Document Detail

Transient limb ischemia induces remote ischemic preconditioning in vivo.
MedLine Citation:
PMID:  12460865     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Ischemic preconditioning reduces local tissue injury caused by subsequent ischemia-reperfusion (IR), but may also have a salutary effect on IR injury of tissues remote from those undergoing preconditioning. We tested the hypothesis that limb ischemia induces remote preconditioning, reduces endothelial IR injury in humans, and reduces experimental myocardial infarct size. METHODS AND RESULTS: Endothelial IR injury of the human forearm was induced by 20 minutes of upper limb ischemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. Remote preconditioning was induced by three 5-minute cycles of ischemia of the contralateral limb. Venous occlusion plethysmography was used to assess forearm blood flow in response to acetylcholine at baseline and 15 minutes after reperfusion. Experimental myocardial infarction was achieved by 40 minutes of balloon occlusion of the left anterior descending artery in 15-kg pigs. Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Triphenyltetrazolium staining was used to assess the extent of myocardial infarction. In the human study, the response to acetylcholine was significantly attenuated in the control group after 15 minutes' reperfusion, but remote preconditioning prevented this reduction. Limb ischemia caused a significant reduction in the extent of myocardial infarction relative to the area at risk compared with control (26+/-9% versus 53+/-8%, P<0.05). CONCLUSION: Remote ischemic preconditioning prevents IR-induced endothelial dysfunction in humans and reduces the extent of myocardial infarction in experimental animals. Transient limb ischemia is a simple preconditioning stimulus with important potential clinical applications.
R K Kharbanda; U M Mortensen; P A White; S B Kristiansen; M R Schmidt; J A Hoschtitzky; M Vogel; K Sorensen; A N Redington; R MacAllister
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  106     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Dec 
Date Detail:
Created Date:  2002-12-03     Completed Date:  2002-12-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2881-3     Citation Subset:  AIM; IM    
University College, London, UK.
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MeSH Terms
Acetylcholine / pharmacology
Blood Flow Velocity / drug effects
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects,  physiopathology*
Forearm / blood supply*,  physiopathology
Ischemic Preconditioning* / methods
Ischemic Preconditioning, Myocardial / methods
Middle Aged
Myocardial Infarction / pathology,  physiopathology*
Reference Values
Regional Blood Flow / drug effects
Reperfusion / methods
Reperfusion Injury / prevention & control*
Stroke Volume
Treatment Outcome
Vasodilator Agents / pharmacology
Reg. No./Substance:
0/Vasodilator Agents; 51-84-3/Acetylcholine
Comment In:
Circulation. 2003 Jun 24;107(24):e218-9; author reply e218-9   [PMID:  12821595 ]

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