Breathing strategy of the adult horse (Equus caballus) at rest

To investigate the mechanism underlying the polyphasic airflow pattern of the equine species, we recorded airflow, tidal volum, rib cage and abdominal motion, and the sequence of activation of the diaphragm, intercostal, and abdominal muscles during quiet breathing in nine adult horses standing at rest. In addition, esophageal, abdominal, and transdiaphragmatic pressures were simultaneously recorded using balloon-tipped catheters. Analysis of tidal flow-volume loops showed that, unlike humans, the horse at rest breathes around, rather than from, the relaxed volume of the respiratory system (Vrx). Analysis of the pattern of electromyographic activities and changes in generated pressures during the breathing cycle indicate that the first part of expiration is passive, as in humans, with deflation toward Vrx, but subsequent abdominal activity is responsible for a second phase of expiration: active deflation to below Vrx. From this end-expiratory volume, passive inflation occurs toward Vrx, followed by a second phase of inspiration: active inflation to above Vrx, brought about by inspiratory muscle contraction. Under these conditions the abdominal muscles appear to share the principal pumping duties with the diaphragm. Adoption of this breathing strategy by the horse may relate to its peculiar thoracoabdominal anatomic arrangement and to its very low passive chest wall compliance. We conclude that there is a passive and active phase to both inspiration and expiration due to the coordinated action of the respiratory pump muscles responsible for the resting adult horse's biphasic inspiratory and expiratory airflow pattern. This unique breathing pattern perhaps represents a strategy of minimizing the high elastic work of breathing in this species, at least at resting breathing frequencies.     

Neural Mechanisms Underlying Breathing Complexity

Breathing is maintained and controlled by a network of automatic neurons in the brainstem that generate respiratory rhythm and receive regulatory inputs. Breathing complexity therefore arises from respiratory central pattern generators modulated by peripheral and supra-spinal inputs. Very little is known on the brainstem neural substrates underlying breathing complexity in humans. We used both experimental and theoretical approaches to decipher these mechanisms in healthy humans and patients with chronic obstructive pulmonary disease (COPD). COPD is the most frequent chronic lung disease in the general population mainly due to tobacco smoke. In patients, airflow obstruction associated with hyperinflation and respiratory muscles weakness are key factors contributing to load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we found that the patients breathed with a higher level of complexity during inspiration and expiration than controls. Using functional magnetic resonance imaging (fMRI), we scanned the brain of the participants to analyze the activity of two small regions involved in respiratory rhythmogenesis, the rostral ventro-lateral (VL) medulla (pre-Bötzinger complex) and the caudal VL pons (parafacial group). fMRI revealed in controls higher activity of the VL medulla suggesting active inspiration, while in patients higher activity of the VL pons suggesting active expiration. COPD patients reactivate the parafacial to sustain ventilation. These findings may be involved in the onset of respiratory failure when the neural network becomes overwhelmed by respiratory overload We show that central neural activity correlates with airflow complexity in healthy subjects and COPD patients, at rest and during inspiratory loading. We finally used a theoretical approach of respiratory rhythmogenesis that reproduces the kernel activity of neurons involved in the automatic breathing. The model reveals how a chaotic activity in neurons can contribute to chaos in airflow and reproduces key experimental fMRI findings.     

Triangularis sterni muscle use in supine humans

The electrical activity of the triangularis sterni (transversus thoracis) muscle was studied in supine humans during resting breathing and a variety of respiratory and nonrespiratory maneuvers known to bring the abdominal muscles into action. Twelve normal subjects, of whom seven were uninformed and untrained, were investigated. The electromyogram of the triangularis sterni was recorded using a concentric needle electrode, and it was compared with the electromyograms of the abdominal (external oblique and rectus abdominis) muscles. The triangularis sterni was usually silent during resting breathing. In contrast, the muscle was invariably activated during expiration from functional residual capacity, expulsive maneuvers, "belly-in" isovolume maneuvers, static head flexion and trunk rotation, and spontaneous events such as speech, coughing, and laughter. When three trained subjects expired voluntarily with considerable recruitment of the triangularis sterni and no abdominal muscle activity, rib cage volume decreased and abdominal volume increased. These results indicate that unlike in the dog, spontaneous quiet expiration in supine humans is essentially a passive process; the human triangularis sterni, however, is a primary muscle of expiration; and its neural activation is largely coupled with that of the abdominals. The triangularis sterni probably contributes to the deflation of the rib cage during active expiration.     

