Positive end-expiratory airway pressure does not aggravate ventilator-induced diaphragmatic dysfunction in rabbits

Introduction

Immobilization of hindlimb muscles in a shortened position results in an accelerated rate of inactivity-induced muscle atrophy and contractile dysfunction. Similarly, prolonged controlled mechanical ventilation (CMV) results in diaphragm inactivity and induces diaphragm muscle atrophy and contractile dysfunction. Further, the application of positive end-expiratory airway pressure (PEEP) during mechanical ventilation would result in shortened diaphragm muscle fibers throughout the respiratory cycle. Therefore, we tested the hypothesis that, compared to CMV without PEEP, the combination of PEEP and CMV would accelerate CMV-induced diaphragm muscle atrophy and contractile dysfunction. To test this hypothesis, we combined PEEP with CMV or with assist-control mechanical ventilation (AMV) and determined the effects on diaphragm muscle atrophy and contractile properties.

Methods

The PEEP level (8 cmH₂O) that did not induce lung overdistension or compromise circulation was determined. In vivo segmental length changes of diaphragm muscle fiber were then measured using sonomicrometry. Sedated rabbits were randomized into seven groups: surgical controls and those receiving CMV, AMV or continuous positive airway pressure (CPAP) with or without PEEP for 2 days. We measured in vitro diaphragmatic force, diaphragm muscle morphometry, myosin heavy-chain (MyHC) protein isoforms, caspase 3, insulin-like growth factor 1 (IGF-1), muscle atrophy F-box (MAFbx) and muscle ring finger protein 1 (MuRF1) mRNA.

Results

PEEP shortened end-expiratory diaphragm muscle length by 15%, 14% and 12% with CMV, AMV and CPAP, respectively. Combined PEEP and CMV reduced tidal excursion of segmental diaphragm muscle length; consequently, tidal volume (VT) decreased. VT was maintained with combined PEEP and AMV. CMV alone decreased maximum tetanic force (Po) production by 35% versus control (P < 0.01). Combined PEEP and CMV did not decrease Po further. Po was preserved with AMV, with or without PEEP. Diaphragm muscle atrophy did not occur in any fiber types. Diaphragm MyHC shifted to the fast isoform in the combined PEEP and CMV group. In both the CMV and combined PEEP and CMV groups compared to controls, IGF-1 mRNAs were suppressed, whereas Caspase-3, MAFbx and MuRF1 mRNA expression were elevated.

Conclusions

Two days of diaphragm muscle fiber shortening with PEEP did not exacerbate CMV-induced diaphragm muscle dysfunction.     

Effects of prolonged mechanical ventilation on respiratory muscle ultrastructure and mitochondrial respiration in rabbits

OBJECTIVE: To investigate in rabbits whether prolonged mechanical ventilation (PMV) leads to ultrastructural changes in respiratory muscles and alters diaphragm mitochondrial respiration. DESIGN AND SETTING: Experimental prospective study in a university laboratory. ANIMALS AND INTERVENTIONS: We studied respiratory muscles of seven rabbits after 49+/-1 h of controlled mechanical ventilation. Ten nonventilated rabbits were used as a control group. MEASUREMENTS AND RESULTS: After mechanical ventilation electron-microscopic observations of the diaphragm and the external intercostal muscles revealed disrupted myofibrils, increased number of lipid vacuoles in the sarcoplasm, and smaller mitochondria with focal membrane disruptions. Volumetric and numerical densities of the mitochondria were significantly lower in the PMV group than the control group. Mitochondrial respiration was quantified in isolated diaphragm muscle-cell mitochondria using two respiratory substrates. There was no difference in oxygen consumption values in the three states of mitochondrial respiration between the two groups except for state 2 (basal state) with pyruvate/malate parameter (53.5+/-20 for the ventilated group vs. 33.8+/-10.2 nmol atom O/mg per minute for the control group). There was no significant difference between groups in ADP/O ratio or respiratory control ratio. CONCLUSIONS: PMV leads to respiratory muscle cell degeneration and minor changes in oxidative phosphorylation coupling in diaphragmatic mitochondria. These phenomena may mediate part of damage of respiratory muscles after inactivity related to PMV.     

