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Biomedical subjects

S G Kelsen

Publications and source records attributed to S G Kelsen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effect of dantrolene on ventilation and respiratory muscle activity in anaesthetized dogs.

The effect of dantrolene on ventilation and ventilatory muscle activity was evaluated in spontaneously breathing anaesthetized dogs. When administered as a bolus of 1.5 mg kg-1 i.v., dantrolene caused hypercapnia. Under isocapnic conditions, with end-tidal PCO2 maintained at 8.1 (SEM 0.3) kPa by adjusting inspired carbon dioxide, dantrolene decreased tidal volume from 475 (66) to 254 (46) ml and breathing rate from 21 (4) to 15 (3) b.p.m. (P less than 0.01 for both). Occlusion pressure was reduced, but the rate of rise of the diaphragm and intercostal EMG were unchanged and peak activity increased only as a result of prolongation of inspiration. Respiratory variables returned gradually to baseline values 1 h after dantrolene administration. Phrenic nerve stimulation revealed a marked reduction in the ability of the diaphragm to generate pressure, particularly at low frequencies of stimulation. Only partial recovery was observed after 1 h. It is concluded that dantrolene causes hypoventilation in the anaesthetized dog when given in large doses i.v.

Action Potentials↗
PubMed1990

Epithelial effects on tracheal smooth muscle tone: influence of muscarinic antagonists.

The tracheobronchial epithelium produces factor(s) that modulate the constrictor and relaxant response of airway smooth muscle. The present study sought to determine whether the tracheobronchial epithelial inhibitory effect on trachealis smooth muscle tension is under muscarinic receptor control. Studies were performed on 195 strips from 13 rabbits. In strips in which the epithelium was intact, pirenzepine (an M1 receptor antagonist) produced a dose-related (10(-8) and 10(-7)M) rightward shift (P less than 0.01 for each) and gallamine (an M2 antagonist) produced a progressive (10(-8) and 10(-7)M) leftward shift of the acetylcholine concentration responses (P less than 0.01 for each). In strips in which the epithelium was removed mechanically, neither pirenzepine nor gallamine had any effect on the acetylcholine responses. In acetylcholine precontracted (5 x 10(-6) M) muscle strips with epithelium intact, addition of pirenzepine (10(-7)M) produced a significant (P less than 0.01) reduction in steady-state tension, whereas administration of gallamine tended to increase tension, (P = NS). Neither pirenzepine nor gallamine had any effect on steady-state tension in strips in which the epithelium was removed. These results indicate that the magnitude of the tracheobronchial epithelial inhibitory effect on smooth muscle tension is under muscarinic control. Specifically, M1 receptor blockade augments and M2 receptor blockade inhibits the magnitude of the tracheobronchial epithelial effect.

Acetylcholine↗
PubMed1990

Measurement of intracellular pH in hamster diaphragm by absorption spectrophotometry.

The regulation of intracellular pH (pHi) is important in controlling muscle contraction. In these experiments, a spectrophotometric method of determining pHi was developed, and the method was then used to study muscle pHi regulation during CO2-induced changes in extracellular pH (pHb). Studies were performed in vitro on 27 diaphragm muscle strips obtained from adult hamsters. pHi was measured from the ratio of the absorbances of the acid (lambda = 530 nm) and alkaline (lambda = 460 nm) forms of a vital dye, neutral red, using the unstained diaphragm spectrum as a reference blank. A standard neutral red calibration curve constructed from eight diaphragm muscle homogenates indicated that the absorbance ratio was highly linear, with pH over the range 6.00-8.00. In intact muscle strips gassed with 95% O2-5% CO2, pHb was 7.45 +/- 0.03 (SE) and pHi was 7.00 +/- 0.01 (SE). When the muscle was aerated with CO2 concentrations from 3 to 30%, pHb and pHi changed rapidly and reached a steady state in 10-15 min. However, when pHb ranged from 6.80-7.80, pHi changed little from the value observed when pHb was 7.40. When pHb was less than 6.80 or greater than 7.80, changes in pHi and pHb were quantitatively similar. The results suggest that, in the isolated diaphragm, overall pHi is stable and effectively buffered over a wide range of CO2-induced changes in buffer solution pH.

Animals↗
PubMed1990

Comparison of scales used to quantitate the sense of effort to breathe in patients with chronic obstructive pulmonary disease.

