Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome.

Respiratory muscle function was assessed in six patients with the Lambert-Eaton myasthenic syndrome. Five had histologically proved small cell carcinoma of the lung; the sixth later developed metastases from an unknown primary site. Two patients had ventilatory failure, one without respiratory symptoms; another, who had emphysema, had dyspnoea and orthopnoea. The remaining three patients had no respiratory symptoms. Four patients had limb muscle weakness as judged by the maximal voluntary contraction of the quadriceps muscle (range for all subjects 32-100% predicted). Transdiaphragmatic pressure (Pdi) was measured during a maximal unoccluded sniff (Pdi: sniff), a maximal sustained inspiratory effort against a closed airway (Pdi: Pimax), and phrenic nerve stimulation (Pdi: twitch). Mild to moderate diaphragmatic weakness was present in all six patients in proportion to the degree of leg weakness (Pdi: sniff 30-64% predicted; r = 0.6; Pdi:Pimax 6-69% predicted, r = 0.8); this was associated with very low or absent Pdi:twitch during phrenic nerve stimulation. Four patients had weakness of the expiratory muscles. Improvement in muscle strength was documented in two patients after tumour chemotherapy and specific treatment with 3,4-diaminopyridine and prednisolone; one patient was still alive five years from first diagnosis. It is concluded that the respiratory muscles may be implicated in this condition more often than has previously been recognised. As the lack of mobility may cause respiratory symptoms to be minimised, the presence of respiratory muscle weakness may remain undiagnosed unless formal measurement of respiratory muscle function is made.     

Can diaphragmatic contractility be assessed by airway twitch pressure in mechanically ventilated patients?

BACKGROUND: In critically ill patients inspiratory muscle function may be assessed by measurements of maximal inspiratory airway pressure and the response of twitch transdiaphragmatic pressure (Pdi tw) to bilateral phrenic nerve stimulation. The first is limited by its total dependence on patient cooperation. Although the second approach is independent of patient volition, it is impractical because it requires oesophageal and gastric balloons. Because airway pressure is easily and non-invasively recorded in patients with artificial airways, we hypothesised that twitch airway pressure (Paw tw) reliably predicts Pdi tw and twitch oesophageal pressure (Poes tw) in mechanically ventilated patients. METHODS: Thirteen mechanically ventilated patients recovering from an episode of acute respiratory failure received phrenic nerve stimulation at end exhalation. The rapid occlusion technique was used to record respiratory system mechanics. RESULTS: Stimulations were well tolerated. Mean (SE) Paw tw at end exhalation was -8.2 (1.2) cm H(2)O and Poes tw and Pdi tw were -7.3 (1.1) and 10.4 (1.8) cm H(2)O, respectively. Stimulations produced a good correlation between Paw tw and Pdi tw (p<0.001), although the limits of agreement were wide. The results were similar for Poes tw. No relationship was found between the Paw tw/Poes tw ratio and respiratory system compliance or airway resistance. Paw tw reproducibility was excellent (mean coefficient of variation 6%, range 3-9%). CONCLUSIONS: Despite a good correlation between Paw tw and Poes tw, Paw tw did not reliably predict Poes tw or Pdi tw in mechanically ventilated patients. Nevertheless, the excellent reproducibility of Paw tw suggests that it may be a useful means of monitoring inspiratory muscle contractility in the routine care of mechanically ventilated patients.     

Effect of abdominal binders on breathing in tetraplegic patients.

We studied the effect on breathing of a conventional and a newly designed abdominal binder in seven patients with complete tetraplegia. The indices of respiratory ability used were the transdiaphragmatic pressure on maximal sniff (sniff Pdi), the maximum static inspiratory mouth pressure (PImax), and the vital capacity (VC). These were measured in patients with and without binders, in the supine position, raised up to 70 degrees on a tilt table, and seated upright. When patients were raised from the supine to the 70 degrees tilt and to the seated posture, sniff Pdi and VC decreased. Both binders improved VC in the seated position and at 70 degrees tilt, and sniff Pdi at 70 degrees tilt. The new binder was as effective as but no better than the conventional binder. PImax was too variable to be a valuable index of inspiratory power. These findings support the view that abdominal binders assist breathing in tetraplegic patients who are seated or raised to near vertical positions.     

