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Diaphragmatic work of breathing in premature human infants.

Present methods of assessing the work of breathing in human infants do not account for the added load when intercostal muscle activity is lost and rib cage distortion occurs. We have developed a technique for assessing diaphragmatic work in this circumstance utilizing measurements of transdiaphragmatic pressure and abdominal volume displacement. Eleven preterm infants without evidence of lung disease were studied. During periods of minimal rib cage distortion, inspiratory diaphragmatic work averaged 5.9 g X cm X ml-1, increasing to an average of 12.4 g X cm X ml-1 with periods of paradoxical rib cage motion (P less than 0.01). Inspiratory work was strongly correlated with the electrical activity of the diaphragm as measured from its moving time average (P less than 0.05). Assuming a mechanical efficiency of 4% in these infants, the caloric cost of diaphragmatic work may reach 10% of their basal metabolic rate in periods with rib cage distortion. When lung disease is superimposed, the increased metabolic demands of the diaphragm may predispose preterm infants to fatigue and may contribute to a failure to grow.

Diaphragm↗

Expiratory activity in transferred intercostal nerves in brachial plexus injury patients.

Involuntary activity of transferred intercostal motor units was examined in patients with brachial plexus injury. Since the internal intercostal nerves were detached from the thorax to reinnervate the musculus biceps brachii, it was possible to record pure intercostal motor activity in humans. Respiratory activity was seen in the latter part of the expiratory phase, thus dividing the phase into two substages (E1 and E2) by the onset of the activity. CO2 rebreathing prolonged the duration of the intercostal motor activity and increased the tidal activity as determined from the integration curve. There was a close linear correlation between these two variables. These observations indicate that expiratory activity and its duration are actively controlled in humans.

Adult↗

Hydraulic conductivity of canine parietal pleura in vivo.

The hydraulic conductivity (Lp) of the parietal pleura was measured in vivo in spontaneously breathing anesthetized dogs in either the supine (n = 8) or the prone (n = 7) position and in an excised portion of the chest wall in which the pleura and its adjacent tissue were intact (n = 3). A capsule was glued to the exposed parietal pleura after the intercostal muscles were removed. The capsule was filled with either autologous plasma or isotonic saline. Transpleural fluid flow (V) was measured at several transpleural hydrostatic pressures (delta P) from the rate of meniscus movement within a graduated pipette connected to the capsule. Delta P was defined as the measured difference between capsule and pleural liquid pressures. The Lp of the parietal pleura was calculated from the slope of the line relating V to delta P by use of linear regression analysis. Lp in vivo averaged 1.36 X 10(-3) +/- 0.45 X 10(-3) (SD) ml.h-1.cmH2O-1.cm-2, regardless of whether the capsule was filled with plasma or saline and irrespective of body position. This value was not significantly different from that measured in the excised chest wall preparation (1.43 X 10(-3) +/- 1.1 X 10(-3) ml.h-1.cmH2O-1.cm-2). The parietal pleura offers little resistance to transpleural protein movement, because there was no observed difference between plasma and saline. We conclude that because the Lp for intact parietal pleura and extrapleural interstitium is approximately 100 times smaller than that previously measured in isolated stripped pleural preparations, removal of parietal pleural results in a damaged preparation.

Animals↗

Direct measurement of interstitial pulmonary pressure in in situ lung with intact pleural space.

