Diaphragmatic Endurance Research Articles

Evaluation of a 5-Minute Endurance Test of Human Diaphragm Muscle

Diaphragmatic function is important in treating respiratory failure. Muscle endurance has been measured using twitch electrical stimulation and accelerometer-based mechanomyography. The purpose of this study was to evaluate the reproducibility and the time to perform an endurance test on the diaphragm muscle using electrical stimulation of the phrenic nerve. Twenty healthy subjects (21.6±1.6yrs) were tested in the supine position on two separate occasions. Stimulation electrodes were placed on the left (n=18) or right (n=2) phrenic nerve underneath the sternocleidomastoid muscle. A tri-axial accelerometer was placed on the abdomen and 5 minutes of submaximal electrical stimulation at 5Hz was performed. The resultant vector of acceleration at peak and end acceleration was analyzed: endurance index = end/peak*100). The test was successfully completed 41/47 times. The endurance index for the two days was 73.8±9.4% and 72.6±11.1%, respectively. The time to find the phrenic nerve was 34.8±13.1s for the first 10 subjects and 13.0±2.8s for the second 10 subjects. For the second group, the mean difference in endurance between days was 0.03% with a 95% confidence interval of -1.6% to 1.5%. In conclusion, the diaphragm endurance test was reproducible with practice.

Elastic Taping’s Effect on Exercise Capacity in Recreational Runner with Inspiratory Muscle Training

Background: Running is a new trend of recreational sports in Indonesia. About 70% of recreational runners have difficulty in improving exercise capacity due to exercise-related transient abdominal pain (ETAP), caused by fatigue of the diaphragmatic muscles. Previous studies have shown that various training methods may increase diaphragmatic muscle strength and endurance, for example, inspiratory muscle training (IMT). Unfortunately, improvement of inspiratory muscle strength and endurance after exercise and IMT are still varies. Therefore, other methods are needed to optimize the effect of IMT. Application of the elastic taping on thoracic wall during exercise allows the inspiratory muscles to contract optimally which might improve functional capacity.Aim: To assess the effect of elastic taping on inspiratory muscle training using the pressure threshold IMT, in increasing the functional exercise capacity of recreational runners. Functional capacity was measured based on VO2max value, rating of perceived breathlessness (RPB) and rating of perceived exertion (RPE).Methods: an experimental study involved 14 nonsmoker recreational runners, ages 20-40 years, at Outpatient Clinic of Physical Medicine and Rehabilitation Department of Dr. Soetomo Hospital Surabaya. Subjects were divided into two groups (pressure threshold IMT with and without elastic taping groups), which were observed for four weeks. IMT was done five times a week, twice a day, with 30 repetitions, and 60% resistance 30 RM using Respironics®. Elastic taping Leukotape® was applied on the first until fifth day in each IMT sessions. The running exercises were done three times a week with EnMill® Treadmill ETB-03195 with a speed of 4.5 mph and 0% inclination. RBP, RPE and VO2max were measured using Borg Dyspneu scale, Borg Scale, and Bruce Treadmill Protocol test, respectively, before the first exercise and after 4 weeks of exercise.Results: There were an improvement of functional exercise capacity in both groups which were marked with a decline of RPB and RPE and increase of VO2max (p values < 0.05). However, there were no significant differences in the decrease of RPB and RPE and an increase of VO2max between groups (p values of were 0.31, 0.83, and 0.13, respectively). The effect of the elastic taping (r2 = 0.99) was not reflected in the differences of RPB, RPE and increasing VO2max.Conclusion: Inspiratory muscle training using pressure threshold IMT with or without the elastic taping for four weeks can improve exercise capacity of recreational runners.

