Rocko J M, Tikellis J, Barillo D, Barbalinardo R, Rush B F
J Surg Res. 1986 Dec;41(6):574-9. doi: 10.1016/0022-4804(86)90081-8.
An understanding of the basic metabolic, functional, and histologic features of skeletal muscle injury secondary to ischemia and reperfusion has thus far been hampered by the lack of an adequate animal model. We have developed an in vivo isolated skeletal muscle preparation amenable to ischemia-reperfusion studies and the investigation of therapeutic modalities. The model is autoperfused and, most importantly, nonheparinized. The use of a nonheparinized model is essential following the work of Hardaway, recently confirmed by Fry, showing that alterations of flow in the shock state occur when heparin is used, invalidating other models as true replicas of clinical situations. The gracilis muscle in the canine hindlimb and its contralateral control are isolated on their neurovascular pedicles after detachment of fascial boundaries and meticulous ligation of all collateral vascular supply. Prolonged arterial occlusion can be accomplished by clamping proximal and distal to the point of origin of the gracilis artery from the superficial femoral artery. In a similar fashion, occlusion above and below the gracilis vein is effected intermittently to collect venous efluent during reperfusion. Preliminary studies of 100 muscle preparations subjected to 3 or 15 hr of ischemia, followed by 2 hr of reperfusion, demonstrate depression of oxygen utilization of 5% of control values during early reperfusion with improvement to 30% of control values over 2 hr. Contractility, abolished during ischemia, returns to 20% of control values after 2 hr of reperfusion.
迄今为止，由于缺乏合适的动物模型，对缺血再灌注继发骨骼肌损伤的基本代谢、功能和组织学特征的理解受到了阻碍。我们已经开发出一种适用于缺血再灌注研究和治疗方式研究的体内分离骨骼肌制备方法。该模型是自体灌注的，最重要的是，未使用肝素。在哈达威的研究之后，使用未肝素化模型至关重要，弗莱最近证实了这一点，研究表明使用肝素时会出现休克状态下血流的改变，这使得其他模型无法作为临床情况的真实复制品。在分离筋膜边界并仔细结扎所有侧支血管供应后，将犬后肢的股薄肌及其对侧对照在其神经血管蒂上分离出来。通过夹住股薄肌动脉从股浅动脉起源点的近端和远端，可以实现长时间的动脉闭塞。以类似的方式，间歇性地对股薄肌静脉上下进行闭塞，以在再灌注期间收集静脉流出物。对100个肌肉制备物进行的初步研究，使其经历3或15小时的缺血，然后再灌注2小时，结果表明在再灌注早期氧利用率降低至对照值的5%，在2小时内改善至对照值的30%。在缺血期间消失的收缩力在再灌注2小时后恢复至对照值的20%。
