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      An isolated perfused pig heart model for the development, validation and translation of novel cardiovascular magnetic resonance techniques

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          Abstract

          Background

          Novel cardiovascular magnetic resonance (CMR) techniques and imaging biomarkers are often validated in small animal models or empirically in patients. Direct translation of small animal CMR protocols to humans is rarely possible, while validation in humans is often difficult, slow and occasionally not possible due to ethical considerations. The aim of this study is to overcome these limitations by introducing an MR-compatible, free beating, blood-perfused, isolated pig heart model for the development of novel CMR methodology.

          Methods

          6 hearts were perfused outside of the MR environment to establish preparation stability. Coronary perfusion pressure (CPP), coronary blood flow (CBF), left ventricular pressure (LVP), arterial blood gas and electrolyte composition were monitored over 4 hours. Further hearts were perfused within 3T (n = 3) and 1.5T (n = 3) clinical MR scanners, and characterised using functional (CINE), perfusion and late gadolinium enhancement (LGE) imaging. Perfusion imaging was performed globally and selectively for the right (RCA) and left coronary artery (LCA). In one heart the RCA perfusion territory was determined and compared to infarct size after coronary occlusion.

          Results

          All physiological parameters measured remained stable and within normal ranges. The model proved amenable to CMR at both field strengths using typical clinical acquisitions. There was good agreement between the RCA perfusion territory measured by selective first pass perfusion and LGE after coronary occlusion (37% versus 36% of the LV respectively).

          Conclusions

          This flexible model allows imaging of cardiac function in a controllable, beating, human-sized heart using clinical MR systems. It should aid further development, validation and clinical translation of novel CMR methodologies, and imaging sequences.

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          Most cited references 31

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          Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study

          Plausible projections of future mortality and disability are a useful aid in decisions on priorities for health research, capital investment, and training. Rates and patterns of ill health are determined by factors such as socioeconomic development, educational attainment, technological developments, and their dispersion among populations, as well as exposure to hazards such as tobacco. As part of the Global Burden of Disease Study (GBD), we developed three scenarios of future mortality and disability for different age-sex groups, causes, and regions. We used the most important disease and injury trends since 1950 in nine cause-of-death clusters. Regression equations for mortality rates for each cluster by region were developed from gross domestic product per person (in international dollars), average number of years of education, time (in years, as a surrogate for technological change), and smoking intensity, which shows the cumulative effects based on data for 47 countries in 1950-90. Optimistic, pessimistic, and baseline projections of the independent variables were made. We related mortality from detailed causes to mortality from a cause cluster to project more detailed causes. Based on projected numbers of deaths by cause, years of life lived with disability (YLDs) were projected from different relation models of YLDs to years of life lost (YLLs). Population projections were prepared from World Bank projections of fertility and the projected mortality rates. Life expectancy at birth for women was projected to increase in all three scenarios; in established market economies to about 90 years by 2020. Far smaller gains in male life expectancy were projected than in females; in formerly socialist economies of Europe, male life expectancy may not increase at all. Worldwide mortality from communicable maternal, perinatal, and nutritional disorders was expected to decline in the baseline scenario from 17.2 million deaths in 1990 to 10.3 million in 2020. We projected that non-communicable disease mortality will increase from 28.1 million deaths in 1990 to 49.7 million in 2020. Deaths from injury may increase from 5.1 million to 8.4 million. Leading causes of disability-adjusted life years (DALYs) predicted by the baseline model were (in descending order): ischaemic heart disease, unipolar major depression, road-traffic accidents, cerebrovascular disease, chronic obstructive pulmonary disease, lower respiratory infections, tuberculosis, war injuries, diarrhoeal diseases, and HIV. Tobacco-attributable mortality is projected to increase from 3.0 million deaths in 1990 to 8.4 million deaths in 2020. Health trends in the next 25 years will be determined mainly by the ageing of the world's population, the decline in age-specific mortality rates from communicable, maternal, perinatal, and nutritional disorders, the spread of HIV, and the increase in tobacco-related mortality and disability. Projections, by their nature, are highly uncertain, but we found some robust results with implications for health policy.
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            Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography.

            The analysis of wall motion abnormalities with dobutamine stress echocardiography (DSE) is an established method for the detection of myocardial ischemia. With ultrafast magnetic resonance tomography, identical stress protocols as used for echocardiography can be applied. In 208 consecutive patients (147 men, 61 women) with suspected coronary artery disease, DSE with harmonic imaging and dobutamine stress magnetic resonance (DSMR) (1.5 T) were performed before cardiac catheterization. DSMR images were acquired during short breath-holds in 3 short-axis views and a 4- and a 2-chamber view (gradient echo technique). Patients were examined at rest and during a standard dobutamine-atropine scheme until submaximal heart rate was reached. Regional wall motion was assessed in a 16-segment model. Significant coronary heart disease was defined as >/=50% diameter stenosis. Eighteen patients could not be examined by DSMR (claustrophobia 11 and adipositas 6) and 18 patients by DSE (poor image quality). Four patients did not reach target heart rate. In 107 patients, coronary artery disease was found. With DSMR, sensitivity was increased from 74.3% to 86.2% and specificity from 69.8% to 85.7% (both P<0.05) compared with DSE. Analysis for women yielded similar results. High-dose dobutamine magnetic resonance tomography can be performed with a standard dobutamine/atropine stress protocol. Detection of wall motion abnormalities by DSMR yields a significantly higher diagnostic accuracy in comparison to DSE.
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              Global mortality, disability and the contribution of risk factors: global burden of disease study

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                Author and article information

                Journal
                J Cardiovasc Magn Reson
                Journal of Cardiovascular Magnetic Resonance
                BioMed Central
                1097-6647
                1532-429X
                2010
                17 September 2010
                : 12
                : 1
                : 53
                Affiliations
                [1 ]King's College London BHF Centre of Excellence, NIHR Biomedical Research Centre and Wellcome Trust and EPSRC Medical Engineering Centre at Guy's and St. Thomas' NHS Foundation Trust, Division of Imaging Sciences, The Rayne Institute, London, UK
                [2 ]German Heart Institute, Berlin, Germany
                [3 ]King's College London BHF Centre of Excellence, NIHR Biomedical Research Centre and Department of Cardiology, Guy's and St. Thomas' NHS Foundation Trust, London, UK
                Article
                1532-429X-12-53
                10.1186/1532-429X-12-53
                2950014
                20849589
                Copyright ©2010 Schuster et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Technical Notes

                Cardiovascular Medicine

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