Home-Based Interventions may Increase Recruitment, Adherence, and Measurement of outcomes in Clinical Trials of Stroke Rehabilitation.

OBJECTIVE: This study aimed to investigate the completion rates of a home-based randomized trial, which examined home-based high-intensity respiratory muscle training after stroke compared with sham intervention. MATERIALS AND METHODS: Completion was examined in terms of recruitment (enrolment and retention), intervention (adherence and delivery of home-visits) and measurement (collection of outcomes). RESULTS: Enrolment was 32% and retention was 97% at post-intervention and 84% at follow-up. Adherence to the intervention was high at 87%. Furthermore, 83% of planned home-visits were conducted and 100% of outcomes were collected from those attending measurement sessions. CONCLUSION: This home-based randomized trial demonstrated high rates of enrolment, retention, adherence, delivery of home-visits, and collection of outcomes. Home-based interventions may help to improve completion rates of randomized trials.

Stimulation of abdominal and upper thoracic muscles with surface electrodes for respiration and cough: Acute studies in adult canines.

OBJECTIVE: To optimize maximal respiratory responses with surface stimulation over abdominal and upper thorax muscles and using a 12-Channel Neuroprosthetic Platform. METHODS: Following instrumentation, six anesthetized adult canines were hyperventilated sufficiently to produce respiratory apnea. Six abdominal tests optimized electrode arrangements and stimulation parameters using bipolar sets of 4.5 cm square electrodes. Tests in the upper thorax optimized electrode locations, and forelimb moment was limited to slight-to-moderate. During combined muscle stimulation tests, the upper thoracic was followed immediately by abdominal stimulation. Finally, a model of glottal closure for cough was conducted with the goal of increased peak expiratory flow. RESULTS: Optimized stimulation of abdominal muscles included three sets of bilateral surface electrodes located 4.5 cm dorsal to the lateral line and from the 8th intercostal space to caudal to the 13th rib, 80 or 100 mA current, and 50 Hz stimulation frequency. The maximal expired volume was 343 ± 23 ml (n=3). Optimized upper thorax stimulation included a single bilateral set of electrodes located over the 2nd interspace, 60 to 80 mA, and 50 Hz. The maximal inspired volume was 304 ± 54 ml (n=4). Sequential stimulation of the two muscles increased the volume to 600 ± 152 ml (n=2), and the glottal closure maneuver increased the flow. CONCLUSIONS: Studies in an adult canine model identified optimal surface stimulation methods for upper thorax and abdominal muscles to induce sufficient volumes for ventilation and cough. Further study with this neuroprosthetic platform is warranted.

Clinimetric properties of the pressure biofeedback unit method for estimating respiratory pressures.

OBJECTIVE: The Pressure Biofeedback Unit (PBU) is used to assess the transversus abdominis muscle activity in order to determine the effectiveness of segmental stabilization, but not to verify its accuracy for measuring the pressure values of breathing from transversus abdominis activation. The objective of this study was to cross-validate the PBU pressure evaluated in transversus abdominis muscle activation with the respiratory pressure assessed through manovacuometry in order to verify the extent to which the PBU can be used to indirectly evaluate the strength of the respiratory muscle in both men and women and verify the reliability of the methods. PARTICIPANTS: A total of 39 healthy subjects. METHODS: Manovacuometry and Pressure Biofeedback Unit tests were performed in three days each with three replications: 1) Maximal Inspiratory Pressure; 2) Maximal Expiratory Pressure; and 3) Pressure Biofeedback Unit. RESULTS: Both tests showed good reliability and low correlation between the Pressure Biofeedback Unit and Maximal Inspiratory Pressure (r = 0.40; p = 0.01) and Maximal Expiratory Pressure (r = 0.33; p = 0.04). High differences were observed between pressures and wide limits of agreement in Bland-Altman analysis. CONCLUSION: It seems that the Pressure Biofeedback Unit is not able to effectively predict the respiratory muscles' strength as routinely evaluated through the use of the manovacuometry presenting a low cross-validation and good reliability.

Slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with chronic heart failure: from modeling to clinical application.

