- Menstrual cycle and the protective effects of remote ischemic preconditioning.
In this study, we complete vascular endothelial function measurements in premenopausal women during their early follicular phase and during ovulation. The objective is to identify the degree to which alterations in female sex hormones (i.e., estradiol and progesterone) during the follicular phase, ovulation and luteal phases of the menstrual cycle interfere with ischemic preconditioning to protect against vascular endothelial injury in premenopausal women. As a payoff, new guidance in scheduling planned medical interventions (e.g., CABG, PCI, organ transplantation/resection surgeries) according to menstrual cycle phase with the greatest potential for cell protection will result.
- Exercise training and vascular endothelial protection.
This project will determine the impact of raising the lactate threshold on vascular endothelial protection against ischemia/reperfusion injury. One major benefit of ischemic preconditioning is its energy-sparing effect - attributed in part to greater lactate uptake. Restoring lactate utilization is expected to have significant cardioprotective value. By shifting net lactate flux towards uptake, the objective of this aim is to advance the development of new clinically innovative therapeutic options aimed at recapturing the cytoprotective benefits of ischemic preconditioning. We determine whether improving the metabolic use of lactate via a lactate-threshold specific exercise training intervention is associated with enhanced cell protection. Ultimately, this project will provide clinical evidence with respect to how lactate threshold-based exercise training can be used as a treatment strategy to restore protection in at-risk adults.
- Influence of cardiovascular risk factors on remote ischemic preconditioning.
These studies are focused on determining the extent that elevated cardiovascular disease risk reduces vascular endothelial protection against ischemia/reperfusion injury. We use measurements of endothelium-dependent vasodilation in the forearm to quantify blood flow changes before and after experimental injury.
- Role of ischemic preconditioning on exercise performance.
In addition to the cardioprotective benefits of ischemic preconditioning, me team has led efforts showing that it may also influence exercise performance. Specifically, results show that ischemic preconditioning, which was previously shown not to improve performance at submaximal workloads, also does not change the economy of exercise. This finding has led to the idea in the exercise physiology field that the putative benefits of ischemic preconditioning on performance are likely to be realized only in events that elicit greater metabolic and neuromuscular stress. This notion has led to new studies in my laboratory focusing on the extent to which ischemic preconditioning increases supramaximal fast glycolytic exercise performance.
Future research will determine the extent to which intravenous lactate administration (i.e., lactate clamp methodology) protects against endothelial injury in humans in vivo. Studies will be complemented by including stable isotope tracer infusions to monitor whole body lactate turnover, as well as lactate turnover in the resting and exercising forearm. Future work will elucidate important mechanisms (e.g., reduced lactate oxidation, increased rate of appearance or poor clearance) underlying diminished remote cell protection.