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Biomedical subjects

S G Kelsen

Publications and source records attributed to S G Kelsen.

At least 73 records · Page 4Linked to original sources
PubMed1987

Structure of abdominal muscles in the hamster: effect of elastase-induced emphysema.

The present study examined the effects of elastase-induced emphysema on the structure of the external oblique and transverse abdominis muscles and a non-respiratory muscle, the extensor digitorum longus. Muscle structure was assessed from the cross-sectional area (CSA) and percent of individual fiber types in histochemically stained sections and from the number of sarcomeres arranged in series along the length of individual fibers. Data were obtained in eight hamsters with emphysema and nine saline-injected controls. In the normal (control) animals the external oblique was thicker but contained fewer sarcomeres than the transverse abdominis. Fiber size was similar in the two muscles. In the transverse abdominis the percents of fast-glycolytic and fast-oxidative fibers were greater and smaller, respectively, than in the external oblique. Lung volume of emphysematous hamsters was 168% of control values (P less than 0.001). In emphysematous compared with control animals, the CSA of fast-twitch fibers in the external oblique and transverse abdominis was significantly reduced. Fiber length and sarcomere number were significantly decreased in the transverse abdominis but not in the external oblique in emphysematous hamsters. In contrast, fiber size and composition of the extensor digitorum longus was similar in emphysematous and control animals. These data indicate that cellular responses of the ventilatory muscles to chronic hyperinflation and altered thoracic geometry induced by emphysema are not present in limb skeletal muscle. We speculate that changes in fiber length and CSA of fast fibers in the abdominal expiratory muscles reflect responses to chronic alterations in the mechanics of breathing that may affect muscle load, length, or the pattern of activity.

Abdominal Muscles↗
PubMed1986

Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters.

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4-5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1986

Effect of alterations in muscle fiber length on diaphragm blood flow.

A variety of studies have examined the response of diaphragmatic blood flow (Qdi) to rhythmic pleiometric (i.e., shortening) and isometric contractions. The effect of changes in diaphragm fiber length on Qdi are, however, unknown. The present study examined the effect of changes in diaphragm fiber length on Qdi and the effect of alterations in length on the response of Qdi to increases in diaphragm contractile activity. Studies were performed on 21 anesthetized mechanically ventilated dogs in which a strip of costal diaphragm was developed in situ. The strip was immobilized in a rigid metal frame that permitted precise adjustment of muscle length. Strip blood flow was assessed with a drop counter attached to a catheter in the branch of the phrenic vein draining the strip. Strips were electrically stimulated via intramuscular electrodes, and the isometric tension developed was measured with a force transducer. Fiber length was expressed as a percentage of the length at which active isometric tension was maximum (Lo). With the diaphragm at rest, steady-state blood flow fell by 59 +/- 6% (SE) (P less than 0.001) as fiber length was increased from 92 to 107% Lo. Blood flow also varied as a function of length when muscles contracted rhythmically (15 contractions/min, duty cycle 50%) to generate isometric tensions equal to 20 and 80% of maximum. As fiber length increased from 92 to 106% Lo, Qdi fell by 36 +/- 6% (SE) when tension was 80% of maximum (P less than 0.01) and by 38 +/- 6% (SE) when tension was 20% of maximum (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Caffeine effect on respiratory muscle endurance and sense of effort during loaded breathing.

The present study examined respiratory muscle endurance and the magnitude of the sense of effort during inspiratory threshold loading following a dose of caffeine (600 mg) previously observed to increase diaphragm strength. Experiments were performed on 12 normal subjects. Respiratory muscle endurance at a given level of load was assessed from the time of exhaustion and from the time course of the change in the power spectrum (centroid frequency) of the diaphragm electromyogram (EMG). The intensity of the sense of effort during loaded breathing was evaluated using a category (Borg) scale. Increasingly severe loads were associated with more rapid onset of fatigue. At a given load, caffeine prolonged the time to exhaustion and decreased the rate of fall of the centroid frequency of the diaphragm EMG. Caffeine also decreased the sense of effort during loaded breathing in 9 of 11 subjects. Changes in respiratory muscle endurance after caffeine administration were not explained by changes in the pressure-time index of the respiratory muscles or the pattern of thoracoabdominal movement. We conclude that caffeine enhances inspiratory muscle endurance, while concomitantly reducing the sense of effort associated with fatiguing inspiratory muscle contractions.

Adult↗
PubMed1986

Changes in chest wall structure and elasticity in elastase-induced emphysema.

