Toshiro Umezaki

Convergence of afferents from the SLN and GPN in cat medullary swallowing neurons

We demonstrated the convergence of information from the pharyngeal and laryngeal mucosa, transmitted by the glossopharyngeal nerve (GPN) and superior laryngeal nerve (SLN), in the nucleus of the tractus solitarius (NTS). First, the distribution of terminals of the GPN and SLN in the NTS was examined by an HPR tracing technique in cats, and the synapse formation of these neurons with NTS neurons was demonstrated by electron microscopy. The HRP-labeled SLN and GPN terminals were localized in a small area of the interstitial subnucleus of the NTS, slightly rostral to the obex, forming synapses with NTS neurons. Next, using extracellular recording in anesthetized cats, we determined whether or not swallowing-related neurons in the medulla oblongata receive peripheral inputs. Convergence of peripheral sensory inputs from the SLN and GPN was observed in more than 80% of the NTS cells. These results suggest that the NTS is not only a sensory-relay nucleus but also integrates information necessary for eliciting protective reflexes of the upper airway, such as swallowing.

Convergence of laryngeal afferents with different natures upon cat NTS neurons

To clarify the convergence of laryngeal afferents within the nucleus tractus solitarius (NTS) in the cat, we examined in the medulla the response characteristics of superior laryngeal nerve (SLN) fibers and NTS neurons to mechanical and chemical stimulation applied to laryngeal mucosa by extracellular recordings. The response was recorded in 75 SLN primary afferent fibers (PAFs) and 92 NTS neurons. PAFs of the SLN consisted of numerous monomodal mechanosensitive fibers and a small number of chemosensitive and polymodal fibers. On the other hand, the majority of NTS neurons had a polymodal nature. Thus, laryngeal information is considered to be integrated in modality into NTS neurons. All mechanosensitive fibers received information from a small restricted field in the larynx. On the contrary, each NTS neuron responded to mechanical stimulation over a wide laryngeal field, indicating that information from different sites spatially converge on NTS neurons. Our results suggest that caudal NTS neurons play a cardinal role in integrating laryngeal afferents, which are thought to elicit laryngeal reflexes.

Contact granulomas of the larynx

Ten cases of intubation granulomas and eight cases of contact granulomas not related to intubation were reviewed for the purpose of clinical analysis and pathological investigation. Granulomas were located primarily at the vocal process of the arytenoid cartilage. Additionally, 58 hemilarynges obtained from 37 cadavers with intubation granulomas were evaluated grossly and histopathologically. The intubation granulomas had no side predilections. All eight contact granulomas occurred in males and had a higher incidence of recurrence (three of eight cases) despite complete removal with laser surgery. In an attempt to explain recurrences of these contact granulomas, all three cases were studied clinically and pathologically. Results indicated that they recurred in singers and vocal abusers, and presumably resulted from the continued hammering of one vocal process against the other. Analysis also demonstrated that vocal rehabilitation was essential prior to or immediately after removal of the granuloma to prevent its recurrence. Pathological evaluation of the contact granulomas revealed focal ulceration and a covering of necrotic tissue with desquamating epithelium. The propria mucosa was edematous and infiltrated by chronic inflammatory cells and neutrophils forming focal granulation tissue in a stroma containing proliferated capillaries. Pathological features around local ulcerations were typical of a secondary granuloma while underlying arytenoid cartilage was partially necrotic.

Laryngeal Reflex Mechanism during Deglutition—Observation of Subglottal Pressure and Afferent Discharge

In this investigation, particular attention was paid to elucidate the laryngeal reflex mechanism of protective closure and the sensory function of the larynx during deglutition. For this purpose, three different experimental procedures were adopted: (1) subglottal pressure of felines was measured during deglutition using a pressure transducer; (2) subglottal pressure of human beings was measured during deglutition using a pressure transducer; and (3) afferent discharges from superior and recurrent laryngeal nerves of felines were recorded. The following conclusions appear justified. (1) Feline and human subglottal pressure during deglutition showed the following pattern. The pressure rises with onset of deglutition, temporarily drops during laryngeal elevation, rises again during the downward movement of the larynx, and drops again at the end of the glutltion. This pattern was not affected by the resection of the unilateral recurrent laryngeal nerve. (2) The superior laryngeal nerve is involved in the sensory function of the pharynx, larynx, and trachea. At least two types of afferent discharges from superficial and infernal sensory nerves are suspected. Afferent discharges from the recurrent laryngeal nerves in the larynx and trachea are not as distinct as those of the superior laryngeal nerve, and this seems to correspond with various changes in the thorax. During deglutition, afferent discharges were recorded from superior to recurrent laryngeal nerves.

