Synergism between the canine left and right hemidiaphragms.

Expansion of the lung during inspiration results from the coordinated contraction of the diaphragm and several groups of rib cage muscles, and we have previously shown that the changes in intrathoracic pressure generated by the latter are essentially additive. In the present studies, we have assessed the interaction between the right and left hemidiaphragms in anesthetized dogs by comparing the changes in airway opening pressure (DeltaPao) obtained during simultaneous stimulation of the two phrenic nerves (measured DeltaPao) to the sum of the DeltaPao values produced by their separate stimulation (predicted DeltaPao). The measured DeltaPao was invariably greater than the predicted DeltaPao, and the ratio between these two values increased gradually as the stimulation frequency was increased; the ratio was 1.

Mechanical effect of muscle spindles in the canine external intercostal muscles.

High-frequency mechanical vibration of the ribcage increases afferent activity from external intercostal muscle spindles, but the effect of this procedure on the mechanical behaviour of the respiratory system is unknown. In the present study, we have measured the changes in external intercostal muscle length and the craniocaudal displacement of the ribs during ribcage vibration (40 Hz) in anaesthetized dogs. With vibration, external intercostal inspiratory activity increased by approximately 50 %, but the respiratory changes in muscle length and rib displacement were unaltered.

Respiratory effects of the scalene and sternomastoid muscles in humans.

Previous studies have shown that in normal humans the change in airway opening pressure (DeltaPao) produced by all the parasternal and external intercostal muscles during a maximal contraction is approximately -18 cmH(2)O. This value is substantially less negative than DeltaPao values recorded during maximal static inspiratory efforts in subjects with complete diaphragmatic paralysis. In the present study, therefore, the respiratory effects of the two prominent inspiratory muscles of the neck, the sternomastoids and the scalenes, were evaluated by application of the Maxwell reciprocity theorem.

Distribution of inspiratory drive to the external intercostal muscles in humans.

The external intercostal muscles in humans show marked regional differences in respiratory effect, and this implies that their action on the lung during breathing is primarily determined by the spatial distribution of neural drive among them. To assess this distribution, monopolar electrodes were implanted under ultrasound guidance in different muscle areas in six healthy individuals and electromyographic recordings were made during resting breathing. The muscles in the dorsal portion of the third and fifth interspace showed phasic inspiratory activity with each breath in every subject.

Relationship between neural drive and mechanical effect in the respiratory system.

The actions of the canine external and internal interosseous intercostal muscles on the lung were assessed by applying the Maxwell reciprocity theorem. The external intercostals in the dorsal part of the cranial interspaces were found to have a large inspiratory effect. However, this effect decreases continuously in the caudal and the ventral direction, such that the muscles in the ventral part of the caudal interspaces have an expiratory effect.

Abnormal pulmonary vascular tone in canine oleic acid lung injury.

Objective: To characterize the endothelium-dependent and endothelium-independent components of abnormal pulmonary vascular tone in canine oleic acid lung injury.

Design: Prospective, interventional study.

Setting: University laboratory.

Coupling between the ribs and the lung in dogs.

In contrast to the conventional theory, the external and internal intercostal muscles show marked rostrocaudal gradients in their actions on the lung. We hypothesized that these gradients are the result of a non-uniform coupling between the ribs and the lung. Rib displacements (X(r)) and the changes in airway opening pressure (P(a,o)) were thus measured in anaesthetized, pancuronium-treated, supine dogs while loads were applied in the cranial direction to individual pairs of odd-numbered ribs and in the caudal direction to individual pairs of even-numbered ribs.

On the respiratory function of the ribs.

To assess the respiratory function of the ribs, we measured the changes in airway opening pressure (Pao) induced by stimulation of the parasternal and external intercostal muscles in anesthetized dogs, first before and then after the bony ribs were removed from both sides of the chest. Stimulating either set of muscles with the rib cage intact elicited a fall in Pao in all animals. After removal of the ribs, however, the fall in Pao produced by the parasternal intercostals was reduced by 60% and the fall produced by the external intercostals was eliminated.

Involvement of peripheral airways during methacholine-induced bronchoconstriction after lung transplantation.

Previous studies have shown that the presence of nonspecific bronchial hyperreactivity (NSBHR) in transplanted subjects is associated with the development of bronchiolitis obliterans, which suggests that NSBHR in these subjects may involve the peripheral airways. We investigated this question by studying the effects of methacholine on the distribution of ventilation using single-breath washouts in 15 heart-lung transplant recipients; 17 nontransplanted subjects with NSBHR were studied for comparison. All subjects had normal baseline lung function, and seven transplanted subjects displayed NSBHR.

Medical therapy of pulmonary hypertension. Conventional therapies.

The 1-, 3-, and 5-year survival rates of the patients included in the National Institute of Health Registry on Primary Pulmonary Hypertension were 77%, 41%, and 27% respectively. It is unclear to what extent better applied conventional therapy contributes to improved survival rates that now are reported with calcium-channel blockers, prostacyclin, or even transplantation. To date, by far the most favorable results are reported with high-dose calcium-channel blockers combined with anticoagulant therapy, with survival rates at 3 years approximately 100%.

Contribution of spindle reflexes to post-inspiratory activity in the canine external intercostal muscles.

