Regulation Of The Cardiac Sodium/proton Exchanger During Ischaemia, Reperfusion And Preconditioning
Funder
National Health and Medical Research Council
Funding Amount
$101,000.00
Summary
Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transp ....Heart attacks are currently treated with drugs to dissolve the clot in the coronary artery or by catheterisation with the aim of restoring blood flow to the ischaemic heart muscle. If restoration of blood flow occurs soon after the heart attack, the ischaemic region can recover completely. However if treatment is delayed, the ischaemic region may not recover. This project concerns the mechanisms that are involved in the myocardial damage which occurs after moderate periods of ischaemia. A transport protein, the sodium-proton exchanger, is involved in recovery and if its action is blocked with an inhibitory drug, recovery of the ischaemic myocardium is improved. However clinical trials of the drug in humans have given variable results. We are investigating the regulation of this exchanger and believe that such information is essential to the efficient use of the inhibitory drugs in humans and may identify other pathways to improving recovery after ischaemia.Read moreRead less
Preventing Myocardial Infarction: A Mouse Model Of Atherosclerotic Plaque Instability/rupture As Unique Tool For Establishing Novel Pharmacological Strategies And Targeted Molecular Imaging
Funder
National Health and Medical Research Council
Funding Amount
$586,965.00
Summary
Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarctio ....Myocardial infarction strikes without warning and thereby causes death or major disability. It is typically caused by sudden rupture of atherosclerotic plaques and occlusion of coronary arteries. Research on this was hampered by the lack of an animal model of plaque rupture. We have newly established a mouse model, which we will now use to generate novel tools to image and identify plaques that are prone to rupture and to develop novel therapies preventing plaque rupture and myocardial infarction.Read moreRead less
Novel Selective Anti-platelet And Clot-specific Anticoagulant Strategies Targeting Conformational States Of GPIIb/IIIa
Funder
National Health and Medical Research Council
Funding Amount
$496,517.00
Summary
The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding compl ....The inhibition of platelets and the inhibition of coagulation factors are among the most widely used drugs in medicine and provide major benefits for numerous patients. Prevention and treatment of thrombosis, emboli, stroke and heart attack are examples of the many diseases where anti-platelet and anticoagulant drugs are administered. However, the downsides of these drugs are bleeding complications, which can result in death or disability. The consequences of these drug-associated bleeding complications are also a major financal burden for our health care system. Thus, progress towards therapeutic strategies with less bleeding complications is highly sought-after. The proposed project aims to generate new antibody-based agents for platelet inhibition. One group of these agents do only block platelets when they are activated. Furthermore, these agents allow an enrichment of potent inhibitors of coagulation factors at the site of the clot. Thus, these inhibitors should predominatly act at the site where they are needed. At the same time the overall concentration of inhibitors of coagulation factors can be kept low and the functions of non-activated platelet can be left intact. Overall, the proposed project aims for the development of novel anti-platelet and anticoagulant strategies with high anti-thrombotic efficacy and low bleeding risks.Read moreRead less
Microvascular Function And Outcome In Patients With Acute Coronary Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$79,514.00
Summary
Damage to the small vessels of the heart is a hallmark of heart attacks. Furthermore, small vessel dysfunction (MVD) is associated with a worse prognosis even in the presence of an unblocked major coronary artery following a heart attack. Using novel invasive assessments, we aim to analyse the prevalence and clinical predictors of MVD, assess the impact of MVD on short and long-term outcome after heart attack and address the impact of new treatments on MVD and heart muscle recovery.
The Access Project - Assessment Of Coronary Artery Disease Using CT Effectively For Stable Symptoms
Funder
National Health and Medical Research Council
Funding Amount
$754,369.00
Summary
Invasive Coronary Angiography (ICA) provides x-ray visualisation of coronary disease (CAD) that is essential for coronary surgery/balloon angioplasty. However many patients undergo this procedure without requiring these therapies despite the associated severe complications. The ACCESS Project screens patients scheduled for ICA, identifying those unlikely to have CAD and referring them for non-invasive CT angiography. This strategy reduces procedure complications and result in major cost savings.
Studying Coronary Physiology Within Human Coronary Arteries Using Computational Fluid Dynamics
Funder
National Health and Medical Research Council
Funding Amount
$383,834.00
Summary
The aim of this project is to combine the recent technological advances within the individual fields of coronary physiology, three-dimensional coronary angiography, and computational fluid dynamics to develop a novel method to calculate realistic coronary blood flow. This technique will provide a simple and clinically applicable method to measure physiological parameters such as microcirculatory resistance and shear stress within _live� human coronary arteries.
Structural And Functional Studies On The Interaction Between Alpha2-Antiplasmin And Plasmin
Funder
National Health and Medical Research Council
Funding Amount
$280,400.00
Summary
Fibrinolysis is the process by which the body dissolves clots. In this proposal we aim to investigate how the fibrinolysis inhibitor alpha2-antiplasmin interacts with the clot dissolving protease enzyme plasmin. These data will be useful for developing new approaches to accelerate plasmin-mediated clot breakdown.
Investigation Of A New Platelet Contractile Mechanism Regulating Thrombus Stability
Funder
National Health and Medical Research Council
Funding Amount
$499,670.00
Summary
Platelets are small blood cells that form clots to stop bleeding. We have found a new contraction process that causes tight packing of platelets in a clot, enabling the clot to avoid detachment under blood flow. We will study this process and explore the possibility that its inhibition may provide a new way in which to loosen clots, promoting their removal. These studies will provide new insight into clot stability, and may provide clinical benefit in the delivery of clot dissolving agents .
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.