Respiratory muscle function and control of breathing in patients with acromegaly

Increase in lung size has been described in acromegalic patients, but data on respiratory muscle function and control of breathing are relatively scarce. Lung volumes, arterial blood gas tensions, and respiratory muscle strength and activation during chemical stimulation were investigated in a group of 10 patients with acromegaly, and compared with age- and sex-matched normal controls. Inspiratory muscle force was evaluated by measuring pleural (Ppl,sn) and transdiaphragmatic (Pdi,sn) pressures during maximal sniffs. Dynamic pleural pressure swing (Ppl,sw) was expressed both as absolute value and as percentage of Ppl,sn. Expiratory muscle force was assessed in terms of maximal expiratory pressure (MEP). In 8 of the 10 patients, ventilatory and respiratory muscle responses to hyperoxic progressive hypercapnia and to isocapnic progressive hypoxia were also evaluated. Large lungs, defined as total lung capacity (TLC) greater than predicted (above 95% confidence limits), were found in five patients. Inspiratory or expiratory muscle force was below normal limits in all but three patients. During unstimulated tidal breathing, respiratory frequency (fR) and mean inspiratory flow (tidal volume/inspiratory time (VT/tI)) were greater, while inspiratory time (tI) was shorter than in controls. Minute ventilation (V'E) and mean inspiratory flow response slopes to hypercapnia were normal In contrast, four patients had reduced delta(VT/tI)/arterial oxygen saturation (Sa,O2) and three had reduced deltaV'E/Sa,O2. Ppl,sw(%Ppl,sn) response slopes to increasing end-tidal carbon dioxide tension (PET,CO2) and decreasing Sa,O2 did not differ from the responses of the normal subjects, suggesting normal central chemoresponsiveness. At a PET,CO2 of 8 kPa or an Sa,O2 of 80%, patients had greater fR and lower tI compared with controls. Pdi,sn and Ppl,sn related both to deltaV'E/deltaSa,O2 (r=0.729 and r=0.776, respectively) and delta(VT/tI)/deltaSa,O2 (r=0.860 and r=0.90, respectively). Pdi,sn also related both to deltaV'E/deltaPET,CO2 (r=0.8) and delta(VT/tI)/deltaPET,CO2 (r=0.76). In conclusion, the data suggest the relative independence of pneumomegaly and respiratory muscle strength. Peripheral (muscular) factors appear to modulate a normal central motor output to give a more rapid pattern of breathing.     

Effects of chest wall counterpressures on lung mechanics under high levels of CPAP in humans

We assessed the respective effects of thoracic (TCP) and abdominal/lower limb (ACP) counterpressures on end-expiratory volume (EEV) and respiratory muscle activity in humans breathing at 40 cmH2O of continuous positive airway pressure (CPAP). Expiratory activity was evaluated on the basis of the inspiratory drop in gastric pressure (DeltaPga) from its maximal end-expiratory level, whereas inspiratory activity was evaluated on the basis of the transdiaphragmatic pressure-time product (PTPdi). CPAP induced hyperventilation (+320%) and only a 28% increase in EEV because of a high level of expiratory activity (DeltaPga = 24 +/- 5 cmH2O), contrasting with a reduction in PTPdi from 17 +/- 2 to 9 +/- 7 cmH2O . s-1 . cycle-1 during 0 and 40 cmH2O of CPAP, respectively. When ACP, TCP, or both were added, hyperventilation decreased and PTPdi increased (19 +/- 5, 21 +/- 5, and 35 +/- 7 cmH2O . s-1 . cycle-1, respectively), whereas DeltaPga decreased (19 +/- 6, 9 +/- 4, and 2 +/- 2 cmH2O, respectively). We concluded that during high-level CPAP, TCP and ACP limit lung hyperinflation and expiratory muscle activity and restore diaphragmatic activity.     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

Hemodynamic changes in patients developing effective hypovolemia after total paracentesis

BACKGROUND/AIMS: In many centers paracentesis is considered the treatment of choice for tense ascites. However, the mechanism of effective hypovolemia after paracentesis, the main complication associated with this procedure, remains unknown. In the current study, systemic hemodynamics was sequentially studied before and after total paracentesis in 46 patients with cirrhosis and tense ascites. The aim of the study was to assess the mechanism of effective hypovolemia after paracentesis. METHODS: Plasma renin activity and aldosterone, mean arterial pressure, cardiac output (ECO-Doppler) and systemic vascular resistance were measured before, and 3 h, 6 h and 6 days after total paracentesis associated with plasma volume expansion. RESULTS: Effective hypovolemia after paracentesis (defined as 50% increase in plasma renin activity up to a level over 4 ng x m(-1) x h(-1) at the 6th day after paracentesis) occurred in 20 cases [plasma renin activity increased from 8+/-17 to 19+/-2.7 ng x m(-1) x h(-1)]. In the remaining 26 cases no changes in plasma renin activity [8.5+/-2.4 vs. 8.7+/-2.2 ng x m(-1) x h(-1)] were observed. The amounts of ascitic fluid volume removed were similar. Effective hypovolemia after paracentesis was associated with a significant decrease in mean arterial pressure (89+/-2 vs. 81+/-3 mmHg) and systemic vascular resistance [1263+/-67 vs. 1014+/-80 dyn x s(-1) x cm(-5)] 6 days after treatment. In contrast, no significant changes in these parameters were observed in patients not developing this complication. In the whole group of patients a significant inverse relation was observed between changes in plasma renin activity and in systemic vascular resistance (r=0.74;p< 0.001). CONCLUSIONS: These results indicate that effective hypovolemia after paracentesis in cirrhosis is predominantly due to an accentuation of the arteriolar vasodilation already present in these patients.     

Expiratory flow limitation and intrinsic positive end-expiratory pressure in obesity

Breathing at very low lung volumes might be affected by decreased expiratory airflow and air trapping. Our purpose was to detect expiratory flow limitation (EFL) and, as a consequence, intrinsic positive end-expiratory pressure (PEEPi) in grossly obese subjects (OS). Eight OS with a mean body mass index (BMI) of 44 +/- 5 kg/m2 and six age-matched normal-weight control subjects (CS) were studied in different body positions. Negative expiratory pressure (NEP) was used to determine EFL. In contrast to CS, EFL was found in two of eight OS in the upright position and in seven of eight OS in the supine position. Dynamic PEEPi and mean transdiaphragmatic pressure (mean Pdi) were measured in all six CS and in six of eight OS. In OS, PEEPi increased from 0.14 +/- 0.06 (SD) kPa in the upright position to 0.41 +/- 0.11 kPa in the supine position (P < 0.05) and decreased to 0.20 +/- 0.08 kPa in the right lateral position (P < 0.05, compared with supine), whereas, in CS, PEEPi was significantly smaller (<0.05 kPa) in each position. In OS, mean Pdi in each position was significantly larger compared with CS. Mean Pdi increased from 1.02 +/- 0.32 kPa in the upright position to 1.26 +/- 0.17 kPa in the supine position (not significant) and decreased to 1. 06 +/- 0.26 kPa in the right lateral position (P < 0.05, compared with supine), whereas there were no significant changes in CS. We conclude that in OS 1) tidal breathing can be affected by EFL and PEEPi; 2) EFL and PEEPi are promoted by the supine posture; and 3) the increased diaphragmatic load in the supine position is, in part, related to PEEPi.     

Relationship of rib cage and abdomen motion to diaphragm function during quiet breathing

Although rib cage (RC) and abdomen (Ab) motion is believed to reflect intercostal and diaphragm contributions to breathing, systematic investigations have failed to confirm this. We measured inspiratory changes in RC and Ab anterior-posterior diameter (delta RC and delta Ab) both corrected for volume equivalence (isovolume) and not corrected (isodistance, observed), and correlated these with simultaneous changes in gastric (delta Pab) and esophageal (delta Ppl) pressure: delta Pab - delta Ppl = delta Pdi, the change in transdiaphragmatic pressure. The delta Pab/delta Pdi was used as an index of the relative contribution of diaphragm motion to the breathing process. Relative abdomen motion was expressed as delta Ab/(delta Ab + delta RC). Isodistance and isovolume delta Ab/(delta Ab + delta RC) correlated, R = 0.69; observed abdomen motion overestimated abdomen-diaphragm contribution to tidal volume. Isodistance delta Ab/(delta Ab + delta RC) was less for women than men; isovolume delta Ab/(delta Ab + delta RC) was similar for the two sexes. Among individuals, isodistance delta Ab/(delta Ab + delta RC) correlated with delta Pab/delta Pdi (R = 0.73, P less than 0.001). Within a given individual, the mean R for seven subjects for delta Pab/delta Pdi vs delta Ab/(delta Ab + delta RC) was 0.90. We conclude that observed rib cage and abdomen motion reflects intercostal and diaphragm contributions to breathing; the correlation is better within a given subject than among individuals.     

Effects of positive end-expiratory pressure on right ventricular function in COPD patients during acute ventilatory failure

OBJECTIVE: To examine the effects of external positive end-expiratory pressure (PEEP) on right ventricular function in chronic obstructive pulmonary disease (COPD) patients with intrinsic PEEP (PEEPi). DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Seven mechanically ventilated flow-limited COPD patients (PEEPi = 9.7 +/- 1.3 cmH2O, mean +/- SD) with acute respiratory failure. INTERVENTION: Hemodynamic and respiratory mechanic data were collected at four different levels of PEEP (0-5-10-15 cmH2O). MEASUREMENTS AND RESULTS: Hemodynamic parameters were obtained by a Swan-Ganz catheter with a fast response thermistor. Cardiac index (CI) and end-expiratory lung volume (EELV) reductions started simultaneously when the applied PEEP was approximately 90% of PEEPi measured on 0 cmH2O (ZEEP). Changes in transmural intrathoracic pressure (PEEPi,cw) started only at a PEEP value much higher (120%) than PEEPi. The reduction in CI was related to a decrease in the right end-diastolic ventricular volume index (RVEDVI) (r = 0.61; p < 0.001). No correlation between CI and transmural right atrial pressure was observed. The RVEDVI was inversely correlated with PEEP-induced changes in EELV (r = -55; p < 0.001), but no with PEEPi,cw (r = -0.08; NS). The relationship between RVEDVI and right ventricular stroke work index, considered an index of contractility, was significant in three patients, i.e., PEEP did not change contractility. In the other patients, an increase in contractility seemed to occur. CONCLUSIONS: In COPD patients an external PEEP exceeding 90% of PEEPi causes lung hyperinflation and reduces the CI due to a preload effect. The reduction in RVEDVI seems related to changes in EELV, rather than to changes in transmural pressures, suggesting a lung/heart volume interaction in the cardiac fossa. Thus, in COPD patients, application of an external PEEP level lower than PEEPi may affect right ventricular function.     

Possible existence of quaternary structure in the high-affinity serotonin transport complex