Influences of slow and deep respiration on steady-state sympathetic nerve activity remain controversial in humans and could vary depending on disease conditions and basal sympathetic nerve activity. To elucidate the respiratory modulation of steady-state sympathetic nerve activity, we modeled the dynamic nature of the relationship between lung inflation and muscle sympathetic nerve activity (MSNA) in 11 heart failure patients with exaggerated sympathetic outflow at rest. An autoregressive exogenous input model was utilized to simulate entire responses of MSNA to variable respiratory patterns. In another 18 patients, we determined the influence of increasing tidal volume and slowing respiratory frequency on MSNA; 10 patients underwent a 15-min device-guided slow respiration and the remaining 8 had no respiratory modification. The model predicted that a 1-liter, step increase of lung volume decreased MSNA dynamically; its nadir (-33 ± 22%) occurred at 2.4 s; and steady-state decrease (-15 ± 5%), at 6 s. Actually, in patients with the device-guided slow and deep respiration, respiratory frequency effectively fell from 16.4 ± 3.9 to 6.7 ± 2.8/min (P < 0.0001) with a concomitant increase in tidal volume from 499 ± 206 to 1,177 ± 497 ml (P < 0.001). Consequently, steady-state MSNA was decreased by 31% (P < 0.005). In patients without respiratory modulation, there were no significant changes in respiratory frequency, tidal volume, and steady-state MSNA. Thus slow and deep respiration suppresses steady-state sympathetic nerve activity in patients with high levels of resting sympathetic tone as in heart failure.

Independent cough flow augmentation by glossopharyngeal breathing plus table thrust in muscular dystrophy.

OBJECTIVE: The purpose of the present study was to compare the unassisted cough peak flow (CPF) of patients affected by muscular dystrophy with CPF augmented by various techniques, including maximal depth glossopharyngeal breathing (GPB) combined with a subsequent self-induced thoracic or abdominal thrust. DESIGN: All of the motorized wheelchair-dependent patients with muscular dystrophy who had previously mastered GPB were trained at home to increase their cough efficacy. This training involved maneuvering their wheelchair against the edge of a specially built table to autonomously produce a thoracic and/or abdominal thrust timed to the opening of the glottis for an independently assisted cough. Both unassisted and variously assisted CPFs were compared. RESULTS: The 18 patients (17 men/1 woman) with muscular dystrophy, aged 21.1 ± 5.4 yrs, achieved variously assisted CPFs that were significantly higher than the spontaneous CPF (P < 0.001), with assisted CPFs but not unassisted CPFs that significantly exceeded a reported efficacious cough threshold value of 160 liters/min (P < 0.001). Moreover, increases in the CPFs by personal assistance including air stacking by manual resuscitator and thoracoabdominal thrust (326.4 ± 79.5 liters/min) or by GPB and thoracoabdominal thrust (326.4 ± 87.5 liters/min) were not significantly different (P = 0.07) from the CPFs independently attained by GPB plus independently maneuvering a wheelchair for a table thrust (310.3 ± 74.7 liters/min). CONCLUSIONS: The independently assisted (GPB plus table thrust) CPF was comparable to the CPFs that required personal assistance for air stacking and abdominal thrusts. Therefore, for patients with muscular dystrophy, this physical medicine technique and cough-assisted techniques that require personal intervention are strongly recommended.

Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation.

The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN neurons) that provide a pH-regulated excitatory drive to the central respiratory pattern generator. Here we test whether ccRTN neurons respond to stimulation of the perifornical hypothalamus (PeF), a region that regulates breathing during sleep, stress and exercise. PeF stimulation with gabazine increased blood pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in isoflurane-anaesthetized rats. Gabazine produced an approximately parallel upward shift of the steady-state relationship between ccRTN neuron firing rate and end-tidal CO(2), and a similar shift of the relationship between PND and end-tidal CO(2). The central respiratory modulation of ccRTN neurons persisted after gabazine without a change in pattern. Morphine administration typically abolished PND and reduced the discharge rate of most ccRTN neurons (by 25% on average). After morphine administration, PeF stimulation activated the ccRTN neurons normally but PND activation and the central respiratory modulation of the ccRTN neurons were severely attenuated. In the same rat preparation, most (58%) ccRTN neurons expressed c-Fos after exposure to hypercapnic hyperoxia (6-7% end-tidal CO(2); 3.5 h; no hypothalamic stimulation) and 62% expressed c-Fos under hypocapnia (approximately 3% end-tidal CO(2)) after PeF stimulation. Under baseline conditions (approximately 3% end-tidal CO(2), hyperoxia, no PeF stimulation) few (11%) ccRTN neurons expressed c-Fos. In summary, most ccRTN neurons are excited by posterior hypothalamic stimulation while retaining their normal response to CNS acidification. ccRTN neurons probably contribute both to the chemical drive of breathing and to the feed-forward control of breathing associated with emotions and or locomotion.

Methazolamide does not impair respiratory work performance in anesthetized rabbits.

