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Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cell ....Atherosclerosis (hardening of the arteries) is the principal cause of heart attack, stroke and blockage of blood flow to the lower limbs. However, to date none of the biological or synthetic grafts used to bypass the narrowed regions of arteries is ideal. We have shown that lengths of silicone tubing placed into the peritoneal cavity of rats or rabbits becomes covered within 2 weeks by a capsule of granulation tissue (smooth-muscle-like cells and collagen) and mesothelial (endothelial-like) cells. The silicone tubing can be removed and the tissue turned inside out such that the endothelial-like cells now line the inside of the tube of living tissue, which resembles a blood vessel. These artificial blood vessels will be grown in the peritoneal cavity of rabbits, then grafted into the right carotid artery to replace a length of removed vessel. Their long-term (3,6,9 and 12 months) patency, reactivity, tensile strength and resistance to clot development will be assessed. Their susceptibility to atherosclerotic plaque development and blockage (as compared with natural carotid artery) will be examined in rabbits fed a cholesterol-enriched diet. Changes in gene expression as the artificial artery progressively develops will be examined, as will the potential to genetically manipulate the artificial artery to improve its functioning. Finally, attempts will be made to grow the vessels entirely in vitro. This novel vascular graft may open new options in the field of arterial reconstructive surgery for replacing or bypassing diseased vessels or as an access vessel for haemodialysis patients with end stage renal failure. This study will also provide new information on the biology of cells found in the peritoneal cavity and their alternative pathways for differentiation.Read moreRead less
This study is testing two drugs in people having heart surgery, to see whether either can reduce serious complications such as heart attack, stroke or death. Aspirin thins the blood and can reduce these risks but it increases bleeding during surgery. Another drug can reduce bleeding, but it may counteract the benefits of aspirin. The study is being done at more than 20 hospitals in Australia and around the world.
Origin Of Cells In The 'artificial' Artery Grown In The Peritoneal Cavity
Funder
National Health and Medical Research Council
Funding Amount
$489,000.00
Summary
Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the s ....Implantation of a foreign object (such as a sterile, flexible plastic tube) into the abdominal cavity of animals induces cells floating in the peritoneal fluid to form a capsule around the object. Over the next 2-3 weeks, the cells differentiate into fibroblasts then myofibroblasts. When this capsule of living tissue (in the appropriate moulded shape) is subsequently grafted into smooth muscle-rich organs such as artery, bladder, uterus or vas deferens to replace excised segments, it gains the structure of the surrounding tissue and the myofibroblasts differentiate further into functional smooth muscle. This raises the question: what is the origin of the cells of the capsule? Our previous studies suggested that monocyte-macrophages stimulated to enter the abdominal cavity in response to the sterile foreign body might be the source of the cells. In the current study we will use transgenic (c-fms EGFP and c-fms Cre Z-AP) mice in which cells of monocyte-macrophage lineage are genetically labelled. These cells can be clearly distinguished from all other cells of the body, and analysis of capsules formed around foreign bodies will give us a definitive answer. We will using micro-array analysis, determine which growth factors-cytokines are important in regulating differentiation of the cells, and the role of physical factors (eg pulsatile stretching). Finally, we will determine whether these cells stimulated to enter the abdominal cavity are capable of differentiating along alternative pathways, such as cardiac muscle or liver cells. Knowledge gained will further the use of the abdominal cavity as a bioreactor in which to engineer tissues for organ replacement therapies. Identification of the mechanisms regulating the (trans)differentiation and biology of the cells may also assist in wound repair strategies to prevent pathologies caused by excessive myofibroblast accumulation and fibrosis.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
Investigation Of Insulin Resistance In Cardiac Surgical Patients - Abnormalities In Nitric Oxide Metabolism Are Associated With Insulin Resistance, And May Contribute To Clinical Cardiovascular Disease In Insulin Resistant Patients
Funder
National Health and Medical Research Council
Funding Amount
$74,439.00
Summary
Insulin resistance and diabetes are strongly associated with developing heart disease. Changes in the metabolism of a substance in blood vessels called nitric oxide are seen in diabetes, and are related to heart disease. I will study the relationship between the levels of insulin resistance and markers of nitric oxide metabolism in human subjects, and investigate how this relates to their clinical outcomes after cardiac surgery.
