Arginine suppletion in free TRAM flap Therefore, there have been a large number of experimental studies using different strategies to reduce ischemia‐reperfusion injury. The main subjects of these studies were aimed at reducing reactive oxygen species, neutrophil influx, depletion of nitric oxide, and necrosis/apoptosis.7,8,33 It is widely accepted that the arginine–nitric oxide pathway plays a pivotal role in the pathophysiology of ischemia‐reperfusion injury. Supplementation of either the precursor arginine or its end product nitric oxide has given strong evidence for its protective effect in reperfusion injury in experimental studies.34–36 In addition, modulating the relevant nitric oxide synthase enzymes in experimental studies has given further confirmation.15,37,38 A recent study showed that arginine protects from endothelial dysfunction in a human reperfusion model.39 Future models Because of the relatively high rate of partial flap loss in the placebo group that most likely is caused by the inclusion of zone IV, subsequent studies should discard the use of zone IV. An alternative model could be the DIEP flap, which has less donor‐site morbidity. However, with a reduction of perforators, there is increased risk of partial flap loss.30 Despite discarding zone IV, the DIEP flap is still vulnerable to minor partial flap loss, as demonstrated in clinical studies using ultrasound.25 Another strategy may be to combine several strategies to have a cumulative or synergistic effect. Nanobashvili et al. demonstrated that a combined treatment with arginine and antioxidants is superior for reducing ischemia‐reperfusion injury when compared with single regiment by means of either arginine or antioxidants.40 Another easily performed and cheap intervention that can be performed in the clinical setting is preconditioning.41 Is arginine a good strategy for reducing injury? This is the first study using arginine in a clinical setting after free tissue transfer. Arginine is a cheap, safe, and easily administrated intervention strategy. We believe that our study gives enough support to start larger studies with arginine intervention in this type of procedure. Conclusions Clinical outcome favors arginine supplementation and leads to an increased microcirculatory blood flow in zone IV. Because of its wide clinical relevance in reconstructive and revascularization procedures, it is important that clinical trials are performed. Reconstructive surgery may be an ideal reperfusion model because of its accessibility for measurement. 95
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