The Validity And Reproducibility Of A 5-minute Endurance Test Of The Diaphragm Muscle

Diaphragmatic function could be important in treating respiratory failure. Electrical stimulation and accelerometer-based mechanomyography have been used to identify the endurance index of various muscles, but not of the diaphragm. PURPOSE: Measure the validity and reproducibility of an endurance test of the diaphragm muscle using electrical stimulation of the phrenic nerve. METHODS: Ten healthy subjects (21.3±1.1 yrs) were tested in the supine position on two separate occasions within one week. Custom-made stimulation electrodes were placed on the left (n=12) or right (n=2) phrenic nerve, which lies underneath the sternocleidomastoid muscle. The stimulation intensity to induce a vigorous contraction was determined. An accelerometer was placed on the abdomen. The endurance test consisted of 5 minutes of electrical stimulation on 5 Hz, with a sampling rate of 400 Hz. The average acceleration per minute was recorded. The endurance index, which equals the ending value/peak value*100, was then calculated. A series of practice tests were performed before data collection. RESULTS: The test was successfully completed 27/30 times. The time to find the phrenic nerve was 43.9±50.4 s for trial 1 and 25.9±26.3 s for trial 2. The average endurance index for trial 1 and 2 were 70.5±11.2% and 70.4±12.4%, respectively (between days, p=0.54, CV=7.71%). CONCLUSIONS: The time to find the phrenic nerve decreased with practice. The endurance test was reproducible and did not have an order effect. With additional training and testing, the diaphragm endurance test may be practical in clinical populations.

Diaphragmatic function in infants and children with congenital diaphragmatic hernia: a cross-sectional study.

Few studies have evaluated long-term diaphragmatic function in congenital diaphragmatic hernia (CDH). The aim of our cross-sectional study was to assess diaphragmatic function in infants and young children with CDH after surgical repair. All the patients with CDH repair followed in our centre between February 2014 and January 2016 were enrolled. Patients with a postnatal diagnosis after 1 month of life were excluded. Breathing pattern and diaphragmatic function were assessed using esophageal and gastric (Pgas) pressure recording after surgery, or at 1 or 5 years of age. Twenty-eight patients (24 left-sided CDH, 6 with diaphragmatic patch) were included. Twelve patients were assessed before hospital discharge (Y0), 6 around the age of 1 year (Y1) and 10 around the age of 5 years (Y5). Mean antenatal estimated pulmonary volume (VLA) was 42 ± 10% (n = 23). Diaphragmatic strength, assessed by transdiaphragmatic pressure during crying/sniff, was low at Y0 (47 ± 18 cmH2O, n = 12) and within normality at Y5 (81 ± 15 cmH2O, n = 7). Diaphragmatic dysfunction, assessed by Pgas during crying/sniff, was present at Y0 (-58 ± 22 cmH2O, n = 12) and Y1 (-53 ± 36 cmH2O, n = 5) and still present at Y5 (3 ± 9 cmH2O, n = 7) but to a lesser extent. The diaphragmatic tension time index (TTdi), which estimates diaphragmatic endurance, was high at Y0 (0.10 ± 0.04, n = 11) and within normality at Y5 (0.03 ± 0.01, n = 6). VLA correlated with neonatal TTdi (r = -0.961, P < 0.001). Infants with CDH have diaphragmatic dysfunction in the neonatal period, which correlates with VLa and normalizes with age. Future longitudinal studies should assess the role of CDH side, size of diaphragmatic defect and patch repair.

Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia

Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to explore the effects of different CIH protocols on respiratory muscle form and function in a rodent model. Adult male Wistar rats were exposed to CIH (n = 32) consisting of 90 s normoxia-90 s hypoxia (either 10 or 5% oxygen at the nadir; arterial O2 saturation ∼ 90 or 80%, respectively] for 8 h per day or to sham treatment (air-air, n = 32) for 1 or 2 weeks. Three additional groups of CIH-treated rats (5% O2 for 2 weeks) had free access to water containing N-acetyl cysteine (1% NAC, n = 8), tempol (1 mM, n = 8) or apocynin (2 mM, n = 8). Functional properties of the diaphragm muscle were examined ex vivo at 35 °C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca(2+)-ATPase isoform distribution, succinate dehydrogenase and glyercol phosphate dehydrogenase enzyme activities, Na(+)-K(+)-ATPase pump content, concentration of thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2 weeks) decreased diaphragm muscle force and endurance. All three drugs reversed the deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH-induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm muscle myosin heavy chain 2B areal density and oxidized glutathione/reduced glutathione (GSSG/GSH) ratio. We conclude that CIH-induced diaphragm dysfunction is reactive oxygen species dependent. N-Acetyl cysteine was most effective in reversing CIH-induced effects on diaphragm. Our results suggest that respiratory muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as such, antioxidant treatment could prove a useful adjunctive therapy for the disorder.

