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
In Vivo Evaluation Of Coronary Atheroma Burden And Its Association With Focal Coronary Endothelial Function
Funder
National Health and Medical Research Council
Funding Amount
$123,736.00
Summary
Heart attacks remain the leading cause of death in the western world. It has been recently identified that the burden of plaque buildup in the coronary arteries is a major predictor of future heart attacks. Furthermore, it also known that impaired relaxation within the coronary arteries also increases the future risk of heart attacks. The dynamic relationship between these two critical factors remains unknown and an understanding of this is important for predicting future heart attacks.
Effects Of Risk Factor Control On Atherosclerosis, Vasoreactivity And Cardiac Ischemia In Patients On Dialysis
Funder
National Health and Medical Research Council
Funding Amount
$212,126.00
Summary
End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing i ....End-stage renal failure is one of the commonest serious chronic diseases; in Australia, over 10,000 patients are in dialysis programs or have functioning transplants. The commonest cause of death in this patient group is coronary artery disease, and attempts are routinely made to identify patients with this problem, with the intent of controlling this risk by angioplasty or bypass surgery. Unfortunately, these procedures may be less effective than usual, because the process of artery narrowing is more aggressive in patients with renal disease. Moreover, this process may cause patients with negative testing for coronary disease at one point in time to develop coronary problems over follow-up. In this study, we propose to use a standard stress testing protocol to stratify the risk of coronary events in a group of at risk patients on dialysis. Those at highest risk will undergo bypass surgery, while those at intermediate and low risk will be randomized to usual care, or an aggressive treatment of atheroma with cholesterol reduction, folic acid supplementation (aiming to normalize homocysteine), blood pressure and blood sugar control. The effects of this approach will be followed by examination of biochemical markers of atherosclerosis, and imaging of arterial thickness and reactivity (reflecting tests of structure and function of the vasculature). We will also assess of the progression or reduction of abnormal cardiac stress responses, and the occurence of events at follow-up. Finally, follow-up data will be used to compare the predictive value of the 2 stress testing protocols. The results of this study will enhance our understanding of the importance of the atherosclerotic process in renal patients, and move the management approach for coronary disease in renal failure toward active risk factor control and away from revascularization.Read moreRead less
Coronary Atherosclerosis And Its Relationship With Platelet Activation
Funder
National Health and Medical Research Council
Funding Amount
$101,039.00
Summary
Blood clots are critical to the development of heart attacks, which kill many thousands of Australians annually. Platelets are cells in the blood that play an essential role in formation of blood clots, and coronary disease is associated with platelet activation. This research study will investigate the nature of platelet activation in the arteries of the human heart, its relationship to activation of inflammatory cells, and to the severity of narrowings in the arteries of the human heart.
Adenosine A1 And A3 Receptor Mediated Cardioprotection In Ischaemic Myocardium
Funder
National Health and Medical Research Council
Funding Amount
$265,698.00
Summary
Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, ....Damage to the heart from coronary vascular disease causes significant morbidity and mortality in Australia. Indeed, ischaemic injury represents the single greatest cause of premature death. Moreover, due to the increasing age of our population the problem is growing - coronary artery disease affects 50% of those older than 65, contributing to an increased incidence of angina pectoris, myocardial infarction, arrhythmia, congestive heart failure, and sudden death. Protective strategies have been, and continue to be, developed to reduce the extent of tissue damage and minimise prolonged reductions in heart function. The success of these interventions has been mixed. This research project takes the novel approach of identifying the true roles of two receptors present in the heart (the adenosine A1 and A3 receptors) which may play a crucial role in enhancing tolerance of the heart to disease and injury. We currently do not fully understand the roles of these receptors, although preliminary findings suggest they can exert powerful protective effects during disease conditions. From a fundamental viewpoint, identifying the roles of these two receptors will significantly advance our understanding of the mechanisms of injury and protection in the heart. From a therapeutic viewpoint, this study will take us closer to the potential use of adenosine receptor-based therapy in protecting the heart from ischaemic injury.Read moreRead less
The Importance Of P38 MAPK Signalling In Aging-Related Ischaemic Intolerance And Failed Cardioprotection
Funder
National Health and Medical Research Council
Funding Amount
$496,302.00
Summary
Ischaemic heart disease is the leading cause of death in Australia, and will rise in coming years with the aging of our population. Our research shows aged hearts become less resistant to damage during ischaemia-heart attack, and insensitive to normally beneficial therapies. This project will identify molecular changes responsible for these changes. By understanding how age impairs the hearts defences, it may be possible to improve therapy of ischaemic heart disease in older patients.
Heart Failure And Its Antecedents: Pathophysiology, Prevention And Treatment
Funder
National Health and Medical Research Council
Funding Amount
$9,061,084.00
Summary
Heart failure is mainly a result of coronary artery disease. It is a major cause of disability and mortality in Australia and is projected to increase markedly over the next two decades. This program brings together clinical and basic science expertise to address aspects of the prevention and control of coronary disease and heart failure. The outcomes that will arise will provide a better understanding of the mechanisms involved in the progression from stable heart disease to failure.