The value of multiple tests of respiratory muscle strength

BACKGROUND: Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. METHODS: The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6-year period were analysed. Thresholds for weakness for each test were determined from published and in-house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. RESULTS: The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (Pimax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non-invasive tests (Pimax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (Pemax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. CONCLUSION: The use of single tests such as Pimax, Pemax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19-56%. Measuring both Pimax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances.     

Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.     

The Effect of Core Exercises on Transdiaphragmatic Pressure

Abdominal exercises, such as sit ups and leg lifts, are used to enhance strength of the core muscles. An overlooked aspect of abdominal exercises is the compression the abdomen, leading to increased diaphragmatic work. We hypothesized that core exercises would produce a variety of transdiaphragmatic pressures. We also sought to determine if some of the easy exercises would produce pressures sufficient for a training stimulus to the diaphragm. We evaluated the effect of 13 different abdominal exercises, ranging in difficulty, on transdiaphragmatic pressure (Pdi), an index of diaphragmatic activity. Six healthy subjects, aged 22 to 53, participated. Each subject was instrumented with two balloon-tipped catheters to obtain gastric and esophageal pressures, from which Pdi was calculated. Prior to initiating the exercises, each subject performed a maximal inspiratory pressure (MIP) maneuver. Resting Pdi was also measured. The exercises were performed from least to most difficult, with five repetitions each. There was a significant difference between the exercises and the MIP Pdi, as well as between the exercises and resting Pdi (p < 0.001). The exercises stratified into three Pdi levels. Seven of the exercises yielded Pdi ≥ 50% of the Pdi during the MIP maneuver, which may provide a training stimulus to the diaphragm if used as a regular exercise. The Pdi measurements also provide insight into diaphragm recruitment during different core exercises, and may aid in the design of exercises to improve diaphragm strength and endurance.

Key points

• Please provide 3-5 bullet points of the study.The study examined the effect of different core exercises of varying difficulty on activation of the diaphragm.
• We found that the exercises yielded different pressures, some of which were greater than 50% of the pressures generated during a maximal inspiratory maneuver.
• The difficulty of the exercise was not always correlated with the magnitude of the pressure.
• Some of these exercises should be easy enough for subjects in rehabilitation programs to perform and still generate high enough pressures to help strengthen the diaphragm.

Key words: Abdominal exercise, diaphragm activation, gastric pressure, esophageal pressure     

Colforsin daropate improves contractility in fatigued canine diaphragm

We studied the effects of colforsin daropate, a water-soluble forskoline derivative, on contractility in fatigued canine diaphragm. Dogs were randomly divided into 4 groups of 8 each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug, Group 2 was infused with small-dose colforsin daropate (0.2 microg. kg(-1). min(-1)), Group 3 was infused with large-dose colforsin daropate (0.5 microg. kg(-1). min(-1)), and Group 4 was infused with nicardipne (5 microg. kg(-1). min(-1)) during colforsin daropate (0.5 microg. kg(-1). min(-1)) administration. After the fatigue-producing period, in each group transdiaphragmatic pressure (Pdi) at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate administration, Pdi to each stimulus increased from fatigued values (P < 0.05). The increase in Pdi was larger in Group 3 than in Group 2 (P < 0.05). In Group 4, the augmentation of Pdi by colforsin daropate was abolished in fatigued diaphragm with an infusion of nicardipine. The integrated diaphragmatic electric activity did not change in any of the groups. We conclude that colforsin daropate improves, in a dose-dependent manner, contractility in fatigued canine diaphragm via its effect on transmembrane calcium movement. IMPLICATIONS: Diaphragmatic fatigue is implicated as a cause of respiratory failure in normal subjects and in patients with chronic obstructive lung disease. Colforsin daropate improves contractile properties during diaphragmatic fatigue.     

