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Biomedical subjects

S G Kelsen

Publications and source records attributed to S G Kelsen.

At least 19 recordsLinked to original sources
PubMed1995

Dilatory effects of upper airway muscle contraction induced by electrical stimulation in awake humans.

During sleep, diminished activity of upper airway dilator muscles (UADMs) is believed to increase upper airway (UAW) resistance and ultimately cause collapse of the UAW. In anesthetized dogs, electrically induced UADM contraction reduces UAW resistance and collapsibility. In this study, we measured the effects of electrically induced contraction of UADMs on pharyngeal resistance (Rph) in seven awake healthy subjects. UAW partial occlusion was achieved by applying external pressure to the submental hyoid region, leading to increased Rph. Transmucosal electrical stimulation (ES) of the base of the tongue was used to preferentially stimulate the genioglossus muscle. Transcutaneous ES using submental and paralaryngeal electrodes were used to preferentially stimulate the geniohyoid and the sternohyoid and sternothyroid muscles, respectively. During the unobstructed state, Rph averaged 6.11 +/- 0.48 cmH2O.l-1.s, and ES produced minimal resistance changes for all stimulation sites tested. In contrast, during the application of external pressure, when Rph was raised to an average of 190 +/- 14% of the baseline value, sublingual ES reduced resistance from 11.67 +/- 1.90 to 6.77 +/- 1.30 cmH2O.l-1.s (P < 0.01). ES at the other sites during the raised Rph state produced only minor statistically insignificant changes in Rph, even when combined submental and paralaryngeal ES was applied. Likewise, only sublingual ES produced measurable anterior movement of the tongue. We conclude that when Rph is raised by exogenous means, sublingual transmucosal ES effectively reduces Rph in awake humans.

Adult↗
PubMed1995

Comparison of diaphragm strength between healthy adult elderly and young men.

To test the hypothesis that aging is associated with a reduction in the diaphragm's force-generating capacity, we compared the maximum transdiaphragmatic pressure (Pdimax) obtained during voluntary maximal inspiratory efforts in nine young (19-28 yr) and ten elderly (65-75 yr) subjects. The relationship between Pdi and lung volume was compared in the two groups by having subjects make maximal inspiratory maneuvers at specified lung volumes (i.e., 20, 40, and 80% vital capacity). Subjects underwent symptom-limited exercise tests to characterize their aerobic capacities and evaluate the relationship between aerobic capacity and Pdimax. The average Pdimax of the elderly subjects (128 +/- 9 cm H2O) was significantly lower (p < 0.003) than the average Pdimax of the younger subjects (171 +/- 8 cm H2O). In the elderly, Pdi was lower across the range of lung volumes tested (p < 0.001), and Pdimax occurred at similar relative lung volumes (elderly, at 47% total lung capacity [TLC]; young, at 50% TLC) in both groups. The elderly subjects were quite fit based on their VO2max, and there was no significant relationship between Pdimax and VO2max. This study suggests that diaphragm strength is reduced in elderly individuals. This age-related decrease in diaphragm strength may predispose elderly patients to diaphragm fatigue in the presence of conditions that impair inspiratory muscle function or increase ventilatory load.

Adult↗
PubMed1995

Eicosanoid production in rabbit tracheal epithelium by adenine nucleotides: mediation by P2-purinoceptors.

Adenosine triphosphate (ATP) acting through epithelial nucleotide receptors exerts multiple physiologic actions on airway mucociliary clearance and caliber. However, the effect of ATP on arachidonate metabolism in the airway remains unknown. In this study, the ability of ATP to regulate eicosanoid production was studied in vitro in full-thickness rabbit tracheal strips and separately in rabbit epithelial explant cultures. In the freshly isolated strips, ATP increased prostaglandin E2 (PGE2) release in a dose-dependent fashion, with an activation threshold at 10 microM ATP and a 3.5-fold increase in PGE2 output at 1 mM ATP. Epithelium removal decreased 1 mM ATP-evoked PGE2 release by 68%. Reverse-phase, high-pressure liquid chromatography (HPLC) of media from 3H-arachidonic acid-incubated epithelial explants exposed to 1 mM ATP demonstrated increased output of the cyclooxygenase products PGE2 and prostaglandin F2a (PGF2a). Other identifiable eicosanoids did not increase. The concentration-response for ATP-induced PGE2 release by explants was similar to that of tracheal strips. PGE2 release by 1 mM ATP was 27% of that elicited by ionomycin (10 microM) and was markedly inhibited by indomethacin (10 microM). Purinoceptor agonist-stimulated PGE2 release by the epithelium yielded a rank order of potency of uridine triphosphate (UTP) > or = ATP > 2-methylthio-ATP (2MeSATP) >> alpha,beta-methyleneadenosine-5'-triphosphate (AMP-CPP) > or = adenosine. These results indicate that ATP, acting primarily through an epithelial P2-purinoceptor similar to the P2a subtype, stimulates eicosanoid metabolism in rabbit airway epithelium via the cyclooxygenase pathway, producing PGE2 as the predominant species.