Several different scaling techniques, i.e., Borg category (BC) and visual analogue (VA) scales have been used to quantitate the intensity of the respiratory sensations elicited during exercise, but their relationship is unclear. Six subjects with stable chronic obstructive lung disease (FEV1 = 1.2 +/- 0.1 SE L) simultaneously rated the sense of effort to breathe with both BC and VA scales during progressive, maximal exercise tests performed three to five times on a cycle ergometer. The VA scores correlated linearly with minute ventilation in all subjects in all trials (r = 0.98 +/- 0.01), and when converted to common units (i.e., Z scores) correlated closely with simultaneous scores obtained using the Borg scale (r = 0.99 +/- 0.01). Furthermore, VA scores varied minimally over several trials. Coefficient of variation for the maximal VA scores was 6 +/- 1%, which was similar to the variation in maximal Borg score (i.e., 3 +/- 1%). We conclude that the visual analogue scale is reproducible and correlates closely with the Borg score when scaling the sense of effort to breathe during exercise in subjects with stable chronic obstructive pulmonary disease.

Aged↗
PubMed1990

Effects of aging on diaphragm contractile function in golden hamsters.

The present study investigated the effects of aging on the contractile properties of the adult diaphragm in 42 Golden Syrian hamsters. Experiments were performed on isolated diaphragm strips from three groups of animals 4.9 +/- 0.4 (SE), 12.8 +/- 0.2, and 18.8 +/- 0.3 months of age. Aging was associated with a decrease in the maximal isometric tension generated per unit cross-sectional area of muscle and slowing in the time-to-peak tension and rate of muscle relaxation. The velocity of muscle shortening at a given load was also significantly less in older than in younger animals, and the force-velocity curve became flatter with advancing age as reflected by increases in the Hill coefficient (a/P0). Changes in maximal active tension and maximal velocity of unloaded shortening with aging correlated weakly (r greater than 0.3; p less than 0.05) and were of similar magnitude (-17 to -21%), suggesting that aging affects these two indices of muscle function in similar fashion. Finally, the diaphragm fatigued more rapidly in older than in younger animals. We conclude that aging depresses the ability of the adult diaphragm to generate tension and to shorten and resist fatigue.

Aging↗
PubMed1989

Relationship between diaphragmatic activation and twitch tension to superimposed electrical stimulation in the cat.

The purpose of these experiments was to evaluate the validity of the 'twitch-occlusion' method as an index of the extent of diaphragmatic activation and to assess the extent of diaphragmatic activation during inspiration. Studies were performed in situ on innervated, perfused muscle strips from the costal region of the diaphragm in ten anesthetized cats. We measured isometric tension generated by the diaphragm during inspiration and following an interpolated electrical stimulation (2 Hz, 100 microseconds, 3.0 x threshold) of the nerve. The extent of MU activation was assessed by comparing twitch amplitudes during electrical stimulation applied in expiration and in inspiration. Spontaneous inspiratory activity was induced by adding CO2 to the inspired oxygen. Within an animal, the relationship between diaphragmatic activation and twitch occlusion was linear (range of r values was from -0.88 to -0.94). The extent of spontaneous diaphragmatic activation was normalized by dividing tension at end inspiration by the average twitch tension caused by stimuli applied during expiration. Across animals, twitch amplitude was inversely related to diaphragmatic activation (y = -0.36x + 1.13, r = -0.94). At a respiratory drive with end-tidal PCO2 approximately 1% above apneic threshold (end-tidal PCO2 between 5 and 6%), twitch occlusion was less than 5.0%. Increasing end-tidal PCO2 to at least 5% above apneic threshold (end-tidal PCO2 between 9 and 11%), twitch occlusion was still less than 50%. These results from a preparation that allows direct measurement of isometric tension of the diaphragm show that the interpolated twitch is linearly related to the extent of muscle activation through a broad range of muscle activity. In addition, these data indicate that a higher respiratory drives there exists a large reserve in the phrenic motor pool.

Animals↗
PubMed1989

Reflex effect of esophageal distension on respiratory muscle activity and pressure.

