Effects of theophylline (T) on diaphragmatic contractility in dogs.
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Animals↗
Biomedical subjects
M Decramer
Publications and source records attributed to M Decramer.
Action and interaction of respiratory muscles in dogs.
How the respiratory muscles, the so-called "vital pump", works is relevant to medicine and nevertheless, poorly understood. The present studies attempt to obtain a better insight in the action and interaction of respiratory muscles by measuring the mechanical outcome of individual respiratory muscle contraction with two different techniques in anesthetized dogs. First, we measured the changes in length undergone by respiratory muscles using sonomicrometry. We observed that the costal and crural parts of the diaphragm frequently behaved differently, supporting the concept that these two parts behave as two different muscles. Moreover, crural diaphragmatic length appeared to be linked to abdominal dimensions, the classical used estimate of diaphragmatic length, whereas costal diaphragmatic length was not. The parasternal or the interchondral parts of the internal intercostals invariably shortened with inspiration supporting their role as inspiratory agonists. By way of contrast, the respiratory length changes in the external and interosseus internal intercostal were variable and not consistently in different directions for the two layers. The changes in length, during rotation of the trunk were consistent, larger and systematically in opposite directions for these two layers, suggesting that these muscles predominantly function as rotators of the trunk or at least that a role in rotation of the trunk explains better the need for two layers of intercostal muscles with different fiber orientation than a respiratory role. Second, we measured changes in intramuscular pressure in the costal and crural parts of the diaphragm, and in the parasternal intercostals, using mini-transducers. In the diaphragm intramuscular pressure appeared to be a complex variable determined by the tension developed by the muscle as well as the pleural and abdominal pressures applied to the muscle. As a consequence, intramuscular pressure often decreased during contraction, suggesting that in contrast to other muscles, diaphragmatic contraction may enhance diaphragmatic blood flow. Conversely, in the parasternal intercostals, intramuscular pressure invariably increased during contraction, and a linear relationship between intramuscular pressure and contractile force was present. The forces developed by these muscles during quiet breathing and other respiratory maneuvers were found to be significant, supporting the important inspiratory role of the parasternal intercostals. Intramuscular pressure thus appeared to be a perfect estimate of the force developed by these muscles. Finally, we examined the changes in respiratory muscle interaction with hyperinflation.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Influence of hypercapnia on rabbit intrapulmonary neuroepithelial bodies: microfluorimetric and morphometric study.
The present investigation was undertaken to investigate the influence of hypercapnia on intrapulmonary neuroepithelial bodies (NEB). Rabbits were mechanically ventilated with a hypercapnic gas mixture (7% carbon dioxide, 20% oxygen, 73% nitrogen). Lung samples were examined by a microspectrographical analysis of the NEB formaldehyde-induced fluorescence to quantify the cytoplasmic 5-hydroxy-tryptamine (5HT) content and by electron microscopy to determine morphometrically the extent of the secretory exocytosis at the basal poles of the NEB epithelial cells. In contrast to our earlier studies on the effects of hypoxia and/or vagal stimulation, hypercapnia did not alter significantly the NEB cytoplasmic fluorescence nor did it affect the corpuscular epithelial exocytosis. NEB appear not to be influenced by hypercapnia to discharge their contents of 5HT and peptides. This investigation appears to support a high selectivity of the intrapulmonary NEB to local hypoxia and changes in vagal efferent output.
Animals↗
Pulmonary function and maximal transrespiratory pressures in ankylosing spondylitis.
Clinical measurements and pulmonary functions, including maximal transrespiratory pressures, were studied in 30 patients (age 43 (SD 10) years) with ankylosing spondylitis. Vital capacity (VC) was slightly reduced to 79 (16)% and forced expiratory volume in one second (FEV1) was similarly reduced to 82 (20)% such that the average FEV1/VC ratio was 77.8 (6.65). Total lung capacity was slightly reduced to 85 (13)%. Transfer factor of the lung for carbon monoxide (TLCO) averaged 88 (17)% and TLCO per unit lung volume was 114 (26)%. Reductions in lung volumes correlated well with clinical measurements. Both maximal expiratory pressures (PEmax) and inspiratory pressures (PImax) were clearly reduced to 56 (17)% and 76 (28)% respectively. This suggests that spirometrically determined volumes were better preserved than respiratory muscle strength in ankylosing spondylitis. It is speculated that the reduction in respiratory muscle strength may be due to intercostal muscle atrophy.
Adult↗
Effects of acute hyperinflation on the mechanical effectiveness of the parasternal intercostals.
