| Summary: | Ischaemia-reperfusion (IR) injury contributes to tissue damage that occurs in myocardial infarction and stroke, and limits the outcome of current reperfusion strategies. Ischaemic preconditioning (IPC) is an innate mechanism that protects tissues from injury during ischaemia and subsequent reperfusion. IPC has systemic effects that protect tissues remote for those undergoing preconditioning (remote IPC RIPC). RIPC might enable the clinical utility of ischaemic preconditioning to be tested, as protection of vital tissues against IR injury could be achieved by remotely preconditioning a non-vital tissue. This thesis sought to determine the optimal conditions for inducing RIPC in humans. The protective effects of RIPC were investigated in healthy volunteers, using an in vivo model of IR injury to the vascular endothelium of the brachial artery. RIPC of the limb protected against IR-induced endothelial dysfunction and the degree of protection depended on the characteristics of the preconditioning stimulus. Two phases of protection by RIPC were evident an early relatively short phase, active immediately, and a second window of protection, which is more prolonged lasting for up to 48 hours following the application of the RIPC stimulus. Repeated application of the RIPC stimulus caused tissue protection for up to 7 days. RIPC was shown to be dependent on intact autonomic function and the opening of ATP-sensitive potassium channels. The protective effects of RIPC were investigated in paediatric patients undergoing renal transplantation. Data from this clinical study are consistent with a beneficial effect of RIPC against IR injury to the renal graft and suggest that RIPC may have therapeutic potential in clinical IR syndromes.
|
|---|
