Mechanism of the lung-deflating action of the canine diaphragm at extreme lung inflation

When lung volume in animals is passively increased beyond total lung capacity (TLC; transrespiratory pressure = +30 cmH(2)O), stimulation of the phrenic nerves causes a rise, rather than a fall, in pleural pressure. It has been suggested that this was the result of inward displacement of the lower ribs, but the mechanism is uncertain. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm and to the tenth rib pair in five dogs, and computed tomography was used to measure the displacement, length, and configuration of the muscle and the displacement of the lower ribs during relaxation at seven different lung volumes up to +60 cmH(2)O transrespiratory pressure and during phrenic nerve stimulation at the same lung volumes. The data showed that 1) during phrenic nerve stimulation at 60 cmH(2)O, airway opening pressure increased by 1.5 ± 0.7 cmH(2)O; 2) the dome of the diaphragm and the lower ribs were essentially stationary during such stimulation, but the muscle fibers still shortened significantly; 3) with passive inflation beyond TLC, an area with a cranial concavity appeared at the periphery of the costal portion of the diaphragm, forming a groove along the ventral third of the rib cage; and 4) this area decreased markedly in size or disappeared during phrenic stimulation. It is concluded that the lung-deflating action of the isolated diaphragm beyond TLC is primarily related to the invaginations in the muscle caused by the acute margins of the lower lung lobes. These findings also suggest that the inspiratory inward displacement of the lower ribs commonly observed in patients with emphysema (Hoover's sign) requires not only a marked hyperinflation but also a large fall in pleural pressure.     

Determinants of diaphragm motion in unilateral diaphragmatic paralysis.

Cranial displacement of a hemidiaphragm during sniffs is a cardinal sign of unilateral diaphragmatic paralysis in clinical practice. However, we have recently observed that isolated stimulation of one phrenic nerve in dogs causes the contralateral (inactive) hemidiaphragm to move caudally. In the present study, therefore, we tested the idea that, in unilateral diaphragmatic paralysis, the pattern of inspiratory muscle contraction plays a major role in determining the motion of the inactive hemidiaphragm. We induced a hemidiaphragmatic paralysis in six anesthetized dogs and assessed the contour of the diaphragm during isolated unilateral phrenic nerve stimulation and during spontaneous inspiratory efforts. Whereas the inactive hemidiaphragm moved caudally in the first instance, it moved cranially in the second. The parasternal intercostal muscles were then severed to reduce the contribution of the rib cage muscles to inspiratory efforts and to enhance the force generated by the intact hemidiaphragm. Although the change in pleural pressure (DeltaPpl) was unaltered, the cranial displacement of the paralyzed hemidiaphragm was consistently reduced. A pneumothorax was finally induced to eliminate DeltaPpl during unilateral phrenic nerve stimulation, and this enhanced the caudal displacement of the inactive hemidiaphragm. These observations indicate that, in unilateral diaphragmatic paralysis, the motion of the inactive hemidiaphragm is largely determined by the balance between the force related to DeltaPpl and the force generated by the intact hemidiaphragm.     

Respiratory effect of the lower rib displacement produced by the diaphragm

The diaphragm acting alone causes a cranial displacement of the lower ribs and a caudal displacement of the upper ribs. The respiratory effect of the lower rib displacement, however, is uncertain. In the present study, two sets of experiments were performed in dogs to assess this effect. In the first, all the inspiratory intercostal muscles were severed, so that the diaphragm was the only muscle active during inspiration, and the normal inspiratory cranial displacement of the lower ribs was suppressed at regular intervals. In the second experiment, the animals were given a muscle relaxant to abolish respiratory muscle activity, and external, cranially oriented forces were applied to the lower rib pairs to simulate the action of the diaphragm on these ribs. The data showed that 1) holding the lower ribs stationary during spontaneous, isolated diaphragm contraction had no effect on the change in lung volume during unimpeded inspiration and no effect on the fall in pleural pressure (Ppl) during occluded breaths; 2) the procedure, however, caused an increase in the caudal displacement of the upper ribs; and 3) pulling the lower rib pairs cranially induced a cranial displacement of the upper ribs and a small fall in Ppl. These observations indicate that the force applied on the lower ribs by the diaphragm during spontaneous contraction, acting through the interdependence of the ribs, is transmitted to the upper ribs and has an inspiratory effect on the lung. However, this effect is very small compared to that of the descent of the dome.     

