bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural regulation of lysozyme secretion from tracheal submucosal glands of ferrets in vivo
Authors: Davis B. , Tseng H. C.
Published: December 2017

To investigate how central and peripheral nerves affect lysozyme secretion from tracheal submucosal glands in ferrets we injected substance P (20 nmol/kg in 200 microliters) intracisternally or intravenously into anesthetized artificially ventilated ferrets. We collected 3-ml samples from a perfused (3 ml/5 min) segment of trachea in situ during 15 min before and 45 min after injection of substance P. Content of lysozyme, a specific marker of tracheal submucosal gland serous cell secretion in ferrets, was measured spectrophotometrically in each sample. Intracisternal substance P increased peak lysozyme output threefold compared with baseline. This increase was abolished completely by cutting both superior laryngeal nerves (SLN) and was partially inhibited by atropine, phentolamine, or propranolol. Intravenous substance P increased peak lysozyme output 10-fold compared with baseline. This increase was partly abolished by cutting both SLN. We concluded that intracisternal substance P stimulated the central nervous system (CNS) and activated cholinergic, adrenergic, and nonadrenergic noncholinergic secretomotor nerves to tracheal glands and that intravenous substance P increased lysozyme secretion both by acting directly on tracheal glands and indirectly on the CNS to activate secretomotor nerves.
Calcium channel blockers inhibit endogenous pyrogen fever in rats and rabbits
Authors: Stitt J. T. , Shimada S. G.
Published: December 2017

We have previously shown that febrile responses in both rats and rabbits are elicited by the intravenous injection of a semipurified endogenous pyrogen (EP) prepared from human monocytes. We are now presenting evidence that these febrile responses are mediated via activation of Ca2+ channels by EP. The febrile responses of male New Zealand White rabbits and Sprague-Dawley rats to a standard dose of EP were determined at their respective thermoneutral ambient temperatures. The animals were then treated with Ca2+ channel blocker verapamil (7.5 mg/kg iv) 30–60 min before the EP challenge. In every case the febrile response to EP was markedly attenuated after verapamil pretreatment, while administration of verapamil by itself had no detectable effect on body temperature. Another Ca2+ channel blocker, nifedipine (5 mg/kg iv), was shown to possess antipyretic activity in rats also. To localize where in the fever pathway these Ca2+ channel blockers were acting, we investigated the effect of verapamil at the same dose on fevers that were produced by microinjection of prostaglandin E (PGE) directly into the brain. These PGE fevers were unaffected by verapamil pretreatment, indicating that the antipyretic action of Ca2+ channel blockers occurs before the formation of PGE in response to EP stimulation. The most likely locus of action is the activation of the enzyme phospholipase A2, which regulates the production of arachidonic acid from cellular phospholipids in the prostanoid cascade.
Nebulized vs. instilled exogenous surfactant in an adult lung injury model
Authors: Lewis J. , Ikegami M. , Higuchi R. , Jobe A. , Absolom D.
Published: December 2017

Three days after subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) to induce lung injury, adult rabbits were mechanically ventilated and lung function was evaluated. Each animal then received either nebulized Survanta (Neb Surv), nebulized saline (Neb Saline), nebulized gas alone (Neb Gas), or tracheally instilled Survanta (Inst Surv). The ventilation efficiency index (VEI) value increased significantly compared with pretreatment values (P less than 0.01) over a 3-h treatment period for the Neb Surv animals, whereas VEI values for the other three groups decreased after treatment (P less than 0.05). Arterial PO2-to-fraction of inspired O2 ratios and dynamic compliance values significantly decreased after treatment for the Inst Surv group (P less than 0.05). Pressure-volume curves demonstrated a significantly greater volume at maximal pressure for the Neb Surv group compared with each of the other groups studied (P less than 0.01). The calculated quantity of surfactant recovered in lung tissue for the Neb Surv group was only 4.9 +/- 1.0 mg lipid/kg compared with 100 mg lipid/kg delivered to the Inst Surv group. Surfactant administered as an aerosol resulted in modest physiological improvements in this model of lung injury and was superior to the tracheal instillation technique.
Lesions in retrotrapezoid nucleus decrease ventilatory output in anesthetized or decerebrate cats
Authors: Nattie E. E. , Li A. H. , St John W. M.
Published: December 2017