In human medicine, the carbonic anhydrase (CA) inhibitor acetazolamide is used to treat irregular breathing disorders. Previously, we demonstrated in the rabbit that this substance stabilized closed-loop gain properties of the respiratory control system, but concomitantly weakened respiratory muscles. Among others, the highly diffusible CA-inhibitor methazolamide differs from acetazolamide in that it fails to activate Ca(2+)-dependent potassium channels in skeletal muscles. Therefore, we aimed to find out, whether or not methazolamide may exert attenuating adverse effects on respiratory muscle performance as acetazolamide. In anesthetized spontaneously breathing rabbits (n = 7), we measured simultaneously the CO(2) responses of tidal phrenic nerve activity, tidal transpulmonary pressure changes, and tidal volume before and after intravenous application of methazolamide at two mean (+/- SE) cumulative doses of 3.5 +/- 0.1 and 20.8 +/- 0.4 mg/kg. Similar to acetazolamide, low- and high-dose methazolamide enhanced baseline ventilation by 52 +/- 10% and 166 +/- 30%, respectively (P < 0.01) and lowered the base excess in a dose-dependent manner by up to 8.3 +/- 0.9 mmol/l (P < 0.001). The transmission of a CO(2)-induced rise in phrenic nerve activity into volume and/or pressure and, hence, respiratory work performance was 0.27 +/- 0.05 ml x kg(-1) x kPa x unit(-1) under control conditions, but remained unchanged upon low- or high-dose methazolamide, at 0.30 +/- 0.06 and 0.28 +/- 0.07 ml x kg(-1) x kPa x unit(-1), respectively. We conclude that methazolamide does not cause respiratory muscle weakening at elevated levels of ventilatory drive. This substance (so far not used for medication of respiratory diseases) may thus exert stabilizing influences on breathing control without adverse effects on respiratory muscle function.

Idiopathic diaphragmatic paralysis--satisfactory improvement of inspiratory muscle function by inspiratory muscle training.

Daily inspiratory muscle strength and endurance training (IMT) was performed in a 44-year-old patient with idiopathic bilateral diaphragmatic paralysis (BDP) in addition to nocturnal non-invasive ventilation (NIV). After 4 months of training inspiratory muscle function improved satisfactorily whereas phrenic nerve latency remained pathological. Due to the improvement of inspiratory muscle capacity nocturnal NIV could be stopped without inducing nocturnal respiratory insufficiency.

Diaphragm training in amyotrophic lateral sclerosis.

There is a continued need for therapies to improve respiratory function and quality of life in patients with amyotrophic lateral sclerosis. In this pilot trial, we studied 8 subjects with amyotrophic lateral sclerosis and respiratory involvement. We measured respiratory function and quality of life at baseline. We then taught subjects diaphragm training, a method of breath control designed to improve respiratory muscle strength and efficiency. We repeated measures of respiratory function and quality of life 6 and 12 weeks later. There was no significant improvement in any outcome measure after instituting diaphragm training. There was a nonsignificant trend toward a slower rate of decline in respiratory function in those subjects who mastered the technique; however, only half the subjects were able to successfully change their pattern of breathing. A larger study of this technique is warranted; however, in determining the sample size for a larger study, the difficulty for patients in mastering the technique must be taken into consideration.

Inspiratory muscle pacing in spinal cord injury: case report and clinical commentary.

BACKGROUND/OBJECTIVE: A significant fraction of patients with cervical spinal cord injury suffer from respiratory muscle paralysis and dependence on chronic mechanical ventilation. In selected patients, diaphragm pacing (DP) through electrical stimulation of the phrenic nerves provides an alternative to mechanical ventilation with significant advantages in life quality. METHODS: A case report of an individual who successfully underwent DP using intramuscular diaphragm electrodes. A brief review of the state of the art of DP including the clinical benefits of DP, patient selection and evaluation, description of equipment, methods of transition from mechanical ventilation to DP, potential complications and side effects, long-term outcome, and potential future developments in this field is included. RESULTS: Several available DP systems are available, including conventional ones in which electrodes are positioned directly on the phrenic nerves through thoracotomy and less invasive systems in which electrodes are placed within the diaphragm through laparoscopy. For patients with only unilateral phrenic nerve function, a combined intercostal and unilateral diaphragm pacing system is under development. CONCLUSIONS: In patients with ventilator-dependent tetraplegia, there are alternative methods of ventilatory support, which offer substantial benefits compared to mechanical ventilation.

Relationship between inspiratory muscle strength and cough capacity in cervical spinal cord injured patients.

