A remission spectroscopy system for in vivo monitoring of hemoglobin oxygen saturation in murine hepatic sinusoids, in early systemic inflammation

Animals submitted to 1 hour bilateral hindlimb ischemia (I) and 3 hours of reperfusion (R) (3.0 h I/R) exhibited lower HbsO2 values when compared with sham. Six hours I/R (1 hour bilateral hindlimb ischemia and 6 hours of reperfusion) and the continuous infusion of endothelin-1 (ET-1) further aggravated the hypoxia in HbsO2. The detected NAD(P)H autofluorescence correlated with the detected HbsO2 values and showed the same developing. Three hours I/R resulted in elevated NAD(P)H autofluorescence compared with sham animals. Animals after 6.0 h I/R and continuous infusion of ET-1 revealed higher NAD(P)H autofluorescence compared with 3.0 h I/R animals. Overall the analysed HbsO2 values correlated with all markers of hepatocellular injury.During the early stages of systemic inflammation, there is a significant decrease in hepatic sinusoidal HbsO2. In parallel, we detected an increasing NAD(P)H autofluorescence representing an intracellular inadequate oxygen supply. Both changes are accompanied by increasing markers of liver cell injury. Therefore, remission spectroscopy in combination with NAD(P)H autofluorescence provides information on the oxygen distribution, the metabolic state and the mitochondrial redox potential, within the mouse liver.Hepatic microcirculatory failure is a major prerequisite for the development of hepatocellular dysfunction in a number of conditions like trauma/hemorrhage, liver transplantation and systemic inflammation. In various inflammatory states, the degree of lethal hepatocyte necrosis can be predicted from the extent of hepatic microcirculatory failure [1], possibly via alterations in the mitochondrial redox state of the liver [2,3]. Previously, our group has shown that the development of systemic inflammation was associated with a disturbance of the hepatic microcirculation, and a subsequent increase in hepatocellular damage [4,5]. The causal mechanisms are not completely understood, but accumulating evidence suggests a dysregulation of