Respiratory muscle assessment in predicting extubation outcome in patients with stroke

BackgroundPatients with cerebral infarction often present impaired consciousness and unsatisfactory extubation. We aimed to assess the respiratory mechanics components that might be associated with the success of extubation in stroke patients.MethodsTwenty consecutive patients with stroke who needed mechanical ventilation support were enrolled. The maximal inspiratory pressure, gastric and the esophageal pressure (Pdi/Pdimax), minute volume, respiratory rate, static compliance, airway resistance, rapid shallow breathing index (RSBI), inspiratory time/total respiratory cycle (Ti/Ttot), and PaO₂/FiO₂ were measured.ResultsThe group who presented success to the extubation process presented 12.5±2.2=days in mechanical ventilation and the group who failed presented 13.1±2=days. The mean Ti/Ttot and Pdi/Pdimax for the failure group were 0.4±0.08 (0.36–0.44) and 0.5±0.7 (0.43–0.56), respectively. The Ti/Ttot ratio was 0.37±0.05 (0.34–0.41; P=.0008) and the Pdi/Pdimax was 0.25±0.05 for the success group (0.21–0.28; P<.0001). A correlation was found between Pdi/Pdimax ratio and the RSBI (r=0.55; P=.009) and PaO₂/FiO₂ (r=?0.59; P=.005). Patients who presented a high RSBI (OR, 3.66; P=.004) and Pdi (OR, 7.3; P=.002), and low PaO₂/FIO₂ (OR, 4.09; P=.007), Pdi/Pdimax (OR, 4.12; P=.002) and Raw (OR, 3.0; P=.02) developed mechanical ventilation extubation failure.ConclusionMuscular fatigue index is an important predicting variable to the extubation process in prolonged mechanical ventilation of stroke patients.     

Twitch pressures in the assessment of diaphragm weakness.

To assess the value of phrenic nerve stimulation in the investigation of diaphragm function, transdiaphragmatic pressures were measured in 20 healthy subjects and in 15 patients with diaphragm weakness, during unilateral and bilateral transcutaneous phrenic nerve stimulation at 1 Hz at functional residual capacity (twitch Pdi). Diaphragm function was initially assessed by measuring transdiaphragmatic pressure during a voluntary manoeuvre, the maximal sniff (sniff Pdi); normal readings were confirmed in the control subjects (102-157 (normal greater than 98) cm H2O in the 10 men, 79-102 (normal greater than 70) cm H2O in the 10 women) and reduced values were found in the 15 patients with diaphragm weakness (7.5-90 cm H2O in the 13 men, 23 and 53 cm H2O in the two women). Twitch Pdi during bilateral phrenic nerve stimulation ranged from 8.8 to 33 cm H2O in the control subjects and from 3.1 to 27 cm H2O in the 10 patients in whom a measurement could be obtained. Bilateral twitch Pdi correlated with sniff Pdi both in the control subjects and in the patients with diaphragm weakness (r = 0.75). Only four patients had a bilateral twitch Pdi below the lowest value seen in the control group, including the three with the lowest sniff Pdi (3.1-8.5 cm H2O). These results indicate that transdiaphragmatic pressure recorded during bilateral phrenic nerve stimulation discriminated between control subjects and patients with known weakness of the diaphragm only when this was severe.     

Recruitment of some respiratory muscles during three maximal inspiratory manoeuvres.