Adenosine Triphosphate↗
PubMed1992

Inspiratory muscle activity during pulmonary edema in anesthetized dogs.

Pulmonary edema is known to induce a rapid and shallow breathing pattern. However, its effects on the level and pattern of distribution of motor activity to the respiratory muscles is unclear. In the present study we evaluated the effect of oleic acid induced pulmonary edema on the electrical activity of the inspiratory muscles (costal and crural diaphragm and parasternal and external intercostal muscles) in the dog, and related it to the transdiaphragmatic pressure and ventilatory parameters over the course of CO2 rebreathing. Pulmonary edema, reflected by a 7.1 +/- 0.6 wet to dry ratio, decreased lung compliance by 57%, increased pulmonary shunt to 35%, and was associated with a rapid and shallow breathing pattern. When compared at equal levels of PCO2 during CO2 rebreathing before and during edema, ventilation and mean inspiratory flow were increased only at lower levels of hypercapnia and their responses to increasing levels of PCO2 were significantly diminished during edema. Transdiaphragmatic pressures were elevated during edema as compared to control values. The rate of rise of the electrical activity of all inspiratory muscles increased significantly during edema at all levels of PCO2. Peak activity, however, remained unchanged, due to shortening of the inspiratory duration. The EMG responses to progressive hypercapnia were not affected by edema. Pulmonary edema did not change the pattern of breathing and neural output to the inspiratory muscles in vagotomized dogs. We conclude that stimulation of pulmonary proprioreceptors during edema increases neural output to all inspiratory muscles. The neural response to hypercapnia is not altered by edema, and is additive to the vagal input. The ventilatory response to CO2 is blunted during severe edema, due to alterations in lung mechanics.

Anesthesia↗
PubMed1992

Expiratory muscle activity during pulmonary edema in the anesthetized dog.

The present study evaluated the reflex response of the expiratory muscles to pulmonary congestion and edema. The electromyograms of two thoracic and four abdominal expiratory muscles were recorded in 12 anesthetized dogs. Pulmonary edema was induced by rapid saline infusion in six dogs and injection of oleic acid into the pulmonary circulation in the remaining six dogs. Both forms of pulmonary edema reduced pulmonary compliance, interfered with gas exchange, and induced a rapid and shallow breathing pattern. The electrical activity of all abdominal muscles was suppressed during both forms of pulmonary edema. In contrast, the electromyogram activity of the thoracic expiratory muscles was not significantly affected by pulmonary edema. Acute pulmonary arterial hypertension produced in two dogs by inflating a balloon in the left atrium had no effect on ventilation or expiratory muscle electrical activity. In two vagotomized dogs, pulmonary edema did not inhibit the expiratory muscles. We conclude that pulmonary edema suppresses abdominal but not thoracic expiratory muscle activity by vagal reflex pathway(s). Extravasation of fluid into the lung appears to be more important than an increase in pulmonary vascular pressure in eliciting this response.

Anesthesia↗
PubMed1992

Effect of lung volume on the respiratory action of the canine pectoral muscles.

Lung volume influences the mechanical action of the primary inspiratory and expiratory muscles by affecting their precontraction length, alignment with the rib cage, and mechanical coupling to agonistic and antagonistic muscles. We have previously shown that the canine pectoral muscles exert an expiratory action on the rib cage when the forelimbs are at the torso's side and an inspiratory action when the forelimbs are held elevated. To determine the effect of lung volume on intrathoracic pressure changes produced by the canine pectoral muscles, we performed isolated bilateral supramaximal electrical stimulation of the deep pectoral and superficial pectoralis (descending and transverse heads) muscles in 15 adult supine anesthetized dogs during hyperventilation-induced apnea. Lung volume was altered by application of a negative or positive pressure (+/- 30 cmH2O) to the airway. In all animals, selective electrical stimulation of the descending, transverse, and deep pectoral muscles with the forelimbs held elevated produced negative intrathoracic pressure changes (i.e., an inspiratory action). Moreover, with the forelimbs elevated, increasing lung volume decreased both pectoral muscle fiber precontraction length and the negative intrathoracic pressure changes generated by contraction of each of these muscles. Conversely, with the forelimbs along the torso, increasing lung volume lengthened pectoral muscle precontraction length and augmented the positive intrathoracic pressure changes produced by muscle contraction (i.e., an expiratory action). These results indicate that lung volume significantly affects the length of the canine pectoral muscles and their mechanical actions on the rib cage.

Animals↗
PubMed1992

Rabbit trachealis tension responses to receptor-mediated agonists are diminished by elastase.

