Project title: Studying Reperfusion Injury in Human Heart; How to Combat Negative Aspects of a Life-saving Therapy (REFINE)
Principal investigator: Marko Ljubkovic, MD, PhD
Clinical coordinator: Cristijan Bulat, MD, PhD
Project duration: 1/10/2017 – 30/09/2021
Research team:
Jasna Marinovic, MD, PhD, University of Split School of Medicine
Ivica Grkovic, MD, PhD, University of Split School of Medicine
Godfrey L. Smith, PhD, University of Glasgow
Martin Bienengraeber, PhD, Medical College of Wisconsin
Ivan Mihanovic, MD, doctoral student
Ivanka Jerić, PhD, Institute Ruđer Bošković
Nadica Maltar Strmečki, PhD, Institute Ruđer Bošković
Project summary:
Mortality due to cardiovascular diseases, despite improved preventive and therapeutic measures that resulted in beneficial trends in the last decades, still remains the main global cause of death. Re-establishment of coronary blood flow following an ischemic period is the main goal of coronary recanalization therapies and is essential for reducing myocardial ischemic damage. However, there is ample evidence that reperfusion itself, besides bringing nutrients and oxygen back to the energy-deprived myocardium, can actually further induce cardiomyocyte death. This reperfusion injury is considered to account up to 50% of the final myocardial damage. Therefore, a great number of research studies focused their efforts on finding various modes of attenuation of the reperfusion injury, with many of them reaching even clinical setting. However, due to negative results of clinical studies, translation of experimental data that showed efficient cardiac protection in cellular and animal models of ischemia-reperfusion has been largely unsuccessful. In the proposed project, we aim to investigate the main culprits of reperfusion injury in myocardial tissue obtained from patients suffering from coronary heart disease and undergoing coronary artery bypass graft (CABG) surgery. We will use state-of-the-art experimental approaches for assessment of free oxygen radicals, mitochondrial damage and metabolomic analysis during ischemia and at the early onset of reperfusion, the time-point which was shown to be responsible for the most of reperfusion injury. Moreover, we propose to develop an experimental platform for investigation of various (potentially) cardioprotective strategies in human cardiac tissue, cells and mitochondria. The purpose of such approach is to bring closer to clinics some of the experimental findings obtained in animal models of the disease and ultimately come closer to reducing the reperfusion injury.
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