Effect of Frequency and Tidal Volume on Pleural Pressure in Rabbits during High Frequency Ventilation

Regional effects of the chest wall on airway pressure transmission were studied during high frequency ventilation in anesthetized rabbits. We measured airway pressure (Paw), esophageal pressure (Pes), and costal pleural pressure (Ppl) by a rib capsule and flow and volume with a calibrated pneumotachograph. Using a closed circuit, pressures and flow were measured at varying frequencies (2–80 Hz) and tidal volumes (2–20 ml). Mean Pes and Ppl increased with flow amplitude above 100–250 ml/s, whereas mean Paw decreased, consistent with air trapping. Paw, Pes, and Ppl amplitudes increased monotonically with flow amplitude except above 400–500 ml/s, where the Ppl amplitude decreased suddenly. The latter occurring simultaneously with a sudden fall in mean Paw indicated airway flow limitation in costal regions. Flow instabilities during flow limitation were consistent with the large increase in the phase difference between Paw and Ppl and its variability, with frequency. By contrast, the phase difference between Paw and Pes and its variability were relatively small. These differences in Pes from Ppl responses might be caused by a difference in the impedance of the airway-mediastinum pathway or a direct transmission of tracheal pressure oscillations to the esophagus. The former suggests that constraints offered by the mediastinum and rib cage resulted in nonuniform ventilation during high frequency ventilation. Accepted for publication: 14 July 1998     

Recruitment and derecruitment during acute respiratory failure: an experimental study.

We aimed to elucidate the relationships between pleural (Ppl), esophageal (Pes), and superimposed gravitational pressures in acute lung injury, and to understand the mechanisms of recruitment and derecruitment. In six dogs with oleic acid respiratory failure, we measured Pes and Ppl in the uppermost, middle, and most dependent lung regions. Each dog was studied at positive end-expiratory pressure (PEEP) of 5 and 15 cm H2O and three levels of tidal volume (VT; low, medium, and high). For each PEEP-VT combination, we obtained a computed tomographic (CT) scan at end-inspiration and end-expiration. The variations of Ppl and Pes pressures were correlated (r = 0.86 +/- 0.07, p < 0.0001), as was the vertical gradient of transpulmonary (PL) and superimposed pressure (r = 0.92, p < 0.0001). Recruitment proceeded continuously along the entire volume-pressure curve. Estimated threshold opening pressures were normally distributed (mode = 20 to 25 cm H2O). The amount of end-expiratory collapse at the same PEEP and PL was significantly lower when ventilation was performed at high VT. End-inspiratory and end-expiratory collapse were highly correlated (r = 0.86, p < 0.0001), suggesting that as more tissue is recruited at end-inspiration, more remains recruited at end-expiration. When superimposed pressure exceeded applied airway pressure (Paw), collapse significantly increased.     

Transmission fatigue of the rabbit diaphragm

This study evaluates the role of transmission fatigue of the diaphragm in rabbits subjected to inspiratory resistive loading (IRL) sufficiently severe to increase peak tidal airway pressure to about 50% of that elicited by 100 Hz phrenic nerve stimulation. After 58 +/- 14 min of IRL, the transdiaphragmatic pressure (Pdi) responses to phrenic nerve stimulation at 20, 60, and 100 Hz were reduced by approximately one third. In contrast, IRL induced no significant change in the response to direct diaphragm stimulation (in the presence of transient neuromuscular blockade). Although respiratory acidosis occurred during IRL (pH 7.04 +/- 0.04, PCO2 90 +/- 10, PO2 131 +/- 38), it was not sufficient to explain the reduced contractility. In a separate series of experiments, the diaphragm compound action potential elicited by unilateral phrenic nerve stimuli was recorded by implanted diaphragm electrodes and the Pdi elicited by contralateral phrenic nerve stimulation at 100 Hz was measured. Both action potential amplitude and Pdi declined during IRL and both improved after 10 min of recovery. These findings demonstrate that transmission fatigue plays a major role in rabbit diaphragm fatigue induced by spontaneous breathing against inspiratory resistance.     

Can diaphragmatic contractility be assessed by twitch airway pressures in patients with chronic obstructive pulmonary disease?

In healthy subjects and in patients without lung diseases, twitch airway pressure (Paw(tw)) responses to phrenic nerve stimulation can be used to predict twitch esophageal pressure (Pes(tw)) and twitch transdiaphragmatic pressure (Pdi(tw)), thus overcoming the need for placement of esophageal and gastric balloons. The aim of this study was to determine whether measurements of Paw(tw) combined with simple maneuvers could be used to predict Pes(tw), and possibly Pdi(tw), in patients with severe chronic obstructive pulmonary disease (COPD) (n = 12). Stimulations delivered at relaxed FRC produced a correlation coefficient (r) between Paw(tw) and Pes(tw) of 0.44 (p < 0.001) and of 0.62 (p < 0.001) during stimulations while patients performed a gentle exhalation from FRC. Stimulations performed during a gentle inhalation produced a good correlation between Paw(tw) and Pes(tw) (r = 0.92, p < 0.001); however, the limits of agreement between Paw(tw) and Pes(tw) were wide. Correlations between Paw(tw) and Pdi(tw) during the three experimental conditions were weak. In conclusion, during a gentle inspiratory effort in patients with severe COPD the correlation between Paw(tw) and Pdi(tw) was weak, whereas the correlation between Paw(tw) and Pes(tw) was good, but it was not sufficient to allow the prediction of Pes(tw) from Paw(tw) in all patients.     

Inspiratory muscle unloading by neurally adjusted ventilatory assist during maximal inspiratory efforts in healthy subjects

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures. METHOD: In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured. RESULTS: During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024). CONCLUSION: In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.     

Physiological role of respiratory-related bronchial constriction]

The respiration-related rhythmic constriction of the fifth-generation bronchi was analyzed in 11 tracheostomized dogs. During spontaneous breathing, the bronchial pressure (Pbr) estimated with a balloon-tipped catheter increased almost in parallel with the pleural pressure (Ppl) in the early inspiratory phase, but decreased in the late inspiratory phase. The parallel duration/inspiratory duration was 0.72 +/- 0.19 (mean +/- SD). This finding was more prominent in hypercapnia, but statistical significance was not obtained. When the efferent phrenic nerve fibers were electrically stimulated (pulse train, 0.1 ms, 30 Hz, 5 V, 2 s), Pbr changed almost in parallel with Ppl during the inspiratory phase, and expiration was completed significantly earlier than during spontaneous breathing (time constant 0.17 +/- 0.06 s vs 0.26 +/- 0.07 s). Bronchial constriction in early expiration may increase airway pressure and keep patency of the peripheral bronchi.     

Central fatigue of the rabbit diaphragm

This study evaluates the importance of central fatigue of the diaphragm in rabbits subjected to inspiratory muscle resistive loading (IRL). Ten rabbits were subjected to constant IRL while unanesthetized and breathing supplemental oxygen. During 10-20 minutes of spontaneous breathing against IRL, there were no significant changes in arterial oxygen saturation or in diaphragm contractility, measured by the quasi-static transdiaphragmatic pressure response to a 0.3-sec train of 100 Hz supramaximal phrenic nerve stimuli. After an initial decrease due to application of the load, the minute ventilation decreased further, by an average of 15%, while arterial pCO2 increased to an average of 59 mmHg (p less than 0.05). The normalized diaphragm pressure-time index initially increased from 0.02 to 0.18 during IRL, then decreased an average of 29% (p less than 0.05). These results show that severe IRL causes a decrease in the level of diaphragmatic effort over time despite increased chemical drive and despite a preserved ability of the muscle to respond to phrenic nerve stimuli. This adaptation may help to prevent peripheral diaphragm fatigue.     