1. The external intercostal muscles have greater post-inspiratory activity than the parasternal intercostal muscles and are more abundantly supplied with muscle spindles. In the present study, the hypothesis was tested that spindle afferent inputs play a major role in determining this activity.

Inhibition of hypoxic pulmonary vasoconstriction by carbon monoxide in dogs.

Objective: We tested the hypothesis that carbon monoxide might participate in the modulation of hypoxic pulmonary vasoconstriction (HPV) by prostacyclin (PGI2) and nitric oxide.

Design: Prospective, interventional study.

Setting: University laboratory.

Respiratory effects of the external and internal intercostal muscles in humans.

The current conventional view of intercostal muscle actions is based on the theory of Hamberger (1749) and maintains that as a result of the orientation of the muscle fibres, the external intercostals have an inspiratory action on the lung and the internal interosseous intercostals have an expiratory action. Recent studies in dogs, however, have shown that this notion is only approximate. In the present studies, the respiratory actions of the human external and internal intercostal muscles were evaluated by applying the Maxwell reciprocity theorem.

Response of the canine internal intercostal muscles to chest wall vibration.

Although high-frequency mechanical vibration of the rib cage reduces dyspnea, its effects on the respiratory muscles are largely unknown. We have previously shown that in anesthetized dogs, vibrating the rib cage during inspiration elicits a marked increase in the inspiratory electromyographic (EMG) activity recorded from the external intercostal muscles but does not affect tidal volume (VT). In the present studies, we have tested the hypothesis that the maintenance of VT results from the concomitant contraction of the internal interosseous (expiratory) intercostals.

Heterogeneity of metabolic activity in the canine parasternal intercostals during breathing.

In the dog, the inspiratory mechanical advantage of the parasternal intercostals shows a marked spatial heterogeneity, whereas the expiratory mechanical advantage of the triangularis sterni is relatively uniform. The contribution of a particular respiratory muscle to lung volume expansion during breathing, however, depends both on the mechanical advantage of the muscle and on its neural input. To evaluate the distribution of neural input across the canine parasternal intercostals and triangularis sterni, we have examined the distribution of metabolic activity among these muscles in seven spontaneously breathing animals by measuring the uptake of the glucose tracer analog [(18)F]fluorodeoxyglucose (FDG).

Effect of preoperative hyperinflation on static lung volumes after lung transplantation.

It is still not known whether persistent increases in functional residual capacity (FRC) and residual volume (RV) after lung transplantation are due to preexisting hyperinflation. Therefore, the aim of this study was to determine the effects of chronic lung hyperinflation on static lung volumes after heart/lung (HLT) and bilateral lung transplantation (BLT). Static lung volumes were measured in 33 patients before and at 6 month intervals for up to 3 yrs after HLT (n=25) or BLT (n=8).

Detection of obliterative bronchiolitis after lung transplantation by indexes of ventilation distribution.

Obliterative bronchiolitis (OB) is the first cause of death of long-term survivors of lung transplantation. The diagnosis is based on pathology and/or on an irreversible decrease in forced expiratory volume in 1 s (FEV(1)) below 80% of the best postoperative value. We tested whether indexes of ventilation distribution may provide evidence of OB before conventional pulmonary function tests (PFTs).

The canine parasternal and external intercostal muscles drive the ribs differently.

1. In the dog, the elevation of the ribs during inspiration results from the combined actions of the parasternal and external intercostal muscles. In the present studies, the hypothesis was tested that co-ordinated activity among these two sets of muscles reduces the distortion of the rib cage.

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).

Response of the canine inspiratory intercostal muscles to chest wall vibration.

High-frequency mechanical vibration of the rib cage reduces dyspnea, but the effect of this procedure on the respiratory muscles is largely unknown. In the present studies, we have initially assessed the electrical and mechanical response to vibration (40 Hz) of the canine parasternal and external intercostal muscles (third interspace) during hyperventilation-induced apnea. When the vibrator was applied to the segment investigated, prominent external intercostal activity was recorded in the seven animals studied, whereas low-amplitude parasternal intercostal activity was recorded in only four animals.

Spatial distribution of external and internal intercostal activity in dogs.

1. The observation that the external and internal interosseous intercostal muscles in the dog show marked regional differences in mechanical advantage has prompted us to re-examine the topographic distribution of electrical activity among these muscles during spontaneous breathing. 2.

Respiratory mechanical advantage of the canine external and internal intercostal muscles.

1. The current conventional view of intercostal muscle actions is based on the theory of Hamberger (1749) and maintains that as a result of the orientation of the muscle fibres, the external intercostals have an inspiratory action on the lung and the internal interosseous intercostals have an expiratory action. This notion, however, remains unproved.

Determinants of rib motion in flail chest.

We have previously developed a canine model of isolated flail chest to assess the effects of this condition on the mechanics of breathing, and these studies have led to the conclusion that the respiratory displacement of the fractured ribs is primarily determined by the fall in pleural pressure (Delta Ppl) and the action of the parasternal intercostal muscles. The present studies were designed to test the validity of this conclusion. A flail was induced in six supine anesthetized animals by fracturing both dorsally and ventrally the second to fifth ribs on the right side of the chest, after which the phrenic nerve roots were bilaterally sectioned in the neck.