Trauma, shock or sepsis, researchers studied the basic mechanisms that drive the pathogenesis of end-organ in- jury and MODS at the cellular, tissue and whole organ- ism levels. Previous studies demonstrated that endorgan injury and subsequent MODS result from a cause-effect relationship between three pathophysiologic events, which likely interact in a time-dependent, tissue-specific fash- ion. First, a persistent and progressive splanchnic vaso- constriction and hypoperfusion leading to relative ische- mia/hypoxia [26,27]; Second, a gut-derived systemic in- flamematory response generated by the ischemic gut [28]; and third, inevitable fluid shifts at both the cellular level due to ionic-disequilibrium and at the capillary level due to alteration of the trans-capillary Starling forces that gov- ern fluid exchange [