Mechanisms And Treatment Of Upper Airway Collapse In Obstructive Sleep Apnoea
Funder
National Health and Medical Research Council
Funding Amount
$328,668.00
Summary
Obstructive sleep apnoea (OSA) is characterized by intermittent closure of the upper airway (throat) resulting in episodes of decreased blood oxygen levels, increased blood pressure and disturbed sleep. Repetitive overnight arousals from sleep cause excessive daytime tiredness and lethargy, which have major consequences for social well-being and productivity in our community. OSA is a common condition, affecting as many as 2 to 4% of middle aged adults, and is associated with an increased cardio ....Obstructive sleep apnoea (OSA) is characterized by intermittent closure of the upper airway (throat) resulting in episodes of decreased blood oxygen levels, increased blood pressure and disturbed sleep. Repetitive overnight arousals from sleep cause excessive daytime tiredness and lethargy, which have major consequences for social well-being and productivity in our community. OSA is a common condition, affecting as many as 2 to 4% of middle aged adults, and is associated with an increased cardiovascular risk, however the mechanisms underlying the increased upper airway collapsibility in individuals with OSA are not well understood. The proposed studies represent a series of investigations into fundamental mechanisms of neural and mechanical control of upper airway patency, how these mechanisms act to stabilize the upper airway, and whether these reflex control mechanisms can be manipulated to provide a novel treatment for OSA.Read moreRead less
In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth wei ....In the last ten years, a remarkable series of public health studies have shown that reduced birth weight is associated with an increased prevalence of high blood pressure, coronary heart disease, diabetes and obesity in adult life. These associations are independent of adult lifestyle or current size, are dependent on events initiated prenatally and are present in cohorts which have a birth weight distribution typical of urban and rural Australia. In all societies, the incidence of low birth weight babies has remained above 5% and in some developing countries, it is greater than 30%. The hormonal responses which help the fetus survive periods of growth restriction in utero, result in a permanent reprogramming of the development of key fetal organs and tissues and the subsequent emergence of high blood pressure in later life. The fetal hormones which have been implicated in causing high blood pressure in adult life are known as glucocorticoids. Fetuses may be exposed to excess glucocorticoids through stress in the womb or through increased transfer of glucocorticoids across the placenta. Currently 85% of Australian obstetricians prescribe repeat courses of antenatal corticosteroids in pregnancies in which the risk of preterm birth persists or recurs. The specific long term outcomes of fetal exposure to excess glucocorticoids are unknown and may depend on the timing, route, dose and type of glucocorticoids involved. We propose to define the mechanisms by which high levels of glucocorticoids act to result in high blood pressure and hormonal disturbances in adult life.Read moreRead less
The Effects Of Tonic Muscle Pain On The Sympathetic And Somatic Motor Systems In Human Subjects
Funder
National Health and Medical Research Council
Funding Amount
$462,948.00
Summary
The main objective of this proposal is to reveal the effects of nociceptive reflexes in humans, and thus identify their functional and clinical implications. By performing invasive recordings from the nerves that control blood vessels and muscles in healthy volunteers subjected to long-lasting (~1 hour) experimental pain, this work will increase our understanding of the adaptive changes that pain induces and improve treatments to prevent pain from becoming chronic.
Effects Of Atrial Natriuretic Peptide On The Sarcolemmal Na-K Pump In Rabbit Myocytes
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
The sodium pump transports sodium ions across cell membranes from the inside of cells to the outside. This maintains the concentration of sodium more than ten-fold lower on the inside than the outside. This transmembrane concentration gradient is essential for normal cell function. It is well established that the sodium pump is regulated by a variety of hormones. In a pilot study we have demonstrated that a hormone secreted by the heart, atrial natriuretic peptide, stimulates the sodium pump in ....The sodium pump transports sodium ions across cell membranes from the inside of cells to the outside. This maintains the concentration of sodium more than ten-fold lower on the inside than the outside. This transmembrane concentration gradient is essential for normal cell function. It is well established that the sodium pump is regulated by a variety of hormones. In a pilot study we have demonstrated that a hormone secreted by the heart, atrial natriuretic peptide, stimulates the sodium pump in single heart cells. This has not been reported previously. This study will examine the cellular mechanisms that mediate the stimulation of the sodium pump by atrial natriuretic peptide. A study on the effect of atrial natriuretic peptide on the regulation of sodium in heart cells is particularly important from the perspective of heart failure, a condition characterised by an inability of the heart to pump a sufficient amount of blood. While the underlying causes of heart failure vary widely activation of several hormone systems is a common feature regardless of the aetiology. It has already been well established in clinical practice that interfering with hormone activation by drugs improves symptoms as well as survival. Drugs have recently been developed that can increase levels of atrial natriuretic peptide. Since raised levels of sodium may contribute to important heart cell abnormalities in heart failure the effect of atrial natriuretic peptide on sodium export from the cells by the pump may have important implications for treatment of this serious and common condition.Read moreRead less