Document Detail


Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.
MedLine Citation:
PMID:  20141596     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.
Authors:
Matthew A Ziegler; Matthew R Distasi; Randall G Bills; Steven J Miller; Mouhamad Alloosh; Michael P Murphy; A George Akingba; Michael Sturek; Michael C Dalsing; Joseph L Unthank
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Microcirculation (New York, N.Y. : 1994)     Volume:  17     ISSN:  1549-8719     ISO Abbreviation:  Microcirculation     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-09     Completed Date:  2010-06-17     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  9434935     Medline TA:  Microcirculation     Country:  England    
Other Details:
Languages:  eng     Pagination:  3-20     Citation Subset:  IM    
Affiliation:
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterial Occlusive Diseases / pathology,  physiopathology*
Collateral Circulation / physiology*
Disease Models, Animal
Extremities / blood supply
Hemodynamics
Humans
Ligation
Mice
Peripheral Vascular Diseases / pathology,  physiopathology*
Rats
Swine
Swine, Miniature
Vasodilation / physiology
Grant Support
ID/Acronym/Agency:
HL062552/HL/NHLBI NIH HHS; HL092012/HL/NHLBI NIH HHS; HL42898/HL/NHLBI NIH HHS; R01 HL042898-13/HL/NHLBI NIH HHS; R01 HL062552-09A2/HL/NHLBI NIH HHS; R01 HL092012-01A2/HL/NHLBI NIH HHS; R01 HL092012-04/HL/NHLBI NIH HHS; R24 RR013223-04/RR/NCRR NIH HHS; RR013223/RR/NCRR NIH HHS
Comments/Corrections

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


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