Pentoxifylline treatment of sepsis in conscious Yucatan minipigs.
Recent evidence suggests that pentoxifylline (PTX) may be useful in the treatment of sepsis. We examined effects of PTX in a conscious swine model of sepsis. Yucatan minipigs (20-30 kg) were anesthetized and instrumented with catheters in the vena cava, aortic arch, pulmonary artery (Swan-Ganz thermodilution catheter), and peritoneum. Twenty-four hours after surgery, sepsis was induced by intraperitoneal (ip) injection of Escherichia coli bacteria (2 x 10(10) cfu/kg). Nonseptic pigs received intraperitoneal saline (5 ml/kg). PTX treatment (3 mg/kg/hr, iv; 1 mg/ml in 0.9% saline) and maintenance fluid (5 ml/kg/hr, iv) were started with bacterial infusion. An additional 60 cc/kg 0.9% saline bolus was administered iv at 1 hr. Pigs were monitored before and 1, 2, 5, and 24 hr after bacterial injection. Intraperitoneal injection of bacteria led to significant reductions in blood pressure and cardiac output and elevations in pulmonary wedge pressure and pulmonary vascular resistance. These effects were attenuated by PTX treatment. All septic animals demonstrated elevated creatinine, blood urea nitrogen, circulating endotoxin (LPS), and tumor necrosis factor concentrations, reductions in white blood cell and platelet counts, and peritonitis. None of these responses was altered by PTX treatment. We conclude that PTX may prove to be a useful therapeutic tool in the early treatment of septic shock but is limited in the scope of its effects.
Law
W R
WR
Septic Shock Research Group, Naval Medical Research Institute, Bethesda, Maryland.
Nadkarni
V M
VM
Fletcher
M A
MA
Nevola
J J
JJ
Eckstein
J M
JM
Quance
J
J
McKenna
T M
TM
Lee
C H
CH
Williams
T J
TJ
D000818:Animals; D003401:Creatine / Q000097:blood; D004195:Disease Models, Animal; D004926:Escherichia coli; D006439:Hemodynamics / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D012772:Shock, Septic / Q000188:drug therapy*; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014508:Urea / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D003401:Creatine; D010100:Oxygen; D010431:Pentoxifylline