Structural And Functional Alterations Of Sarcomeric Proteins In Reperfused Myocardium
Funder
National Health and Medical Research Council
Funding Amount
$271,786.00
Summary
Coronary artery disease remains the major cause of mortality for the adult population in our society. Despite the advances of coronary artery bypass surgery and medical treatment for reperfusion of occluded coronary arteries, the problem of impaired pump function of the heart remains a major obstacle. Although blood flow can be restored to the jeopardised heart muscle by either clot dissolving drugs, balloon angioplasty, or coronary artery surgery, the heart muscle may not regain pump function f ....Coronary artery disease remains the major cause of mortality for the adult population in our society. Despite the advances of coronary artery bypass surgery and medical treatment for reperfusion of occluded coronary arteries, the problem of impaired pump function of the heart remains a major obstacle. Although blood flow can be restored to the jeopardised heart muscle by either clot dissolving drugs, balloon angioplasty, or coronary artery surgery, the heart muscle may not regain pump function for days to weeks after the event. This delayed recovery of pump function, known as myocardial stunning, can lead to heart failure and slow down a patient's recovery from heart surgery or heart attack. The cause of this myocardial stunning is unknown. We suggest that stunning results from damage to essential proteins in the contractile apparatus of the heart, which requires a prolonged time period for repair. This project aims to identify the site and extent of protein damage occurring in the heart following interruption and subsequent restoration of cardiac blood flow. In concert with this, we seek to determine the mechanism of protein damage. The findings of this project should allow us to subsequently investigate new treatment approaches for acute pump dysfunction in patients with ischaemic heart disease.Read moreRead less
Evaluation Of Long-Term Clinical And Health Service Outcomes Following Coronary Artery Revascularisation In Western Australia: Future Implications
Funder
National Health and Medical Research Council
Funding Amount
$638,412.00
Summary
Heart attacks occur when arteries of the heart become blocked, and current treatment involves unblocking the affected vessel by inserting a stent fed through a leg artery or using bypass surgery. There are different types of stents and whether they offer better outcomes than surgery in the long-term is currently undecided. We will evaluate whether patients who receive stents have better outcomes after 5 years than patients who have surgery, and what the various costs are to the health system.
Human RIPC-derived Regulatory Molecules For Cardioprotection Against Ischemic And Cardiopulmonary Bypass Injury
Funder
National Health and Medical Research Council
Funding Amount
$642,083.00
Summary
Our previous work indicates that evoked human blood borne factors confer protection against injury, due to loss of blood flow in heart muscle, when a brief stress is remotely applied to a limb (remote ischemic preconditioning). We have identified these proteins that appear to activate genetic and metabolic regulation of adaptive cell survival processes. We will now test their individual and combined capacity, efficiency and mechanisms of protection in the heart using cell and clinical models.
Evaluation And Planning Of Coronary Revascularization Services.
Funder
National Health and Medical Research Council
Funding Amount
$591,527.00
Summary
This project concerns operations to unblock or bypass the coronary arteries that supply the muscle of the heart. The project has two parts. One is concerned with checking that changes in medical and surgical treatment of coronary artery disease have been followed by improvements in survival of affected patients. The second will use data on changes in the Australian population, changes in the frequency of heart disease and changes in treatments for heart disease to predict how many coronary opera ....This project concerns operations to unblock or bypass the coronary arteries that supply the muscle of the heart. The project has two parts. One is concerned with checking that changes in medical and surgical treatment of coronary artery disease have been followed by improvements in survival of affected patients. The second will use data on changes in the Australian population, changes in the frequency of heart disease and changes in treatments for heart disease to predict how many coronary operations will be needed in Australia over the next decade. This is a vital step in planning hospital services for patients with coronary disease.Read moreRead less