I am a neurophysiologist interested in brain regulation of homeostatic and autonomic functions in health and disease. I am endeavouring to discover the brain pathways for these vital functions, and to translate my findings from animal research to humans.
Patients With Obstructive Sleep Apnoea And Motor Control
Funder
National Health and Medical Research Council
Funding Amount
$302,798.00
Summary
Obstructive Sleep Apnoea is a major health concern, affecting at least 4% of the population, associated with obesity, and aging. The symptoms of sleep apnoea are definitively associated with cardiovascular complications. I am focused on understanding how sleep apnoea patients are remodelled with the rewiring of connections between the brain and muscles. Using neurophysiological techniques, this project will study how the anatomy and functional connections of circuits change with sleep apnoea.
Understanding Factors Involved In The Development Of Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$757,492.00
Summary
High blood pressure is a major cause of cardiovascular diseases. Currently intervention occurs after the cardiovascular system is damaged. Our interest is in the development of high blood pressure, to determine whether early intervention could stop its progression. We identified that excitation of the sympathetic nervous system by the circuits that control breathing is important. We seek to further understand this interaction to identify novel approaches to treat high blood pressure.
The Role Of Sleep And Cardiorespiratory Control In The Pathogenesis Of Pre-eclampsia
Funder
National Health and Medical Research Council
Funding Amount
$235,095.00
Summary
Pre-eclampsia occurs in 7-10 % of the pregnant population. This makes it one of the most common diseases associated with pregnancy in the Western world. The cause of pre-eclampsia remains elusive, however, recent research suggests that the initiating factor is abnormal implantation of the placenta into the uterus. This in turn leads to poor flow of blood through the placenta (known as placental ischaemia) resulting in release of mediators (including substances known as cytokines) into the matern ....Pre-eclampsia occurs in 7-10 % of the pregnant population. This makes it one of the most common diseases associated with pregnancy in the Western world. The cause of pre-eclampsia remains elusive, however, recent research suggests that the initiating factor is abnormal implantation of the placenta into the uterus. This in turn leads to poor flow of blood through the placenta (known as placental ischaemia) resulting in release of mediators (including substances known as cytokines) into the maternal circulation which cause widespread damage to the endothelium (the protective layer of cells which line all of the blood vessels throughout the circulation). Furthermore, the greater the demand on the placenta, the more of these toxic substances will be released into the maternal circulation. During sleep, a large proportion of pregnant women snore and consequently have partial reduction in the volume of each breath. In women with healthy placental function, this is not a concern. However, we suggest that in women with pre-eclampsia, this results in further disruption to the blood flow through the placenta, which leads to a greater output of toxic substances from the placenta. We have shown that by controlling snoring during pregnancy in women with pre-eclampsia with the use of nasal continuous positive airway pressure (nasal CPAP), we are able to markedly reduce blood pressure over the night. In this project, we would like to investigate changes occurring during sleep in cytokines in the maternal circulation, and in maternal blood pressure both on and off nasal CPAP in order to establish whether a mechanism during sleep is contributing to the disease process of pre-eclampsia. Furthermore, we intend to investigate whether the long term use of nasal CPAP improves the outcome of pre-eclampsia.Read moreRead less
How Does The Central Respiratory Generator Amplify Sympathetic Activity In Hypertension?
Funder
National Health and Medical Research Council
Funding Amount
$290,113.00
Summary
High blood pressure causes many life-threatening cardiovascular diseases, including heart failure and stroke. The cause of most high blood pressure is not known. Using an animal model of high blood pressure we have shown that an interaction, in the brain, between the nerve pathways that generate respiratory activity and regulate blood pressure is altered. This occurs early in life and our evidence strongly suggests this may be a cause of high blood pressure.
Respiratory Modulation Of RVLM Premotor Neurons: Role In The Sympathetic Over-activity Of Hypertension.
