title: Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury.
abstract: BACKGROUND
  Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced superficial femoral artery vasorelaxation. The purpose of this study was to evaluate the effect of intraarterial pentoxyfylline (PTX) on this endothelial injury.
  
  
  METHODS
  New Zealand white rabbits underwent 3 hr of complete hindlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 microM PTX or normal saline was infused over 20 min via the circumflex iliac artery at initiation of reperfusion. Superficial femoral artery rings were then evaluated in vitro for endothelial cell-mediated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percentage relaxation was measured. Sections of arteries were also sent for hematoxylin and eosin staining.
  
  
  RESULTS
  Similar contraction responses following NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 +/- 3.64, 23.17 +/- 5.61, and 31.84 +/- 8.43% in response to acetylcholine doses of 6 x 10(-8), 1 x 10(-7), and 1.5 x 10(-7) M, respectively. In contrast, PTX-treated segments relaxed a mean of 47.52 +/- 8.88, 62.32 +/- 6.83, and 76.73 +/- 4.91% to the same doses of acetylcholine. Differences in relaxation between control and PTX-treated vessels were significantly different at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium without morphologic differences between the two groups.
  
  
  CONCLUSIONS
  In this model of rabbit hindlimb ischemia, endothelial cell-mediated vasorelaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation responses could not be attributed to altered arterial contractility in response to norepinephrine, or explained by histologic changes in the arterial wall. These studies demonstrate a potential modality for therapeutic intervention to reduce reperfusion injury after acute limb ischemia.
authors.affiliation: Department of Vascular Surgery, Medical College of Wisconsin, Milwaukee, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Coe
authors.forename: J A
authors.initials: JA
authors.lastname: Freischlag
authors.forename: D
authors.initials: D
authors.lastname: Johnson
authors.forename: J H
authors.initials: JH
authors.lastname: Mudaliar
authors.forename: S A
authors.initials: SA
authors.lastname: Kosciesza
authors.forename: D K
authors.initials: DK
authors.lastname: Traul
authors.forename: P C
authors.initials: PC
authors.lastname: Chiang
authors.forename: R A
authors.initials: RA
authors.lastname: Cambria
authors.forename: G R
authors.initials: GR
authors.lastname: Seabrook
authors.forename: J B
authors.initials: JB
authors.lastname: Towne
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005263:Femoral Artery / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy*; D009638:Norepinephrine / Q000494:pharmacology; D010431:Pentoxifylline / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D011189:Potassium Chloride; D000109:Acetylcholine; D010431:Pentoxifylline; D009638:Norepinephrine