We developed an experimental approach to measure the pulmonary interstitial pressure with the micropuncture technique in in situ lungs with an intact pleural space. Experiments were done in anesthetized paralyzed rabbits that were oxygenated via an endotracheal tube with 50% humidified oxygen and kept in either the supine or the lateral position. A small area of an intercostal space was cleared of the intercostal muscles down to the endothoracic fascia. Subsequently a "pleural window" was opened by stripping the endothoracic fascia over a 0.2-cm2 surface and leaving the parietal pleura (approximately 10 microns thick). Direct micropuncture through the pleural window was performed with 2- to 3-microns-tip pipettes connected to a servo-null pressure-measuring system. We recorded pleural liquid pressure and, after inserting the pipette tip into the lung, we recorded interstitial pressure from subpleural lung tissue. Depth of recording for interstitial pressure averaged 263 +/- 122 (SD) microns. We report data gathered at 26, 53, and 84% lung height (relative to the most dependent portion of the lung). For the three heights, interstitial pressure was -9.8 +/- 3, -10.1 +/- 1.6, and -12.5 +/- 3.7 cmH2O, respectively, whereas the corresponding pleural liquid pressure was -3.4 +/- 0.5, -4.4 +/- 1, and -5.2 +/- 0.3 cmH2O, respectively.

Animals↗

No evidence for mesothelial cell contact across the costal pleural space of sheep.

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1-2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.

Animals↗

Parenchymal stress affects interstitial and pleural pressures in in situ lung.

After resecting the intercostal muscles and thinning the endothoracic fascia, we micropunctured the lung tissue through the intact pleural space at functional residual capacity (FRC) and at volumes above FRC to evaluate the effect of increasing parenchymal stresses on pulmonary interstitial pressure (Pip). Pip was measured at a depth of approximately 230 microns from the pleural surface, at 50% lung height, in 12 anesthetized paralyzed rabbits oxygenated via a tracheal tube with 50% humidified O2. Pip was -10 +/- 1.5 cmH2O at FRC. At alveolar pressure of 5 and 10 cmH2O, lung volume increased by 8.5 and 19 ml and Pip decreased to -12.4 +/- 1.6 and -12.3 +/- 5 cmH2O, respectively. For the same lung volumes held by decreasing pleural surface pressure to about -5 and -8.5 cmH2O, Pip decreased to -17.4 +/- 1.6 and -23.8 +/- 5 cmH2O, respectively. Because Pip is more negative than pleural pressure, the data suggest that in intact pulmonary interstitium the pressure of the liquid phase is primarily set by the mechanisms controlling interstitial fluid turnover.

Animals↗

Permeability-surface area product and reflection coefficient of the parietal pleura in dogs.

The parameters describing the permeability of the parietal pleura to liquid and total plasma proteins were measured in five anesthetized adult dogs. Small areas of parietal pleura (approximately 1 cm2) and the underlying endothoracic fascia were exposed through resection of the skin and the intercostal muscles. The portion of the thorax containing the pleural windows was removed from the chest and fixed over a bath of whole autologous plasma, the inner parietal pleural surface facing the bath. Small hemispheric Perspex capsules (surface area 0.28 cm2) connected to a pressure manometer were glued to the pleural windows; a subatmospheric pressure was set into the capsule chamber to create step hydraulic transpleural pressure gradients (delta P) ranging from 5 to 60 cmH2O. Transpleural liquid flows (Jv) and protein concentration of the capsular filtrate (Cfilt) and of the plasma bath were measured at each delta P. The transpleural protein flux (Js) at each delta P was calculated by multiplying Jv by the corresponding Cfilt. The hydraulic conductivity (Lp) of the parietal pleura was obtained from the slope of the Jv vs. delta P linear regression. The average Lp from 14 capsules was 9.06 +/- 4.06 (SD) microliters.h-1.cmH2O-1.cm-2. The mathematical treatment of the Js vs. Jv relationship allowed calculation of the unique Peclet number at the maximal diffusional protein flux and a corresponding osmotic permeability coefficient for plasma protein of 1 x 10(-5) +/- 0.97 x 10(-5) cm/s. The reflection coefficient calculated from the slope of the linear phase of the Js vs. Jv relationship was 0.11 +/- 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of ventilation frequency and tidal volume on pleural space thickness in rabbits.