Kainic acid (KA) injections into the retrotrapezoid nucleus (RTN) of anesthetized deafferented cats profoundly decreased phrenic activity (PA) and CO2 sensitivity (J. Appl. Physiol. 68: 1157–1166, 1990). In this study small electrolytic lesions of the RTN produced the same results, indicating that the KA destroyed cells. We then asked whether anesthetic depression or the absence of peripheral chemoreceptors could explain the degree of respiratory depression observed. In decerebrate cats electrolytic lesions of the RTN resulted in a decrease in PA similar to that seen under anesthesia. CO2 sensitivity was decreased by RTN lesions that extended into the caudal RTN but less so than under anesthesia. KA injections resulted in an initial increase in PA followed by a continuous decrease, a pattern similar to that seen under anesthesia but with a slower time course. CO2 sensitivity was essentially absent. Peripheral chemodenervation produced a small further decrease in PA and a downward shift of the CO2 response without change in slope. Blood pressure was unaffected by RTN lesions but was decreased by more-caudal lesions without respiratory effects. The RTN appears to be necessary for the maintenance of eupneic phrenic activity and CO2 sensitivity even in decerebrate cats with intact peripheral chemoreceptors.
Role of the epithelium in airway smooth muscle responses to relaxant agonists
Authors: Yang J. N. , Mitzner W. , Hirshman C.
Published: December 2017

We studied the role of the guinea pig tracheal epithelium in modulating tracheal smooth muscle responses to the relaxant agonists albuterol, sodium nitroprusside, and theophylline. We used an in vitro preparation that allowed separation of the fluids bathing the luminal (internal) and serosal (external) surfaces of the trachea, and bronchodilators were administered to either surface of carbachol-contracted tracheae. All three drugs produced dose-dependent relaxation. However, albuterol and nitroprusside were less potent (concentration that produced half-maximal effect increased by 100- and 32-fold, respectively) when given to the epithelial side with the epithelium intact compared with the epithelium denuded or compared with serosal administration with the epithelium intact. These differences were not observed for theophylline, where smooth muscle responses were independent of either the side of stimulation or of the presence or absence of the epithelium. Direct measurements of the diffusion of theophylline across the tracheal wall in the presence or absence of epithelium showed that after 5 h of incubation with a fixed luminal concentration of theophylline, only 1.7% had diffused across the tracheal wall with the epithelium intact. This increased to only approximately 3.3% when the epithelium was denuded. These results suggest that the epithelial is a relatively weak barrier for lipophilic agents but has a major role as a diffusion barrier to hydrophilic substances.
Extracellular Ca2+ mobilization in potential-dependent contraction of trachealis of maturing swine
Authors: Mitchell R. W. , Murphy T. M. , Kelly E. , Leff A. R.
Published: December 2017

We studied the effect of maturation on potassium-induced parasympathetic activation and Ca2+ entry in tracheal smooth muscle (TSM) from fifteen 2-wk-old (2ws) and sixteen 10-wk-old (10ws) male domestic farm swine. Atropine (10(-7) M) caused inhibition of the maximal contraction elicited by potassium to 50.3 +/- 2.6% maximum of control response (P less than 0.001) in TSM from 2ws but had no significant effect in TSM from 10ws (94.6 +/- 4.2% maximum; P = NS vs. control). Verapamil (10(-7) M) plus 10(-7) M atropine reduced contraction elicited by potassium in both 2ws (23.7 +/- 5.8% maximum; P less than 0.001 vs. control) and 10ws (50.6 +/- 6.3% maximum; P less than 0.001 vs. control, P less than 0.05 vs. 2ws); 10(-6)M verapamil caused greater than 95% blockade of contraction caused by potassium in both 2ws and 10ws. In separate studies, atropine-treated strips were equilibrated with extracellular Ca2+ concentrations ([Ca2+]o) ranging from normal (1X [Ca2+]o) to four times normal (4x [Ca2+]o). Increasing [Ca2+]o increased maximal contractile response in atropine-treated TSM strips from 68.7 +/- 3.8% maximum for 1x [Ca2+]o to 100.8 +/- 4.8% maximum for 4x [Ca2+]o (P less than 0.001) in 2ws. Neither atropine nor [Ca2+]o affected maximal responses of TSM in 10ws (103.5 +/- 3.0% maximum for 1x [Ca2+]o; P = NS vs. control). However, in the presence of atropine and verapamil, 4x [Ca2+]o augmented KCl-elicited contraction of TSM from both 2ws (46.9 +/- 6.3% maximum; P less than 0.01 vs. control) and 10ws (78.6 +/- 2.3% maximum; P less than 0.005 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of chronic and acute exercise on cardiovascular beta-adrenergic responses
Authors: Martin W. H. , Spina R. J. , Korte E. , Ogawa T.
Published: December 2017

beta-Adrenergic receptor density and responsiveness may be increased in experimental animals by physical conditioning, and the opposite effects have been observed after a single bout of exercise. To determine whether the chronic and acute effects of exercise include similar alterations in cardiovascular function in humans, we characterized heart rate, blood pressure, and distal lower extremity blood flow responses to graded-dose isoproterenol infusion in 15 young healthy subjects before and after exercise training and with and without a single preceding bout of prolonged exercise of either low or high intensity (61 +/- 1 or 82 +/- 1% maximal heart rate). VO2max was increased 18% after exercise training (43.2 +/- 2.7 to 51.1 +/- 3.3 ml.kg-1.min-1; P less than 0.001). Despite a concomitant fall in resting heart rate (59 +/- 3 to 50 +/- 2 beats/min; P less than 0.001), chronotropic and lower extremity blood flow responses to isoproterenol remained unchanged. Similarly, 1 h of acute high-intensity treadmill exercise altered baseline heart rate (58 +/- 4 to 74 +/- 5 beats/min; P less than 0.02), but neither low- nor high-intensity acute exercise influenced heart rate or lower extremity blood flow responses to isoproterenol. In contrast, the systolic pressure response to isoproterenol was blunted after high- but not low-intensity prolonged exercise (P less than 0.02). These data indicate that cardiac chronotropic (primarily beta 1) and vascular (beta 2) adrenergic agonist responses are not altered in humans by training or acute exercise. The systolic blood pressure response to beta-adrenergic stimulation is decreased by a single bout of high-intensity prolonged exercise by mechanisms that remain to be defined.
Initiation of oral breathing in lambs in response to airway obstruction: mechanisms
Authors: Harding R. , Hooper S. B. , Wood G. A.
Published: December 2017

Our aim was to assess the mechanisms determining the reflex formation of an oral airway in response to nasal obstruction (NO) and tracheal obstruction (TO). In nine conscious lambs (14–37 days old) NO was effected by blockade of nasal tubes; TO was later effected by blockade of an endotracheal tube. We measured arterial O2 saturation, PO2, PCO2, and pH and the depth and duration of inspiratory efforts when mouth opening (MO) occurred. Responses were compared when NO and TO followed breathing of room air, rebreathed air, and 100% O2. After both NO and TO, MO was initiated most rapidly after lambs rebreathed air and least rapidly after they breathed 100% O2. Similar changes in blood gases and pH were measured when MO occurred after air breathing and rebreathing; however, the extent of these changes was greater during TO than during NO. After 100% O2 was breathed, MO occurred when lambs were still hyperoxic, but they were more hypercapnic and acidemic than after breathing air or rebreathed air. There were no differences, related to prebreathed gases or site of airway occlusion, in the depth of inspiratory efforts at the time of MO. We conclude that the formation of an oral airway requires a critical level of inspiratory drive in the presence of airway obstruction. After the prebreathing of different gases, differences in response latency and blood gases at the time of MO can be attributed to the attainment of this threshold level of inspiratory drive. The formation of an oral airway is facilitated by, but not dependent on, receptors in the upper airway.
Role of thromboxane A2 in airway microvascular leakage induced by inhaled platelet-activating factor
Authors: Tokuyama K. , Lotvall J. O. , Morikawa A. , Barnes P. J. , Chung K. F.
Published: December 2017

We studied the effects of OKY-046 (1, 10, and 30 mg/kg iv), a selective thromboxane synthase inhibitor, and of ICI 192605 (0.5 mg/kg), a selective thromboxane A2 receptor antagonist, on airflow obstruction and airway microvascular leakage induced by inhaled platelet-activating factor (PAF). Extravasated Evans blue dye content was measured as a reflection of airway microvascular leakage. In control animals, PAF caused a significantly higher increase in extravasation of dye and significantly less increase in lung resistance (RL) than histamine. OKY-046 significantly inhibited both changes in RL and airway microvascular leakage after PAF in a dose-dependent manner, whereas it inhibited histamine-induced airway microvascular leakage only at main bronchi, without any significant effect on RL. ICI 192605 significantly inhibited both RL and airway microvascular leakage induced by PAF, but not after histamine. After both PAF and histamine, changes in RL correlated significantly with the degree of microvascular leakage. Airway microvascular leakage and airflow obstruction after PAF, but not after histamine, may be dependent on thromboxane A2 generation.
Influences of gender and sex hormones on hypoxic ventilatory response in cats
Authors: Tatsumi K. , Hannhart B. , Pickett C. K. , Weil J. V. , Moore L. G.
Published: December 2017