STUDY DESIGN: Prospective single centre study. OBJECTIVES: Pulmonary rehabilitation focuses on improving the expiratory muscle function in order to increase the reduced cough capacity in patients with cervical spinal cord injuries (SCI). However, an improvement in the inspiratory function is also important for coughing effectively. Therefore, this study was to examine the significance of the inspiratory muscle strength on the cough capacity in the patients with a cervical SCI. SETTING: SCI unit, Yonsei Rehabilitation Hospital, Seoul, Korea. METHODS: The vital capacity (VC), maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP) were measured. Moreover, the unassisted peak cough flow (PCF) and assisted PCF under three conditions were evaluated. RESULTS: All three assisted cough methods showed a significantly higher value than the unassisted method (P < 0.001). The VC correlated with the voluntary cough capacity and the MIP (R = 0.749) correlated more significantly with the VC than the MEP (R = 0.438) (P < 0.01). The MIP showed a higher correlation with both the unassisted PCF and all three assisted PCFs than the MEP (P < 0.001). CONCLUSIONS: The management of the inspiratory muscle strength should be considered in the pulmonary rehabilitation at cervical SCI patients.

Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques.

Respiratory complications are a leading cause of morbidity and mortality in patients with spinal cord injury. Several techniques, currently available or in development, have the capacity to restore respiratory muscle function allowing these patients to live more normal lives and hopefully reduce the incidence of respiratory complications. Bilateral phrenic nerve pacing, a clinically accepted technique to restore inspiratory muscle function, allows patients with ventilator dependent tetraplegia complete freedom from mechanical ventilation. Compared to mechanical ventilation, phrenic nerve pacing provides patients with increased mobility, improved speech, improved comfort level and reduction in health care costs. The results of clinical trials of laparoscopically placed intramuscular diaphragm electrodes suggest that diaphragm pacing can also be achieved without the need for a thoracotomy and associated long hospital stay, and without manipulation of the phrenic nerve which carries a risk of phrenic nerve injury. Other clinical trials are being performed to restore inspiratory intercostal function. In patients with only unilateral phrenic nerve function who are not candidates for phrenic nerve pacing, combined intercostal and unilateral diaphragm pacing appears to provide benefits similar to that of bilateral diaphragm pacing. Clinical trials are also underway to restore expiratory muscle function. Magnetic stimulation, surface stimulation and spinal cord stimulation of the expiratory muscles are promising techniques to restore an effective cough mechanism in this patient population. These techniques hold promise to reduce the incidence of respiratory tract infections, atelectasis and respiratory failure in patients with spinal cord injury and reduce the morbidity and mortality associated with these complications.

Effects of selective hypoglossal nerve stimulation on canine upper airway mechanics.

Electrical stimulation of the hypoglossal (XII) nerve has been demonstrated as an effective approach to treating obstructive sleep apnea. The physiological effects of conventional modes of stimulation (i.e., genioglossus activation or whole XII nerve stimulation), however, have yielded inconsistent and only partial alleviations of hypopneic or apneic events. Although selective stimulation of the multifasciculated XII nerve offers many stimulus options, it is not clear how these will functionally affect the upper airway (UAW). To study these effects, animal experiments in eight beagles were performed to investigate changes in the UAW resistance and critical pressure during simulated expiration (n = 4) and inspiration (n = 4). During expiration, nonselective XII nerve stimulation yielded the greatest improvement in UAW resistance (-0.66 +/- 0.11 cm H2O x l(-1) x min(-1)), compared with that for selective activation of the geniohyoid (-0.29 +/- 0.09 cm H2O x l(-1) x min(-1)), genioglossus (-0.31 +/- 0.12 cm H2O x l(-1) x min(-1)), and hyoglossus/styloglossus (0.37 +/- 0.06 cm H2O x l(-1) x min(-1)) muscles. For simulated inspiration, on the other hand, only whole XII nerve stimulation (-0.9 +/- 0.4 cm H2O) and coactivation of the genioglossus + hyoglossus/styloglossus muscles (-1.18 +/- 0.6 cm H2O) produced significant (P < 0.05) improvements in UAW stability (i.e., lowered critical pressure), compared with baseline (-0.52 +/- 0.32 cm H2O). The results of this study suggest that a multicontact nerve electrode can be used to achieve both UAW dilation and patency, comparable to that obtained with nonselective stimulation, by selectively activating the various branches of the XII nerve.

Electrical and mechanical properties and mode of innervation in scorpionfish sound-producing muscle fibres.

