Chronic ethanol consumption exacerbates liver injury following hemorrhagic shock: role of sinusoidal perfusion failure.
Although the deleterious effect of chronic ethanol consumption on subsequent stressful events has long been recognized, the pathophysiological mechanisms are incompletely understood. This study tested whether chronic ethanol consumption in doses that increase sinusoidal contractility increases susceptibility to hepatic microvascular failure and liver 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 levels. Mean sinusoidal blood flow was neither impaired by chronic ethanol 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 controls (11%), reflecting substantial flow heterogeneity. Failing sinusoids had substantially smaller diameters than sinusoids conducting flow with a more profound and sustained response in ethanol-fed rats. At 24 h marked pericentral necrosis and increase in serum alanine aminotransferase levels were observed in six of nine surviving ethanol-fed animals but only in 1 of 10 pair fed controls and correlated with microvascular failure. These data suggest that early as well as late microvascular failure in this model of hemorrhagic shock and resuscitation is primarily mediated at the level of individual sinusoids. Chronic ethanol feeding exacerbates microvascular and hepatocellular injury after shock/resuscitation, probably involving increased sinusoidal contractile responsiveness.
Bauer
I
I
Johns Hopkins University School of Medicine, Department of Pediatric Surgery, Baltimore, Maryland 21287, USA.
Bauer
M
M
Pannen
B H
BH
Leinwand
M J
MJ
Zhang
J X
JX
Clemens
M G
MG
D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D000431:Ethanol; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase