Theme : Dreams

Muscle Fibre Type and Obstructive Sleep Apnea

Luigi Ferini-Strambi, Salvatore Smirne, Ugo Moz, Barbara Sferrazza and Sandro Iannaccone
State University of Milano and IRCSS H S. Raffaele, Sleep Disorders Center, Milan 20127, Italy
Abstract
Muscular pharyngeal structural changes, as fibre type disproportion, have been described in patients affected by Obstructive Sleep Apnea (OSA) and in an animal experimental OSA model. The unsolved question is whether these muscular abnormalities are either secondary to a compensatory increased activity or due to a constitutionally determined reduction of slow-alpha motor neurons. In the present study Medium Pharyngeal Constrictor Muscles (MPCM) of OSA (n = 13) and non-OSA (n = 9) patients have been morphologically evaluated. In addition a needle biopsy of Vastus Lateralis Muscle (VLM) was performed in 5 randomly selected patients of each group. Our results confirmed a specific fibre type disproportion of MPCM of OSA patients compared to non-OSA ones with a type II predominance and aspecific myopathic changes such as fibrosis and central nuclei. No difference was found in the VLM of the two groups. This finding could be explained by a secondary adaptive transformation consequent to nocturnal upper airway resistance in OSA. In fact, it has been demonstrated in human muscle that heavy-resistance training may produce preferential type II fibre hypertrophy in stimulated muscle.

Current Claim: There is a specific fibre type disproportion of type II fibres in MPCM of OSA patients compared to non-OSA ones.

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Recent studies in patients with Obstructive Sleep Apnea (OSA) have indicated that pharyngeal muscles undergo changes in structure probably as a direct consequence of their increased activity level during sleep (Woodson et al., 1991; Series et al., 1995). In these investigations the muscular abnormalities appeared to be more pronounced in OSA patients than in the snorers without OSA. However, as suggested by Petrof et al. (1996) the use of snorers as a control group could underestimate potential differences between normal individuals and those with OSA.
Another recent experimental study showed a pharyngeal myopathy of loaded upper airway in bulldogs with OSA compared to control dogs without OSA (Petrof et al., 1994). Importantly, no difference between bulldogs and control dogs were observed in limb musculature, suggesting that the changes in bulldog pharyngeal muscles were indeed due to the presence of OSA.

In a previous paper (Smirne et al., 1991) we reported our studies on the histological and histochemical characteristics of the MPCM in subjects with Habitual Snoring (HS) and Non-Snorers (NS). In HS we found an abnormal distribution of fibre types, there being a low percentage of type I and IIb fibres and a high percentage of type IIa fibres compared with NS. We suggested two possible hypotheses to explain the abnormal distribution of fibre types in HS. First, the reduction of slow alpha-motor neurons and, hence, of type I fibres was constitutionally determined. Second, motor neurons changed their patterns of discharge and, therefore, of MPCM activation, as an adaptation to anatomical characteristics of upper airway and habitual snoring. In order to clarify these aspects, the aim of the present study was to evaluate the MPCM and the VLM muscle of OSA patients compared to non-OSA non-snorer subjects.

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Twenty-two men who had laryngeal carcinoma in situ and who later underwent total laryngectomy were selected according to the following criteria: body mass index (BMI) less than 28, no previous radiotherapy, chemotherapy or corticosteroid treatment and no other organic diseases. The OSA diagnosis was made on the basis of clinical symptoms and on the results of a digital recording device (MESAM 4) which was applied to each patient to evaluate snoring and the number of respiratory disturbances per hour (RDI). The snoring percentage (percentage of the night spent snoring) and RDI were scored by visual analysis according to Bearpark et al. (1995) criteria. RDI values obtained using MESAM 4 and this visual scoring method are highly correlated with those obtained by polysomnography, even if by MESAM device there is no direct measurement of respiration in the form of respiratory effort or flow, and there is no information about sleep (Bearpark et al., 1995).
All patients gave informed consent and had a sample of muscle tissue taken from the MPCM during surgery. In addition a needle biopsy of VLM was performed in randomly selected patients from the OSA (5/9 patients) and non-OSA (5/13 patients) groups.

All the muscle samples were processed for morphological and morphometrical analysis. The muscles were immediately frozen in isopentane cooled by liquid nitrogen, and transverse sections (8µm) were processed for hematoxylin and eosin (H&E), modified Gomori trichrome, NADH dehydrogenase, ATPase (preincubation at pH 4.3, 4.5 and 9.4).

Light microscopy morphometric analysis was performed by a video-computer-assisted method (ImageMeasure, Phoenix Technology Inc., Seattle, WA); the histological pattern of muscle specimens was evaluated by the criteria of Dubowitz (1985), the fiber type distribution was calculated for types I, IIa, and IIb, diameter measurements were made of "lesser fiber diameter" defined as the maximum diameter across the lesser aspect of the muscle fiber (Dubowitz, 1985).

