LISOFYLLINE DECREASES WHITE CELL ADHESIVENESS AND IMPROVES SURVIVAL AFTER EXPERIMENTAL HEMORRHAGIC-SHOCK

Objective: Lisofylline is an enantiomer-specific, alkyl-substituted me thylxanthine, which has specific and potent activity in down regulatin g leukocyte activation. This study was designed to test the efficacy o f lisofylline in the resuscitation of rats subjected to experimental h emorrhagic shock. Design: Prospective, randomized, and blinded surviva l stud ies were performed with two lisofylline dosing regimens added t o fluid resuscitation in a shock model. in addition, white cell adhesi veness was measured to assess the effects of lisofylline. Setting: Ani mal laboratory. Subjects: Sixty Sprague-Dawley rats. Interventions: Li sofylline or placebo was added to the resuscitation regimen, either as a single dose or over 24 hrs. Measurements and Main Results: The 72-h r survival rate, white blood cell count, and platelet adhesiveness wer e determined. When a single, 1-hr infusion of lisofylline was added to the initial resuscitation regimen, the 72-hr survival rate increased from 20% in controls to 50% (p < .009). When repeated doses of lisofyl line were given over 24 hrs, the 72-hr survival rate increased from 40 % in controls to 70% (p < .02). Control animals significantly increase d leukocyte adhesiveness after shock and resuscitation. This increased adhesiveness was completely eliminated by lisofylline infusion. Plate let adhesiveness was not affected by lisofylline. Conclusions: Lisofyl line improves survival in this model of hemorrhagic shock. Its benefic ial effect may be related to downregulation of leukocyte adhesiveness.