Reducing The Burden Of Orthostatic Intolerance - Delineating Mechanisms And Improving Therapy
Funder
National Health and Medical Research Council
Funding Amount
$411,735.00
Summary
Orthostatic intolerance (OI) represents a heterogenous group of complex disorders which are poorly understood and lack effective treatment. They are frequently disabling and may severely impact on quality of life. In the proposed project, we will undertake a systematic investigation of _sympathetic nervous system� in OI patients and assess the clinical effect of a drug _L-DOPS� in subjects suffering from OI.
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.
Plasmapheresis As A Novel Treatment Of Postural Tachycardia Syndrome: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$97,081.00
Summary
We aim to conduct a randomized controlled trial to test our hypothesis that the removal of autoantibodies (through plasmapheresis) will reduce the severity of symptoms in patients with postural tachycardia syndrome. We will be measuring symptom scores, cardiovascular fitness on exercise testing, heart rate and blood pressure responses during valsalva and orthostatic stress as well as the metabolic profiles and presence of autoantibodies in the blood of patients participating in the trial.
A common medical problem is the inability to maintain normal blood pressure while standing. This can cause blackouts, falls and injury. The available medical treatment is very deficient, because the various body mechanisms at play are poorly understood, so it has not been possible to specifically target the root cause. This grant application aims to study patients with these “postural hypotension” disorders, to better understand how the problems develop, and consequently, to provide better medic ....A common medical problem is the inability to maintain normal blood pressure while standing. This can cause blackouts, falls and injury. The available medical treatment is very deficient, because the various body mechanisms at play are poorly understood, so it has not been possible to specifically target the root cause. This grant application aims to study patients with these “postural hypotension” disorders, to better understand how the problems develop, and consequently, to provide better medical treatment.Read moreRead less
Neurotransmitters In Synaptic Inputs To Medullary Neurons Subserving The Baroreflex
Funder
National Health and Medical Research Council
Funding Amount
$470,500.00
Summary
The baroreflex rapidly adjusts arterial blood pressure to meet changing physiological needs. The reflex alters vascular resistance and changes the rate, volume and force at which blood is expelled from the heart, ensuring that organs are adequately supplied with blood-borne nutrients and oxygen. Changes in baroreflex function occur during exercise, correlate with increased mortality and morbidity from heart failure and myocardial infarction and are responsible for postural hypotension in the eld ....The baroreflex rapidly adjusts arterial blood pressure to meet changing physiological needs. The reflex alters vascular resistance and changes the rate, volume and force at which blood is expelled from the heart, ensuring that organs are adequately supplied with blood-borne nutrients and oxygen. Changes in baroreflex function occur during exercise, correlate with increased mortality and morbidity from heart failure and myocardial infarction and are responsible for postural hypotension in the elderly. Three areas in the brainstem are critical for transmission of the arterial baroreflex. However, it is still not known exactly which chemicals (neurotransmitters) are used to convey baroreflex information to and between neurons in these key sites. In this project, we will use state-of-the-art anatomical techniques to examine nerve pathways that subserve the arterial baroreflex. By changing blood pressure and specifically tagging nerve cells that respond, we can focus on neurons activated by baroreflex stimuli. Concentrating on neurotransmitters known to affect blood pressure control in the medulla, we will then label one or more of these in nerve fibers surrounding the barosensitive neurons. Finally, we will determine by light and electron microscopy the relationships between the labelled nerve fibers and the barosensitive neurons. These relationships will show which neurotransmitters could influence barosensitive neurons directly, which indirectly and which not at all. This project will increase our understanding of the baroreflex by clarifying which neurochemicals convey baroreflex information amongst the key groups of brainstem neurons. These data will form the foundation for new studies on changes in nerve pathways that underlie baroreflex dysfunction in such conditions as postural hypotension. Identifying transmitters for the baroreflex may also point to, or rule out, new drug treatments for disturbances in baroreflex function.Read moreRead less
Orthostatic Tolerance During FES-evoked Stepping In Paraplegia: A Safety And Viability Study
Funder
National Health and Medical Research Council
Funding Amount
$244,900.00
Summary
In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES ....In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES present the SCI person with a means of restoring upright mobility and reinstating functional tasks. Yet, while this technological innovation remains promising for optimising functional outcomes after SCI, there remains a distinct lack of knowledge of the physiological stresses placed upon the individual. In this preliminary safety and viability study, the physiological implications central to enhanced upright mobility will be investigated during FES-evoked prolonged stepping. The responses during FES-stepping will be contrasted with the responses observed during stepping performed without FES. The study will investigate the blood pressure responses during FES-gait, but also address possible physiological mechanisms underlying those blood pressure responses. The findings from this study will identify whether there is a phsiological limitation to the performance of FES-evoked functional mobility. Current physiotherapy practice recognises blood pressure control and orthostatic hypotension as a significant barrier to functional standing and stepping, yet little is known about the physiology underpinning the condition. If FES does present a limitation to the performance of upright functional activities, this study will also assist in devising alternative physiotherapy gait training regimens.Read moreRead less
Facilitating The Increase In Pulmonary Blood Flow At Birth
Funder
National Health and Medical Research Council
Funding Amount
$617,729.00
Summary
Pulmonary hypertension in newborn infants is a significant problem that is very difficult to treat because we do not understand how blood flow through the lungs increases at birth. We have recently shown that currently believed mechanisms controlling blood flow at birth are incorrect and additional factors exist. Our experiments will determine factors that affect blood flow through the lungs at birth. This information will be used to improve the care of newborns with pulmonary hypertension.
An Integrated Approach To Inotropic Support In Preterm Neonates
Funder
National Health and Medical Research Council
Funding Amount
$694,449.00
Summary
Poor cardiovascular function in preterm babies can lead to inadequate blood flow to the brain and brain injury. Current treatments to improve heart function are often ineffective. This study will examine the effects of treatment on different parts of the cardiovascular system, and how these effects interact. It will identify reasons for the lack of effectiveness and provide insight which will help to design better treatments for preterm babies.