During exercise, dynamic hyperinflation-induced intrinsic positive end-expiratory pressure (PEEPi) and decreased dynamic lung compliance (CL,dyn) of patients with chronic obstructive pulmonary disease (COPD) increase the elastic work of inspiration (Wi) more than would be predicted from the increase in tidal volume (VT). This contributes significantly to their exertional breathlessness. In 10 stable patients with COPD, the dynamic Wi was measured during incremental bicycle exercise to exhaustion. The total Wi was then partitioned into the portion required to overcome PEEPi (Wi,PEEPi) and nonPEEPi elastic load (Wi,nonPEEPi). The latter is used to overcome the increase in the total respiratory system elastance during inflation. From resting breathing to peak exercise, Wi more than doubled (p<0.001). This increase was largely due to Wi,PEEPi, which significantly rose from 1.7+/-0.3 to 5.3+/-0.8 L x cm H2O(-1) (p<0.001). In comparison, Wi,nonPEEPi increased from only 3.0+/-0.4 to 5.1+/-0.5 L x cm H2O(-1) (p<0.01). Consequently, Wi,PEEPi as a fraction of total Wi increased from 35.5+/-5.6 to 51.0+/-3.3% (p<0.02). In addition, the measured Wi,nonPEEPi at peak exercise, when expressed as a percentage of its value during resting breathing, was 25% more than that predicted from the increase in VT alone. Assuming a constant chest wall compliance, this can be attributed to the exercise-induced decrease in CL,dyn, which was 0.27+/-0.04 and 0.17+/-0.02 L x cm H2O(-1) (p<0.01), respectively, during resting breathing and peak exercise. In conclusion, the dynamic hyperinflation-induced intrinsic positive end-expiratory pressure is more important than the increase in tidal volume in raising the work of inspiration during exercise in patients with chronic obstructive pulmonary disease; the decrease in dynamic lung compliance plays a definite but less important role.     

Cardiovascular, renal, and neurohumoral responses to single large-volume paracentesis in patients with cirrhosis and diuretic-resistant ascites

OBJECTIVE: Large volume paracentesis is an effective treatment for refractory ascites, but the need for routine infusion of albumin or other volume expanders remains controversial. The aim of this study was to assess the short term effects of a single 5-L paracentesis without albumin replacement on total central blood volume, systemic and renal hemodynamics, sodium homeostasis, and neurohumoral factors. PATIENTS AND METHODS: Twelve patients with biopsy-proven cirrhosis and tense, diuretic-resistant ascites were studied before and 48 h after a single 5-L paracentesis without albumin infusion. Systemic hemodynamics and total central blood volume were assessed using radionuclide angiography. Glomerular filtration rate and effective renal plasma flow were measured by inulin and para-aminohippurate clearances, respectively. Lithium clearance was used as an index of proximal tubular reabsorption of sodium. In addition, plasma concentrations of neurohumoral factors were determined. RESULTS: Total central blood volume was 2.41 +/- 0.33 L/m2 (mean +/- SEM) before and 2.34 +/- 0.18 L/m2 48 h after large volume paracentesis (p = 0.76). Similarly, no differences were detected in the cardiac index, glomerular filtration rate, effective renal plasma flow, urinary sodium excretion, hematocrit, plasma renin activity, or concentrations of plasma aldosterone, norepinephrine, or atrial natriuretic factor. CONCLUSIONS: A single large volume paracentesis without albumin replacement causes no disturbances in systemic and renal hemodynamics 48 h after the procedure. These results suggest that a single 5-L paracentesis without albumin infusion is a safe and satisfactory short term option for the management of patients with cirrhosis and tense, diuretic-resistant ascites.     

Respiratory mechanics in normal hamsters

Lung volumes and quasi-static deflation volume-pressure relationships were measured in male golden hamsters anesthetized with pentobarbital. Volume was measured with a pressure plethysmograph, and pleural pressure was estimated by the use of a water-filled esophageal catheter. Mean body weight +/- SE was 122.3 +/-3.0 g, mean lung weight was 0.74 +/- 0.2 g or about 0.6% of body weight. Mean lung volume at 25 cmH2O transpulmonary pressure (TLC25) was 7.2 +/- 0.14 ml, 9.78 +/- 0.17 ml/g lung weight or 5.92 +/- 0.06 ml/100 g body weight. Mean functional residual capacity was 2.4 +/- 0.06 ml or 33.3% of TLC25. Mean vital capacity was 5.2 +/- 0.13 ml. Mean quasi-static compliance of lung was 0.63 +/- 0.03 ml/cmH2O. Chord compliance of chest wall between lung volumes of 1 and 4 ml above RV was 3.39 +/- 0.53 ml/cmH2O. At FRC, the chest wall recoiled inward, so that pleural pressure was positive (1.4 +/- 0.13 cmH2O) and the lung was resisting further collapse. The slope of the lung's deflation volume-pressure curve changed at FRC, ERV was small (0.36 +/- 0.03 ml), and RV was determined by complete airway closure. Thus the mechanisms determining FRC are unusual and include an influence of airway closure.     

