Enkephalin Metabolism In Cardiac Ischemia, Heart Failure And Cardiac Surgery
Funder
National Health and Medical Research Council
Funding Amount
$327,037.00
Summary
It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during ....It has recently been discovered in animal studies that heart muscle can make its own opioid proteins. Previously, it was thought that only nerves made and released opioids. We have recently found that a class of opioids called enkephalins are made and then depleted from the heart during the stress of oxygen and nutrient deprivation. Enkephalins have been found to have potent metabolic effects on the heart. Previous work has shown that opioids can protect the heart against injury incurred during disease that restricts energy and oxygen supply to the blood vessels and heart. We wish to demonstrate this for the first time in human heart, and we will explore whether the production of enkephalins is altered by the stresses of cardiac surgery and heart failure. Understanding how the human heart attempts to protect itself in disease and how enkephalins work under these conditions, may prove valuable in the development of new drug therapy with synthetic drugs which mimic the action of enkephalins for heart protection during cardiac surgery, heart transplantation and ischemic heart disease. We will test whether specific enkephalins may be used to improve donor heart viability for transplantation by improving the duration and quality of preservation during storage. Understanding what happens to enkephalin production and metabolism in the failing hearts of patients may allow us to find new therapeutic targets in heart failure.Read moreRead less
Outcomes Of The Arterial Switch Operation: A Multi-centre Study
Funder
National Health and Medical Research Council
Funding Amount
$86,733.00
Summary
The arterial switch operation is the surgery of choice for children born with transposition of the great arteries, a congenital heart defect where the main two vessels of the heart arise from wrong pumping chambers of the heart. There are very few studies looking at adults after this operation. We aim to study all patients who have had an arterial switch. The results of this study will further increase our knowledge of the long term consequences of having the arterial switch operation.
The Neurovascular Territories Of The Human Body: Anatomic Study And Clinical Applications
Funder
National Health and Medical Research Council
Funding Amount
$186,650.00
Summary
A Melways Roadmap of the anatomy of the large and small nerves, arteries and veins of the human body is underway and will take a further three years to complete. The aim is to evolve or modify Reconstructive Plastic Surgery techniques taking tissue from a hidden site and, where possible, include a nerve supply with the transplant so that feeling can be restored to skin flaps and function to transferred muscle. The fundamental objective is to improve the quality of the patients life. We have alre ....A Melways Roadmap of the anatomy of the large and small nerves, arteries and veins of the human body is underway and will take a further three years to complete. The aim is to evolve or modify Reconstructive Plastic Surgery techniques taking tissue from a hidden site and, where possible, include a nerve supply with the transplant so that feeling can be restored to skin flaps and function to transferred muscle. The fundamental objective is to improve the quality of the patients life. We have already completed a thorough examination of the following regions: (i) head and neck (ii) forearm (iii) leg These have received international acclaim and awards. We are currently examining: (i) hand and foot (ii) thigh and buttock. Still to be commenced: (i) arm and shoulder (ii) torso (iii) back. Reconstructive surgery involves the treatment and the reconstruction of defects throughout the whole human body. These defects may arise in any member of the family. With modern reconstructive techniques a problem can often be solved in one operation thus avoiding multiple operations and long periods of hospitalisation which can be devastating to both patient and family. These new techniques nevertheless have demanded a reappraisal of the basic sciences, especially the anatomy of the blood and nerve supply to the potential transplant. This is essential so that they can be designed with not only precision and safety but in such a way that there is minimal disability at the donor site. As well as restoring shape and form, the patient can have tremendous improvement in quality of life and independence if function is also restored. In order to provide function (feeling and movement) a working nerve supply must be included in the reconstruction. Therefore our research must continue to investigate the complex patterns of nerve supply to tissues of the body and correlate this information with the blood supply which is needed to keep the tissue alive.Read moreRead less
Clinical Feasibility Study Of Omega-3 PUFA Therapy For The Reduction Of Post-cardiac Surgery Atrial Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$442,092.00
Summary
The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be li ....The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be linked to low incidence of AF. The main aim is to provide a cheap and safe preventative therapy against post-operative atrial fibrillation (AF), a key heart rhythm disorder that occurs in at least 1 in 4 patients after heart surgery and increases post-operative complications, limits recovery and increases hospital stay and cost. Biochemical study elements are important to gain valuable insight into the molecular mechanisms (directly in human heart) that underlie post-operative heart rhythm disorder and may delineate new more precise molecular targets for therapy. No previous clinical study has ever examined whether omega-3 PUFA therapy prevents post-operative heart rhythm disorder. Use of 3g-day omega-3 PUFA pre-treatment in the surgical setting has been shown to be safe in a number of small studies, including our own. Our preliminary data indicates that therapy increases heart and blood content of omega-3 PUFA ~2-fold, and reduces the incidence of AF. Post-operative AF is an expensive resource burden in all cardiothoracic surgery units of Australian hospitals and targets key health priorities. Due to the non-patentable nature of omega-3 PUFA, significant industry based support for clinical research is limited. A positive outcome would rapidly pave the way for widespread use in elective surgery. Reduced length of hospital stay, cost-savings, and the increase in productivity as healthy individuals return to their communities would nationally repay the investment many fold.Read moreRead less
Identification Of A Plasma Factor Of Remote Ischemic Preconditioning And Its Effect On The Proteome After Heart Surgery
Funder
National Health and Medical Research Council
Funding Amount
$385,197.00
Summary
Heart surgery with the heart placed into arrest causes inflammation and tissue damage due to interrupted circulation. We know that prior brief interruption and restoration of blood supply called remote ischemic preconditioning (IPC) can protect heart and lungs against damage. Our previous studies indicate that IPC involves a circulating factor that protects the tissue by optimizing energy preservation. This knowledge can be applied to organ transplants, protection from stroke and heart attack.
