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
Atrial fibrillation is the most common heart rhythm disturbance with a prevalence of approximately 1% but which increases markedly with age. It causes debilitating symptoms, heart failure, stroke and increased mortality. It is an important determinant of neuro-cognitive decline and dementia. The studies in this proposal will help define the mechanism of this rhythm disturbance and its associated symptoms. They will help design improved treatment strategies including interventional approaches.
Phospholipase Cbeta 1b, A Target To Limit Atrial Dilatation
Funder
National Health and Medical Research Council
Funding Amount
$544,847.00
Summary
We have identified a heart specific protein that is involved in perpetuating dilatation of the upper chambers of the heart and thereby contributing to cardiac disease. Inhibitors of this protein provide a suitable target for therapy to limit heart disease. The current studies aim to test such inhibitors in vivo as proof-of-concept that such treatment effectively limits cardiac dysfunction.
The Role Of Mechanoelectric Feedback In Cardiac Arrhythmogenesis
Funder
National Health and Medical Research Council
Funding Amount
$307,550.00
Summary
Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. ....Arrhythmias are disruptions of the normal electrical rhythm of the heart, and can vary from asymptomatic to fatal. It used to be thought that the electrical and mechanical functions of the heart muscle were essentially separate: the electrical activity triggered contraction something like pulling the trigger of a gun- once events were in motion, the electrical events played no further role. However, in recent years it has become apparent that this is an over-simplification of the real situation. In fact, the electrical activity of the heart is influenced strongly by the degree and timing of stretch to which the heart muscle is subjected, a process called Mechano-electric feedback. Since it can be demonstrated in isolated tissues, mechano-electric feedback must be an intrinsic property of the heart muscle. It has been shown in isolated heart preparations that passive stretch produces electrical disturbances in the normal action potential shape and propagation and that these electrical disturbances can be powerful enough to generate severe arrhythmias. There are paralells in human diseases. For example, atrial arrhythmias are common in older people, and it seems that these may be due to chronic stretch of the atria, as a consequence of high blood pressure. In addition, in those patients recovering from a heart attack, it seems likely that the damaged part of the heart muscle subjects the surrounding tissue to unusual mechanical stresses, and may trigger arrhythmias. This project aims to investigate the mechanisms underlying this mechano-electric feedback, in an attempt to understand some types of arrhythmias. Using molecular biology techniques, we will look at the gene expression of a novel type of stretch-activated potassium channel in both healthy and diseased animal hearts, with the aim of seeing if changes in the level of expression of these channels is correlated with changes in the response of the heart to stretch.Read moreRead less
Atrial Electrical Remodeling Due To Chronic Stretch: Defining The Substrate For Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$428,250.00
Summary
Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood ....Background: Cardiac failure is a common heart disorder in which the pumping function of the heart is significantly weakened. Mitral regurgitation is a common condition where there is a leakage of blood from the left ventricle (lower heart chamber) back into the left atrium (upper heart chamber) during normal cardiac contraction. This puts a strain on the heart and may cause heart failure. Atrial septal defect is a common form of congenital heart disease which may not be diagnosed until adulthood. There are several forms but the basic problem is leakage of blood from the left atrium into the right atrium .This also puts a strain on the heart and can cause heart failure. All 3 conditions are associated with a significantly increased risk of atrial fibrillation (AF). This abnormal fast irregular cardiac rhythm makes the pumping of the heart inefficient. People with AF may feel short of breath, tired, or develop palpitations. AF is an important cause of stroke and premature death and is the most common heart rhythm disturbance occurring in upto 10% of the over 70 age group. Even after repair of the leaky valve or atrial septal defect there is still a high risk of developing this rhythm. Purpose of the study: This study will try to understand why patients with these conditions are at risk of developing atrial fibrillation, and why this risk might persist after surgical correction when this is possible (mitral regurgitation and atrial septal defect). The study will utilise sophisticated new mapping techniques to gain original insights into the mechanism of this very common and as yet poorly understood heart rhythm disturbance. The study has the potential to determine the cause of atrial fibrillation in these patient groups and as such represent a quantum advance in our understanding of he mechanism of atrial fibrillation. It would be expected to form a foundation on which development of curative and preventative approaches may be based.Read moreRead less
Analysis Of Atrial Electrical Remodelling In Patients With Paroxysmal And Persistent Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$127,516.00
Summary
I am a cardiologist undertaking further training in the management of electrical abnormalities of the heart. My research will focus on the mechanisms responsible for atrial fibrillation, the most common serious heart rhythm disorder. I intend to do this by examining the nature of the electrical activity in patients with atrial fibrillation and comparing this to electrical activity in patients without this disorder, who are undergoing treatment procedures for their electrical disorder.