Spontaneous recovery of diaphragmatic strength in unilateral diaphragmatic paralysis

The aim of the present study was to evaluate diaphragmatic strength in patients with unilateral diaphragmatic paralysis and to determine whether patients with recent diaphragm paralysis develop lower inspiratory pressure than patients with longstanding diaphragmatic paralysis. Twenty patients (16 men and 4 women, 62+/-12 years) and six control subjects were included (4 men and 2 women, 53+/-15 years) in the study. Esophageal pressure during sharp sniff (Pes,sniff), bilateral cervical phrenic nerve magnetic stimulation (Pes,cms) and unilateral phrenic nerve stimulation (Pes,ums) (in nine patients) were measured. Sixteen patients presented right diaphragmatic paralysis and four, left diaphragmatic paralysis. Pes,sniff was higher in control subjects than in patients with diaphragmatic paralysis (respectively 110+/-22 cmH2O and 82+/-24 cmH2O, P<0.05). There was no difference in Pes,cms between patients with diaphragmatic paralysis and control subjects (14+/-7 cmH2O vs. 16+/-4 cmH2O; ns). Pes,ums after stimulation of the affected phrenic nerve was less than 4 cmH2O, was 8+/-2 cmH2O after stimulation of the intact phrenic nerve and was correlated to Pes,cms (R=0.87, P<0.01). There was a positive correlation between Pes,cms, Pes,ums of the intact hemidiaphragm, Pes,sniff and the time from the onset of symptoms and the diaphragmatic explorations (respectively R=0.86, P<0.0001; R=0.72, P<0.05; R=0.48, P<0.05). In conclusion, diaphragmatic strength after unilateral diaphragmatic paralysis seems to improve with time.     

Esophageal and mouth pressure during sniffs with and without nasal occlusion.

The sniff maneuver has recently been advocated for assessing inspiratory muscle strength. We characterized the relationship between mouth pressure (Pmo) and esophageal pressure (Pes) during sniffs performed with open, semi-occluded, and occluded nose. In seven normal subjects, pressure was simultaneously measured with a mouthpiece (Pmo) an esophageal balloon (Pes) during high- and low-intensity sniffs performed from FRC. With open nose, the mean ratio Pmo/Pes was 0.96 +/- 0.05 (mean +/- SE). The mean ratio Pmo/Pes was not significantly different in high- and low-intensity sniffs. With one nostril occluded, the mean ratio Pmo/Pes was 1.03 +/- 0.04. The ratio Pmo/Pes was significantly higher than with open nose for all sniffs (P less than 0.05) and low-intensity sniffs (P less than 0.01). With both nostrils occluded, the mean ratio Pmo/Pes was 1.06 +/- 0.03, with occasional marked overestimation of Pes by Pmo. We conclude that Pmo generally reflects Pes during sniffs performed with open and semi-occluded nose, but not with complete nasal occlusion.     

Esophageal-directed pressure support ventilation in normal volunteers

STUDY OBJECTIVES: To ascertain whether inspiratory pressure support (IPS) can be triggered reliably from and targeted at esophageal pressures (Pes), and to compare the work of breathing and time delay to initiation of inspiratory flow between conventional pressure support and esophageal-directed pressure support (EDPS). DESIGN: Prospective laboratory study. SETTING: University medical school. PATIENTS OR PARTICIPANTS: Five normal volunteers. INTERVENTIONS: IPS at a level to achieve tidal volume of 10 mL/kg, and EDPS with a target Pes of 0 cm H2O via full facemask. MEASUREMENTS AND RESULTS: Pes, airway pressure, and inspiratory flow were measured during spontaneous breathing. Peak Pes and pressure time product (PTP) of Pes were calculated during spontaneous breathing and through linear resistances. Measurements were repeated during IPS and EDPS ventilation. At rest, PTP was 7.56 (+/- 3.6) and peak Pes was -5.8 cm H2O (+/- 1.44). When subjects were breathing through the resistors, PTP increased to 12.4 (+/- 8.1) and 30.3 (+/- 8.9) and peak Pes decreased to -7.2 and -15.3 cm H2O respectively. With facemask IPS, unloaded PTP fell to 1.7 (+/- 1.3) and peak Pes fell to -3.3 cm H2O (+/- 1.3). When ventilated through the highest resistance with IPS, mean PTP increased to 21.9 and peak Pes increased to -11.9 (+/- 4.2) cm H2O relative to baseline. During EDPS with the resistor, PTP fell to 1.5+/-1.1 (p < 0.007) and peak Pes fell to -1.9+/-1.1 cm H2O (p < 0.0001). CONCLUSIONS: It was possible to initiate supported breathing from Pes values. The work performed, as measured by PTP, was lower during EDPS than during either unsupported breathing or conventional IPS.     

