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11.
Increased SR Ca2+ cycling contributes to improved contractile performance in SERCA2a-overexpressing transgenic rats 总被引:6,自引:0,他引:6
Maier LS Wahl-Schott C Horn W Weichert S Pagel C Wagner S Dybkova N Müller OJ Näbauer M Franz WM Pieske B 《Cardiovascular research》2005,67(4):636-646
OBJECTIVE: Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transgenic rat hearts (TG) results in improved contractility. However, it was not clear whether TG have improved contractility due to frequency-dependent improved SR Ca2+ handling. METHODS: Therefore, we characterized TG (n=35) vs. wild-type (WT) control rats (n=39) under physiological conditions (37 degrees C, stimulation rate <8 Hz). Twitch force, intracellular Ca2+ transients ([Ca2+]i), and SR Ca2+ content were measured in isolated muscles. The contribution of transsarcolemmal Ca2+ influx (I(Ca)) through L-type Ca2+ channels (LTCC) and reverse mode NCX (I(Na/Ca)) to Ca2+ cycling were studied in isolated myocytes. RESULTS: With increasing frequency, force increased in TG muscles by 168+/-35% (8 Hz; P<0.05) and SR Ca2+ content increased by maximally 118+/-31% (4 Hz; P<0.05). In WT, there was a flat force-frequency response without changes in SR Ca2+ content. Relaxation parameters of force and [Ca2+]i decay were accelerated at each frequency in TG vs. WT by approximately 10%. At prolonged rest intervals (<240 s), force and SR Ca2+ content increased significantly more in TG. Consequently, absolute SR Ca2+ content measured in myocytes was increased approximately 2-fold in TG. Transsarcolemmal Ca2+ fluxes estimated by I(Ca) (at 0 mV -10.2+/-1.1 vs. -16.9+/-1.3 pA/pF) and I(Na/Ca) (0.17+/-0.02 vs. 0.46+/-0.05 pA/pF) were decreased in TG vs. WT (P<0.05), whereas NCX and LTCC protein expression was only slightly reduced (P=n.s.). CONCLUSION: In summary, SERCA2a-overexpression improved contractility in a frequency-dependent way due to increased SR Ca2+ loading whereas transsarcolemmal Ca2+ fluxes were decreased. 相似文献
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Tim C. van den Beukel Carlo Lucci Jeroen Hendrikse Wilko Spiering Huiberdina L. Koek Mirjam I. Geerlings Pim A. de Jong 《Journal of neuroradiology. Journal de neuroradiologie》2021,48(4):248-253
Background and purposeVertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan.Materials and methodsAll patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤ 0.90, ≥ 1.30, continuous), internal carotid artery stenosis ≥ 70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex.ResultsOf the 471 patients included (57% male, median age 58 [interquartile range 47–63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years = 1.70 [95%CI 1.46–1.99]), DM (RR = 1.45 [95%CI 1.03–2.06]), obesity (RR = 1.53 [95%CI 1.10–2.12]), ABI ≤ 0.90 (RR = 1.57 [95%CI 1.02–2.41]), and an increased carotid IMT (RR = 2.60 per mm [95%CI 1.20–5.62]). Other measurements were not associated with VBAC.ConclusionsWe identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention. 相似文献
13.
Nienke A. Hoffmans-Holtzer Daan Hoffmans Max Dahele Ben J. Slotman Wilko F.A.R. Verbakel 《Strahlentherapie und Onkologie》2015,191(3):272-280
Purpose
The purpose of this work was to investigate whether adapting gantry and collimator angles can compensate for roll and pitch setup errors during volumetric modulated arc therapy (VMAT) delivery.Methods
Previously delivered clinical plans for locally advanced head-and-neck (H&N) cancer (n?=?5), localized prostate cancer (n?=?2), and whole brain with simultaneous integrated boost to 5 metastases (WB + 5M, n?=?1) were used for this study. Known rigid rotations were introduced in the planning CT scans. To compensate for these, in-house software was used to adapt gantry and collimator angles in the plan. Doses to planning target volumes (PTV) and critical organs at risk (OAR) were calculated with and without compensation and compared with the original clinical plan. Measurements in the sagittal plane in a polystyrene phantom using radiochromic film were compared by gamma (γ) evaluation for 2 H&N cancer patients.Results
For H&N plans, the introduction of 2°-roll and 3°-pitch rotations reduced mean PTV coverage from 98.7 to 96.3?%. This improved to 98.1?% with gantry and collimator compensation. For prostate plans respective figures were 98.4, 97.5, and 98.4?%. For WB + 5M, compensation worked less well, especially for smaller volumes and volumes farther from the isocenter. Mean comparative γ evaluation (3?%, 1 mm) between original and pitched plans resulted in 86?% γ <?1. The corrected plan restored the mean comparison to 96?% γ <?1.Conclusion
Preliminary data suggest that adapting gantry and collimator angles is a promising way to correct roll and pitch set-up errors of <?3° during VMAT for H&N and prostate cancer.14.
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Astrid Rauh-Pfeiffer Uschi Handel Hans Demmelmair Wolfgang Peissner Mareile Niesser Diego Moretti Vanessa Martens Sheila Wiseman Judith Weichert Moritz Heene Markus Bühner Berthold Koletzko 《European journal of nutrition》2014,53(7):1445-1456