No description available.

Heart disease is the principal cause of death in most industrialised countries. In the U.S.A. for example, 2.3 million individuals suffer from chronic heart failure, with an annual increase in numbers of 17%. It is estimated that 17,000 to 35,000 of them per year will die from this disease if they are not given either a heart transplant or an artificial heart. Unfortunately, the numbers of heart donors cannot meet the demand for transplantation, and, at present, the artificial heart is a prohibitively expensive alternative. The total artificial heart (TAH) intended for the total replacement of the natural heart is still some years away from realisation. However, the ventricular assist device (VAD) which is used temporarily to maintain an ailing heart is available now, although only in restricted numbers due to difficulties in processing the biocompatible materials used during manufacture. Consequently, such devices are expensive, costing anywhere from AUS$30,000 for the pump head to AUS$200,000 for a complete system. In this study, the Australian designed $quot;Spiral Vortex$quot; VAD was used to investigate fabrication techniques for use in the eventual cost-effective manufacture of a pump head costing approximately AUS$4,000. A second VAD originally designed at the Kolff Laboratory, University of Utah, U.S.A. was also used for comparative evaluation. The hard-shell Spiral Vortex VAD is intended to be used outside the body, while the soft-shell Kolff VAD has the advantage of being implantable for long-term use. They were cast from epoxy resin and vacuum formed from polyurethane, respectively. Several units of each were fabricated, including 60 of the Kolff VAD, for use in vitro and in vivo experiments. From these experiments it was found that both the Spiral Vortex and Kolff VADs could be fabricated to quality controllable standards. The Kolff VAD was used exclusively in chronic animal experiments, and was able to sustain sheep and goats for periods of up to five weeks. Furthermore, it became evident that techniques used in fabrication of the Kolff VAD could be adopted for use in the mass production of the Spiral Vortex VAD. The two other areas investigated in this study were the prosthetic heart valves and drive systems used for an artificial heart. A high percentage of the cost of an artificial heart is accounted for by the inflow/outflow valves. The trileaflet valve used in the Kolff VAD, which mimics the natural heart valve, was fabricated using inexpensive vacuum-forming techniques. Quality control was found to be adequate, with good flow characteristics which could be maintained for several weeks in animal experiments. Both the Spiral Vortex and Kolff VADs are pulsation pumps which require a pneumatic driver unit. This driver is the single most expensive component in a VAD system, costing upwards of AUS$150,000. The theoretical efficiency of a compact hydromechanical drive unit was investigated using a test rig to simulate an original design based primarily on proprietary components. Results obtained so far indicate that the proposed driver can operate only under limited conditions as a result of its severe reduction in size. By adopting mass production techniques wherever possible in the fabrication of the VAD (pump head) and valves, and by reducing the cost and size of the driver unit, it may therefore be possible to produce a cost effective ventricular assist device system.

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Strong clinical and experimental evidence has suggested the involvement of Chlamydia pneumoniae (C. pneumoniae) in the development of atherosclerosis. However, the direct role of C. pneumoniae infection in vascular remodelling processes in the absence of a host immune response remains undetermined. To study the direct effect of this pathogen within the arterial wall, we developed a novel ex vivo porcine coronary artery model that supported bacterial growth for up to two weeks in culture. Employing this approach, we demonstrated that C. pneumoniae infection could alter vascular functions parameters, including endothelial-dependent relaxation responses. This impairment was associated with a decrease in eNOS expression and increased oxidative stress, changes that are also noted in atherosclerotic plaques. We further demonstrated that C. pneumoniae infection initiates medial thickening via vascular smooth muscle cell (VSMC) proliferation. This proliferative response was associated with an increase in expression of endogenous heat shock protein 60 (Hsp60) and alterations in nuclear protein import machinery. Additionally, C. pneumoniae infection and Hsp60 overexpression in primary VSMCs resulted in alteration in nuclear protein import parameters leading to the cell proliferation. Using a rabbit atherosclerotic model, we demonstrated that Hsp60 is induced during atherosclerotic lesion growth and correlated with both the proliferative status and the expression of protein involved in nuclear protein import within the atherosclerotic vessel. In summary, our work has demonstrated the feasibility of studying the molecular mechanisms of infection-induced atherosclerosis using an ex vivo coronary culture system. Importantly, our data has provided the first direct evidence that an active C. pneumoniae infection alone, without contributions from a host immune system, can mediate endothelial dysfunction and stimulate arterial thickening, two key remodelling processes present during atherosclerotic progression. Our findings further suggest the involvement of Hsp60 as a key contributor in growth-based pathologies like C. pneumoniae-mediated atherosclerosis possibility through modulation of nuclear protein import.

No description available.

No description available.

No description available.

No description available.

Strong clinical and experimental evidence has suggested the involvement of Chlamydia pneumoniae (C. pneumoniae) in the development of atherosclerosis. However, the direct role of C. pneumoniae infection in vascular remodelling processes in the absence of a host immune response remains undetermined. To study the direct effect of this pathogen within the arterial wall, we developed a novel ex vivo porcine coronary artery model that supported bacterial growth for up to two weeks in culture. Employing this approach, we demonstrated that C. pneumoniae infection could alter vascular functions parameters, including endothelial-dependent relaxation responses. This impairment was associated with a decrease in eNOS expression and increased oxidative stress, changes that are also noted in atherosclerotic plaques. We further demonstrated that C. pneumoniae infection initiates medial thickening via vascular smooth muscle cell (VSMC) proliferation. This proliferative response was associated with an increase in expression of endogenous heat shock protein 60 (Hsp60) and alterations in nuclear protein import machinery. Additionally, C. pneumoniae infection and Hsp60 overexpression in primary VSMCs resulted in alteration in nuclear protein import parameters leading to the cell proliferation. Using a rabbit atherosclerotic model, we demonstrated that Hsp60 is induced during atherosclerotic lesion growth and correlated with both the proliferative status and the expression of protein involved in nuclear protein import within the atherosclerotic vessel. In summary, our work has demonstrated the feasibility of studying the molecular mechanisms of infection-induced atherosclerosis using an ex vivo coronary culture system. Importantly, our data has provided the first direct evidence that an active C. pneumoniae infection alone, without contributions from a host immune system, can mediate endothelial dysfunction and stimulate arterial thickening, two key remodelling processes present during atherosclerotic progression. Our findings further suggest the involvement of Hsp60 as a key contributor in growth-based pathologies like C. pneumoniae-mediated atherosclerosis possibility through modulation of nuclear protein import.

No description available.