The electrical activity of the respiratory skeletal muscles is altered in response to reflexes originating in the gastrointestinal tract. The present study evaluated the reflex effects of esophageal distension (ED) on the distribution of motor activity to both inspiratory and expiratory muscles of the rib cage and abdomen and the resultant changes in thoracic and abdominal pressure during breathing. Studies were performed in 21 anesthetized spontaneously breathing dogs. ED was produced by inflating a balloon in the distal esophagus. ED decreased the activity of the costal and crural diaphragm and external intercostals and abolished all preexisting electrical activity in the expiratory muscles of the abdominal wall. On the other hand, ED increased the activity of the parasternal intercostals and expiratory muscles located in the rib cage (i.e., triangularis sterni and internal intercostal). All effects of ED were graded, with increasing distension exerting greater effects, and were eliminated by vagotomy. The effect of increases in chemical drive and lung inflation reflex activity on the response to ED was examined by performing ED while animals breathed either 6.5% CO2 or against graded levels of positive end-expiratory pressure (PEEP), respectively. Changes in respiratory muscle electrical activity induced by ED were similar (during 6.5% CO2 and PEEP) to those observed under control conditions. We conclude that activation of mechanoreceptors in the esophagus reflexly alters the distribution of motor activity to the respiratory muscles, inhibiting the muscles surrounding the abdominal cavity and augmenting the parasternals and expiratory muscles of the chest wall.

Animals↗
PubMed1989

Effect of hypercapnia and PEEP on expiratory muscle EMG and shortening.

The present study examined the effects of hypercapnia and positive end-expiratory pressure (PEEP) on the electromyographic (EMG) activity and tidal length changes of the expiratory muscles in 12 anesthetized, spontaneously breathing dogs. The integrated EMG activity of both abdominal (external oblique, internal oblique, rectus abdominis, and transverse abdominis) and thoracic (triangularis sterni, internal intercostal) expiratory muscles increased linearly with increasing PCO2 and PEEP. However, with both hypercapnia and PEEP, the percent increase in abdominal muscle electrical activity exceeded that of thoracic expiratory muscle activity. Both hypercapnia and PEEP increased the tidal shortening of the external oblique and rectus abdominis muscles. Changes in tidal length correlated closely with simultaneous increases in muscle electrical activity. However, during both hypercapnia and PEEP, length changes of the external oblique were significantly greater than those of the rectus abdominis. We conclude that both progressive hypercapnia and PEEP increase the electrical activity of all expiratory muscles and augment their tidal shortening but produce quantitatively different responses in the several expiratory muscles.

Animals↗
PubMed1989

Effects of progressive hypoxia on parasternal, costal, and crural diaphragm activation.

The distribution of motor drive to the costal and crural diaphragm and parasternal intercostal muscles was evaluated during progressive isocapnic hypoxia in anesthetized dogs. Bipolar stainless steel wire electrodes were placed unilaterally into the costal and crural portions of the diaphragm and into the parasternal intercostal muscle in the second or third intercostal space. Both peak and rate of rise of electromyographic activity of each chest wall muscle increased in curvilinear fashion in response to progressive hypoxia. Both crural and parasternal intercostal responses, however, were greater than those of the costal diaphragm. The onset of crural activation preceded that of the costal portion of the diaphragm and parasternal intercostal muscle activation. Despite differences in the degree of activation among the various chest wall muscles, the rate of increase in activation for any given muscle was linearly related to the rate of increases for the other two. This suggests that respiratory drive during progressive hypoxia increases in fixed proportion to the different chest wall inspiratory muscles. Our findings lend further support to the concept that the costal and crural diaphragm are governed by separate neural control mechanisms and, therefore, may be considered separate muscles.

Animals↗
PubMed1989

Epithelial modulation of trachealis muscle tension is calcium and temperature dependent.

The tracheobronchial epithelium produces inhibitory substance(s) that alter the tracheal smooth muscle tension. This study examined the effect of changes in extracellular Ca2+ and temperature in vitro on the tension response of rabbit trachealis muscle to mechanical removal of the epithelium. Tension during acetylcholine- and KCl-induced contractions was examined at 0, 0.75, 1.5, 2.5, and 5 mM bath Ca2+ concentrations and at 37, 30, 23, and 41 degrees C bath temperature. At most extracellular Ca2+ concentrations (i.e., 0.75, 1.5, 2.5, and 5 mM), epithelial removal shifted the acetylcholine concentration response approximately one-half log to the left (P less than 0.001 for each condition) but had no effect on the responses to KCl (P = NS). Reductions in bath Ca2+ to 0 mM eliminated the epithelial inhibitory effect on the acetylcholine response. In contrast to the effects of reductions in Ca2+, cooling the airway to 30 and 23 degrees C progressively diminished the magnitude of the epithelial inhibitory effect. Our results indicate that the influence of the tracheal epithelium on tracheal smooth muscle responses to constrictor agonists is substance specific and can be diminished by reductions in tracheal temperature and extracellular Ca2+ concentration.

