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 hypotheses that this pacemaker mechanism is also fundamental to mammalian heart pacemaking and conduction. Positive support for our hypotheses, as indicated by our findings on amphibian hearts and from 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
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
The Role Of Connexin40 In The Pathogenesis Of Atrial Fibrillation Probed By Targeted In Vivo Gene Transfer
Funder
National Health and Medical Research Council
Funding Amount
$529,015.00
Summary
Atrial fibrillation (AF) is a fast and irregular heart rhythm that can predispose sufferers to heart failure and stroke. AF occurs as the result of abnormal electrical conduction in the upper heart chambers. We have found that a protein called Cx40 causes abnormal conduction in heart cells when grown in culture. The aim of this research is to see if AF occurs when Cx40 is increased and prevented when Cx40 is decreased in an AF animal model, potentially defining Cx40 as new therapeutic target.
The Role Of Antibody In Inflammatory Demyelinating Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$218,566.00
Summary
The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antib ....The causes and disease mechanism of inflammatory neuropathy remain unknown. Although treatments have been developed (intravenous immunoglobulin and plasma exchange) they are extremely expensive and non specific in action and beyond the means of the worlds most populous nations. These studies plan to illuminate the mechanism of disease production so that better and more affordable therapy can be developed. We have shown that antibodies which cause nerve damage are present in patients serum. Antibodies bind to specific target molecules and our work is close to identifying that target on nerve. We also plan to study how antibody leaks into nerve. This knowledge should allow more specific and effective treatment to be developed.Read moreRead less
Investigation Of Neural Mechanisms Of 670 And 830nm Laser Acupuncture In Pain Relief, Using Rat
Funder
National Health and Medical Research Council
Funding Amount
$326,207.00
Summary
Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigat ....Background Chronic pain is common and costs $10 billion dollars per year in Australia. Drug therapies are widely used but serious side effects limit use. Patients actively seek non-drug treatments and laser acupuncture is one of the most commonly sought therapies for chronic pain, however, how it works is not well understood. Our previous work Researchers propose that laser acupuncture reduces pain by direct effects on nerves, altering how pain signals are transmitted to the brain. To investigate this we (CI A and CI B) previously undertook a study of infrared laser on nerve cell cultures. This followed on from a positive clinical study with the same laser wavelength in the treatment of neck pain, undertaken by CI B. We established that laser temporarily interrupts the nerve transport system, which is made up of a series of minute tubes, called microtubules. These act as a “monorail” system for transport of mitochondria, which provide energy for all nerve functions. We propose that temporary interruption of this system, called fast axonal transport, disrupts the conduction of pain signals along the nerve, resulting in pain relief. Important unanswered questions The mechanism by which 830nm laser acupuncture relieves pain clinically remains poorly understood. For its acceptance into mainstream clinical practice it is important to determine the effect of laser on the peripheral nerves and in particular the pain carrying fibres. We know from an earlier study that a single exposure causes significant but reversible changes in pain fibres including axonal microtubule disruption, decrease in mitochondrial membrane potential and block of fast axonal flow. These events would result in conduction failure. The question is whether the repeated irradiations, comparable to those delivered clinically result in the same changes. This would provide a scientific basis for understanding the clinical effectiveness of laser acupuncture. We also do not know if 670nm laser acupuncture would act in the same way. There is evidence that this may be more effective so that this remains another important unanswered question. Further, there is no evidence regarding which wavelength would be cost and time effective as it is desirable to deliver lower dose. We need to determine the most effective dose and wavelength so that clinical trials could be carried out as was done for the trials by CIB (Chow and Barnsley, 2006).Read moreRead less
Structural And Functional Determinants Of Spatiotemporal Periodicity In Cardiac Impulse Propagation
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Abnormal heart rhythms (cardiac arrhythmias) are responsible for much morbidity and excess mortality in Australia. Although many abnormalities leading to an abnormal heart rhythm may be successfully treated by medications or minimally invasive operative procedures there are several important ones which are not. These include the most common significant cause of an abnormal heart rhythm, atrial fibrillation, and the arrhythmias responsible for approximately half of sudden deaths, ventricular tach ....Abnormal heart rhythms (cardiac arrhythmias) are responsible for much morbidity and excess mortality in Australia. Although many abnormalities leading to an abnormal heart rhythm may be successfully treated by medications or minimally invasive operative procedures there are several important ones which are not. These include the most common significant cause of an abnormal heart rhythm, atrial fibrillation, and the arrhythmias responsible for approximately half of sudden deaths, ventricular tachycardia and ventricular fibrillation. Atrial fibrillation is a leading cause of stroke. Sudden death is associated with aging and is an increasing problem because of the rising mean age of the population. Recent negative attention on the side effects of medications used for the treatment of cardiac arrhythmias has appropriately increased interest in curative approaches requiring no onging medications. These procedures usually rely on mapping electrical activity in the heart and interrupting abnormal electrical pathways using radiofrequency electrical current. The procedures are unsuccessful when existing techniques fail to identify the underlying mechanism responsible for the abnormal heart rhythm or when the source of the abnormal beating cannot be localised within the heart. In this project we investigate the fundamental basis for a new approach to these problems. By examining the variability of the beat rate and the variability of the beat rate at different points within the heart we may be able to identify arrhythmia mechanisms and localise arrhythmia sources. In this project we will examine in groups of cells the structures and types of electrical circuits which give rise to certain types of beat-to-beat variability in the heart. This information will be essential for the interpretation of information obtained in later human studies and the subsequent development of new curative procedures for these problems.Read moreRead less