Central Aortic Blood Pressure In Children: Establishing A Gold Standard Non-invasive Assessment Of Cardiovascular Risk
Funder
National Health and Medical Research Council
Funding Amount
$694,342.00
Summary
The best way of assessing early risk of cardiovascular disease involves measuring blood pressure near the heart (central pressure), but existing devices used in adults for this purpose are inaccurate in children. We will develop a children-specific method and apply it to study early cardiovascular risk in a comprehensive health study of 2000 children Australia-wide. We will also investigate why children with congenital heart disease frequently develop ‘older-adult’ heart disease at a young age.
Evaluation Of The Efficacy And Safety Of Health Service Dialysate Sodium Practice On Clinical Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$1,958,205.00
Summary
Concerns the delivery of haemodialysis may be contributing to sodium retention and poor outcomes has led many health services to modify practice. However this modification is occurring in an unmeasured and haphazard manner leaving the impact unknown. This simple, pragmatic research will generate definitive evidence on the effect of health service dialysate sodium practices on the key clinical outcomes of death and cardiovascular events as well as health service utilisation.
Sleep loss and disordered sleep is now recognised as contributing to mortality, chronic disease and economic health burden. The CCRE in Interdisciplinary Sleep Health (CRISH) aims to investigate the biology of sleep, and to prevent and to treat disorders of sleep through a uniquely interdisciplinary approach. The centre will support world-class interventional research aimed to inform clinical practice and alter health policy. The next generation of sleep researchers will be fostered through nati ....Sleep loss and disordered sleep is now recognised as contributing to mortality, chronic disease and economic health burden. The CCRE in Interdisciplinary Sleep Health (CRISH) aims to investigate the biology of sleep, and to prevent and to treat disorders of sleep through a uniquely interdisciplinary approach. The centre will support world-class interventional research aimed to inform clinical practice and alter health policy. The next generation of sleep researchers will be fostered through national and international collaborations.Read moreRead less
THE VASCULAR CONSEQUENCES OF SNORING AND OBSTRUCTIVE SLEEP APNOEA
Funder
National Health and Medical Research Council
Funding Amount
$476,052.00
Summary
Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading ....Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading to cessation of breathing for short periods of time. Sleep apnoea is among the commonest chronic disorders of adult males occurring in 5% of men over the age of 45 years. Increasingly, it is now recognised that snoring, without sleep apnoea, may be an independent risk factor for the development of both of these very common and significant medical disorders. However, there have been no studies exploring the mechanisms by which snoring might contribute to the development of stroke and hypertension. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which is the main blood supply to the brain. We propose that the chronic vibration of this artery leads to disease such as atherosclerosis and hypertension. Our studies will help to prove that this is a common mechanism whereby both snoring and sleep apnoea may contribute to the development of important vascular diseases. Studies will also establish the prevalence of carotid atherosclerosis in snorers (with and without OSA), and the prevalence of habitual snoring and OSA in patients at risk of developoing completed stroke. The recognition of snoring as an independent risk factor for vascular disease will clearly have important and wide ranging implications for the future management of snoring in the prevention of stroke and hypertension.Read moreRead less
Vascular And Neurogenic Determinants Of Hypertension In Chronic Kidney Disease
Funder
National Health and Medical Research Council
Funding Amount
$508,142.00
Summary
You are as old as your arteries, and people with kidney disease have arteries that age fast. They also have overactive sympathetic nerves, and it is not clear if the blood vessels or nerves are responsible for the high blood pressure that puts strain on the heart and other organs of these patients. We will use an animal model to determine if therapy for hypertension reduces the stiffness of blood vessels or elevated nerve activity. Our results will enable better treatments for kidney failure.