The present study examined the effects of elastase-induced emphysema on the structure and elasticity of the chest wall. Specifically, we examined the passive pressure-volume relationship of the intact chest wall in anesthetized animals and the stress-strain relationship of the isolated rib cage devoid of respiratory musculature. The structure of the isolated rib cage was assessed by measuring its circumferential, anterior-posterior, and transverse dimensions, the angles of articulation of the ribs at the costovertebral and sternochondral joints, and the length of the sternum and individual ribs. Studies were performed in 10 Syrian Golden hamsters, 26-27 wk after intratracheal injection of elastase, and 9 saline-injected hamsters that served as controls. Mean functional residual capacity of emphysematous animals was 239% of the value obtained in control animals. In emphysematous animals, the pressure-volume curve of the chest wall was shifted parallel and to the left of the curve obtained in controls. That is, at any given esophageal pressure, lung volume was significantly greater in emphysematous animals compared with controls, but the slope of the pressure-volume relationship was similar in the two groups. In the relaxed position, the circumference, anterior-posterior, transverse, and rostral-caudal dimensions of the thorax were significantly greater in emphysematous than control animals. Although the length of the thoracic spinal column was the same in both groups, the length of the ribs and sternum were greater in emphysematous animals and the angles of articulation of the ribs with the vertebrae and sternum were altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The effects of undernutrition on the respiratory muscles.

During prolonged undernutrition, the mass of skeletal muscle represents the body's main store of protein and energy. Although it is known that cardiac striated muscle is relatively spared in undernutrition, and that disease-induced reductions in lean body mass do not spare respiratory muscle, the effects of undernutrition per se on the structure and function of the respiratory muscle are largely unstudied in humans. Available data are reviewed.

Animals↗
PubMed1986

Comparative effects of theophylline and adenosine on respiratory skeletal and smooth muscle.

This study compared the effects of theophylline and adenosine on the contractile activity of respiratory smooth and skeletal muscles in vitro. Studies were performed on isolated strips of tracheal smooth and diaphragmatic skeletal muscle from 22 Hartley strain guinea pigs. The changes in diaphragm and tracheal smooth muscle tension in response to electrical stimulation and histamine-induced contraction, respectively, were assessed over a range of theophylline and adenosine concentrations (10(-7) to 10(-3) M for each). Theophylline increased diaphragmatic tension and reversed histamine-induced smooth muscle contractions in a dose-dependent fashion. Theophylline, however, decreased tracheal tension at concentrations an order of magnitude lower than those that increased diaphragmatic tension. Adenosine mimicked the effect of theophylline on tracheal muscle but had no effect on the force of diaphragm contraction. Moreover, adenosine failed to alter the theophylline dose-response curve for diaphragmatic tension. This study demonstrates that airway smooth muscle is more sensitive than is respiratory skeletal muscle to the effects of theophylline. Furthermore, these data suggest that the effects of theophylline on diaphragm skeletal muscle are not mediated by adenosine receptor blockade.

Adenosine↗
PubMed1985

Effects of prolonged undernutrition on structure and function of the diaphragm.

The present study examined the effect of prolonged undernutrition on diaphragmatic structure and force-generating ability. Studies were performed on 58 Syrian hamsters in which the feed was reduced by 33% for a 4-wk period. Sixty animals fed a similar diet ad libitum served as controls. Diaphragm muscle structure was assessed from its mass (wet and dry weight), thickness, fiber composition, and fiber size. Isometric force produced in vitro by isolated muscle strips in response to electrical stimulation of the phrenic nerve was examined over a range of muscle lengths (length-tension relationship). In undernourished animals, body weight decreased 25 +/- 5%. Diaphragm wet and dry weight, muscle thickness, and the cross-sectional area of fast-glycolytic (FG) and fast-oxidative (FO) fibers were significantly less in undernourished than control animals and correlated with reductions in body weight. The cross-sectional area of slow-oxidative (SO) fibers was the same in the two groups. The percentage of FG fibers in undernourished animals was decreased slightly and the percentage of SO fibers increased. Maximum isometric tension was reduced in undernourished animals as compared with controls, but the position and shape of the length-tension relationship was the same in the two groups. Reductions in muscle force appeared to be explained by decreases in muscle mass, since tension corrected for cross-sectional area or tissue weight was the same in the two groups. Therefore muscle mechanical efficiency appeared to be unaffected by undernutrition. These data indicate that prolonged undernutrition causes deleterious changes in diaphragm muscle structure that impair its ability to generate force.

Animals↗
PubMed1985

Effects of hypercapnia on inspiratory and expiratory muscle activity during expiration.

