Chapter 8 were treated conservatively, and three patients had more severe PFL/FN and required surgical intervention to correct this. Favorable results on clinical outcome in the arginine group were observed but this was, however, not significant. As shown in chapters 4 and 5, tissue perfusion after IR in the distal part of the flap remains ischemic shortly after reperfusion and gradually increased over the course of several hours. This study demonstrated that arginine accelerates the gradual increase in tissue perfusion in distal parts of the flap (P<0.04). Arginine supplementation reduces the prolonged ischemic period that occurs in the distal part of the MS‐TRAM flap after reperfusion injury. The potential benefit is that arginine may reduce ischemia period and reduce IR injury in the distal part of the flap. This in turn may reduce flap complications such as PFL and FN. Arginine demonstrates promising results in this study, with a relatively small sample. Therefore, this study needs to be repeated in a larger population to validate results. Because breast reconstruction techniques evolved during the course of this study, the study design has to be adapted as well. Secondary breast reconstruction is performed less frequently as primary reconstruction is the primary method of reconstruction in our center. Skin perfusion measurements are not possible because the native skin envelope is spared. Preferably, a multicenter study, with objective and quantitative methods such as ultrasound or magnetic resonance imaging to assess FN, could be used in primary breast reconstruction cases. In addition, a more uniform classification system for PFL and FN should be implemented to allow objective and comparative studies.16 Chapter 7 Short ischemic period using an experimental model induced IR‐related PFL. Physiologic perfusion classification dividing the flap into three zones: a central zone, a zone that is vulnerable to IR injury, and a zone of distal ischemia should be used instead of the classic TRAM flap zone classification. In chapter 7, PFL in the DIEP/TRAM flap model is investigated in relation to the duration of ischemia. In a mouse TRAM flap model based on the deep inferior epigastric vessels, distal ischemia was assessed and animals were exposed to increasing ischemia period. The animals were assigned to three groups: (1) nonischemic control, (2) 30 minutes of ischemia, and (3) 60 minutes of ischemia. PFL was expressed in percentages; in addition, the patterns of flap loss were described. In group 1, PFL was 10.7%±4.3%. PFL occurred mostly in the so‐called classic zone IV, as anticipated. The area of PFL was significantly increased when the flaps were subjected to ischemia and reperfusion injury (groups 2 and 3) (P=0.045). Interestingly, the extent of PFL did not correlate to 118
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