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Stretch Induced Pulmonary Vein Remodelling: Implications For The Initiation And Maintenance Of Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$569,823.00
Summary
Atrial fibrillation (AF) is the most common heart rhythm disorder to affect humans, occurring in 2% of adults. It is a chaotic rhythm disorder of the top chambers of the heart that results in frequent hospitalization for falls, chest pain, palpitations, heart failure and stroke. In addition, it is associated with an increased mortality. Evidence suggests an important role of the pulmonary veins (PV; veins draining blood from the lungs back to the heart) in the initiation and maintenance of AF. H ....Atrial fibrillation (AF) is the most common heart rhythm disorder to affect humans, occurring in 2% of adults. It is a chaotic rhythm disorder of the top chambers of the heart that results in frequent hospitalization for falls, chest pain, palpitations, heart failure and stroke. In addition, it is associated with an increased mortality. Evidence suggests an important role of the pulmonary veins (PV; veins draining blood from the lungs back to the heart) in the initiation and maintenance of AF. However, why these structures promote AF remains unknown. Several conditions predisposing to the development of AF are associated with atrial stretch (such as heart failure). These conditions have documented abnormalities within the atria but the changes that occur within the PVs are unknown. It has even been suggested that pulsatile stretch, as caused by blood flow, in the appropriately predisposed patient, may be enough to trigger AF. As such there has been an intensive search to identify the abnormalities that occur within the PVs. In patients with AF, the PVs demonstrate distinctive electrophysiological properties compared to those without AF. However, the effect of stretch, a common predisposing factor, on the electrophysiological properties of the PV is not known. Preventing electrical activity from the PVs interacting with the heart by ablation has provided a glimpse at our ability to cure AF. However, further improvements in our procedural technique, the ability to prevent the occurrence of this rhythm disorder, and the development of noninvasive strategies to cure AF, hinges on the better understanding of the mechanisms initiating and maintaining this condition. In particular, the electrophysiological changes within the PVs that predispose patients to the development of AF need to be investigated. This series of studies will evaluate the effect of acute and chronic stretch on the PVs in humans to determine why these structures promote AF.Read moreRead less
Randomized Controlled Trial Of CPAP On Cardiac Function In Patients With Heart Failure And Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$140,906.00
Summary
Heart failure is a very common condition associated with disabling symptoms. The main symptoms are breathlessness, usually during sleep or upon exercise, and fatigue. Recent research has identified that sleep apnoea, a condition that occurs in about 50% of subjects with heart failure, is likely to be responsible for these symptoms. Moreover, treatment specifically aimed at sleep apnoea, namely continuous positive airway pressure (CPAP) delived via a small electric pump and nasal mask worn during ....Heart failure is a very common condition associated with disabling symptoms. The main symptoms are breathlessness, usually during sleep or upon exercise, and fatigue. Recent research has identified that sleep apnoea, a condition that occurs in about 50% of subjects with heart failure, is likely to be responsible for these symptoms. Moreover, treatment specifically aimed at sleep apnoea, namely continuous positive airway pressure (CPAP) delived via a small electric pump and nasal mask worn during sleep, may also improve the symptoms of heart failure. The study will involve subjects with stable heart failure on optimal drug treatment who have evidence of obstructive sleep apnea on an overnight sleep study. Obstructive sleep apnoea (OSA) is a condition in which the throat intermittently narrows or blocks during sleep (often associated with snoring) causing cessation of airflow or apnoeas. Associated with the apnoeas are vigorous efforts by the chest muscles to breathe (creating negative vacuum-like pressures within the chest - and around the heart) at a time of falling oxygen levels. Previous research has suggested that these obstructive apnoeas are detrimental to the heart. Volunteers will be randomized to either a control or a CPAP treated group for a three month period. The control and CPAP groups will receive intensive advice about good eating and sleeping habits as weight gain and sleep loss are factors known to aggravate heart failure and obstructive sleep apnoea. In addition to the lifestyle advice, the CPAP group will also be treated with nasal CPAP. The variables which we will measure include severity of sleep apnoea, exercise capacity, heart function at rest and symptoms. Symptoms will be measured using 4 very detailed and validated questionnaires.Read moreRead less
Heart failure (HF) is the most common cause of hospital admission in those over 65y, and has significant morbidity and mortality. We need to develop new strategies to treat HF. Plasma vasopressin (AVP) levels are elevated in HF, and may contribute to adverse outcomes. This proposal will assess the utility of blocking the vasopressin V1 and V2 receptors in a rat model of HF. We shall also measure AVP in humans with HF. The results of this work may result in new approaches to treat HF patients.
Duty Ratio: A Simple Method For Quantifying Loop Gain During Breathing Instability
Funder
National Health and Medical Research Council
Funding Amount
$343,514.00
Summary
This proposal presents a new method for calculating the severity of sleep disordered breathing in patients. The proposal also tests the effectiveness of our method in experiments in animals and humans. The method, which requires no intervention in the patient, offers promise as a means for testing the efficacy of treatments for the unstable breathing pattern found in patients with heart failure in whom the presence of unstable breathing is associated with poor outcome.