Effects of fenoterol on inspiratory effort sensation and fatigue during inspiratory threshold loading

We studied the effects of a single dose of fenoterol on the relationship between inspiratory effort sensation (IES) and inspiratory muscle fatigue induced by inspiratory threshold loading in healthy subjects. The magnitude of the threshold was 60% of maximal static inspiratory mouth pressure (PI,mmax) at functional residual capacity, and the duty cycle was 0.5. Subjects continued the threshold loaded breathing until the target mouth pressure could no longer be maintained (endurance time). The intensity of the IES was scored with a modified Borg scale. Either fenoterol (5 mg) or a placebo was given orally 2 h before loading in a randomized double-blind crossover protocol. The endurance time with fenoterol (34.4 +/- 8.6 min) was longer than that with the placebo (22.2 +/- 7.1 min; P < 0.05). The ratio of high- to low-frequency power of the diaphragmatic electromyogram (EMGdi) decreased during loading; the decrease was less with fenoterol (P < 0.05). The EMGdi also decreased with loading; the decrease was greater on fenoterol treatment (P < 0.01). The PI,mmax and maximal transdiaphragmatic pressure (Pdi) were similarly decreased after loading on either treatment. The intensity of the IES rose with time during loading in both groups but was lower with fenoterol than with the placebo (P < 0.05). The ratio of Pdi to integrated activity of the EMGdi increased with fenoterol (P < 0.05). Fenoterol treatment increased both superimposed Pdi twitch and Pdi twitch of relaxed diaphragm and decreased the value of (1-superimposed Pdi twitch/Pdi twitch of relaxed diaphragm). Thus we conclude that in normal subjects fenoterol reduces diaphragmatic fatigue and decreases the motor command to the diaphragm, resulting in a decrease in IES during inspiratory threshold loading and a prolongation of endurance.     

Use of mouth pressure twitches induced by cervical magnetic stimulation to assess voluntary activation of the diaphragm

There is a need for a simple method to assess the adequacy of diaphragm activation during voluntary inspiratory efforts in patients with suspected respiratory muscle weakness. We have compared mouth (Pmo,t), oesophageal (Poes,t) and transdiaphragmatic (Pdi,t) twitch pressure elicited by cervical magnetic stimulation (CMS) in five normal men (mean (SD) age 32.2 (1.8) yrs) on two separate study days. Single magnetic stimuli were delivered at functional residual capacity during relaxation and during graded voluntary inspiratory efforts against a closed airway. As voluntary-effort transdiaphragmatic and oesophageal pressure increased, Pdi,t and Poes,t decreased linearly (r range, respectively, 0.82-0.98 and 0.87-0.95). During relaxation, Pmo,t was unreliable due to the poor transmission of intrathoracic pressure, but during inspiratory efforts, the relation between voluntary mouth pressure and Pmo,t was also linear (r range 0.84-0.95). On average, our subjects voluntarily generated 99, 100 and 102% of the maximum transdiaphragmatic, oesophageal and mouth pressures predicted by the respective linear regression equations. Pmo,t was correlated to both Poes,t and Pdi,t during inspiratory efforts, but not during relaxation. These studies confirm that twitch pressures induced by CMS during inspiratory efforts can be assessed at the mouth in normal subjects, providing a simple and non-invasive technique for assessing diaphragm activation during voluntary inspiratory efforts. Potentially, this technique could be made more sensitive and accurate and applied to detect submaximal efforts in patients.     

