Document Detail

Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury.
MedLine Citation:
PMID:  9070176     Owner:  NLM     Status:  MEDLINE    
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. CONCLUSION: 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.
D A Coe; J A Freischlag; D Johnson; J H Mudaliar; S A Kosciesza; D K Traul; P C Chiang; R A Cambria; G R Seabrook; J B Towne
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of surgical research     Volume:  67     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  1997 Jan 
Date Detail:
Created Date:  1997-04-03     Completed Date:  1997-04-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21-5     Citation Subset:  IM    
Department of Vascular Surgery, Medical College of Wisconsin, Milwaukee, USA.
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MeSH Terms
Acetylcholine / pharmacology
Endothelium, Vascular / drug effects*,  pathology
Femoral Artery / drug effects,  pathology,  physiology
Ischemia / drug therapy*
Norepinephrine / pharmacology
Pentoxifylline / pharmacology*
Potassium Chloride / pharmacology
Reperfusion Injury / prevention & control*
Reg. No./Substance:
51-41-2/Norepinephrine; 51-84-3/Acetylcholine; 6493-05-6/Pentoxifylline; 7447-40-7/Potassium Chloride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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