Beneficial Effects of Melatonin on Diaphragmatic Contractility and Fatigability in Escherichia coli Endotoxemic Rats

Sepsis impairs diaphragmatic contractility and endurance capacity and increases diaphragmatic fatigability. Several investigations have shown that administration of a number of free radical scavengers, such as N-acetylcysteine (NAC), protects the diaphragm from the development of endotoxin-mediated diaphragmatic dysfunction. The aim of this study was to evaluate the effects of melatonin (CAS 73-31-4), a naturally occurring potent antioxidant, on diaphragmatic contractility and lipid peroxidation as a marker of oxidative stress in endotoxemic rats. Rats were randomly divided into four groups: control group, endotoxemic group, melatonin group and endotoxemic plus melatonin group. Melatonin was administered by intraperitoneal injection 30 min before endotoxin inoculation to animals. Diaphragmatic function and malondialdehyde (MDA) level analysis as an indicator of lipid peroxidation were assessed 17 h after endotoxin or saline inoculation. Endotoxemia decreased the development of diaphragm fatigue and diaphragmatic MDA levels. The effects of endotoxemia on diaphragmatic contractions and fatigability were reversed and returned to control levels by melatonin administration. However, melatonin did not prevent the increase in muscle MDA content. In conclusion, the present study demonstrated that melatonin attenuated the endotoxin-induced impairment of diaphragm function. This effect of melatonin does not seem to be related to its antioxidant properties.

Physiologic determinants of prolonged mechanical ventilation in patients after major surgery

PurposeThe aim of the study was to evaluate the physiologic determinants of ventilator dependency in patients who underwent major surgery. Materials and MethodsIn this observational study, 43 stable tracheostomized patients undergoing prolonged ventilation (>14 days) were evaluated. Diaphragmatic muscle function was assessed invasively by the tension-time index of the diaphragm (TTdi), an indicator of diaphragm endurance time. The TTdi was calculated as transdiaphragmatic pressure/maximum transdiaphragmatic pressure × inspiratory time/total respiratory time and was recorded either when weaning from mechanical ventilation had finally been successful (n = 28 patients) or at the end of the fifth week in those patients in whom weaning failed (FW) (n = 15). Furthermore, the characteristics of survivors (n = 33) were compared with those of nonsurvivors (n = 10). ResultsSuccessfully weaned patients had a lower breathing frequency/tidal volume or rapid shallow breathing index compared with FW patients (93.9 ± 45.5 vs 142.4 ± 60.3, respectively; P < .005). The TTdi was significantly higher in FW than in successfully weaned patients (0.107 ± 0.050 vs 0.148 ± 0.059; P < .023) and in nonsurvivors than in survivors (0.106 ± 0.046 vs 0.174 ± 0.058, P < .0001, respectively). A transdiaphragmatic pressure/maximum transdiaphragmatic pressure ratio of more than 40% was an independent predictor of mortality, whereas an increased frequency/tidal volume ratio and TTdi were independent predictors of weaning failure. ConclusionsDifficult-to-wean patients after major surgery have overall a limited diaphragm endurance time, in particular, FW breathe very close to the fatigue threshold, and they adopt a rapid shallow breathing respiratory pattern to avoid crossing this threshold.

Respiratory Muscle Dysfunction in COPD: From Muscle to Cell

Respiratory muscle dysfunction is a cardinal feature of acute and chronic respiratory failure in COPD. Diaphragm and accessory inspiratory muscles face increased load due to increased lung resistance and elastance, as well as increased ventilatory demands. Concomitantly, the capacity of the inspiratory muscles to generate pressure is decreased due to mechanical disadvantage imposed by hyperinflation. Additionally, inflammation and oxidative stress impair muscle fiber specific force generation and increase diaphragm susceptibility to sarcomer disruption during acute inspiratory loading. In response to this increased load diaphragm presents unique adaptations in its cellular structure and passive and contractile mechanical properties, and displays a more efficient metabolic armamentarium. A shift of muscle fiber type towards slow-twitch, oxidative type I fibers, which are more fatigue-resistant, increases diaphragmatic endurance but protein degradation and a significant reduction in myosin content decrease its force generating capacity. Furthermore, diaphragm adapts to chronic hyperinflation by sarcomere deletion so that its overall length is shortened, in an attempt to preserve optimum force-length relationship. Adaptation however may not be complete, or may be overwhelmed by pathophysiologic derangements during exercise or acute exacerbations, leading to obvious "dysfunction" of the respiratory muscles, and if sustained, ultimately to muscle fatigue and respiratory pump failure.

Duration of mechanical ventilation on the result of diaphragmatic function in weaning

Objective To investigate the influence of duration of mechanical ventilation on the diaphragmatic function.Methods Patients included in this study were those who mechanically ventilated for at least 24 h and were preparing to wean from December 2008 to December 2009 in ICU of Nanjing Zhong da Hospital.Patients,according to the duration of mechanical ventilation,were divided into group A (ventilated less than three days) and group B (ventilated more than three days).30 min Spontaneous breathing test (SBT) was carried on the patients satisfying the weaning permission.Indices of diaphragm function,such as electrical activity of diaphragm (Edi),neuro-muscular strength index ( NMS),neuromechanical coupling (NMC) and neuro-ventilatory coupling (NVC) at 0 min,5 min and 30 min of SBT were monitored.Results 44 patients were included finally,of whom 19 patients (43.2％) ventilated more than three days (group B).44 patients ventilated less than three days (group A).①There was no significant difference in Edi,NMS,NMC or NVC at 0 min of SBT between the two groups.②Edi and NMS in group B were largely more than group A at 5 min of SBT.③At SBT 30 min,Edi and NMS in group B both were significantly higher than group A [( 23 ± 11 ) μV vs ( 15 ± 8) μV,( 598 ± 309) μV ·cpm vs (363±224) μV · cpm,P ＜0.05].Whereas,NVC in group B was lower than group A ( P ＜0.05).Conclusions The contractility and endurance of diaphragm decreased in patients whom ventilated more than three days at 30 min of SBT.It seemed that incremental duration of mechanical ventilation could exacerbate the diaphragm dysfunction,which might be one of the important factors leading to failed weaning. Key words: Duration of mechanical ventilation; Diaphragm function; Electrical activity of diaphragm; Neuro-muscular strength index; Neuro-mechanical coupling; Neuro-ventilatory coupling

Antioxidant overexpression reduces diaphragm maximal specific tension but does not alter resistance to fatigue

Skeletal muscle contraction during exercise leads to increased production of reactive oxygen species (ROS). Because oxidative stress is linked to muscle fatigue development, we hypothesized that diaphragms from mice overexpressing antioxidant enzymes would be more resistant to contraction induced fatigue. To test this postulate, diaphragm fiber bundles from transgenic mice overexpressing the specific antioxidant enzymes: catalase (Cat; n=6), manganese superoxide dismutase (MnSOD; n=6), and copper-zinc superoxide dismutase (CuZnSOD; n=9) were examined to determine maximal specific tension, endurance, and recovery from fatigue. Wild-type littermates (WT; n=8) served as controls. Diaphragms from antioxidant overexpressing animals demonstrated lower (p<0.05) submaximal and maximal specific tension values compared to WT controls; with diaphragms from MnSOD overexpressing animals exhibiting the greatest decrement. However, no differences in diaphragm endurance or recovery from fatigue were observed between groups (p>0.05). Moreover, protein carbonyl levels of the stimulated fiber bundles did not differ between groups (p>0.05). Collectively, these results suggest that cellular ROS are critical to normal diaphragm contractile function and chronic overexpression of antioxidant enzymes is not sufficient to alleviate the development of fatigue. Funded by 1R01HL072789 (SKP)

