Tachycardia in adults with cystic fibrosis is associated with normal autonomic function.

BACKGROUND: Whether autonomic dysfunction contributes to tachycardia in cystic fibrosis (CF) is unknown. METHODS: Heart rate variability (HRV) was assessed to determine high frequency power and the low/high frequency power ratio (HF, LF/HF) as markers of vagal and sympathovagal balance, respectively, under spontaneous and controlled breathing (15 breaths per minute (bpm)) conditions in 17 CF and 17 healthy control subjects. RESULTS: Under spontaneously breathing conditions, the CF group was tachycardic (75.4 ± 11.2 vs 60.2 ± 9.0 br/min P < 0.001) and tachypnoeic (22.6 ± 5.8 vs 13.6 ± 4.1 br/min, P= 0.001) compared with controls. No significant difference in HRV was observed between groups during spontaneous or controlled breathing. Coexistent diabetes mellitus and ß(2) agonist use were not associated with altered autonomic control. During controlled breathing, the CF group showed a negative correlation between forced expiratory volume in 1 s (FEV(1)) % predicted and HF power (P= 0.013, r=-0.59) and a positive correlation between FEV(1) % predicted and LF/HF ratio (P= 0.002, r= 0.69) suggesting an exaggerated normal vagal response. CONCLUSION: CF patients have normal autonomic function.

Adaptive servo-ventilation and deadspace: effects on central sleep apnoea.

Central Sleep Apnoea (CSA) occurs commonly in heart failure. Adaptive servo-ventilation (ASV) and deadspace (DS) have been shown in research settings to reverse CSA. The likely mechanism for this is the increase of PaCO(2) above the apnoeic threshold. However the role of increasing FiCO(2) on arousability remains unclear. To compare the effects of ASV and DS on sleep and breathing, in particular effects on Arousal Index (ArI), ten male patients with heart failure and CSA were studied during three nights with polysomnography plus measurements of PetCO(2). The order of the interventions control (C), ASV and DS was randomized. ASV and DS caused similar reductions in apnoea-hypopnoea index [(C) 30.0 +/- 6.6, (ASV) 14.0 +/- 3.8, (DS) 15.9 +/- 4.7 e h(-1); both P < 0.05]. However, DS was associated with decreased total sleep time compared with C (P < 0.02) and increased spontaneous ArI compared to C and ASV (both P < 0.01). Only DS was associated with increased DeltaPetCO(2) from resting wakefulness to eupnic sleep [(C) 2.1 +/- 0.9, (ASV) 1.3 +/- 1.0, (DS) 5.6 +/- 0.5 mmHg; P = 0.01]. ASV and DS both stabilized ventilation however DS application also increased sleep fragmentation with negative impacts on sleep architecture. We speculate that this effect is likely to be mediated by increased PetCO(2) and respiratory effort associated with DS application.

Effect of CO2 inhalation on central sleep apnea and arousals from sleep.

BACKGROUND: CO(2) inhalation reduces central sleep apnea (CSA) in patients with congestive heart failure (CHF) and idiopathic CSA. CO(2) is also a stimulus for cortical arousal, which has been linked to increased sympathetic nerve activity (SNA) and increased mortality in CHF patients with CSA. OBJECTIVE: We have tested the hypothesis that during sleep, inhalation of CO(2) sufficient to reduce the apnea-hypopnea index (AHI) would not reduce the arousal index (AroI). METHODS: In 10 male patients with CSA (7 with CHF and 3 with idiopathic CSA), the inspired CO(2) concentration was increased to raise the sleeping end-tidal CO(2) by 2-4 mm Hg during established stage 2 sleep. Each intervention was maintained for a 10-min period. Sleep stage was monitored with electroencephalograms, electrooculograms, submental electromyogram, airflow with pneumotachometer and respiratory effort and blood gases with oxygen saturation and end-tidal CO(2). During periods of air and CO(2) breathing, AHI and AroI were compared with paired t tests; patients acted as their own controls. RESULTS: Inhalation of CO(2) produced a significant reduction in AHI (mean +/- SEM) from 74.4 +/- 12.4 events/h during air breathing to 25.8 +/- 7.8 events/h with CO(2) inhalation (p = 0.002). However, the AroI was not significantly different between the two conditions, air 67.8 +/- 12.3 events/h and CO(2) inhalation 52.8 +/- 12.4 events/h (p = 0.264). CONCLUSION: CO(2) inhalation reverses CSA but not arousals from sleep. Our findings highlight the need for treatment options that reduce both respiratory events and decrease arousals from sleep, with their associated SNA sequelae.

