title: Pentoxifylline does not prevent microvascular injury in normotensive, septic rats.
abstract: OBJECTIVE
  To determine if treatment with pentoxifylline would decrease the tissue injury that occurs in a normotensive model of sepsis.
  
  
  METHODS
  Random assignment to control, cecal ligation-perforation, or cecal ligation-perforation plus pentoxifylline groups for a 24-hr study.
  
  
  METHODS
  Animal laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Sepsis was induced by cecal ligation-perforation with aggressive fluid resuscitation (normal saline 10 mL/kg/hr). Pentoxifylline was administered as a 2-mg/kg bolus, followed by a continuous infusion of 6 mg/kg/hr.
  
  
  RESULTS
  Compared with controls, rats in the cecal ligation-perforation group had an increased heart rate (432 +/- 12 vs. 399 +/- 10 beats/min) and respiratory rate (129 +/- 6 vs. 94 +/- 7 breaths/min). Blood pressure was slightly decreased (104 +/- 4 vs. 125 +/- 5 mm Hg), while cardiac index was not significantly different (50.1 +/- 5.7 vs. 40.7 +/- 3.9 mL/min/100 g). Blood pressure (103 +/- 4 mm Hg) was the only parameter that was significantly different in the cecal ligation-perforation plus pentoxifylline group compared with controls. When compared with controls, tissue wet/dry weight ratios were increased in the diaphragm of the cecal ligation-perforation group and in the liver, pancreas, small bowel, and large bowel of the cecal ligation-perforation, and the cecal ligation-perforation plus pentoxifylline groups. Tissue/plasma albumin ratios were increased in the diaphragm of the cecal ligation-perforation group and in the liver, pancreas, and large bowel of the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups. There were no significant differences between the cecal ligation-perforation and the cecal ligation-perforation plus pentoxifylline groups.
  
  
  CONCLUSIONS
  Normotensive sepsis is accompanied by increased vascular permeability in the diaphragm and intra-abdominal organs. Pentoxifylline appears to attenuate some of the systemic manifestations of sepsis. However, pentoxifylline did not prevent the development of protein-rich tissue edema.
authors.affiliation: A.C. Burton Vascular Biology Laboratory, University of Western Ontario, London, Canada.
authors.forename: F J
authors.initials: FJ
authors.lastname: Flammand
authors.forename: W J
authors.initials: WJ
authors.lastname: Sibbald
authors.forename: M J
authors.initials: MJ
authors.lastname: Girotti
authors.forename: C M
authors.initials: CM
authors.lastname: Martin
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects*; D002432:Cecum; D006339:Heart Rate; D008026:Ligation; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D009929:Organ Size; D010431:Pentoxifylline / Q000494:pharmacology*; D011677:Punctures; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D018805:Sepsis / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D012709:Serum Albumin / Q000032:analysis
chemical_list: D012709:Serum Albumin; D010431:Pentoxifylline