The laryngeal mask airway and positive-pressure ventilation

BACKGROUND: The utility of the laryngeal mask airway during positive-pressure ventilation has yet to be determined. Our study was designed to assess whether significant leaks occurred with positive-pressure ventilation and if leaks were associated with gastroesophageal insufflation. METHODS: Forty-eight patients undergoing elective surgery were studied. After induction of anesthesia and paralysis, controlled ventilation was used with four different peak pressure settings in each patient (15, 20, 25, and 30 cmH2O). The order of ventilator pressure settings was assigned from a randomized block schedule. Data collected included inspiratory and expiratory volumes, qualitative assessments of gastroesophageal insufflation, and leak at the neck. After data collection during laryngeal mask use, the anesthesiologist intubated the trachea and measurements were repeated for tracheal tube ventilation. Leak was calculated by subtracting the expiratory from the inspiratory volume and expressed as a fraction of the inspiratory volume. RESULTS: Ventilation with the laryngeal mask airway was adequate at all ventilation pressures and comparable with tracheal tube ventilation. Leak fraction (mean +/- SD) at 15, 20, 25, and 30 cmH2O for laryngeal mask ventilation were 0.13 +/- 0.15, 0.21 +/- 0.18, 0.25 +/- 0.16 and 0.27 +/- 0.17, respectively, and 0.03 +/- 0.03, 0.05 +/- 0.03, 0.05 +/- 0.03 and 0.04 +/- 0.03, respectively, for tracheal tube ventilation. Leak fractions for ventilation with the laryngeal mask were consistently greater than those measured for tracheal tube ventilation at similar ventilation pressures. Leak fraction with laryngeal mask ventilation increased with increasing airway pressures, whereas leak with tracheal tube ventilation remained unchanged. The frequency of gastroesophageal insufflation ranged from 2.1% at a ventilation pressure of 15 cmH2O to 35.4% at 30 cmH2O. CONCLUSIONS: Ventilation using the laryngeal mask appears to be adequate if airway resistance and pulmonary compliance are normal. Gastroesophageal insufflation of air will become a problem in the presence increased ventilation pressure.     

Physiological determinants of inspiratory effort sensation during CO2 rebreathing in normal subjects

1. The physiological basis of inspiratory effort sensation remains uncertain. Previous studies have suggested that pleural pressure, rather than inspiratory muscle fatigue, is the principal determinant of inspiratory effort sensation. However, only a limited range of inspiratory flows and breathing patterns have been examined. We suspected that inspiratory effort sensation was related to the inspiratory muscle tension-time index developed whatever the breathing pattern or load, and that this might explain the additional rise in sensation seen with hypercapnia. 2. To investigate this we measured hypercapnic rebreathing responses in seven normal subjects (six males, age range 21-38 years) with and without an inspiratory resistive load of 10 cm H2O. Pleural and transdiaphragmatic pressures, mouth occlusion pressure and breathing pattern were measured. Diaphragmatic and ribcage tension-time indices were calculated from these data. Inspiratory effort sensation was recorded using a Borg scale at 30s intervals during each rebreathing run. 3. Breathing pattern and inspiratory pressure partitioning were unrelated to changes in inspiratory effort sensation during hypercapnia. Tension-time indices reached pre-fatiguing levels during both free breathing and inspiratory resistive loading. 4. Stepwise multiple regression analysis using pooled mechanical, chemical and breathing pattern variables showed that pleural pressure was more closely related to inspiratory effort sensation than was transdiaphragmatic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of ventricular fluid osmolality on bulk flow of nascent fluid into the cerebral ventricles of cats

