Cardiovascular magnetic resonance assessment of acute cardiovascular effects of voluntary apnoea in elite divers.

BACKGROUND: Prolonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system. The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea. METHODS: Seventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold. RESULTS: Mean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels. CONCLUSION: Compensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted. TRIAL REGISTRATION: This prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226 . Registered 29 October 2014).

The role of muscle strength on tendon adaptability in old age.

PURPOSE: The purpose of the study was to determine: (1) the relationship between ankle plantarflexor muscle strength and Achilles tendon (AT) biomechanical properties in older female adults, and (2) whether muscle strength asymmetries between the individually dominant and non-dominant legs in the above subject group were accompanied by inter-limb AT size differences. METHODS: The maximal generated AT force, AT stiffness, AT Young's modulus, and AT cross-sectional area (CSA) along its length were determined for both legs in 30 women (65 ± 7 years) using dynamometry, ultrasonography, and magnetic resonance imaging. RESULTS: No between-leg differences in triceps surae muscle strength were identified between dominant (2798 ± 566 N) and non-dominant limb (2667 ± 512 N). The AT CSA increased gradually in the proximo-distal direction, with no differences between the legs. There was a significant correlation (P < 0.05) of maximal AT force with AT stiffness (r = 0.500) and Young's modulus (r = 0.414), but only a tendency with the mean AT CSA. However, region-specific analysis revealed a significant relationship between maximal AT force and the proximal part of the AT, indicating that this region is more likely to display morphological adaptations following an increase in muscle strength in older adults. CONCLUSIONS: These findings demonstrate that maximal force-generation capabilities play a more important role in the variation of AT stiffness and material properties than in tendon CSA, suggesting that exercise-induced increases in muscle strength in older adults may lead to changes in tendon stiffness foremost due to alterations in material rather than in its size.

B7x/B7-H4 modulates the adaptive immune response and ameliorates renal injury in antibody-mediated nephritis.

Kidney disease is one of the leading causes of death in patients with lupus and other autoimmune diseases affecting the kidney, and is associated with deposition of antibodies as well as infiltration of T lymphocytes and macrophages, which are responsible for initiation and/or exacerbation of inflammation and tissue injury. Current treatment options have relatively limited efficacy; therefore, novel targets need to be explored. The co-inhibitory molecule, B7x, a new member of the B7 family expressed predominantly by non-lymphoid tissues, has been shown to inhibit the proliferation, activation and functional responses of CD4 and CD8 T cells. In this study, we found that B7x was expressed by intrinsic renal cells, and was up-regulated upon stimulation with inflammatory triggers. After passive administration of antibodies against glomerular antigens, B7x(-/-) mice developed severe renal injury accompanied by a robust adaptive immune response and kidney up-regulation of inflammatory mediators, as well as local infiltration of T cells and macrophages. Furthermore, macrophages in the spleen of B7x(-/-) mice were polarized to an inflammatory phenotype. Finally, treatment with B7x-immunoglobulin (Ig) in this nephritis model decreased kidney damage and reduced local inflammation. We propose that B7x can modulate kidney damage in autoimmune diseases including lupus nephritis and anti-glomerular basement membrane disease. Thus, B7x mimetics may be a novel therapeutic option for treatment of immune-mediated kidney disease.

Assessment of arterially hyper-enhancing liver lesions using virtual monoenergetic images from spectral detector CT: phantom and patient experience.

