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
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.
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.
Optimizing Implanted Cell Survival Using A Tissue Engineering Model
Funder
National Health and Medical Research Council
Funding Amount
$589,175.00
Summary
Cell therapy and tissue engineering involve the insertion of specific cells into damaged tissues or into a bioraector in a patient's body to generate new replacement tissues. This project seeks to improve two factors associated with inserting cells : 1. The innate survival characteristics of the cells being inserted, and 2. The blood vessel supply at the site of insertion. These techniques will greatly improve the survival of inserted cells.
Alternative Insufflation Gases For Laparoscopic Surgery
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
It is now recognised that laparoscopic (keyhole) surgery for cancer can be associated with the spread of tumour to surgical wounds, i.e. port sites. However, whether this is more likely following laparoscopy than conventional open surgery is controversial. Isolated case reports and the recent results of experimental studies suggest that the problem is important. Previous studies suggest that carbon dioxide gas used to inflate the abdomen during laparoscopy may be the specific cause of this probl ....It is now recognised that laparoscopic (keyhole) surgery for cancer can be associated with the spread of tumour to surgical wounds, i.e. port sites. However, whether this is more likely following laparoscopy than conventional open surgery is controversial. Isolated case reports and the recent results of experimental studies suggest that the problem is important. Previous studies suggest that carbon dioxide gas used to inflate the abdomen during laparoscopy may be the specific cause of this problem. A four to fivefold increase in the rate of cancer spread has been shown in previous experiments, and this can be reduced by using an inert gas such as helium. We propose to further investigate this issue using a combination of small and large animal models, and will also commence clinical trials of helium during clinical surgery. These studies aim will determine the gas of choice during laparoscopic surgery. They will also clarify advantages demonstrated for the use of helium in previous animal studies, and better investigate the safety of helium use. If our preliminary findings are supported by these studies, helium (or other inert gases) should be considered for routine use during clinical laparoscopy.Read moreRead less
Reevaluation Of The Anatomy Of The Human Lymphatic Vessel Network
Funder
National Health and Medical Research Council
Funding Amount
$539,750.00
Summary
The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of ....The mode of spread of cancer cells from a primary tumour to other parts of the body is still not completely understood, although the lymphatic system is known to be important in this process. Lymph vessels are tiny transparent channels that form a network over the entire body. They transport tissue fluid to regional lymph glands in the neck, armpits, groin, chest and abdomen where the immune response maybe initiated to combat foreign agents such as bacteria and cancer cells. Current knowledge of the anatomy of these tiny vessels is based on work done by Sappey more than a century ago. There is an urgent need to update this work as many of his conclusions have been found to be inaccurate. We will use our pioneering methods of microsurgical tissue transfer- now being used worldwide - and our extensive experience in delineating fine channels, to address some of the basic questions about the anatomical pathways of spread of cancer. We hope to discover for example: why cancer on one side of the back can spread to glands in the opposite groin or armpit, thought by Sappey to be impossible; why cancer on one side of the tongue can spread to lymph glands on the opposite side of the neck; and why there is sometimes swelling of the limbs following lymph gland ablation by surgery or radiotherapy of glands in the groin or armpit. Currently it is thought that the only major connections with the venous system are at the base of the neck. Our initial work has shown unexpected connections with blood vessels in the periphery and unreported lymphatic vessel pathways between the skin and deep tissues. The results of this research will give information that will aid in localizing and treating the spread of malignancies and will underlie future treatment of obstructed lymph vessels that are the cause of painful, disabling swelling (lymphoedema) of the limbs.Read moreRead less
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
The Sentinel Lymph Node Territories Of The Whole Body And Their Clinical Implications: A Human Cadaver Study
Funder
National Health and Medical Research Council
Funding Amount
$602,984.00
Summary
Lymph gland screening with isotopes (Lymphoscintigraphy) has revealed unexpected pathways of cancer spread. This study, using an X-ray injection technique in human cadavers, is re-evaluating the outdated Melways Roadmap of lymph vessel pathways. The aims are to give accurate predictions of cancer spread, explain unusual clinical manifestations and to provide a new method of treating lymphoedema, the incapacitating swelling of limbs that may complicate lymph gland surgery or radiotherapy.
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