Persistence of inspiratory muscle activity during the early phase of expiratory airflow slows the rate of lung deflation, whereas heightened expiratory muscle activity produces the opposite effect. To examine the influence of increased chemoreceptor drive and the role of vagal afferent activity on these processes, the effects of progressive hypercapnia were evaluated in 12 anesthetized tracheotomized dogs before and after vagotomy. Postinspiratory activity of inspiratory muscles (PIIA) and the activity of expiratory muscles were studied. During resting breathing, the duration of PIIA correlated with the duration of inspiration but not with expiration. Parasternal intercostal PIIA was directly related to that of the diaphragm. Based on their PIIA, dogs could be divided into two groups: one with prolonged PIIA (mean 0.57 s) and the other with brief PIIA (mean 0.16 s). Hypercapnia caused progressive shortening of the PIIA in the dogs with prolonged PIIA during resting breathing. The electrical activity of the external oblique and internal intercostal muscles increased gradually during CO2 rebreathing in all dogs both pre- and postvagotomy. After vagotomy, abdominal activity continued to increase with hypercapnia but was less at all levels of PCO2. The internal intercostal response to hypercapnia was not affected by vagotomy. The combination of shorter PIIA and augmented expiratory activity with hypercapnia might, in addition to changes in lung recoil pressure and airway resistance, hasten exhalation.

Abdominal Muscles↗
PubMed1985

The effects of acute bronchoconstriction on respiratory activity in patients with chronic obstructive pulmonary disease.

Attacks of acute airway obstruction often complicate the course of chronic obstructive pulmonary disease (COPD). In asthmatic subjects, bronchospasm triggers an increase in respiratory drive, which results in hyperventilation and hypocapnia. In the present study, we assessed the effects of acute bronchoconstriction induced by aerosolized methacholine on breathing and lung mechanics in 12 patients with stable COPD. Even low doses of methacholine markedly increased airway resistance and caused hyperinflation and decreased inspiratory muscle performance in the patients. Increasing airway obstruction produced a progressive rise in PCO2 despite an increase in minute ventilation. Breathing frequency and average inspiratory flow were greater, but tidal volume decreased because of shortening of the inspiratory duration. The magnitude of CO2 retention during acute bronchoconstriction was inversely related to the changes in tidal volume and inspiratory time (p less than 0.01 for each). In subjects with COPD, the occlusion pressure response to progressive hypercapnia failed to increase during bronchoconstriction. These results show that patients with COPD retain CO2 during acutely increasing airway obstruction induced by bronchoconstriction partly because of a rapid shallow breathing pattern that reduces alveolar ventilation.

Aged↗
PubMed1985

Comparative effects of aminophylline on diaphragm and cardiac contractility.

The mechanisms by which aminophylline increases inspiratory muscle contractility are unclear. The present study compared the effects of aminophylline on cardiac as well as on diaphragm contractility and examined the interaction of aminophylline with verapamil, a calcium channel-blocking agent, on both types of muscle. Experiments were performed in mongrel dogs anesthetized with pentobarbitone. Diaphragm contractility was assessed from transdiaphragmatic pressure (Pdi) developed during supramaximal electrical stimulation of the cervical phrenic rootlets, and cardiac contractility was assessed from peak left ventricular (LV) pressure and its rate of rise (dPv/dt). Measurements were made before and after each of 3 sequential IV infusions of aminophylline (6 mg/kg) and subsequent IV infusions of verapamil (0.1 mg/kg bolus and 0.02 mg/kg/min for 5 to 7 min.). Transient decreases in Pdi were frequently observed immediately after aminophylline infusion in association with decreases in mean arterial blood pressure. With recovery of mean blood pressure, Pdi increased above baseline values. Aminophylline increased Pdi in a dose-dependent fashion over the entire frequency range studied (1 to 40 Hz). Aminophylline increased the rate of rise of Pdi (dPd/dt) without affecting the period over which pressure was developed or dissipated during single twitches. Aminophylline increased both peak LV pressure and dPv/dt. The magnitude of the cardiac response was greater than the diaphragmatic response. Subsequent verapamil infusion completely reversed the effects of aminophylline on LV contractility but had only a small effect on diaphragm contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1985

Respiratory pressure sensation. Relationship to changes in breathing pattern and PCO2 during acute increase in airway resistance in patients with chronic obstructive pulmonary disease.

