Relationship between Respiratory Load Perception and Perception of Nonrespiratory Sensory Modalities in Subjects with Life-Threatening Asthma

Subjects with life-threatening asthma (LTA) have reported decreased sensitivity to inspiratory resistive (R) loads. It is unknown if decreased sensitivity is specific for inspiratory R loads, other types of respiratory loads, or a general deficit affecting sensory modalities. This study hypothesized that impairment is specific to respiratory stimuli. This study tested perceptual sensitivity of LTA, asthmatic (A), and nonasthmatic (NA) subjects to 4 sensory modalities: respiratory, somatosensory, auditory, visual. Perceptual sensitivity was measured with magnitude estimation (ME): respiratory loads ME, determined using inspiratory R and pressure threshold (PT) loads; somatosensory ME, determined using weight ranges of 2–20 kg; auditory ME, determined using graded magnitudes of 1 kHz tones delivered for 3 seconds bilaterally; visual ME, determined using gray-to-white disk intensity gradations on black background. ME for inspiratory R loads lessened for LTA over A and NA subjects. There was no significant difference between the 3 groups in ME for PT inspiratory loads, weight, sound, and visual trials. These results demonstrate that LTA subjects are poor perceivers of inspiratory R loads. This deficit in respiratory perception is specific to inspiratory R loads and is not due to perceptual deficits in other types of inspiratory loads, somatosensory, auditory, or visual sensory modalities

Cortical Gating of Oropharyngeal Sensory Stimuli

Somatosensory evoked potentials provide a measure of cortical neuronal activation in response to various types of sensory stimuli. In order to prevent flooding of the cortex with redundant information various sensory stimuli are gated cortically such that response to stimulus 2 (S2) is significantly reduced in amplitude compared to stimulus 1 (S1). Upper airway protective mechanisms, such as swallowing and cough, are dependent on sensory input for triggering and modifying their motor output. Thus, it was hypothesized that central neural gating would be absent for paired-air puff stimuli applied to the oropharynx. Twenty-three healthy adults (18–35 years) served as research participants. Pharyngeal sensory evoked potentials (PSEPs) were measured via 32-electrode cap (10–20 system) connected to SynAmps2 Neuroscan EEG System. Paired-pulse air puffs were delivered with an inter-stimulus interval of 500 ms to the oropharynx using a thin polyethylene tube connected to a flexible laryngoscope. Data were analyzed using descriptive statistics and a repeated measures analysis of variance. There were no significant differences found for the amplitudes S1 and S2 for any of the four component PSEP peaks. Mean gating ratios were above 0.90 for each peak. Results supports our hypothesis that sensory central neural gating would be absent for component PSEP peaks with paired-pulse stimuli delivered to the oropharynx. This may be related to the need for constant sensory monitoring necessary for adequate airway protection associated with swallowing and coughing

Spatiotemporal regulation of the cough motor pattern

The purpose of this study was to identify the spatiotemporal determinants of the cough motor pattern. We speculated that the spatial and temporal characteristics of the cough motor pattern would be regulated separately. Electromyograms (EMG) of abdominal muscles (ABD, rectus abdominis or transversus abdominis), and parasternal muscles (PS) were recorded in anesthetized cats. Repetitive coughing was produced by mechanical stimulation of the lumen of the intrathoracic trachea. Cough inspiratory (CTI) and expiratory (CTE) durations were obtained from the PS EMG. The ABD EMG burst was confined to the early part of CTE and was followed by a quiescent period of varying duration. As such, CTE was divided into two segments with CTE1 defined as the duration of the ABD EMG burst and CTE2 defined as the period of little or no EMG activity in the ABD EMG. Total cough cycle duration (CTTOT) was strongly correlated with CTE2 (r2>0.8), weakly correlated with CTI (r2<0.3), and not correlated with CTE1 (r2<0.2). There was no significant relationship between CTI and CTE1 or CTE2. The magnitudes of inspiratory and expiratory motor drive during cough were only weakly correlated with each other (r2<0.36) and were not correlated with the duration of any phase of cough. The results support: a) separate regulation of CTI and CTE, b) two distinct subphases of CTE (CTE1 and CTE2), c) the duration of CTE2 is a primary determinant of CTTOT, and d) separate regulation of the magnitude and temporal features of the cough motor pattern

The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells.

BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality because of impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular, it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.This work was supported by British Heart Foundation Grants PG/12/54/29734 (to W. L., P. D. U., and N. W. M.) and CH/09/001/25945 (to N. W. M.). He Jiang was supported by the Cambridge Wellcome Trust 4-year Ph.D Programme in Metabolic and Cardiovascular Disease.This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology via http://dx.doi.org/10.1074/jbc.M115.68329

Neural Processing of Respiratory Sensations when Breathing Becomes More Difficult and Unpleasant

The accurate perception of respiratory sensations is important for the successful management and treatment of respiratory diseases. Previous studies demonstrated that external stimuli such as affective pictures and distracting films can impact the perception and neural processing of respiratory sensations. This study examined the neural processing of respiratory sensations when breathing as an internal stimulus is manipulated and becomes more difficult and unpleasant. Sustained breathing through an inspiratory resistive load was used to increase perceived breathing difficulty in 12 female individuals without respiratory disease. Using high-density EEG, respiratory-related evoked potentials (RREP) to short inspiratory occlusions were recorded at early versus late time points of sustained loaded breathing. Ratings of perceived intensity and unpleasantness of breathing difficulty showed an increase from early to late time points of loaded breathing (p < 0.01 and p < 0.05, respectively). This was paralleled by significant increases in the magnitudes of RREP components N1, P2, and P3 (p < 0.01, p < 0.05, and p < 0.05, respectively). The present results demonstrate increases in the neural processing of respiratory sensations when breathing becomes more difficult and unpleasant. This might reflect a protective neural mechanism allowing effective response behavior when air supply is at risk