Critical care medicine · 1996
Lisofylline decreases white cell adhesiveness and improves survival after experimental hemorrhagic shock.
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Waxman K, Daughters K, Aswani S, Rice G
Аннотация
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.
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.