To obtain information about the neural mechanism underlying sound production in teleost fish, we studied the electrical and mechanical properties and mode of innervation in the swimbladder muscle (SBM) fibres of scorpionfish Sebastiscus marmoratus. Action potentials of the SBM fibres in response to direct electrical stimulation neither exhibited overshoot nor propagated along the fibre. Stimulation of the motor nerve, however, uniformly evoked action potentials along the fibre. When neuromuscular transmission was blocked by curare, motor nerve stimulation uniformly evoked endplate potentials along the fibre. These results indicate that action potentials propagate along the nerve branches but not along the SBM fibre membrane. In accordance with the above results, histochemical studies showed that motor nerve branches run along the SBM fibres to form many endplates with cholinesterase activity, indicating multiterminal innervation. The SBM consisted of about 600 fibres, while its motor nerve contained about 100 axons, giving an innervation ratio of about 1:6. Like mammalian fast muscle fibres, the SBM fibres exhibited a low succinic dehydrogenase activity and a high ATPase activity. These results are discussed in connection with the function of the SBM fibres in producing sound.

Pericranial muscular, respiratory, and heart rate components of the orienting response.

We have earlier found that voluntary attention to weak auditory stimuli induces inhibition of respiration, heart rate, and electromyographic (EMG) activity of masticatory and lower facial muscles and that these responses lower the auditory threshold for low-frequency sounds. In the current study, we examined whether this inhibitory response pattern also occurs during involuntary orienting to novel, nonsignal sounds. Environmental sounds of low intensity were presented unexpectedly during the performance of a reading task. Orienting responses (ORs) were elicited as indicated by heart rate deceleration and skin conductance responses. Inhibitory respiratory and pericranial EMG responses appeared to be intrinsic components of the OR. Together with the autonomic responses, they habituated when a nonsignal auditory stimulus was repeatedly presented. Our results also suggest that eye and pinna movements occurred toward the sound source. The results of the current study are consistent with the hypothesis of Sokolov (1963) that the primary function of the OR is enhancement of sensory sensitivity.

The effectiveness of neuromuscular release massage therapy in five individuals with chronic obstructive lung disease.

The purpose was to examine neuromuscular release massage therapy (NRMT) as an intervention for individuals with chronic obstructive lung disease (COLD) to improve pulmonary function, respiratory muscle strength, and quality of life. Variables measured were thoracic gas volume, peak flow, oxygen saturation, blood pressure, heart rate, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC, and quality of life to determine if improvement occurred with 24 weekly treatments of NRMT. Four of five participants had an increase in thoracic gas volume, peak flow, and FVC. Paired differences t test resulted in significant changes in heart rate, oxygen saturation, and time of breath hold. Repeated measured analysis of variance indicated a significant interaction between participant and time for heart rate, oxygen saturation, and systolic blood pressure. The results suggest that individuals with COLD do benefit from NRMT, but the exact physiological mechanism for the changes warrants additional study.

Computer aided adjustment of the phrenic pacemaker: automatic functions, documentation, and quality control.

Electrical stimulation of the phrenic nerves of patients with complete ventilatory insufficiency with the Vienna respiratory pacemaker has been in clinical use since 1983. During the adjustment of stimulation parameters with this device, the following problems have occurred: for some measurements like the recruitment curve, series of complete inspiration cycles have to be stimulated, which causes the danger of muscle fatigue for unconditioned patients. The documentation is completed predominantly by hand, taking time and increasing the possibility of error. As a first step to solve these problems, we developed a new stimulation and measurement system. It consists of a PC with data acquisition hardware, the necessary sensors, and amplifier circuitry. The implanted stimulator is controlled via the parallel interface. The new system offers some advantages: computer control shortens the time for measurement and documentation, and the stress on the patient and the risk of error is reduced; synchronized measurement makes it possible to use single stimulation pulses instead of bursts and ramps to reduce diaphragm fatigue; digital signal processing improves measurement results and reproducibility; and help functions and self tests are provided, together with a graphical user interface. We used sensors for air flow, diaphragm EMG, and acceleration, on up to 8 channels simultaneously. Combined sample rates of up to 100 kS/s were possible. The system could be adapted for other uses involving functional electrical stimulation with our implantable nerve stimulators. Using this equipment saves a lot of effort, and the adjustment process can be focused on improved stimulation results and better performance for the patient. Current research is studying implementation of automatic functions like acquisition of stimulation thresholds. This could result in a predominantly automated adjustment of the phrenic pacemaker and even in a closed-loop controlled system in the future.