The intensity of sensations experienced during breathing by patients with chronic obstructive pulmonary disease (COPD) might influence their ventilatory response to altered lung mechanics. In 8 patients with COPD (mean FEV1, 1.6 +/- 0.6 L SD) the acuity with which changes in intrathoracic pressure were perceived was studied by a standard psychophysical technique, magnitude production of inspiratory pressure. Subjects voluntarily produced mouth pressures proportional to numbers randomly presented, and the sensory acuity to changes in pressure was assessed from the slope of log-log plots of numbers versus pressures. These slopes were then related to the ventilatory responses of the patients to external resistive loads of 10 cm H2O/L/s, applied during both inspiration and expiration, and methacholine-induced bronchoconstriction, which doubled baseline specific airway resistance. Both modes of increase in airway resistance caused an increase in end-tidal PCO2 in all patients (range, 0.5 to 11 mmHg). The magnitude of CO2 retention correlated significantly with the change in tidal volume during both external loading and bronchoconstriction (r = -0.77, p less than 0.01); decreases in tidal volume were associated with increases in PCO2. The slope for magnitude production of pressure was inversely related to changes in tidal volume during both modes of increases in airway resistance (r = 0.61, p less than 0.01 for both bronchoconstriction and external resistive loads). Patients with the highest exponents for pressure changes (highest slopes) demonstrated the greatest decreases in tidal volume. Consequently, a direct relationship was found between the magnitude of the exponent and the magnitude of CO2 retention during loaded breathing and bronchoconstriction (r = 0.81, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1984

Respiratory response to partial paralysis in anesthetized dogs.

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1984

Respiratory responses to external resistive loads during vagal blockade in awake dogs.

The present study examined the possibility that mechanoreceptors in the chest wall structures (rib cage and diaphragm) contribute to the increase in the neuromuscular drive to breathe (occlusion pressure) when the load on the respiratory muscles is increased in conscious animals and humans. Studies were carried out in 4 awake dogs in which external resistive loads (12 cmH2O/L/s) were applied during inspiration to increase the load on the respiratory muscles. Loads were applied via a tracheostomy during complete vagal blockade performed by cooling exteriorized cervical vagal loops. The ventilatory and occlusion pressure responses to the load were compared over the same range of chemical drive by applying loads during CO2 rebreathing. During vagal blockade, inspiratory resistive loads had no consistent effect on the duration of inspiration or expiration and decreased the ventilatory response to hypercapnia by decreasing average inspiratory flow rate. In all animals, however, inspiratory loading increased the occlusion pressure (P100) response to hypercapnia. The P100 at PCO2 = 55 mmHg increased during flow loading in all 4 animals, and the slope of the change in P100 produced for a given change in PCO2 (delta P100/delta PCO2) increased in 3 of the 4. Flow loading had no effect on end-expiratory lung volume at rest and did not influence the decrease in lung volume observed during hypercapnia. The present study indicated that the neuromuscular drive to breathe, as assessed from the occlusion pressure, is increased in conscious animals subjected to ventilatory loads during vagal blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

The effects of caffeine and theophylline on diaphragm contractility.

The present study examined the effect of single, orally administered, doses of caffeine (600 mg) on diaphragmatic muscle contractility in 6 normal subjects and compared the magnitude of the effect with that of theophylline. The force-generating ability of the diaphragm was assessed from measurements of transdiaphragmatic pressure (Pdi) obtained via catheters in the esophagus and stomach, and the level of diaphragmatic excitation was assessed from the diaphragmatic electromyogram recorded with an esophageal electrode. Caffeine increased Pdi at all levels of diaphragmatic electromyographic activity in all 6 subjects. Increases in the ability of the diaphragm to generate pressure were caused by increases in muscle contractility rather than by changes in end-expiratory lung volume or thoracoabdominal configuration. Theophylline administered in a dose equal to that of caffeine increased Pdi in 5 of the 6 subjects. The magnitude of the increase in Pdi was greater with caffeine than with theophylline, however. The greater effect of caffeine than of theophylline on Pdi was not explained by differences in the blood concentrations of the 2 drugs. Neither drug produced consistent changes in blood pressure or heart rate. We conclude that caffeine, which, like theophylline, augments respiratory muscle contractility, may prove useful in the treatment of selected patients with respiratory muscle weakness.

Adult↗
PubMed1983

Effect of histamine on respiratory chemosensitivity in conscious goats.

The effect of histamine on occlusion pressure and electrical activity of the diaphragm was studied in 5 conscious goats under conditions of changing respiratory drive by exposing the animals in separate trials to progressive hypercapnia produced by rebreathing technique. Both electrical activity of the diaphragm and occlusion pressure increased with hypercapnia. At any level of PCO2, occlusion pressure and diaphragm electrical activity were greater after histamine than in the control state at the same level of chemical stimulation. Both parameters changed proportionally, and a linear correlation was found between them (r greater than 0.9). These results in conscious unsedated animals indicate that (1) histamine causes an increase of inspiratory neuromuscular drive, and (2) occlusion pressure satisfactorily indicates changes in respiratory neuron motor output.

Animals↗