The thickness of the pleural space was measured by fluorescence video-microscopy during mechanical ventilation in anesthetized paralyzed rabbits. A transparent parietal pleural window was made in the fourth or sixth intercostal space near midchest by dissection of intercostal muscle and endothoracic fascia. Fluorescence-labeled (fluorescein isothiocyanate) dextran solution (1 ml) was injected into the pleural space via a rib capsule and allowed to mix with the pleural liquid. With the rabbit in the left lateral decubitus position and the pleural window superior, the light emitted from the pleural liquid through the pleural window was measured through the videomicroscope. Both ventilation frequency and tidal volume were varied. Pleural space thickness was determined by in vitro calibration of the pleural liquid at the end of the experiment. At a frequency of 40 breaths/min and a tidal volume of 20 ml, pleural space thickness averaged 35 +/- 15 (SD) microns (n = 7). When frequency was reduced to 8 breaths/min, this value was reduced by 40% to 22 +/- 11 microns. A reduction in tidal volume from 20 to 6 ml at a frequency of 40 breaths/min produced a similar reduction in pleural space thickness. During apnea, pleural space thickness averaged 11 +/- 3 microns. Cardiogenic motion had no measurable effect on pleural space thickness. The increased pleural space thickness with ventilation might serve to reduce the power dissipated due to sliding of the lung relative to the chest wall. Results support the concept of lubrication as the primary function of the pleural space.

Animals↗

Stress wave velocity measured in intact pig lungs with cross-spectral analysis.

In anesthetized pigs (25-40 kg), we generated stress waves in the lung by rapid deflation of an esophageal balloon. The source distortion was measured by an accelerometer (1 g wt) bonded to the balloon. Stress waves were detected by three accelerometers bonded to intercostal muscle and to the skin near midchest. The distance between the source and chest receivers were measured radiographically. Cross-spectral analysis was used to calculate transit times. We measured stress wave velocities at airway pressures of 0 (functional residual capacity) and 25 cmH2O. Transpulmonary pressure (Ptp) was measured by an esophageal balloon. In vivo, stress wave velocities increased from 291 +/- 117 (SD) cm/s at 3.0 +/- 0.9 cmH2O Ptp to 573 +/- 73 cm/s at 13.8 +/- 3.5 cmH2O Ptp (n = 6). These velocities agreed with longitudinal wave velocities measured in isolated sheep lungs and predictions based on the elastic moduli of lung parenchyma. Post-mortem edema was induced by intratracheal instillation of 200 ml of saline, resulting in a wet-to-dry weight ratio of 7.7 +/- 1.4 (n = 5). At 15 cmH2O Ptp, stress wave velocities decreased from 565 +/- 155 cm/s before edema to 445 +/- 130 cm/s after edema. This decrease correlated well with predictions based on the increased lung density, as dictated by elasticity theory.

Animals↗

Linkage of hiccup with heartbeat.

We explored a possible link between the cardiac cycle and the timing of recurrent hiccups in 10 patients with chronic, intractable hiccups. Recordings made during daytime naps in a sleep laboratory included sleep state; electrocardiogram; and respiration by means of a thermistor to detect airflow, bands around the rib cage and abdomen to assess expansion, and a bipolar surface electrode electromyogram over parasternal intercostal muscles. Hiccups could be detected on the abdominal bands and the parasternal electromyogram. The time of occurrence of each hiccup and each R wave in a continuous tracing of 100 or more hiccups were recorded and analyzed together with semiquantitive estimates of the phase of hiccup respiration. Whereas the hiccup rate ranged from approximately one-third to one-eighth of heart rate and was more variable than heart rate, hiccups showed a tendency, stronger in some subjects than others, to occur in midsystole. Variation in R-wave-R-wave (R-R) interval in association with hiccups was found in five patients. In three of these patients, hiccups were synchronized with respiration so that the cyclic change in R-R interval posthiccup could be explained as sinus arrhythmia, but, in two patients, the hiccups were not synchronized with respiration, so that hiccups are most likely responsible for the variation in heart rate. Also, the variation of R-R interval with hiccups suggests that there is some phasic autonomic efferent activity associated with hiccups.

