Jenner, WJ; (2013) In Vivo Characterisation of Ischaemic Preconditioning in Rodents and Humans. Doctoral thesis , UCL (University College London).

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Abstract

Prolonged arterial occlusion results in ischaemic cell death. Reperfusion is necessary to prevent irreversible tissue infarction, but paradoxically contributes to some cell death. The composite ischaemia-reperfusion (IR) injury, contributes to tissue damage in common clinical conditions, and reducing IR injury remains a validated therapeutic target. Ischaemic preconditioning (IPC) attenuates IR injury and is elicited by non-lethal periods of ischaemia in advance of a prolonged arterial occlusion. IPC also exerts a systemic protective effect, remote ischaemic preconditioning (RIPC), which is believed to occur through activation of humoral and neural pathways. Experiments in this thesis investigated IPC and RIPC using four in vivo models. Firstly, in a rat model of stroke caused by transient occlusion of the middle cerebral artery, RIPC induced by limb ischaemia reduced infarct size. Secondly, in healthy volunteers in vivo, vascular occlusion caused endothelial IR injury of the brachial artery and this model was used to determine whether physical exercise elicited a protective phenotype similar to RIPC. In these experiments, only IPC has an effect to reduce IR injury. Thirdly, the inflammatory response to cantharidin was used in healthy volunteers to model the innate immune response, and to compare the anti-inflammatory effects of aspirin and IPC. Aspirin reduced inflammation in subjects with an early resolution phenotype, but IPC had no effect on the immune response. Fourthly, the effect of IPC on the response to exercise was investigated in healthy cyclists. IPC did not alter exercise capacity but increased skeletal muscle oxygenation in humans during an incremental exercise test. The results in this thesis complement certain previous observations and provide evidence of heterogeneity in the protective phenotype of IPC and RIPC.

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