Evaluation Of Aspirin And Tranexamic Acid In Coronary Artery Surgery: The ATACAS Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,185,000.00
Summary
This large study will compare two types of drug treatment in 4600 patients undergoing heart surgery, to see whether either can reduce the risk of death or major complications. The complications after surgery we are measuring include heart attack, stroke, lung embolism, bleeding around the heart, breathing failure, kidney failure, major haemorrhage, serious wound infection, and death. The first drug being tested is low-dose aspirin. It is believed that aspirin can reduce the risk of a further hea ....This large study will compare two types of drug treatment in 4600 patients undergoing heart surgery, to see whether either can reduce the risk of death or major complications. The complications after surgery we are measuring include heart attack, stroke, lung embolism, bleeding around the heart, breathing failure, kidney failure, major haemorrhage, serious wound infection, and death. The first drug being tested is low-dose aspirin. It is believed that aspirin can reduce the risk of a further heart attack or stroke in patients with pre-existing heart disease. There is some evidence that aspirin may have similar effects in people undergoing heart surgery, but such use is constrained by a concern that there may be an increased risk of bleeding after surgery. For this reason, most patients having heart surgery are advised to stop their aspirin about one week before surgery. But patients could be missing out on aspirin's beneficial effects. At present, we do not know whether the benefits of aspirin could outweigh the risk of excesive bleeding. The second drug being tested is tranexamic acid. This drug prevents blood clot being broken down at the stitching sites of surgery, and probably reduces the amount of blood loss during and after heart surgery. It is known that use of this drug reduces the need for a blood transfusion. It is possible that this could avoid other more serious complications after surgery. Both of these drugs are being tested individually, but in addition we are testing whether they may have an extra beneficial effect when used together. The study is being done by a partnership of anaesthetitsts and surgeons at more than 20 hospitals around Australia.Read moreRead less
Preconditioning: The Molecular Basis For Protection From Hepatic Ischemia-reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of da ....When the blood supply to the liver is cut off temporarily (ischemia) and later restored (reperfusion) the liver is damaged by a process called ischemia-reperfusion (IR) injury. This is a major problem during liver surgery and is also an underlying problem in liver transplantation; following storage of a donor liver ready for placing into the recipient it can undergo a similar process called preservation injury. We now understand a lot about how IR comes about, particularly by the formation of damaging oxygen radicals within liver cells to start a process of programmed cell death, but it remains difficult to prevent or treat IR injury. A recent breakthrough has been recognition that subjecting the liver to only a short period (5 or 10 minutes) of ischemia protects against a later period of prolonged ischemia or IR. In the investigator s mouse model, for example, such preconditioning was 60 to 90% protective (depending on the time after IR). This project seeks to understand how preconditioning works to protect the liver against IR injury. Our idea is that preconditioning generates a limited amount of oxygen radicals, and that these turn on signalling pathways in the cell that regulate certain protective genes. Genes that encode antioxidant and other anti-stress pathways are likely to be important, but so are genes that prepare the cell to enter the cell cycle and divide into new cells that regenerate the liver. Conversely, genes that program cell death may be turned off. The outcomes of this research will be to understand the molecular and cellular basis of how preconditioning protects against ischemia-reperfusion injury of the liver. This will allow drug treatments to be devised that, by simulating preconditioning, prevent this common and severe type of liver damage.Read moreRead less