A Program Of Research Addressing The Transition From Health To Advanced Cardiovascular Disease.
Funder
National Health and Medical Research Council
Funding Amount
$13,017,057.00
Summary
Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treat ....Cardiovascular disease (CVD) is the major cause of death and disability in Australia and worldwide. This burden will increase without new knowledge. We will address knowledge gaps that delay more effective prevention and control. Our team has a strong track record of influencing clinical practice of CVD prevention, treatment and technology transfer. For many, the first indication of a heart problem is sudden heart attack or death. By understanding mechanisms we aim to develop new tests and treatments that prevent heart attack, heart failure and other serious consequences of atherosclerosis.Read moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
The Role Of Diffuse Myocardial Fibrosis In Myocardial Stiffness
Funder
National Health and Medical Research Council
Funding Amount
$378,032.00
Summary
Collagen, a major component of scar, accumulates in some hearts and we may expect this to increase stiffness, threatening heart function. We have shown poor heart relaxation correlates with increased collagen on heart magnetic resonance imaging (MRI). We aim to establish a link between MRI findings and direct measures of heart stiffness, a link between degree of stiffness and amount of collagen and effects of anti-fibrotic therapy on heart collagen; aiding diagnosis, prognosis and outcome.
Annexin-A1 Agonists Rescue Cardiac Contractile Function After Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$621,419.00
Summary
Myocardial infarction (or heart attack, a result of reduced coronary blood flow) and subsequent heart failure are the major cause of death in Western societies; this is expanding to all corners of the globe. New treatments for heart attack are thus essential. We have discovered that the natural hormone annexin-A1 rescues heart muscle function over the short-term, and propose that drugs based on annexin-A1 will prevent cardiac dysfunction of heart muscle up to several weeks after heart attack.
The Effect Of Dietary Fatty Acids On Cellular Calcium Handling Mechanisms In Cardiac Muscle
Funder
National Health and Medical Research Council
Funding Amount
$275,765.00
Summary
A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from ....A major health problem in the developed countries is cardiovascular disease, which is manifest as high blood pressure, stroke, heart attack and abnormalities of heart rhythm, or cardiac arrhythmias. A western diet, ie. one high in animal fat, or saturated fats, may be to blame. Human epidemiological studies have shown that consumption of a diet high in saturated fats is correlated with a propensity to arrhythmias while a diet high in polyunsaturated fatty acids (PUFAs) can confer protection from coronary heart disease and cardiac arrhythmias. The mechanisms underlying these effects are not fully understood. The contraction of the heart depends on changes in calcium inside the individual muscle cells. Abnormalities of the way calcium is handled in the cells leads to abnormalities of contraction and to a certain types of arrhythmia. Over the last 5 to 10 years, technological developments have enabled us to examine changes in calcium in living heart cells at microscopic level. It is possible to fill individual living cells with a fluorescent dye which changes either the magnitude or the wavelength of its fluorescence according to the ambient calcium concentration. Cells filled with these dyes are examined with a laser scanning confocal microscope, in which a very tightly focussed laser beam excites the dye and the resulting fluorescence is gathered by a computer controlled image analysis system. In this way we can measure the calcium concentration within the cells with a spatial resolution of about 1-1000 of a millimetre, and a time resolution of about 1-100 of a second. Using these techniques, we have found that supplementing the diet of rats with either PUFAs or saturated fats produces a dramatic change in the way that calcium is stored and released in their heart cells. This effect of dietary fats has not been reported before, and it may represent an important clue as to how these substances protect against many cardiac arrhythmias.Read moreRead less
Role Of Microparticles In Cardiac Ischemia Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Interventional cardiology has reduced the mortality rate associated with heart attack, unfortunately the prevalence of heart failure has subsequently increased, caused in part by reperfusion injury of previously occluded vessels. We aim to identify novel insights into the pathogenesis of IR injury in the heart, as well as the development of new approaches to prevent cardiac damage during cardiac surgery, transplantation, post-angioplasty and coronary artery stenting.
Enhanced Vascularisation And Growth Of Stem Cell Derived Human Myocardial Grafts
Funder
National Health and Medical Research Council
Funding Amount
$382,346.00
Summary
300 000 Australians currently have heart failure with 400 new cases weekly. New therapies are urgently needed. We can now create heart muscle grafts that can be transplanted after ñheart attackî but graft survival in this hostile environment is low. This project will investigate use of different combinations of human cell types that will cooperate together to improve survival/function of heart muscle grafts, advancing this promising strategy towards being a viable new treatment for heart failure
Macrophage Migration Inhibitory Factor (MIF): Pathological And Therapeutic Significance In Post- Infarct Inflammation
Funder
National Health and Medical Research Council
Funding Amount
$547,577.00
Summary
Ischemic heart injury mediated by the inflammatory response has a significant impact on the prognosis. MIF is a central factor mediating and amplifying the inflammatory response but its role in heart disease remains largely untested. This project will study, for the first time, the crucial role of MIF in ischemic heart disease and will establish important experimental evidence for developing new anti-inflammation therapeutic strategies against ischemic heart injury.
Research Fellowship: Protection Of Myocardial Function In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$631,010.00
Summary
Heart failure (HF) is a major cause of death in Australia. A/Prof Rebecca Ritchie heads Heart Failure Pharmacology at Baker IDI. Her research focuses on new drug strategies to maintain heart function in response to diabetes & heart attack, common precursors of HF. Many of the treatments discovered from this work are naturally-occurring antioxidants; enhancing their activity will ultimately reduce progression to HF & death in the >3 million Australians affected by these disorders.
Determinants Of Tissue Response To Nitric Oxide In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$385,432.00
Summary
The endothelium, or inner lining layer of blood vessels, exerts a controlling influence on the tendency of blood vessels to constrict or dilate, and on the likelihood that clots will form by aggregation of platelets within the blood vessel. This process is largely mediated by release of nitric oxide (NO) from the endothelium. Importanly, NO is also the active chemical formed when patients are given nitroglycerine (NTG) for the treatment of angina pectoris. There is evidence that conditions predi ....The endothelium, or inner lining layer of blood vessels, exerts a controlling influence on the tendency of blood vessels to constrict or dilate, and on the likelihood that clots will form by aggregation of platelets within the blood vessel. This process is largely mediated by release of nitric oxide (NO) from the endothelium. Importanly, NO is also the active chemical formed when patients are given nitroglycerine (NTG) for the treatment of angina pectoris. There is evidence that conditions predisposing towards development of angina or of heart attacks (such as high cholesterol levels or high blood pressure) are associated with dysfunction of the endothelium, so that less NO is available. The precise cause of this process is uncertain. However, our recent experiments show that in patients with angina, circulating platelets respond poorly to NO. The research to be undertaken will explore the link between blood vessel and platelet function, examing the impact of race (Aboriginals compared to Caucasians) and coronary risk factors. It will also examine the implications of endothelial dysfunction on initial and long-term responses to NTG. The results will shed light on factors predisposing to development of heart attacks, and identify factors preventing optimal responses to anti-anginal treatment.Read moreRead less