Transdiaphragmatic pressure (Pdi) and expiratory flow (V) were monitored during vital capacity single breath N2 washouts in 7 seated subjects. Transient increases in V were produced (1) actively, by subjects increasing mouth pressure while expiring through a constant resistance of (2) passively, by the operator transiently decreasing the resistance. Voluntary contraction of the diaphragm (increased Pdi) was achieved when abdominal muscles were tensed while maintaining V constant. In 5 subjects a transient increase in Pdi of 25-150 cm H2O consistently produced a transient increase in expired N2 concentration of 1.80 +/- 0.06% (Mean +/- 1 SE); in 1 subject N2 concentration decreased by 0.8% to 2.7% N2, and in one subject the alveolar plateau was uninfluenced by changes in Pdi. Passive increases in V up to 21/sec had no effect on FEN2 in any of the subjects. Active increase in V changed FEN2 only when associated with increases in Pdi. Qualitatively similar results were obtained during helium (He) bolus washouts. However, whereas diaphragmatic contraction, maintained throughout expiration, had no measurable influence on the N2 washout, it changed the slope of the He alveolar plateau in 6 out of 7 subjects. We conclude that in normal subjects the alveolar N2 plateau is relatively insensitive to flow variations up to 21/sec. The fluctuations in FEN2 observed when the expiratory flow is varied are due to concomittant changes in Pdi. We propose that diaphragmatic contraction changes the pattern of lung emptying by altering the vertical gradient of pleural pressure.     

Phrenic motoneuron discharge during sustained inspiratory resistive loading

I determined whether prolonged inspiratory resistive loading (IRL) affects phrenic motoneuron discharge, independent of changes in chemical drive. In seven decerebrate spontaneously breathing cats, the discharge patterns of eight phrenic motoneurons from filaments of one phrenic nerve were monitored, along with the global activity of the contralateral phrenic nerve, transdiaphragmatic pressure, and fractional end-tidal CO2 levels. Discharge patterns during hyperoxic CO2 rebreathing and breathing against an IRL (2,500-4,000 cmH2O.1-1.s) were compared. During IRL, transdiaphragmatic pressure increased and then either plateaued or decreased. At the highest fractional end-tidal CO2 common to both runs, instantaneous discharge frequencies in six motoneurons were greater during sustained IRL than during rebreathing, when compared at the same time after the onset of inspiration. These increased discharge frequencies suggest the presence of a load-induced nonchemical drive to phrenic motoneurons from unidentified source(s).     

Mechanical advantage of the canine diaphragm

The mechanical advantage (mu) of a respiratory muscle is defined as the respiratory pressure generated per unit muscle mass and per unit active stress. The value of mu can be obtained by measuring the change in the length of the muscle during inflation of the passive lung and chest wall. We report values of mu for the muscles of the canine diaphragm that were obtained by measuring the lengths of the muscles during a passive quasistatic vital capacity maneuver. Radiopaque markers were attached along six muscle bundles of the costal and two muscle bundles of the crural left hemidiaphragms of four bred-for-research beagle dogs. The three-dimensional locations of the markers were obtained from biplane video-fluoroscopic images taken at four volumes during a passive relaxation maneuver from total lung capacity to functional residual capacity in the prone and supine postures. Muscle lengths were determined as a function of lung volume, and from these data, values of mu were obtained. Values of mu are fairly uniform around the ventral midcostal and crural diaphragm but significantly lower at the dorsal end of the costal diaphragm. The average values of mu are -0.35 +/- 0.18 and -0.27 +/- 0.16 cmH2O. g-1. kg-1. cm-2 in the prone and supine dog, respectively. These values are 1. 5-2 times larger than the largest values of mu of the intercostal muscles in the supine dog. From these data we estimate that during spontaneous breathing the diaphragm contributes approximately 40% of inspiratory pressure in the prone posture and approximately 30% in the supine posture. Passive shortening, and hence mu, in the upper one-third of inspiratory capacity is less than one-half of that at lower lung volume. The lower mu is attributed primarily to a lower abdominal compliance at high lung volume.     

