Development of ‘No-Reflow’ Phenomenon in Ischemia/Reperfusion Injury: Failure of Active Vasomotility and Not Simply Passive Vasoconstriction

Abstract

Background/Aim: Local blood flow failure (no-reflow phenomenon) during ischemia/reperfusion (I/R) injury may be mediated by interstitial edema formation (passive vasoconstriction) and/or microvascular spasm (active vasoconstriction). The development of the no-reflow phenomenon in the rabbit hind limb I/R model and the influence of treatment with L-arginine and/or antioxidative vitamins were investigated. Methods: Untreated rabbits were compared with those treated with L-arginine (4 mg/kg/min) or antioxidative vitamins (0.4 ml/kg) alone or in combination during hind limb I/R (2.5/2 h). Interstitial edema formation and microvessel diameter alterations were measured morphometrically. Capillary blood perfusion was measured continuously with laser Doppler flowmetry. Results: I/R injury was expressed by interstitial edema formation (interstitial space increase by 80%), microvascular constriction (microvessel cross-sectional area decrease by 30%), and development of no-reflow phenomenon (blood flow reduction by 60%). Treatment with antioxidative vitamins alone or L-arginine alone reduced interstitial edema by 22 and 31%, consequently, while combined L-arginine/antioxidative vitamin treatment showed a more pronounced edema reduction by 40%. Treatment with only antioxidative vitamins failed to influence the development of no-reflow, although interstitial edema formation was reduced. L-Arginine treatment alone or in combination with antioxidative vitamins prevented microvascular constriction and preserved blood flow after reperfusion without development of no-reflow despite still apparent interstitial edema. Conclusions: Affections of active vasomotility and not merely passive changes of external pressure (i.e., interstitial edema formation) should be considered important in the development of microvascular constriction during ‘no-reflow’ phenomenon.