Search

Ischemia of the myocardium is generally accepted to be characterized by swelling of myocytes resulting in cardiac dysfunction. However, data are limited concerning the molecular mechanisms of fast water fluxes across cell membranes in ischemic hearts. Since aquaporin-4 (AQP4) is a water channel with an enormous water flux capacity, we investigated in this study whether this water channel protein might play a role in myocyte swelling following myocardial infarction. For this purpose, we studied the expression of AQP4 mRNA at different time points of ischemia in a murine model of myocardial infarction. We observed a significant correlation between the upregulation of AQP4 mRNA and the size of the infarction. In situ hybridization experiments showed comparably higher expression levels of AQP4 mRNA in ischemic myocytes, and anti-AQP4 immunoreactivity was found to be stronger in the sarcolemma of ischemic myocytes. Our findings imply a role of AQP4 in the formation of myocardial edema and this might be important for future prevention and treatment strategies of this distressing situation in order to minimize cardiac dysfunction and mortality in a variety of cardiac diseases in which cell swelling is prevalent., (2007 S. Karger AG, Basel)

Background: Respiratory muscle weakness is one of the most important causes of hypercapnia in patients with COPD. There is evidence that stable hypercapnic patients will benefit from long-term oxygen therapy (LTOT)., Objectives: The prognostic role of reversible hypercapnia in COPD is still unclear. Early implementation of LTOT in these patients may influence endurance time and mortality., Methods: In this pilot study, we investigated 28 patients (26 males, 49-74 years) with COPD, advanced airflow limitation [forced expiratory volume in 1 s (percentage of predicted value) 40.8 +/- 10.2] and mild hypoxaemia (pO(2) 66.5 +/- 6.3 mm Hg). All patients had developed a moderate reversible hypercapnia during an acute exacerbation or during exercise testing (peak pCO(2) 48.0 +/- 2.5 mm Hg). Patients were allocated randomly to a control group (n = 14) or an LTOT group (n = 14). The two groups were well matched in terms of physiological data. Lung function, endurance time (cycle ergometer), dyspnoea score, blood gases and LTOT compliance were measured at baseline and every 6 months over a period of 3 years., Results: Endurance time increased from 6.4 +/- 2.7 min at baseline to 7.1 +/- 2.7 min after 1 year in the LTOT group and decreased from 6.1 +/- 3.0 to 4.9 +/- 3.8 min in the controls (p < 0.05). After 1 year, the end-exercise dyspnoea score was significantly lower in the LTOT group (4.5 +/- 1.5) than in the controls (5.7 +/- 1.9)., Conclusion: COPD patients with reversible hypercapnia and mild hypoxaemia benefit from LTOT in terms of endurance time and a reduction of exertional dyspnoea after 1 year., (Copyright 2004 S. Karger AG, Basel)

Background: In the treatment of obstructive sleep apnea (OSA), mandibular advancing devices (MAD) are usually individually fabricated on plaster casts of both jaws from polymethyl-methacrylate. The potential disadvantages of these devices are (1) the costs and (2) the time required to construct the device., Objective: In this study, the efficacy and feasibility of a cheap MAD consisting of thermoplastic material (SnorBan((R))), which can be directly moulded intraorally, were evaluated., Methods: In a prospective study, the effect of an MAD consisting of thermoplastic material was investigated in 22 consecutive patients with OSA [respiratory disturbance index (RDI) 32.6 +/- 18.4/h]. Polysomnographic sleep was recorded prior to treatment and after 3 months of treatment with the MAD., Results: Three of the 22 patients who did not tolerate the MAD were excluded from the analysis, whereas 11 patients were classified as responders. In the responder group, the mean RDI decreased from 27.6 +/-7.3 to 7.3 +/- 2.9 (p < 0. 01), correspondingly the sleep quality and the Epworth Sleepiness Scale improved (p < 0.05). Eight patients proved to be non-responders without relevant changes for the measured parameters., Conclusions: In 50% (11 of 22) of the patients, the MAD improved the OSA to a clinically relevant degree. In contrast to the majority of established MAD, the MAD investigated is cheap and immediately adaptable and thus a feasible strategy to 'screen' the efficacy of this therapeutic principle. Thus the construction of unnecessary MAD is avoided., (Copyright 2000 S. Karger AG, Basel)

Acute exacerbation of chronic obstructive pulmonary disease (COPD) is associated with dyspnea and, consequently, reduced mobility. Immobility is a recognized risk factor of deep-vein thrombosis (DVT), but few data exist regarding the prevalence of DVT in patients with acute exacerbation of COPD. Real-time B-mode ultrasonography (US) is a noninvasive screening method for the diagnosis of DVT. We therefore used US to investigate the prevalence of DVT in patients with an acute exacerbation of COPD. In a prospective cohort study, 196 patients with COPD were studied [110 males, 86 females, age: 66.9 +/- 9.1 years, weight: 63.5 +/- 12.7 kg, forced expiratory volume in 1 s (FEV1): 0.7 +/- 0.2 liters, and a ratio of FEV1 to vital capacity (VC): 37 +/- 6%] in a respiratory intensive care unit on the day of admission. Patients with reduced mobility due to other disease were excluded. All US were performed by one experienced person with a 5-MHz linear scanner. The views of the lower extremity were subdivided into three segments: (1) the common femoral, (2) superficial femoral veins including the long saphenous vein and (3) the popliteal vein. In 21 of 196 COPD patients (10.7%), DVT were demonstrated; 18 of these were asymptomatic. Bilateral DVT were not found. In 6 patients, additional diagnoses were: Baker's cyst (n = 3), inguinal lymph node (n = 1) and knee joint effusion (n = 2). There were no differences between patients with and with DVT with respect to age, hemoglobin, PO2, PCO2, pH, FEV1, VC or dyspnea scale. DVT in the lower extremity, which was not detectable on clinical examination, was relatively common in patients with an acute exacerbation of COPD. All clinical variables measured (age, weight, dyspnea scale, lung function, hemoglobin, hematocrit and blood gases) failed to predict patients more likely to have DVT.

Apnea and hypopnea during sleep are often viewed as different expressions of the same sleep-related breathing disorder. In our point of view, both symptoms are two different entities which can occur in the same patient. We discuss the hypothesis that sleep apnea is a disorder associated with recurrent arousals and chronic activation of the sympathetic nervous system, leading to daytime sleepiness and disturbances in the autonomic system. Hypoventilation results from reduced alveolar ventilation and is associated with hypercapnia. In rare cases it is caused by genuine disorders of the breathing center, like Odine's curse. In most cases, hypoventilation is secondary to an underlying disease and a strategy of the body, to avoid respiratory muscle failure. Treatment trials of hypoventilation of the respiratory muscles by stimulating the breathing center failed to be beneficial. However, unloading treatment with long-term oxygen and/or home mechanical ventilation improves arterial blood gases, physical activity and prognosis.

Acute exposure to sublethal doses of chlorine gas resulted in persistent pulmonary symptoms in 3 patients who had no past history of respiratory disease. The patients complained of intermittent dyspnea in association with respiratory irritants and physical exertion for more than 2.5 years postexposure. Four months after the accident bronchoalveolar lavage showed an inflammatory cell reaction, whereas 16 months later the differential cytology proved nearly normal. Moderate to severe nonspecific bronchial hyperresponsiveness was assessed in intervals of 4, 20 and 30 months after the accident. All patients showed the typical features of the reactive airways dysfunction syndrome defined as an asthma-like occupational illness after an acute exposure to highly concentrated respiratory irritants. We conclude that a single high exposure to chlorine gas may lead both to acute respiratory injury and to long-term reactive airway dysfunction with typical symptoms of inflammatory changes of the airways and nonspecific bronchial hyperresponsiveness.