THE AUTONOMIC, SOMATIC AND CENTRAL NEURAL RESPONSES TO DEEP AND SUPERFICIAL PAIN IN HUMAN SUBJECTS
Funder
National Health and Medical Research Council
Funding Amount
$375,750.00
Summary
Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes ....Pain is a subjective experience, the intensity of which can be readily influenced by personal experience. Despite this, pain originating from a particular part of the body will usually be described by all individuals as having similar character. For example, pain arising from the skin is commonly described as being sharp or burning and is usually easy to localise, whereas pain arising from muscle is commonly dull, throbbing and diffuse. In addition to producing sensory changes, pain also evokes changes in blood pressure, heart rate and motor activity (often in an attempt to remove the source of the pain). The proposed research aims to characterise the cardiovascular and motor patterns associated with pain originating in skin and in muscle and to examine the brain regions that produce these changes. More specifically, microelectrodes will be used to investigate changes in peripheral nerve activity during transient painful skin and muscle events in awake human subjects. In a separate investigation functional magnetic resonance imaging will be used to determine brain sites that are activated by skin or muscle pain.Read moreRead less
THE BAROREFLEX IN SNORING AND THE OBSTRUCTIVE SLEEP APNOEA HYPOPNOEA SYNDROME
Funder
National Health and Medical Research Council
Funding Amount
$436,261.00
Summary
The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including snoring and cessation of breathing for short periods of time. OSAHS is amongst the commonest of chronic disorders of adult males, occuring in 5% of men over the age of 45 years. It is now recognised that one of the major complications of OSAHS is the development of high blood pressure and heart disease. In the proposed studies, we ....The obstructive sleep apnoea hypopnoea syndrome (OSAHS) refers to a condition in which throat blockage occurs during sleep leading to breathing difficulties, including snoring and cessation of breathing for short periods of time. OSAHS is amongst the commonest of chronic disorders of adult males, occuring in 5% of men over the age of 45 years. It is now recognised that one of the major complications of OSAHS is the development of high blood pressure and heart disease. In the proposed studies, we will examine the proposal that snoring alone, without significant associated OSAHS, can also lead to high blood pressure in habitual snorers both awake and asleep. In particular, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which is the main blood supply to the brain. We propose that the chronic vibration of this artery can alter pressure sensors in the artery wall, which then results in the persistance of high blood pressure. Our studies will help to prove that this is a mechanism whereby both snoring and OSAHS may contribute to the development of high blood pressure. The recognition of snoring as an independent risk factor for high blood pressure will clearly have important and wide ranging implications for the future management of snoring in the prevention of high blood pressure.Read moreRead less
Identification Of Heterogeneity In Vasodilator Function In Human And Rat Resistance Vessels: Potential Drug Targets?
Funder
National Health and Medical Research Council
Funding Amount
$595,330.00
Summary
The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not w ....The balance between the ways that blood vessels decrease in size (constrict) and increase in size (dilate) determine how blood vessels normally function. There are many differences in the ways that blood vessels control this balance in different parts of the body. Such differences are altered in vascular diseases, such as hypertension and diabetes, which are prevalent in obesity, such that constriction generally outweighs dilation. However, what these differences are and how they occur are not well understood. While current drugs for treating vascular disease either reduce vessel constriction or increase dilation, they are not specific for individual arteries; a situation that would allow us to control vascular diseases in a very specific manner. Recently, we have described differences between the ways that individual vessels are controlled. These changes relate to differences in the way that different vessels dilate. AIMS - To further understand normal blood vessel function and the changes that occur in blood vessels in cardiovascular disease, with a focus on the ways that blood vessels dilate in normal states and in obesity-related diseases, such as in hypertension and diabetes. - The eventual aim is to identify the specific ways that arteries function, so that artery-specific drug targets can be identified to treat disease-related changes in cardiovascular disease in a very specific manner. EXPECTED OUTCOMES This project will contribute to understanding blood vessel function in health and disease. The expected eventual outcome is the identification of the mechanisms that underlie the function of different arteries in different parts of the body, so that specific individual vessel function can be targeted to treat vascular disease. Additionally, this work will also verify the relevance of the diet-induced obesity animal model, in terms of the characteristics and causes of human obesity and related cardiovascular disease.Read moreRead less
Molecular Mechanisms Of Receptor Activation And Signalling
Funder
National Health and Medical Research Council
Funding Amount
$571,980.00
Summary
Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several ....Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.Read moreRead less