Effects of spontaneous breathing during airway pressure release ventilation on respiratory work and muscle blood flow in experimental lung injury

STUDY OBJECTIVES: To evaluate the effects of spontaneous breathing at ambient airway pressure (Paw) and during airway pressure release ventilation (APRV) on respiratory work and respiratory muscle blood flow (RMBF) in experimental lung injury. DESIGN: Prospective experimental study. SETTING: Research laboratory of a university hospital. SUBJECTS: Twelve hemodynamically stable, analgosedated, and tracheotomized domestic pigs. MEASUREMENTS: Respiratory work was estimated by the inspiratory pressure time product (PTPinsp) of esophageal pressure, and RMBF was measured with colored microspheres. Lung injury was induced with IV boli of oleic acid. The first set of measurements was performed before induction of lung injury while pigs were breathing spontaneously at ambient Paw, the second after induction of lung injury while breathing spontaneously at ambient Paw, and the third with lung injury and spontaneous breathing with APRV. RESULTS: After induction of lung injury PTPinsp increased from 138 +/- 14 to 214 +/- 32 cm H2O s/min when pigs breathed spontaneously at ambient Paw (p < 0.05) and returned to 128 +/- 27 cm H2O s/min during APRV. While systemic hemodynamics and blood flow to the psoatic and intercostal muscles did not change, diaphragmatic blood flow increased from 0.34 +/- 0.05 before to 0.54 +/- 0.08 mL/g/min after induction of lung injury and spontaneous breathing at ambient Paw (p < 0.05) and returned to 0.32 +/- 0.05 mL/g/min during APRV (p < 0.05 vs spontaneous breathing at ambient Paw [lung injury]). CONCLUSION: Respiratory work and RMBF are increased in acute lung injury when subjects breathe spontaneously at ambient Paw. Supporting spontaneous breathing with APRV decreases respiratory work and RMBF to physiologic values.     

Automatic tube compensation-assisted respiratory rate to tidal volume ratio improves the prediction of weaning outcome

OBJECTIVE: To assess whether the respiratory rate to tidal volume ratio (RVR) measured while receiving automatic tube compensation (ATC) [RVRATC] would have a better predictive value as a weaning measure than unassisted RVR. DESIGN: Prospective cohort study. SETTING: General ICU of a tertiary-care university hospital. PATIENTS: Forty-three patients who received mechanical ventilation for > 24 h and were considered ready for weaning. INTERVENTIONS: All patients underwent a 60-min spontaneous breathing trial (SBT) [positive end-expiratory pressure of 5 cm H(2)O; ATC, 100%]. Patients tolerating the trial (n = 35) were extubated immediately. The following parameters were measured at the onset and end of the SBT: RVR, RVRATC, peak airway pressure (Paw), airway occlusion pressure, and minute ventilation. The outcome measure was successful extubation (ability to maintain spontaneous breathing for > 48 h). MEASUREMENTS AND RESULTS: Median age was 55 years (range, 25 to 88 years), median APACHE (acute physiology and chronic health evaluation) II score was 15.5 (range, 3 to 29), and median duration of mechanical ventilation prior to the SBT was 7 days (range, 1 to 40 days). Extubation was successful in 25 patients (72%). There were no significant differences in baseline characteristics between patients successfully extubated (group 1) and those requiring reintubation. On multivariate analysis, RVRATC measured at 60 min (RVR(60)ATC) was most predictive of successful extubation (p = 0.03). The area under the receiver operator characteristic curve was also highest for RVR(60)ATC (0.81 +/- 0.03) as compared to RVR (0.77 +/- 0.03), RVRATC (0.75 +/- 0.04), and RVR measured at 60 min (0.69 +/- 0.05). The ratio of RVR(60)ATC to Paw was the best predictor (0.84 +/- 0.02). CONCLUSIONS: RVRATC measured at the end of the SBT was the best predictor of successful extubation. A new ratio (ratio of RVRATC to Paw) was most predictive and deserves further study.     

Central fatigue of the rabbit diaphragm

This study evaluates the importance of central fatigue of the diaphragm in rabbits subjected to inspiratory muscle resistive loading (IRL). Ten rabbits were subjected to constant IRL while unanesthetized and breathing supplemental oxygen. During 10–20 minutes of spontaneous breathing against IRL, there were no significant changes in arterial oxygen saturation or in diaphragm contractility, measured by the quasi-static transdiaphragmatic pressure response to a 0.3-sec train of 100 Hz supramaximal phrenic nerve stimuli. After an initial decrease due to application of the load, the minute ventilation decreased further, by an average of 15%, while arterial pCO₂ increased to an average of 59 mmHg (p < 0.05). The normalized diaphragm pressure-time index initially increased from 0.02 to 0.18 during IRL, then decreased an average of 29% (p < 0.05). These results show that severe IRL causes a decrease in the level of diaphragmatic effort over time despite increased chemical drive and despite a preserved ability of the muscle to respond to phrenic nerve stimuli. This adaptation may help to prevent peripheral diaphragm fatigue.     

Effects of aminophylline on diaphragmatic fatigue during acute respiratory failure

The effects of aminophylline on diaphragmatic fatigue and recovery in the face of hypoxemia and hypercapnic acidosis were studied in anesthetized, spontaneously breathing, dogs. The phrenic nerves were stimulated supramaximally at 10, 20, 50, and 100 Hz during 2 s with electrodes placed around the fifth roots, and the resulting transdiaphragmatic pressure (Pdi) was measured with balloon catheters. The dogs were occluded before the stimulations at functional residual capacity. The latter was monitored by measuring the end-expiratory transpulmonary pressure, which remained constant throughout the experiment. Diaphragmatic fatigue was produced by resistive loaded breathing. At the end of the runs, which lasted 15 +/- 2 min, all the dogs were severely hypoxemic (30 +/- 5 mmHg), hypercapnic (65 +/- 4 mmHg), and acidotic (7.1 +/- 0.05). During the fatigue runs, phrenic stimulation resulted in a marked decrease in Pdi, which amounted at 20 Hz to 70 +/- 8% and 45 +/- 12% of the control values 5 min after the onset of the fatigue runs and at the end, respectively. After recovery (3 h), Pdi and arterial blood gas determinations returned to control values. Identical fatigue runs were repeated with aminophylline infusion (loading dose, 6 mg/kg in 10 min and maintenance dose, 1 mg/kg/h), leading to a plasmatic concentration of 16.4 +/- 2 mg/l. Aminophylline protected the diaphragm against fatigue, and despite the presence of hypoxemia and hypercapnic acidosis, the Pdi generated for a 20 Hz stimulation of the phrenic nerves at identical times of the preceding run amounting to 100 +/- 15% and 85 +/- 10% of control values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Snoring during NREM sleep: respiratory timing, esophageal pressure and EEG arousal