Angiotensin 1‐7 protects against ventilator‐induced diaphragm dysfunction

Mechanical ventilation (MV) is a life‐saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator‐induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin‐angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1‐7 (Ang1‐7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1‐7 protects the diaphragm against MV‐induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1‐7 shielded diaphragm fibers against MV‐induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1‐7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1‐7 has the therapeutic potential to protect against VIDD by preventing MV‐induced contractile dysfunction and atrophy of both slow and fast muscle fibers.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Prolonged mechanical ventilation results in ventilator‐induced diaphragm dysfunction (VIDD). This is significant because VIDD is a major risk factor for problems in weaning patients from the ventilator. Currently, no standard treatment exists to prevent VIDD. However, emerging evidence reveals that pharmacological inhibition of the classical axis of the renin‐angiotensin system (RAS) protects against VIDD. Although angiotensin 1‐7 (Ang1‐7) activates the nonclassical arm of the RAS and antagonizes classical RAS signaling, the therapeutic potential of Ang1‐7 to protect against VIDD remains unknown.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Is Ang1‐7 a viable therapy to prevent VIDD?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Treatment of animals with Ang1‐7 protected the diaphragm against both MV‐induced diaphragmatic contractile dysfunction and fiber atrophy. Importantly, Ang1‐7 protected against MV‐induced atrophy of both fast and slow‐type fibers and contractile dysfunction.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These new findings provide a foundation for future testing of Ang1‐7, a potential therapy to protect against VIDD.     

Rocuronium exacerbates mechanical ventilation-induced diaphragm dysfunction in rats

OBJECTIVE: Nondepolarizing neuromuscular blocking agents are commonly used in the intensive care setting, but they have occasionally been associated with development of myopathy. In addition, diaphragmatic atrophy and a reduction in diaphragmatic force were reported after short-term controlled mechanical ventilation in animal models. We hypothesized that infusion of rocuronium, an aminosteroidal neuromuscular blocking agent, during 24 hrs of controlled mechanical ventilation would further alter diaphragm function and would enhance activation of the ubiquitin- proteasome pathway. DESIGN: Randomized, controlled experiment. SETTING: Basic animal science laboratory. SUBJECTS: Male Wistar rats, 14 wks old. INTERVENTIONS: Rats were divided into four groups: a control group, a group of anesthetized rats breathing spontaneously for 24 hrs, and two groups submitted to mechanical ventilation for 24 hrs, receiving a continuous infusion of either 0.9% NaCl or rocuronium. MEASUREMENTS AND MAIN RESULTS: In vitro diaphragm force was decreased more significantly after 24 hrs of mechanical ventilation combined with rocuronium infusion than after mechanical ventilation alone (e.g., tetanic force, -27%; p < .001 vs. mechanical ventilation). Similarly, the decrease in diaphragm type IIx/b fiber dimensions was more pronounced after mechanical ventilation with rocuronium treatment than with saline treatment (-38% and -29%, respectively; p < .001 vs. control). Diaphragm hydroperoxide levels increased similarly in both mechanically ventilated groups. Diaphragm muscle RING-finger protein-1 (MURF-1) messenger RNA expression, an E3 ligase of the ubiquitin-proteasome pathway, increased after mechanical ventilation (+212%, p < .001 vs. control) and increased further with combination of rocuronium (+320%, p < .001 vs. control). Significant correlations were found between expression of MURF-1 messenger RNA, diaphragm force, and type IIx/b fiber dimensions. CONCLUSIONS: Infusion of rocuronium during controlled mechanical ventilation leads to further deterioration of diaphragm function, additional atrophy of type IIx/b fibers, and an increase in MURF-1 messenger RNA in the diaphragm, which suggests an activation of the ubiquitin-proteasome pathway. These findings could be important with regard to weaning failure in patients receiving this drug for prolonged periods in the intensive care unit setting.     

