Assessment of dynamic changes in cerebral autoregulation.

Cerebral autoregulation (CA) is a control mechanism that adjusts cerebral vasomotor tone in response to changes in arterial blood pressure (ABP) to ensure a nearly constant cerebral blood flow. Patient treatment could be optimized if CA monitoring were possible. Whereas the concept of static CA assessment is simply based on comparison of mean values obtained from two stationary states (e.g., before and after a pressure change), the evaluation of dynamic CA is more complex. Among other methods, moving cross-correlation analysis of slow waves in ABP and cerebral blood flow velocity (CBFV) seems to be appropriate to monitor CA quasi-continuously. The calculation of an "instantaneous transfer function" between ABP and CBFV oscillations in the low-frequency band using the Wigner-Ville distribution may represent an acceptable compromise in time-frequency resolution for continuous CA monitoring.

Continuous cerebral autoregulation monitoring by improved cross-correlation analysis: comparison with the cuff deflation test.

OBJECTIVES: To improve the cross-correlation method for noninvasive, continuous monitoring of cerebral autoregulation, to evaluate this method in humans with intact and impaired autoregulatory capacity, and to compare it to the cuff deflation test. DESIGN AND SETTING: Prospective study in the intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Fourteen patients with severe head injury, six patients with subarachnoid hemorrhage, and nine healthy volunteers. INTERVENTIONS AND MEASUREMENTS: Middle cerebral artery flow velocities and arterial blood pressure were monitored continuously. Aaslid's thigh cuff tests were performed and results were scored using Tiecks' model for autoregulation index. Data were then collected without any patient manipulation. The mean time delay between slow spontaneous oscillations of blood pressure and middle cerebral artery flow velocity was calculated by cross-correlation analysis. Data are expressed as median (lower/upper quartile). RESULTS: Healthy subjects had a higher autoregulation index than patients, 5.0 (5.0/5.5) vs. 3.3 (2.0/4.5). Slow oscillations of blood pressure and middle cerebral artery flow velocity showed a time delay of -2.0 s (-2.7/-1.7) in healthy subjects but were almost synchronal in patients, -0.07 s (-0.5/0.45). Inter-method agreement in diagnosing an intact or impaired cerebral autoregulation was obtained in 108 of 147 examinations of autoregulation (73.5%) and was considered moderate. CONCLUSIONS: Cross-correlation analysis may serve as a simple, noninvasive, and continuous measure of cerebral autoregulation. The time delay of -2.0[Symbol: see text]s in healthy subjects is in good agreement with other studies. Short-term autoregulation tests and monitoring techniques based on slow spontaneous oscillations should not be used interchangeably.

Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution.

BACKGROUND & AIMS: Ulcerative colitis (UC) is characterized by a Th2 immune response with inflammation and epithelial barrier dysfunction. So far, Th2 cytokines have not been shown to directly influence epithelial barrier function. METHODS: Lamina propria mononuclear cells (LPMCs) were stimulated and interleukin (IL)-13 was measured by enzyme-linked immunosorbent assay. Functional IL-13 and IL-4 effects were studied on HT-29/B6 colonic epithelial cells in Ussing chambers and by conductance scanning. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. IL-13/IL-4 receptors were analyzed by reverse-transcription polymerase chain reaction and immunofluorescence. Western blotting combined with immunofluorescence was used to detect tight junction proteins. Furthermore, restitution velocity was measured. Finally, mucosal biopsy specimens from patients with UC were compared with cultured cells for these features. RESULTS: LPMCs from patients with UC produced large amounts of IL-13 (985 +/- 73 pg/mL), much more than from controls or patients with Crohn's disease. IL-13Ralpha1 and IL-4Ralpha receptors were present in HT-29/B6 cells and colonic epithelial cells of control patients and patients with UC. IL-13 had a dose-dependent effect on transepithelial resistance of HT-29/B6 monolayers (reduction to 60% +/- 4%), whereas IL-4 had no effect. This was due to an increased number of apoptotic cells (5.6-fold +/- 0.9-fold) and an increased expression of the pore-forming tight junction protein claudin-2 to 295% +/- 37%, both of which contributed equally. Finally, epithelial restitution velocity decreased from 15.1 +/- 0.6 to 10.6 +/- 0.5 microm/h after treatment with IL-13. Parallel changes were observed in human samples, with an increase in claudin-2 expression to 956% +/- 252%. CONCLUSIONS: IL-13 was identified as an important effector cytokine in UC that impairs epithelial barrier function by affecting epithelial apoptosis, tight junctions, and restitution velocity.