title: Pentoxifylline preloading reduces endothelial injury and permeability in cardiopulmonary bypass.
abstract: Pentoxifylline (PTX), a methyl xanthine derivative, reduces endothelial permeability. A double blind, prospective, randomized, placebo controlled, parallel study was undertaken to assess the effect of PTX on leukotriene B4, complement fragment C3a, interleukin 6 (IL6), endothelial injury as measured by von Willebrand factor (vWf), and endothelial permeability as measured by urinary albumin excretion (expressed as excreted urinary albumin to creatinine ratio [ACR]) in patients undergoing cardiopulmonary bypass (CPB) for elective coronary artery bypass grafting. Twenty patients were recruited into each treatment arm and given either PTX 400 mg or placebo three times daily for 1 week before surgery. Patients were well matched. All operations were performed using one anesthetic, CPB, and a myocardial protection technique. Blood and urine samples were taken after anesthetic induction (baseline); 20 min after the start of CPB; 5 min after removal of the cross clamp; and 5 min and 2, 6, and 24 hr after the end of CPB. Pentoxifylline did not reduce IL6, C3a, and LTB4 release but reduced Factor VIIIRAg and urinary albumin excretion preoperatively (PTX vs placebo, ACR 1q.0 vs 2.1 mg/mmol, vWf 0.8 vs 1.3 IU/ml, p < 0.05) and peak levels (PTX vs placebo, ACR 8.9 vs 16.2, vWf 1.2 vs 2.2, p < 0.05) after CPB. These results suggest that PTX may attenuate the endothelial injury and permeability seen in CPB.
authors.affiliation: Cardiothoracic Surgical Unit, University Hospital, Birmingham, United Kingdom.
authors.forename: G M
authors.initials: GM
authors.lastname: Tsang
authors.forename: S
authors.initials: S
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Pagano
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: T R
authors.initials: TR
authors.lastname: Graham
authors.forename: R S
authors.initials: RS
authors.lastname: Bonser
mesh_terms: D000419:Albuminuria / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015926:Complement C3a / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D010726:Phosphodiesterase Inhibitors; D014841:von Willebrand Factor; D007975:Leukotriene B4; D015926:Complement C3a; D010431:Pentoxifylline