Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount ....Electrophysiological and Anatomical Characterization of the Coronary Sinus Musculature and its Relationship to the Atria. This series of experiments will characterise the normal coronary sinus musculature and its connectivity to the atria of the heart and establish their electrical relationships. The underlying characteristics of the muscular connections will also be evaluated with a view to possible future manipulations of the system. Understanding normal heart impulse propagation is paramount before we can understand and develop treatments for dealing with heart problems. This information will facilitate the development of techniques to treat and prevent heart rhythm disorders that are a common cause of morbidity in the community.Read moreRead less
Mechanisms Responsible For Hypertension Caused By Perinatal Omega-3 Fatty Acid Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$280,650.00
Summary
Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) ....Does the nourishment we receive as babies, or even before birth, affect our adult health? The recent findings from Barker, Meaney, Langley-Evans and their co-workers, has established that intra-uterine and early post-natal factors, particularly nutrition, influence adult neural development and cardiovascular function. It appears that the dietary intake of omega-3 fatty acids in early life may be a critical factor in the development of hypertension. We reported (Nature Medicine 2001, 7: 258-259) for the first time that the essential omega-3 fatty acid, alpha-linolenic acid (ALA), supplied in the early developmental period, affects blood pressure later in life. The work showed that moderate omega-3 fatty acid deficiency in the perinatal period resulted in hypertension, despite reversal of the deficiency at a time months before the assessment of blood pressure. These findings are suggestive of a critical period, during which time the development of normal blood pressure control mechanisms appears, at least partially, dependent upon the supply of omega-3 fatty acids. These findings suggest that omega-3 deficiency early in life may affect fatty acid metabolism, transport or uptake systems, such that re-feeding of the nutrients is functionally ineffective. Alternatively, deficiency of omega-3 fatty acids early in life may arrest development of one or more of the key signalling pathways in the control of blood pressure, such as the Brain Angiotensin System. The influence of dietary omega-3 fatty acid supply, relative to the critical period, on expression of genes involved in the control of blood pressure as well as in fatty acid metabolism, will be defined. Also, the role of the brain angiotensin system in omega-3 fatty acid deficiency-induced hypertension will be determined. We expect that the results of this study will profoundly affect hypertension research, as well as nutrition, particularly that for infants.Read moreRead less
Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard ....Regenerating lizard tails: A model for understanding the process of lymphangiogenesis. In humans, impaired lymphatic drainage in limbs causes the debilitating swelling termed lymphoedema. Lymphoedema affects 500,000,000 people worldwide. In the developed world lymphoedema predominantly results from surgery for cancer, and occurs in approximately 25% of breast cancer patients. We will examine lymph vessel regeneration (lymphangiogenesis) in a naturally regenerating, complex structure (the lizard tail), to describe the regrowth process and determine the abundance, location, functional properties and molecular control of the new lymphatics. Furthermore, if reptilian lymphatic growth factors can promote lymphangiogenesis in mammals, we can design novel therapeutic approaches using reptilian ligands to promote lymphangiogenesis in lymphoedematous human tissues.Read moreRead less
Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will ass ....Impact of shear stress on vascular adaptations in humans. Large arteries are important for the delivery of blood and oxygen to organs such as the heart and brain. A primary physiological stimulus which controls the size and function of these crucial arteries is the magnitude of flow or, more accurately, shear force that the inner wall of the artery is exposed to. We have developed novel software which enables non-invasive assessment of arterial wall velocity, diameter and blood flow. We will assess the impact of acute and chronic changes in wall flow and shear on arterial size and function. We will also develop new software which measures other aspects of artery wall behaviour. These basic human physiology studies have direct implications for assessment of artery health in humans.Read moreRead less
Assessing a model of the physiological changes at arousal from sleep. Arousals from sleep are common in the elderly and have adverse consequences. This project will investigate a model of the changes in bodily processes (muscle, brain and cardiovascular activation) that occur when humans awaken from sleep.
Examining the links between obesity and insulin resistance. Obesity prevalence is rapidly increasing in Australia and contributes to the onset of many chronic diseases, such as diabetes, heart disease and cancer. This project will examine how obesity contributes to disease risk and how modifying nutrient delivery and other interventions that protect from cellular stress reduces these risks.
Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human deve ....Over the next five years, I will further expand and continue to translate my basic and clinical research programs in women’s health to deliver outcomes to the Australian and international health care systems. In particular, I will target the concept of pregnancy as a determinant of future community health and wellbeing. There is now substantial consensus that environmental influences (including, but not limited to, maternal nutrition) during early life can have a fundamental impact on human development, with consequences for biological and social function and behaviour throughout the lifecourseRead moreRead less
Study Of The Functional Consequences Of Angiotensin II Induced Increases In Renal Innervation
Funder
National Health and Medical Research Council
Funding Amount
$393,750.00
Summary
Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely imperv ....Hypertension (high blood pressure) is a major public health problem in Australia, being a key risk factor for cardiovascular diseases such as heart attack and stroke. More ominously, recent WHO reports show that cardiovascular disease is the major health burden facing developing countries, particularly in our region. Although some of the burden of cardiovascular diseases may be reduced by effective public health measures (e.g., to reduce saturated fat intake), hypertension remains largely impervious to preventative public health measures. While treatment of established high blood pressure can reduce the incidence of cardiovascular disease, preventing the development of hypertension in the first place is not possible at this time. A major impediment to the development of effective public health measure is our lack of knowledge of the pathological mechanisms involved, despite over 100 years of active research effort. The experiments planned in this study will probe below the surface of two important facts known about hypertension but not previously brought together - that the kidney's blood vessels and nerves are remodeled in hypertension, and that the kidney's control of the level of blood pressure must be changed in order for high blood pressure to develop in the first place. We hope that pursuit of this experimental line of enquiry will provide new clues on where to look for initiating factors in human hypertension.Read moreRead less