The influence of ischaemic injury and manipulation of the nitric oxide synthesis pathway on pulsatile machine perfused porcine kidneys

Aims of the study: 1. To assess the use of machine perfusion in predicting the severity of injury in porcine kidneys subjected to warm ischaemic damage. 2. To assess the use of machine perfusion in predicting the severity of injury in porcine kidneys subjected to warm plus cold ischaemic damage. 3. To assess the potential therapeutic effect of nitric oxide donors and nitric oxide synthase inhibitors on porcine kidneys subjected to prolonged periods of warm plus cold ischaemia. Results: In study 1, a significant relationship between the length of WIT and IRR was found. During pulsatile MP, the IRR reduced in all WIT groups. Nitrate concentration and eNOS expression tended to become higher as the WIT increased. In study 2, the kidneys subjected to the shorter WIT demonstrated a significant linear relationship between the CIT and the IRR. This relationship was not found in the kidneys subjected to a longer WIT. As the CIT increased the nitrate concentration tended to decrease, however the eNOS expression decreased. In study 3, manipulation of the NOS pathway with NO donors and NOS inhibitors did not significantly affect the IRR or eNOS expression. Conclusions: Of the indices measured, IRR had the closest and most convincing relationship with WIT. It would seem possible that this could be used as a viability assessment measure. The fact that in all studies IRR decreased over the six hours of pulsatile MP provides positive evidence of the potential benefit of MP in minimising the deleterious effects of warm and cold ischaemia. The relationship between CIT and IRR was not so clear, but certainly when the kidneys investigated were relatively ischaemically undamaged there was a linear relationship between the two. This study did not find any evidence of an association between ischaemic damage and the NO pathway.