Date of Award
Doctor of Philosophy
Warren D Franke
Remote ischemic preconditioning (RIPC), induced by intermittent periods of sublethal ischemia and reperfusion, may be a practical, non-invasive intervention to confer protection from ischemia-reperfusion (IR) injury. Early animal studies reliably demonstrate that prior RIPC attenuates infarct size about 23% compared to IR injury group without RIPC. Since infarct size attenuation from 20% to 12% is associated with lowered mortality, RIPC may provide clinical benefits to patients with high cardiovascular disease (CVD) risks. However, recent large clinical studies in humans found inconsistent results with respect to RIPC eliciting cardioprotection or improving clinical outcomes. These disparate results may be explained by the use of propofol as the anesthetic, coexisting conditions (e.g., diabetes, obesity, and hypertension), and other factors (e.g., medications, age, and RIPC protocol). Thus, an experimental model that is able to control for these factors is needed in order to elucidate the underlying protective mechanisms of RIPC as it applies to humans.
In vivo experimental models capable of examining mechanisms of myocardial function in humans are limited. As an alternative, the cutaneous circulation is an accessible microvascular bed to non-invasively test human microvascular function in vivo. Skin microvascular function is a good indicator of global microvascular function because functional changes that evolve here parallel other circulations including the coronary microvasculature. A series of studies in the Department of Kinesiology Hemodynamics Laboratory have tested the effects of RIPC on skin microvascular function. We found that maximum vasodilatory capacity increased after seven consecutive days of RIPC; however, we did not observe an improvement in NO-mediated vasodilation. In a follow-up study, we found that one and two weeks of RIPC improved endothelial dependent vasodilation. However, the amount of skin microvascular improvement was not different between these seven consecutive days and two weeks of RIPC. Whether shorter periods of RIPC (i.e., less than 7 days) elicits similar functional improvements is unknown. The effects of a single bout of RIPC are thought to exhibit a two-phase response, an initial (lasting ~4 hours) and a delayed window of protection (lasting 3-4 days). Therefore, different frequencies of RIPC training may stimulate protective pathways differently. Thus, there may be an optimal frequency and duration of RIPC that induces prolonged improvements in microvascular responsivity without long intervention periods.
It is important from a clinical standpoint to know the threshold dose needed to elicit beneficial effects of an intervention. This type of information will be useful in optimizing an RIPC-based intervention protocol aimed at improving microvascular function. Thus, the purpose of this study is to assess the extent to which shorter intervention periods (3 days of RIPC separated by rest days; 3QOD RIPC) elicit sustained skin microvascular functional alterations. Our hypothesis was that 3QOD RIPC will induce sustained skin endothelial dependent and independent vasodilation.
Kim, Jahyun, "Repeated remote ischemic preconditioning and cutaneous microvascular responses" (2020). Graduate Theses and Dissertations. 18012.
Available for download on Thursday, June 16, 2022