We studied the mechanical effectiveness of the parasternal intercostals at FRC and near TLC in 14 supine, vagotomized, and anesthetized dogs. First, we determined the relationship between parasternal intramuscular pressure (Pps), measured with Gaeltec 12 CT-mini-transducers, and parasternal EMG activity (Eps) during breathing at FRC and near TLC. Second, we examined the changes in Pps and the changes in parasternal force (Fps) generated during bilateral parasternal stimulation at FRC and near TLC with a given supramaximal stimulus. Before phrenicotomy, the inspiratory increases in Pps remained relatively constant near TLC (FRC, 50.4 +/- 16.5 versus TLC, 48.7 +/- 13.3 cm H2O, NS), whereas the Eps clearly decreased (82.9 +/- 5.5% FRC, p less than 0.01). This indicates that the gain converting electrical activity into pressure for the parasternals is greater near TLC than at FRC. A similar pattern of changes in Pps and in Eps was observed during quiet inspiration at FRC and near TLC after phrenicotomy. During bilateral parasternal stimulation the increases in Pps near TLC tended to be greater than those at FRC (140.7 +/- 28.6 versus 100 +/- 28.3 cm H2O, NS), whereas the increases in Fps were significantly greater near TLC than at FRC (277.4 +/- 60.6 versus 214.2 +/- 47.1 g, p less than 0.05). Therefore, we conclude that the mechanical effectiveness of the parasternal contraction near TLC remains relatively unchanged and is even greater in relation to that at FRC.
Acute Disease↗
Corticosteroid-induced myopathy and the respiratory muscles. Report of two cases.
Two women with connective tissue disease developed a characteristic steroid-induced myopathy. Reduced maximal transrespiratory pressures indicated reduced respiratory muscle strength. Gradual steroid dosage tapering resulted in prompt clinical improvement and marked increases in respiratory muscle strength, maximal inspiratory pressure increasing by 33 percent in one patient and by 70 percent in the other. This reversible steroid-induced respiratory muscle weakness may be of great significance in reconsidering long-term steroid therapy in patients with underlying lung disease.
Connective Tissue Diseases↗
Effects of hyperinflation on the respiratory muscles.
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Airway Resistance↗
Theophylline and the respiratory muscles: where are we?
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Animals↗
A subtractive method for decomposing muscle tension into individual twitches.
When an isolated strip of skeletal muscle tissue is held at fixed length and stimulated electrically with a very brief pulse of electricity it responds with a transient increase in tension known as a twitch. If the same strip is stimulated repetitively with short pulses it produces a tension that can be considered to be composed of individual twitches arising from each stimulus. We present a subtractive method for decomposing a muscle tension curve into individual twitches of various heights. The locations of the twitches are known a priori from the times at which each stimulus was applied to the muscle. The shape of each twitch is assumed the same as that of a single twitch obtained just prior to the repetitive stimulation tension signal. We therefore find the heights of the individual twitches composing a tension curve. We find that most of a tension signal from isolated dog diaphragm strips can be accounted for as the sum of twitches of the same shape but different heights. We also derive a refractory factor, for stimulation at a given frequency, that describes how the heights of the twitches in a tension curve are attenuated as a function of stimulation frequency.
Animals↗
Mechanical coupling of upper and lower canine rib cages and its functional significance.
We studied rib cage distortability and reexamined the mechanical action of the diaphragm and the rib cage muscles in six supine anesthetized dogs by measuring changes in upper rib cage cross-sectional area (Aurc) and changes in lower rib cage cross-sectional area (Alrc) and the respective pressures acting on them. During quiet breathing in the intact animal the rib cage behaved as a unit (Aurc: 14.6 +/- 7.9 vs. Alrc: 15.1 +/- 9.6%), whereas considerable distortions of the rib cage occurred during breathing after bilateral phrenicotomy (Aurc: 21.0 +/- 5.1 vs. Alrc: 7.0 +/- 4.8%). These distortions were even more pronounced during phrenic nerve stimulation and separate stimulation of the costal and crural parts of the diaphragm (e.g., phrenic nerve stimulation; Aurc: -7.1 +/- 5.1 vs. Alrc: 6.9 +/- 3.5%). During the latter maneuvers the upper rib cage deflated along the relationship between upper rib cage dimensions and pleural pressure obtained during passive deflation, whereas the lower rib cage inflated close to the relationship between lower rib cage dimensions and abdominal pressure obtained during passive inflation. The latter relationship is expected to differ between costal and crural stimulation, since costal action has both an appositional and insertional component and crural action only has an appositional component. The difference between costal and crural stimulation, however, was relatively small, and the slopes were only slightly steeper for the costal than for the crural stimulation (2.9 +/- 1.2 vs. 2.2 +/- 1.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Volume quantification of chest wall motion in dogs.
