Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failu ....Heart failure is a severely debilitating condition with a poor prognosis. It is characterized by retention of fluid and high nervous activity especially to the kidneys and the heart. Even with the best current treatment available, patients with heart failure still suffer from abnormally high nerve activity to the further detriment of this condition. The successful completion of this project will provide considerable insight into the role of the brain in the elevated nerve activity in heart failure. It will also provide us with a significant understanding of the role in reflex sympathetic nerve regulation of an important brain region known as the hypothalamic paraventricular nucleus (PVN). Our findings will help us understand the nature of the neurotransmitters contributing to the reflex nerve regulation and the specific neurons within the PVN involved. This knowledge could help us to identify novel potential therapeutic targets within the brain to alleviate the problems observed in heart failure.Read moreRead less
Hypothalamic Regulation Of Cardiovascular Function In Hypertension And Stress
Funder
National Health and Medical Research Council
Funding Amount
$570,880.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In some people stress can trigger an extreme reaction, called a panic disorder, characterised by intense sympathetic activation, which also increases the risk of heart attacks. A region in the brain called the hypothalamus plays a key role in generating these increases in sympathetic nerve activity. This project aims first to identify the precise region or regions in the hypothalamus that are responsible for causing increased sympathetic activity in high blood pressure, and also in response to acute stress. There is also evidence from studies in humans that drugs which act on a particular type of receptor in the brain (called a serotonin receptor) can strongly inhibit the normal response to stress. We also aim to determine exactly where and how such drugs work. These studies may lead to much more effective treatments for high blood pressure and stress-related disorders.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
Resistant Hypertension: Causes, Consequences, And Novel Therapeutic Approaches
Funder
National Health and Medical Research Council
Funding Amount
$713,517.00
Summary
Two thirds of all strokes and half of all coronary artery disease world-wide can be attributed to uncontrolled blood pressure. Patients with resistant hypertension are at specifically high risk. While the exact reasons remain obscure, work from my group suggests that sympathetic nervous system activation represents a common pathway. Based on these findings the ultimate goal of my research program is to develop novel and more effective treatment strategies for resistant hypertension.
Opposite poles of blood pressure disorders will be tested. The first is low blood pressure disorders causing blackouts while standing. My hypothesis is that the mechanism is subnormal reflex sympathetic nervous system responses (the sympathetic nervous system is the stimulant division of the automatic branch of the nervous system(. The second focus is patients with severe high blood pressure, with high sympathetic activity, who I will treat with a device silencing the nerves of the kidneys.
Role Of The Medial Amygdala In Developing Neurogenic Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
We aim to investigate the underlying mechanisms and pathways that regulate the activity of neurons located in the medial amgydala during stress that contribute long term to the development of hypertension. This study is highly relevant to people who inappropriately respond to typical daily stressors and we aim to provide direction for developing specific therapies to interrupt the adverse cardiovascular consequences of chronic stress.
Stress Hyperglycaemia And Mortality In Critical Illness: Defining The Association And Underlying Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$125,526.00
Summary
The relationship between high blood sugar levels (hyperglycaemia) and mortality in critically ill patients remains an area of controversy with conflicting results between studies. This PhD thesis will attempt to resolve this by firstly evaluating whether relative hyperglycaemia as measured using a novel new measure better predicts mortality outcome in such patients; and secondly, attempt to establish possible mechanisms which contributes to this.