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fructose 1,6-diphosphate augments paraquat injury in isolated dog lungs
Authors: Shibamoto T. , Parker J. C.
Published: December 2017

Paraquat (PQ; 1,1'-dimethyl-4,4′-bipyridylium dichloride), a widely used herbicide, causes pulmonary edema by a cyclic oxidation and reduction reaction with oxygen molecules with the production of oxygen free radicals. Because fructose 1,6-diphosphate (FDP) has recently been shown to inhibit the generation of oxygen free radicals by activated neutrophils, we determined the effects of FDP on PQ-induced increase in microvascular permeability in isolated blood-perfused dog lungs. Vascular permeability was assessed using the capillary filtration coefficient (Kf,c) and isogravimetric capillary pressure (Pc,i). There was no change in these variables over 5 h in the control lungs treated with saline (n = 5). A significant increase in Kf,c and a decrease in Pc,i, both of which indicated increased vascular permeability, were observed at 5 h of perfusion with 4 x 10(-3) M PQ (n = 5). Unexpectedly, an increase in microvascular permeability occurred within 4 h after administration of PQ in the lungs that were pretreated with FDP (2.7–14.2 mM, n = 6). Moreover the increases of Kf,c in the FDP-pretreated lungs were significantly greater than those in the lungs treated with PQ alone. Also, the final-to-initial lung weight ratio of the FDP-pretreated group was greater than those of the other groups. Thus the FDP dose used in the present study accentuated rather than prevented the PQ lung injury.
Accuracy of respiratory inductive plethysmograph in measuring tidal volume during sleep
Authors: Whyte K. F. , Gugger M. , Gould G. A. , Molloy J. , Wraith P. K. , Douglas N. J.
Published: December 2017

Respiratory inductance plethysmography (RIP) has been widely used to measure ventilation during sleep, but its accuracy in this role has not been adequately tested. We have thus examined the accuracy of the RIP by comparing tidal volume measured with RIP with that measured by a pneumotachograph in eight unrestrained normal subjects during sleep. We have also studied the effect of posture on the accuracy of the RIP. In all sleep stages the correlation between RIP tidal volume measurements and expired volume showed relatively poor correlations (mean r = 0.49–0.60), and the bias of the measurements varied widely. Changes in posture altered the correlations between the two measurements, with no systematic differences between positions. When the subjects resumed a position, the 95% confidence intervals of tidal volume measurement did not overlap the original confidence limits in that posture on 13 of 25 occasions. This study shows that the RIP does not accurately measure tidal volume during sleep in unrestrained subjects and should only be used for semiquantitative assessment of ventilation during sleep.
Effects of gender, age, and fitness level on response of VO2max to training in 60-71 yr olds
Authors: Kohrt W. M. , Malley M. T. , Coggan A. R. , Spina R. J. , Ogawa T. , Ehsani A. A. , Bourey R. E. , Martin W. H. , Holloszy J. O.
Published: December 2017

The adaptive response of maximal aerobic power (VO2max) to endurance exercise training was compared in 53 men and 57 women, aged 60–71 yr. The subjects were healthy and had been sedentary for at least 2 yr. Pretraining VO2max was measured during graded treadmill walking on two occasions. These values were reproducible (24.4 +/- 4.7 vs. 24.4 +/- 4.6 (SD) ml.min-l.kg-1; r = 0.96). Subjects trained primarily by walking and running for 9–12 mo, averaging 3.9 +/- 0.6 days/wk and 45 +/- 5 min/day at 80 +/- 5% of maximal heart rate (HRmax). Average improvement in VO2max (ml.min-1.kg-1) was 24 +/- 12% (range 0–58%). Relative improvement was not significantly different in men and women (26 +/- 12 vs. 23 +/- 12%, ml.min-1.kg-1; 21 +/- 10 vs 19 +/- 10%, l/min). When subjects were divided into three groups by age (60–62, 63–66, 67–71 yr), there were no significant differences among the groups in the relative increase in VO2max (21% vs. 19% vs. 18%, 1/min). Correlation analysis also yielded a nonsignificant relationship between improvement and age (r = -0.13). To examine the effect of initial fitness level on the adaptive response to exercise, pretraining VO2max was correlated with the absolute improvement in VO2max. This relationship was not significant in either men (r = 0.04) or women (r = -0.23). In conclusion, in healthy people aged 60–71 yr, VO2max adapts to endurance exercise training to the same relative extent as in young people, and this adaptation is independent of gender, age, and initial level of fitness.
Multiple muscarinic receptor subtypes in the canine pulmonary circulation
Authors: el-Kashef H. A. , Hofman W. F. , Ehrhart I. C. , Catravas J. D.
Published: December 2017