Heavy snoring with upper airway resistance syndrome may induce intrinsic positive end-expiratory pressure

We studied eight heavy snorers with upper airway resistance syndrome to investigate potential effects of sleep on expiratory airway and lung resistance, intrinsic positive end-expiratory pressure, hyperinflation, and elastic inspiratory work of breathing (WOB). Wakefulness and non-rapid-eye-movement sleep with high- and with low-resistance inspiratory effort (H-RIE and L-RIE, respectively) were compared. No differences in breathing pattern were seen across the three conditions. In contrast, we found increases in expiratory airway and lung resistance during H-RIE compared with L-RIE and wakefulness (56 +/- 24, 16 +/- 4, and 11 +/- 4 cmH2O . 1(-1) . s, respectively), with attendant increases in intrinsic positive end-expiratory pressure (5.4 +/- 1.8, 1.4 +/- 0.5, and 1.3 +/- 1.3 cmH2O, respectively) and elastic WOB (6.1 +/- 2.2, 3.7 +/- 1.2, and 3.4 +/- 0.7 J/min, respectively). The increase in WOB during H-RIE is partly caused by the effects of dynamic pulmonary hyperinflation produced by the increased expiratory resistance. Contrary to the Starling model, a multiple-element compliance model that takes into account the heterogeneity of the pharynx may explain flow limitation during expiration.     

Subanesthetic concentrations of isoflurane suppress learning as defined by the category-example task

It has been shown that chronic oral steroid therapy (ST) does not induce respiratory muscle dysfunction in normal and asthmatic subjects. As corticosteroids are sometimes chronically used in the treatment of the patients with chronic obstructive pulmonary disease (COPD), the aim of our study was to verify whether ST could cause respiratory muscle impairment and, since ST also affects the central nervous system, whether ST could influence the ventilatory pattern. We retrospectively studied 12 COPD patients (group A), on long-term therapy (for at least 4 consecutive months, range 4-18 months) with an oral steroid, deflazacort, 15 mg.d-1. The subjects were strictly matched, with regard to age, sex, height, weight, forced expiratory volume in one second (FEV1), residual volume (RV), arterial oxygen tension (PaCO2), arterial carbon dioxide tension (PaCO2) and pH, with 12 COPD patients (Group B) who had never taken oral steroids. To assess respiratory muscle strength, we measured maximal inspiratory (MIP) and expiratory (MEP) pressures, while mouth occlusion pressure (P0.1) was employed to assess neuromuscular drive; ventilatory pattern and airway impedence were also evaluated. Effectiveness of ST was confirmed by the plasmatic levels of endogenous cortisol. No significant differences were observed between the two groups with regard to MIP (A 72.2 +/- 9.7 vs B: 70 +/- 7.2 cmH2O) and MEP (A 91.6 +/- 10.5 vs B 94.4 +/- 7.6 cmH2O) whilst P0.1 was significantly higher in group A (2.6 +/- 0.3 cmH2O) than in group B (1.8 +/- 0.1 cmH2O). No significant differences were found among all the ventilatory parameters, but the impedence was significantly higher in group A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of lung expansion with computed tomography and comparison with quantitative histology

The total and regional lung volumes were estimated from computed tomography (CT), and the pleural pressure gradient was determined by using the milliliters of gas per gram of tissue estimated from the X-ray attenuation values and the pressure-volume curve of the lung. The data show that CT accurately estimated the volume of the resected lobe but overestimated its weight by 24 +/- 19%. The volume of gas per gram of tissue was less in the gravity-dependent regions due to a pleural pressure gradient of 0.24 +/- 0.08 cmH2O/cm of descent in the thorax. The proportion of tissue to air obtained with CT was similar to that obtained by quantitative histology. We conclude that the CT scan can be used to estimate total and regional lung volumes and that measurements of the proportions of tissue and air within the thorax by CT can be used in conjunction with quantitative histology to evaluate lung structure.