Respiratory circuits: development, function and models

Breathing is a rhythmic motor behavior generated and controlled by hindbrain neuronal networks. Respiratory motor output arises from two distinct, but functionally interacting, rhythmogenic networks: the pre-B?tzinger complex (preB?tC) and the retrotrapezo?d nucleus/parafacial respiratory group (RTN/pFRG). This review outlines recent advances in delineating the genetic specification of the neuronal constituents of these two rhythmogenic networks, their respective roles in respiratory function and how they interact to constitute a functional respiratory circuit ensemble. The often lethal consequences of disruption to these networks found in naturally occurring developmental disorders, transgenic animals, and highly specific lesion studies are described. In addition, we discuss how recent computational models enhance our understanding of how respiratory networks generate and regulate respiratory behavior.     

Effects of midline laparotomy on expiratory muscle activation in anesthetized dogs

Abdominal surgery has a marked inhibitory influence on the diaphragm, but its effect on the expiratory muscles is not known. Therefore, we have recorded the electromyograms of the triangularis sterni, abdominal external oblique, and transversus abdominis before and after a midline laparotomy in 10 anesthetized, spontaneously breathing dogs. Measurements were obtained during quiet breathing in the supine posture, during breathing against expiratory threshold loads, during head-up tilting, and during hyperoxic hypercapnia. Expiratory activation of the transversus abdominis in all conditions was considerably reduced after laparotomy. This reduction was real, as no change in the compound muscle action potential during single pulse stimulation was observed. In contrast, expiratory recruitment of either the triangularis sterni or the abdominal external oblique was maintained or increased. We therefore conclude that laparotomy inhibits not only activation of the diaphragm during inspiration but also activation of the transversus abdominis during expiration. Visceral afferents thus affect in concert the two respiratory muscles lining the peritoneum. The present findings also emphasize the important fact that the pattern of activation of a particular abdominal muscle is not necessarily representative of the entire abdominal musculature.     

Relative contributions of rib cage and abdomen to breathing in normal subjects.

By use of the method of Konno and Mead and the respiratory magnetometer, the partition of respired gas volumes into rib cage and diaphragm-abdomen components was accomplished in 81 normal subjects including 32 young and middle-aged men, 29 young and middle-aged women, and 20 elderly men. Studied were isovolume maneuvers and the relaxation configuration over the inspiratory capacity range, quiet tidal breathing, increased amplitudes of slow breathing, rapid inspirations and expirations, and both quiet and forceful phonation. No major differences were noted between men and women or between the young and the elderly during any respiratory acts. During quiet breathing most normal subjects are abdominal breathers when supine and thoracic breathers when upright. Rapid respiratory maneuvers were accomplished mostly through rib cage displacement suggesting that rib cage muscles are capable of more rapid action than diaphragm and abdominal muscles. Data from deep breathing and rapid maneuvers supported the view that abdominal and rib cage muscles often act to optimize the mechanical (length-tension) advantage of the diaphragm.     

Effect of mechanical loading on displacements of chest wall during breathing in humans

Using a respiratory inductive plethysmograph (Respitrace) we studied thoracoabdominal movements in eight normal subjects during inspiratory resistive (Res) and elastic (El) loading. The magnitude of loads was chosen so as to produce a fall in inspiratory mouth pressure of 20 cmH2O. The contribution of rib cage (RC) to tidal volume (VT) increased significantly from 68% during quiet breathing (QB) to 74% during El and 78% during Res. VT and breathing frequency did not change significantly. During loading a phase lag was present on inspiration so that the abdomen led the rib cage. However, outward movement of the abdomen ceased in the latter part of inspiration, and the RC became the sole contributor to VT. These observations suggest greater recruitment of the inspiratory musculature of the RC than the diaphragm during loading, although changes in the mechanical properties of the chest wall may also have contributed. Indeed, an increase in abdominal end-expiratory and end-inspiratory pressures was observed in five out of six subjects, indicating abdominal muscle recruitment which may account for part of the reduction in abdominal excursion. Both Res and El increased the rate of emptying of the respiratory system during the ensuing unloaded expiration as a result of a reduction in rib cage expiratory-braking mechanisms. The time course of abdominal displacements during expiration was unaffected by loading.     

