Posterior Cricoarytenoid Research Articles

Posterior cricoarytenoid muscle electrophysiologic changes are predictive of vocal cord paralysis with recurrent laryngeal nerve compressive injury in a canine model.

Injury to the recurrent laryngeal nerve (RLN) is a dreaded complication of endocrine surgery. Intraoperative neural monitoring (IONM) has been increasingly utilized to assess the functional status of the RLN. Although the posterior cricoarytenoid muscle (PCA) is innervated by the RLN as the abductor of the larynx, PCA electromyography (EMG) is infrequently recorded during IONM and PCA activity after RLN compressive injury remains poorly characterized. Single-subject prospective animal study. We employed a canine model to identify postcricoid EMG correlates of postoperative vocal cord paralysis (VCP). Postcricoid electrode recordings were obtained before and after compressive RLN injury associated with VCP. Normative postcricoid recordings revealed mean amplitude of 1288 microvolt (μV) and latency of 8.2 millisecond (ms) with maximum (1 milliamp [mA]) vagal stimulation, and mean amplitude of 1807 μV and latency of 3.5 ms with maximum (1 mA) RLN stimulation. Following injury that was associated with VCP, there was 62.1% decrement in postcricoid EMG amplitude with maximum vagal stimulation and 80% decrement with maximum RLN stimulation. Threshold stimulation of the vagus increased by 23%, and there was a corresponding 42% decrease in amplitude. For RLN stimulation, latency increased by 17.3% following injury, whereas threshold stimulation increased by 61% with 35.5% decrement in EMG amplitude. Thus, if RLN amplitude decreases by ≥ 80%, with absolute amplitude of ≤ 300 μV or less and latency increase of ≥ 10%, RLN injury is likely associated with VCP. Our results predict postoperative VCP based on postcricoid electromyographic IONM and may guide surgical decision making. NA Laryngoscope, 126:2744-2751, 2016.

Blockade of glial-derived neurotrophic factor in laryngeal muscles promotes appropriate reinnervation.

Synkinetic reinnervation of the laryngeal muscles is one of the causes of the poor functional recovery after a recurrent laryngeal nerve (RLN) injury. Glial-derived neurotrophic factor (GDNF) is elevated in rat laryngeal muscles during RLN reinnervation. The specific aim of this investigation was to evaluate the effect of anti-GDNF on RLN reinnervation. Anti-GDNF antibody was injected into the posterior cricoarytenoid (PCA) 3 days following RLN transection and anastomosis. Larynges were harvested at 7, 14, 28, 56, and 112 days post injury (DPI). Prior to sacrifice, the vocal fold mobility was assessed. Immunostaining to identify neuromuscular junctions was used to evaluate the extent of axonal reinnervation of the PCA, lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA). After anti-GDNF injection into PCA, RLN reinnervation in all muscles was altered when compared to the controls. PCA innervation was delayed. At 7 DPI, only a few axons made synapses in the PCA. In contrast, axons prematurely innervated the LTA and MTA when compared to controls. Innervation was similar to controls at 56 and 112 DPI. Vocal fold motion was enhanced in 10 of 24 animals studied. After injection of anti-GDNF into the PCA, early arriving axons bypass the PCA and enter the LTA. Later arriving axons innervate the PCA and MTA. Vocal fold function is improved as compared to controls. Anti-GDNF injection into the PCA influences the pattern of reinnervation and may result in less synkinetic, more functional innervation. NA Laryngoscope, 126:E337-E342, 2016.

Synovial tissue morphology of the cricoarytenoid joint in the elderly: a histological comparison with the cricothyroid joint.

We compared the age-related morphology of the cricothyroid (CT) joint with that of the cricoarytenoid (CA) joint using 18 specimens from elderly cadavers in terms of their elastic fiber contents as well as the cells composing the joint capsule and synovial tissues. In contrast to an almost flat-flat interface in the CT joint, the CA joint was similar to a saddle joint. The CA joint capsule was thin and contained few elastic fibers, and in contrast to the CT joint, external fibrous tissues were not exposed to the joint cavity, there being no injury to the CA joint capsule. The lateral and posterior aspects of the CA joint were covered by the lateral and posterior CA muscles, respectively, and the fascia of the latter muscle was sometimes thick with abundant elastic fibers. However, due to possible muscle degeneration, loose connective tissue was often interposed between the fascia and the capsule. The medial and anterior aspects of the CA joint faced loose tissue that was continuous with the laryngeal submucosal tissue. Therefore, in contrast to the CT joint, a definite supporting ligament was usually absent in the CA joint. Synovial folds were always seen in the CA joint, comprising a short triangular mass on the posterior side and long laminar folds on the anterior side. The synovial folds usually contained multiple capillaries and a few CD68-positive macrophages. High congruity of the CA joint surfaces as well as strong muscle support to the arytenoid cartilage appeared to provide the specific synovial morphology.

Neurotrophin expression and laryngeal muscle pathophysiology following recurrent laryngeal nerve transection.

Laryngeal palsy often occurs as a result of recurrent laryngeal or vagal nerve injury during oncological surgery of the head and neck, affecting quality of life and increasing economic burden. Reinnervation following recurrent laryngeal nerve (RLN) injury is difficult despite development of techniques, such as neural anastomosis, nerve grafting and creation of a laryngeal muscle pedicle. In the present study, due to the limited availability of human nerve tissue for research, a rat model was used to investigate neurotrophin expression and laryngeal muscle pathophysiology in RLN injury. Twenty-five male Sprague-Dawley rats underwent right RLN transection with the excision of a 5-mm segment. Vocal fold movements, vocalization, histology and immunostaining were evaluated at different time-points (3, 6, 10 and 16 weeks). Although vocalization was restored, movement of the vocal fold failed to return to normal levels following RLN injury. The expression of brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor differed in the thyroarytenoid (TA) and posterior cricoarytenoid muscles. The number of axons did not increase to baseline levels over time. Furthermore, normal muscle function was unlikely with spontaneous reinnervation. During regeneration following RLN injury, differences in the expression levels of neurotrophic factors may have resulted in preferential reinnervation of the TA muscles. Data from the present study indicated that neurotrophic factors may be applied for restoring the function of the laryngeal nerve following recurrent injury.

Synkinesis following recurrent laryngeal nerve injury: A computer simulation.

When the recurrent laryngeal nerve (RLN) is injured, functional recovery may be limited by the number of axons that regrow across the site of injury, and by the proportions of these axons that reinnervate the antagonistic muscle (synkinesis). This process was investigated in a computer model of RLN recovery. Computer simulation. The developed computer program accepted as inputs: number of RLN axons; proportions of axons originally innervating adductor versus abductor, fraction of axons transected, fraction of axons that grow back, and width of 1 standard deviation about the mean. The program employed random sampling from a normal distribution to model various degrees of recovery, using random numbers to assign each axon to the correct muscle, an incorrect muscle, or no recovery. Each simulation was run 1,000×, and the mean, highest, and lowest degrees of synkinesis were determined. More severe injuries were associated with greater degrees of synkinesis. Extremes of synkinesis were possible but were rare. One example result, for a 50% injury with a 50% recovery rate, found: in the adductor muscles, 74.8% of axons will be innervated, of which 49.2% are the original uninjured axons, 19.4% are recovered adductor axons, and 6.2% are misdirected abductor axons. In the posterior cricoarytenoid (PCA), these values were 75.7%, 50.8%, 6.1%, and 18.8%, respectively. Results of many such simulations are plotted. Laryngeal synkinesis can be simulated based on known anatomic ratios and estimated recovery rates. The PCA is invariably much more affected by synkinetic reinnervation than are the adductor muscles. NA Laryngoscope, 126:1600-1605, 2016.

Microarray Analysis Gene Expression Profiles in Laryngeal Muscle After Recurrent Laryngeal Nerve Injury.

The pathophysiology of recurrent laryngeal nerve (RLN) transection injury is rare in that it is characteristically followed by a high degree of spontaneous reinnervation, with reinnervation of the laryngeal adductor complex (AC) preceding that of the abducting posterior cricoarytenoid (PCA) muscle. Here, we aim to elucidate the differentially expressed myogenic factors following RLN injury that may be at least partially responsible for the spontaneous reinnervation. F344 male rats underwent RLN injury (n = 12) or sham surgery (n = 12). One week after RLN injury, larynges were harvested following euthanasia. The mRNA was extracted from PCA and AC muscles bilaterally, and microarray analysis was performed using a full rat genome array. Microarray analysis of denervated AC and PCA muscles demonstrated dramatic differences in gene expression profiles, with 205 individual probes that were differentially expressed between the denervated AC and PCA muscles and only 14 genes with similar expression patterns. The differential expression patterns of the AC and PCA suggest different mechanisms of reinnervation. The PCA showed the gene patterns of Wallerian degeneration, while the AC expressed the gene patterns of reinnervation by adjacent axonal sprouting. This finding may reveal important therapeutic targets applicable to RLN and other peripheral nerve injuries.

