| The mortality rates from septic shock and its complications remain high in spite of the newer advances in the field of trauma and critical care. The invading organisms and other insults result in the release of cytokines and secondary mediators by the host that produces alteration in cellular, metabolic and physiological functions leading to septic shock. A generalized inflammatory response to severe inflammatory stimuli leads to systemic inflammatory response syndrome (SIRS). One of the hallmarks for SIRS is hepatic failure and the propensity for the failure results from altered vascular reactivity, leading to microcirculatory dysfunction and ultimately a mismatch of blood supply to metabolic demand. Trauma and infection are a common clinical scenario and may predispose the microcirculation to failure, leading to end organ damage. In this study, we first determined if endothelin-1 contributed to the local mismatch between oxygen delivery and metabolic demand in the liver by acting at the sinusoidal level. Second, we determined if the mismatch between supply and demand of oxygen is potentiated during stress conditions such as endotoxemia. Thirdly, we determined if there is an increase in the microvascular reactivity to endothelin-1 during trauma or sepsis that could potentiate the local mismatch between oxygen delivery and metabolic demand leading to hepatic injury. Taken together, the study gives us insights into the role of microcirculatory dysfunction leading to a mismatch in the oxygen supply and metabolic demand that could contribute to the end organ damage in the liver during trauma and sepsis. |
