Role of microcirculatory derangements in manifestation of portal triad cross-clamping-induced hepatic reperfusion injury.

Postischemic liver dysfunction following portal triad cross-clamping (PTC) predisposes patients for the development of multiple system organ failure (MSOF) and is associated with increased mortality of MSOF. The deterioration of the hepatic microcirculation may play a pivotal role in the pathophysiologic sequelae of PTC-induced reperfusion injury. We quantitatively analyzed in vivo the role of microcirculatory derangements in the manifestation of hepatic reperfusion injury following ischemia by PTC. Sprague-Dawley rats were subjected to 20 min PTC followed by 60 min reperfusion (PTC, n = 18). Sham-operated animals without ischemia served as controls (sham, n = 15). Within 45-60 min of reperfusion, hepatic microcirculation (sinusoidal perfusion, leukocyte-endothelial cell interaction) was analyzed by means of intravital fluorescence microscopy; tissue oxygenation was assessed using a platinum multiwire surface electrode. Liver enzymes and bile flow were determined as indicators of hepatocellular integrity and liver function. In vivo analysis of postischemic hepatic microcirculation revealed the induction of leukocyte-endothelial cell interaction within sinusoids and postsinusoidal venules and concomitant sinusoidal perfusion deficits associated with tissue hypoxia. In addition, PTC resulted in increased serum levels of liver enzymes and a marked reduction of bile flow. Regression analyses demonstrated significant correlations between hepatocellular desintegration/liver dysfunction and PTC-induced microcirculatory disorders. These results underline the predominant role of microcirculatory disturbances in the development of PTC-induced hepatic reperfusion injury and support the concept that normalization of postischemic microcirculation may be a most effective therapeutic regimen to prevent hepatocellular damage and liver dysfunction.