Heparinoids with low anticoagulant potency attenuate postischemic endothelial cell dysfunction

Sternbergh, W. C. and Makhoul, R. G. (1995) Heparinoids with low anticoagulant potency attenuate postischemic endothelial cell dysfunction. Journal of Vascular Surgery, 21 3: 477-483. doi:10.1016/S0741-5214(95)70290-3

Author Sternbergh, W. C.
Makhoul, R. G.
Title Heparinoids with low anticoagulant potency attenuate postischemic endothelial cell dysfunction
Journal name Journal of Vascular Surgery   Check publisher's open access policy
ISSN 0741-5214
Publication date 1995-03
Sub-type Article (original research)
DOI 10.1016/S0741-5214(95)70290-3
Volume 21
Issue 3
Start page 477
End page 483
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Mosby
Language eng
Formatted abstract
Purpose: Although standard heparin has been demonstrated to reduce endothelial cell dysfunction in acute ischemia-reperfusion injury, its mechanism of action remains unknown. We hypothesized that heparin's salutary endothelial effects are independent of its conventional anticoagulant activity and are not caused by nonspecific polyanion effects.

Methods: Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched crystalloid buffer. After 60 minutes of normothermic ischemia, endothelial function was assessed by measurement of endothelial-dependent vasodilation by log increment infusion of acetylcholine. Endothelial-independent vasodilation was measured by exposure to nitroprusside. Some groups were pretreated with heparinoids possessing minimal or intermediate anticoagulant activity.

Results: Treatment with heparinoids with low anticoagulant activity significantly increased endothelial-dependent vasodilation when compared with the nontreated ischemic group and were statistically indistinguishable from the nonischemic control. Treatment with dextran sulfate, a randomly sulfated polymer with size and charge characteristics similar to heparin, did not change postischemic vasodilation. Endothelial-independent vasodilation was largely unaffected by ischemia-reperfusion or drug treatment.

Conclusions: A heparinoid with negligible antithrombin-binding activity (Astenose) attenuated postischemic endothelial dysfunction, suggesting that its mechanism of action was independent of anticoagulant activity. Failure of dextran sulfate to be protective implied that the effect was not caused by nonspecific polyanion action.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 14 Mar 2011, 10:05:40 EST