Silomon M, Pizanis A, Larsen R, Rose S
Department of Anesthesiology, University of Saarland, Homburg/Saar, Germany.
Crit Care Med. 1998 Mar;26(3):494-500. doi: 10.1097/00003246-199803000-00021.
To evaluate the effect of pentoxifylline on altered hepatocyte calcium regulation and hepatocyte oxidant injury after hemorrhagic shock.
Prospective, randomized, controlled study.
University research laboratory.
Anesthetized, male Sprague-Dawley rats, weighing 220 to 300 g.
Hemorrhagic shock was induced by bleeding rats to a mean arterial blood pressure of 40 mm Hg for 60 min. Rats were then resuscitated with 60% of shed blood and three-fold the bleed out volume of lactated Ringer's solution without and with pentoxifylline (50 mg/kg body weight). After hepatocyte isolation by portal collagenase perfusion, the rate of hepatocyte calcium influx (Ca2+in) in the absence and presence of epinephrine (100 nM), both cellular Ca2+ uptake (Ca2+up) and membrane Ca2+ flux (Ca2+flux) were determined, using 45Ca2+ incubation techniques. Hepatocyte lipid peroxidation was fluorometrically determined by thiobarbituric acid-reactive substances.
Pentoxifylline inhibited the significant increase of hepatocyte Ca2+in, Ca2+up, and Ca2+flux observed in untreated rats subjected to hemorrhage/resuscitation. In shocked rats, pentoxifylline restored the impaired epinephrine-induced Ca2+ influx response and prevented increased hepatocyte lipid peroxidation.
The protective effects of pentoxifylline could be attributed to its known anti-inflammatory properties reducing excessive in vivo stimulation of hepatocytes by Ca2+ agonistic mediators and attenuating oxygen radical-related disturbances of transmembrane Ca2+ transport mechanisms. Since altered cellular Ca2+ regulation is a key event of cellular dysfunction, resuscitation with pentoxifylline after hemorrhagic shock/resuscitation may provide an adjuvant therapeutic tool to prevent postischemic hepatic failure.