BACKGROUND--A study was undertaken to determine the level of recruitment of the muscles used in the generation of respiratory muscle force, and to ascertain whether maximal diaphragmatic force and maximal inspiratory muscle force need to be measured by separate tests. The level of activity of three inspiratory muscles and one expiratory muscle during three maximal respiratory manoeuvres was studied: (1) maximal inspiration against a closed airway (Muller manoeuvre or maximal inspiratory pressure (MIP)); (2) maximal inspired manoeuvre followed by a maximal expiratory effort (combined manoeuvre); and (3) maximal inspiratory sniff through the nose (sniff manoeuvre). METHODS--All the manoeuvres were performed from functional residual capacity. The gastric (PGA) and oesophageal (POES) pressures and their difference, transdiaphragmatic pressure (PDI), and the integrated EMG activity of the diaphragm (EDI), the sternomastoid (ESTR), the intercostal parasternals (ERIC), and the rectus abdominis muscles (ERA) were recorded. RESULTS--Mean (SD) PDI values for the Muller, combined, and sniff manoeuvres were: 127.6 (19.4), 162.7 (22.2), and 136.6 (24.8) cm H2O, respectively. The pattern of rib cage muscle recruitment (POES/PDI) was similar for the Muller and sniff manoeuvres (88% and 80% respectively), and was 58% in the combined manoeuvre, confirming data previously reported in the literature. Peak EDI amplitude was greater during the sniff manoeuvre in all subjects (100%) than during the combined (88.1%) and Muller (61.1%) manoeuvres. ESTR and EIC were more active in the Muller and the sniff manoeuvres. The contribution of the expiratory muscle (ERA) to the three manoeuvres was 100% in the combined, 26.1% for the sniff, and 11.5% for the Muller manoeuvre. CONCLUSIONS--Each of these three manoeuvres results in different mechanisms of inspiratory and expiratory muscle activation and the intrathoracic and intra-abdominal pressures generated are a reflection of the interaction between the various muscle groups. The Muller and sniff manoeuvres reflect mainly the force of the inspiratory muscles and the combined manoeuvre that of the diaphragm.     

Mechanical Significance of Respiratory Muscle Activity in Humans during Halothane Anesthesia

Background: Prior human studies have shown that halothane attenuates activity in the parasternal intercostal muscle and enhances phasic activity in respiratory muscles with expiratory actions. This expiratory muscle activity could contribute to reductions in the functional residual capacity produced by anesthesia. Termination of this activity could contribute to the maintenance of inspiratory rib cage expansion. The purpose of this study was to estimate in humans the mechanical significance of expiratory muscle activity during halothane anesthesia and to search for the presence of scalene muscle activity during halothane anesthesia that might contribute to inspiratory rib cage expansion.

Methods: Six subjects (3 males, 3 females) were studied while awake and during 1.2 MAC halothane anesthesia, both during quiet breathing and during carbon dioxide rebreathing. Respiratory muscle activity was measured using fine-wire electromyography electrodes. Chest wall configuration was determined using images of the thorax obtained by three-dimensional, fast computed tomography and respiratory impedance plethysmography. Functional residual capacity was measured by a nitrogen dilution technique. Measurements were obtained after paralysis with 0.1 mg/kg vecuronium and mechanical ventilation.

Results: Phasic inspiratory activity was present in the scalene muscle of four anesthetized subjects during quiet breathing and all anesthetized subjects during rebreathing. Phasic inspiratory activity was present in the parasternal intercostal muscle during halothane anesthesia in only the three female subjects and was enhanced by rebreathing; parasternal intercostal muscle activity was never present in anesthetized males. During anesthesia with quiet breathing, phasic expiratory activity was observed in the transversus abdominis muscles of only the three male subjects. Despite these differences in the pattern of respiratory muscle use, the pattern of chest wall responses to rebreathing was similar between males and females. When expiratory muscle activity was present, paralysis increased the end-expiratory thoracic volume by expanding the rib cage, demonstrating that this activity reduced thoracic volume in these subjects. Changes in thoracic blood volume were significant determinants of the change in functional residual capacity produced by paralysis.     

Respiratory effects of expiratory flow-resistive loading in conscious and anesthetized humans