The actual deposition pattern of micronized drugs from metered dose inhalers (MDI) is incompletely known because there are no methods available to label the drugs (beta 2-agonists) with gamma-emitters. Indirect measurements of the distribution of the drug in man differed greatly due to the method used. Our method uses the better solubility of 99mTcO4- in the beta 2-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the 99mTcO4- from the original water phase into the liquid phase of the propellant with ethyl methyl ketone. For labeling the micronized drug particles, the original MDI must be cooled to -60 degrees C and some labeled propellant (including surfactant) with high specific activity of 99mTcO4- is added through an aperture in the bottom of the container. The aperture is sealed with a screw. After rewarming the MDI, more than 90% of the added 99mTcO4- is dissolved in the beta 2-agonist-micronized drug in relation to its volume. This is proved by comparing the distribution of the radioactivity component with chemical analysis. The pattern of deposition of both MDIs - placebo and beta 2-agonist-micronized drug - was shown to be similar in healthy volunteers. With a labeled MDI a preliminary study with 2 different inhaling maneuvers was performed in 7 volunteers: inhaling from residual volume after a pause of 2 s the intrabronchial deposition was 18.7%, and inhaling at 50% of vital capacity maneuver the intrabronchial deposition was 33.0%. The data obtained with actual measurement of the inhaled drug from MDI suggest greater intrabronchial deposition than was assumed before in the literature.

We measured the mucociliary clearance rates and lung function data of 40 normal subjects, of 30 smokers with chronic bronchitis and of 64 patients with bronchial carcinoma. The mucociliary clearance rate of cancer patients was significantly lower than that of normal subjects and of patients with chronic bronchitis who smoked the same amount of cigarettes. The fast clearing phase of the central bronchial tree is more delayed than the peripheral mucociliary clearance rate in smokers with and without carcinoma. With our mucociliary clearance measurement we assessed the self-cleaning filter function of about the first 10 generations of the branching bronchial tree where also most bronchial carcinomas develop. The correlation between lung function data (MMEF) and smoking habits is much better (r = 0.73) than with the measured mucociliary clearance rates (r = 0.3), suggesting that inborn errors of mucociliary transport are nearly as important as external lung damage due to smoking and infection in the development of chronic bronchitis and bronchial carcinoma.

With a new method for easy labeling of beta 2-agonists we measured intra- and extrapulmonary aerosol deposition after the administration of a bolus from a metered-dose inhaler at residual volume (RV) inhaling after a pause of 2 s and after immediate administration into the inspiratory flow at functional residual capacity (FRC). Immediate administration during a slow inspiratory vital capacity maneuver gives the highest intrapulmonary deposition (30-40%). Compressed air and ultrasonic nebulizers with a particle distribution pattern of 2-5 micron aerodynamic mass median diameter (AMMD) allow in normal subjects to achieve an intrapulmonary deposition of 30-60% during standardized tidal breathing at rest, the magnitude of the deposition depending mainly on each subject's larynx geometry. The outlet system leads to different deposition patterns in aerosol generators with the same AMMD. Many commercially available aerosol generators do not fulfill the criteria for any intrapulmonary aerosol deposition. For drug administration into the lungs, condensation aerosol generators ('steam boiler nebulizers') are useless as well as compressed-air, ultrasonic and steam driven nebulizers with a particle size of more than 10 micron AMMD.

14 patients with chronic bronchitis were subdivided into 2 groups of 7 patients. They were given at random 10 puffs of placebo or ipratropium bromide (0.2 mg). The mucociliary clearance rate was measured immediately after ipratropium inhalation (group 1) or 24 h after ipratropium inhalation (group 2). In group 1, the mucociliary clearance after ipratropium bromide was significantly better than after placebo (p less than 0.01). In group 2 there was no difference in the mucociliary clearance rates measured after ipratropium bromide or placebo, but the clearance rate still tended in favour of ipratropium bromide. We conclude that ipratropium bromide should be inhaled in high doses (0.2 mg) by hypersecretory patients with chronic bronchitis to improve mucociliary transport.