NOVEL CGMP-BASED THERAPIES PREVENT LEFT VENTRICULAR REMODELLING
Funder
National Health and Medical Research Council
Funding Amount
$533,433.00
Summary
Over 300,000 Australians are affected by heart failure. Current drugs for cardiac remodelling (the decline in heart pumping function and changed structure that precede heart failure) slow but not reverse disease progression. We have identified a new, nitrovasodilator-based therapy superior to those currently available. We propose it represents a more effective treatment for reversing abnormalities in both structure and function in the remodelled heart, preventing or delaying heart failure.
TARGETING ROS-INDUCED DAMAGE RESCUES THE DIABETIC HEART
Funder
National Health and Medical Research Council
Funding Amount
$487,669.00
Summary
Over 1 million Australians have diabetes. Many of these patients die from cardiovascular disease. We have identified free radicals as a major cause of decreased pumping function and impaired recovery from each heartbeat in the diabetic heart. Stronger antioxidant approaches and-or activation of protective protein pathways is a more effective treatment for reversing impaired function in the diabetic heart, preventing or delaying heart failure in patients with diabetes.
Heart-lung Interactions Determine Right Ventricular Function In The Perinatal Period.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, ....Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, as many as 5,000 require intensive care primarily for cardiorespiratory complications. Accurate diagnosis and effective treatment of these infants demands knowledge of the normal heart adaptations that accompany birth, adaptations that are critically linked to the way in which the heart and the lungs interact. This project investigates how interactions between the heart and the lungs determines heart function throughout life. By understanding this process we will provide essential information that will aid the diagnosis and treatment of sick neonates undergoing intensive care.Read moreRead less
Structural And Functional Consequences Of Left Ventricular Hypertrophy Regression.
Funder
National Health and Medical Research Council
Funding Amount
$293,036.00
Summary
Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and s ....Left ventricular hypertrophy (LVH) is a thickening of the heart muscle walls that occurs in a variety of cardiovascular diseases, including high blood pressure, coronary artery disease, cardiac valve disorders and heart dilatation. The presence of LVH increases the risk of developing heart attacks, heart failure and death. Treatment of these disorders is a major component of our escalating health-care costs. Consequently, reversal of LVH may have significant benefits to individual patients and society in general. We propose to develop a mouse model of an inherited form of LVH that is caused by gene mutations in heart muscle proteins. This model will enable us to study in detail the disease processes that cause LVH and the effects of reversing LVH. This information will be invaluable for determining the best ways of treating patients with LVH.Read moreRead less
Value Of Central Blood Pressure For GUIDing ManagEment Of Hypertension (BP GUIDE Study)
Funder
National Health and Medical Research Council
Funding Amount
$339,553.00
Summary
A pressure pulse may be felt at the wrist with every heart beat. New technology allows the analysis of this pulse and measurement of blood pressure (BP) at the heart (central BP) . This information may help doctors improve the decision making process regarding a patient's risk related to BP as well as the effect of drug treatment. The study aims to test this theory. It is expected that the new technology will improve the way people with high BP are identified and treated.
Regulatory Pathways Of Compensatory Left Ventricular Hypertrophy
Funder
National Health and Medical Research Council
Funding Amount
$309,536.00
Summary
An increase in muscle bulk (hypertrophy) of the major pumping chamber of the heart, the left ventricle, occurs as a compensatory mechanism to maintain cardiac function in a wide variety of common cardiovascular diseases, such as hypertension. Nevertheless, this compensatory mechanism appears to be strongly associated with an increased risk of death from cardiovascular disease. Consequently, the prevention or reversal of left ventricular hypertrophy is one of the major goals of the treatment of p ....An increase in muscle bulk (hypertrophy) of the major pumping chamber of the heart, the left ventricle, occurs as a compensatory mechanism to maintain cardiac function in a wide variety of common cardiovascular diseases, such as hypertension. Nevertheless, this compensatory mechanism appears to be strongly associated with an increased risk of death from cardiovascular disease. Consequently, the prevention or reversal of left ventricular hypertrophy is one of the major goals of the treatment of patients with cardiovascular disease. This project aims to improve our understanding of the complex chemical messengers in the heart muscle that control the development of hypertrophy to provide a basis for more specific drug treatments to control this process, with the aim of reducing the morbidity and mortality associated with hypertrophy.Read moreRead less
Utility Of Direct Endocardial Visualisation To Characterise Scar Morphology And Ablation Lesion Formation
Funder
National Health and Medical Research Council
Funding Amount
$421,285.00
Summary
Endocardial visualisation is a new technique in which a catheter is used to look at the internal surface of the heart without the need for surgery. We will use the visualisation catheter to find a better way of placing small burns within the heart to stop atrial fibrillation (one of the most common heart diseases). We will also use the visualisation catheter to find a better way of locating the scarred areas of the heart responsible for ventricular tachycardia (another common heart disease).
Controlling the concentration of calcium inside cells is extremely important for normal cell function. For example, a brief increase in calcium concentration inside muscle cells is essential for muscle contraction and the normal heart beat. This calcium is kept stored in sacs inside cells and is rapidly released when needed through calcium channels known as ryanodine receptors. We have discovered that some proteins (glutathione transferases and intracellular chloride channel proteins) inside cel ....Controlling the concentration of calcium inside cells is extremely important for normal cell function. For example, a brief increase in calcium concentration inside muscle cells is essential for muscle contraction and the normal heart beat. This calcium is kept stored in sacs inside cells and is rapidly released when needed through calcium channels known as ryanodine receptors. We have discovered that some proteins (glutathione transferases and intracellular chloride channel proteins) inside cells can affect how much calcium flows through these calcium channels. The proteins were thought to have other functions and our discovery of their effect on ryanodine receptor calcium channels has caused considerable excitement. We now plan to explore how they do this. We will mutate specific regions of the proteins to discover which regions are important and which are not. We will also look at whether closely related proteins have similar effects. The new class of ion channel modulator that we are studying has the capacity to alter not only respiration, movement and cardiac contraction, but also other aspects cardiovascular function, neuronal activity and immune responses. Understanding the way in which soluble proteins can interact with ion channels may reveal a novel target for drugs that affect ryanodine receptor calcium channel function and allow the rational design of specific drugs to regulate ion channels or ion channel modulators.Read moreRead less
Unique Isoform-specific Regulation Of Cardiac Ryanodine Receptors By Calcium Store Proteins
Funder
National Health and Medical Research Council
Funding Amount
$421,160.00
Summary
The importance of proteins that regulate calcium stores of heart muscle is graphically illustrated by massive changes in cell structure and function, which lead to ventricular fibrillation and fatality when the proteins are disrupted. We recently made the remarkable discovery that the proteins have a unique action in the heart which enhances cardiac contraction. We will discover the interaction sites between the proteins and will define novel therapeutic targets for heart failure.