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The calcium sensitizer levosimendan improves human diaphragm function.

Acquired diaphragm muscle weakness is a key feature in several chronic diseases including chronic obstructive pulmonary disease, congestive heart failure, and difficult weaning from mechanical ventilation. However, no drug is available to improve respiratory muscle function in these patients. Recently, we have shown that the calcium sensitizer levosimendan enhances force generating capacity of isolated diaphragm fibers.

OBJECTIVES: To investigate the effects of the calcium sensitizer levosimendan on in vivo human diaphragm function.

METHODS: In a double-blind randomized crossover design, 30 healthy subjects performed two identical inspiratory loading tasks. After the first loading task, subjects received levosimendan (40 µg/kg bolus followed by 0.1/0.2 µg/kg/min continuous infusion) or placebo. Transdiaphragmatic pressure, diaphragm electrical activity and their relationship (neuro-mechanical efficiency) were measured during loading. Magnetic phrenic nerve stimulation was performed before the first loading task and after bolus administration to asses twitch contractility. Center frequency of diaphragm electrical activity was evaluated to study the effects of levosimendan on muscle fiber conduction velocity.

MEASUREMENTS AND MAIN RESULTS: The placebo group showed a 9% (P=0.01) loss of twitch contractility after loaded breathing, whereas no loss in contractility was observed in the levosimendan group. Neuro-mechanical efficiency of the diaphragm during loading improved by 21% (P<0.05) in the levosimendan group. Baseline center frequency of diaphragm electrical activity was reduced after levosimendan administration (P<0.05).

CONCLUSIONS: The calcium sensitizer levosimendan improves both neuro-mechanical efficiency and contractile function of the human diaphragm. Our findings suggest a new therapeutic approach to improve respiratory muscle function in patients with respiratory failure.

Six Minute Walk Distance Predictors, Including Computed Tomography Measures, in the COPDGene(R) Cohort.

Exercise tolerance in COPD is only moderately well predicted by airflow obstruction assessed by forced expiratory volume in 1 second (FEV(1)). We determined whether other phenotypic characteristics, including computerized tomography (CT) measures, are independent predictors of 6 minute walk distance (6MWD) in the COPDGene(®) cohort.

METHODS:COPDGene(®) recruits non-Hispanic Caucasian and African-American current and ex-smokers. Phenotyping measures include post-bronchodilator FEV(1)%predicted, inspiratory and expiratory CT lung scans. We defined %emphysema as percent lung voxels below -950 Hounsfield Units (HU) on the inspiratory scan and %gas trapping as percent lung voxels below -856 HU on the expiratory scan.

RESULTS:Data of the first 2,500 participants of the COPDGene(®) cohort were analyzed. Participant age was 61±9 y; 51% were men; 76% were non-Hispanic Caucasians and 24% were African-Americans. Fifty-six percent had spirometrically-defined COPD with 9.3%, 23.4%, 15.0% and 8.3%, in GOLD stages I-IV respectively. Higher %emphysema and %gas trapping predicted lower 6MWD (p<0.001). However, in a given spirometric group, after adjustment for age, gender, race, and BMI, neither %emphysema nor %gas trapping, nor their interactions with FEV(1)%predicted, remained a significant 6MWD predictor. In a given spirometric group, only 16-27% of variance in 6MWD could be explained by age, male gender, Caucasian race and lower BMI as significant predictors of higher 6MWD.

CONCLUSIONS:In this large cohort of smokers, in a given spirometric stage phenotypic characteristics were only modestly predictive of 6MWD. CT measures of emphysema and gas trapping were not predictive of 6MWD after adjustment for other phenotypic characteristics.

Evolution of Dyspnea during Exercise in COPD: Impact of Critical Volume Constraints.

CONCLUSIONS: Regardless of the exercise test protocol, the inflection (or plateau) in the VT response marked the point where dyspnea intensity rose abruptly and there was a transition in the dominant qualitative descriptor choice from "work/effort" to "unsatisfied inspiration". Intensity and quality of dyspnea evolve separately and are strongly influenced by mechanical constraints on VT expansion during exercise in COPD. PMID: 21885624 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory and Critical Care Medicine)

Forced Vital Capacity in Patients with Idiopathic Pulmonary Fibrosis: Test Properties and Minimal Clinically Important Difference.

CONCLUSIONS: FVC is a reliable, valid, and responsive measure of clinical status in patients with IPF, and a decline of 2-6%, although small, represents a clinically important difference. PMID: 21940789 [PubMed - as supplied by publisher] (Source: American Journal of Respiratory and Critical Care Medicine)

Detection of Pulmonary tuberculosis: comparing MR imaging with HRCT.

Detection of Pulmonary tuberculosis: comparing MR imaging with HRCT.

BMC Infect Dis. 2011 Sep 16;11(1):243

Authors: Busi Rizzi E, Schinina V, Cristofaro M, Goletti D, Palmieri F, Bevilacqua N, Lauria FN, Girardi E, Bibbolino C

Abstract
ABSTRACT: BACKGROUND: Computer Tomography (CT) is considered the gold standard for assessing the morphological changes of lung parenchyma. Although novel CT techniques have substantially decreased the radiation dose, radiation exposure is still high. Magnetic Resonance Imaging (MRI) has been established as a radiation- free alternative to CT for several lung diseases, but its role in infectious diseases still needs to be explored further. Therefore, the purpose of our study was to compare MRI with high resolution CT (HRCT) for assessing pulmonary tuberculosis. METHODS: 50 patients with culture-proven pulmonary tuberculosis underwent chest HRCT as the standard of reference and were evaluated by MRI within 24 h after HRCT. Altogether we performed 60 CT and MRI examinations, because 10 patients were also examined by CT and MRI at follow- up. Pulmonary abnormalities, their characteristics, location and distribution were analyzed by two readers who were blinded to the HRCT results. RESULTS: Artifacts did not interfere with the diagnostic value of MRI. Both HRCT and MRI correctly diagnosed pulmonary tuberculosis and identified pulmonary abnormalities in all patients. There were no significant differences between the two techniques in terms of identifying the location and distribution of the lung lesions, though the higher resolution of MRI did allow for better identification of parenchymal dishomogeneity, caseosis, and pleural or nodal involvement. CONCLUSION: Technical developments and the refinement of pulse sequences have improved the quality and speed of MRI. Our data indicate that in terms of identifying lung lesions in non-AIDS patients with non- miliary pulmonary tuberculosis, MRI achieves diagnostic performances comparable to those obtained by HRCT but with better and more rapid identification of pulmonary tissue abnormalities due to the excellent contrast resolution.

PMID: 21923910 [PubMed - as supplied by publisher]

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