Reports of research work funded by grants prior to 2012
Victoria University of Wellington
The effect of remote ischaemic preconditioning on the immune response in healthy volunteers
AC La Flamme, J Williams and R Beasley
School of Biological Sciences
Medical Research Institute of New Zealand
Remote ischaemic preconditioning (RIPC) is the phenomenon whereby brief periods of ischaemia (reduced oxygen delivery) in one organ can have a protective effect against subsequent prolonged ischaemic insults in other organs. This technique is most commonly applied by inflating a blood pressure tourniquet on the upper arm to induce three five-minute cycles of ischaemia, with intervening periods of reperfusion. Application of RIPC in clinical trials with cardiac surgery patients has repeatedly been shown to reduce the levels of myocardial and renal injury; however, the underlying pathways involved in this protection are currently unclear. Studies using animal models have shown RIPC has a significant influence on gene expression and cellular function, including changes in cytokine production and leukocyte activation. There is increasing evidence that inflammation may be involved in the mechanism of RIPC and this is being explored in the present study by applying RIPC in healthy volunteers and collecting blood samples to investigate the impact on inflammatory biomarker expression, peripheral leukocyte populations, and neutrophil and T cell function. Performing the study in healthy volunteers allows the direct effects of RIPC to be isolated from the response to surgery and other co-morbidites frequently encountered in trials involving surgery patients. This study will contribute to understanding the mechanism through which RIPC exerts its beneficial effects, which will be essential to harness the maximum benefit RIPC stands to offer in the clinical setting.
Progress: This project is currently in the optimisation phase, where the assays required for assessing changes in immune cell populations are being tested. To date, we have established and validated flow cytometry protocols to quantify and characterize cell surface marker expression in peripheral blood cells, including CD4, CD8, natural killer and regulatory T-cells, as well as monocytes, neutrophils, and natural killer cells. We are currently optimising a protocol for assessing intracellular cytokine production in lymphocytes and granulocytes. We anticipate we will complete this and begin study recruitment within the next two months.