Pentoxifylline reduces venular leukocyte adherence ("reflow paradox") but not microvascular "no reflow" in hepatic ischemia/reperfusion.
Postischemic reperfusion injury is caused by microcirculatory disturbances, including both nutritive perfusion failure (no reflow) and leukocyte activation (reflow paradox). Recent studies brought evidence that pentoxifylline (PTX) reduces tissue injury, decreases enzyme release, and improves survival after normothermic liver ischemia/reperfusion. The mechanisms of action, however, by which PTX protects postischemic tissue from injury have not been elucidated yet. With the use of fluorescence microscopy in a rat hepatic ischemia/reperfusion model, we studied in vivo the action of PTX on the manifestation of postischemic sinusoidal perfusion failure and microvascular leukocyte adherence. Microvascular reperfusion after 20 min portal triad cross-clamping was characterized by the cessation of blood flow within individual sinusoids (no reflow) and accumulation of leukocytes within the hepatic microvasculature, with stasis in sinusoids and rolling and firm adherence in postsinusoidal venules. PTX (20 mg/kg x hr i.v.) significantly (P < 0.05) attenuated microvascular leukocyte accumulation (44,600 +/- 1833 mm(-3) vs 67,684 +/- 2620 mm(-3) in saline-treated controls) and firm adherence of leukocytes in postsinusoidal venules (316.9 +/- 40.9 mm(-2) vs 522.9 +/- 95.0 mm(-2)); however, PTX did not influence manifestation of individual sinusoidal perfusion failure. Since reperfusion-induced parenchymal cell damage was found reduced in treated animals, we conclude that PTX attenuates postischemic injury in rat liver by reduction of leukocytic/inflammatory response but not by prevention of nutritive perfusion failure.
Müller
J M
JM
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
Vollmar
B
B
Menger
M D
MD
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008099:Liver / Q000098:blood supply*; D008833:Microcirculation; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline