Interaction between left and right intercostal muscles in airway pressure generation.

The interactions between the different rib cage inspiratory muscles in the generation of pleural pressure remain largely unknown. In the present study, we have assessed in dogs the interactions between the parasternal intercostals and the interosseous intercostals situated on the right and left sides of the sternum. For each set of muscles, the changes in airway opening pressure (DeltaPao) obtained during separate right and left activation were added, and the calculated values (predicted DeltaPao) were then compared with the DeltaPao values obtained during symmetric, bilateral activation (measured DeltaPao). When the parasternal intercostals in one or two interspaces were activated, the measured DeltaPao was commonly greater than the predicted value. The difference, however, was only 10%. When the interosseous intercostals were activated, the measured DeltaPao was nearly equal to the predicted value. These observations strengthen our previous conclusion that the pressure changes produced by the rib cage inspiratory muscles are essentially additive. As a corollary, the rib cage can be considered as a linear elastic structure over a wide range of distortion.     

Partitioning of inspiratory pressure swings between diaphragm and intercostal/accessory muscles

We tested the hypothesis that the inspiratory pressure swings across the rib-cage pathway are the sum of transdiaphragmatic pressure (Pdi) and the pressures developed by the intercostal/accessory muscles (Pic). If correct, Pic can only contribute to lowering pleural pressure (Ppl), to the extent that it lowers abdominal pressure (Pab). To test this we measured Pab and Ppl during during Mueller maneuvers in which deltaPab = 0. Because there was no outward displacement of the rib cage, Pic must have contributed to deltaPpl, as did Pdi. Under these conditions the total pressure developed by the inspiratory muscles across the rib-cage pathway was less than Pdi + Pic. Therefore, we rejected the hypothesis. A plot of Pab vs. Ppl during relaxation allows partitioning of the diaphragmatic and intercostal/accessory muscle contributions to inspiratory pressure swings. The analysis indicates that the diaphragm can act both as a fixator, preventing transmission of Ppl to the abdomen and as an agonist. When abdominal muscles remain relaxed it only assumes the latter role to the extent that Pab increases.     

Interaction of fatigue and hypercapnia in the canine diaphragm

We studied 10 open-chest dogs and measured the pressure across the diaphragm (Pdi) in each period of the protocol during stimulation at frequencies of 1, 20, 50, and 80 Hz. Three ranges of arterial PCO2 (PaCO2) were examined: less than or equal to 26, 36-50, and greater than or equal to 89 Torr. The diaphragm was fatigued with repetitive phrenic stimulation (30 Hz). During the fatiguing activity, five of the animals were subjected to hypercapnia and the other five to hypocapnia. A frequency-Pdi curve was generated for each period in the protocol. The data show that 1) fatiguing to 50% of the initial Pdi value during hypercapnia was significantly more rapid than during hypocapnia; 2) both the prefatigue and postfatigue mean Pdi values over all interactions of frequency, fatigue, and PaCO2 were unaffected by the fatiguing environment (hypercapnia vs. hypocapnia); 3) the percent reduction of Pdi by hypercapnia was the same at all four frequencies; 4) hypocapnia did not alter either the pre- or postfatigue frequency-Pdi curve; and 5) one-half relaxation time, unaffected by PaCO2, was prolonged by fatigue. We conclude that the hypercapnic diaphragm has less endurance than the hypocapnic diaphragm and that although both fatigue and hypercapnia decrease Pdi, they appear to be separate entities working through different mechanisms.     

Action of intercostal muscles on the lung in dogs

The action on the lung of interosseous intercostal muscles located in the third and the seventh interspaces was studied in 15 anesthetized-curarized supine dogs. Changes in pleural pressure, airflow rate, and lung volume produced by maximal stimulation of both intercostal muscle layers were measured at and above functional residual capacity (FRC). In five animals measurements were also obtained during isolated stimulation of the internal layer. At FRC, intercostal stimulation in the upper interspaces had invariably an inspiratory effect on the lung but no effect was detectable in the lower interspaces. Qualitatively similar results were obtained during isolated stimulation of the internal layer. Increasing lung volume reduced the inspiratory action of the upper intercostals and conferred an expiratory action to the lower intercostals. These results indicate the following: 1) when contracting in a single interspace, the external and internal intercostals have a qualitatively similar action on the lung; and 2) this action, however, depends critically on their location along the cephalocaudal axis of the rib cage: in the upper portion of the rib cage, both muscle layers have an inspiratory effect at and above FRC; in the lower portion of the rib cage, they have no respiratory action at FRC and act in the expiratory direction at higher lung volumes.     

Effect of spaceflight on oxidative and antioxidant enzyme activity in rat diaphragm and intercostal muscles

There are limited data regarding changes in oxidative and antioxidant enzymes induced by simulated or actual weightlessness, and any additional information would provide insight into potential mechanisms involving other changes observed in muscles from animals previously flown in space. Thus, the NASA Biospecimen Sharing Program was an opportunity to collect valuable information. Oxidative and antioxidant enzyme levels, as well as lipid perioxidation, were measured in respiratory muscles from rats flown on board Space Shuttle mission STS-54. The results indicated that there was an increasing trend in citrate synthase activity in the flight diaphragm when compared to ground based controls, and there were no significant changes observed in the intercostal muscles for any of the parameters. However, lipid peroxidation was significantly (p<0.05) decreased in the flight diaphragm. These results indicate that 6 day exposure to microgravity may have a different effect on oxidative and antioxidant activity in rat respiratory muscles when compared to data from previous 14 day hindlimb suspension studies.     

Role of pleural pressure in the coupling between the intercostal muscles and the ribs.

The inspiratory intercostal muscles elevate the ribs and thereby elicit a fall in pleural pressure (DeltaPpl) when they contract. In the present study, we initially tested the hypothesis that this DeltaPpl does, in turn, oppose the rib elevation. The cranial rib displacement (Xr) produced by selective activation of the parasternal intercostal muscle in the fourth interspace was measured in dogs, first with the rib cage intact and then after DeltaPpl was eliminated by bilateral pneumothorax. For a given parasternal contraction, Xr was greater after pneumothorax; the increase in Xr per unit decrease in DeltaPpl was 0.98+/-0.11 mm/cmH2O. Because this relation was similar to that obtained during isolated diaphragmatic contraction, we subsequently tested the hypothesis that the increase in Xr observed during breathing after diaphragmatic paralysis was, in part, the result of the decrease in DeltaPpl, and the contribution of the difference in DeltaPpl to the difference in Xr was determined by using the relation between Xr and DeltaPpl during passive inflation. With diaphragmatic paralysis, Xr during inspiration increased approximately threefold, and 47+/-8% of this increase was accounted for by the decrease in DeltaPpl. These observations indicate that 1) DeltaPpl is a primary determinant of rib motion during intercostal muscle contraction and 2) the decrease in DeltaPpl and the increase in intercostal muscle activity contribute equally to the increase in inspiratory cranial displacement of the ribs after diaphragm paralysis.     

Gas exchange during separate diaphragm and intercostal muscle breathing.

In patients with diaphragm paralysis, ventilation to the basal lung zones is reduced, whereas in patients with paralysis of the rib cage muscles, ventilation to the upper lung zones in reduced. Inspiration produced by either rib cage muscle or diaphragm contraction alone, therefore, may result in mismatching of ventilation and perfusion and in gas-exchange impairment. To test this hypothesis, we assessed gas exchange in 11 anesthetized dogs during ventilation produced by either diaphragm or intercostal muscle contraction alone. Diaphragm activation was achieved by phrenic nerve stimulation. Intercostal muscle activation was accomplished by electrical stimulation by using electrodes positioned epidurally at the T(2) spinal cord level. Stimulation parameters were adjusted to provide a constant tidal volume and inspiratory flow rate. During diaphragm (D) and intercostal muscle breathing (IC), mean arterial Po(2) was 97.1 +/- 2.1 and 88.1 +/- 2.7 Torr, respectively (P < 0.01). Arterial Pco(2) was lower during D than during IC (32.6 +/- 1.4 and 36.6 +/- 1.8 Torr, respectively; P < 0.05). During IC, oxygen consumption was also higher than that during D (0.13 +/- 0.01 and 0.09 +/- 0.01 l/min, respectively; P < 0.05). The alveolar-arterial oxygen difference was 11.3 +/- 1.9 and 7.7 +/- 1.0 Torr (P < 0.01) during IC and D, respectively. These results indicate that diaphragm breathing is significantly more efficient than intercostal muscle breathing. However, despite marked differences in the pattern of inspiratory muscle contraction, the distribution of ventilation remains well matched to pulmonary perfusion resulting in preservation of normal gas exchange.     

Regional deformation of the canine diaphragm.

To follow regional deformation of the diaphragm in dogs, radiopaque markers were implanted under surgical anesthesia into different anatomic regions of the muscle in triangular arrays (approximately 1 cm to a side). After recovery from surgery, changes in area and shape of the triangles were followed with biplane cinefluorography during quiet breathing and during inspiratory efforts against an occluded airway (Mueller maneuvers). From changes in shape of the triangles during contraction, area changes were decomposed into a major direction and magnitude of shortening (Eg1) and a minor length change (Eg2) perpendicular to Eg1, both expressed as a fraction of initial length at end expiration. With the use of these techniques, systematic differences in regional area change were observed in different parts of the diaphragm during inspiratory efforts at different lung volumes. Regional area always decreased during contraction in the crural and midcostal zones of apposition to the rib cage. Area decreased less and often increased during inspiratory efforts in the costal dome near the central tendon and in the costal region near its rib cage insertion. Differences in regional area change were not due to differences in the Eg1 in different parts of the diaphragm but were a consequence of differences in widening of the muscle along Eg2 perpendicular to the direction of Eg1. As lung volume was passively increased above functional residual capacity, regional area decreased in all parts of the diaphragm except in the costal regions near rib cage insertion, where area increased.     

Effect of lung volume on the respiratory action of the canine pectoral muscles.

Lung volume influences the mechanical action of the primary inspiratory and expiratory muscles by affecting their precontraction length, alignment with the rib cage, and mechanical coupling to agonistic and antagonistic muscles. We have previously shown that the canine pectoral muscles exert an expiratory action on the rib cage when the forelimbs are at the torso's side and an inspiratory action when the forelimbs are held elevated. To determine the effect of lung volume on intrathoracic pressure changes produced by the canine pectoral muscles, we performed isolated bilateral supramaximal electrical stimulation of the deep pectoral and superficial pectoralis (descending and transverse heads) muscles in 15 adult supine anesthetized dogs during hyperventilation-induced apnea. Lung volume was altered by application of a negative or positive pressure (+/- 30 cmH2O) to the airway. In all animals, selective electrical stimulation of the descending, transverse, and deep pectoral muscles with the forelimbs held elevated produced negative intrathoracic pressure changes (i.e., an inspiratory action). Moreover, with the forelimbs elevated, increasing lung volume decreased both pectoral muscle fiber precontraction length and the negative intrathoracic pressure changes generated by contraction of each of these muscles. Conversely, with the forelimbs along the torso, increasing lung volume lengthened pectoral muscle precontraction length and augmented the positive intrathoracic pressure changes produced by muscle contraction (i.e., an expiratory action). These results indicate that lung volume significantly affects the length of the canine pectoral muscles and their mechanical actions on the rib cage.     

Postinspiratory activity of the parasternal and external intercostal muscles in awake canines.

Previous studies have shown in awake dogs that activity in the crural diaphragm, but not in the costal diaphragm, usually persists after the end of inspiratory airflow. It has been suggested that this difference in postinspiratory activity results from greater muscle spindle content in the crural diaphragm. To evaluate the relationship between muscle spindles and postinspiratory activity, we have studied the pattern of activation of the parasternal and external intercostal muscles in the second to fourth interspaces in eight chronically implanted animals. Recordings were made on 2 or 3 successive days with the animals breathing quietly in the lateral decubitus position. The two muscles discharged in phase with inspiration, but parasternal intercostal activity usually terminated with the cessation of inspiratory flow, whereas external intercostal activity persisted for 24.7 +/- 12.3% of inspiratory time (P < 0.05). Forelimb elevation in six animals did not affect postinspiratory activity in the parasternal but prolonged postinspiratory activity in the external intercostal to 45.4 +/- 16.3% of inspiratory time (P < 0.05); in two animals, activity was still present at the onset of the next inspiratory burst. These observations support the concept that muscle spindles are an important determinant of postinspiratory activity. The absence of such activity in the parasternal intercostals and costal diaphragm also suggests that the mechanical impact of postinspiratory activity on the respiratory system is smaller than conventionally thought.     

Antioxidants and mitochondrial respiration in lung, diaphragm, and locomotor muscles: effect of exercise.

Previous studies have shown that exhaustive exercise may increase reactive oxygen species (ROS) generation in oxidative muscles that may in turn impair mitochondrial respiration. Locomotor muscles have been extensively examined, but there is few report about diaphragm or lung. The later is a privileged site for oxygen transit. To compare the antioxidant defense system and mitochondrial function in lung, diaphragm and locomotor muscles after exercise, 24 young adult male rats were randomly assigned to a control (C) or exercise (E) group. E group rats performed an exhaustive running test on a motorized treadmill at 80-85% VO2max Mean exercise duration was 66+/-2.7 min. Lung, costal diaphragm, mixed gastrocnemius, and oxidative muscles (red gastrocnemius and soleus: RG/SOL homogenate) were sampled. Mitochondrial respiration was assessed in tissue homogenates by respiratory control index (RCI: rate of uncoupled respiration/rate of basal respiration) measurement. Lipid peroxidation was evaluated by malondialdehyde concentration (MDA) and we determined the activity of two antioxidant enzymes: superoxide dismutase (SOD) and glutathione peroxidase (GPX). We found elevated basal (C group data) SOD and GPX activities in both lung and diaphragm compared to locomotor muscles (p<.001). Exercise led to a rise in GPX activity in red locomotor muscles homogenate (GR/SOL; C = 10.3+/-0.29 and E = 14.4+/-1.51 micromol x min(-1) x gww(-1); p<.05), whereas there was no significant change in lung and diaphragm. MDA concentration and mitochondrial RCI values were not significantly changed after exercise. We conclude that lung and diaphragm had higher antioxidant protection than locomotor muscles. The exercise test did not lead to significant oxidative stress or alteration in mitochondrial respiration, suggesting that antioxidant function was adequate in both lung and diaphragm in the experimental condition.