Acetylcholine↗
PubMed1988

Effect of fatiguing resistive loads on the level and pattern of respiratory activity in awake goats.

The effect of respiratory muscle fatigue on inspiratory muscle electrical activity (EMG), transdiaphragmatic pressure and ventilation during spontaneous breathing was examined in three awake goats. Studies were performed during progressive hypercapnia before and immediately after inspiratory muscle fatigue induced by flow resistive loading (IRL). IRL caused a decrease in the high-low ratio of the diaphragm and intercostal EMG and a decrease in Pdi during electrophrenic stimulation. After IRL, inspiratory time, the breathing duty cycle (inspiratory time/total breath cycle time), peak integrated activity of the diaphragm and external intercostal EMG per breath and per minute were all decreased at any given level of PCO2. Changes in the timing of respiratory motor activity and reduced muscle performance after IRL resulted in a decrease in transdiaphragmatic pressure and ventilation during hypercapnia. In conscious goats studied during spontaneous, chemically stimulated breathing, inspiratory muscle fatigue is associated with reductions in diaphragm and external intercostal muscle electrical activity and reductions in transdiaphragmatic pressure and ventilation.

Animals↗
PubMed1988

Effect of theophylline on the velocity of diaphragmatic muscle shortening.

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Relationship of changes in diaphragmatic muscle blood flow to muscle contractile activity.

The effect of increases in diaphragmatic muscle contractile activity on diaphragm blood flow remains unclear. The present study examined the effect of electrically induced isometric diaphragmatic muscle contractions on diaphragmatic blood flow. Studies were performed on diaphragmatic muscle strips prepared in anesthetized mechanically ventilated dogs. Diaphragmatic contractile activity was quantitated as the tension-time index (TTI) (i.e., the product of tension magnitude and duration). Blood flow to the strip (Qdi) was measured from the volume of the phrenic venous effluent using a drop counter. The separate effects on Qdi of 30-s periods of continuous and rhythmic contractions were examined. Qdi increased with increases in TTI and peaked at a TTI of 20-30% of maximum after which Qdi fell progressively with further increases in TTI. At levels of TTI greater than 30%, the pattern of muscle contraction significantly affected blood flow. Qdi was significantly lower during activity and the postcontraction hyperemia significantly greater at a given TTI when contractions were continuous than when contractions were intermittent. Above a TTI of 30%, Qdi during contraction decreased linearly with increases in duty cycle and curvilinearly with increases in tension. We conclude that during isometric diaphragmatic contractions, diaphragmatic blood flow may become mechanically impeded, and the magnitude of the impediment in blood flow depends on the pattern of diaphragmatic contractions. With increases in contractile activity above a critical level, changes in duty cycle exert progressively greater effects on diaphragmatic blood flow than changes in muscle tension.

Animals↗
PubMed1987

Effect of inspiratory muscle fatigue on perception of effort during loaded breathing.

The present study examined the relationship between the intensity of the sense of effort during inspiratory threshold loading and the severity of inspiratory muscle fatigue. Studies were performed on normal subjects in whom the magnitude of airway pressure developed (Pm) and the duty cycle of breathing (TI/TT) were constrained to achieve a pressure-time integral (i.e., Pm/Pmax X TI/TT) 24% of maximum. In separate trials, the same pressure-time index (24%) was achieved using two widely different patterns of pressure magnitude and duty cycle to allow the effects of changes in the pattern of inspiratory muscle contraction on sensation and fatigue to be assessed. The intensity of the sense of effort was assessed using a category (Borg) scale. The severity of inspiratory muscle fatigue was assessed both from changes in the centroid frequency of the diaphragm electromyogram and from changes in the maximum static inspiratory pressure. Loaded breathing produced inspiratory muscle fatigue and a progressive increase in the sense of effort over time in all subjects. The rate at which the inspiratory muscles fatigued was the same with the two patterns of loading. In contrast, the rate of growth in the intensity of the sense of effort varied significantly as a function of the pattern of loaded breathing. The sense of effort increased at a faster rate with the high pressure-short duty cycle pattern of contraction as compared with the low pressure-long duty cycle pattern. As a result, the intensity of the sense of effort was not uniquely related to the severity of inspiratory muscle fatigue.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effects of bronchoconstriction on respiratory muscle activity during expiration.