Aged↗

Polygraphic study of periodic breathing and hypersomnolence in a patient with severe hypothyroidism.

A 67-year-old woman with primary hypothyroidism, who had Pickwickian syndrome as well, was studied electrophysiologically. A polygraphic study with simultaneous recordings of electroencephalography, actograms of the abdominal walls, the mentum and the anterior neck, and electromyogram of the intercostal muscles revealed a cyclic appearance of apnea in the sleep phase and gasping preceding arousal, which, together with macroglossia and sleep in the sitting position, suggested a cyclic obstruction of the upper airway. The obstruction appeared responsible for both alveolar hypoventilation and disturbance of consciousness.

Aged↗

Sleep and oxyhemoglobin desaturation patterns in chronic obstructive pulmonary diseases.

A polysomnographic study with noninvasive oxyhemoglobin saturation (HbSaO2) monitoring has been conducted in 11 consecutive male nonobese subjects with chronic obstructive pulmonary disease (COPD). The patients with a high arterial CO2 level and markedly reduced functional residual capacity appeared to be more prone to undergo HbSaO2 desaturation during sleep compared to patients with less severe functional and clinical respiratory impairment. The HbSaO2 desaturations were mostly linked to REM sleep and appeared to be concomitant to the inhibition of the tone of the intercostal muscles. Regarding sleep architecture, the patients with less severe COPD and scarce or absent tendency to HbSaO2 desaturation during sleep showed light and fragmented sleep with a marked tendency to arousals and awakenings.

Aged↗

Respiratory patterns during sleep in mitochondrial myopathies with ophthalmoplegia.

Nocturnal polygraphic recordings (electroencephalography, electro-oculography, submental and intercostal muscle electromyography, electrocardiography, respiration by thoracic strain gauges and oronasal thermistors) with continuous monitoring of arterial oxyhemoglobin saturation by pulse oximeter were performed in 8 patients with ophthalmoplegia plus. All patients except 1 had normal blood gas values and normal lung volumes associated with a diminished ventilatory response to inhaled CO2 during wakefulness. Four patients showed pathological sleep-related breathing patterns consisting of sleep apneic polygraphic tracings mainly of the central type or of REM-related hypoventilation episodes. It is suggested that these disorders in patients with ophthalmoplegia plus may have a central origin and be related to the underlying metabolic disturbance.

Adult↗

Primary and secondary heart tumors in mice maintained on various diets.

Two mice of the TM strain, maintained on Purina chow supplemented with refined coin oil plus free fatty acids, in one case, and with refined corn oil without free fatty acids, in the other case, developed primary heart rhabdomyosarcomas. The tumors metastasized to the lungs and the kidney, in the first case, and to the lungs alone in the second case. One mouse of the TM strain, on the diet supplemented with corn oil plus free fatty acids, developed a fibrosarcoma behind the right anterior extremity. Metastases from the tumor were found in the liver, lungs and myocardium. Another mouse of the C57 Bl. strain, injected subcutaneously, in the interscapular region, at the age of 7 days, with a single dose of 30 mug of Delestrogen, developed, at the point of injection, a large rhabdomyosarcoma. At the age of 5333 days, when the animal was killed, metastases from the tumor were found in the intercostal muscles and in the heart. Three mice, one of the TM strain, on a diet supplemented with corn oil and cholesterol, and two of the C57 Br. strain, on a diet supplemented with raw egg yolk (rich in cholesterol) had organized blood clots in the atria (in two mice) and one extending into the ventricle.

Animals↗

Spontaneous malignant histiocytoma with metastasis in a rhesus monkey [Macaca mulatta].

A malignant histiocytoma was observed on the left arm of a recently imported rhesus monkey. Rapid invasion of deep tissues and tumor growth on the face prompted euthanasia. Necropsy revealed additional neoplastic foci in the lungs, diaphragm, intercostal muscles, pericardium and liver. Microscopically the predominant cell type was histiocytic; some cells had a distinct epithelioid appearance and other were spindle-shaped.

