Influence of pentoxifylline and albifylline on liver microcirculation and leukocyte adhesion after hemorrhagic shock in the rat.
The aim of this study was to evaluate the effects of two xanthine derivates, pentoxifylline (PTX) and its more metabolically stable analogue, albifylline (HWA 138), on hepatic sinusoidal perfusion and leukocyte endothelial interactions in the liver after hemorrhagic shock. Sprague-Dawley rats (n = 8 per group) were exposed to hemorrhagic shock at 40 mm Hg for 60 minutes and subsequently resuscitated with 60% of shed blood and lactated Ringer's solution before intravital microscopy of the liver 3 hours after resuscitation. Using fluorescence markers, quantitative evaluations of red blood cell (RBC) and white blood cell (WBC) velocities and WBC endothelium interactions were performed. Animals were chosen randomly and blindly to receive either PTX or HWA 138 in a dosage of 25 mg/kg body weight 1 minute before resuscitation, or they received placebo. This was followed by a further infusion of 25 mg/kg body weight during the 3-hour resuscitation period. Although systemic parameters were comparable in all groups, both xanthine derivates enhanced the reduced velocity of RBCs and WBCs of the placebo group. Pathological values of WBC endothelium adhesion in the placebo group (adhesion index: 126.7 +/- 19.5 s/100 WBCs, mean +/- SE) was significantly reduced by PTX (64.4 +/- 10.5, p < 0.05) and HWA 138 (71.9 +/- 10.7, p < 0.05). The results indicate a significant reduction of shock-induced leukocyte adhesions to the sinusoidal endothelium in the liver. In addition, both xanthine derivates led to improved microvascular blood flow in the liver. Thus, PTX and HWA 138 reveal multiple positive effects on early shock-induced alterations in the liver, supporting earlier studies which indicated their potential application in shock therapy.
Marzi
I
I
Department of Trauma Surgery, University of Saarland, Homburg, Saar, Germany.
Maier
M
M
Herzog
C
C
Bauer
M
M
D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D008102:Liver Circulation / Q000187:drug effects*; D010431:Pentoxifylline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000503:physiopathology; D016037:Single-Blind Method; D014665:Vasodilator Agents / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D014665:Vasodilator Agents; C062028:1-(5-hydroxy-5-methylhexyl)-3-methylxanthine; D010431:Pentoxifylline