Serotonin-induced contractile and structural changes in fast and slow skeletal muscles in mice

The effects of serotonin on the contractile properties of the soleus and extensor digitorum longus muscles in mice were studied after chronic intraperitoneal administration with and without a recovery period, and compared to contractile studies of the same muscles performed after acute administration of serotonin. A curarized in vitro preparation of both muscles was used throughout for the contractile studies. In addition, structural changes were studied in the chronic preparations. Chronic serotonin administration produced histologic changes in type 1 and 2A fibers and a reduction in twitch and tetanic tension and the rate of twitch and tetanic tension development limited to the slow (aerobic) soleus muscle. Acute in vitro administration of serotonin altered the contractile properties of both soleus and extensor digitorum longus muscles with the latter being more involved. The effects of chronic serotonin administration appear to be primarily related to ischemia while the effects of acute administration appear to be mediated by direct, nonvascular action on skeletal muscle.     

Triamcinolone and prednisolone affect contractile properties and histopathology of rat diaphragm differently.

Diaphragm atrophy and weakness occur after administration of massive doses of corticosteroids for short periods. In the present study the effects of prolonged administration of moderate doses of fluorinated and nonfluorinated steroids were investigated on contractile properties and histopathology of rat diaphragm. 60 rats received saline, 1.0 mg/kg triamcinolone, or 1.25 or 5 mg/kg i.m. prednisolone daily for 4 wk. Respiratory and peripheral muscle mass increased similarly in control and both prednisolone groups, whereas triamcinolone caused severe muscle wasting. Maximal tetanic tension averaged 2.23 +/- 0.54 kg/cm2 (SD) in the control group. An increased number of diaphragmatic bundles in the 5-mg/kg prednisolone group generated maximal tetanic tensions < 2.0 kg/cm2 (P < 0.05). In addition, fatigability during the force-frequency protocol was most pronounced in this group (P < 0.05). In contrast, triamcinolone caused a prolonged half-relaxation time and a leftward shift of the force-frequency curve (P < 0.05). Histological examination of the diaphragm showed a normal pattern in the control and 1.25-mg/kg prednisolone group. Myogenic changes, however, were found in the 5-mg/kg prednisolone group and, more pronounced, in the triamcinolone group. Selective type IIb fiber atrophy was found in the latter group, but not in the prednisolone groups. In conclusion, triamcinolone induced type IIb fiber atrophy, resulting in reduced respiratory muscle strength and a leftward shift of the force-frequency curve. In contrast, 5 mg/kg prednisolone caused alterations in diaphragmatic contractile properties and histological changes without fiber atrophy.     

Electrical stimulation of sciatic nerve of rats after partial denervation of soleus muscle

The purpose of this study was to determine the effect of electrical stimulation of the sciatic nerve on the recovery of the weight and tension of partially denervated rat soleus muscle. Electrodes were implanted unilaterally adjacent to the sciatic nerve in 30 adult female Wistar rats. Fifteen rats underwent bilateral partial nerve section (PNS) of the sciatic nerve to stimulate the plantar flexors. Both the normal and partially nerve sectioned animals were stimulated unilaterally with 4 ms, 2-4 mA current given at 10 pulses per second. Groups of five normal and five partially denervated animals were stimulated for two, four or eight hours per day, five days per week for six weeks. The soleus muscles were evaluated for muscle weight (MW), twitch (Pt) and tetanic (Po) tension, contraction time (CT) and fiber areas of the type 1 and type 2 fibers. The MW, Pt, Po, CT and area of the type 1 and 2 muscle fibers of the normal soleus muscles were 114 +/- 15 mg, 21 +/- 4 mg, 95 +/- 20 mg, 95 +/- 21 ms, 1532 +/- 84 microns m2 and 1267 +/- 136 microns m2 respectively. The electrical stimulation had no effect on the normal soleus muscles. The MW, Pt, Po, CT and area of type 1 and 2 muscles fibers of the partially denervated control soleus muscles were 59 +/- 12 mg, 9 +/- 4 mg, 22 +/- 14 mg, 104 +/- 32 ms, 1028 +/- 514 microns m2, and 849 +/- 292 microns m2 respectively. Two hours of electrical stimulation significantly increased the MW (87 +/- 17 g), Pt (17 +/- 6g), and Po (49 +/- 23 g) but not the type 1 and 2 fiber areas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detrimental effects of short-term mechanical ventilation on diaphragm function and IGF-I mRNA in rats

