Beneficial cardiopulmonary effects of pentoxifylline in experimental sepsis are lost once septic shock is established
P. C. Ridings, A. C. Windsor, H. J. Sugerman, E. Kennedy, M. M. Sholley, C. R. Blocher, B. J. Fisher and A. A. Fowler
Department of Surgery, Medical College of Virginia, Richmond.
OBJECTIVE: To determine the effects of pretreatment and posttreatment with
pentoxifylline in a porcine model of gram-negative sepsis. DESIGN:
Nonrandomized controlled trial. STUDY SUBJECTS: Young Yorkshire swine.
INTERVENTIONS: Six groups of ventilated swine were studied for 5 hours.
Group 1 swine (control, n = 8) received saline solution only. Group 2 swine
(sepsis, n = 8) received a 1-hour infusion of Pseudomonas aeruginosa.
Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg
bolus followed by a 6 mg/kg per hour infusion of pentoxifylline. Group 3
swine (n = 6) received pentoxifylline prior to the onset of sepsis; group 4
swine (n = 6) received pentoxifylline at 1 hour and group 5 swine (n = 4)
at 2 hours after the onset of the P aeruginosa infusion. Group 6 swine
(control pentoxifylline, n = 3) received pentoxifylline only. OUTCOME
MEASURES: Hemodynamic variables, neutrophil counts and CD18 expression,
tumor necrosis factor activity, and arterial blood gases were measured
hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure
neutrophil and protein content. RESULTS: All variables remained unchanged
in the control and control pentoxifylline groups. Both pretreatment and
posttreatment with pentoxifylline significantly attenuated lung injury and
improved arterial PaO2. The cardiac index was significantly improved by
administration of pentoxifylline in groups 3 and 4. Administration of
pentoxifylline to group 5 animals in established septic shock caused
uncontrolled, fatal systemic hypotension in two of the four animals. Plasma
tumor necrosis factor activity, blood polymorphonuclear leukocyte counts,
and CD18 expression were unaffected by the administration of
pentoxifylline. CONCLUSIONS: Pentoxifylline protects against pulmonary and
systemic hemodynamic derangements in fulminant sepsis and protects against
pulmonary dysfunction. Pentoxifylline has a "therapeutic window" when given
in established sepsis; if administration is delayed until overt septic
shock occurs, it may then have deleterious effects.
