Division Head: Professor Michael Feneley
The Cardiovascular Mechanics Program investigates the contractile properties of the heart and how these properties can change under different conditions. In addition, it is actively involved in clinical studies of coronary artery disease. Contractility of the heart is a major determinant of its ability to pump blood around the body, which is required for the functions of all organs. Because the heart is a muscle, it can adapt to different conditions/requirements that directly affect its contractility and efficiency. However, evaluating heart contractility is difficult, both experimentally and in the living human being, because changes in blood pressure and flow due to alterations in blood vessels can markedly alter the pumping efficiency of the heart, in a manner that is independent of its intrinisic ability to contract.
Professor Michael Feneley's Laboratory
The Cardiovascular Mechanics Research Program, headed by Professor Feneley, has developed sophisticated approaches to directly measuring heart muscle contractility. Moreover, his laboratory is broad-based, performing studies extending from the isolated heart muscle cell (or cardiac myocyte) to integrated physiological experiments in mice and rats (performed in our Small Animal Physiology Laboratory), to cardiac transplantation and myocardial preservation in pigs (performed in our the Large Animal Laboratory), to clinical research in patients with dilated cardiomyopathies and other causes of heart failure.
Of particular interest to the program are genetically-engineered animal models of human heart diseases. By isolating heart cells from these models and then investigating their contractile function, a detailed understanding can be obtained into the mechanisms whereby specific genes and the proteins they encode can alter heart contractile function. Using the same isolated cardiac cells as well as intact animal, the group is also able to investigate how important factors, such as blood pressure, hormones and aging, can affect contractility of the individual heart cells or the intact organ.
These approaches should provide new insight into the initial changes in heart muscle function which ultimately lead to heart disease and failure. The group's main areas focus on establishing what pathways control the development of left ventricular hypertrophy (abnormal thickening of heart muscle) in an attempt to understand ways in which this very important disorder can be prevented.
A/Professor David Muller's Laboratory
Finally, under the direction of Associate Professor David Muller, the program is also actively investigating new treatments to prevent, treat and reverse coronary artery disease, the cause of heart attacks, particularly in patients who have received a heart transplant.
Laboratory Head: Professor Michael O'Rourke
The focus of the Vascular-Ventricular Interactions Program has been the study of human aging and human arterial disease. In conjunction with the Cardiology department at St Vincent's Hospital and the Graduate School of Bioengineering at UNSW, the program has been focusing on the effects of arterial stiffening with age on pulse wave transmission and reflection, and on how arterial stiffening adversely effects left ventricular load and function upstream and small vessel structure and function downstream.
Professor O'Rourke's studies have also introduced the technique of arterial tonometry and new methods for analysing and interpreting the arterial pulse, as recorded non-invasively at the wrist or from the carotid artery in the neck. New techniques are also being established to assess the effects of aging change and of disease on ventricular/vascular interactions.
Professor O'Rourke's group had predicted that interpretation of diastolic blood pressure in hypertension should be re-evaluated and that in older humans central aortic systolic and pulse pressure would be the best predictors of cardiovascular events in population studies. These predictions have been confirmed in epidemiological and drug studies. As a consequence of these studies the group is currently investigating the pressure-related determinants of cardiac failure and atrial fibrillation in the elderly.
Laboratory Heads: Professor Anne Keogh & Professor Peter Macdonald
Heart transplantation remains a major treatment for patients with end-stage heart failure. However a major limitation to long term survival is the recurrence of obstruction in the arteries of the heart. Trials with new immunosuppressive drugs conducted within the program over the past 3 years have gone a long way toward overcoming this impediment to long term survival.
The transplant program is also actively involved in studies examining the effects of new drugs for the treatment of pulmonary arterial hypertension. This debilitating disease is usually fatal within 3-5 years if misdiagnosed or left untreated. At present, only one drug is approved for use in Australia, however several promising new therapies are being evaluated in clinical trials run by the Transplant Program. Another aspect of this program's work is the development of improved techniques for preservation of donor organs.
Good preservation of donor organs is critical to the successful transplantation of all organs. Our group is working in collaboration with kidney and liver transplant specialists from other institutions to develop a uniform preservation technique that optimises the quality of all internal organs (heart, lung, liver, kidney and pancreas) that are used for transplantation. It is anticipated that the application of these techniques to human transplantation will increase both the number and quality of donor organs that are used for transplantation.
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