The Overwhelming Majority but not All Motor Fibers of the Bifid Recurrent Laryngeal Nerve are Located in the Anterior Extralaryngeal Branch.

BackgroundFew small studies reported that motor fibers are located exclusively in the anterior branch of the bifid recurrent laryngeal nerve (RLN). The aim of this study was to investigate the location of the motor fibers to the intrinsic muscles of the larynx among the bifid RLNs, and assess the prevalence of RLN injury with respect to nerve branching in a pragmatic trial.MethodsThis was a prospective cohort study of 1250 patients who underwent total thyroidectomy with intraoperative neural monitoring. The primary outcome was the position of the motor fibers in the bifid nerves. Adduction of the vocal folds was detected by the endotracheal tube electromyography and abduction by finger palpation of muscle contraction in the posterior cricoarytenoid. The secondary outcomes were the prevalence of the RLN branching and the prevalence of RLN injury in bifid versus non-bifid nerves.ResultsThe bifid RLNs were identified in 613/2500 (24.5 %) nerves at risk, including 92 (7.4 %) patients with bilateral bifurcations. The motor fibers were present exclusively in the anterior branch in 605/613 (98.7 %) bifid nerves, and in both the RLN branches in 8/613 (1.3 %) bifid nerves. Prevalence of RLN injury was 5.2 versus 1.6 % for the bifid versus non-bifid nerves (p < 0.001), odds ratio 2.98 (95 % confidence interval 1.79–4.95; p < 0.001).ConclusionsThe motor fibers of the RLN are located in the anterior extralaryngeal branch in the vast majority of but not in all patients. In rare cases, the motor fibers for adduction or abduction are located in the posterior branch of the RLN. As the bifid nerves are more prone to injury than non-branched nerves, meticulous dissection is recommended to assure preservation of all the branches of the RLN during thyroidectomy.

Effects of Functional Electrical Stimulation on Denervated Laryngeal Muscle in a Large Animal Model.

Bilateral vocal fold paralysis (BVCP) is a life-threatening condition that follows injury to the Recurrent Laryngeal nerve (RLn) and denervation of the intrinsic laryngeal musculature. Functional electrical stimulation (FES) enables restoration and control of a wide variety of motor functions impaired by lower motor neuron lesions. Here we evaluate the effects of FES on the sole arytenoid abductor, the posterior cricoarytenoid (PCA) muscle in a large animal model of RLn injury. Ten horses were instrumented with two quadripolar intramuscular electrodes in the left PCA muscle. Following a 12-week denervation period, the PCA was stimulated using a once-daily training session for 8 weeks in seven animals. Three animals were used as unstimulated controls. Denervation produced a significant increase in rheobase (P < 0.001). Electrical stimulation produced a 30% increase in fiber diameter in comparison with the unstimulated control group (33.9 ± 2.6 µm FES+, 23.6 ± 4.2 µm FES-, P = 0.04). A trend toward a decrease in the proportion of type 1 (slow) fibers and an increase in type 2a (fast) fibers was also observed. Despite these changes, improvement in PCA function at rest was not observed. These data suggest that electrical stimulation using a relatively conservative set of stimulation parameters can reverse the muscle fiber atrophy produced by complete denervation while avoiding a shift to a slow (type 1) fiber type.

