaric oxygen (HBO) is a possible adjunctive therapy for treatment of sepsis. However, due to limited pre-clinical and clinical research data available, there is significant resistance to using this therapy by many physicians. Rigorous pre-clinical study is required to overcome the existing medical bias towards HBO as an adjunctive disease therapy. Current research in sepis suggests that improvement in disease outcome may be mediated through limiting early apoptosis of lymphocytes, creating a cytokine environment stimulating an active vs anergic adaptive immune response, and limiting lung inflammation that may lead to lung organ failure. There are no pre-clinical studies addressing the effect of HBO on these currently described pathophysiologic processes important to the development of sepsis. Prior pre-clinical studies have suggested that HBO may be effective in treating sepsis, however, most studies employed disease models and HBO treatments that were not clinically relevant. Our overall hypothesis is that HBO therapy may induce favorable changes in host defenses during the development of sepsis via novel oxidant-dependent signaling mechanisms. Our specific aims are as follows: AIM I: To define the mechanisms by which HBO treatment improves outcome during the early phase of sepsis development. A. What is the mechanism of HBO action in promoting enhanced innate immune cell function during early sepsis? B. What is the mechanism of HBO in prevention of lymphocyte apoptosis during sepsis? C. What is the mechanism of HBO action in reducing lung inflammation development during sepsis? Results of such studies will provide background support for clinical studies of HBO and may change practitioner bias against this therapy. Results from these studies may also have implications for general cell biology by elucidating novel pathways of oxidant signaling at both the intracellular and intercellular level.