Decrease In Slope Of Phase Research Articles

Mechanisms of Orthopnea in Stable Obese Subjects.

The present study explored the role of closing volume as a determinant of orthopnea in stable obese subjects. We hypothesized that: (1) increase in closing volume in supine position would be greater in orthopneic than in non-orthopneic subjects, and (2) the relationship of change in closing volume to change in dyspnea with position would be dependent on expiratory flow limitation in the sitting position. In stable obese subjects, in sitting and supine positions, we measured the Borg dyspnea score, static lung volumes, expiratory flow limitation during tidal breathing, and single-breath nitrogen expiration test. From the latter, we determined closing volume and closing capacity, slope of phase III, and opening capacity. Orthopnea was defined as any increase in the Borg score in the supine position from its value in the sitting position. Twenty-one subjects (13 women), median age (interquartile range) 55 (49-57) y and with body mass index of 39 (38-42) kg/m(2) were included, of whom 12 were orthopneic and 11 had expiratory flow limitation while seated. In the sitting position, orthopneic and non-orthopneic subjects were similar for age, body mass index, and pulmonary function tests, including single-breath nitrogen expiration test-derived variables. In the orthopneic subjects, there were no changes in any respiratory variable between positions. In the non-orthopneic subjects, there was a significant decrease in slope of phase III in the supine position from 1.67 (1.33-3.60) to 1.40 (1.25-1.66)%/L (P = .008). Overall, the subjects' Borg score significantly correlated with the slope of phase III (r = 0.63, P = .002) and opening capacity (r = -0.47, P = .03). In 10 subjects without expiratory flow limitation, it correlated with slope of phase III (r = 0.68, P = .03). In stable obese subjects, magnitude of orthopnea correlated with an increase in the slope of phase III in subjects without expiratory flow limitation. Expiratory flow limitation should be taken into account in obese patients.

TRPC3 regulates the automaticity of embryonic stem cell-derived cardiomyocytes

BackgroundCardiac pacemaking is a complex phenomenon that is not completely understood. Canonical transient receptor potential isoform 3 (TRPC3) channel is a cation channel that permeates both Ca2+ and Na+. TRPC3 was previously found to express in adult cardiomyocytes. However, its role in cardiac pacemaking is unexplored. Here we used mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) to investigate whether TRPC3 regulates the spontaneous automaticity and the underlying mechanism involved. Methods and resultsImmunocytochemistry results showed that TRPC3 is expressed at the T-tubules of mESC-CMs. Whole-cell patch clamping showed that single mESC-CMs contain TRPC3 current. Confocal Ca2+ imaging showed that the TRPC3-specific blocker Pyr3 decreased Ca2+ transients and local Ca2+ release (LCR) of mESC-CMs. Combined current and voltage clamp recordings from the same cell showed that reducing the TRPC3 current, either by Pyr3 or a dominant negative (loss-of-function) construct of TRPC3, decreased the pacemaker activity of mESC-CMs as reflected by a decrease in action potential rate, a depolarized maximum diastolic potential and a decrease in slope of phase 4 diastolic depolarization. Furthermore, decreasing the TRPC3 current diminished, while increasing the TRPC3 current augmented the sodium–calcium exchanger (NCX) current in mESC-CMs. Lastly, decrease in TRPC3 current decreased the phosphorylation of ryanodine receptor isoform 2 at Ser2809 and phospholamban at Thr17. ConclusionsTRPC3 positively regulates diastolic depolarization of spontaneous action potential by increasing LCR and NCX current and therefore is an important determinant in pacemaking of mESC-CMs.

Correlations between capnographic waveforms and peak flow meter measurement in emergency department management of asthma

BackgroundThe usual method for initial assessment of an acute asthma attack in the emergency room includes the use of peak flow measurement and clinical parameters. Both methods have their own disadvantages such as poor cooperation/effort from patients (peak flow meter) and lack of objective assessment (clinical parameters). We were looking into other methods for the initial asthma assessment, namely the use of capnography. The normal capnogram has an almost square wave pattern comprising phase 1, slope phase 2, plateau phase 3, phase 4 and angle α (between slopes 2 and 3). The changes in asthma include decrease in slope of phase 2, increase in slope 3 and opening of angle α.AimsOur objective was to compare and assess the correlation between the changes in capnographic indices and peak flow measurement in non-intubated acute asthmatic patients attending the emergency room.MethodsWe carried out a prospective study in a university hospital emergency department (ED). One hundred and twenty eight patients with acute asthma were monitored with peak flow measurements and then had a nasal cannula attached for microstream sampling of expired carbon dioxide. The capnographic waveform was recorded onto a PC card for indices analysis. The patients were treated according to departmental protocols. After treatment, when they were adjudged well for discharge, a second set of results was obtained for peak flow measurements and capnographic waveform recording. The pre-treatment and post-treatment results were then compared with paired samples t-test analysis. Simple and canonical correlations were performed to determine correlations between the assessment methods. A p value of below 0.05 was taken to be significant.ResultsPeak flow measurements showed significant improvements post-treatment (p < 0.001). On the capnographic waveform, there was a significant difference in the slope of phase 3 (p < 0.001) and alpha angle (p < 0.001), but not in phase 2 slope (p = 0.35). Correlation studies done between the assessment methods and indices readings did not show strong correlations either between the measurements or the magnitude of change pre-treatment and post-treatment.ConclusionPeak flow measurements and capnographic waveform indices can indicate improvements in airway diameter in acute asthmatics in the ED. Even though the two assessment methods did not correlate statistically, capnographic waveform analysis presents several advantages in that it is effort independent and provides continuous monitoring of normal tidal respiration. They can be proposed for the monitoring of asthmatics in the ED.