Cricoarytenoid Articulation in Elderly Japanese With Special Reference to Morphology of the Synovial Tissue

To clarify composite fibers and cells in the synovial tissues of the cricoarytenoid joint (CA joint). Routine histology and immunohistrochemistry using sagittal or nearly sagittal sections obtained from 18 elderly cadaveric specimens. The CA joint capsule was thin and contained few elastic fibers. A limited supportive ligament, namely, a thickened fascia of the posterior cricoarytenoid muscles, was sometimes evident on the lateral aspect of the CA joint. However, even in the weaker medial aspect of the joint, no marked destruction of the synovial tissues was found. The CA joint always contained synovial folds--a short medial fold and long lateral folds--but these contained no or few macrophages, lymphocytes, and blood capillaries. In 2 exceptional specimens showing inflammatory cell infiltration in the submucosal tissue of the larynx, the macrophage-rich area extended toward the capsule and medial synovial fold. The lateral aspect of the CA joint was likely to be supported mechanically by the muscle-associated tissues. Strong support of the arytenoid by muscles might reduce the degree of CA joint injury with age. However, some patients with hoarseness due to mucosal inflammation of the larynx might have accompanying synovitis and subsequent cartilage injury in the CA joint.

Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray.

Neurochemical microstimulation in different parts of the midbrain periaqueductal gray (PAG) in the cat generates four different types of vocalization, mews, howls, cries, and hisses. Mews signify positive vocal expression, whereas howls, hisses, and cries signify negative vocal communications. Mews were generated in the lateral column of the intermediate PAG and howls and hisses in the ventrolateral column of the intermediate PAG. Cries were generated in two regions, the lateral column of the rostral PAG and the ventrolateral column of the caudal PAG. To define the specific motor patterns belonging to mews, howls, and cries, the following muscles were recorded during these vocalizations: larynx (cricothyroid, thyroarytenoid, and posterior cricoarytenoid), tongue (genioglossus), jaw (digastric), and respiration (diaphragm, internal intercostal, external abdominal oblique, and internal abdominal oblique) muscles. Furthermore, the frequency, intensity, activation cascades, and turns and amplitude analyses of the electromyograms (EMGs) during these vocalizations were analyzed. The results show that each type of vocalization consists of a specific, circumscribed motor coordination. The nucleus retroambiguus (NRA) in the caudal medulla serves as the final premotor interneuronal output system for vocalization. NRA neurochemical microstimulation also generated vocalizations (guttural sounds). Analysis of the EMGs demonstrated that these vocalizations consist of only small parts of the emotional voalizations generated by neurochemical stimulation in the PAG. These results demonstrate that motor organization of positive and negative emotional vocal expressions are segregated in the PAG and that the PAG uses the NRA as a tool to gain access to the motoneurons generating vocalization.

Functional Electrical Stimulation of the Feline Larynx With a Flexible Ribbon Electrode Array.

Success of laryngeal reanimation through neurorrhaphy has been limited by synkinesis and preoperative muscle atrophy. The objective of this study was to investigate the use of epimysial electrode arrays as a means of delivering electrical stimulation to the posterior cricoarytenoid muscles in order to control laryngeal abduction. Ribbon electrode arrays with 4 or 8 electrode contacts were used. Four cats underwent implantation of electrode arrays along the surface of the posterior cricoarytenoid muscles. The glottis was visualized with a 0° telescope while electrodes were stimulated at different amplitudes and pulse-width durations. Recordings of stimulated vocal folds were analyzed, and the degree of vocal fold abduction was measured in order to create recruitment curves for the left and right posterior cricoarytenoid. Recruitment curves from electrode channels within the array were compared. Electrodes oriented along the medial aspect of the posterior cricoarytenoid stimulated graded physiologic degrees of abduction depending on the amplitude of stimulation. Electrodes oriented laterally along the posterior cricoarytenoid stimulated greater degrees of simultaneous adduction with abduction. Acute studies of ribbon surface electrode arrays placed onto the posterior cricoarytenoid reproduce graded degrees of abduction necessary for the precise function of respiration and speech.

Pre-clinical evaluation of a minimally invasive laryngeal pacemaker system in mini-pig.

Microlaryngoscopic enlargement techniques have been the standard treatment for bilateral vocal fold paralysis (BVFP) for decades. Laryngeal pacing is a promising alternative treatment based on the electrostimulation of the posterior cricoarytenoid (PCA) muscle. This paper reports on the results of a pre-clinical study aiming to evaluate this method. Eight Göttingen mini-pigs were implanted with a laryngeal pacemaker (LP) implant prototype and with two LP electrodes, one in each PCA muscle. The 6-week follow-up included endoscopic stimulation controls in general anaesthesia and radiographic controls of electrode integrity and position stability. Stimulation parameters for optimal glottal opening were evaluated via videolaryngoscopy. Histopathology was performed upon conclusion of the study. 7/8 (87.5 %) animals were successfully implanted with the LP implant prototype and two LP electrodes. In general, stimulation was effectively delivered and correlated with the expected PCA muscle activation. 2/14 (14.3 %) electrodes dislocated and 1/14 (7.1 %) electrode tip broke. The LP system used in this experiment to induce vocal fold abduction by means of selective functional electrical stimulation of the PCA showed promising results. It may be a valid alternative to the current golden standard for BVFP treatment. Clinical studies are needed to confirm the medical relevance of the LP.