Coronary artery disease is the largest single cause of death in Australia, and commonly manifests as heart attack and angina. Congenital heart disease is the most common birth defect. We have identified a gene, Crim1, that is important for heart and coronary artery development. Investigating how this gene functions will lead to a greater understanding of congenital heart disease and may lay the foundation for therapeutics to regenerate damaged hear tissue.
Role Of Calcium Stores And Phosphate Channels In Muscle Fatigue
Funder
National Health and Medical Research Council
Funding Amount
$221,640.00
Summary
Muscles become weaker when ever they are used intensively; this is the familiar muscle fatigue. We are studying the mechanism of muscle fatigue and believe it is caused by depletion of a store of calcium inside the muscle. We suspect the store of calcium declines because phosphate, which is a product of muscle metabolism, enters the calcium store and precipitates as calcium phosphate. Currently we are trying to prove this hypothesis and extend it by studying the channels through which phosphate ....Muscles become weaker when ever they are used intensively; this is the familiar muscle fatigue. We are studying the mechanism of muscle fatigue and believe it is caused by depletion of a store of calcium inside the muscle. We suspect the store of calcium declines because phosphate, which is a product of muscle metabolism, enters the calcium store and precipitates as calcium phosphate. Currently we are trying to prove this hypothesis and extend it by studying the channels through which phosphate passes from the muscle cell into the calcium store. It may be possible to find or design drugs which minimise the movement of phosphate through this channel and such a drug might reduce the component of fatigue caused by this mechanism. Such a drug might benefit patients whose normal activities are limited by muscle fatigue; this includes patients with any disabling muscle disease, such as muscular dystrophy or stroke, and patients with heart failure. In addition elderly people suffer a loss of muscle bulk and the remaining muscle is easily fatigued causing loss of mobility and independence; so the elderly might also benefit from such a drug.Read moreRead less
Neural Control Of Renal Function: Functionally Specific Populations Of Sympathetic Nerves
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney wi ....The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney will causes different effects with in the kidney . We therefore suggest that salt excretion , the control of blood flow to the kidney and the release of hormones by the kidney can be seperately regulated by the nerves. Using techinques only practise in a handful of laboratories around the world, we aim to determine to how the nerves control kidney function normally. These studies will suggest new directions in which the renal nerves may be implicated in disease.Read moreRead less
Understanding The Role Of Supracollicular Nuclei In The Generation Of Basal Sympathetic Vasomotor Tone.
Funder
National Health and Medical Research Council
Funding Amount
$238,500.00
Summary
Increased activity from the parts of the brain which regulate blood pressure is observed in patients with cardiovascular diseases, including high blood pressure and heart failure. In some cases this increased activity might actually cause the high blood pressure. In all cases this increased activity can lead to serious complications including arrhythmias of the heart, enlargement of the heart and blood vessels, and even sudden cardiac death. This project aims to understand in more detail the par ....Increased activity from the parts of the brain which regulate blood pressure is observed in patients with cardiovascular diseases, including high blood pressure and heart failure. In some cases this increased activity might actually cause the high blood pressure. In all cases this increased activity can lead to serious complications including arrhythmias of the heart, enlargement of the heart and blood vessels, and even sudden cardiac death. This project aims to understand in more detail the parts of the brain that generate this activity. This information will enable more selective and effective treatments to be developed for people with high blood pressure or heart failure.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.
Congestive Heart Failure: A Longitudinal Study Of Its Impact On Brain Function And Structure In Later Life.
Funder
National Health and Medical Research Council
Funding Amount
$612,130.00
Summary
This project aims to clarify the long-term impact of congestive heart failure (CHF) on brain function and structure. CHF is a common complication of most diseases of the heart, with over 30,000 new cases being diagnosed annually in Australia. Of all CHF hospitalisations, 75% are made up of people aged 70 years or over. Consequently, as the Australian population ages, the number of people with CHF is expected to rise sharply. CHF is associated with increased mortality and significant morbidity. I ....This project aims to clarify the long-term impact of congestive heart failure (CHF) on brain function and structure. CHF is a common complication of most diseases of the heart, with over 30,000 new cases being diagnosed annually in Australia. Of all CHF hospitalisations, 75% are made up of people aged 70 years or over. Consequently, as the Australian population ages, the number of people with CHF is expected to rise sharply. CHF is associated with increased mortality and significant morbidity. It also impacts upon quality of life in other ways. The daily life of patients is often limited by the direct effects of CHF, such as exertional dyspnoea, fatigue and weakness; associated medical conditions, such as ischaemic heart disease, hypertension and diabetes, as well as depression and memory impairment. Of note, cognitive impairment is a leading cause of years of life lost due to disability in Australia. This project aims to clarify the factors that contribute to the development of cognitive deficits in people with CHF. Its results should serve as a basis for the development of effective preventative strategies to halt or slow down the development of such deficits. In addition, we expect that the findings of the study will improve our understanding of other common disorders associated with cognitive decline in later life, such as Alzheimer's disease.Read moreRead less