Effect of diaphragmatic contraction on the action of the canine parasternal intercostals.

The inspiratory intercostal muscles enhance the force generated by the diaphragm during lung expansion. However, whether the diaphragm also alters the force developed by the inspiratory intercostals is unknown. Two experiments were performed in dogs to answer the question. In the first experiment, external, cranially oriented forces were applied to the different rib pairs to assess the effect of diaphragmatic contraction on the coupling between the ribs and the lung. The fall in airway opening pressure (deltaPa(O)) produced by a given force on the ribs was invariably greater during phrenic nerve stimulation than with the diaphragm relaxed. The cranial rib displacement (Xr), however, was 40-50% smaller, thus indicating that the increase in deltaPa(O) was exclusively the result of the increase in diaphragmatic elastance. In the second experiment, the parasternal intercostal muscle in the fourth interspace was selectively activated, and the effects of diaphragmatic contraction on the deltaPa(O) and Xr caused by parasternal activation were compared with those observed during the application of external loads on the ribs. Stimulating the phrenic nerves increased the deltaPa(O) and reduced the Xr produced by the parasternal intercostal, and the magnitudes of the changes were identical to those observed during external rib loading. It is concluded, therefore, that the diaphragm has no significant synergistic or antagonistic effect on the force developed by the parasternal intercostals during breathing. This lack of effect is probably related to the constraint imposed on intercostal muscle length by the ribs and sternum.     

Mechanics of the parasternal intercostals during occluded breaths in dogs

The electrical activity and the respiratory changes in length of the third parasternal intercostal muscle were measured during single-breath airway occlusion in 12 anesthetized, spontaneously breathing dogs in the supine posture. During occluded breaths in the intact animal, the parasternal intercostal was electrically active and shortened while pleural pressure fell. In contrast, after section of the third intercostal nerve at the chondrocostal junction and abolition of parasternal electrical activity, the muscle always lengthened. This inspiratory muscle lengthening must be related to the fall in pleural pressure; it was, however, approximately 50% less than the amount of muscle lengthening produced, for the same fall in pleural pressure, by isolated stimulation of the phrenic nerves. These results indicate that 1) the parasternal inspiratory shortening that occurs during occluded breaths in the dog results primarily from the muscle inspiratory contraction per se, and 2) other muscles of the rib cage, however, contribute to this parasternal shortening by acting on the ribs or the sternum. The present studies also demonstrate the important fact that the parasternal inspiratory contraction in the dog is really agonistic in nature.     

Interaction between the canine diaphragm and intercostal muscles in lung expansion.

Changes in intrathoracic pressure produced by the various inspiratory intercostals are essentially additive, but the interaction between these muscles and the diaphragm remains uncertain. In the present study, this interaction was assessed by measuring the changes in airway opening (DeltaPao) or transpulmonary pressure (DeltaPtp) in vagotomized, phrenicotomized dogs during spontaneous inspiration (isolated intercostal contraction), during isolated rectangular or ramp stimulation of the peripheral ends of the transected C(5) phrenic nerve roots (isolated diaphragm contraction), and during spontaneous inspiration with superimposed phrenic nerve stimulation (combined diaphragm-intercostal contraction). With the endotracheal tube occluded at functional residual capacity, DeltaPao during combined diaphragm-intercostal contraction was nearly equal to the sum of the DeltaPao produced by the two muscle groups contracting individually. However, when the endotracheal tube was kept open, DeltaPtp during combined contraction was 123% of the sum of the individual DeltaPtp (P < 0.001). The increase in lung volume during combined contraction was also 109% of the sum of the individual volume increases (P < 0.02). Abdominal pressure during combined contraction was invariably lower than during isolated diaphragm contraction. It is concluded, therefore, that the canine diaphragm and intercostal muscles act synergistically during lung expansion and that this synergism is primarily due to the fact that the intercostal muscles reduce shortening of the diaphragm. When the lung is maintained at functional residual capacity, however, the synergism is obscured because the greater stiffness of the rib cage during diaphragm contraction enhances the DeltaPao produced by the isolated diaphragm and reduces the DeltaPao produced by the intercostal muscles.     

Inspiratory muscle interaction in the generation of changes in airway pressure

The mechanical interaction of the inspiratory muscles in the generation of changes in airway pressure is unclear. Using upper thoracic spinal cord stimulation to activate the intercostal muscles (IC) and bilateral supramaximal phrenic nerve stimulation to activate the diaphragm (D), we measured the changes in airway pressure produced by separate and combined IC and D activation over a wide range of lung volumes. Changes in parasternal IC and D length were assessed by sonomicrometry. With increasing lung volume, activation of the IC and D resulted in progressive decrements in generated airway pressure. Combined IC and D contraction produced greater negative swings in airway pressure than the arithmetic sum of separate IC and D contraction alone, indicating a synergistic effect. Moreover, synergism increased progressively with increasing lung volume. During combined muscle contraction, both the IC and D shortened less than during contraction of either muscle group alone. The tendency for the parasternal muscle to lengthen for a given change in airway pressure during D contraction alone increased with increasing lung volume, suggesting that the tendency for the rib cage to recoil inward increased progressively with increasing lung volume. Likewise, the tendency of the D to lengthen for a given change in airway pressure during IC contraction alone also increased progressively with increasing lung volume, suggesting that the tendency for the abdomen-D compartment to recoil inward also increased with increasing lung volume. We conclude that the IC and D interact synergistically to produce changes in airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanics of the canine diaphragm in pleural effusion

Pleural effusion is a complicating feature of many diseases of the lung and pleura, but its effects on the mechanics of the diaphragm have not been assessed. In the present study, radiopaque markers were attached along muscle bundles in the midcostal region of the diaphragm in anesthetized dogs, and the three-dimensional location of the markers during relaxation before and after the stepwise introduction of liquid into the left or right pleural space and during phrenic nerve stimulation in the same conditions was determined using computed tomography. From these data, accurate measurements of diaphragm muscle length and displacement were obtained, and the changes in pleural and abdominal pressure were analyzed as functions of these parameters. The effect of liquid instillation on the axial position of rib 5 was also measured. The data showed that 1) liquid leaked through the dorsal mediastinal sheet behind the pericardium so that effusion was bilateral; 2) effusion caused a caudal displacement of the relaxed diaphragm; 3) this displacement was, compared with passive lung inflation, much larger than the cranial displacement of the ribs; and 4) the capacity of the diaphragm to generate pressure, in particular pleural pressure, decreased markedly as effusion increased, and this decrease was well explained by the decrease in active muscle length. It is concluded that pleural effusion has a major adverse effect on the pressure-generating capacity of the diaphragm and that this is the result of the action of hydrostatic forces on the muscle.     

Diaphragm curvature modulates the relationship between muscle shortening and volume displacement

During physiological spontaneous breathing maneuvers, the diaphragm displaces volume while maintaining curvature. However, with maximal diaphragm activation, curvature decreases sharply. We tested the hypotheses that the relationship between diaphragm muscle shortening and volume displacement (VD) is nonlinear and that curvature is a determinant of such a relationship. Radiopaque markers were surgically placed on three neighboring muscle fibers in the midcostal region of the diaphragm in six dogs. The three-dimensional locations were determined using biplanar fluoroscopy and diaphragm VD, curvature, and muscle shortening were computed in the prone and supine postures during spontaneous breathing (SB), spontaneous inspiration efforts after airway occlusion at lung volumes ranging from functional residual capacity (FRC) to total lung capacity, and during bilateral maximal phrenic nerve stimulation at those same lung volumes. In supine dogs, diaphragm VD was approximately two- to three-fold greater during maximal phrenic nerve stimulation than during SB. The contribution of muscle shortening to VD nonlinearly increases with level of diaphragm activation independent of posture. During submaximal diaphragm activation, the contribution is essentially linear due to constancy of diaphragm curvature in both the prone and supine posture. However, the sudden loss of curvature during maximal bilateral phrenic nerve stimulation at muscle shortening values greater than 40% (ΔL/L(FRC)) causes a nonlinear increase in the contribution of muscle shortening to diaphragm VD, which is concomitant with a nonlinear change in diaphragm curvature. We conclude that the nonlinear relationship between diaphragm muscle shortening and its VD is, in part, due to a loss of its curvature at extreme muscle shortening.     

Mechanics of the canine diaphragm in ascites: a CT study.

Ascites causes an increase in the elastance of the abdomen and impairs the lung-expanding action of the diaphragm, but its overall effects on the pressure-generating ability of the muscle remain unclear. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm in five dogs, and the three-dimensional locations of the markers during relaxation and during phrenic nerve stimulation in the presence of increasing amounts of ascites were determined using a computed tomographic scanner. From these data, accurate measurements of muscle length and quantitative estimates of diaphragm curvature were obtained, and the changes in transdiaphragmatic pressure (Pdi) were analyzed as functions of muscle length and curvature. With increasing ascites, the resting length of the diaphragm increased progressively. In addition, the amount of muscle shortening during phrenic nerve stimulation decreased gradually. When ascites was 100 ml/kg body wt, therefore, the muscle during contraction was longer, leading to a 20-25% increase in Pdi. As ascites increased further to 200 ml/kg, however, muscle length during contraction continued to increase, but Pdi did not. This absence of additional increase in Pdi was well explained by the increase in the diameter of the ring of insertion of the diaphragm to the rib cage and the concomitant increase in the radius of diaphragm curvature. These observations indicate that the pressure-generating ability of the diaphragm is determined not only by muscle length as conventionally thought but also by muscle shape.     

Relative strengths of the chest wall muscles

We hypothesized that during maximal respiratory efforts involving the simultaneous activation of two or more chest wall muscles (or muscle groups), differences in muscle strength require that the activity of the stronger muscle be submaximal to prevent changes in thoracoabdominal configuration. Furthermore we predicted that maximal respiratory pressures are limited by the strength of the weaker muscle involved. To test these hypotheses, we measured the pleural pressure, abdominal pressure (Pab), and transdiaphragmatic pressure (Pdi) generated during maximal inspiratory, open-glottis and closed-glottis expulsive, and combined inspiratory and expulsive maneuvers in four adults. We then determined the activation of the diaphragm and abdominal muscles during selected maximal respiratory maneuvers, using electromyography and phrenic nerve stimulation. In all subjects, the Pdi generated during maximal inspiratory efforts was significantly lower than the Pdi generated during open-glottis expulsive or combined efforts, suggesting that rib cage, not diaphragm, strength limits maximal inspiratory pressure. Similarly, at high lung volumes, the Pab generated during closed-glottis expulsive efforts was significantly greater than that generated during open-glottis efforts, suggesting that the latter pressure is limited by diaphragm, not abdominal muscle, strength. As predicted, diaphragm activation was submaximal during maximal inspiratory efforts, and abdominal muscle activation was submaximal during open-glottis expulsive efforts at midlung volume. Additionally, assisting the inspiratory muscles of the rib cage with negative body-surface pressure significantly increased maximal inspiratory pressure, whereas loading the rib cage muscles with rib cage compression decreased maximal inspiratory pressure. We conclude that activation of the chest wall muscles during static respiratory efforts is determined by the relative strengths and mechanical advantage of the muscles involved.     

Dysfunction of the canine respiratory muscle pump in ascites.

Ascites, a complicating feature of many diseases of the liver and peritoneum, commonly causes dyspnea. The mechanism of this symptom, however, is uncertain. In the present study, progressively increasing ascites was induced in anesthetized dogs, and the hypothesis was initially tested that ascites increases the impedance on the diaphragm and, so, adversely affects the lung-expanding action of the muscle. Ascites produced a gradual increase in abdominal elastance and an expansion of the lower rib cage. Concomitantly, the caudal displacement of the diaphragm and the fall in airway opening pressure during isolated stimulation of the phrenic nerves decreased markedly; transdiaphragmatic pressure during phrenic stimulation also decreased. To assess the adaptation to ascites of the respiratory system overall, we subsequently measured the changes in lung volume, the arterial blood gases, and the electromyogram of the parasternal intercostal muscles during spontaneous breathing. Tidal volume and minute ventilation decreased progressively as ascites increased, leading to an increase in arterial PCO2 and parasternal intercostal inspiratory activity. It is concluded that 1) ascites, acting through an increase in abdominal elastance and an expansion of the lower rib cage, impairs the lung-expanding action of the diaphragm; 2) this impairment elicits a compensatory increase in neural drive to the inspiratory muscles, but the compensation is not sufficient to maintain ventilation; and 3) dyspnea in this setting results in part from the dissociation between increased neural drive and decreased ventilation.     

Different effects of halothane on diaphragm and hindlimb muscle in rats

The effects of halothane administration on diaphragm and tibialis anterior (TA) muscle were investigated in 30 anesthetized mechanically ventilated rats. Diaphragmatic strength was assessed in 17 rats by measuring the abdominal pressure (Pab) generated during supramaximal stimulation of the intramuscular phrenic nerve endings at frequencies of 0.5, 30, and 100 Hz. Halothane was administered during 30 min at a constant minimum alveolar concentration (MAC): 0.5, 1, and 1.5 MAC in three groups of five rats. For each MAC, Pab was significantly reduced for all frequencies of stimulation except at 100 Hz during 0.5 MAC halothane exposure. The effects of halothane (0.5, 1, and 1.5 MAC) on diaphragmatic neuromuscular transmission were assessed in five other rats by measuring the integrated electrical activity of the diaphragm (Edi) during electrical stimulation of the phrenic nerve. No change in Edi was observed during halothane exposure. In five other rats TA contraction was studied by measuring the strength of isometric contraction of the muscle during electrical stimulation of its nerve supply at different frequencies (0.5, 30, and 100 Hz). Muscle function was unchanged during administration of halothane in a cumulative fashion from 0.5 to 1.5 MAC. These results demonstrate that halothane does not affect hindlimb muscle function, whereas it had a direct negative inotropic effect on rat diaphragmatic muscle.     

Asymmetrical action of the canine diaphragm after single-lung inflation

Single-lung transplantation (SLT) in patients with emphysema leads to a cranial displacement of the diaphragm on the transplanted side and a shift of the mediastinum toward the transplanted lung. The objective of the present study was to assess the effect of unilateral lung inflation on the mechanics of the diaphragm. Two endotracheal tubes were inserted in the two main stem bronchi of six anesthetized dogs, and radiopaque markers were attached along muscle fibers in the midcostal region of the two halves of the diaphragm. The animals were then placed in a computed tomographic scanner, the left or the right lung was passively inflated, and the phrenic nerves were stimulated while the two endobronchial tubes were occluded. As lung volume increased, the fall in airway opening pressure (ΔPao) in the inflated lung during stimulation decreased markedly, whereas ΔPao in the noninflated lung decreased only moderately (P < 0.001). Also, the two hemidiaphragms shortened both during relaxation and during phrenic stimulation, but the ipsilateral hemidiaphragm was consistently shorter than the contralateral hemidiaphragm. In addition, the radius of curvature of the ipsilateral hemidiaphragm during stimulation increased, whereas the radius of the contralateral hemidiaphragm remained unchanged. These observations indicate that 1) in the presence of unilateral lung inflation, the respiratory action of the diaphragm is asymmetric; and 2) this asymmetry is primarily determined by the differential effect of inflation on the length and curvature of the two halves of the muscle. These observations also imply that in patients with emphysema, SLT improves the action of the diaphragm on the transplanted side.     

Length and curvature of the dog diaphragm.

Transdiaphragmatic pressure is a result of both tension in the muscles of the diaphragm and curvature of the muscles. As lung volume increases, the pressure-generating capability of the diaphragm decreases. Whether decrease in curvature contributes to the loss in transdiaphragmatic pressure and, if so, under what conditions it contributes are unknown. Here we report data on muscle length and curvature in the supine dog. Radiopaque markers were attached along muscle bundles in the midcostal region of the diaphragm in six beagle dogs of approximately 8 kg, and marker locations were obtained from biplanar images at functional residual capacity (FRC), during spontaneous inspiratory efforts against a closed airway at lung volumes from FRC to total lung capacity, and during bilateral maximal phrenic nerve stimulation at the same lung volumes. Muscle length and curvature were obtained from these data. During spontaneous inspiratory efforts, muscle shortened by 15-40% of length at FRC, but curvature remained unchanged. During phrenic nerve stimulation, muscle shortened by 30 to nearly 50%, and, for shortening exceeding 52%, curvature appeared to decrease sharply. We conclude that diaphragm curvature is nearly constant during spontaneous breathing maneuvers in normal animals. However, we speculate that it is possible, if lung compliance were increased and the chest wall and the diameter of the diaphragm ring of insertion were enlarged, as in the case of chronic obstructive pulmonary disease, that decrease in diaphragm curvature could contribute to loss of diaphragm function.     

Effect of muscle length on electromyogram in a canine diaphragm strip preparation

The relationship between diaphragm electromyogram (EMG), isometric force, and length was studied in the canine diaphragm strip with intact blood supply and innervation under three conditions: supramaximal tetanic (100 Hz) phrenic nerve stimulation (STPS; n = 12), supramaximal phrenic stimulation at 25 Hz (n = 15), and submaximal phrenic stimulation at 25 Hz (n = 5). In the same preparation, the EMG-length relationship was also examined with direct muscle stimulation when the neuromuscular junction was blocked. EMG from three different sites and via two types of electrodes (direct or sewn-in and surface) were recorded during isometric contraction at different lengths. Direct EMGs were recorded from two bipolar electrodes sutured into the strip, one near its central end and the other near its costal end. A third EMG electrode configuration summed potentials from the whole strip by recording potentials between central and costal sites. Surface EMGs were recorded by a bipolar spring clip electrode that made contact with upper and lower surfaces of the muscle strip with light pressure. In all conditions of stimulation with different types of electrodes, all EMGs decreased significantly (P less than 0.05) when muscle length was changed from 50 to 120% of resting length (L0). Minimal and maximal force outputs were observed at 50 and 120% of L0, respectively, in all experiments. The results of this study indicated that the muscle length is a significant variable that affects the EMG recording and that the diaphragmatic EMG may not be an accurate reflection of phrenic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of digitalis on the diaphragm in anesthetized dogs

We examined the effect of digitalis on diaphragmatic contractility and fatigability in 19 anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. In a first group of five dogs, Pdi-stimulus frequency relationships were compared before and after administration of ouabain in doses of 0.01, 0.02, and 0.04 mg/kg. In a second group, diaphragmatic fatigue was produced by bilateral phrenic nerve stimulation at 30 Hz. Ten seconds of stimulation and 15 s of mechanical ventilation were repeated for 30 min. The rates of decrease in Pdi were compared between two groups, one of 0.05 mg/kg deslanoside-treated dogs (n = 7) and one of nontreated dogs (n = 7). After ouabain administration Pdi was significantly greater at each frequency in a dose-dependent manner. On the other hand, the rate of decrease in Pdi in the deslanoside group was significantly smaller than that in the nontreated group, whereas deslanoside did not greatly change the Pdi-frequency curves in fresh diaphragm. We conclude that ouabain improves contractility of the fresh diaphragm and that deslanoside has a protective effect against fatigability.     

Impact of diaphragmatic contraction on the stiffness of the canine mediastinum

To assess the coupling between a particular hemidiaphragm and the individual lungs, the left and right phrenic nerves were separately stimulated in anesthetized dogs, and the mean changes in pleural pressure over the two lungs were evaluated by measuring the changes in airway opening pressure (DeltaPao) in the two bronchial trees. Stimulation induced a fall in Pao in both lungs. However, DeltaPao in the contralateral lung was only 65% of that in the ipsilateral lung. Thus, although the canine ventral mediastinum is a delicate structure, it sustained a significant pressure gradient. The hypothesis was then considered that this gradient was allowed to develop through the stretching and stiffening of the mediastinum caused by the descent of the diaphragm, and it was tested by measuring DeltaPao in the two lungs during isolated, unilateral contraction of the inspiratory intercostal muscles. In this condition, DeltaPao in the contralateral lung was 92% of that in the ipsilateral lung. A model analysis of the respiratory system led to the estimate that mediastinal elastance was approximately 25 times greater during hemidiaphragmatic contraction than during unilateral intercostal contraction. These observations indicate that 1) a particular hemidiaphragm has an expanding action on both lungs and 2) during contraction, however, it makes the mediastinum stiffer so that the pressure transmission from the ipsilateral to the contralateral pleural cavity is reduced. These observations imply that the mediastinum may play a significant role in determining the pressure-generating ability of the diaphragm.     

Contractile properties of the human diaphragm in vivo

The mechanical properties of the human diaphragm have been studied at fractional residual capacity in normal seated subjects with closed glottis. The transdiaphragmatic pressure (Pdi) developed in response to single shocks or to trains of stimuli at increasing frequency was approximately 3 times greater during bilateral than unilateral stimulation. During unilateral phrenic nerve stimulation the Pdi twitches increased as the interval (0-200 ms) of a preceding conditioning stimulus to the contralateral phrenic nerve was decreased suggesting that the two hemidiaphragms are mechanically coupled in series. The contraction time and half-relaxation time of single bilateral twitches as well as the Pdi-frequency relationship (5-35 Hz) during bilateral tetanic stimulation indicate that the contractile properties of the human diaphragm are intermediate between those of fast- and slow-twitch muscle fibers. The results suggest that the contractile properties of the human diaphragm are well illustrated by single bilateral twitches recorded from the relaxed muscle, but that the responses to unilateral stimulation are misleading due to distortion by abnormal changes in the muscle geometry.     

Stimulation of groups III and IV phrenic afferents reflexly decreases total lung resistance in dogs

Little is known about the reflex effect on airway caliber evoked by stimulation of phrenic afferents. Therefore, in chloralose-anesthetized, paralyzed dogs, we recorded airflow, airway pressure, arterial pressure, and heart rate while electrically stimulating a phrenic nerve. Total lung resistance was calculated breath by breath. The phrenic nerve was stimulated at 3, 5, 20, 70, 140, and 200 times motor threshold and the compound action potential was recorded. Stimulation of the phrenic nerve at three and five times threshold, which activated groups I, II, and a few group III fibers, had no effect on any of the variables measured. Stimulation at 20 times threshold, which activated many group III fibers and groups I and II fibers, reflexly decreased resistance. Stimulation at 70, 140, and 200 times threshold, which activated groups I-IV fibers, evoked progressively greater decreases in lung resistance. The reflex bronchodilation evoked by phrenic nerve stimulation was unaffected by propranolol or phentolamine but was abolished by atropine. We conclude that activation of groups III and IV phrenic nerve afferents reflexly decreased total lung resistance by withdrawing cholinergic tone to airway smooth muscle.