We employed high-speed multisliced X-ray-computed tomography to determine the relative volume contributions of rib cage (delta Vrc) and diaphragmatic motion (delta Vdi) to tidal volume (VT) during spontaneous breathing in 6 anesthetized dogs lying supine. Mean values were 40 +/- 6% (SE) for delta Vrc and 62 +/- 8% of VT for delta Vdi. The difference between VT and changes in thoracic cavity volume was taken to represent a change in thoracic blood volume (2 +/- 3% of VT). To estimate how much of delta Vrc was caused by diaphragmatic contraction and how much of delta Vdi was caused by rib cage motion, delta Vrc and delta Vdi were determined during bilateral stimulation of the C5-C6 phrenic nerve roots in the apneic dog and again during spontaneous breathing after phrenicotomy. Thoracic cavity volume (Vth) measured during hypocapnic apnea was consistently larger than Vth at end expiration, suggesting that relaxation of expiratory muscles contributed significantly to both delta Vrc and delta Vdi during spontaneous inspiration. Phrenic nerve stimulation did not contribute to delta Vrc, suggesting that diaphragmatic contraction had no net expanding action on the rib cage above the zone of apposition. Spontaneous breathing after phrenicotomy resulted in small and inconsistent diaphragmatic displacement (8 +/- 4% of VT). We conclude that the diaphragm does not drive the rib cage to inflate the lungs and that rib cage motion does not significantly affect diaphragmatic position during spontaneous breathing in anesthetized dogs lying supine.
Abdomen↗
Effects of acute hyperinflation on chest wall mechanics in dogs.
We studied chest wall mechanics at functional residual capacity (FRC) and near total lung capacity (TLC) in 14 supine anesthetized and vagotomized dogs. During breathing near TLC compared with FRC, tidal volume decreased (674 +/- 542 vs. 68 +/- 83 ml; P less than 0.025). Both inspiratory changes in gastric pressure (4.5 +/- 2.5 vs. -0.2 +/- 2.0 cmH2O; P less than 0.005) and changes in abdominal cross-sectional area (25 +/- 17 vs. -1.0 +/- 4.2%; P less than 0.001) markedly decreased; they were both often negative during inspiration near TLC. Parasternal intercostal shortening decreased (-3.0 +/- 3.7 vs. -2.0 +/- 2.7%), whereas diaphragmatic shortening decreased slightly more in both costal and crural parts (costal -8.4 +/- 2.9 vs. -4.3 +/- 4.1%, crural -22.8 +/- 13.2 vs. -10.0 +/- 7.5%; P less than 0.05). As a result, the ratio of parasternal to diaphragm shortening increased near TLC (0.176 +/- 0.135 vs. 0.396 +/- 0.340; P less than 0.05). Electromyographic (EMG) activity in the parasternals slightly decreased near TLC, whereas the EMG activity in the costal and crural parts of the diaphragm slightly increased. We conclude that 1) the mechanical outcome of diaphragmatic contraction near TLC is markedly reduced, and 2) the mechanical outcome of parasternal intercostal contraction near TLC is clearly less affected.
Abdomen↗
Effects of unilateral vagal stimulation on intrapulmonary neuroepithelial bodies.
We studied the influence of unilateral vagal stimulation on intrapulmonary neuroepithelial bodies (NEB) in rabbits. The left vagus nerve was cut and electrically stimulated for 10 min. Animals were killed and the lungs studied with fluorescence and electron microscopy. Intensity of formaldehyde-induced fluorescence, which reflects the serotonin content in NEB, was higher on the stimulated side than on the nonstimulated side (118 +/- 7 vs. 100%, n = 8, P less than 0.001). The latter difference was found to correlate with the stimulus amplitude (r = 0.9, P less than 0.05). Ultrastructurally a decrease in the number of exocytotic dense-cored vesicle (DCV) profiles at the level of the NEB basal epithelial cell membrane was found on the stimulated side (0.32 +/- 0.10 vs. 0.45 +/- 0.16 DCV/micron of basal epithelial cell membrane, n = 8, P less than 0.05). Section of the left vagus nerve without electrical stimulation affected neither the fluorescence intensity nor the number of exocytotic DCV profiles. In animals with supranodosal or infranodosal chronic vagotomy the observed effects of unilateral vagal stimulation were no longer present. We conclude that 1) vagal stimulation increases the serotonin content of NEB; 2) it decreases the number of exocytotic DCV profiles; 3) this effect depends on the amplitude of the stimulus; 4) it is obtained through efferent vagal fibers; 5) these results are the opposite of the effects seen after exposing normal NEB to acute hypoxia; and 6) these physiological experiments corroborate a vagal innervation of NEB, which may play an important role in modulating the sensitivity and reaction of NEB to various stimuli.