OBJECTIVES: Because respiratory muscle weakness appears to play an important role in weaning from mechanical ventilation, we developed an animal model of mechanical ventilation with appropriate controls in order to determine whether 24 h of mechanical ventilation already affected diaphragmatic function. DESIGN AND INTERVENTIONS: Fifty-two male Wistar rats were randomized into three groups: a non-anesthetized control group (C, n=10), an anesthetized spontaneously breathing group (SB, n=9 out of 26), and an anesthetized and mechanically ventilated group (MV, n=12 out of 16). RESULTS: After 24 h, in vitro diaphragmatic force was decreased in SB group but even more so in MV group (i.e., 80 Hz: -15% in SB, P<0.005 vs C and -34% in MV group, P<0.005 vs C and SB). This was associated with a significant decrease in the diaphragm type I and type IIa dimensions in the SB group, which was more pronounced in the MV group. Interestingly, diaphragm IGF-I mRNA was decreased in the SB group (-14%, P<0.05 vs C), but more so in MV group (-29%, P<0.001 vs C and P<0.01 vs SB). Moreover, there was a significant correlation between diaphragm force and IGF-I mRNA (at 80 Hz r=0.51, P=0.0056). CONCLUSIONS: We conclude that 24 h of mechanical ventilation in rats, independently of anesthesia, already significantly reduced diaphragm force, fiber dimensions, and its IGF-I mRNA levels.     

The effects of therapeutic electric stimulation on acute muscle atrophy in rats after spinal cord injury.

OBJECTIVE: To evaluate the effects of electric stimulation in preventing acute muscle atrophy after spinal cord transection in rats. DESIGN: A randomized experimental design. SETTING: Animal facilities for experimental medicine. ANIMALS: Fifty-six adult male Wistar rats assigned to control, low-frequency, and high-frequency groups. INTERVENTIONS: The rats were implanted with a percutaneous intramuscular electrode in the vicinity of the peroneal nerve; then the spinal cord was transected in a T9 level. The stimulation frequency was low (20Hz) or high (100Hz). The stimulation cycle was 4 seconds of stimulation every 8 seconds. MAIN OUTCOME MEASUREMENTS: The lesser fiber diameters from type 1, 2A, and 2B muscle fibers were measured. In another assessment, maximal contraction force was measured. The muscle force produced at 20 and 100Hz was expressed as increasing values in tetanic force. RESULTS: Comparison between nonstimulated and stimulated tibialis anterior muscles found that atrophy of type 1 fibers (p < .01) and type 2B fibers (p < .05) at both stimulated levels and of type 2A fibers at 100-Hz level (p < .05) was prevented by therapeutic electric stimulation (TES). There were significant differences in the size of muscle fiber diameter between nonstimulated and stimulated muscles at 100Hz in type 2A and, markedly, in type 2B. The increasing value of muscle force was significantly greater at 100Hz than at 20Hz (p < .05). No significant histologic differences were observed between high- and low-frequency stimulated fibers of any of the 3 muscle types. CONCLUSIONS: Acute atrophy of muscle fibers was more effectively prevented by high-frequency stimulation (100Hz) than by no stimulation or low-frequency stimulation (20Hz). The increasing value of muscle force was significantly greater at high-frequency than low-frequency stimulation, suggesting that the clinical application of high-frequency stimulation in acute spinal cord injury should be studied.     

Can continuous physical training counteract aging effect on myoelectric fatigue? A surface electromyography study application

OBJECTIVES: To compare the myoelectric onset of muscle fatigue in physically active trained young skiers with respect to elderly skiers and to test whether continuous training can counteract the selective loss of type II muscle fibers usually observed with aging. DESIGN: An observational, cross-sectional study of the myoelectric onset of muscle fatigue in the left tibialis anterior muscles. SETTING: Surface electromyography recorded with portable devices at a downhill ski rescue lodge in the Italian Alps. PARTICIPANTS: Fifty-four physically trained, active skiers (43 men, 11 women; age range, 24-85y). INTERVENTIONS: Questionnaire on physical activity and 2 sustained isometric voluntary contractions at 20% and 2 at 80% of the maximal voluntary contraction level. MAIN OUTCOME MEASURES: Isometric contractions and mean and median spectral frequencies calculated to monitor the myoelectric manifestations of muscle fatigue. RESULTS: Fatigue indices did not differ significantly between younger and older subjects and, thus, did not show a correlation between myoelectric manifestations of muscle fatigue and age in physically active subjects. CONCLUSION: It appears possible that aging skeletal muscles subjected to continuous exercise develop an adaptive response that counteracts the selective loss of type II muscle fibers usually observed in the muscles of elderly sedentary subjects. Our results suggest that physical activity could be considered in the elderly within a broad rehabilitative framework in which appropriate and even tailored physical training could be planned to counteract the physiologic effects of aging on muscle fiber distribution.     

Detrimental effects of short-term glucocorticoid use on the rat diaphragm

BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of short-term, high doses of glucocorticoids on both body and diaphragm weights as well as contractile characteristics of the rat diaphragm. SUBJECTS: Adult, female Sprague-Dawley rats were divided into 2 groups: a control group (n=16) and a prednisolone group (n=16). METHODS: The prednisolone group received prednisolone at a dosage of 5 mg/kg, and the control group received sham saline injections for 5 days. Animals were weighed prior to and after completion of the drug injection period. At the completion of the drug injection period, the animals were sacrificed, and the diaphragm, soleus, and extensor digitorum longus muscles were removed and weighed. A small strip of the costal diaphragm was connected to a force transducer, and the following contractile characteristics were measured: maximal specific isometric tetanic tension, peak isometric twitch specific tension, one-half relaxation time, and time to peak tension. RESULTS: Both body and diaphragm weights decreased by 15% in the prednisolone group as compared with the control group. Maximal specific isometric tetanic tension was reduced 13% in the prednisolone group as compared with the control group. There was no difference in any twitch contractile characteristics between the 2 groups. CONCLUSION AND DISCUSSION: These data support the hypothesis that glucocorticoid treatment over a 5-day period results in a decrease in specific tension as well as diaphragm and body weight. These results may have implications for the treatment of patients receiving high doses of glucocorticoids for acute medical conditions.     

Hypercapnia attenuates ventilator-induced diaphragm atrophy and modulates dysfunction

Introduction

Diaphragm weakness induced by prolonged mechanical ventilation may contribute to difficult weaning from the ventilator. Hypercapnia is an accepted side effect of low tidal volume mechanical ventilation, but the effects of hypercapnia on respiratory muscle function are largely unknown. The present study investigated the effect of hypercapnia on ventilator-induced diaphragm inflammation, atrophy and function.

Methods

Male Wistar rats (n = 10 per group) were unventilated (CON), mechanically ventilated for 18 hours without (MV) or with hypercapnia (MV + H, Fico₂ = 0.05). Diaphragm muscle was excised for structural, biochemical and functional analyses.

Results

Myosin concentration in the diaphragm was decreased in MV versus CON, but not in MV + H versus CON. MV reduced diaphragm force by approximately 22% compared with CON. The force-generating capacity of diaphragm fibers from MV + H rats was approximately 14% lower compared with CON. Inflammatory cytokines were elevated in the diaphragm of MV rats, but not in the MV + H group. Diaphragm proteasome activity did not significantly differ between MV and CON. However, proteasome activity in the diaphragm of MV + H was significantly lower compared with CON. LC3B-II a marker of lysosomal autophagy was increased in both MV and MV + H. Incubation of MV + H diaphragm muscle fibers with the antioxidant dithiothreitol restored force generation of diaphragm fibers.

Conclusions

Hypercapnia partly protects the diaphragm against adverse effects of mechanical ventilation.     

Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm

AbstractMechanical ventilation (MV) is a clinical tool providing adequate alveolar ventilation in patients that require respiratory support. Although a life‐saving intervention for critically ill patients, prolonged MV results in the rapid development of inspiratory muscle weakness due to both diaphragmatic atrophy and contractile dysfunction; collectively known as “ventilator‐induced diaphragm dysfunction” (VIDD). VIDD is a severe clinical problem because diaphragmatic weakness is a risk factor for difficulties in weaning patients from MV. Currently, no standard treatment to prevent VIDD exists. Nonetheless, growing evidence reveals that hydrogen sulfide (H₂S) possesses cytoprotective properties capable of protecting skeletal muscles against several hallmarks of VIDD, including oxidative damage, accelerated proteolysis, and mitochondrial damage. Therefore, we used an established animal model of MV to test the hypothesis that treatment with sodium sulfide (H₂S donor) will defend against VIDD. Our results confirm that sodium sulfide was sufficient to protect the diaphragm against both MV‐induced fiber atrophy and contractile dysfunction. H₂S prevents MV‐induced damage to diaphragmatic mitochondria as evidenced by protection against mitochondrial uncoupling. Moreover, treatment with sodium sulfide prevented the MV‐induced activation of the proteases, calpain, and caspase‐3 in the diaphragm. Taken together, these results support the hypothesis that treatment with a H₂S donor protects the diaphragm against VIDD. These outcomes provide the first evidence that H₂S has therapeutic potential to protect against MV‐induced diaphragm weakness and to reduce difficulties in weaning patients from the ventilator. Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Mechanical ventilation (MV) results in diaphragm atrophy and contractile dysfunction, known as ventilator‐induced diaphragm dysfunction (VIDD). VIDD is important because diaphragm weakness is a risk factor for problems in weaning patients from MV. Currently, no accepted treatment exists to protect against VIDD. Growing evidence reveals that hydrogen sulfide (H₂S) donors protect skeletal muscle against ischemia‐reperfusion‐induced injury. Nonetheless, it is unknown if treatment with a H₂S donor can protect against VIDD.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Can treatment with an H₂S donor protect against VIDD?

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study provides the first evidence that treatment with a H₂S donor protects against VIDD.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

These new findings provide the basis for further exploration of H₂S donors as a therapy to prevent VIDD and reduce the risk of problems in weaning patients from MV.     

Reproducibility of contractile properties of the human paralysed and non‐paralysed quadriceps muscle

This study assessed the reproducibility of electrically evoked, isometric quadriceps contractile properties in eight people with spinal cord injury (SCI) and eight able‐bodied (AB) individuals. Over all, the pooled coefficients of variation (CV_ps) in the SCI group were significantly lower (ranging from 0·03 to 0·15) than in the AB group (ranging from 0·08 to 0·21) (P<0·05). Furthermore, in all subjects, the variability of force production increased as stimulation frequency decreased (P<0·01). In subjects with SCI, variables of contractile speed are clearly less reproducible than tetanic tension or resistance to fatigue. Contractile properties of quadriceps muscles of SCI subjects were significantly different from that of AB subjects. Muscles of people with SCI were less fatigue resistant (P<0·05) and produced force–frequency relationships that were shifted to the left, compared with AB controls (P<·01). In addition, fusion of force responses resulting from 10 Hz stimulation was reduced (P<·05) and speed of contraction (but not relaxation) was increased (P<0·05), indicating an increased contractile speed in paralysed muscles compared with non‐paralysed muscles. These results correspond with an expected predominance of fast glycolytic muscle fibres in paralysed muscles. It is concluded that quadriceps dynamometry is a useful technique to study muscle function in non‐paralysed as well as in paralysed muscles. Furthermore, these techniques can be reliably used, for example, to assess therapeutic interventions on paralysed muscles provided that expected differences in relative tetanic tension and fatigue resistance are larger than ～5% and differences in contractile speed are larger than ～15%.     

Physiologic, metabolic, and muscle fiber type characteristics of musculus uvulae in sleep apnea hypopnea syndrome and in snorers.

