Transient limb ischemia induces remote ischemic preconditioning in vivo

• Published in: Circulation (New York, N.Y.) N.Y.), 2002-12, Vol.106 (23), p.2881-2883
• Main Authors: KHARBANDA, R. K, MORTENSEN, U. M, WHITE, P. A, KRISTIANSEN, S. B, SCHMIDT, M. R, HOSCHTITZKY, J. A, VOGEL, M, SORENSEN, K, REDINGTON, A. N, MACALLISTER, R
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Adult; Animals; Biological and medical sciences; Blood Flow Velocity - drug effects; Cardiology. Vascular system; Coronary heart disease; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Forearm - blood supply; Forearm - physiopathology; Heart; Humans; Ischemic Preconditioning - methods; Ischemic Preconditioning, Myocardial - methods; Medical sciences; Middle Aged; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Plethysmography; Reference Values; Regional Blood Flow - drug effects; Reperfusion - methods; Reperfusion Injury - prevention & control; Stroke Volume; Swine; Treatment Outcome; Vasodilator Agents - pharmacology
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.0000043806.51912.9b

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. 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