PURPOSE: To investigate a benefit from virtual monoenergetic reconstructions (VMIs) for assessment of arterially hyper-enhancing liver lesions in phantom and patients and to compare hybrid-iterative and spectral image reconstructions of conventional images (CI-IR and CI-SR). METHODS: All imaging was performed on a SDCT (Philips Healthcare, Best, The Netherlands). Images of a non-anthropomorphic phantom with a lesion-mimicking insert (containing iodine in water solution) and arterial-phase images from contrast-enhanced patient examinations were evaluated. VMIs (40-200 keV, 10 keV increment), CI-IR, and CI-SR were reconstructed using different strengths of image denoising. ROIs were placed in lesions, liver/matrix, muscle; signal-to-noise, contrast-to-noise, and lesion-to-liver ratios (SNR, CNR, and LLR) were calculated. Qualitatively, 40, 70, and 110 keV and CI images were assessed by two radiologists on five-point Likert scales regarding overall image quality, lesion assessment, and noise. RESULTS: In phantoms, SNR was increased threefold by VMI40keV compared with CI-IR/SR (5.8 ± 1.1 vs. 18.8 ± 2.2, p ≤ 0.001), while no difference was found between CI-IR and CI-SR (p = 1). Denoising was capable of noise reduction by 40%. In total, 20 patients exhibiting 51 liver lesions were assessed. Attenuation was the highest in VMI40keV, while image noise was comparable to CI-IR resulting in a threefold increase of CNR/LLR (CI-IR 1.3 ± 0.8/4.4 ± 2.0, VMI40keV: 3.8 ± 2.7/14.2 ± 7.5, p ≤ 0.001). Subjective lesion delineation was the best in VMI40keV image (p ≤ 0.01), which also provided the lowest perceptible noise and the best overall image quality. CONCLUSIONS: VMIs improve assessment of arterially hyper-enhancing liver lesions since they increase lesion contrast while maintaining low image noise throughout the entire keV spectrum. These data suggest that to consider VMI screening after arterially hyper-enhancing liver lesions.

Effects of repetitive prolonged breath-hold in elite divers on myocardial fibrosis and cerebral morphology.

BACKGROUND: Prolonged apnea by breath-hold (BH) divers leads to hypoxemia and compensatory mechanisms of the cardiovascular system (i.e. increase of total peripheral resistance, increase of systolic blood-pressure, left-ventricular enlargement) to maintain oxygen supply to oxygen sensitive organs such as the brain. All these changes may result in structural myocardial or subclinical brain alterations. Therefore, the aim of this study was to investigate mid-term effects of repetitive prolonged apnea using cardiac magnetic resonance imaging (CMR) and magnetic resonance imaging of the brain. MATERIALS AND METHODS: 17 elite BH divers (15 males) were investigated at baseline, from whom 9 (7 males) were investigated again at follow-up one year later. CMR included functional imaging and tissue characterization using T1- and T2-mapping as well as late gadolinium enhancement. Results were compared intra-individually and with 50 age matched controls. RESULTS: Mean BH time were 297 ±â€¯52 s (entire cohort) and 315 ±â€¯56 s (sub-cohort) at initial, and 334 ±â€¯104 s at follow-up examination. Apnea resulted in a progressive increase of the left ventricle and impaired function, whichfully resolved after cessation of apnea. At rest, no dilation of the left ventricle was notable (LV-EDV: 106.7 ±â€¯28.8 ml; LV-EDV/BSA: 52.2 ±â€¯12.7 ml/m2). Compared to controls, the apnea group showed significantly lower volumes (LV-EDV: 106.7 ±â€¯28.8 ml vs. 140.9 ±â€¯36.3 ml, p = .008; LV-EDV/BSA: 52.2 ±â€¯12.7 ml/m2 vs. 73.7 ±â€¯12.8 ml/m2). In contrast, LV-EF showed no significant differences between both groups (61.0 ±â€¯7.0% vs. 60.9 ±â€¯3.6%). T1- and T2-mapping revealed no significant differences, neither intra-individually nor in comparison with age matched controls. (T1 pre-contrast: 974.1 ±â€¯12.9 ms vs. 969.4 ±â€¯29.0 ms, p = .2; T1 post-contrast: 368.9 ±â€¯38.5 ms vs. 966.7 ±â€¯40.5 ms, p = .4; ECV: 29.2 ±â€¯1.5% vs. 29.8 ±â€¯1.6%, p = .3; T2. 52 ±â€¯2 ms vs. 52 ±â€¯3 ms; p = .4). Except for one old embolic lesion no structural changes were found in brain imaging. CONCLUSION: Although, prolonged apnea leads to impressive adaptions of the cardiovascular system (i.e. dilation of the left ventricle) and hypertension due to peripheral vasoconstriction no mid-term morphological changes could be observed in both, the myocardium and the brain. BH divers are suitable as a model to investigate acute physiological changes of prolonged apnea and hypoxemia, but not as a model for chronic alterations.

Comparison of magnetic resonance feature tracking with harmonic phase imaging analysis (CSPAMM) for assessment of global and regional diastolic function.