Upper airway dilator muscles play an important role in the pathophysiology of sleep apnea hypopnea syndrome (SAHS). The mechanical and structural characteristics of these muscles remain unknown. The aim of this study was to compare the physiologic, metabolic, and fiber type characteristics of one upper airway dilator muscle (musculus uvulae, MU) in 11 SAHS and in seven nonapneic snorers. The different analyses were done on MU obtained during uvulo-palato-pharyngoplasty. Snorers and SAHS differed only in their apnea + hypopnea indices (11.5 +/- 5.9 and 34.2 +/- 14.6/h, respectively, mean +/- SD). Absolute twitch and tetanic tension production of MU was significantly greater in SAHS than in snorers while the fatigability index was similar in the two groups. Protein content and anaerobic enzyme activities of MU were significantly greater in SAHS than in snorers; no difference was observed for aerobic enzyme activities. The total muscle fiber cross-sectional area of MU was significantly higher in SAHS (2.2 +/- 0.9 mm2) than in snorers (1.1 +/- 0.7 mm2). The surface occupied by type IIA muscle fibers of MU was larger in SAHS (2.00 +/- 0.96) than in snorers (0.84 +/- 0.63 mm2). We conclude that the capacity for tension production and the anaerobic metabolic activity of MU are greater in SAHS than in snorers.     

骨关节病患者肌纤维萎缩类型及其与日常活动的相关性

背景:骨关节病患者因制动等原因可出现严重的肌纤维萎缩,但目前对这类肌纤维萎缩的微观分类及其与日常活动的研究较少。目的:观察骨关节病患者肌肉萎缩类型以及其与日常活动的相关性。方法:纳入24例老年女性骨关节病患者,应用功能独立性评定量表对患者习惯性的日常运动进行了评价,在进行关节置换过程中对患者肌纤维进行了测定并通过活检进行组织病理学侧量。同时选取同期因骨折需要进行修复的4例女性患者为对照组。观察患者的肌纤维(Ⅰ型、ⅡA型和ⅡB型)发生萎缩类型和比率变化。结果与结论:骨关节病患者根据发生萎缩的肌纤维类型不同,分为1型、2B型何1+2AB型。Ⅰ型的肌纤维肌横截面积明显小于ⅡA型和ⅡB型肌纤维(P<0.05)。大部分骨关节病患者在得病过程中仅发生同一种肌纤维类型的萎缩,而非所有的肌纤维均出现萎缩。功能独立性评定量表评分从1+2AB型,2B型和1型逐渐减少(P<0.05)。结果证实,肌肉萎缩1+2AB型对骨关节病患者日常活动影响最大,而单纯的2B型影响最小。     

Changes in ultrasonic attenuation and backscatter of muscle with state of contraction

We have previously demonstrated that backscatter (uncompensated for attenuation) of canine myocardium varies systematically throughout the cardiac cycle and in relation to regional contractile performance. To elucidate these phenomena under conditions independent of blood flow and complex myofibrillar architecture, we measured attenuation with a phase-insensitive receiver and backscatter over a wide range of frequencies in an intermittently tetanized (10 stimulations), isolated frog gastrocnemius preparation (n = 12 muscles). Muscle contraction, as compared with relaxation, was associated with increased values of slope of attenuation (0.78 +/- 0.04 vs 0.58 +/- 0.03 dB/(cm MHz); p less than 0.001) and increased values of integrated backscatter (-29.5 +/- 0.9 vs -35.5 +/- 0.8 dB; p less than 0.005). Differences in attenuation and backscatter diminished with the number of muscle stimulations (as the muscle fatigued). Thus, quantitative ultrasonic indices of skeletal muscle vary systematically with the contractile performance of the tissue. Extrapolation of these results to cardiac muscle suggests that the sensitivity of these indices to contractile function of muscle may provide an approach for noninvasive assessment of intrinsic properties of myocardium that determines its performance.     