The vascular response to the muscarinic receptor agonist acetylcholine (ACh) in the presence of selected antagonists was examined in the isolated blood-perfused canine left lower lung lobe under conditions of normal (resting) and elevated vascular tone. At normal vascular tone, ACh (1–5 mumol) produced a dose-dependent increase in pulmonary arterial pressure (Ppa), total pulmonary vascular resistance (PVR), and downstream resistance (Rds) without altering upstream resistance (Rus). Pirenzepine (50 and 100 nM), the prototype M1-selective antagonist, and gallamine, an M2-selective antagonist, as well as atropine (50 nM) and secoverine (100 nM), nonselective antagonists, attenuated (P less than 0.05) the ACh-induced increase in Ppa and Rds. With elevated vascular tone induced by serotonin infusion, ACh produced a dose-dependent increase in Ppa in 19 of 25 lobes, although Rus decreased while Rds increased in all lobes. At high vascular tone, pirenzepine or gallamine attenuated the ACh-induced increase in Rds, whereas Rus was not affected. Secoverine and atropine antagonized ACh-induced increases in both Rds and Rus. The pA2 values (i.e., the negative log antagonist concentration requiring a doubling of ACh dose for an equivalent increase in Rds) for gallamine, pirenzepine, secoverine, and atropine were 6.1 +/- 0.1, 7.4 +/- 0.1, 8.3 +/- 0.2, and 10.2 +/- 0.3, respectively. These results suggest that 1) ACh increases PVR in the dog by constricting the venous segments (downstream) of the pulmonary circulation via activation of pulmonary vascular muscarinic receptors under conditions of both normal and elevated vascular tone, 2) both M1- and non-M1-muscarinic receptor subtypes appear to participate in mediating the ACh-induced increase in Rds, and 3) ACh moderately relaxes the upstream (arterial) vessels, especially under conditions of elevated tone.
Effect of age and hypoxia on beta-adrenergic receptors in rat heart
Authors: Mader S. L. , Downing C. L. , Van Lunteren E.
Published: December 2017

Previous reports suggest that hypoxia downregulates cardiac beta-adrenergic receptors from young rats. Because aging alters response to stress, we hypothesized an age-related alteration in the response to hypoxia. Male Fischer-344 rats, aged 3 and 20 mo, were divided into control and hypoxic groups. The hypoxic rats were exposed to hypobaric hypoxia (0.5 atm) for 3 wk. After hypoxic exposure, body weight decreased, hematocrit increased, right ventricular weight increased, and left ventricular weight decreased in all animals. beta-Adrenergic receptor density declined after hypoxic exposure in the young but not in the older animals, a change that was confined to the left ventricle. beta-Adrenergic receptor density in the right ventricle was significantly lower in the older animals than in the young animals. Plasma catecholamines (norepinephrine, epinephrine) drawn after the animals were killed (stress levels) decreased in young rats and increased in old rats after the exposure to hypoxia. Hypoxia is a useful physiological stress that elucidates age-related changes in cardiac beta-adrenergic receptor and catecholamine regulation that have not previously been described.
Elevated rectal temperature produced by all-night bright light is reversed by melatonin infusion in men
Authors: Strassman R. J. , Qualls C. R. , Lisansky E. J. , Peake G. T.
Published: December 2017

Early morning rectal body temperature is lowest when melatonin levels are highest in humans. Although pharmacological doses of melatonin are hypothermic in humans, the relationship between endogenous melatonin and temperature level has not been investigated. We measured rectal body temperature in nine normal men whose melatonin levels were suppressed by all-night sleep deprivation in bright light and compared values with those seen in sleep in the dark, sleep deprivation in dim light (to control for the stimulatory effect of wakefulness on temperature), and sleep deprivation in bright light with an infusion of exogenous melatonin that replicated endogenous levels. Minimum rectal temperature, calculated from smoothed temperature data from 2300 to 0515 h, was greater in bright-light sleep deprivation, resulting in suppression of melatonin, than in conditions of sleep deprivation in dim light or sleep in the dark. An exogenous melatonin infusion in bright light returned the minimum temperature to that seen in dim-light sleep deprivation. A nonsignificant elevation in mean and minimum temperature was noted in all conditions of sleep deprivation relative to sleep. We conclude that melatonin secretion contributes to the lowering of core body temperature seen in the early morning in humans.
Relationship among cardiac output, shunt, and inspired O2 concentration
Authors: Wagner P. D. , Schaffartzik W. , Prediletto R. , Knight D. R.
Published: December 2017

