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

Microinjection of codeine into the region of the caudal ventral respiratory column suppresses cough in anesthetized cats

We investigated the influence of microinjection of codeine into the caudal ventral respiratory column (cVRC) on the cough reflex. Experiments were performed on 36 anesthetized spontaneously breathing cats. Electromyograms (EMGs) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) muscles and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. The unilateral microinjection of codeine (3.3 mM, 20–32 nl) in the cVRC reduced cough number by 29% (P < 0.01) and expiratory cough amplitudes of esophageal pressure by 33% (P < 0.05) as well as both ipsilateral and contralateral ABD EMGs by 35% and 48% (P < 0.01 and P < 0.01, respectively). No cough depression was observed after microinjections of vehicle. There was no significant effect of microinjection of codeine in the cVRC (3.3 mM, 30–40 nl) on ABD activity induced by a microinjection of d,l-homocysteic acid (30 mM, 27–40 nl) in the same location. However, a cumulative dose of codeine (0.1 mg/kg, 330 nmol/kg) applied into the brain stem circulation through the vertebral artery reduced the ABD motor response to cVRC d,l-homocysteic acid microinjection (30 mM, 28–32 nl) by 47% (P < 0.01). These results suggest that 1) codeine can act within the cVRC to suppress cough and 2) expiratory premotoneurons within the cVRC are relatively insensitive to this opioid

Molecular Mechanisms of Dysautonomia During Heart Failure. Focus On “Heart Failure-Induced Changes of Voltage-Gated CA2+ Channels and Cell Excitability in Rat Cardiac Postganglionic Neurons”

We tested the hypothesis, motivated in part by a coordinated computational cough network model, that alterations of mean systemic arterial blood pressure (BP) influence the excitability and motor pattern of cough. Model simulations predicted suppression of coughing by stimulation of arterial baroreceptors. In vivo experiments were conducted on anesthetized spontaneously breathing cats. Cough was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) of inspiratory parasternal, expiratory abdominal, laryngeal posterior cricoarytenoid (PCA), and thyroarytenoid muscles along with esophageal pressure (EP) and BP were recorded. Transiently elevated BP significantly reduced cough number, cough-related inspiratory, and expiratory amplitudes of EP, peak parasternal and abdominal EMG, and maximum of PCA EMG during the expulsive phase of cough, and prolonged the cough inspiratory and expiratory phases as well as cough cycle duration compared with control coughs. Latencies from the beginning of stimulation to the onset of cough-related diaphragm and abdominal activities were increased. Increases in BP also elicited bradycardia and isocapnic bradypnea. Reductions in BP increased cough number; elevated inspiratory EP amplitude and parasternal, abdominal, and inspiratory PCA EMG amplitudes; decreased total cough cycle duration; shortened the durations of the cough expiratory phase and cough-related abdominal discharge; and shortened cough latency compared with control coughs. Reduced BP also produced tachycardia, tachypnea, and hypocapnic hyperventilation. These effects of BP on coughing likely originate from interactions between barosensitive and respiratory brainstem neuronal networks, particularly by modulation of respiratory neurons within multiple respiration/cough-related brainstem areas by baroreceptor input. cough is initiated by stimulation of mechano- and chemosensitive sensory endings of cough receptors and also may be influenced by a cough-related subgroup of rapidly adapting “irritant” receptors and C fibers within tracheobronchial and laryngeal mucosa (23, 24, 148). However, the pattern of coughing (the number of coughs and their strength and timing; Refs. 67, 149) is profoundly affected by other peripheral and central afferent inputs (17, 49), particularly during pathological processes such as infection, inflammation, and allergic reactions (28, 118). Stimuli within the larynx (141) and nose (109, 110) enhance cough induced from the tracheal-bronchial region. Stimulation of cardiac receptors (140), chemoreceptors (138), and pulmonary as well as bronchial C fibers in anesthetized animals (139) reduces coughing. Afferent signaling from muscles, joints, skin, and possibly the viscera may also alter the expression of cough (66, 67, 118). Coughing induces vigorous intrathoracic and intra-abdominal pressure oscillations and changes of sympathetic and parasympathetic nervous activities (27, 67, 145) that significantly affect the cardiovascular system including dynamic changes of blood pressure (BP) and regional blood flow (60, 67). Coughing is associated with peaks in systemic arterial blood pressure during systole and cough expulsions followed by post-tussive hypotension (unpublished observations; Refs. 67, 127). This relationship involves central reflex mechanisms (27, 127, 145); it is observed also in neuromuscular-blocked decerebrate animals (unpublished observations). However, very little is known about the effects of systemic BP and baroreceptor afferent input on the excitability and patterning of cough. Available data were mostly obtained with stimulation of multiple sensory afferents resulting in expression of the chemoreflex (96, 140), and the results suggested either no changes (139, 140) or only transient alterations of the cough reflex (96) during reduced BP. The respiratory neuronal network is a crucial component in the generation of cough and the transmission of its central motor pattern to the respiratory muscles (54, 119, 123–125). There is a close relationship between the control of the respiratory and cardiovascular systems. It is well established that an increase in blood pressure resulting in the baroreflex (83, 98, 135) can prolong expiration, significantly reduce breathing frequency, and reduce inspiratory drive by an action on selected populations of brainstem respiratory neurons (2, 35, 72, 76, 107) sensitive to afferent impulses originating from baroreceptors. Thus baroreceptor reflex feedback mechanisms that modulate breathing may also limit cough intensity and/or number. Hence, changes in cough excitability and/or the pattern of coughing due to the stimulation of baroreceptors (and alternatively by their unloading) are consistent with the multifunctional role of the respiratory pattern generator in controlling cough and breathing. Motivated by this consideration, we undertook a computational modeling study of the respiratory/cough neuronal network and in vivo experiments to test the role of blood pressure changes in modulation of cough motor pattern. The study also allowed us to address a more general hypothesis that this model could be used to predict, not just motor patterns and neuronal responses of the brainstem respiratory network, but regulation of this system as well. Models simulating concurrent cough and baroreceptor perturbations of breathing predicted that an increase of mean systemic arterial BP would alter the motor pattern and excitability of the cough reflex