Ratio of active to passive muscle shortening in the canine diaphragm.

Active and passive shortening of muscle bundles in the canine diaphragm were measured with the objective of testing a consequence of the minimal-work hypothesis: namely, that the ratio of active to passive shortening is the same for all active muscles. Lengths of six muscle bundles in the costal diaphragm and two muscle bundles in the crural diaphragm of each of four bred-for-research beagle dogs were measured by the radiopaque marker technique during the following maneuvers: a passive deflation maneuver from total lung capacity to functional residual capacity, quiet breathing, and forceful inspiratory efforts against an occluded airway at different lung volumes. Shortening per liter increase in lung volume was, on average, 70% greater during quiet breathing than during passive inflation in the prone posture and 40% greater in the supine posture. For the prone posture, the ratio of active to passive shortening was larger in the ventral and midcostal diaphragm than at the dorsal end of the costal diaphragm. For both postures, active shortening during quiet breathing was poorly correlated with passive shortening. However, shortening during forceful inspiratory efforts was highly correlated with passive shortening. The average ratios of active to passive shortening were 1.23 +/- 0.02 and 1.32 +/- 0.03 for the prone and supine postures, respectively. These data, taken together with the data reported in the companion paper (T. A. Wilson, M. Angelillo, A. Legrand, and A. De Troyer, J. Appl. Physiol. 87: 554-560, 1999), support the hypothesis that, during forceful inspiratory efforts, the inspiratory muscles drive the chest wall along the minimal-work trajectory.     

Correlated Variability in the Breathing Pattern and End-Expiratory Lung Volumes in Conscious Humans

In order to characterize the variability and correlation properties of spontaneous breathing in humans, the breathing pattern of 16 seated healthy subjects was studied during 40 min of quiet breathing using opto-electronic plethysmography, a contactless technology that measures total and compartmental chest wall volumes without interfering with the subjects breathing. From these signals, tidal volume (V_T), respiratory time (T_TOT) and the other breathing pattern parameters were computed breath-by-breath together with the end-expiratory total and compartmental (pulmonary rib cage and abdomen) chest wall volume changes. The correlation properties of these variables were quantified by detrended fluctuation analysis, computing the scaling exponentα. V_T, T_TOT and the other breathing pattern variables showed α values between 0.60 (for minute ventilation) to 0.71 (for respiratory rate), all significantly lower than the ones obtained for end-expiratory volumes, that ranged between 1.05 (for rib cage) and 1.13 (for abdomen) with no significant differences between compartments. The much stronger long-range correlations of the end expiratory volumes were interpreted by a neuromechanical network model consisting of five neuron groups in the brain respiratory center coupled with the mechanical properties of the respiratory system modeled as a simple Kelvin body. The model-based α for V_T is 0.57, similar to the experimental data. While the α for T_TOT was slightly lower than the experimental values, the model correctly predicted α for end-expiratory lung volumes (1.045). In conclusion, we propose that the correlations in the timing and amplitude of the physiological variables originate from the brain with the exception of end-expiratory lung volume, which shows the strongest correlations largely due to the contribution of the viscoelastic properties of the tissues. This cycle-by-cycle variability may have a significant impact on the functioning of adherent cells in the respiratory system.     

Diaphragm function and respiratory response after upper abdominal surgery in dogs

Decreased diaphragm activity has been demonstrated after cholecystectomy in humans (Am. Rev. Respir. Dis. 127: 431-436, 1983). To investigate the mechanism(s) of postoperative diaphragm dysfunction we have established a dog model. Three groups of mongrel dogs were studied under general anesthesia: six dogs received no surgery (control); nine dogs underwent upper abdominal surgery (cholecystectomy); and six dogs underwent lower abdominal surgery (pseudoappendectomy). Diaphragm function was assessed by changes in transdiaphragmatic pressure swings, the ratio of changes in gastric to esophageal pressure swings, and the ratio of changes in abdominal to rib cage diameters during quiet tidal breathing. In the upper abdominal surgery group there were significant postoperative decreases in all parameters of diaphragm function and an increase in minute ventilation and respiratory frequency. However, there were no significant postoperative changes in the parameters of diaphragm function in the control or lower abdominal surgery groups. These studies establish that general anesthesia is not responsible for the reduced diaphragm activity seen postoperatively and that diaphragm function is not affected by lower abdominal surgery in dogs.     