In comparing gas exchange responses of the methacholine- (MCh) challenged mongrel dog with leukotriene receptor blockers and placebo at different inspiratory O2 fractions (FIO2), we previously noted systematically different values of cardiac output as a function of drug administration and/or FIO2. This confounds identification of the effects of FIO2 and/or drugs on gas exchange, because shunt is well known to vary directly with cardiac output when other factors are equal. Accordingly, in six dogs we examined the dependence of combined shunt and low ventilation-perfusion (VA/Q) blood flow (“shunt”) on cardiac output in the MCh-challenged mongrel dog. Two dogs breathed 100% O2, another two breathed room air, and the final pair breathed 12% O2 while cardiac output was altered several times by sequentially opening and closing arteriovenous fistulas every 10 min for approximately 90 min after a standard MCh challenge. On 100% O2, shunt increased by 11.0% of the cardiac output per 1-l/min increase in cardiac output. On room air, the value was 7.4%. With 12% O2 breathing shunt rose by only 2.2% per 1-l/min rise in blood flow. This FIO2 -dependent behavior of the shunt-cardiac output relationship was highly reproducible, both within and between animals. It suggests that the increase in shunt with cardiac output depends more on vascular tone of noninjured areas than on tone of the low VA/Q regions (which are hypoxic at all FIO2 values).
Mandible position and activation of submental and masseter muscles during sleep
Authors: Hollowell D. E. , Suratt P. M.
Published: December 2017

Movement of the mandible could influence pharyngeal airway caliber because the mandible is attached to the tongue and to muscles that insert on the hyoid bone. In normal subjects and patients with obstructive sleep apnea (OSA) we measured jaw position during sleep with strain gauges, as well as masseter and submental electromyograms, airflow, esophageal pressure, oximetry, electroencephalograms, and electrooculograms. Jaws of patients with OSA were open more than those of normal subjects at end expiration and opened further at end inspiration, particularly at the termination of apneas when the masseter and submental muscles contracted. Masseter activation occurred only in patients with OSA and in a pattern similar to that of submental muscles. Jaw opening at end expiration could narrow the upper airway, whereas opening at end inspiration could reflect efforts to expand the airway with tracheal tug and with submental muscle activation and efforts to open the mouth to allow mouth breathing. Masseter contraction does not close the jaw but may serve to stabilize it.
Respiratory responses induced by the activation of somatic nociceptive afferents in humans
Authors: Duranti R. , Pantaleo T. , Bellini F. , Bongianni F. , Scano G.
Published: December 2017

To further investigate the role of somatic nociceptive afferents in the neural control of breathing, we studied the respiratory effects of their activation by means of either electrical stimulation or ischemic pain in 14 healthy volunteers. Painful electrical cutaneous stimulation increased respiratory frequency (f), mean inspiratory flow (VT/TI), and rate of rise (XP/TI) of integrated electromyographic activity of diaphragm (IEMGdi). Painful muscular electrical stimulation caused similar but larger changes accompanied by increases in tidal volume (VT), peak XP of IEMGdi, and ventilation (VE); it also entrained respiratory rhythm. Ischemic pain, which was characterized by a progressively increasing intensity, caused augmentation in respiratory activity that displayed an increasing trend: VE, f, VT, XP, VT/TI, and XP/TI increased. In the light of available literature, it seems conceivable to suggest that respiratory responses to painful electrical stimulation are mediated through the activation of cutaneous (A delta) and muscular (group III) fine-myelinated afferents, and responses to ischemic pain are mediated by the activation of both fine myelinated (group III) and unmyelinated (group IV) muscular afferents. The input conveyed by these afferents may constitute an effective stimulus to respiration in humans.
Intravascular anti-IgE challenge in perfused lungs: mediator release and vascular pressor response
Authors: Walmrath D. , Schneider U. , Kreusler B. , Grimminger F. , Ennis M. , Seeger W.
Published: December 2017

