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.
Importance Of The Transmural Distribution Of Viable Myocardium To Outcome Of Patients After Revascularization
Funder
National Health and Medical Research Council
Funding Amount
$268,800.00
Summary
After a heart attack, up to 50% of tissue showing reduced function can recover if blood supply is returned to normal with bypass surgery or balloon angioplasty. Because these procedures may be risky in cardiac patients, the investigators have used various imaging approaches including radionuclide and ultrasound techniques to predict regions where function will recover after intervention. The results of these tests may be discordant because they assess separate attributes of cardiac muscle, and s ....After a heart attack, up to 50% of tissue showing reduced function can recover if blood supply is returned to normal with bypass surgery or balloon angioplasty. Because these procedures may be risky in cardiac patients, the investigators have used various imaging approaches including radionuclide and ultrasound techniques to predict regions where function will recover after intervention. The results of these tests may be discordant because they assess separate attributes of cardiac muscle, and selection of patients for intervention on the basis of recovery of regional function ignores some other aspects that may be important. These include avoidance of heart enlargement, improvement of exercise capacity, and avoidance of heart rhythm disturbances and even other heart attacks. In this study, the investigators seek to define the importance of the proportion and site of live (viable) myocardium to the parameters listed above. A new magnetic resonance technique will be used to identify whether radionuclide and ultrasound techniques assess different parts of the heart wall. The relative importance of these sites will be identified by comparing the outcome of patients who have live tissue in the inner half, compared with the outer half of the heart wall. This study will involve 180 patients who will undergo testing with magnetic resonance and radionuclide imaging. A subgroup will undergo dobutamine echocardiography. Their responses over follow-up will be assessed by accurate evaluation of heart size, exercise response, heart rhythm abnormalities and clinical events.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
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.
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
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.
Efficacy And Mechanisms Of Exercise Training In Diastolic Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$385,250.00
Summary
Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrom ....Heart failure is modern epidemic which presents a significant public health burden, due to a high mortality, frequent hospital admissions and impaired functional capacity. Although the typical heart failure patient presents with a reduced contractile function, many patients have typical heart failure symptoms but with normal contraction. The problem in these patients seems to relate to the heart's ability to fill with blood, and this entity is known as diastolic heart failure (DHF). This syndrome is most frequently due to ischemic or hypertensive heart disease, and most commonly occurs in the elderly. The optimal management of DHF is not well defined, although some drug trials are currently in progress. A number of studies have shown exercise training to improve functional capacity by 15-20% in typical heart failure. However, training has not so far been trialled in DHF. In this multicenter, multi-disciplinary study, we will study a training and control group to determine whether exercise capacity and DHF symptoms are responsive to exercise training. This work will teach us about the optimum exercise prescription, in terms of the duration and nature of training, as well as the safety and effectiveness of exercise training. By using a number of sensitive measurements of heart and vessel function (in which our group has special expertise), we will identify whether exercise training exerts its effect through improvement in vascular function and myocardial properties. If successful, the clinical implications of this study are that; 1. Exercise training will be adopted to improve functional capacity and symptoms of DHF 2. The merits of aerobic and strength training will be identified in DHF 3. Abnormal blood vessel function will be identified as a major and reversible contributor to DHFRead moreRead less
Cardiac-specific Therapy Targeting Hypertrophy And Apoptotis
Funder
National Health and Medical Research Council
Funding Amount
$542,683.00
Summary
We have discovered that certain pathological responses in the heart are mediated by an unusual type of signalling protein. The aim of the proposed studies is to determine whether this unusual signalling mechanism can provide a good target for development of new therapeutic approaches to prevent or treat heart failure.
Linking Early Heart Growth Stress And Adult Cardiopathology: A New Role For Autophagy
Funder
National Health and Medical Research Council
Funding Amount
$524,013.00
Summary
An enlarged heart at maturity is a major risk factor. The goal of this project is to understand how cardiac growth abnormality in the neonate contributes to adult growth pathology. We have recently discovered that a type of stress-triggered cell death (autophagy) is increased in rodent neonatal hearts which later become enlarged, and that this cell death is regulated by the hormone angiotensin II. We will study the mechanisms involved to identify intervention opportunities to normalize growth.
The Role Of Mechanoelectric Feedback In Cardiac Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$307,550.00
Summary
Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. ....Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. In fact, the electrical activity of the heart is influenced strongly by the degree and timing of stretch to which the heart muscle is subjected, a process called Mechano-electric feedback. Since it can be demonstrated in isolated tissues, mechano-electric feedback must be an intrinsic property of the heart muscle. It has been shown in isolated heart preparations that passive stretch produces electrical disturbances in the normal action potential shape and propagation and that these electrical disturbances can be powerful enough to generate severe arrhythmias. There are paralells in human diseases. For example, atrial arrhythmias are common in older people, and it seems that these may be due to chronic stretch of the atria, as a consequence of high blood pressure. In addition, in those patients recovering from a heart attack, it seems likely that the damaged part of the heart muscle subjects the surrounding tissue to unusual mechanical stresses, and may trigger arrhythmias. This project aims to investigate the mechanisms underlying this mechano-electric feedback, in an attempt to understand some types of arrhythmias. Using molecular biology techniques, we will look at the gene expression of a novel type of stretch-activated potassium channel in both healthy and diseased animal hearts, with the aim of seeing if changes in the level of expression of these channels is correlated with changes in the response of the heart to stretch.Read moreRead less