The effect of methacholine-induced bronchoconstriction on the electrical activity of respiratory muscles during expiration was studied in 12 anesthetized spontaneously breathing dogs. Before and after aerosols of methacholine, diaphragm, parasternal intercostal, internal intercostal, and external oblique electromyograms were recorded during 100% O2 breathing and CO2 rebreathing. While breathing 100% O2, five dogs showed prolonged electrical activity of the diaphragm and parasternal intercostals in early expiration, postinspiratory inspiratory activity (PIIA). Aerosols of methacholine increased pulmonary resistance, decreased tidal volume, and elevated arterial PCO2. During bronchoconstriction, when PCO2 was varied by CO2 rebreathing, PIIA was shorter at low levels of PCO2, and external oblique and internal intercostal were higher at all levels of PCO2. Vagotomy shortened PIIA in dogs with prolonged PIIA. After vagotomy, methacholine had no effects on PIIA but continued to increase external oblique and internal intercostal activity at all levels of PCO2. These findings indicate that bronchoconstriction influences PIIA through a vagal reflex but augments expiratory activity, at least in part, by extravagal mechanisms.

Animals↗
PubMed1987

Length-tension relationship of abdominal expiratory muscles: effect of emphysema.

The present study examined the active and passive length-tension relationship of the abdominal expiratory muscles in vitro during electrically stimulated contractions. Studies were performed on isolated strips of transverse abdominis and external oblique muscle from nine adult hamsters with normal lung function. The effect of chronic hyperinflation on the two muscles was assessed in eight hamsters with elastase-induced emphysema. In normal animals the maximal active tension per cross-sectional area (Po) was equal in the two muscles. The absolute muscle fiber length at which Po occurred (Lo) was less for the external oblique than the transverse abdominis and the length-tension curve operated at shorter fiber lengths. However, the change in tension produced by an increase or decrease in muscle length expressed in relative terms (i.e., as %Lo) was greater for the transverse abdominis than the external oblique. Mean total lung capacity of emphysematous animals was 198% of control. Po of the transverse abdominis and external oblique were the same in emphysematous and control animals. However, Lo and the length-tension curve of the transverse abdominis occurred at shorter fiber lengths in emphysematous animals because of a reduction in the number of sarcomeres in series along the fiber. The length-tension curve and the number of sarcomeres in the external oblique was the same in emphysematous and control animals. These results in normal animals indicate that the magnitude of the change in active and passive tension produced by a change in muscle length differs in the transverse abdominis and external oblique. Moreover, chronic hyperinflation of the thorax produced by elastase injection alters the length-tension relationships of some but not all the expiratory muscles.

Abdomen↗
PubMed1987

Contractile properties of expiratory abdominal muscles: effect of elastase-induced emphysema.

The present study examined the intrinsic contractile properties and endurance of the transverse abdominis and external oblique abdominal expiratory muscles in adult hamsters and compared their performance with the diaphragm. Experiments were performed in vitro on isolated bundles of muscle stimulated electrically. In control animals peak twitch tension was similar in the two muscles. In contrast, the twitch contraction time and one-half relaxation time of the transverse abdominis were significantly greater than that of the external oblique. The isometric tension generated over a range of stimulus frequencies (i.e., the force-frequency relationship) was a greater percent of the maximum value in response to subtetanizing frequencies (10-40 Hz) in the transverse abdominis than in the external oblique. For both abdominal muscles, however, the tension generated over this range of stimulus frequencies was less than that of the diaphragm. The endurance of the transverse abdominis during repeated contractions was significantly greater than that of the external oblique but similar to the diaphragm. The effect of chronic hyperinflation produced by elastase-induced emphysema on the contractile function of the two muscles was assessed in a second group of adult hamsters. In emphysematous animals peak twitch tension, contraction time, and one-half relaxation time of the twitch and force-frequency curves of muscles from emphysematous animals were similar to values obtained in control animals for both the external oblique and transverse abdominis. However, the endurance of both the transverse abdominis and external oblique muscles was greater in emphysematous than control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