Intravascular application of goat anti-rabbit immunoglobulin E (IgE) was used to stimulate parenchymal mast cells in situ in perfused rabbit lungs. Sustained pulmonary arterial pressure rise was evoked in the absence of lung vascular permeability increase and lung edema formation. Early prostaglandin (PG) D2 and histamine release into the perfusate was documented, accompanied by more sustained liberation of cysteinyl leukotrienes (LT), LTB4, and PGI2. The quantities of these inflammatory mediators displayed the following order: histamine greater than cysteinyl-LT greater than PGI2 greater than LTB4 greater than PGD2. Pressor response and inflammatory mediator release revealed corresponding bell-shaped dose dependencies. Cyclooxygenase inhibition (acetylsalicylic acid) suppressed prostanoid generation, increased LT release, and did not substantially affect pressor response and histamine liberation. BW755 C, a cyclo- and lipoxygenase inhibitor, blocked the release of cysteinyl-LT and markedly reduced the liberation of the other inflammatory mediators as well as the pressor response. The H1-antagonist clemastine caused a moderate reduction of the anti-IgE-provoked pressure rise. We conclude that intravascular anti-IgE challenge in intact lungs provokes the release of an inflammatory mediator profile compatible with in situ lung parenchymal mast cell activation. Pulmonary hypertension represents the predominant vascular response, presumably mediated by cysteinyl-LT and, to a minor extent, histamine liberation.
Phenylephrine-induced hypertension acutely decreases genioglossus EMG activity in awake humans
Authors: Garpestad E. , Basner R. C. , Ringler J. , Lilly J. , Schwartzstein R. , Weinberger S. E. , Weiss J. W.
Published: December 2017

To investigate the relationship between systemic blood pressure (BP) and upper airway dilator muscle activity, we recorded genioglossus electromyograms (EMGgg) during pharmacologically induced acute increases in BP in five healthy humans (ages 27–40 yr). EMGgg was measured with perorally placed fine-wire electrodes; phasic EMGgg was expressed as percentage of baseline activity. Subjects were studied supine, awake, and breathing through a face mask with their mouths taped. End-tidal PCO2 was monitored with a mass spectrometer; minute ventilation was measured with a pneumotachograph. Digital BP was monitored continuously with the Penaz method (Finapres, Ohmeda). Mean arterial pressure (MAP) at baseline was 89 +/- 6 (SD) mmHg. Phenylephrine was infused until MAP reached 15–25 mmHg above baseline (107 +/- 7 mmHg). Recording was continued until MAP returned to baseline (90 +/- 7 mmHg). Elevated BP was associated with a significantly decreased phasic EMGgg (P less than 0.005). With return of MAP to baseline, phasic EMGgg returned toward normal (P less than 0.01). Minute ventilation and end-tidal PCO2 did not differ among conditions. Genioglossus activity appears to be influenced by acute changes in systemic BP. We speculate that BP elevations accompanying obstructive apneas during sleep may decrease upper airway tone and facilitate subsequent apneas.
In vivo recording of electrical activity of canine tracheal smooth muscle
Authors: Kondo T. , Tamura K. , Onoe K. , Takahira H. , Ohta Y. , Yamabayashi H.
Published: December 2017

Electrical activity of the tracheal smooth muscle was studied using extracellular bipolar electrodes in 37 decerebrate, paralyzed, and mechanically ventilated dogs. A spontaneous oscillatory potential that consisted of a slow sinusoidal wave of 0.57 +/- 0.13 (SD) Hz mean frequency but lacked a fast spike component was recorded from 15 dogs. Lung collapse accomplished by bilateral pneumothoraxes evoked or augmented the slow potentials that were associated with an increase in tracheal muscle contraction in 26 dogs. This suggests that the inputs from the airway mechanoreceptors reflexly activate the tracheal smooth muscle cells. Bilateral vagal transection abolished both the spontaneous and the reflexly evoked slow waves and provided relaxation of the tracheal smooth muscle. Electrical stimulation of the distal nerve with a train pulse (0.5 ms, 1–30 Hz) evoked slow-wave oscillatory potentials accompanied by a contraction of the tracheal smooth muscle in all the experimental animals. Our observations in this in vivo study confirm that the electrical activity of tracheal smooth muscle consists of slow oscillatory potentials and that tracheal contraction is at least partly coupled to the slow-wave activity of the smooth muscle.
Effect of the chest wall and blood volume on pulmonary distensibility
Authors: Colebatch H. J. , Ng C. K. , Berend N. , Maccioni F. J.
Published: December 2017