Decreased chemotaxis of human peripheral phagocytes exposed to a strong static magnetic field.

The chemotaxis of human peripheral phagocytes, neutrophils and monocytes was examined in a strong static magnetic field (0.317+/-0.012 Tesla). The chemotaxis of the suspension of purified neutrophils and monocytes was tested in the Boyden chamber using C5a as a chemotactic signal. The chambers were placed into a temperature regulated (36.6 degrees C) equipment producing a strong static magnetic field (0.317 Tesla) for 60 minutes. The movement of cells proceeded into a nitrocellulose membrane toward the north-pole of the magnet, i.e. in the direction of the Earth's gravitational pull. The C5a induced chemotaxis of human neutrophils decreased significantly in the strong static magnetic field. Monocytes were not significantly effected. The strong static magnetic field decreased the chemotactic movement of neutrophils and this phenomenon may have implications when humans are exposed to magnetic resonance imaging for extended periods of time.

A novel flow cytometric assay to quantify soluble CD14 concentration in human serum.

BACKGROUND: CD14, the major lipopolysaccharide (LPS)-binding protein of myeloid cells, is found as a soluble molecule in human serum. Recent data describe the presence of elevated soluble CD14 (sCD14) concentration in various disorders, confirming disease activity. A novel, easy, and rapid flow cytometric assay was developed to measure sCD14 levels in serum. METHODS: The assay is based on the competition between membrane-expressed CD14 of isolated monocytes from healthy volunteers and sCD14 in the sample sera for binding to anti-CD14 monoclonal antibodies (mAb; 26ic or 60bca). The amount of cell-associated mAb is determined with a fluorescein isothiocyanate (FITC)-labeled anti-mouse conjugate and flow cytometry. The fluorescence signal is inversely proportional with the amount of serum sCD14. Using dilutions of a standard serum, the concentration of sCD14 in the samples is calculated and compared with results obtained by a commercial sCD14 enzyme-linked immunosorbent assay (ELISA). RESULTS: After optimization, the assay showed log-log linearity of 122.1-984.7 ng/ml sCD14 using mAb 26ic and 29.5-246.2 ng/ml sCD14 using mAb 60bca. It revealed similar results as the ELISA (mAb 26ic: r = 0.88, mAb 60bca: r = 0.92) and provided significantly elevated sCD14 levels in systemic lupus erythematosus patients compared with controls (26ic: 2,213 versus 1,676 ng/ml, P < 0.002; 60bca: 2,625 versus 1,907 ng/ml, P < 0.0002). Receiver operating characteristic curve analysis suggested a reasonable diagnostic efficacy of sCD14 quantification in this autoimmune disease. CONCLUSIONS: The method is easy, rapid, sensitive, and can be used in the follow-up of patients suffering from sepsis or chronic inflammatory disorders.

Ceramide stimulates the uptake of neutral red in human neutrophils, monocytes, and lymphocytes.

Neutral red is a vital stain known to be accumulated in the lysosomes of neutrophils and monocytes. It is used mainly to identify and detect the activated state of these cells. We have found that the extracellular application of physiological ceramide, i.e., a product of sphingomyelin hydrolysis and a newly defined intracellular second-messenger substance, increased the uptake of neutral red in a dose-dependent manner in human neutrophils, monocytes, and lymphocytes, as demonstrated by flow cytometry. Staurosporine was able to totally block this phenomenon, suggesting the involvement of protein kinase C in the process. These results indicate that the flow-cytometric analysis of ceramide-induced uptake of neutral red can be a new method for the evaluation of lysosome-related activation processes in both phagocytes and lymphocytes.