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- Spaak, Jonas
(författare)
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Cardiovascular function after long-term bed rest
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- On earth, daily activities involve standing, changes of posture and various types of muscle action, all of which challenge the cardiovascular regulation. Removal of the orthostatic stress for a longer period, as during spaceflight or head-down tilt bed rest, consistently results in cardiovascular deconditioning. The principal aim of this thesis was to improve the understanding of cardiovascular deconditioning, as reflected in altered structure and control after long-term spaceflight and bed rest. Apart from an initial methodological study, all results are based on two head-down tilt bed rest experiments with durations of 42 and 120 clays, and on five spaceflights with durations of 6 to 13 months. In the initial study, the separate effects of voluntary motor activation and muscle chemoreflex activation on arterial baroreflexes in healthy young men were examined. It was found that the elevation of arterial blood pressure is mainly caused by muscle ischemia, whereas the heart rate response is entirely due to somatomotor activation. These conclusions provided a basis for the following study, aiming to characterized the cardiovascular responses to isometric muscle action during and after spaceflight and after bed rest. The responses to isometric lower arm contraction were determined, and it was concluded that impaired cardiovascular responses to isometric muscle action do contribute to the cardiovascular deconditioning after spaceflight and bed rest. In the two bed rest studies, cardiac output (CO) and stroke volume (SV) were determined, and marked reductions were found in both CO and SV, in both supine and upright posture, during rest and during 50 watt pedalling. The time-course of the deconditioning and recovery of SV in the different conditions indicates that SV reductions in the upright posture after bed rest are mainly due to an impaired preload, and recuperate swiftly as plasma volume recovers. On the other hand, SV reductions in the supine posture during exercise, showed a slow, progressive decline during bed rest, and a protracted recovery after bed rest, strongly suggesting an altered cardiac morphology and probably a decreased heart size. In the 120-day bed rest study, impairments in blood pressure control during rest and exercise were also assessed. It was found that bed rest causes markedly increased blood pressure deviations during rapid tilts at exercise, indicating impaired reflex and/or effector organ function. Furthermore, it was found that bed rest causes attenuated baroreflex sensitivity for chronotropic responses to arterial pressure stimuli, although this appears to be of modest functional significance. The finding of a reduced degree of mechanical interaction between the two ventricles provided indirect evidence of reduced cardiac size during and after bed rest. Hemodynamic and baroreflex impairments had similar time courses, suggesting that reductions of cardiac size may be a common denominator for both of these types of hemodynamic and baroreflex impairments. Despite these changes, the ability to maintain the arterial blood pressure during steady state conditions was found to be preserved after bed rest.
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| 4. |
- Wu, Ping-Hsun, 1982-
(författare)
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Influence of bone-associated and cardiovascular biomarkers on vascular events and mortality in relation to renal dysfunction
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biomarkers can help physicians identify subjects with an increased cardiovascular risk. Apart from the clinical factors, some biomarkers have been recognized as important predictors and risk factors for cardiovascular disease in renal disease. The applicability of biomarkers may be limited in patients with kidney disease due to the complex etiology of cardiovascular disease, which warrants separate evaluations, including established and novel biomarkers. The overall aim of the thesis was to investigate the association between bone-associated markers and cardiovascular proteins on death and vascular events in the elderly male population and patients with kidney disease.Study I included 3,014 participants in Swedish multicenter prospective Osteoporotic Fractures in Men (MrOS) cohort and investigated the associations between Klotho single-nucleotide polymorphism and mortality. Two potentially damaging single-nucleotide polymorphisms (rs9536314 and rs9527025) in the Klotho gene were not associated with mortality.Study II investigated the association between mineral bone markers and all-cause mortality / cardiovascular mortality. The composite evaluation of elevated fibroblast growth factor-23 levels, vitamin D deficiency, and renal impairment was associated with mortality.Study III evaluated the bone-associated proteins and mortality/composite vascular events in the 331 Demark hemodialysis patients. Osteoprotegerin, as one of the most promising bone-related proteins, was associated with composite vascular events independent of cytokine.Study IV investigated the association between 92 proteins measured by proximity extension assay and mortality/composite vascular events in hemodialysis patients. A higher level of Interleukin-8, T-cell immunoglobulin and mucin domain 1, C-C motif chemokine 20, and lower level of stem cell factor and galanin peptides were associated with poor outcomes.This thesis addressed the issue of bone-vascular axis and cardiovascular disease. We evaluated from gene levels to circulating protein levels and from the general population to patients with kidney disease. Based on our research findings, more evidence was linked between bone and vascular complications. We also identified several cardiovascular proteins considered potentially important predictors for cardiovascular disease in patients with renal failure, especially hemodialysis patients.
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