Beneficial cardiopulmonary effects of pentoxifylline in experimental sepsis are lost once septic shock is established.
OBJECTIVE
To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis.


METHODS
Nonrandomized controlled trial.


METHODS
Young Yorkshire swine.


METHODS
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.


METHODS
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.
Department of Surgery, Medical College of Virginia, Richmond.
P C
PC
Ridings
A C
AC
Windsor
H J
HJ
Sugerman
E
E
Kennedy
M M
MM
Sholley
C R
CR
Blocher
B J
BJ
Fisher
A A
AA
Fowler
D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid; D002319:Cardiovascular System / Q000187:drug effects*; D016130:Immunophenotyping; D007958:Leukocyte Count / Q000187:drug effects; D008168:Lung / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D011552:Pseudomonas Infections / Q000503:physiopathology; D012137:Respiratory System / Q000187:drug effects*; D018805:Sepsis / Q000382:microbiology / Q000503:physiopathology*; D012772:Shock, Septic / Q000382:microbiology / Q000503:physiopathology*; D013481:Superoxides / Q000097:blood; D013552:Swine; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009195:Peroxidase; D010431:Pentoxifylline