The Role of Nitric Oxide in the Initiation of Inflammation in Shock

Inadequate tissue perfusion occurs in a number of settings in critically ill patients. Septic patients experience bouts of hypotension and inadequate perfusion and may experience regional ischemia due to dysregulation of the microcirculation. Organ ischemia may result from vascular occlusive events such as myocardial infarction or stroke, or from transient vascular occlusion during surgical procedures. Multisystem trauma involving both tissue destruction and hemorrhage can result in localized tissue ischemia at the site of injury as well as systemic hypoperfusion due to blood loss. Hemorrhagic shock in the absence of infection or tissue damage due to injury or surgical procedures is the purest form of global ischemia. Common to all events involving sustained, reduced organ perfusion is organ damage and inflammation that becomes evident upon reperfusion. Efforts to understand how ischemia and reperfusion initiate inflammation and lead to organ damage have focused on models of isolated organ ischemia and reperfusion in hemorrhagic shock.