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

Discharge Identity of Medullary Inspiratory Neurons is Altered during Repetitive Fictive Cough

This study investigated the stability of the discharge identity of inspiratory decrementing (I-Dec) and augmenting (I-Aug) neurons in the caudal (cVRC) and rostral (rVRC) ventral respiratory column during repetitive fictive cough in the cat. Inspiratory neurons in the cVRC (n = 23) and rVRC (n = 17) were recorded with microelectrodes. Fictive cough was elicited by mechanical stimulation of the intrathoracic trachea. Approximately 43% (10 of 23) of I-Dec neurons shifted to an augmenting discharge pattern during the first cough cycle (C1). By the second cough cycle (C2), half of these returned to a decrementing pattern. Approximately 94% (16 of 17) of I-Aug neurons retained an augmenting pattern during C1 of a multi-cough response episode. Phrenic burst amplitude and inspiratory duration increased during C1, but decreased with each subsequent cough in a series of repetitive coughs. As a step in evaluating the model-driven hypothesis that VRC I-Dec neurons contribute to the augmentation of inspiratory drive during cough via inhibition of VRC tonic expiratory neurons that inhibit premotor inspiratory neurons, cross-correlation analysis was used to assess relationships of tonic expiratory cells with simultaneously recorded inspiratory neurons. Our results suggest that reconfiguration of inspiratory-related sub-networks of the respiratory pattern generator occurs on a cycle-by-cycle basis during repetitive coughing

Short reflex expirations (expiration reflexes) induced by mechanical stimulation of the trachea in anesthetized cats

Fifty spontaneously breathing pentobarbital-anesthetized cats were used to determine the incidence rate and parameters of short reflex expirations induced by mechanical stimulation of the tracheal mucosa (ERt). The mechanical stimuli evoked coughs; in addition, 67.6% of the stimulation trials began with ERt. The expiration reflex mechanically induced from the glottis (ERg) was also analyzed (99.5% incidence, p < 0.001 compared to the incidence of ERt). We found that the amplitudes of abdominal, laryngeal abductor posterior cricoarytenoid, and laryngeal adductor thyroarytenoid electromyograms (EMG) were significantly enhanced in ERg relative to ERt. Peak intrathoracic pressure (esophageal or intra-pleural pressure) was higher during ERg than ERt. The interval between the peak in EMG activity of the posterior cricoarytenoid muscle and that of the EMG of abdominal muscles was lower in ERt compared to ERg. The duration of thyroarytenoid EMG activity associated with ERt was shorter than that in ERg. All other temporal features of the pattern of abdominal, posterior cricoarytenoid, and thyroarytenoid muscles EMGs were equivalent in ERt and ERg

Central antitussive activity of the NK(1) and NK(2) tachykinin receptor antagonists, CP-99,994 and SR 48968, in the guinea-pig and cat

1. The purpose of this study was to investigate the antitussive activity and sites of action of the NK(1) and NK(2) tachykinin receptor antagonists, CP-99,994, SR 48968, and the racemate of SR 48968, SR 48212A in the cat and guinea-pig. 2. Guinea-pigs were dosed subcutaneously (s.c.) with CP-99,994, SR 48212A or SR 48968 one hour before exposure to aerosols of capsaicin (0.3 mM) to elicit coughing. Coughs were detected with a microphone and counted. 3. Intracerebroventricular (i.c.v.) cannulae were placed in the lateral cerebral ventricles of anaesthetized guinea-pigs. Approximately one week later, the animals were dosed with CP-99,994 or SR 48212A (i.c.v.) and exposed to aerosols of capsaicin (0.3 mM) to elicit coughing. 4. Cough was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was monitored from electromyograms of respiratory muscle activity. Cannulae were placed for intravenous (i.v.) or, in separate groups of animals, intravertebral arterial (i.a.) administration of CP-99,994, SR 48212A or SR 48968. Dose-response relationships for i.v. and i.a. administration of each drug were generated to determine a ratio of i.v. ED(50) to i.a. ED(50), known as the effective dose ratio (EDR). The EDR will be 20 or greater for a centrally active drug and less than 20 for a peripherally active drug. 5. In the guinea-pig, CP-99,994 (0.1–30 mg kg(−1), s.c.), SR 48212A (1.0–30 mg kg(−1), s.c.), and SR 48968 (0.3–3.0 mg kg(−1), s.c.) inhibited capsaicin-induced cough in a dose-dependent manner. Capsaicin-induced cough was also inhibited by i.c.v. administration of CP-99,994 (10 and 100 μg) or SR 48212A (100 μg). 6. In the cat, both CP-99,994 (0.0001–0.3 mg kg(−1), i.a., n=5; 0.003–3.0 mg kg(−1), i.v., n=5) and SR 48212A (0.003–1.0 mg kg(−1), i.a., n=5; 0.01–3.0 mg kg(−1), i.v., n=5) inhibited mechanically induced cough by either the i.v. or i.a. routes in a dose-dependent manner. SR 48968 (0.001–0.3 mg kg(−1), i.a., n=5; 0.03–1.0 mg kg(−1), i.v., n=5) inhibited cough when administered by the i.a. route in a dose-dependent manner, but had no effect by the i.v. route up to a dose of 1.0 mg kg(−1). Intravenous antitussive potencies (ED(50), 95% confidence interval (CI)) of these compounds were: CP-99,994 (0.082 mg kg(−1), 95% CI 0.047–0.126), SR 48212A (2.3 mg kg(−1), 95% CI 0.5–20), and SR 48968 (>1.0 mg kg(−1), 95% CI not determined). The intra-arterial potencies of these compounds were: CP-99,994 (1.0 μg kg(−1), 95% CI 0.4–1.8), SR 48212A (25 μg kg(−1), 95% CI 13–52), and SR 48968 (8.0 μg kg(−1), 95% CI 1–32). The derived EDRs for each compound were: CP-99,994, 82; SR 48212A, 92; and SR 48968, >125. 7. We concluded that CP-99,994 and SR 48968 inhibit cough in the guinea-pig and cat by a central site of action. In the cat, the antitussive action of these compounds appears to be solely by a central site