AIMS: Complex post-processing is required for strain-derived assessment of diastolic dysfunction (DD) using CMR-tagging (TAG). Feature-tracking (FT), allows for rapid systolic strain assessment using conventional steady-state free precession (SSFP)-Cine sequences. Aim of this study was to investigate whether FT may be employed for the clinically applicable quantification of DD. METHODS AND RESULTS: 40 individuals (20 patients with DD I-III°, 20 controls) were investigated. CSPAMM and SSFP-Cine sequences were acquired in identical short-axis locations. Global and regional early diastolic strain rate (EDSR), peak diastolic strain rate (PDSR), twist, untwist and torsion were calculated from tagged and SSFP-Cine datasets. DD indices were compared, intra- as well inter-observer variability assessed. RESULTS: for global EDSR correlated strongly (r=0.94), revealed good agreement and no significant differences between both methods. Correlation for regional EDSR was lower, results differed significantly in the anterior wall (p<0.05). Correlation for PDSR was moderate (r=0.63), results in the healthy control group differed significantly (p<0.05). FT derived rotational indices correlated poorly with TAG (twist: r=0.28; untwist: r=0.02; torsion: r=0.26), subgroup analysis revealed significant differences (p<0.05). Intra- and inter-observer variability for FT derived global EDSR and PDSR were comparable to TAG, but significantly higher for regional EDSR and rotational indices. CONCLUSION: FT derived global EDSR allows for rapid clinical determination of diastolic dysfunction, revealing good agreement with TAG and low intra- as well as interobserver variability. However, TAG analysis not only yields higher accuracy and reproducibility of global- and regional diastolic strain, but also delivers reliable information about diastolic rotational and untwisting dynamics.

Renal denervation: results of a single-center cohort study.

PURPOSE: To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. MATERIALS AND METHODS: Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. RESULTS: Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ±â€Š3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ±â€Š20.3/103.8 ±â€Š20.4 mmHg and 155.2 ±â€Š20.5/93.7 ±â€Š14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ±â€Š14.9/89.5 ±â€Š12.1 (p < 0.05). ABPM values remained unchanged (147.9 ±â€Š20.3/90.3 ±â€Š15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ±â€Š2.0 vs. 4.2 ±â€Š1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. CONCLUSION: After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension. KEY POINTS: • Renal denervation showed no significant effects on 24-h ambulatory blood pressure measurements. • A significant decrease in office blood pressure measurements may be explained by a potential detection bias. • Renal artery alterations were not observed on follow-up MRI scans.

Mechanisms of circumduction and axial rotation of the carpometacarpal joint of the thumb.

Osteoarthritis of the carpometacarpal joint of the thumb (CMCJ) is a frequent clinical problem. The aim of the study was to discuss the mechanisms of circumduction and axial rotation of the CMCJ considering geometrical properties of the articulating surfaces and the configuration of the muscle system acting over the CMCJ. 28 CMCJ from 7 female and 7 male corpses (age: 81 yrs (median), 53-91 yrs (interval), which did not show any sign of arthrosis, were investigated. Contours in flexion/extension: in saddle point O, the contour of the proximal surface is stronger curved. For 23 of the 28 joints the contours showed an eye-catching difference. Contours in ab-/adduction: all 28 joints showed the respective incongruity. Straight lines and their included angles: in both articulating surfaces, the angles between the straight lines through the saddle point showed values which were close to 90 degrees. Out of neutral position a small axial rotation (maximal range: 3.5 degrees) is possible without that the contact at the saddle points is changed. But, when one of the straight lines of the proximal surface meets a respective straight line of the distal surface, the contact "point" is enlarged to a contact "line". When the axial rotation is further increased, the contact "line" splits into two contacts "points", which are located at outer areas of the articulating surfaces.

Gamma-aminobutyric acid pathway and modified tricarboxylic acid cycle activity during growth and sporulation of Bacillus thuringiensis.

Enzymatic analyses of Bacillus thuringiensis extracts suggest that a modified Krebs tricarboxylic acid cycle (without alpha-ketoglutarate dehydrogenase) can operate during sporulation in conjunction with the glyoxylic acid cycle and the gamma-aminobutyric acid pathway.