Relationship between diaphragm length and abdominal dimensions

We examined the relationship between changes in abdominal cross-sectional area, measured by respiratory inductive plethysmography, and changes in length in the costal and crural parts of the diaphragm, measured by sonomicrometry, in nine supine, anesthetized dogs. During passive inflation, both parts of the diaphragm shortened and abdominal cross-sectional area increased. During passive deflation, both parts of the diaphragm lengthened and abdominal cross-sectional area decreased. We subsequently used the relationship between costal and crural diaphragmatic length, respectively, and abdominal cross-sectional area during passive inflation-deflation to predict the length changes in the costal and crural diaphragm during quiet breathing before and after bilateral phrenicotomy. In the intact animal the inspiratory shortening in the crural diaphragm was almost invariably greater than predicted from the relationship during passive inflation. During inspiration after phrenicotomy the crural diaphragm invariably lengthened, whereas the costal diaphragm often shortened. In general there was a good correlation between the measured and predicted length change for the crural diaphragm (r = 0.72 before and 0.79 after phrenicotomy) and a poor one for the costal diaphragm (r = 0.05 before and 0.19 after phrenicotomy).     

Arytenoideus muscle activity in normal adult humans during wakefulness and sleep

The respiratory-related activity of the arytenoideus (AR) muscle, a vocal cord adductor, was investigated in 10 healthy adults during wakefulness and sleep. AR activity was measured with intramuscular hooked-wire electrodes implanted by means of a fiber-optic nasopharyngoscope. Correct placement of the electrodes was confirmed by discharge patterns during voluntary maneuvers. The AR usually exhibited respiratory-related activity during quiet breathing in all awake subjects. Tonic activity was frequently present throughout the respiratory cycle. The pattern of phasic discharge during wakefulness exhibited considerable intrasubject variability both in timing and level of activity. Phasic activity usually began in midinspiration and terminated in mid- to late expiration. Periods of biphasic discharge were observed in four subjects. Phasic discharge primarily confined to expiration was also commonly observed. During quiet breathing in wakefulness, the level of phasic AR activity appeared to be directly related to the time of expiration. The AR was electrically silent in the six subjects who achieved stable periods of non-rapid-eye-movement sleep. Rapid-eye-movement sleep was observed in three subjects and was associated with sporadic paroxysmal bursts of AR activity. The results during wakefulness indicate that vocal cord adduction in expiration is an active phenomenon and suggest that the larynx may have an active role in braking exhalation.     

Changes in mechanics of breathing during experimental cough and sneeze in anaesthetized cats

Pleural pressure, airflow and tidal volume during experimental cough and sneeze elicited by mechanical stimulation of the tracheobronchial and nasal mucous membranes were investigated in fifty anaesthetized cats (pentobarbital, 40 mg/kg i.p.). Pressure-volume, pressure-flow and flow-volume relations were studied during these expulsive processes. In comparison to quiet breathing there was a decrease in dynamic lung compliance in both respiratory tract reflexes (p less than 0.001), especially in their expiratory phases. As compared to quiet breathing, the total work of breathing was significantly increased (p less than 0.001) in cough (20 times) as well as in sneeze (13 times). The total lung resistance increased markedly (p less than 0.001) in both cough and sneeze compared to quiet breathing. In these expulsive processes there was also a high "cough index" (resistance calculated from the peak flow and instantaneous pressure). The flow-volume curve in cough, in contradistinction to sneeze, indicated a significantly reduced airflow of the end of expiration (at 85% of the expired volume), demonstrating a concomitant bronchoconstriction.     

