**2. Principles behind the use of normothermic regional perfusion in donation after circulatory death**

During warm ischemia, ATP degradation leads to the progressive accumulation of xanthine and hypoxanthine, important sources of superoxide radical at organ reperfusion [3]. A period of post-ischemic NRP in DCD donors is useful to restore cellular energy substrates [4], reduce levels of nucleotide degradation products [5], improve the concentrations of endogenous antioxidants [6], and even stimulate processes of cellular repair prior to graft recovery [7] (**Figure 1**). An experimental study demonstrates that by blocking the A2 receptors of adenosine, the beneficial effects of NRP are abolished, indicating that NRP mediates its effect, at least in part, through adenosine as a form of ischemic preconditioning [8]. Post-ischemic NRP may also be useful to reduce the vasoconstrictive effects of cold graft washout with the static cold storage solution [9] and offers an opportunity to assess organ viability prior to recovery [10, 11].

#### **Figure 1.**

*During ischemia, the concentrations of adenine nucleotides (ATP, ADP, AMP) and nucleosides (adenosine, inosine) progressively decline. Also, the concentrations of nucleotide breakdown products (xanthine, hypoxanthine) increase, thereby leading to the production of oxygen free radicals upon reperfusion. Normothermic regional perfusion is capable of reversing these processes and increases the concentrations of endogenous antioxidants, effectively recharging and reconditioning organs in the abdomen and chest prior to recovery for transplantation.*