Animals↗

Measurement of lung microvascular pressure in the intact anesthetized rabbit by the micropuncture technique.

We have developed a micropuncture technique for the measurement of microvascular pressure in the intact lung of rabbit. We anesthetized 16 rabbits (halothane, 0.8%) and mechanically ventilated them through a tracheotomy. Then, we exposed the right lung by rib resection over the right anterior chest. We measured pulmonary artery, left atrial, and systemic pressures by direct catheterization and cardiac output by the thermodilution technique. For micropuncture, we stabilized the lung on a shelf and stopped ventilation for 3-4 minutes at an airway pressure of 7 cm H2O. We injected pancuronium intravenously to paralyze the diaphragm and intercostal muscles. Of the total pulmonary vascular pressure drop, 52% occurred in the microvascular segment between arterioles and venules of 20 micron diameter, 28% occurred in the arterial segment, and 20% occurred in the venous segment. We conclude that in the intact lung of rabbit, the major pressure drop occurs in the microvascular segment.

Anesthesia↗

Respiratory flutter syndrome: an underrecognized cause of respiratory failure in neonates.

We report the clinical and respiratory data of three neonates with flutter of the diaphragm and intercostal muscles, presenting soon after birth with respiratory failure. The breathing pattern was dirhythmic with superimposed frequencies, one regular and slow (60/min) representing the underlying respiratory rate, the other fast (> 300/min) and limited to inspiration. Nasal continuous positive airway pressure immediately normalized the breathing pattern in one infant, and improved ventilation in the two others. Pharmacologic therapy with chlorpromazine terminated the respiratory flutter and permitted weaning of ventilatory support within a few hours. Coexistent dysphagia suggested a disorder of brainstem function, although the children were otherwise developmentally normal at 8, 10, and 26 mo old. Laryngomalacia and gastroesophageal reflux were also present. We propose that the occurrence of respiratory flutter, dysphagia, laryngomalacia, and gastroesophageal reflux in a neonate constitutes a distinct clinical entity, termed the "respiratory flutter syndrome." The diagnosis of three infants with this presentation during an 18-mo period suggests that this may be a more frequent cause of respiratory failure in newborns than previously recognized.

Diaphragm↗

Comparison of diaphragm EMG centroid frequencies: esophageal versus chest surface leads.

Previous work has suggested that diaphragm EMGs recorded from the lower thoracic wall yield spuriously low centroid frequencies (Fc). For this reason we compared EMGs recorded from two anterolateral thoracic wall locations with EMGs recorded simultaneously from a bipolar esophageal electrode in 11 stable quadriplegic patients. Their maximal inspiratory pressures (Pdimax) ranged from 31 to 85, averaging 55 cm H2O. Quadriplegic patients were selected to exclude EMG contamination of surface recordings by intercostal muscle activity. Recordings were made during resting breathing, voluntary hyperventilation, CO2-stimulated hyperventilation, and inspiratory resistance breathing at 50% of Pdimax. Centroid frequencies were consistently lower from surface recordings than from esophageal recordings. Centroid frequencies (Hz) recorded from the esophagus were 86.9 +/- 3.0 (SEM) resting, 93.4 +/- 3.7 during voluntary hyperventilation, 85.8 +/- 4.2 during CO2-stimulated ventilation, and 88.5 +/- 1.4 during inspiratory resistance breathing. Corresponding Fc values from simultaneous thoracic surface recordings were 62.6 +/- 3.6, 62.0 +/- 2.8, 58.6 +/- 3.1, and 58.8 +/- 2.5. On several subjects, decreases in Fc that occurred during sustained maximal inspiratory efforts were present in esophageal recordings but not in surface recordings. We conclude that thoracic surface recordings of the diaphragmatic EMG do not accurately reflect frequency information.

Airway Resistance↗