Development of a novel larynx pacemaker multichannel array electrode: In vivo animal analysis.

Electrical stimulation of posterior cricoarytenoid muscle offers a physiological approach to retain the function of the paralyzed larynx muscle after paralysis. The aim of this study was to develop and evaluate a durable, biocompatible, and atraumatic array electrode for inclusion in a larynx pacemaker. In addition to developing the electrode array, an evaluation methodology using in vivo multichannel electromyography was assessed. In vivo test procedures for material evaluation: an animal model. Over the research period, 42 array electrodes representing nine different prototypes were implanted in the triceps brachii muscle of 21 rats. Biocompatibility and atraumatic functions were evaluated via observation. Electrode function and durability were determined by comparison of daily electromyographic measurements of the muscle activity of the front leg (triceps brachii muscle) during locomotion. The used animal model demonstrated electrode material problems that could not be material evaluation from in vitro tests alone. Through use of this in vivo method, it was found that an array tip that is durable, biocompatible, and atraumatic should consist of many small electrode plates cast in flexible silicone. The connecting wires to the individual electrode plates should be Litz wire, which consists of multiple strands. The here demonstrated in vivo test method was a suitable animal model for designing and evaluating electrodes to be further developed for inclusion in human implants. N/A.

Features of Vocal Fold Adductor Paralysis and the Management of Posterior Muscle in Thyroplasty

To present the pathologic characteristics of unilateral recurrent nerve adductor branch paralysis (AdBP), and to investigate the management of posterior cricoarytenoid (PCA) muscle on the basis of our experience of surgical treatment for AdBP. This is a retrospective review of clinical records Four cases of AdBP, in which surgical treatment was performed, are presented. AdBP shows disorders of vocal fold adduction because of paralysis of the thyroarytenoid and lateral cricoarytenoid muscles. The PCA muscle, dominated by the recurrent nerve PCA muscle branch, does not show paralysis. Thus, this type of partial recurrent nerve paresis retains the abductive function and is difficult to distinguish from arytenoid cartilage dislocation because of their similar endoscopic findings. The features include acute onset, and all cases were idiopathic etiology. Thyroarytenoid muscle paralysis was determined by electromyography and stroboscopic findings. The adduction and abduction of paralytic arytenoids were evaluated from 3 dimensional computed tomography (3DCT). In all cases, surgical treatments were arytenoid adduction combined with thyroplasty. When we adducted the arytenoid cartilage during inspiration, strong resistance was observed. In the two cases where we could cut the PCA muscle sufficiently, the maximum phonation time was improved to ≥30 seconds after surgery, from 2 to 3 seconds preoperatively, providing good postoperative voices. In contrast, in the two cases of insufficient resection, the surgical outcomes were poorer. Because the preoperative voice in AdBP patients is typically very coarse, surgical treatment is needed, as well as ordinary recurrent nerve paralysis. In our experience, adequate PCA muscle resection might be helpful in surgical treatment of AdBP.

Transition of myosin heavy chain isoforms in human laryngeal abductors following denervation.

