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Regulation Of RyR2 Channels By Calmodulin In Healthy And Diseased Hearts
Funder
National Health and Medical Research Council
Funding Amount
$614,421.00
Summary
In the heart, RyR2 is responsible for intracellular Ca2+ release. The RyR2 is comprised of a Ca2+ channel and accessory proteins such as CaM that regulate channel activity. Evidence suggests that RyR2 regulation by CaM is altered in heart failure and human arrhythmia syndromes, but there has been no direct evidence for this. We will provide this direct evidence plus determine how CaM regulates RyR2 channels and intracellular Ca2+ release and how this leads to cardiac arrhythmias.
CCR4/NOT Complex Is A Conserved Regulator Of Heart Function
Funder
National Health and Medical Research Council
Funding Amount
$467,567.00
Summary
Cardiovascular diseases kill an Australian every 11 minutes. The goal of this proposal is to characterize the role of the conserved heart regulators in cardiac function and disease. Our combined multi-species and informatics approach has identified a major disease locus for sudden cardiac death in humans, which we propose to characterize. This work can lead to new classes of drugs to improve cardiac health and also aid in early diagnosis of patients susceptible to sudden cardiac death.
Surgical Management Of The Pulmonary Circulation In Children
Funder
National Health and Medical Research Council
Funding Amount
$114,328.00
Summary
Congenital disorders of the lung circulation are rare. These children often present during infancy with symptoms of heart failure and require surgery to correct these defects. Without surgery, the prognosis of these conditions are poor. Our understanding of these conditions are limited. The proposed study aims to review all patients who underwent surgical repair of abnormalities of lung arteries and veins at the Royal Children’s Hospital.
Atrial Fibrillation And Hypertension: Reverse Cardiac Remodelling Post Renal Denervation
Funder
National Health and Medical Research Council
Funding Amount
$90,144.00
Summary
Patients with hypertension are at increased risk of heart rhythm disorders, yet little is known if treatment of high blood pressure will improve abnormal rhythm. Renal denervation is a new and effective treatment for severe hypertension; this study will assess the adverse changes in heart structure and function due to severe hypertension, and investigate whether renal denervation can ameliorate these changes on a structural and electrical level.
Genetic Predisposition To Abnormal Atrial Substrate In Atrial Fibrillation (GENE-AF Study)
Funder
National Health and Medical Research Council
Funding Amount
$100,531.00
Summary
Atrial fibrillation (AF) is the most common heart rhythm disorder worldwide and its incidence is growing. Our world-first research aims to demonstrate that individuals who carry specific genetic variants are more likely to develop abnormal electrical and structural changes in the heart, which predispose to AF. In doing so, we intend to find the link between genetics and AF, paving the way for research into novel targeted therapies to better manage this complex and difficult to treat disease.
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$10,053,131.00
Summary
Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as wel ....Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as well as integrated heart development, biology, physiology and function as a prerequisite for the development of major advances in the prevention and treatment of these disorders.Read moreRead less
Ryanodine Receptor Inhibitors As Therapy For Ca2+ Store Overload Induced Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$555,892.00
Summary
This study investigates a new therapeutic action recently discovered for flecainide, an antiarrhythmic agent that we find to completely prevent and inherited form of stress-induced arrhythmias called CPVT. The findings will provide the first detailed mechanistic understanding of an antiarrhythmic drug, findings that will also give a new direction for drug design to control common arrhythmias such as occur in diseases such as coronary artery disease.
Ventricular Remodelling In Cardiomyopathy _ Impact On Ventricular Physiology And Cardiovascular Outcome.
Funder
National Health and Medical Research Council
Funding Amount
$123,337.00
Summary
Diffuse myocardial fibrosis is the widespread deposition of scar tissue in heart muscle and is a common final pathway of cardiac disease. A new technique (contrast-enhanced T1 mapping) using cardiac magnetic resonance imaging can non-invasively detect this scarring. The proposed research intends to further determine the significance of diffuse myocardial fibrosis in cardiac disease, evaluate its link with diastolic heart failure and examine the potential therapeutic role of anti-fibrotic agents.
Single-Beat Preload Recruitable Stroke Work Measurement Of Cardiac Contractility In Three Mammalian Models.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
The accurate measurement of the inherent pumping capacity of the heart muscle is difficult because (i) most measurements currently in use cannot accurately discriminate between the contribution of the heart muscle and that of the vascular system to the results obtained, and (ii) the measurements which can discriminate currently require invasive measurements and procedures that frequently restrict their use. The overall purpose of this proposal is to more rigorously validate a promising method we ....The accurate measurement of the inherent pumping capacity of the heart muscle is difficult because (i) most measurements currently in use cannot accurately discriminate between the contribution of the heart muscle and that of the vascular system to the results obtained, and (ii) the measurements which can discriminate currently require invasive measurements and procedures that frequently restrict their use. The overall purpose of this proposal is to more rigorously validate a promising method we have developed that will (i) make accurate assessment possible from a single cardiac beat in both experimental animals and human subjects; (ii) reduce the number of experimental animals required for such measurements by permitting sequential measurements in the same animals; (iii) make it possible to perform such measurements non-invasively in human subjects.Read moreRead less