Clinical Research Directory

Ischemic Preconditioning - Perspectives of Use Vivio/in Vitro Studies

Both in sports and medicine, methods that can significantly contribute to improving the ability of tissues to perform their functions are constantly being searched. One of those methods that is increasingly used also in sports is remote ischemic preconditioning (RIPC). Mostly, this procedure involves repeated brief cycles of limb ischemia/reperfusion. This method is often referred as ischemic blood reperfusion and helps to increase the tolerance of treated tissues to the occurrence of possible ischemic episodes in the future. Numerous studies have shown that RIPC induces changes that lead to increased resistance to hypoxia and other stressors in organs (brain, heart, liver). In addition, it has been proven that induction of arterial occlusion in the area of selected limbs before performing physical exercises can affect the improvement of their function, and thus can translate into sports results. In addition, an adaptation of such fibres to damage is mostly associated with the secretion of many factors that influence body function. That's why we conclude that it may affect protein kinases (such like c-Jun N-terminal kinases (JNKs) or serine-threonine kinase = protein kinase B (AKTs)) whose main role is regulation of the activity of a wide spectrum of substrates, influencing cells proliferation, apoptosis, responses to cellular stress and inflammatory process in normal and cancer cells. Concluding that presented kinases activity is associated with cells differentiation and RIPC and physical activity may affect them and the inflammation process that may lead to cytotoxic activity against cancer cells (especially if the effects are combined together). The beneficial increase of anti-tumour activity of the blood serum against pathological isolated tumour cells of prostate cancer (cell lines - LNCaP and PC- 3) was confirmed in our pilot studies. We observed an increase in the anti-cancer properties of serum taken from people that attended RIPC training and performed physical activity. However, the exact mechanism and associated changes in the proteome of blood serum people attending in the RIPC training have not yet been determined. This knowledge would allow us to determine the exact mechanisms of the reperfusion/reocclusion training on the human body and its beneficial activity. Considering that the skeletal muscle is an organ capable of synthesis and release of a number of proteins, cytokines and low molecular weight compounds, especially during physical activity, it should be assumed that intermittent muscle ischemic episodes will lead to increased release of factors that will increase the resistance of muscles and other tissues to stress. At the same time, it was noticed that under conditions of muscular stress induced changes in iron metabolism occur. The binding of free iron through the ferritin protein at the cell level leads to its greater resistance to stressors. In the prism of the above considerations, the results of our preliminary studies showing that the upper limb RIPC procedures cause changes in iron metabolism in white blood cells and may suggest that the procedure of RIPC leads to changes that allow storing iron in a safe form in as ferritin. At the same time, with the increasing interest in iron metabolism, the role and function of amyloid precursor protein (APP) and hepcidin are increasing. It has been proven that APP is a protein that works with ferroportin, thus taking part in iron export from a cell. Moreover, it has been shown that the post-translational modification of APP leads to the formation of amyloid α (determines positive changes) and amyloid β (negative changes). Because there are some indications that sAPPα may be modified by iron changes and associated with cfDNA changes, which substantially increase during i.e. tissue damage, we would like to explore those correlations more deeply. The same decrease in the APP protein level will lead to the inhibition of iron export from the cell and an increase of its concentration in the cell. The nature of such changes in iron metabolism should be considered as adaptive to the ischemic stress on which muscle is exposed during the RIPC procedure. The increase in ferritin in the cell leads to a decrease in the concentration of free iron and thus a reduction in iron-dependent ROS formation. This project will have an impact on the development of the current state of knowledge of the mechanisms of biochemical response to the specific tissue-affecting method in form of remote ischemic preconditioning and will allow determining the role of sAPPα and Cathepsin C and other trophic factors and changes in iron metabolism in this process, taking into account the role of hepcidin and vitamin D. Moreover, the present project may contribute to the determination of the role of presented procedures on cells proliferation, as an example of anti-tumour proprieties, and changes of human serum proteomes.

Therapeutic Strategies to Reduce Endothelial Ischemia-reperfusion Injury

The objective of this clinical trial is to better understand how lactate, a naturally occurring energy substance, can be used to lessen damage to the vascular system in adults with a high cardiovascular disease risk. The main questions it aims to answer are: 1. Does giving lactate intravenously reduce injury to the vascular system? 2. Does giving lactate intravenously together with blood flow occlusion - known as ischemic preconditioning, reduce vascular injury better than blood flow occlusion by itself? 3. How does lactate help the vascular system? Researchers will compare lactate to a placebo (a look-alike substance that contains no lactate) to see if lactate works to lessen vascular injury. Researchers will also compare lactate to blood flow occlusion to see which one is better at preventing vascular injury. Researchers will also compare lactate and blood flow occlusion together to see if combining them works better than either one alone. In one visit to the laboratory, participants will: Obtain a measurement of vascular health in an arm Be given liquid lactate, a liquid placebo, and/or arm blood flow occlusion Obtain a second measurement of vascular health in an arm.

Effects of Remote Ischemic Preconditioning on Peripheral Blood Biomarkers in Healthy Adults (EMINENT)

The aim of this study is to investigate the effects of remote ischaemic preconditioning on the peripheral blood characteristics of healthy adults and to explore the possible mechanisms for improving ischaemia/reperfusion injury and its protective effects on the cardiovascular system.

Effect of CoQ10 on the Endocrine Function of Skeletal Muscle

Recent studies have also shown that repeated episodes of ischemia, followed by reperfusion (IPC), can contribute to the development of adaptive changes not only in the area of the heart muscle, but also in the structure of the skeletal muscles. In the project, several research questions will be evaluated e.g. what is the relationship between oxidative stress parameters, uric acid concentration and nitric oxide degradation products in groups of people undergoing two-week training in ischemic training, or what is the relationship between the expression of genes associated with muscle cell growth (e.g. myostatin gene) and the effect of ischemia preconditioning training etc.

Remote Ischemic Conditioning Combined With Endovascular Stenting for Symptomatic Intracranial Atherosclerotic Stenosis

The purpose of this registry is to evaluate the safety and efficacy of RIC for patients with symptomatic intracranial atherosclerotic stenosis (sICAS) undergoing endovascular therapy.