Heart rhythm devices have revolutionised the survival of patients with heart disease. However we still do not know precisely what the outcomes are in patients attending our local hospitals. We will develop a registry for these devices to monitor and benchmark their performance throughout the state. The development of a registry enables us to assess the quality of health services at a local level. This project has the potential to improve the health outcomes of 4 million people with heart disease
Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which w ....Heartbeats are considered to arise through specialised pacemaker cells establishing rhythmically generated (i.e. pacemaker) action potentials, which then trigger propagating action potentials in heart muscle causing contraction and pumping of blood. This research proposal aims to challenge the physical model that is used to describe this pacemaker process and resultant heart conduction. Our reasons for doing this derive from our discovery of an alternative pacemaker-conduction mechanism, which we have shown to operate in various smooth muscles. This mechanism, termed store-based pacemaking, is entirely different to the currently held cardiac model but could readily achieve the same outcome. We will investigate the hypothesis that this pacemaker mechanism is also fundamental to heart pacemaking and conduction. Positive support for our hypothesis, as indicated by our pilot findings, may severely challenge the present model for cardiac pacemaking. Such an outcome will have major ramifications on present interpretation of cardiac function in health and disease and will be particularly important to interpretation of disorders associated with cardiac arrhythmias and heart conduction.Read moreRead less
Control Of Gastrointestinal Motility By Interstitial Cells And Neuronal Projections
Funder
National Health and Medical Research Council
Funding Amount
$845,540.00
Summary
The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells ....The gastrointestinal tract moves contents along its length in an ordered manner, so allowing digestion and absorption of gut contents. These movements are controlled by the properties of the cells in the muscle layers which in part make up the wall of the gastrointestinal tract, by activity in the nerves that innervate the gut and by hormonal factors. Recently we have shown that a key part of the control system lies in a set of special cells, interstitial cells, that lie amongst the muscle cells. This project will determine how these cells exert their control. These cells generate large long lasting waves of voltage which flow to nearby muscle cells so causing them to contract. The first aim is to determine how the special cells generate the command signals and the second aim is to determine how the signals spread to the muscle cells. The subsequent section of the project will determine how the behavior of the cells in the gastrointestinal tract are controlled by nervous influences. Disorders of the intestine are frequent and these appear to involve disrupted muscle contraction either because the intrinsic control system is malfunctioning or because the nervous system is unable to exert its normal influence. This project will determine how the normal control system works, invariably when this has been done with other systems, disease states are easier to rectify.Read moreRead less
The Role Of Na-Ca Exchange Current In Cardiac Pacemaker Cells
Funder
National Health and Medical Research Council
Funding Amount
$263,100.00
Summary
The heart rate is controlled by a small group of pacemaker cells within the heart. The pacemaker cells fire spontaneously and this intrinsic rate is modified by the sympathetic and parasympathetic nerves of the autonomic nervous system. We are studying a new current in the pacemaker cells which helps to control the firing rate. This new current is controlled by the intracellular calcium inside the cells so we are also studying the way in which intracellular calcium changes when the autonomic ner ....The heart rate is controlled by a small group of pacemaker cells within the heart. The pacemaker cells fire spontaneously and this intrinsic rate is modified by the sympathetic and parasympathetic nerves of the autonomic nervous system. We are studying a new current in the pacemaker cells which helps to control the firing rate. This new current is controlled by the intracellular calcium inside the cells so we are also studying the way in which intracellular calcium changes when the autonomic nervous system is active. This project will provide new insights into the function of this small group of critical cells and may allow treatment of some cardiac arrhythmias without the expense and surgery involved in the use of artificial pacemakers.Read moreRead less
Defining The Colonic Abnormality Underlying Severe Constipation And Evaluating The Efficacy Of A Novel Treatment Therapy
Funder
National Health and Medical Research Council
Funding Amount
$487,990.00
Summary
This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions along the colon in these patients. Furthermore by examining the in vivo colonic motor response to electrical stimulation of pelvic floor nerves, we will help to determine the potential of this new form of treatment for constipation. T ....This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions along the colon in these patients. Furthermore by examining the in vivo colonic motor response to electrical stimulation of pelvic floor nerves, we will help to determine the potential of this new form of treatment for constipation. The aims of these projects will be to try and identify abnormal motor patterns responsible for constipation as well as determining a possible inductor of normal colonic motility so that future studies can target appropriate treatment at the responsible defect.Read moreRead less
Molecular Diagnosis And Therapy Of Autoimmune Disease Using Translational And Reverse Translational Approaches
Funder
National Health and Medical Research Council
Funding Amount
$2,331,372.00
Summary
We plan to translate our recent discoveries on human gene variants and molecules produced by immune cells (follicular T cells) into effective therapies for autoimmune diseases. This will involve understanding the mechanisms by which the genes and molecules regulate immune tolerance, stratifying patients with autoimmune disease using newly identified biomarkers, trialling existing biologicals according to affected molecular pathway, and taking novel targets through to commercialisation.