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

Article

关键词: SKELETAL-MUSCLE;    VASCULAR-SURGERY;    PATHOPHYSIOLOGY;    HYPOTHERMIA;    DISEASE;   

DOI  :  10.1161/CIRCULATIONAHA.108.787754

来源: SCIE

【 摘 要 】

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. (Circulation. 2008; 118: 1920-1928.)

【 授权许可】

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