Dynamic interactions between musical, cardiovascular, and cerebral rhythms in humans.

BACKGROUND: Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. METHODS AND RESULTS: Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccini's "Turandot") or orchestral (Beethoven's 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdi's arias "Va pensiero" and "Libiam nei lieti calici"), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded.Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases. Vocal and orchestral crescendos produced significant (P=0.05 or better) correlations between cardiovascular or respiratory signals and music profile, particularly skin vasoconstriction and blood pressures, proportional to crescendo, in contrast to uniform emphasis, which induced skin vasodilation and reduction in blood pressures. Correlations were significant both in individual and group-averaged signals. Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables. No qualitative differences in recorded measurements were seen between musicians and nonmusicians. CONCLUSIONS: Music emphasis and rhythmic phrases are tracked consistently by physiological variables. Autonomic responses are synchronized with music, which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases.

S-CMC-Lys protective effects on human respiratory cells during oxidative stress.

The mucoactive drug S-carbocysteine lysine salt monohydrate (S-CMC-Lys) stimulates glutathione (GSH) efflux from respiratory cells. Since GSH is one of the most important redox regulatory mechanisms, the aim of this study was to evaluate the S-CMC-Lys effects on GSH efflux and intracellular concentration during an oxidative stress induced by the hydroxyl radical (xOH). Experiments were performed on cultured human respiratory WI-26VA4 cells by means of patch-clamp experiments in whole-cell configuration and of fluorimetric analyses at confocal microscope. xOH exposure induced an irreversible inhibition of the GSH and chloride currents that was prevented if the cells were incubated with S-CMC-Lys. In this instance, the currents were inhibited by the specific blocker CFTR(inh)-172. CFT1-C2 cells, which lack a functional CFTR channel, were not responsive to S-CMC-Lys, but the stimulatory effect of the drug was restored in LCFSN-infected CFT1 cells, functionally corrected to express CFTR. Fluorimetric measurements performed on the S-CMC-Lys-incubated cells revealed a significant increase of the GSH concentration that was completely hindered after oxidative stress and abolished by CFTR(inh)-172. The cellular content of reactive oxygen species was significantly lower in the S-CMC-Lys-treated cells either before or after xOH exposure. As a conclusion, S-CMC-Lys could exert a protective function during oxidative stress, therefore preventing or reducing the ROS-mediated inflammatory response.

Effect of treatment with nasal continuous positive airway pressure on ventilatory response to hypoxia and hypercapnia in patients with sleep apnea syndrome.

BACKGROUND: The increase in peripheral chemoreflex sensitivity in patients with obstructive sleep apnea (OSA) is associated with activation of autonomic nervous system and hemodynamic responses. Nasal CPAP (nCPAP) is an effective treatment for OSA, but little is known on its effect on chemoreflex sensitivity. OBJECTIVES: To assess the effect of nCPAP treatment or placebo (sham nCPAP) on ventilatory control in patients with OSA. SETTING: Sleep laboratory of Azienda Ospedaliera Garibaldi. PATIENTS: Twenty-five patients with moderate-to-severe OSA. DESIGN AND MEASUREMENTS: Patients were randomly assigned to either therapeutic nCPAP (use of optimal pressure, n = 15) or sham nCPAP (suboptimal pressure of 1 to 2 cm H2O, n = 10) in a double-blind fashion and treated for 1 month. A rebreathing test to assess ventilatory response to normocapnic hypoxia and normoxic hypercapnia was performed at basal condition and after 1 month of treatment. RESULTS: The use of therapeutic nCPAP or sham nCPAP did not affect daytime percentage of arterial oxygen saturation (SaO2%) or end-tidal P(CO2). The normocapnic hypoxic ventilatory response was reduced after 1 month of treatment with nCPAP (the slope was 1.08 +/- 0.02 L/min/SaO2% at basal condition and 0.53 +/- 0.07 L/min/SaO2% after 1 month of treatment, p = 0.008) [mean +/- SD], but not in patients treated with sham nCPAP (slope, 0.83 +/- 0.09 L/min/SaO2% and 0.85 +/- 0.19 L/min/SaO2% at basal condition and after 1 month, respectively). The normoxic hypercapnic ventilatory response remained unchanged after 1 month in both groups. No changes in ventilatory response to either hypoxia or hypercapnia were observed after a single night of nCPAP treatment. CONCLUSION: The ventilatory response to hypoxia is reduced during regular treatment, but not after short-term treatment, with nCPAP. Readjusted peripheral oxygen chemosensitivity during nCPAP treatment may be a side effect of both reduced sympathetic activity and increased baroreflex activity, or a possible continuous positive airway pressure-related mechanism leading to a reduced activation of autonomic nervous system per se.

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells.

Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10(-4) M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclear-related factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10(-8) M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin V-positive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSE-mediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

Cough management: a practical approach.

Cough is one of the most common symptoms for which patients seek medical attention from primary care physicians and pulmonologists. Cough is an important defensive reflex that enhances the clearance of secretions and particles from the airways and protects the lower airways from the aspiration of foreign materials. Therapeutic suppression of cough may be either disease-specific or symptom related. The potential benefits of an early treatment of cough could include the prevention of the vicious cycle of cough. There has been a long tradition in acute cough, which is frequently due to upper respiratory tract infections, to use symptom-related anti-tussives. Suppression of cough (during chronic cough) may be achieved by disease-specific therapies, but in many patients it is often necessary to use symptomatic anti-tussives, too. According to the current guidelines of the American College of Chest Physician on "Cough Suppressants and Pharmacologic Protussive Therapy" and additional clinical trials on the most frequent anti-tussive drugs, it should be possible to diagnose and treat cough successfully in a majority of cases. Among drugs used for the symptomatic treatment of cough, peripherally acting anti-tussives such as levodropropizine and moguisteine show the highest level of benefit and should be recommended especially in children. By improving our understanding of the specific effects of these anti-tussive agents, the therapeutic use of these drugs may be refined. The present review provides a summary of the most clinically relevant anti-tussive drugs in addition to their potential mechanism of action.