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Figure 1

Figure 2

Thirteen (non-OSA) patients, aged 38-72 (mean 55.6, SD 8.0) did not report habitual snoring and, according to the MESAM results, had a snoring percentage <10% (mean 5.2, SD 2.7) and an RDI <5 (mean 2.1, SD 1.9, range 0-4). Nine (OSA) patients, aged 50-68 (mean 59.7, SD 5.7) reported habitual snoring and complained of excessive daytime sleepiness; these patients had a snoring percentage >25% (mean 38.2, SD 13.7) and an RDI >5 (mean = 21.7, SD 9.9, range 12-37).
Table 1 shows the diameter and percentage of fibre types in MPCM of OSA and non-OSA patients. In OSA patients type IIa fibre diameter was significantly greater than that of non-OSA subjects. Table 2 shows the diameter and percentage of fibre types in MPCM and VLM of 5 OSA and 5 non-OSA patients. In both of these subgroups the MPCM fibres were smaller than VLM fibres, but no difference was found in VLM fibre diameter between OSA and non-OSA patients. The distribution of VLM fibres was similar in the two subgroups, in contrast to the results obtained in MPCM fibre distribution.

At light microscopy VLM in OSA and non-OSA patients, as well as MPCM in non-OSA patients, had the usual polygonal aspect and eccentric nuclei (Fig. 1). An increase of endomysial connective tissue was observed in pharyngeal muscles of OSA patients (Fig. 2).

Few MPCM fibres in the OSA group revealed structural abnormalities such as central nucleation, splitting and moth-eaten fibres.

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Our data show in MPCM of non-OSA non-snorer patients only about 10% fast-twitch fatigue sensitive fibres (type IIb) and nearly 90% fatigue-resistant fibres (including slow-twitch oxidative fibres, type I, and fast-twitch oxidative-glycolytic fibres, type IIa). Since type I muscle fibres are well endowed with mitochondria and type IIa fibres may increase their oxidative capacity, it follows that most muscle fibres in normal human MPCM are metabolically fit for fatigue resistance.
The fibre type disproportion we previously found in MPCM of HS (Smirne et al., 1991) has been confirmed in our OSA patients.

An abnormal distribution of fibre types with a lower percentage of type I fibres and higher percentage of type IIa fibres has been found in OSA patients compared to non-OSA subjects.

It has been demonstrated in human muscle that heavy-resistance training or low-repetition and high-load exercise may produce a slow (type I) to fast (type II) fibres transition with compensatory increase of muscle mass (Proctor et al., 1995; Tesh et al., 1989). In OSA patients MPCM may adapt itself to repeated high-tension contractions similar to those of resistance-training exercises. The increased proportion of type IIa fibres that we found in MPCM of OSA patients has been also reported in uvula tissue of OSA by Series et al. (1995).

The fibre type disproportion observed in pharyngeal muscles of OSA patients is present in other human muscle diseases, such as "congenital fibre type disproportion" (Brooke, 1973). This pathology is not selective, involving all muscles. In our previous study (Smirne et al., 1991) one hypothesis to explain the abnormal distribution of fibre types found in HS was the presence of a constitutionally determined reduction of slow alpha-motor neurons and as consequence of type I muscle fibers. To test this hypothesis in the present study a limb muscle biopsy in randomly selected OSA and non-OSA patients was performed. No difference between the two groups was found in VLM. Thus, the selective muscle pathology of MPCM found in our OSA patients suggests an acquired rather than constitutional activity-induced modification in the pharyngeal muscles. This activity-induced chronic process of remodeling of fibre types could cause, as secondary phenomena, muscle injury consisting in fibrosis, central nuclei, and muscle splitting. These muscle alterations, present in MPCM of our OSA patients and described by other authors (Stauffer et al., 1989) in different upper-airway muscles of OSA patients, could cause a reduction of muscle efficiency but are not indicative of a specific myopathic disease.

Our results are in accordance to those of an animal experimental model of OSA. Petrof et al. (1994) found in bulldog sternohyoid muscles an increase in the proportion of type II fibres compared to that in control dogs without OSA. The same fibres showed signs of muscle injury such as splitting fibres, central nuclei, and moth-eaten fibers. No difference between bulldogs with OSA and control dogs were found for limb musculature. Petrof et al. (1991) concluded that the specific abnormality of pharyngeal muscle was indeed due to the presence of OSA.

The studies on the muscle characteristics of upper airway in OSA patients generally evaluated male subjects. It has been demonstrated that women, in comparison to men, have augmented pharyngeal dilator muscle activity that could render the female airway more stable and less collapsible, thus reducing the incidence of OSA (Popovic et al., 1995). Further studies on pharyngeal muscle structure in female OSA patients are needed in order to ascertain the importance of upper airway muscle abnormalities in the pathogenesis of OSA.

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