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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 +/- 52 s (entire cohort) and 315 +/- 56 s (sub-cohort) at initial, and 334 +/- 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 +/- 28.8 ml; LV-EDV/BSA: 52.2 +/- 12.7 ml/m(2)). Compared to controls, the apnea group showed significantly lower volumes (LV-EDV: 106.7 +/- 28.8 ml vs. 140.9 +/- 36.3 ml, p = .008; LV-EDV/BSA: 52.2 +/- 12.7 ml/m(2) vs. 73.7 +/- 12.8 ml/m2). In contrast, LV-EF showed no significant differences between both groups (61.0 +/- 7.0% vs. 60.9 +/- 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 +/- 12.9 ms vs. 969.4 +/- 29.0 ms, p = .2; T1 post-contrast: 368.9 +/- 38.5 ms vs. 966.7 +/- 40.5 ms, p = .4; ECV: 29.2 +/- 1.5% vs. 29.8 +/- 1.6%, p = .3; T2. 52 +/- 2 ms vs. 52 +/- 3 ms; p = .4). Exc

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea.MATERIALS AND METHODS: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31P-/1H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed.RESULTS: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02].CONCLUSIONS: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hyp

This pCASL and 31P/1H-MRS study explored the cerebrovascular reactivity (CVR) and its efficacy on brain metabolic stability during a five-minute breathhold in fifteen experienced freedivers. Cerebral blood flow (CBF) increase occurred later than the decrease of the recently discovered arterial transit time correlate, spatial CoV. The latter may thus be an early CVR biomarker. CBF varied between vessel territories, gray and white matter and usually lowered with more experience. MRS showed near stable physiological cerebral ATP and pH concentrations despite peripheral lactate acidosis. In conclusion, this trial revealed that CVR sufficiently compensates the metabolic challenge of a five minute breath-hold. In conclusion, this trial revealed that cerebral perfusion increase sufficiently compensates the metabolic challenge of a five-minute breath-hold.

BACKGROUND AND PURPOSE: Experienced freedivers can endure prolonged breath-holds of up to eleven minutes despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity (CVR). This multi-parametric study investigates CBF, the spatial coefficient of variation (ASL-sCoV), as a correlate of arterial transit time, and brain metabolism dynamics during prolonged apnea. MATERIALS AND METHODS: Fifteen male freedivers (median age: 36.0, CI 32.0–50.0, years; median previous prolonged breath-holds >2.5 mins.: 384, CI 24.0–4,536) underwent repetitive 3T pseudo-continuous arterial spin labeling and 31P-/1H-MR spectroscopy scans before, during and after a five-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. CVR was temporally and regionally compared to blood gases and previous experience. RESULTS: ASL-sCoV decreased during the early breath-hold phase (-30.0%, P=.002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%; P<.0001). CVR differed between the anterior and the posterior circulation during all phases (e.g. late breath-hold: MCA 57.3±14.2 vs. PCA 42.7±10.8 mL/100 g/min.; P=.001). There was an association between breath-hold experience and lower CBF (1,000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min.; CI 0.15 –1.1 mL/100 g/min., P=.01). While breath-hold caused peripheral lactate rise (+18.5 %) and hypoxemia (SpO2 -24.0%), cerebral lactate and ATP remained within physiological ranges, despite early signs of oxidative stress (-6.4% phosphocreatine/(ATP+ADP); P=.02). CONCLUSIONS: The CVR responses to prolonged apnea are complex, but guarantee the maintenance of a physiological brain metabolism in trained individuals for at least five minutes.

The purpose of this study was to establish an MRI protocol on a clinical scanner for assessment of left (LV) and right (RV) ventricular myocardial function of the murine heart, and to apply this protocol for the first in vivo assessment of myocardial function in a mouse model of cardiomyopathy (Desmin-/-). MRI was performed on a clinical 3 T whole body MRI system using a dedicated solenoid receive-only coil. Contiguous short axis slices were acquired covering the entire heart using a spoiled cine gradient echo sequence (TR 9-12 ms, TE 3-4 ms, alpha 25A degrees, 1.0 x 0.23 x 0.23 mmA(3)). Global LV- and RV-myocardial functional parameters such as end-diastolic ventricular volume, ejection fraction (EF), LV mass and cardiac output (CO) of Desmin-/- mice and age-matched controls were determined. Global myocardial functional data of healthy controls (n = 4) were in very good agreement with previously reported data. The transgenic mice (n = 8) revealed a significantly reduced LV- and RV-EF as well as CO. Body weight-normalized LV- and RV-end-diastolic volumes and LV mass were significantly increased. In addition desmin deficient mice exhibited segmental wall thinning and akinesia, suggesting myocardial necrosis. This study demonstrates that clinical 3 T MRI-systems may reliably be used for non-invasive assessment of LV- and RV-myocardial function in normal and in genetically engineered mice with cardiomyopathies. In addition, this proof of principle study presents first in vivo MRI data of the cardiac phenotype of desmin knock-out mice.

Interleukin (IL)-22 is an effector cytokine, which acts primarily on epithelial cells in the skin, gut, liver and lung. Both pro- and anti-inflammatory properties have been reported for IL-22 depending on the tissue and disease model. In a murine model of allergic airway inflammation, we found that IL-22 is predominantly produced by innate lymphoid cells in the inflamed lungs, rather than TH cells. To determine the impact of IL-22 on airway inflammation, we used allergen-sensitized IL-22-deficient mice and found that they suffer from significantly higher airway hyperreactivity upon airway challenge. IL-22-deficiency led to increased eosinophil infiltration lymphocyte invasion and production of CCL17 (TARC), IL-5 and IL-13 in the lung. Mice treated with IL-22 before antigen challenge displayed reduced expression of CCL17 and IL-13 and significant amelioration of airway constriction and inflammation. We conclude that innate IL-22 limits airway inflammation, tissue damage and clinical decline in allergic lung disease.

Contains fulltext : 88059.pdf (publisher's version ) (Closed access), PURPOSE: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. PATIENTS AND METHODS: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine the eligibility for APBI: invasive ductal adenocarcinoma of < or =3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. RESULTS: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). CONCLUSION: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.

Volume reduction of bilateral hippocampus, bilateral EC and right amygdala supports the concept of SMI as a very early manifestation of AD prior to MCI. SMI may indicate awareness of a degenerative process that can still be functionally compensated.

Udgivelsesdato: 2008/8