Glottic Closure during Swallowing in the Recurrent Laryngeal Nerve-Paralyzed Cat

Glottic closing pressure and time were quantitatively analyzed during deglutition and in reflex glottic closure elicited by superior laryngeal nerve stimulation by means of a catheter pressure transducer in the cat. Duration and peak pressure of glottic closure during deglutition were 322.6 ± 32.2 msec (mean ± SE) and 57.5 ± 6.0 mmHg, respectively, whereas peak pressure of the reflex glottic closure was 21.7 ± 6.1 mmHg in control animals. When the recurrent laryngeal nerve was denervated unilaterally, decrease in peak glottic closing pressure on swallowing was only about 36%, whereas the peak pressure of reflex glottic closure was markedly diminished to 4.5 ± 4.6%. When bilateral recurrent laryngeal nerves denervated, decrease in peak pressure during deglutition showed no greater significance than It did after unilateral denervation. Inferior constrictors myotomy in addition to bilateral recurrent laryngeal nerve denervation reduced peak pressure to nearly zero. These results indicate that on swallowing, the inferior constrictors cooperate with the intrinsic laryngeal adductors, thus playing a very important role in reinforcing glottic closure, a function that is unlikely during reflex glottic closure.

Intracordal Injection Increases Glottic Closing Force in Recurrent Laryngeal Nerve Paralysis

Glottic closing pressure during swallowing was measured in the cat with a catheter pressure transducer to study the effectiveness of intracordal injection in increasing glottic pressure in unilateral recurrent laryngeal nerve paralysis. Swallows were elicited by pouring water into the pharynx while the animal was under light anesthesia with ketamine. Peak pressure of the glottic closure for the control group during deglutition was 68.0 ± 10.5 mm Hg (mean ± standard deviation). Peak pressure decreased to 22.0 ± 3.6 mm Hg just after sectioning of the unilateral recurrent laryngeal nerve, and rose to 39.8 ± 8.3 mm Hg by silicon injection into the paralyzed vocal fold. In a study of chronic cases 1 month or more after unilateral recurrent laryngeal nerve section, peak pressure was 49.1 ± 23.4 mm Hg, and varied widely from 21 to 92 mm Hg because of differences in the position of the paralyzed vocal fold and the degree of compensation by the unaffected vocal fold. In the group that had the paralyzed vocal fold fixed in the median position, peak pressure was almost the same as that of the control group. When the paralyzed vocal fold was fixed in either the paramedian or lateral position, peak pressure was 33.3 ± 7.0 mm Hg. This value was significantly elevated to 45.8 ± 10.4 mm Hg by injection of silicon, though it remained lower than that of the control. These results suggest that the decrease in glottic closing force during swallowing as a result of unilateral recurrent laryngeal nerve lesion is compensated for by the unaffected vocal fold to some degree and is improved by intracordal injection.

Changes in laryngeal muscle activities during hypercapnia in the cat

The larynx has three functions: phonation, airway protection, and respiration. Few studies have dealt with laryngeal respiratory function. To elucidate respiratory regulation by the larynx, we studied the changes in the activity of the intrinsic laryngeal muscles during hypercapnia in decerebrated cats. The electromyographic activities of the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded simultaneously with an electromyogram of the diaphragm, endotracheal pressure, and concentrations of O2 and CO2. The activity of the intrinsic laryngeal muscles during hypercapnia (end-tidal CO2, 8% to 10%) was analyzed in comparison with that during eucapnia. In hypercapnia, both the PCA and TA muscles increased their activities, and the endotracheal pressure during expiration was elevated to a higher level than that in eucapnia. TA muscle activities returned to the level during eucapnia after ligation of the common carotid arteries. These findings suggest that hypercapnia causes a further widening of the glottis during inspiration to decrease inspiratory resistance and a further narrowing of the glottis during expiration to prevent alveolar collapse. Thus it may be concluded that the larynx actively participates in respiratory regulation under the control of the brain stem through a process of peripheral inputs from the carotid receptors.

