Clinical Research Directory

Age Related Chromatin Remodelling as a Therapeutic Target for Organ Protection in Cardiac Surgery

People who have multiple long-term conditions (MLTC) like kidney disease or lung disease are at higher risk of developing organ damage and poor quality of life following heart surgery. Decades of research have failed to identify drugs or treatments that prevent this. Our research has shown that people with MLTC have changes in their heart cells before surgery that are referred to by researchers as Biological Ageing. These changes combine to make people with MLTC more susceptible to organ damage after heart surgery, have delayed recovery, and lower quality of life. This research programme will investigate the processes linking MLTC, changes in heart cells, and organ damage. Our previous research suggests that MLTC lead to the infiltration of white cells from the blood into the heart muscle, a process called inflammageing. This alters the DNA in heart cells, reduces their pumping function and leaves them more likely to be damaged by surgery. We have also shown that these changes are affected by obesity. We have also shown that changes in other types of heart cells with ageing are associated with damage to the lining of blood vessels, bleeding and damage to the kidneys. We will use existing clinical data from previous studies and molecular data from heart cells obtained at surgery to better understand the molecular changes underlying our previous observations. This includes data from previous trials of drugs and dietary modification that aimed to modify the cellular DNA changes caused by inflammageing. Using external data, we will check whether similar results are evident in other studies. We will then select the most likely processes underlying our observations and test whether these relationships are causal using genomic analysis and the UK Biobank data. Finally, we will use established analytical methods to identify potential drugs that may target these processes. Positive results will provide a better understanding of the heart damage that is often seen in people with MLTC as well as new treatments for evaluation on further research.

Use of PRP in Open Surgery for Type A Aortic Dissection

The goal of this clinical trial is to determine if autologous platelet rich plasma (PRP) can reduce the need for blood transfusions in patients undergoing open surgery for Type A aortic dissection. It will also evaluate the potential organ-protective effects of autologous PRP. The main questions it aims to answer are: 1. Does PRP reduce the amount of allogeneic red blood cell transfusions for participants? 2. Does PRP administration provide protective effects on organs (heart, liver, lungs, kidneys, brain) in participants? Researchers will compare the administration of autologous PRP with no PRP infusion to assess whether PRP can reduce blood transfusions and provide organ-protective effects in patients undergoing open surgery for Type A aortic dissection. Participants will: 1. Receive autologous PRP infusion during surgery 2. Undergo multiple checkups and tests before and after surgery 3. Be recorded for allogeneic red blood cell usage within 24 hours perioperatively and all allogeneic blood products usage during the entire hospitalization 4. Be assessed for organ function (heart, liver, lungs, kidneys, brain) and symptom-related outcomes through clinical evaluations