CHRONIC ETHANOL-CONSUMPTION EXACERBATES LIVER-INJURY FOLLOWING HEMORRHAGIC-SHOCK - ROLE OF SINUSOIDAL PERFUSION FAILURE

Although the deleterious effect of chronic ethanol consumption on subs equent stressful events has long been recognized, the pathophysiologic al mechanisms are incompletely understood. This study tested whether c hronic ethanol consumption in doses that increase sinusoidal contracti lity increases susceptibility to hepatic microvascular failure and liv er injury after hemorrhagic shock Liver microcirculation was assessed by in vivo microscopy during hemorrhage and up to 24 h after onset of resuscitation and was compared with liver histology and serum enzyme l evels. Mean sinusoidal blood flow was neither impaired by chronic etha nol feeding at baseline nor during hemorrhage and early resuscitation. However, failure of individual sinusoids to conduct flow was observed more frequently after fluid resuscitation in ethanol-fed animals (e.g ., at 1 h after onset of volume therapy: 26% of sinusoids) than in con trols (11%), reflecting substantial flow heterogeneity. Failing sinuso ids had substantially smaller diameters than sinusoids conducting flow with a more profound and sustained response in ethanol-fed rats. At 2 4 h marked pericentral necrosis and increase in serum alanine aminotra nsferase levels were observed in six of nine surviving ethanol-fed ani mals but only in 1 of 10 pair fed controls and correlated with microva scular failure. These data suggest that early as well as late microvas cular failure in this model of hemorrhagic shock and resuscitation is primarily mediated at the level of individual sinusoids. Chronic ethan ol feeding exacerbates microvascular and hepatocellular injury after s hock/resuscitation, probably involving increased sinusoidal contractil e responsiveness.