The objective of this study was to investigate the myofiber subtype transition of human posterior cricoarytenoid (PCA) muscle after the injury to recurrent laryngeal nerve (RLN). PCA muscle specimens were obtained from 38 bilateral vocal fold paralysis patients underwent arytenoidectomy. According to the duration of RLN injury, all the cases were divided into five denervation groups: 6-12 months, 1-2, 2-3, 3-6, and >6 years. The normal PCA muscles from total laryngectomy patients were chosen as controls. Immunofluorescence was adopted to detect the expression level of myosin heavy chain (MHC)-I and MHC-II in PCA muscle. Quantitative real-time PCR was also used to assess the transcriptional level of MHC subtypes (MHC-I, MHC-IIa, MHC-IIb, MHC-IIx, embryonic-MHC, and peri-natal-MHC). Immunofluorescence showed that MHC-I-positive myofibers in denervation groups were much lower than control group, respectively, while MHC-II-positive myofibers were significantly higher than control group (P < 0.05). With the extension of denervation, the number of MHC-I-positive myofibers gradually decreased, while MHC-II gradually increased and peaked in 1- to 2-year group. Transcriptional level of MHC-I, MHC-IIa, and MHC-IIb in denervation groups significantly down-regulated compared with the control (P < 0.05), respectively. However, MHC-IIx, embryonic-MHC, and peri-natal-MHC significantly up-regulated in all denervation groups, and the highest level was in 1- to 2-year denervation group. Data from the present study demonstrated that the maximum transition of MHC subtypes in human PCA muscles occurred in 1-2 years after denervation, suggesting that laryngeal reinnervation before the occurrence of irreversible transition of MHC subtypes could maintain the structural integrity of laryngeal PCA muscles.

Response of Aging Laryngeal Muscles to Chronic Electrical Stimulation

Objective: Laryngeal muscle dysfunction in the aged contributes to dysphagia and increases the risk of aspiration, factors that lead to higher rates of mortality and morbidity.These changes also compromise voice quality, impairing the ability to communicate and reducing quality of life. We examined how chronic electrical stimulation remodels the aging posterior cricoarytenoid and thyoarytenoid laryngeal muscles. Methods: We used 36 Fischer 344BN rats, 6- and 30-mo of age. Nerve cuff electrodes were implanted around the right recurrent laryngeal nerve. Rats were placed in either a 2-week stimulation (100Hz, 500ms duration, 0.20 trains/sec) or sham group. Stimulation occurred 2 times a day for 1 hour each. Rats were killed and muscles isolated for histology. Results: In thyoarytenoid muscle, mean muscle fiber area significanly increased at 6-mo and 30-mo on both sides in the stim group compared to sham. Central nucleation increased significanly at 30-mo in the stim group compared to 6-mo. There were no changes in neuromuscular junction quantity with stimulation. In 6-mo posterior cricoarytenoid muscle, mean muscle fiber area increased significanly in the stim group compared to sham. At 30-mo, there was a significant decrease in mean fiber area in the right stimulated side and an increase in the left stimulated side compared to sham. There was no change in central nucleation. Conclusions Rat laryngeal muscles are capable of remodeling in response to chronic electrical stimulation. Changes observed between age and muscle suggests a need for further study. Study results will serve as the basis for future work in treatment approaches for human laryngeal disorders.

3D Rendering of Porcine Recurrent Laryngeal Neuroanatomy

Recurrent laryngeal nerve (RLN) palsy is a common post‐operative complication of many head and neck surgeries. The best treatment to restore partial function to a damaged RLN is reinnervation of the posterior cricoarytenoid (PCA) muscle via anastomosis of the RLN and phrenic nerves. The pig is an excellent model of human laryngeal anatomy and physiology. A thorough knowledge of porcine laryngeal anatomy is necessary before the pig can be used to improve existing surgical strategies, and develop new ones. This study provides state of the art 3D renderings of the porcine larynx and the location of the RLN and its branches. Anatomical variation of primary RLN branching was analyzed in 25 specimens to reveal 3 major branching patterns. Pattern A (44%) consisted of a medial primary branch that bifurcated into two secondary branches. Pattern B (32%) consisted of three primary branches. Pattern C (24%), consisted of two primary branches. Several heat maps depict the relative spatial variability of 32 bilateral specimens of RLN trunks and primary branches. We show a high degree of variability in whole nerve medial/lateral location within the larynx in left RLN specimens as compared to right RLNs. However, the location of RLN primary branches was more highly conserved among left RLNs. We intend this study to be useful to groups using a porcine model to study PCA reinnervation techniques. This research is funded by the BYU College of Life Sciences Start‐Up Mentoring Grant.

