Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock

Objective Lisofylline is an enantiomer-specific, alkyl-substituted methylxanthine, which has specific and potent activity in down-regulating leukocyte activation. This study was designed to test the efficacy of lisofylline in the resuscitation of rats subjected to experimental hemorrhagic shock. Design Prospective, randomized, and blinded survival studies were performed with two lisofylline dosing regimens added to fluid resuscitation in a shock model. In addition, white cell adhesiveness was measured to assess the effects of lisofylline. Setting Animal laboratory. Subjects Sixty Sprague-Dawley rats. Interventions Lisofylline or placebo was added to the resuscitation regimen, either as a single dose or over 24 hrs. Measurements and Main Results The 72-hr survival rate, white blood cell count, and platelet adhesiveness were 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 lisofylline were given over 24 hrs, the 72-hr survival rate increased from 40% in controls to 70% (p < .02). Control animals significantly increased leukocyte adhesiveness after shock and resuscitation. This increased adhesiveness was completely eliminated by lisofylline infusion. Platelet adhesiveness was not affected by lisofylline. Conclusions Lisofylline improves survival in this model of hemorrhagic shock. Its beneficial effect may be related to down-regulation of leukocyte adhesiveness. (Crit Care Med 1996; 24:1724-1728)