Mitochondria as mediators of ischemia-reperfusion injury in rats with high or low intrinsic exercise capacity

• Applicant: Dr. Estelle Heyne
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2022 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499175292

Mechanisms underlying ischemia-reperfusion (IR) injury in the heart are not fully elucidated. However, the disruption of substrate and oxygen supply affects cardiac function severely by disabling ATP production. Mitochondria harbor essential enzymes required for substrate oxidation and ATP generation. It is thus not surprising that several investigations have created a close link between mitochondria and recovery of contractile function upon IR. Previously, we studied IR effects on cardiac contractility in the isolated working hearts from rats with high (HCR) and low (LCR) intrinsic running capacity and found that LCR showed better contractile recovery after IR. Based upon the aforementioned, we hypothesized that adaptation processes in cardiac mitochondria of LCR confer the observed beneficial effects. In order to test this hypothesis and to study the role of mitochondria for cardiac contractile recovery after ischemia in general, I aim to employ conplastic rat strains, where mitochondria have been exchanged through specific breeding strategies between the original HCR and LCR. I expect that the exchange of mitochondria will revert the observed differences in recovery of function in our IR model and I will relate our observation on recovery of contractile function to functional assessments of mitochondria including substrate oxidation, oxidative stress and calcium metabolism. The results will provide important insight into the role of mitochondria in IR and its link to recovery of contractile function. This project together with my previous experience with the rat model of HCR and LCR will lay the foundations for promising future projects.

• DFG Programme: Research Grants