Funder
National Health and Medical Research Council
Funding Amount
$338,605.00
Summary
Hypertension is a common health disorder in all societies and is a major risk factor for the development of life threatening cardiovascular diseases, including heart failure and stroke. Whilst some effective therapies are available, many patients are not adequately treated or have reduced quality of life due to serious side effects. There is a great need for alternative therapies. The central nervous system is clearly involved in hypertension although the level of that involvement is not well un ....Hypertension is a common health disorder in all societies and is a major risk factor for the development of life threatening cardiovascular diseases, including heart failure and stroke. Whilst some effective therapies are available, many patients are not adequately treated or have reduced quality of life due to serious side effects. There is a great need for alternative therapies. The central nervous system is clearly involved in hypertension although the level of that involvement is not well understood- i.e. is it a causal factor or just a contributor to the maintenance of established hypertension? The experiments outlined in this application are based on the observation that modulation of nervous activity to blood vessels is more influenced by the respiratory system in people with high blood pressure, than in normotensive people. We aim to test whether this increased respiratory modulation might be involved in the generation of the high blood pressure.Read moreRead less
Investigation Of A Novel Sympathetic Vasomotor Pathway
Funder
National Health and Medical Research Council
Funding Amount
$354,586.00
Summary
Blood pressure is regulated by sympathetic nerves to the heart and blood vessels, and it is believed that overactive sympathetic nerves contribute to many cases of hypertension. Overactive sympathetic nerves also contribute to, and worsen the disease process, in heart failure as well as other cardiovascular diseases. The regulation of sympathetic nerves is thus central to the understanding and treatment of cardiovascular disorders. The present proposal is specifically relevant to the hypertensio ....Blood pressure is regulated by sympathetic nerves to the heart and blood vessels, and it is believed that overactive sympathetic nerves contribute to many cases of hypertension. Overactive sympathetic nerves also contribute to, and worsen the disease process, in heart failure as well as other cardiovascular diseases. The regulation of sympathetic nerves is thus central to the understanding and treatment of cardiovascular disorders. The present proposal is specifically relevant to the hypertension which accompanies airway obstruction during sleep (obstructive sleep apnoea - OSA). We plan to study a novel class of sympathetic nerves ('accessory' sympathetic nerves), which are likely to be centrally involved in the hypertension of OSA, and probably also other conditions where sympathetic nerve activity is pathologically raised. 'Accessory' sympathetic nerves can cause a long-lasting amplification of the activity in the 'regular' sympathetic nerve pathway, enhancing its actions on the heart and blood vessels. The brain pathways that drive 'accessory' sympathetic nerves are essentially unknown. We seek to find out those pathways, study how they amplify the activity in the 'regular' pathway and explore their significance in an animal model of OSA. The outcomes of this study will be first, essential basic knowledge of a novel, but probably important, mechanism whereby the brain controls the cardiovascular system in health and disease. Second, the relevance of that mechanism to a specific type of neurogenic hypertension will have been defined.Read moreRead less
DEVELOPMENT OF CARDIOVASCULAR CONTROL DURING SLEEP IN HUMAN INFANTS AFTER PRETERM BIRTH
Funder
National Health and Medical Research Council
Funding Amount
$358,537.00
Summary
Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater dur ....Infants spend the major part of their life in sleep, and the period between birth and 6 months of age sees dramatic changes in their sleep organisation. Coincidently, there are dramatic developmental changes in the infant's heart and blood pressure control systems, and the ability to compensate for stress such as falls of blood pressure (hypotension) or in the level of oxygen in the blood (hypoxaemia). In infants born preterm, the risks of hypoxaemia, and even death are significantly greater during sleep than during wakefulness, but why this is so is uncertain. This study will examine the ability of infants to respond to stress during sleep. Four groups of infants will be examined: healthy infants born at normal gestation; healthy infants born prematurely (preterm); preterm infants who have experienced mild hypoxaemia soon after birth; and preterm infants who have suffered more severe hypoxaemia because of lung disease. Infants will be studied in a sleep laboratory during day-time sleep, and their ability to control blood pressure will be determined. By contrasting the effectiveness of blood pressure control between the infant groups we aim to determine whether preterm infants have lasting problems as a result of their premature birth, or their exposure to hypoxaemia. By contrasting infants in sleep and wakefulness, we aim to assess whether the risks of poorer blood pressure control are greater in sleep.Read moreRead less