Publications

D40 is a cell surface protein belonging to the tumor necrosis factor (TNF) receptor family. Ligation of monocyte CD40 by the T cell-derived CD40 ligand can trigger the production of various mediators, the transcription and activation of enzymes, and the upregulation of costimulatory molecules involved in the pathogenesis of sepsis. To test the hypothesis that CD40 is expressed on the surface of monocytes during sepsis, we measured CD40 expression by flow cytometry on freshly sampled monocytes from 40 patients with severe sepsis, including 15 patients with bacteremia, and from eight healthy volunteers. Plasma concentrations of interleukin (IL) 6, IL-10, and IL-13 were also measured. We detected CD40 only on monocytes from patients with sepsis (mean 6.5 +/- 0.4 median channel fluorescence). There was an inverse correlation between peak CD40 expression and survival (P = 0.05), particularly in the patients with bacteremia (P = 0.019). In the bacteremic group, there was an inverse correlation between CD40 expression and bilirubin levels (r2 = 0.52, P = 0.004) and plasma IL-6 concentrations (r2 = 0.30, P = 0.04). Our results showed that upregulation of CD40 expression on peripheral blood monocytes is a protective phenomenon during severe sepsis. Monocyte deactivation reflected by low CD40 expression may represent impairment of immune function associated with severity of illness and poor outcome. Further studies on monocyte phenotype and function may help to assess the immune status of patients with sepsis and perhaps be useful to guide immunomodulatory strategy in the future.

Introduction: Therapeutic hypothermia (TH) can improve neurological outcome after cardiac arrest (CA); little is known about how cooling actually affects brain dynamics after resuscitation from CA. Hypothesis: The aim of this study was to investigate the effects of TH on brain microcirculation and metabolism after CA. Methods: 10 anesthetized, invasively monitored and mechanically ventilated domestic pigs were randomized into two groups (n=5): normothermia (NT, 39.5 ± 1.0 °C) and therapeutic hypothermia (TH, 34.0 ± 1.0°C). After 3 min of untreated ventricular fibrillation, cardiopulmonary resuscitation (CPR) was started and continued for 3 min before defibrillation. Hypothermia was induced at the start of CPR using IV infusion of 30 mL/kg cold saline for 60 min, trans-nasal evaporative cooling (Rhinochill, Benechill Inc, USA) and surface cooling with ice packs. Cooling was maintained for 6 hours, followed by controlled rewarming to baseline temperature. Intraparenchymal probes were used to measure brain temperature (Licox CC1.SB, Integra, NeuroSciences Ltd., Hamphsire, UK) and the lactate-pyruvate ratio (LPR, microdialysis CMA20, CMA, Sweden) hourly. After left craniectomy, the microvascular network of the frontal cortex was evaluated using Sidestream Dark-Field videomicroscopy (Microscan, MicroVision Medical, Netherlands) at baseline (T0), 1 hour after cooling induction (T1), at the end of hypothermia (T2) and after rewarming (T3). The proportion of perfused cerebral small vessels (PPV) was calculated using standard formulas. Results: Time to return of spontaneous circulation was similar in both groups (7 [6-22] mins for NT and 9 [6-21] mins for TH). Microvascular perfusion was significantly decreased after CA, but was better preserved in the TH than in the NT group (PPV: T0 87 ± 3 vs 86 ± 2, T1 37 ± 13 vs 29 ± 3, T2 36 ± 15 vs 24 ± 7, T3 58 ± 7 vs 17 ± 3 – p<0.01). The LPR was higher in the NT than in the TH group throughout the study period (T0 14.1 ± 3.6 vs 13.4 ± 2.6, T1 27.4 ± 9.7 vs 21.7 ± 4.4, T2 43.7 ± 20.4 vs 35.4 ± 9.4, T3 110.4 ± 57.3 vs 62.8 ± 12.6, p<0.05). Conclusions: The cerebral microcirculation was significantly altered after resuscitated CA; TH attenuated these microvascular alterations and had a protective effect on brain metabolism.

In this acute endotoxic shock model, CVVH with the polyacrylonitrile membrane improved cardiac performance when compared with the polysulphone membrane. These effects could be caused by a more effective adsorption of inflammatory mediators other than tumor necrosis factor. Whether the polyacrylonitrile membrane should be preferred over the polysulphone membrane for CVVH in severe sepsis warrants further experimental and clinical study.