Effects of xenon anesthesia on cerebral blood flow in humans: a positron emission tomography study

BACKGROUND: Animal studies have demonstrated a strong neuroprotective property of xenon. Its usefulness in patients with cerebral pathology could be compromised by deleterious effects on regional cerebral blood flow (rCBF). METHODS: 15O-labeled water was used to determine rCBF in nine healthy male subjects at baseline and during 1 minimum alveolar concentration (MAC) of xenon (63%). Anesthesia was based solely on xenon. Absolute changes in rCBF were quantified using region-of-interest analysis and voxel-based analysis. RESULTS: Mean arterial blood pressure and arterial partial pressure for carbon dioxide remained unchanged. The mean (+/-SD) xenon concentration during anesthesia was 65.2+/-2.3%. Xenon anesthesia decreased absolute rCBF by 34.7+/-9.8% in the cerebellum (P<0.001), by 22.8+/-10.4% in the thalamus (P=0.001), and by 16.2+/-6.2% in the parietal cortex (P<0.001). On average, xenon anesthesia decreased absolute rCBF by 11.2+/-8.6% in the gray matter (P=0.008). A 22.1+/-13.6% increase in rCBF was detected in the white matter (P=0.001). Whole-brain voxel-based analysis revealed widespread cortical reductions and increases in rCBF in the precentral and postcentral gyri. CONCLUSIONS: One MAC of xenon decreased rCBF in several areas studied. The greatest decreases were detected in the cerebellum, the thalamus and the cortical areas. Increases in rCBF were observed in the white matter and in the pre- and postcentral gyri. These results are in clear contradiction with ketamine, another N-methyl-D-aspartate antagonist and neuroprotectant, which induces a general increase in cerebral blood flow at anesthetic concentrations.     

Method for patient-specific finite element modeling and simulation of deep brain stimulation

Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.     

The role of macrophage-derived urokinase plasminogen activator in myocardial infarct repair: Urokinase attenuates ventricular remodeling

Cardiac plasmin activity is increased following myocardial ischemia. To test the hypothesis that macrophage-derived uPA is a key mediator of repair following myocardial infarction, we performed myocardial infarction on mice with macrophage-specific over-expression of uPA (SR-uPA mice). SR-uPA^+/0 mice and wild-type littermates were sacrificed at 5 days or 4 weeks after infarction and cardiac content of macrophages, collagen, and myofibroblasts was quantified. Cardiac function and dimensions were assessed by echocardiography at baseline and at 4 weeks post-infarction. At 4 weeks after myocardial infarction, macrophage counts were increased in SR-uPA^+/0 mice in the infarct (13.1 vs. 4.9%, P < 0.001) and distant uninfarcted regions (5.9 vs. 2.4%, P < 0.001). Infarct scar was thicker in SR-uPA^+/0 mice (0.54 ± 0.03 mm vs. 0.45 ± 0.03 mm, P < 0.05) and infarct cardiac collagen content was increased (72.4 ± 3.3% vs. 63.0 ± 3.6%, P < 0.06). Functionally, these changes resulted in mildly improved fractional shortening in SR-uPA^+/0 mice compared to controls (24.6 ± 1.68 vs. 19.8 ± 1.3%, P = 0.03). At 5 days after infarction there was increased collagen content in the scar without increases in macrophages or myofibroblasts. To understand the mechanisms by which macrophage-derived uPA increases collagen, cardiac fibroblasts were treated with macrophage-conditioned medium or plasmin and expression of ColIα1 measured by qPCR. Conditioned media from SR-uPA^+/0 or plasmin-treated non-transgenic macrophages but not plasmin alone increased collagen expression in isolated cardiac fibroblasts. We hypothesize that plasmin generation in the heart in response to injury may induce activation of macrophages to a profibrotic phenotype to allow rapid formation of collagenous scar.     

