title: Pentoxifylline protects the small intestine after severe ischemia and reperfusion.
abstract: OBJECTIVE
  Pentoxifylline, a methylxanthine derivative with significant hemorheologic properties, is used for claudication in patients with peripheral vascular disease, and experimentally for ischemic injury to organs because of its antioxidant and antiinflammatory effects. We used a rat model of severe small intestinal ischemia and reperfusion to determine the ability of pentoxifylline in improving survival, molecular response, and pathological protection.
  
  
  METHODS
  We used 6 groups of male Wistar rats (n=25 each). The superior mesenteric artery was occluded for 120 minutes. Laboratory and tissue studies were done on 5 animals, 1 hour after reperfusion, and animal survival was assessed at 7 days. There were 2 control groups that received normal saline, either before ischemia or during reperfusion. The 4 treated groups received pentoxifylline 1 or 10 mg/kg at the same times mentioned above. Laboratory studies included measuring serum lactic acid dehydrogenase, tumor necrosis factor-α, interleukin-1β, and interleukin-6.Intestinal tissue malondialdehyde and myeloperoxidase in small intestine tissue also were measured. Histology and laser vascular blood flow at baseline and reperfusion were obtained, and survival was determined 7 days after ischemia.
  
  
  RESULTS
  A significant survival benefit in the animals treated with 10 mg/kg of pentoxifylline at reperfusion was noted. This coincided with a reduction in biochemical markers of cell damage - specifically, serum lactic acid dehydrogenase, and tissue malondialdehyde, ischemia, and reperfusion. Additionally, we saw decreased levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6. Improved postreperfusion blood flow shown by laser Doppler technology also was seen in the treated groups. Histologically, we observed less neutrophil infiltration in the intestine of ischemic-treated rats. Also seen in the control animals were increased necrotic lesions in the microvilli with a higher presence of lysozyme in the Paneth cells. Survival was significantly better at 7 days (70% vs 40%) when we compared the pentoxifylline group treated at reperfusion (10 mg/kg) to the ischemic controls.
  
  
  CONCLUSIONS
  Pentoxifylline had a significant protective effect on severely ischemic bowel when administered during reperfusion at a dosage of 10 mg/kg. Better survival, improved histology, and molecular response should urge consideration of the consideration of applying these findings in some general surgery and transplant conditions.
authors.affiliation: Universidad Católica de Valencia and the Department of Surgery and Research at the University of Valencia, Spain. jm_lloris@mac.com
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Lloris Carsi
authors.forename: Dolores
authors.initials: D
authors.lastname: Cejalvo Lapeña
authors.forename: Alexander Horacio
authors.initials: AH
authors.lastname: Toledo
authors.forename: Cristobal
authors.initials: C
authors.lastname: Zaragoza Fernandez
authors.forename: Luis Horacio
authors.initials: LH
authors.lastname: Toledo Pereyra
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D019610:Cytoprotection; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D017078:Laser-Doppler Flowmetry; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008641:Mesenteric Vascular Occlusion / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects; D010431:Pentoxifylline / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D010431:Pentoxifylline