Crossing inputs of the superior laryngeal nerve afferents to medullary swallowing-related neurons in the cat

To understand the neural mechanism for generation of synchronous activity on both sides during swallowing, we examined the convergence of inputs from the bilateral superior laryngeal nerves (SLNs) in the urethane-anesthetized cat medulla and we also examined the changes in swallowing outputs after a longitudinal brain-stem split in decerebrate cats. Twenty-six (31%) of 84 swallowing-related neurons (SRNs) that were oligosynaptically activated by ipsilateral SLN stimulation and recorded mostly in the reticular formation received contralateral inputs, which were confirmed by orthodromic spike responses (n = 16) or were detected as subliminal facilitatory or inhibitory inputs (n = 10) using conditioning-test stimuli. The rate of convergence of inputs from bilateral SLNs in these SRNs was significantly higher than that (4%) in the SRNs that were regarded as sensory-relay neurons in the nucleus tractus solitarius (NTS). The SRNs receiving signals from the contralateral SLN were located diffusely from the NTS and the adjacent reticular formation to the nucleus ambiguus (NA) and the reticular formation dorso-medial to the NA. A midsagittal split from 3 mm caudal to 6 mm rostral to the obex could change symmetrical swallowing to unilateral swallowing. Thus the crossing projections to the contralateral SRNs appear to contribute to symmetrical swallowing.

Origin of laryngeal sensory-evoked potentials (LSEPs) in the cat

Sensory-evoked potentials elicited by electrical stimulation of the superior laryngeal nerve were recorded at the dural surface on the cortex and the caudal medulla in anesthetized cats as a reflection of activities in the central afferent systems. These evoked potentials were named laryngeal sensory evoked potentials (LSEPs). LSEP was mainly composed of five components, N1, N2, N4, N12, and large biphasic potential (LBP). The peak latencies of these components were as follows: N1, 1.09 +/- 0.18 ms; N2, 1.93 +/- 0.19 ms; N4, 3.97 +/- 0.19 ms; and N12, 12.48 +/- 1.01 ms. LBP was a large component lasting from approximately 6 ms to 18 ms. The generator sources of these components were identified as follows: N1, nodose ganglion; N2, presynaptic potentials of the nucleus tractus of solitarius (NTS); N4, NTS complex including the postsynaptic potentials; and N12, activities of the frontal part of the orbital gyrus. The LBP was speculated to be generated from certain subcortical structures, such as the amygdala, the thalamus, the hypothalamus, and the basal ganglia.

Characteristics of laryngeal receptors analyzed by presynaptic recording from the cat medulla oblongata

In order to clarify the neural mechanisms for the protective laryngeal reflex, we conducted physiological analysis of laryngeal sensory receptors. In the present study, presynaptic unit activities, which might accurately reflect characteristics of the laryngeal receptor, were recorded with a glass microelectrode in the nucleus of the tractus solitarius of the medulla oblongata in ketamine-urethane anesthetized cats, and the responses to the mechanical and/or chemical stimuli were analyzed. From the results, it was demonstrated that highly sensitive mechanoreceptors and polymodal receptors exist in the laryngeal mucosa; they are particularly numerous in the laryngeal surface of the epiglottis and arytenoid region, and uncommon in the vocal fold. Mechanoreceptors on the laryngeal mucosa were classified into a rapidly adapting group and a slowly adapting group, while all polymodal receptors adapted rapidly to mechanical stimulation. These results suggest that these non-specific polymodal and rapidly adapting receptors may correspond to more superficial receptors such as free nerve endings and some taste buds, and also monomodal slowly adapting mechanoreceptors may correspond to deeper terminals in the subepithelium. It is also considered possible that the structures and the characteristics of these receptors are appropriate to elicit the protective laryngeal reflexes by non-specifically detecting various kinds of stimuli.