Preventive effects of bortezomib on denervation-induced atrophy of the intrinsic laryngeal muscles: an experimental study in the rat

Conclusion: Bortezomib was effective in attenuating atrophy of the posterior cricoarytenoid (PCA) muscle, but not the thyroarytenoid (TA) muscle. This was probably due to differences in the fiber composition of the two muscles. The PCA muscle is composed of a combination of fast- and slow-twitch fibers, and therefore is more resistant to atrophy than the TA muscle, which is composed solely of fast-twitch fibers. Objectives: To investigate the preventive effects of bortezomib on denervation-induced atrophy of the TA and PCA muscles in the rat. Methods: Following transection of the left recurrent laryngeal nerve, bortezomib (100 μg/kg) was administered subcutaneously on post-denervation days 1 and 4, followed by a 10-day rest period every 14 days; each 2-week period constituted a single treatment cycle. In controls, saline was administered instead. Animals were killed for histological examination at 4 (n = 6), 8 (n = 7), and 12 (n = 7) weeks post-denervation. Muscle atrophy was assessed using three indices: wet muscle weight, muscle fiber cross-sectional area, and the number of muscle fibers/mm2. The effects of bortezomib were evaluated by comparing the left (L) and right (R) muscles, with sequential changes in the L/R ratio assessed. Results: In saline-administered animals, atrophy of the left-sided TA and PCA muscles progressed rapidly during the first 4 weeks post-denervation, following which progression slowed. Atrophy was greater in the TA compared with the PCA muscle, although this difference was not statistically significant. In bortezomib-administered animals, atrophy of the PCA muscle was attenuated significantly at post-denervation weeks 8 and 12; no such reduction in atrophy was observed for the TA muscle.

Effect on laryngeal adductor function of vincristine block of posterior cricoarytenoid muscle 3 to 5 months after recurrent laryngeal nerve injury.

It has been shown in a canine model that a single injection of vincristine into the posterior cricoarytenoid (PCA) muscle at the time of recurrent laryngeal nerve (RLN) injury effectively blocks its reinnervation and results in improved adductor strength. But clinically, such injuries are usually diagnosed weeks or months after onset. Vincristine injection does not affect a muscle that is already innervated; thus, there is a limited time frame following RLN injury during which a vincristine injection could effectively improve ultimate laryngeal adductor functional recovery. A series of delayed injections was performed in a canine model and results assessed. Animal (canine) experiment. The RLN was transected and repaired, and vincristine (0.4 mg) was injected into the PCA muscle at the time of injury (n=12) or 3, 4, and 5 months later (n=8 each study group). Six months after RLN injury, laryngeal adductor function was measured. Results of vincristine injection without RLN injury (n=6) and longer-term (12 months) follow-up for time zero injections (n=4) are also reported. The animals injected at time zero had better adductor function than non-injected controls, as reported previously, and this result was further increased at 12 months. The 3-month delay gave results similar to the time zero group. The 5-month delay group showed no vincristine benefit, and the 4-month delay group gave an intermediate result. Vincristine to the PCA had no effect on adductor function when the RLN was left intact. Plasma levels showed 19% of injected vincristine reached systemic circulation, which was cleared within 69 hours. Vincristine injection of the PCA muscle after RLN injury, which blocks this antagonist muscle from synkinetic reinnervation, leads to improved laryngeal adductor functional recovery. The window of opportunity to apply this treatment closes by 4 months after RLN injury in the canine model. Human RLN recovery follows a similar time course and can reasonably be expected to have a similar therapeutic window.

3D reconstruction and heat map of porcine recurrent laryngeal nerve anatomy: branching and spatial location.

Recurrent laryngeal nerve palsy is a common post-operative complication of many head and neck surgeries. Theoretically, the best treatment to restore partial function to a damaged recurrent laryngeal nerve would be reinnervation of the posterior cricoarytenoid muscle via anastomosis of the recurrent laryngeal and phrenic nerves. The pig is an excellent model of human laryngeal anatomy and physiology but a more thorough knowledge of porcine laryngeal anatomy is necessary before the pig can be used to improve existing surgical strategies, and develop new ones. This study first identifies the three most common recurrent laryngeal nerve branching patterns in the pig. Secondly, this study presents three-dimensional renderings of the porcine larynx onto which the recurrent laryngeal nerve patterns are accurately mapped. Lastly, heat maps are presented to display the spatial variability of recurrent laryngeal nerve trunks and primary branches on each side of 15 subjects (28 specimens). We intend for this study to be useful to groups using a porcine model to study posterior cricoarytenoid muscle reinnervation techniques.