Animals↗
Hypertrophic cardiomyopathy caused by hyperparathyroidism. Report of a case and review of the literature.
Hyperparathyroidism is a rare, recently recognized cause of hypertrophic cardiomyopathy. Elevated serum levels of parathyroid hormone, rather than a rise in the extracellular calcium concentration, appear to be associated with left ventricular hypertrophy. This report describes the history of a patient who developed left ventricular hypertrophy during a 17 years lasting period of recurrent nephrocalcinosis, prior to the diagnosis of hyperparathyroidism. Cardiac function tests remained unchanged fifteen years after parathyroidectomy, suggesting that the latter intervention did not reverse the pathological process but only prevented further cardiac deterioration.
Cardiomyopathy, Hypertrophic↗
Respiratory and postural changes in intercostal muscle length in supine dogs.
In an attempt to assess the physiological function(s) of the external (E) and internal interosseous (I) intercostal muscles, we measured the changes in intercostal muscle length during spontaneous breathing, during passive inflation, and during passive rotation of the trunk. Studies were performed on 46 muscles from 16 supine anesthetized dogs, and changes in muscle length were assessed by sonomicrometry. The changes were small during spontaneous breathing, whether before or after bilateral phrenicotomy, and the pattern was variable among animals and among interspaces. The E, however, particularly in the lower interspaces, often lengthened with inspiration, and the I, in particular in the upper interspaces, often shortened with inspiration. Only occasionally did the E and I in one interspace change in length in opposing directions. This was also true during passive inflation, where both E and I usually shortened in the upper interspaces and lengthened in the lower interspaces. By contrast, during passive rotation of the trunk, the E and I systematically changed in length in opposing directions, and either muscle could successively lengthen and shorten a substantial amount depending on the side of rotation. These results suggest that 1) the E and I in supine dogs do not behave as antagonistic muscles during moderate respiratory efforts; and 2) they do behave as antagonistic muscles during rotation of the trunk. A primary function of these muscles as rotators of the trunk, unlike breathing, may explain why two layers of intercostal muscles with different fiber orientation exist between the ribs.
Animals↗
Coupling between triangularis sterni and parasternals during breathing in dogs.
The purpose of the present studies was to assess the functional coupling between the parasternal intercostals and the triangularis sterni (transversus thoracis) muscles during resting breathing, and we measured the electrical activity and the respiratory changes in length of these two muscles in 13 supine anesthetized dogs. The changes in muscle length were defined relative to their respective in situ relaxation length (Lr). During inspiration, the parasternal intercostals were active and shortened below Lr, causing the triangularis sterni to be passively stretched above Lr. Shortly after the cessation of parasternal contraction, the triangularis sterni became active and shortened below Lr, and in nine animals this active shortening was associated with a forcible distension of the parasternal intercostals above Lr. Deactivation of the triangularis sterni at end expiration caused both muscles to return to their respective Lr. This pattern was essentially unchanged after supplemental anesthesia and bilateral phrenicotomy. We conclude that in dogs breathing quietly the length of the rib cage muscles during the expiratory pause is not passively determined as conventionally thought.
Anesthesia↗
Respiratory resistance with histamine challenge by single-breath and forced oscillation methods.
Relaxed expirations were obtained from five anesthetized dogs under control conditions and during various rates of intravenous infusion of histamine. All volume vs. time curves obtained from 20 ms to 2 s after the start of expiration were poorly described by a single exponential function but were fitted very well by a biexponential function. The resistance of the respiratory system as a function of frequency from 2 to 26 Hz was also determined by the forced oscillation method in the same dogs. Three two-compartment models of the respiratory system were identified from the exponentials fitted to the relaxed expiration data, and the one that had the most plausible parameter values under control conditions consisted of a homogeneous lung compartment connected to a viscoelastic compartment. Although a two-compartment model is arguably appropriate for describing relaxed expirations in normal dogs, physiological considerations suggest that there should be more than two interacting components with histamine infusion. We cannot identify all these components from our data, however. The equivalent complex impedance of the respiratory system was also calculated from the biexponential curves and showed significant variation in resistance over the frequency range from 0 to 2 Hz and negligible variation above 2 Hz. The calculated resistances at 2 Hz were consistently higher than those obtained by the forced oscillation method, which may be due to the nonlinear behavior of the respiratory system during relaxed expiration. We conclude that the single-breath and forced oscillation methods should be viewed as providing complimentary information about respiratory resistance.
Airway Resistance↗
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).
Abdomen↗