Abnormal palatopharyngeal muscle morphology in sleep-disordered breathing
Introduction
Sleep-disordered breathing (SDB) is characterised by loud snoring, repetitive episodes of upper airway obstruction occurring during sleep and daytime sleepiness [1]. In its severe form, SDB has received increased attention because of the increased risk of diurnal hypertension, nocturnal dysrhythmia, pulmonary hypertension, ventricular failure, myocardial infarction and stroke [1]. SDB is recognised as a partial or complete upper airway collapse, with or without hypopneas or apneas. The obstruction of the pharynx may occur at one or more sites in the upper airway system [2], [3], [4]. Videoradiographic recordings and high speed MRI have demonstrated that the obstruction is often located in the velopharyngeal region [4], [5]. As the functional activity of the muscles of the upper airways is of vital importance in order to maintain the stability and patency of the upper airway during inspiration, a muscle dysfunction might be one cause of SDB. Information on the muscular role in the pathophysiology and pathogenesis behind the airway instability and development of SDB is so far limited.
Morphological analysis of the muscle structure, fibre type composition and expression of myosin heavy chain (MyHC) isoforms gives reliable information on muscle function and dysfunction. Human muscle fibres can generally be classified into types I and II fibres on the basis of the differences in enzyme-histochemical reaction for myofibrillar ATPase (mATPase). The type II fibres can be further subdivided into types IIA, IIAB and IIB and IIC depending on their staining density following preincubation in acid pH [6], [7]. The usefulness of fibre typing comes with the close correlation between the mATPase activity and the physiological properties of the muscle fibres [8], [9], [10]. The mATPase activity is located in the myosin heavy chain (MyHC) molecule, which is the major contractile protein in the muscles. MyHCs exist in multiple isoforms and the MyHC composition of the fibres, thereby dictates their contractile velocity and contraction force [11], [12]. The major MyHC isoforms expressed in adult human limb muscles are slow MyHC, fast A MyHC and fast X MyHC [13], [14], [15], [16]. Slow MyHC is present in type I fibres and is co-expressed with fast MyHC in type IIC/IM fibres. Fast A MyHC is mainly present in type IIA fibres and fast X in type IIB fibres. A gene homologue to the rodent fast B MyHC has also been identified in humans [17], but no myosin related to this gene has so far been identified in human skeletal muscles. Additional MyHC isoforms such as fetal, embryonic and α-cardiac are not normally expressed in adult limb muscle fibres but are present in normal human adult masticatory [18], [19], [20], [21], [22] and soft palate muscles [23] as well as intrafusal fibres in muscle spindles [24]. However, during pathological conditions, and mainly those including regeneration, expression of fetal and embryonic MyHCs can be induced in limb muscles [25], [26], [27]. In the present study, we have investigated whether morphological signs of a localised myogenic or neurogenic myopathy can be detected in two of the soft palate muscles, the palatopharyngeus and uvula muscles, in individuals with a long duration of SDB. The muscle samples were thoroughly analysed with morphological, enzyme-histochemical, immunohistochemical and biochemical methods to evaluate muscle and muscle fibre morphology, fibre type composition and expression of MyHC isoforms. The data from the patient muscles were compared with the data from corresponding muscles from the reference subjects.
Section snippets
Subjects and muscle sampling
Eleven consecutive patients scheduled for uvulo-palatopharyngoplasty (UPPP) due to socially handicapping snoring were included in the study (10 males and 1 female, mean age 51.5 years, range 31–65). Muscle samples were obtained from the palatopharyngeus and uvula muscles in connection with the surgical removal of the distal portion of the soft palate with or without tonsillectomy. For comparison, muscle specimens from the corresponding muscles and sites were taken during autopsy from five
Patients
The 11 patients diagnoses consisted of three patients with socially handicapping snoring alone (case nos. 2, 4, 10) and eight with snoring together with anamnestic signs of apnea or hypopnea. The mean duration of snoring among the patients was 16 years (range 4–30). The anamnestic signs of hypopneas or apneas were based on apneic periods according to bedtime partner, restless sleep and daytime somnolence. Over night sleep registration showed snoring between 10% and 60% of estimated sleeping
Discussion
In the present investigation, we found several morphological abnormalities in the soft palate muscles of SDB patients. The samples obtained from the patients differed markedly from the normal references by having an increased amount of connective tissue, abnormal fibre size distribution and fibre form and a significantly higher proportion of fibres containing developmental MyHC isoforms. Other observations were alterations in fibre type and MyHC composition, fibre type grouping and the presence
Acknowledgements
This work was supported by grants from the Swedish Medical Research Council (3934 and 6874), Medical and Odontological Faculties, Umeå University, the County Medical Council of Östergötland, the Swedish Society for Medical Research, Public Dental Health in Skåne, and the Swedish Dental Society. We thank Professor Lars Ödqvist, University Hospital, Department of Oto-Rhino-Laryngology, University Hospital, Linköping for the clinical examination and sleep recordings and for providing biopsy
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