Effect of restraint stress on the population of intestinal intraepithelial lymphocytes in mice

The impact of restraint stress on the intestinal immune system, particularly on intestinal intraepithelial lymphocytes (i-IEL), has not been described in detail. Thus, the purpose of this study was to assess the effects of restraint stress, including those produced by increases in glucocorticoids and catecholamines, on the population of i-IEL. Mice were exposed to 1 or 4h restraint stress for 4 day, and the number of IEL in the mucosa of the proximal small intestine was determined by immunohistochemistry. The effects of restraint were also analyzed in mice submitted to different procedures: adrenalectomy, chemical sympathectomy, and treatment with a glucocorticoid antagonist (RU486), dexamethasone, and epinephrine. The main findings were that: (1) chronic restraint-stress reduced the i-IEl population in the small intestine; (2) adrenalectomy, treatment with RU-486 and chemical sympathectomy decreased the number of gammadelta, CD4+ and CD8+ T cells in non-stressed groups; (3) dexamethasone reduced the number of gammadelta and CD8+ T cells, and (4) epinephrine reduced the number of gammadelta, CD4+ and CD8+ T cells. These results demonstrated that restraint stress decreased the number of i-IEL in the proximal small intestine of mice, mainly by the combined action of higher concentrations of catecholamines and glucocorticoids, and that lower concentrations of glucocorticoids and catecholamines in unstressed mice preserved the population of i-IEL.     

Comparison of peri-prosthetic bone density in cemented and uncemented total knee arthroplasty

The aim of our study was to assess the effect of knee replacement with or without bone cement on periprosthetic bone density. Periprosthetic bone density in two comparable groups (30 each) of cemented and uncemented knee replacements was measured with DEXA scanner. Bone loss was more in the area posterior to the anterior femoral flange in the cemented subgroup, nearing statistical significance (p = 0.059). In both groups, the reported bone density at a median of four years postoperatively was reduced at several periprosthetic sites. However, the method of fixation could not be clearly demonstrated to influence the bone loss differentially. This brings into question the use of the more expensive cementless implants. Reduction in bone density in both groups at several periprosthetic sites remains a concern. Whether or not this can be addressed with medical intervention like post arthroplasty bisphosphonate treatment needs further consideration.     

Measurement of GABAA receptor binding in vivo with [11C]flumazenil: a test-retest study in healthy subjects

[(11)C]Flumazenil is widely used in positron emission tomography (PET) studies to measure GABA(A) receptors in vivo in humans. Although several different methods have been applied for the quantification of [(11)C]flumazenil binding, the reproducibility of these methods has not been previously examined. The reproducibility of a single bolus [(11)C]flumazenil measurements was studied by scanning eight healthy volunteers twice during the same day. Grey matter regions were analyzed using both regions-of-interest (ROI) and voxel-based analysis methods. Compartmental kinetic modelling using both arterial and reference region input function were applied to derive the total tissue distribution volume (V(T)) and the binding potential (BP) (BP(P) and BP(ND)) of [(11)C]flumazenil. To measure the reproducibility and reliability of each [(11)C]flumazenil binding parameter, absolute variability values (VAR) and intraclass correlation coefficients (ICC) were calculated. Tissue radioactivity concentration over time was best modelled with a 2-tissue compartmental model. V(T) showed with all methods good to excellent reproducibility and reliability with low VARs (mean of all brain regions) (5.57%-6.26%) and high ICCs (mean of all brain regions) (0.83-0.88) when using conventional ROI analysis. Also voxel-based analysis methods yielded excellent reproducibility (VAR 5.75% and ICC 0.81). In contrast, the BP estimates using pons as the reference tissue yielded higher VARs (8.08%-9.08%) and lower ICCs (0.35-0.80). In conclusion, the reproducibility of [(11)C]flumazenil measurements is considerably better with outcome measures based on arterial input function than those using pons as the reference tissue. The voxel-based analysis methods are proper alternative as the reliability is preserved and analysis automated.