The present study examined the effects of elastase, in concentrations present in respiratory secretions, on airway smooth muscle contractile responses in vitro and the magnitude of the airway epithelial inhibition of smooth muscle tension. Experiments were performed on 126 full-thickness tracheal strips from 25 rabbits. Isometric tension responses to acetylcholine (10(-8) to 10(-4) M) and potassium chloride (10 to 110 mM) were examined before and after a 5-min exposure to either porcine pancreatic elastase (PPE) or human neutrophil elastase (HNE). PPE (5 to 40 micrograms/100 microliters) reduced the tension response to acetylcholine but had no effect on the tension response to potassium chloride. PPE and HNE (20 micrograms/100 microliters) produced similar effects. Mechanical removal of the epithelium per se significantly (P less than 0.005) decreased the ED50 response to acetylcholine but did not affect maximal tension. However, the airway epithelial inhibitory effect on the acetylcholine tension response was similar in the presence and absence of PPE (20 micrograms/100 microliters). These data suggest that the diminution of tracheal smooth muscle tension responses to receptor-mediated agonists induced by elastase is a direct effect on the muscle and is not mediated by an effect of elastase on the respiratory epithelium.

Acetylcholine↗
PubMed1992

A technique to harvest viable tracheobronchial epithelial cells from living human donors.

The ability to obtain airway epithelial cells from the lower respiratory tract in living human donors will facilitate study of the biologic properties of these cells. We report our experience harvesting tracheobronchial epithelial cells from living human donors by brushing the mucosal surface of the trachea and mainstem bronchi. Cells were obtained on 21 occasions from 18 healthy adult subjects under direct vision with a brush-tipped catheter during fiberoptic bronchoscopy. The average number of cells harvested per subject was 14 +/- 2 x 10(6), and cell viability determined by trypan blue exclusion averaged 36 +/- 4%. Of note, cell viability was significantly enhanced when lidocaine was confined to the nares. Lidocaine was also observed to diminish cell viability in vitro in a dose-dependent fashion. Morphologic and staining properties were used to classify harvested cells into the three major cell types present in the mucosa (i.e., ciliated, secretory, and basal cells). All three subtypes were obtained. The percentage of ciliated, secretory, and basal-like cells was 24 +/- 2%, 11 +/- 1%, 29 +/- 1%, respectively, while the remaining 36% were difficult to type. In one subject in whom brushing was performed on three occasions over a 7-wk period, the percentage of each of the three subtypes was similar across procedures. Harvested cells could be successfully placed in primary culture with a plating efficiency of 50 to 60% and could be subcultured for up to seven passages. Acutely dissociated cells could be used to study the beta-adrenergic receptor adenylyl cyclase system since they produced cAMP in response to isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Effects of branched-chain amino acids on nitrogen metabolism in patients with cirrhosis.

This study was conducted to determine whether an amino acid solution enriched with branched-chain amino acids altered protein catabolic rates and plasma ammonia in patients with cirrhosis. Nine stable subjects were given two peripheral intravenous infusions: a standard amino acid solution (solution A) and a branched-chain-enriched solution containing 97% more leucine (solution B). Each solution was given for separate 9-day (group 1, n = 6) or 3-day (group 2, n = 3) periods. Amino acid solutions delivered 0.7 gm protein.kg-1.day-1. Diets provided an additional 0.3 gm protein plus maintenance calories. Protein turnover was assessed by a primed continuous infusion of [1-14C] leucine in six patients (three patients in group 1 and three patients in group 2). Nitrogen balance and urinary 3-methyl histidine excretion were determined in group 1 patients. Compared with solution A, solution B increased leucine flux and leucine oxidation but had no significant effect on protein synthesis or catabolism based on the plasma specific activity of either leucine or alpha-ketoisocaproic acid. The additional leucine infused with solution B was quantitatively oxidized. Nitrogen balance did not differ with the two solutions and there was also no difference in the urinary excretion of 3-methyl histidine, suggesting that muscle protein catabolism was unchanged. Plasma ammonia concentration decreased significantly during the infusion of solution B and was associated with a slight fall in plasma glucagon concentration. The results indicated that a branched-chain-enriched amino acid solution did not alter protein synthesis or catabolism although it did lower the plasma ammonia when compared with a standard amino acid formula in stable cirrhotic patients.

Amino Acids↗
PubMed1990

Distribution of motor activity to expiratory muscles during sciatic nerve stimulation in the dog.

The present study examined the effect of increasing sensory input from the lower limbs (assessed from the response to electrical stimulation of the sciatic nerve) on the distribution of electrical activity to the expiratory muscles. Expiratory muscle response to sciatic nerve stimulation (SNS) was compared to the response of the inspiratory muscles, and to their response to hypercapnia. In 16 anesthetized dogs afferent SNS increased ventilation and augmented the integrated EMG of all six expiratory muscles studied. Increases in abdominal muscle electrical activity were not uniform, being greater in the transversus abdominis and external oblique as compared to the internal oblique and the rectus abdominis. Increases in thoracic expiratory and inspiratory muscle activity during SNS were similar in magnitude. SNS performed while dogs were breathing 7% CO2, produced increased neural activity similar to those observed during O2 breathing. During CO2 rebreathing, at equal levels of minute ventilation, expiratory muscle responses to SNS and to CO2 were similar. In contrast, the rate of rise of the inspiratory muscle EMGs was greater during SNS. The present study indicates that the abdominal muscles participate in the respiratory response to afferent neural drive from skeletal muscles. The magnitude of their response is independent of their pre-stimulation level of activity and is similar to that observed during CO2 stimulated breathing.

Abdominal Muscles↗
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↗