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(Circulation. 2008;118:1920-1928.)
© 2008 American Heart Association, Inc.

Cardiovascular Surgery

Basic Control of Reperfusion Effectively Protects Against Reperfusion Injury in a Realistic Rodent Model of Acute Limb Ischemia

Florian Dick, MD^*; Jianhui Li, MD^*; Marie-Noëlle Giraud, PhD; Christoph Kalka, MD; Juerg Schmidli, MD; Hendrik Tevaearai, MD, eMBA

From the Department of Cardiovascular Surgery (F.D., J.L., M.-N.G., J.S., H.T.) and Division of Angiology (C.K.), Inselspital, and University of Berne, Berne, Switzerland; Imperial College Vascular Surgery Research Group, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Charing Cross Hospital, London, UK (F.D.); and Department of Hepatobiliary Pancreatic Surgery, Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Medical College, Zhejiang University, Zhejiang, China (J.L.).

Correspondence to Marie-Noëlle Giraud, PhD, Department of Cardiovascular Surgery, Inselspital, and University of Bern, 3010 Berne, Switzerland. E-mail marie-noelle.giraud-flueck{at}insel.ch

Received April 22, 2008; accepted September 3, 2008.

Background— Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model.

Methods and Results— Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159±44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65±13% (P=0.016) and 45±34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132±16% versus 185±42%; P=0.011) and muscle viability (74±11% versus 57±9%; P=0.004) and contraction force (68±40% versus 26±7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027).

Conclusions— Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.

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Circulation 2008 118: 1911-1912. [Extract] [Full Text]