Biomechanics and regulation of external respiration under conditions of five-day dry immersion

The functional state of external respiration and the features of its regulation in healthy persons were studied under conditions of microgravity simulated using dry immersion. The lung volume, the ratio of thoracic and abdominal components during quiet breathing and performing various respiratory maneuvers, as well as the parameters that characterize the regulation of breathing (the duration of breath holding and the ability to voluntarily control respiratory movements), were recorded during the baseline period, on days 2 and 4 of dry immersion, and after the end of the dry immersion. It has been shown that the breathing pattern did not significantly change under conditions of dry immersion compared to the baseline period; however, the inspiratory reserve volume increased (p < 0.05), while the expiratory reserve volume decreased (p < 0.01). Dry immersion did not alter pulmonary ventilation, yet most of the subjects trended toward an increase in the contribution of the abdominal component of breathing movements during quiet breathing and demonstrated a statistically significant increase in this parameter during the lung vital capacity maneuver. The durations of the inspiratory and expiratory maximal breath holding under conditions of immersion did not differ from the background values. During the immersion, the accuracy of voluntary control of breathing increased. We believe that immersion, similar to microgravity, leads to changes in the reserve lung volume, which are partly because of changes in the body position; changes in relative contributions of the thoracic and abdominal components in the breathing movements; and changes in voluntary breath regulation.     

Regulation of end-expiratory lung volume during sleep in premature infants

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.     

Electromyographic activity of expiratory muscles in the rat

We examined the participation of expiratory muscles on breathing in the rat. The experiments were performed on 16 male rats in halothane [1.5%] or urethane [1.3 g/kg i.p.] anaesthesia. We recorded the electromyographic [EMG] activity of intercostal and abdominal muscles with a concentric needle electrode during quiet breathing, breathing against increased pressure in the airways and during the expiration reflex. In halothane anaesthesia the EMG expiratory phasic activity was observed only in internal intercostal muscles in 40% of spots examined during quiet breathing and in 58.5% when breathing against increased pressure. The EMG activity during the expiratory reflex was difficult to evaluate. In the abdominal muscles permanent EMG activity was found in 66% of trials. In urethane anaesthesia no phasic expiratory EMG activity was observed in intercostal or abdominal muscles. In abdominal muscles in 9% of trials a permanent activity was found.     

Arousal and cardiopulmonary responses to hyperoxic hypercapnia in lambs

Experiments were done to investigate the arousal and cardiopulmonary responses to hyperoxic hypercapnia in 8 lambs. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of arterial blood pressure and haemoglobin oxygen saturation. No sooner than 3 days after surgery, measurements were made in quiet sleep and active sleep during control periods when the animal was breathing 21% oxygen and during experimental periods of hyperoxic hypercapnia when the animal was breathing 10% carbon dioxide and 30% oxygen. Hyperoxic hypercapnia was terminated during each epoch by returning the inspired gas mixture to 21% oxygen once the animal aroused from sleep. Arousal occurred from both sleep states during hyperoxic hypercapnia but was delayed in active sleep compared to quiet sleep (active sleep 58 +/- 17 s; quiet sleep 21 +/- 10 s; mean +/- 1SD). There were no significant changes in heart rate or blood pressure during hyperoxic hypercapnia before arousal. However, respiratory rate and diaphragm electrical activity did increase during hyperoxic hypercapnia before arousal. Thus, our data provide evidence that hypercapnia can initiate arousal from sleep in young lambs. The mechanisms responsible for this response are yet to be determined.     

Dynamics of chest wall in preterm infants

The chest wall of the preterm infant has visible paradoxical movement during breathing, because of its greater flexibility than those of older children and adults. We studied the dynamics of the chest wall in 10 preterm infants to describe the interaction of the chest wall volume, as partitioned by the inductance plethysmograph, and the transthoracic and abdominal pressures. There was considerable hysteresis between the chest wall volume and the transthoracic pressure, and it had linear pressure-volume behavior during airway occlusion, late inspiration, and early expiration. The slope of this pressure-volume relationship, or the instantaneous chest wall compliance, averaged 0.89 +/- 0.16 and 0.94 +/- 0.18 ml/cmH2O for the respiratory effort during airway occlusion and early expiration, respectively. The dynamic compliance was considerably greater, averaging 7.8 +/- 2.3 ml/cmH2O. This resistive pressure-volume behavior was not related to the absolute value of or the rate of development of the esophageal or abdominal pressures. This additional degree of freedom of motion of the chest wall suggests that its linkage to the diaphragm is flexible, which provides a braking force for expiration and allows free movement of the diaphragm for breathing movements before birth.