Eight men who were regular heavy snorers were monitored while awake and during nocturnal sleep. All subjects were known to be free of lung disease, obstructive sleep apnea syndrome, and oxygen drops during sleep. For each subject, two snoring periods of 3-31 min with a mean of 12.7 min were randomly selected for comparison with periods of normal, non-snoring NREM sleep breathing. A mean of 150 respiratory cycles per period were analyzed. For each respiratory cycle, respiratory inductive plethysmography and measurements of peak flow, laryngeal sounds, and esophageal pressure (Pes) were used to calculate breathing frequency (bf), inspiratory time (Ti), expiratory time (Te), total respiratory cycle length (Ttot), and Pes at its nadir. During NREM sleep silent breathing, the Ti/Te ratio was analogous to that already measured in normal subjects. With the onset of snoring, an immediate increase in Ti, Te, and Pes nadir were noted. Mean peak Pes nadir increased 120 +/- 37%, and mean Ttot increased by 18%. Through the duration of the snoring period, a further increase in Ti (mean = 10.4 +/- 3.4%) and a decrease in Te were noted, with a mean change in Ti/Ttot of 12 +/- 3.1%. The shape of the esophageal pressure wave during expiration shifted from its normal dynamics. The percentage of Te decreased by a mean of -9.8 +/- 2.3% (P less than 0.0001), and the rise time in Pes increased a mean of 37%. When Pes nadir was the most negative, a mean peak flow decrease of 43 +/- 13.6% from baseline was observed. Tidal volume had decreased by a mean of 22% and minute ventilation by a mean of 21% at the end of the snoring period. Separate investigation of each subject indicates that the evolutions of Ti, Te and Pes during snoring were not the same for all subjects. At least two different groups of snorers exist; these groups may be differentiated by the evolution of Pes over time during snoring. Modifications in the 'braking' role of inspiratory muscles during expiration may explain the changes in the Pes wave dynamics snoring which lead to repetitive EEG arousals, termination of snoring periods, and some sleep fragmentation.     

Determinants of rib motion in flail chest

We have previously developed a canine model of isolated flail chest to assess the effects of this condition on the mechanics of breathing, and these studies have led to the conclusion that the respiratory displacement of the fractured ribs is primarily determined by the fall in pleural pressure (Delta Ppl) and the action of the parasternal intercostal muscles. The present studies were designed to test the validity of this conclusion. A flail was induced in six supine anesthetized animals by fracturing both dorsally and ventrally the second to fifth ribs on the right side of the chest, after which the phrenic nerve roots were bilaterally sectioned in the neck. Sectioning the phrenic nerves caused a 34% decrease in Delta Ppl, associated with a 39% increase in parasternal intercostal inspiratory EMG activity (p < 0.05), and resulted in a marked reduction in the inspiratory inward displacement of the ribs. In three animals, the inward rib displacement was even reversed into a small outward displacement. When the airway was then occluded at end-expiration to increase Delta Ppl during the subsequent inspiration, all animals again showed a clear-cut inward rib displacement. These observations therefore confirm that in dogs with flail chest, the inspiratory displacement of the fractured ribs is set by the balance between the force related to pleural pressure and that generated by the parasternal intercostals. These observations also point to the critical importance of the pattern of inspiratory muscle activation in determining the magnitude of rib cage paradox in such patients.     

Airway anesthesia during positive and negative inspiratory pressure breathing in man.

We have measured the effects of airway anesthesia (aerosolized 5% lidocaine) on the respiratory pattern during positive or negative inspiratory pressure in 8 resting subjects. The subjects breathed through a 600 ml dead space (peak inspiratory airway pressure, Paw = -2 cmH2O) without or with negative (approx. -5 or -10 cmH2O) or positive (approx. +5 or +10 cmH2O) inspiratory pressure, provided by a laminar flow resistance or a positive pressure source, respectively. Control measurements were performed before and after measurements with airway anesthesia. Measurements included tidal volume, respiratory frequency, ventilation, inspiratory and expiratory duration, occlusion pressure (P0.1) and end-tidal PCO2. None of the parameters measured was significantly altered by airway anesthesia, which was effective in suppressing the cough reflex. We conclude that information from lung afferents that are suppressed with the elimination of the cough reflex is not important for the breathing pattern during resting ventilation with elevated tidal volume (dead space load) and with positive or negative inspiratory pressure.     

Low-dose acetazolamide does affect respiratory muscle function in spontaneously breathing anesthetized rabbits

