Effect of H2S on ultimate outcome of critical illness

Abstract

Multiple studies implicated H2S in many physiological processes, as well as in various forms of neurological, cardiovascular, metabolic diseases, and in critical illness. The biological character of H2S in health and disease is determined by a complex interplay between three factors: (1) expression/activity of H2S-producing enzymes; (2) redox status and reactive oxygen/nitrogen species production and (3) tissue hypoxia/acidosis. Our objective is study the modulation of blood flow, tissue oxygen extraction and organ function by H2S during endotoxic shock and sepsis. The overall hypothesis is that overexpression of H2S-producing enzymes in various tissues in response to bacterial lipopolysaccharide (LPS), acting in concert with acidosis and tissue hypoxia, will lead to diminished tissue oxygen utilization and will promote organ dysfunction. If this hypothesis is correct, pharmacological inhibition of H2S production will be beneficial in these conditions, while further administration of H2S will be detrimental. (AU)