Short-Duration Mechanical Ventilation Enhances Diaphragmatic Fatigue Resistance but Impairs Force Production

s: Mechanical ventilation (MV) is a life-support measure for patients who cannot maintain adequate alveolar ventilation. Following prolonged MV, difficulty in weaning patients from the ventilator can occur, and it has been postulated that difficult weaning is linked to respiratory muscle dysfunction. We tested the hypothesis that 18 h of controlled MV will diminish diaphragmatic maximal tetanic specific tension (force per cross-sectional area of muscle) without impairing diaphragmatic fatigue resistance. To test this postulate, adult Sprague-Dawley rats were randomly classified into one of two experimental groups: (1) control group (n = 8), and (2) 18-h MV group (n = 6). MV-treated animals were anesthetized, tracheostomized, and received room air ventilation. Animals in the control group were acutely anesthetized but did not receive MV. Muscle strips from the mid-costal diaphragm were removed from both experimental groups, and contractile properties were studied in vitro to determine the effects of MV on diaphragmatic endurance and maximal force production. Diaphragmatic endurance was investigated by measuring tension development during repeated contractions throughout a 30-min fatigue protocol. MV resulted in a reduction (p < 0.05) in diaphragmatic maximal specific tension (control group, 26.8 +/- 0.2 Newtons/cm(2) vs MV group, 21.3 +/- 0.6 Newtons/cm(2)). Compared to the control group, diaphragms from MV-treated animals maintained higher (p < 0.05) percentages of the initial force production throughout the fatigue protocol. The observed improvement in fatigue resistance was associated with an increase in diaphragmatic oxidative and antioxidant capacity as evidenced by increases (p < 0.05) in both citrate synthase and superoxide dismutase activities. However, by comparison to the control group, diaphragms from MV-treated animals generated less (p < 0.05) absolute specific force throughout the fatigue protocol. These data indicate that 18 h of MV enhances diaphragmatic fatigue resistance but impairs diaphragmatic specific tension.

Mechanisms of diaphragm fatigue.

The importance of respiratory muscle fatigue, particularly of the diaphragm, has become well recognized in the last decade. If the diaphragm muscle fails, so does effective ventilation and tissue respiration. Balance between energy supply and demand determines diaphragmatic endurance. An imbalance between energy supply and demand leads to the development of diaphragmatic fatigue. It has become clear that the process of fatigue is a complex phenomenon with multiple mechanisms accounting for changes in muscle performance. The various mechanisms involved are probably interdependent, synergistic, and integrative in nature. This article focuses on the concept of diaphragm fatigue and explores the mechanisms occurring with diaphragm fatigue including sodium-potassium derangements, which cause a decrease in velocity of propagation of muscle action; inhibition of calcium release from the sacroplasmic reticulum; and increased oxygen free radical formation related to cellular energetics. Additionally, review of therapeutic approaches to the treatment of diaphragm fatigue are presented.

Exercise-induced changes in diaphragmatic bioenergetic and antioxidant capacity.

The primary inspiratory muscle in mammals is the diaphragm. Endurance exercise elevates both the oxidative and antioxidant capacity of the costal and crural diaphragm. These exercise-induced changes in oxidative and antioxidant capacity occur rapidly after the onset of training and are associated with reduced oxidative injury and improved diaphragmatic endurance.

NG-NITRO-L-ARGININE METHYL ESTER(L-NAME) REDUCE DIAPHRAGM ENDURANCE TIME IN RAT

S152 INTRODUCTION: We have previously demonstrated that Human recombinant interleukin 1 beta (HrIL-1 beta) decreases diaphragm endurance time in vitro. L-NAME, nitric oxide synthase inhibitor, was administrated to the experimental bath, to prevent diaphragm function before adding HrIL-1. But there were no improvements in endurance time. The aim of this study was to investigate the effect of L-NAME in normal rat diaphragm. METHODS: Male Sprague-Dawley rats(150[similar]175g) were anesthetized with sodium pentobarbital. Two, 10mm wide muscle strips without phrenic nerve were dissected from medial aspect of each diaphragm. The strips were mounted in a water jacketed tissue bath containing Krebs solution and 0.1% bovine serum albumin(BSA). The central tendon was attached to an isometric force transducer. Baths were maintained at 37[degree sign]C. The pH of the bath were maintained approximately 7.4 during the experiment. 95% O2 and 5% CO2 were bubbled into the bath and D-tubocurarine was added. Supramax, stimulation voltage and optimal muscle length were determined for each strip. L-NAME(final bath concentrations of 300,30 and 3 [micro sign] M) or D-NAME(300 [micro sign] M) was added with 0.1% BSA into the bath. An equal volume of 0.1% BSA was added to control baths. After 1 hour, single twitch force(2 ms duration) and tetanic forces(400 ms trains of 2 ms impulses at 10,20, 60,100 Hz) were measured. Syrips were fatigued (20Hz, 0.33s trains, 1 train/sec.) until 50% of initial maximal tension was achieved. Single twitch and force frequency relationships were measured immediately, 10,30 and 60 min. after fatigue. Force measurements were normalized for cross sectional area. Endurance time was defined as the time in seconds required to achieved 50% initial maximal tension. Post-fatigue forse divided by baseline force defined fatigue resistance (FRI). The data was analyzed using unpaired t-test and ANOVA analysis. RESULTS: (Table 1)Table 1At 300 [micro sign]M L-NAME there was a statistical significant difference in endurance time. At 30 and 3 [micro sign] M L-NAME there were no differences. Comparing D-NAME vs. 300 [micro sign] M L-NAME, there was a significant difference in endurance time. However, there was no difference between control and D-NAME. There were no significant difference in FRI, 1/2 relaxation time and contraction time. CONCLUSIONS: L-NAME at higher concentrations in this model is associated with a decrease endurance time. Whereas D-NAME did not impair diaphragm function. This data suggests that NO may play a role in the respiratory muscle function.

Effects of prolonged controlled mechanical ventilation on diaphragmatic function in healthy adult baboons.

To study diaphragmatic strength and endurance after a prolonged period of mechanical ventilation. Prospective animal study. Animal research laboratory. Seven uninjured adult baboons (Papio cynocephalus) were anesthetized with ketamine, sedated, paralyzed, and mechanically ventilated. Animals were monitored with pulmonary arterial and peripheral arterial catheters. Mechanical ventilation was provided for 11 days with an FIO2 of 0.21 and tidal volume of 15 mL/kg. Pulmonary function tests, including lung volumes, arterial blood gases, and chest radiographs were also monitored. Nursing care procedures included frequent turning, chest physiotherapy, and endotracheal suction. Antacids and prophylactic antibiotics (intravenous penicillin, topical polymyxin B, and gentamicin sulfate) were administered. In three animals, fishhook electrodes were surgically placed around both phrenic nerves on both day 0 and after 11 days of mechanical ventilation for diaphragmatic stimulation. On day 0, the electrodes were removed after phrenic nerve stimulation studies were performed. After 11 days of mechanical ventilation, animals were electively killed and full autopsy performed. Hemodynamic and pulmonary function parameters were measured at baseline and every day during the 11 days of mechanical ventilation. Diaphragmatic strength and endurance were measured on days 0 and 11. Diaphragmatic endurance was determined by an inspiratory resistive loading protocol. There were no significant changes in hemodynamics, lung volumes, or gas exchange during the period of mechanical ventilation. On day 7, the chest radiographs showed patchy lobar atelectasis in six animals, which cleared by day 11 in all but two of the animals. Lung pathology showed mild, focal pneumonitis. By day 11, maximum transdiaphragmatic pressure had decreased by 25% from day 0 and diaphragmatic endurance had decreased by 36%. Eleven days of mechanical ventilation and neuromuscular blockade in healthy baboons resulted in nonsignificant changes in hemodynamics, oxygenation, and/or lung function. However, significant impairment in diaphragmatic endurance and strength were seen. Based on these results, it is likely that prolonged mechanical ventilation by itself impairs diaphragmatic function independent of underlying lung disease.

Effects of nitric oxide on diaphragmatic muscle endurance and strength in pigs.

The aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventilated pigs, divided into three groups. The animals were pre-treated with indomethacin (3 mg kg-1, i.v.) to block the cyclo-oxygenase pathway. To group 1 pigs (n = 6) NG-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1 i.v.) was administered as a bolus to block endogenous NO production, while group 2 pigs (n = 6) were infused with sodium nitroprusside (SNP, 0.023 mg kg-1, i.v.), a donor of NO. Group 3 pigs (n = 3) were used as the controls. We evaluated diaphragmatic strength by measuring the transdiaphragmatic pressure (P di) generated during bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30s stimulation at 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak force between single twitches performed before and after the 30 s stimulation west. We also evaluated mean systemic (MAP) and pulmonary (MPAP) arterial pressures, pulmonary wedge pressure (PW), systemic (SVR) and pulmonary vascular resistance (PVR) and cardiac output (CO). L-NAME increased MAP, MPAP, PW, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, PW and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was not significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decline in diaphragmatic blood flow, as evidenced by the increase in SVR and the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attributed to a direct action of NO on skeletal muscle.

Effects of steroid on diaphragmatic functions in rabbits.

The effects of steroid on diaphragmatic contractility and endurance were examined in 24 New Zealand rabbits. Diaphragmatic contractility was determined by measuring gastric pressure (Pga) with the lower thorax and the abdomen of the animal being fixed with a rigid cast. Endurance procedure was done by continuous 15 Hz stimulation of the bilateral phrenic nerves, and diaphragmatic endurance was expressed as the time from the initiation of the endurance procedure to the moment when transdiaphragmatic pressure 15 Hz (Pdi-15 Hz) decreased to 25% of Pdimax-15 Hz. Our data suggested that intravenous administration of dexamethasone 2.5 mg daily for 7 days did not affect the diaphragmatic contractility significantly, but could cause a significant decrease in diaphragmatic endurance. When delivered intravenously at the dose of 2.0 mg daily for 14 days, dexamethasone induced a significant decrease both in diaphragmatic contractility and endurance. The recovery of the diaphragmatic strength from fatigue, however, was not influenced by dexamethasone in either circumstance. The influence of dexamethasone on diaphragmatic contractility and endurance may have important clinical implications.

Effects of cortisone and testosterone on diaphragmatic function and biochemistry in the rabbit.

The effects of cortisone and testosterone on in vivo diaphragmatic function and biochemistry were assessed in rabbits to determine whether androgens can prevent the effects of corticosteroids on diaphragmatic function and biochemistry and what mechanisms of muscle function may be altered. Cortisone altered respiratory muscle endurance and diaphragmatic glycogen and lactate levels but had little effect on diaphragmatic strength. Testosterone had no significant impact on diaphragmatic strength, endurance, or biochemistry. However, concomitant administration of testosterone with cortisone blunted the effect of cortisone on respiratory muscle endurance, even though it failed to block the effects of cortisone on diaphragmatic glycogen and lactate levels. Alterations in respiratory muscle endurance were not due to low- or high-frequency contractile fatigue of the diaphragm or diaphragmatic glycogen depletion or lactate accumulation in any of the treatment conditions. On the other hand, alterations in central drive played a dominant role, as evidenced by alterations in inspiratory duty cycle and a falloff in the intensity of central drive during loading. Although the exact mechanisms underlying the alterations in central drive remain unknown, concomitant administration of androgens with corticosteroids blunted the impact of corticosteroids on respiratory muscle function.

Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm

The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne muscular dystrophy. The present study examined alterations in diaphragm contractile properties and myosin heavy chain (MHC) expression in young (3-4 mo) and old (22-24 mo) control and mdx mice. In young mdx mice, maximum isometric tension (Po) was reduced to 50% of control values. An increase in fibers coexpressing types I (slow) and IIa MHC as well as regenerating fibers expressing embryonic MHC occurred, whereas IIx/b fibers were decreased. In the old mdx group, Po underwent a further reduction to 25% of control, and there was a slowing of twitch kinetics along with markedly increased diaphragm endurance. These changes were associated with an approximate sevenfold increase in type I MHC fibers and virtual elimination of the IIx/b fiber population; there was no detectable embryonic MHC expression. We conclude that the mdx diaphragm responds to progressive muscle degeneration with transition to a slower phenotype associated with reduced power output and augmented muscle endurance. In the setting of progressive muscle fiber destruction, these changes may help preserve contractile function and promote greater survival of remaining muscle fibers by decreasing cellular energy requirements.

Effects of hyperphosphatemia on diaphragmatic strength and endurance.

Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue.