The role of hydrogen sulphide in ischaemia reperfusion injury

Warm ischaemic injury occurs when an organ or region of the body is starved of oxygenated blood under normothermic conditions. Two important clinical examples of warm ischaemia are donation after circulatory death (DCD) kidney transplantation and abdominal aortic aneurysm (AAA) repair. The tissue injury that results from warm ischaemia can lead to organ dysfunction, which has important clinical consequences. In kidney transplantation warm ischaemic injury can lead to delayed graft function, increased rates of primary non-function and poorer long-term outcomes. In open AAA repair occlusion of the abdominal aorta leads to remote injury to organs such as the kidneys. Renal failure following AAA repair can cause significant morbidity including the need for renal replacement therapy. Hydrogen sulphide (H2S) is an endogenously produced gas that been shown to be protective against ischaemia-reperfusion injury. The aims of this thesis were twofold. First, the effect of H2S on ischaemia-reperfusion injury in a porcine model of direct renal ischaemia was assessed. Second, the effect of H2S on inflammation and remote renal injury was assessed using a rodent model of aortic occlusion. This research demonstrated that hydrogen sulphide, delivered as an exogenous agent, preserved renal function and reduced inflammation in a large animal model of renal warm ischaemia. Furthermore, in a rodent model of remote renal injury hydrogen sulphide also reduced systemic and renal inflammation but had no effect on renal function. In addition, there were no significant side effects from the administration of hydrogen sulphide.