The response of breathing patterns to increased expiratory resistance is not only of physiologic interest, with respect to the control of breathing, but also of clinical interest because of its clinical relevance to obstructive diseases such as asthma and emphysema. To elucidate the response of breathing patterns to increased expiratory resistance during anesthesia, the respiratory effects of expiratory flow-resistive loading on breathing patterns were studied in 15 conscious and 10 lightly anesthetized subjects. Inspiratory time, expiratory time, respiratory frequency, inspiratory duty cycle, tidal volume, minute ventilation, and mean inspiratory flow rate were determined from a respiratory inductive plethysmograph. End-tidal CO2 was continuously recorded. In awake subjects, respiratory frequency was reduced without change in tidal volume or mean inspiratory flow rate, and minute ventilation was significantly decreased; the synchrony between rib cage and abdomen wall motion was well maintained during the loads. In contrast, in anesthetized subjects, respiratory frequency was reduced with remarkable increases in tidal volume, mean inspiratory flow rate, and minute ventilation, whereas coordination between rib cage and abdomen compartments was disturbed. End-tidal CO2 did not change in conscious subjects, but it increased in anesthetized subjects during the loads. These results indicate that there are differences between conscious and anesthetized subjects in breathing patterns during expiratory loading, and suggest that the ability to coordinate rib cage-abdomen wall motion is easily disturbed during anesthesia in patients with expiratory flow limitation.     

The effect of inhaled colforsin daropate on contractility of fatigued diaphragm in dogs

We studied the effect of inhaled colforsin daropate, a water-soluble forskolin derivative, on the contractility of fatigued diaphragm in dogs. Animals were divided into 3 groups of 8. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation applied for 30 min. Immediately after the end of the fatigue-producing period, Group 1 received inhaled vehicle, Group 2 received inhaled colforsin daropate 0.1 mg/mL, and Group 3 received inhaled colforsin daropate 0.2 mg/mL. We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After fatigue was produced, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), and there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, during colforsin daropate inhalation, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was significantly larger in Group 3 than in Group 2. The integrated electrical activity of the diaphragm did not change in any group. We conclude that inhaled colforsin daropate causes an increase in contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Inhaled colforsin daropate improves, in a dose-dependent manner, the contractility of fatigued diaphragm in dogs.     

The dose-range effects of propofol on the contractility of fatigued diaphragm in dogs.

Diaphragmatic fatigue may contribute to the development of respiratory failure. We studied the dose-range effects of propofol on the contractility of fatigued diaphragm in dogs. Animals were divided into three groups of eight each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20-Hz stimulation for 30 min. Immediately after the end of a fatigue-producing period, Group 1 received no study drug; Group 2 was infused with small-dose propofol (0.1 mg/kg initial dose plus 1.5 mg x kg(-1) x h(-1) maintenance dose); Group 3 was infused with large-dose propofol (0.1 mg/kg initial dose plus 6.0 mg x kg(-1) x h(-1) maintenance dose). We assessed diaphragmatic contractility by transdiaphragmatic pressure (Pdi). After the fatigue-producing period, in each group, Pdi at low-frequency (20-Hz) stimulation decreased from baseline values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups 2 and 3, with an infusion of propofol, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05). Compared with Group 1, Pdi at 20-Hz stimulation decreased from fatigued values (P < 0.05) during propofol administration in Groups 2 and 3. The decrease in Pdi was more in Group 3 than in Group 2 (P < 0.05). We conclude that propofol decreases the contractility of fatigued canine diaphragm in a dose-related fashion. IMPLICATIONS: Propofol is a widely used IV anesthetic for the induction and maintenance of general anesthesia and sedation. It decreases, in a dose-related fashion, the contractility of fatigued diaphragm in dogs.     

Recovery of costal and crural diaphragmatic contractility from partial paralysis

Since the two muscles (costal and crural) that constitute the diaphragm are separate and histologically different, their individual recovery pattern from neuromuscular blockade also may be different. Therefore, we studied the recovery of force and shortening in the in vivo diaphragm from atracurium-induced neuromuscular blockade in seven pentobarbital anesthetized dogs to assess segmental differences. Transdiaphragmatic pressure (Pdi), shortening of costal and crural segments, integrated electromyogram (EMG), and tidal volume (VT) were measured during spontaneous breathing. After atracurium had reduced VT to 30% of control, breathing parameters were followed until recovered to 90% of control values. In addition, force-frequency curves generated by supramaximal tetanic stimuli of the phrenic nerve were measured. Recovery times for tidal Pdi, tidal EMG, tidal shortening, low-frequency shortening, and twitch Pdi were twice as fast as for VT (40 +/- 4 min), reflecting a slower rate of recovery of accessory inspiratory muscles. High-frequency recovery was typically slower than that of VT. During tidal breathing and tetanic stimulation, costal and crural shortening recovered simultaneously. On the other hand, comparison between costal and crural by analysis of pressure-shortening relationships showed a segmental difference (crural shortened 30% more than costal at the same Pdi), which implied reduced afterload on the crural segment. However, since shortening and pressure were linearly related during paralysis and recovery, measurements of Pdi alone can accurately reflect changes in contractile mass when heterogeneity and afterload are controlled.     