Patients with chronic obstructive pulmonary diseases (COPD) and/or central sleep apnea are sometimes treated with the carbonic anhydrase inhibitor acteazolamide to improve blood gas values. Studies have shown that this agent may have a complicated effect on lung ventilation, because carbonic anhydrase has a widespread distribution within the body, particularly in tissues involved in the control of breathing. To investigate whether acetazolamide may have (neuro)muscular effects on respiration, we measured the responses of ventilation, phrenic nerve activity, and transpulmonary pressure to changes in arterial PCO2 before and after intravenous administration of a low-dose (4.6 +/- 0.2 mg x kg(-1), mean +/- SEM) of this inhibitor in anesthetized spontaneously breathing rabbits. The agent decreased the mean resting end-tidal PCO2 by 1 kPa and increased ventilation from 258 +/- 15 to 292 +/- 14 ml x min(-1) x kg(-1) (p < or = 0.05). The ventilatory and tidal volume responses to CO2 were reduced, and the response curves were shifted to lower PCO2 values. At the level of phrenic activity, however, the response was shifted leftward without altering CO2 sensitivity. With an unchanged lung compliance, the slopes of the relationships between tidal volume and phrenic activity and that between the tidal change in transpulmonary pressure and phrenic amplitude were both reduced by about 40%, indicating an action of acetazolamide on (neuro)muscular level. The results raise the suggestion that treatment of some hypercapnic COPD patients with acetazolamide may have undesired clinical implications, particularly in those with already weakened respiratory muscles.     

Proportional assist ventilation. Results of an initial clinical trial.

The response to proportional assist ventilation (PAV) was tested in four normal subjects during heavy exercise and in five ventilator-dependent patients recovering from assorted medical disorders. The apparatus consisted of a rolling-seal piston coupled to a motor that generated pressure in proportion to inspired flow and inspired volume, with the gains adjusted such that the proportionality between airway pressure (Paw) and instantaneous patient-generated pressure (Pmus) was approximately 1:1 (i.e., machine-amplified patient effort by a factor of 2). Normal subjects responded to PAV by decreasing their own effort, as judged from esophageal pressure, such that the changes in ventilation and breathing pattern were rather small (VE: 64.8 +/- 3.6 during PAV versus 56.0 +/- 4.3, p less than 0.01; VT: 2.39 +/- 0.24 versus 2.02 +/- 0.17, p less than 0.05; f: 27.5 +/- 1.9 versus 28.0 +/- 2.2, NS). In patients, elastance ranged from 20 to 35 cm H2O cm/L, resistance ranged from 5 to 10 cm H2O/L/s, and maximal inspiratory pressure ranged from -16 to -65 cm H2O. After a period of observation during synchronized intermittent mechanical ventilation (SIMV) the patient was switched to PAV and maintained on it for 1 to 3 h. No patient had to be replaced on SIMV because of discomfort or deterioration in any of the monitored variables. During PAV peak airway pressure was less than half the value observed with the IMV breaths (16.6 +/- 2.4 versus 35.4 +/- 3.4 cm H2O, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory and skeletal muscles in hypogonadal men with chronic obstructive pulmonary disease

Hypogonadism, found in about one-third of patients with chronic obstructive pulmonary disease (COPD), has potential for decreasing muscle mass and muscle performance. Compared with eugonadal patients, we hypothesized that hypogonadal patients with COPD have decreased respiratory and skeletal muscle performance. Nineteen hypogonadal and 20 eugonadal men with COPD (FEV(1) 1.14 +/- 0.08 and 1.17 +/- 0.11 L [standard error], respectively) were studied. Diaphragmatic contractility, assessed as transdiaphragmatic twitch pressure generated by phrenic nerve stimulation, was similar in hypogonadal and eugonadal patients: 20.6 +/- 2.2 and 19.8 +/- 2.5 cm H(2)O, respectively. During progressive inspiratory threshold loading, hypogonadal and eugonadal patients had similar respiratory muscle endurance times (302 +/- 29 and 313 +/- 48 seconds, respectively) and airway pressure sustained during the last minute of loading (38.2 +/- 3.0 and 40.5 +/- 4.7 cm H(2)O, respectively) (similar to predicted values in healthy subjects). Hypogonadal and eugonadal patients had equivalent limb muscle strength and endurance. During cycle exercise to exhaustion, exercise performance, gas exchange, and respiratory muscle recruitment (estimated by esophageal and gastric pressure swings during tidal breathing) were similar in both groups. In conclusion, hypogonadism does not decrease respiratory or limb muscle performance and exercise capacity in men with moderate-to-severe COPD who, for the most part, are not underweight.