Gonadectomy and reduced physical activity: effects on skeletal muscle

OBJECTIVES: To examine the effects of testosterone (TST) loss on skeletal muscle contractile function and the potential interactive effects of TST loss and physical inactivity. DESIGN: Randomized control trial. ANIMALS: Forty-eight male rats (age, 6mo) were placed into control (Con) or gonadectomized (Orx) groups. INTERVENTION: Two weeks after Orx or sham surgery, half the Con and Orx rats were hind-limb unloaded (HLU) to reduce muscle activity for 2 weeks. Subsequently, in situ contractile function tests were performed on the soleus (SOL), plantaris (PLAN), peroneus longus (PER), and extensor digitorum longus (EDL). These 4 muscles and gastrocnemius (GAST) then were removed, weighed, sectioned, and stained with adenosine triphosphatase for fiber typing and fiber area measures. MAIN OUTCOME MEASURES: Peak tetanic tension (P(0)), time to peak twitch contraction (TPT), half relaxation time (RT(1/2)), muscle mass, fiber area, and specific tension (ratio of P(0)/muscle mass). RESULTS: Body weight and muscle mass were similar in the Con and Orx groups. The ratio of P(0) to muscle mass was significantly (p <.05) reduced with Orx in SOL (20%), PLAN (18%), PER (28%), and EDL (20%). TPT and RT(1/2) were significantly faster after Orx in PLAN, PER, and EDL. HLU significantly reduced muscle mass in SOL, PLAN, and GAST in Orx and intact groups. HLU also caused a significant decline in SOL and PLAN P(0). The loss in P(0) in the Orx-HLU rats was no greater than the decline in P(0) with HLU alone. CONCLUSIONS: Gonadectomy results in a loss of P(0) regardless of muscle fiber type or function, it is likely to speed up TPT and RT(1/2), and it does not exacerbate HLU-related atrophy and P(0) loss. Findings may have implications for men with reduced TST levels, as in aging, for instance.     

Diaphragm weakness and mechanical ventilation - what's the critical issue?

While animal studies indicate that controlled mechanical ventilation (MV) induces diaphragm weakness and myofiber atrophy, there are no data in humans that confirm MV per se produces diaphragm weakness. Whether or not diaphragm weakness results from MV, sepsis, corticosteroids, hyperglycemia, or a combination of these factors, however, is not the most important issue raised by the recent study from Hermans and colleagues. This study makes an important contribution by providing additional evidence that many critically ill patients have profound diaphragm weakness. If diaphragm weakness of this magnitude is present in most mechanically ventilated patients, a strong argument can be made that respiratory muscle weakness is a major contributor to respiratory failure.     

Fatigability and variable-frequency train stimulation of human skeletal muscles

BACKGROUND AND PURPOSE: The quadriceps femoris (QF) and tibialis anterior (TA) muscles are often activated through the use of electrical stimulation by physical therapists. These 2 muscles are fundamentally different in regard to their fiber-type composition. Whether protocols developed using a given muscle can be applied to another muscle has seldom been questioned, even if they differ in fiber type. The purpose of this study was to test the hypothesis that torque augmentation during variable-frequency train (VFT) stimulation as compared with constant-frequency train (CFT) stimulation in the fatigued state would not differ between these muscles, even though the TA muscle has 50% relatively more slow fibers than the QF muscle relative to each muscle's overall composition. SUBJECTS: Ten recreationally active men with no history of lower-extremity pathology participated in the study (mean age=25 years, SD=4, range=19-31; mean height=179 cm, SD=5, range=170-188; mean body mass=80 kg, SD=15, range=63-111). METHODS: The subjects' TA and QF muscles were stimulated with CFTs (six 200-microsecond square waves separated by 70 milliseconds) or VFTs (first interpulse interval=5 milliseconds) that evoked an isometric contraction. RESULTS: After potentiation, the torque-time integral and peak torque were not different for the VFT and CFT stimulation. Rise time was longer for the TA muscle than for the QF muscle and for CFT stimulation versus VFT stimulation (both approximately 40%). After 180 CFTs (50% duty cycle), peak torque decreased 56% overall, with no differences between muscles. Enhancement of the torque-time integral (25%) by VFT stimulation was not different between fatigued QF and TA muscles. Torque augmentation was due to the VFT stimulation evoking 27% greater peak torque and less slowing of rise time than the CFT stimulation (15% versus 30%). DISCUSSION AND CONCLUSION: The results indicate that the QF muscle may not necessarily fatigue more than the TA muscle. The results suggest that VFTs augment the force of fatigued, human skeletal muscle irrespective of fiber type.