Inspiratory muscle relaxation rate assessed from sniff nasal pressure.

BACKGROUND--Slowing of the maximum relaxation rate (MRR) of inspiratory muscles measured from oesophageal pressure (POES) during sniffs has been used as an index of the onset and recovery of respiratory muscle fatigue. The purpose of this study was to measure MRR at the nose (PNASAL MRR), to investigate its relationship with POES MRR, and to establish whether PNASAL MRR slows with respiratory loading. METHODS--Five normal subjects were studied. Each performed sniffs before and after two minutes of maximal isocapnic ventilation (MIV). In a separate session the subjects performed submaximal sniffs. POES and PNASAL were recorded during sniffs and the MRR (% pressure fall/10 ms) for each sniff was determined. RESULTS--Before MIV mean POES MRR was 8.9 and PNASAL MRR was 9.3. The mean (SD) difference between PNASAL MRR and POES MRR during a maximal sniff was 0.48 (0.34) (n = 64) and during submaximal sniffs was 0.28 (0.46) (n = 526). The subjects showed a mean decrease in sniff POES MRR of 27.4% (range 22.5-36%) after MIV and a similar reduction in sniff PNASAL MRR of 28.5% (range 24.1-41.3%). Both returned to control values within 5-10 minutes. CONCLUSIONS--PNASAL MRR reflects POES MRR over a wide range of sniff pressures, PNASAL MRR of maximal sniffs reflects POES MRR in normal subjects at rest and following MIV, so measurement of PNASAL MRR may be a useful non-invasive method for measuring inspiratory muscle MRR, thereby providing an index of respiratory muscle fatigue.     

Measurement of twitch transdiaphragmatic pressure: surface versus needle electrode stimulation.

The transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 1 Hz from surface stimulating electrodes was compared with pressures obtained from needle electrodes inserted under local anaesthesia. Surface electrodes were used to obtain diaphragmatic electromyograms and magnetometers to monitor rib cage and abdominal configuration. Twitch Pdi was recorded at functional residual capacity in three normal subjects. Mean (SD) twitch Pdi in the three subjects during stimulation with surface electrodes was 19.4 (1.8), 22.5 (1.1), and 29.3 (2.2) cm H2O compared with 12.9 (1.5), 17:4 (1.3), and 22.6 (3.0) cm H2O with needle stimulating electrodes. Thus phrenic nerve stimulation with needle electrodes was more complicated and more invasive than stimulation with surface electrodes and resulted in lower transdiaphragmatic pressures.     

Lung function, hypoxic and hypercapnic ventilatory responses, and respiratory muscle strength in normal subjects taking oral theophylline.

Methylxanthines are known to be respiratory stimulants and are thought by some to augment hypercapnic and hypoxic ventilatory drive and improve respiratory muscle strength. Hypoxic and hypercapnic ventilatory responses were measured in 10 normal subjects before, during, and after administration of theophylline for three and a half days. Pulmonary function, carbon dioxide production, and mouth pressures during maximal static inspiratory and expiratory efforts were also measured. The mean (SD) serum theophylline concentration was 13.8 (3.2) mg/l. Lung volumes and flow rates did not change significantly with theophylline. The mean (SD) values for maximum static inspiratory pressure were 152 (27), 161 (25), and 160 (24) cm H2O, respectively before, during, and after theophylline. Neither these values nor peak expiratory pressure measurements were significantly changed. The slopes of the hypercapnic ventilatory responses were 2.9 (0.9), 3.3 (1.2), and 3.3 (1.4) l/min/mm Hg carbon dioxide tension (PCO2) respectively before, during, and after theophylline administration. The respective values for the slopes of the hypoxic response were -1.4 (0.9), -1.3 (0.8), and -1.1 (0.9) l/min/1% oxyhaemoglobin saturation. None of these values changed significantly with theophylline. Theophylline, however, increased carbon dioxide production (200 to 236 ml/min) and alveolar ventilation (4.7 to 5.7 l/min) significantly, with a concomitant fall of end tidal PCO2 (35.5 to 32.9 mm Hg). It is concluded that in man oral theophylline at therapeutic blood concentrations increases carbon dioxide production and ventilation without changing pulmonary function, respiratory muscle strength, or the hypoxic or hypercapnic ventilatory response significantly.     

