Liver endothelial cell dysfunction occurs early following hemorrhagic shock and persists despite crystalloid resuscitation.
Although hepatocellular function is depressed early following hemorrhage, it remains unknown whether liver endothelial cell function is also compromised under such conditions. The aim of this study, however, was to determine if liver endothelial cell function is depressed during hemorrhage and persists following crystalloid resuscitation. To study this, rats underwent a 5-cm laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximal bleedout volume was returned in the form of Ringer's lactate. The animals were then resuscitated with 4 times the volume of maximal bleedout volume with Ringer's lactate. Arterial blood was taken before and during hemorrhage and after resuscitation. Plasma hyaluronic acid (HA) levels were determined using a Pharmacia assay kit. To determine whether the elevated HA is due to a decrease in its removal, HA clearance was assessed at 0 and 24 hr after resuscitation by injecting 30 microgram/100 g body wt HA intravenously. The results indicate that plasma HA levels increased significantly at the time of maximal bleedout, which persisted even 24 hr after the completion of resuscitation. Hyaluronic acid clearance decreased significantly at 0 and 24 hr after resuscitation, suggesting that the decreased HA clearance plays a major role in producing the elevated plasma HA levels. Since circulating HA is cleared exclusively by liver endothelial cells, these results, taken together, indicate that liver endothelial cell dysfunction (i.e., the increased plasma HA levels and decreased HA clearance) occurs early during hemorrhage (i.e., approximately 44 min after the onset of the insult) and persists despite resuscitation. Thus, the depressed liver endothelial cell function may directly or indirectly contribute to hepatocellular dysfunction observed under such conditions.
Wang
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P
Shock and Trauma Research Institute, Department of Surgery, Michigan State University, East Lansing 48824, USA.
Ba
Z F
ZF
Biondo
A
A
Chaudry
I
I
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D004727:Endothelium / Q000503:physiopathology; D006400:Hematocrit; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology*; D014947:Wounds and Injuries
D015415:Biomarkers; D006820:Hyaluronic Acid