Document Detail


Transient limb ischemia induces remote preconditioning and remote postconditioning in humans by a K(ATP)-channel dependent mechanism.
MedLine Citation:
PMID:  17724264     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Transient limb ischemia administered before a prolonged ischemic insult has systemic protective effects against ischemia-reperfusion (IR) injury (remote ischemic preconditioning [RIPC]). It has been demonstrated that protection from IR can be achieved by brief periods of ischemia applied at a remote site during an injurious ischemic event (remote postconditioning [RPostC]). Using an in vivo model of endothelial IR injury, we sought to determine whether RPostC occurred in humans and whether it shared mechanistic similarities with RIPC. METHODS AND RESULTS: Endothelial function was assessed by flow-mediated dilation before and after IR (20 minutes of arm ischemia followed by reperfusion). RIPC was induced by conditioning cycles of 5 minutes of ischemia and reperfusion on the contralateral arm or leg before IR. For RPostC induction, conditioning cycles were administered during the ischemic phase of IR. Oral glibenclamide was used to determine the dependence of RIPC and RPostC on K(ATP) channels. IR caused a significant reduction in flow-mediated dilation in healthy volunteers (baseline, 9.3+/-1.2% versus post-IR, 3.3+/-0.7%; P<0.0001) and patients with atherosclerosis (baseline, 5.5+/-0.6% versus post-IR, 2.3+/-0.5%; P<0.01). This reduction was prevented by RIPC (post-IR+RIPC: healthy volunteers, 7.2+/-0.5% [P<0.0001 versus post-IR]; patients, 4.5+/-0.3% [P<0.01 versus post-IR]) and RPostC (post-IR+RPostC: 8.0+/-0.5%; P<0.0001 versus post-IR). The protective effects of RIPC and RPostC were blocked by glibenclamide. CONCLUSIONS: This study demonstrates for the first time in humans that RPostC can be induced by transient limb ischemia and is as effective as RIPC in preventing endothelial IR injury. RIPC and RPostC share mechanistic similarities, with protection being dependent on K(ATP) channel activation. These results suggest that remote conditioning stimuli could be protective in patients with acute ischemia about to undergo therapeutic reperfusion.
Authors:
Stavros P Loukogeorgakis; Rupert Williams; Anna T Panagiotidou; Shyamsunder K Kolvekar; Ann Donald; Tim J Cole; Derek M Yellon; John E Deanfield; Raymond J MacAllister
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-27
Journal Detail:
Title:  Circulation     Volume:  116     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-18     Completed Date:  2007-10-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1386-95     Citation Subset:  AIM; IM    
Affiliation:
Vascular Physiology Unit, Institute of Child Health, University College London, 34 Great Ormond St, London, WC1N 3JE, UK. s.loukogeorgakis@ich.ucl.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Atherosclerosis / physiopathology
Brachial Artery / physiopathology*
Endothelium, Vascular / drug effects,  physiopathology
Female
Forearm / blood supply*
Glyburide / pharmacology
Hemorheology / drug effects
Humans
Hyperemia / physiopathology
Ischemia / physiopathology,  therapy*
Ischemic Preconditioning / methods*
Leg / blood supply*
Male
Middle Aged
Organ Specificity
Potassium Channel Blockers / pharmacology
Potassium Channels / drug effects,  physiology*
Receptors, Drug / drug effects,  physiology*
Reperfusion Injury / physiopathology,  prevention & control*
Time Factors
Vasodilation / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Potassium Channel Blockers; 0/Potassium Channels; 0/Receptors, Drug; 0/glibenclamide receptor; 10238-21-8/Glyburide
Comments/Corrections
Comment In:
Circulation. 2007 Sep 18;116(12):1344-5   [PMID:  17875980 ]

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


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