The effect of olprinone compared with milrinone on diaphragmatic muscle function in dogs.

We compared the effect of olprinone with milrinone on the contractility of fatigued diaphragms in dogs. Animals were divided into four groups of 10 each. In each group, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. After producing fatigue, Group I received only maintenance fluids; Group II was given a bolus injection (50 microg/kg) followed by continuous infusion (0.5 microg x kg(-1) x min(-1)) of milrinone; Group III was infused with olprinone (10 microg/kg initial dose plus 0.3 microg x kg(-1) x min(-1) maintenance dose); Group IV was infused with nicardipine (5 microg x kg(-1) x min(-1)) during olprinone administration. After the fatigue-producing period in each group, transdiaphragmatic pressure (Pdi) at low-frequency (20 Hz) stimulation decreased from the prefatigued values (P < 0.05), whereas there was no change in Pdi at high-frequency (100-Hz) stimulation. In Groups II and III, during study drug infusion, Pdi at both stimuli increased from fatigued values (P < 0.05). The increase in Pdi was larger in Group III than in Group II (P < 0.05). In Group IV, the augmentation of Pdi by olprinone was abolished in the fatigued diaphragm with an infusion of nicardipine. We conclude that olprinone is more effective than milrinone for the improvement of contractility in he fatigued diaphragm and that the potentiating mechanism of olprinone may be closely related to the transmembrane calcium movement. IMPLICATIONS: Diaphragmatic fatigue may contribute to the development of respiratory failure. Compared with milrinone, olprinone improves the contractility in fatigued diaphragm in dogs.     

Effects of isoflurane on contractile properties of diaphragm

Isoflurane has been shown to depress skeletal muscle force in vitro, but data are not available regarding the effects of isoflurane on diaphragmatic muscle function in vivo. To answer this question, 15 rats anesthetized with pentobarbital and mechanically ventilated were studied. They were divided into three groups of five animals each, according to the administered concentration of isoflurane. Diaphragmatic function was assessed by measuring the transdiaphragmatic pressure (Pdi) generated during bilateral supramaximal phrenic nerve stimulation at 0.5 Hz, 20 Hz, 50 Hz, and 100 Hz under quasi-isometric conditions. After a control measurement (C), isoflurane was administered at a constant concentration (0.5, 1, or 1.5 MAC) and Pdi measurements were repeated after 30 min of isoflurane exposure (T1) and 30 min after discontinuing isoflurane (T2). In the group breathing 1.5 MAC isoflurane, the time constant of diaphragmatic relaxation (tau) and integrated electrical activity of the diaphragm (Edi) were also assessed. The Pdi amplitude generated by single twitch (0.5 Hz) was unchanged at the three isoflurane concentrations. A significant increase in Pdi at 20 Hz was observed at T1, which returned to control after 30 min recovery (T2). No change in Pdi during 50 Hz stimulation was noted during 0.5 and 1 MAC isoflurane exposure, whereas it was reduced at T1 during 1.5 MAC. For 100 Hz stimulation, a significant decrease in Pdi was noted for all groups at T1, which returned toward control values at T2. Edi was markedly reduced for 50 and 100 Hz stimulation, but this reduction was also transient, since Edi returned toward control values at T2.(ABSTRACT TRUNCATED AT 250 WORDS)