Attenuation of postischemic reperfusion injury in striated skin muscle by diaspirin-cross-linked Hb

Abstract

Hemoglobin-based oxygen carriers have been suggested to enhance the formation of oxygen free radicals, especially under conditions of ischemia-reperfusion (I/R), in which activation and adhesion of leukocytes play a pivotal role for propagation of reperfusion injury. This study investigates the effects of the hemoglobin-based oxygen carrier diaspirin-cross-linked hemoglobin (DCLHb) in an I/R model of hamster striated skin muscle. The dorsal skinfold chamber model in the awake Syrian golden hamster was used for analysis of the microcirculation and local tissue [Formula: see text]in striated skin muscle utilizing the technique of intravital fluorescence microscopy and a multiwire platinum surface (Clark type) electrode. Measurements were made before 4 h of pressure-induced ischemia and at 0.5, 2, and 24 h of reperfusion. Animals were treated with 5 ml/kg body wt of either 10% DCLHb ( n = 8), 6% Dextran 60 (Dx-60; 60 kDa, n = 8), or 0.9% NaCl ( n = 7), which was given intravenously 15 min before reperfusion. In animals treated with DCLHb or Dx-60, a significant decrease of leukocytes rolling along and sticking in postcapillary venules, associated with a recovery of functional capillary density and red blood cell velocity, was observed compared with saline-treated controls. In the early reperfusion period (0.5 h), DCLHb and Dx-60 efficiently restored local tissue[Formula: see text], whereas tissue[Formula: see text] decreased from 18.3 ± 1.9 to 15.3 ± 5.3 mmHg in 0.9% NaCl-treated animals. Electron microscopic analysis of the postischemic tissue at 24 h of reperfusion revealed markedly reduced tissue damage in animals treated with DCLHb compared with Dx-60 or isotonic saline. These results indicate that DCLHb attenuates postischemic reperfusion injury of striated skin muscle, presumably through alterations of leukocyte-endothelial cell interactions.

Artificial Oxygen Carriers as Red Blood Cell Substitutes – Perfluorocarbons and Cell-Free Hemoglobin

“…There is evidence from animal studies that the vasoconstrictive side effects associated with HBOC treatment, whether they are caused by NO scavenging [78], endothelin release [79] or modulation of alpha-adrenoreceptors [80], are more than compensated by the enhanced oxygen off-load through capillaries. This has been demonstrated in models of an artificial arterial or coronary stenosis [81,82] and in reperfusion experiments, showing increased tissue oxygen tensions and decreased reperfusion injuries with different HBOC [83][84][85]. These results offer the opportunity to apply HBOC in patients with stroke and myocardial infarction.…”

Normovolemic hemodilution with Hb vesicle solution attenuates hypoxia in ischemic hamster flap tissue

“…However, the potential benefit of maintaining tissue oxygen tension above a specific threshold is suggested by the results from a study of Pickelmann et al (19), who used similar techniques for measuring tissue oxygen tension in a hamster skinfold model. It was reported that a reduction of tissue oxygen tension over several hours coincided with histomorphological signs of ischemic tissue damage.…”

Blood Substitutes

“…The infusion of HBOC consistently effected a sustained stabilization of hemodynamics and tissue oxygenation and significantly decreased mortality [35,64,90,103]. Moreover, the postischemic interaction between leukocytes and the endothelium could be attenuated by infusion of HBOCs based on human [42,79] as well as bovine Hb [6].…”