To determine the reason for increased pulmonary distensibility in excised lungs, we performed deflation pressure-volume (PV) studies in 24 dogs. Exponential analysis of PV data gave K, an index of distensibility. Lung volume was measured by dilution of neon. Compared with measurements obtained in the supine position, with the chest closed, and with esophageal pressure (Pes) to obtain transpulmonary pressure, K was not changed significantly with the chest strapped, with pleural pressure to obtain transpulmonary pressure, or with the chest open. From displacement of PV curves obtained in the supine position and with the chest closed or open, we estimated that Pes was 0.18 kPa greater than average lung surface pressure. An increase in K in the prone and head-up positions was attributed to a traction artifact decreasing Pes. Exsanguination increased K and produced a relative increase in gas volume. These results show that overall pulmonary distensibility is unaffected by an intact chest wall. An increase in K and gas volume after exsanguination probably reflects a decreased pulmonary blood volume, with collapse of capillaries increasing the alveolar volume-to-surface ratio.
Mechanical properties of human tracheal cartilage
Authors: Rains J. K. , Bert J. L. , Roberts C. R. , Pare P. D.
Published: December 2017

Biomechanical changes in airway cartilage could influence the mechanics of maximal expiratory flow and cough and the degree of shortening of activated airway smooth muscle. We examined the tensile stiffness of small samples of human tracheal cartilage rings in specimens obtained at autopsy from 10 individuals who ranged in age from 17 to 81 yr. The tensile properties of the cartilage were compared with its content of water (%water), glycosaminoglycans (chondroitin sulfate equivalents, mg/mg dry wt), and hydroxyproline content (mg hydroxyproline/mg dry weight). The average values for tensile stiffness ranged between 1 and 15 MPa and increased significantly with increasing age [tensile stiffness = 0.19 x (age in yr) + 2.02; r = 0.83, P less than 0.05]. The outermost layer of cartilage was the most stiff in all individuals, and the deeper layers were progressively less stiff. Water content and hydroxyproline content both decreased with increasing age. Thus tensile stiffness correlated inversely with water content and hydroxyproline content [tensile stiffness = -0.83 x (%water) + 16.4; r = 0.82, P less than .05 and tensile stiffness = -342 x (hydroxyproline content) + 25; r = 0.87, P less than 0.05]. Total tissue content of glycosaminoglycans did not change with age, although changes in glycosaminoglycan type and proteoglycan structure with increasing age have been described. We conclude that there are age-related changes in the biomechanical properties and biochemical composition of airway cartilage that could influence airway dynamics.
Effect of acetazolamide on gas exchange and acid-base control after maximal exercise
Authors: Kowalchuk J. M. , Heigenhauser G. J. , Sutton J. R. , Jones N. L.
Published: December 2017

To investigate the interactions between the systems that contribute to acid-base homeostasis after severe exercise, we studied the effects of carbonic anhydrase inhibition on exchange of strong ions and CO2 in six subjects after 30 s of maximal isokinetic cycling exercise. Each subject exercised on two randomly assigned occasions, a control (CON) condition and 30 min after intravenous injection of 1,000 mg acetazolamide (ACZ) to inhibit blood carbonic anhydrase activity. Leg muscle power output was similar in the two conditions; peak O2 uptake (VO2) after exercise was lower in ACZ (2,119 +/- 274 ml/min) than in CON (2,687 +/- 113, P less than 0.05); peak CO2 production (VCO2) was also lower (2,197 +/- 241 in ACZ vs. 3,237 +/- 87 in CON, P less than 0.05) and was accompanied by an increase in the recovery half-time from 1.7 min in CON to 2.3 min in ACZ. Whereas end-tidal PCO2 was lower in ACZ than in CON, arterial PCO2 (PaCO2) was higher, and a large negative end-tidal-to-arterial difference (less than or equal to 20 Torr) was present in ACZ on recovery. In ACZ, postexercise increases in arterial plasma [Na+] and [K+] were greater but [La-] was lower. Arteriovenous differences across the forearm showed a greater uptake of La- and Cl- in CON than in ACZ. Carbonic anhydrase inhibition with ACZ, in addition to impairing equilibration of the CO2 system to the acid-base challenge of exercise, was accompanied by changes in equilibration of strong inorganic ions. A lowered plasma [La-] was not accompanied by greater uptake of La- by inactive muscle.
Effect of corticosteroids on diaphragm fatigue, SDH activity, and muscle fiber size
Authors: Lewis M. I. , Monn S. A. , Sieck G. C.
Published: December 2017

The influence of dexamethasone on diaphragm (DIA) fatigue, oxidative capacity, and fiber cross-sectional areas (CSA) was determined in growing hamsters. One group received dexamethasone by daily subcutaneous injection for 21 days (D animals), while pair-weight (P) and free-eating controls (CTL) received saline subcutaneously. Isometric contractile properties of the DIA were determined in vitro by supramaximal direct muscle stimulation in the presence of curare. DIA fatigue resistance was determined through repetitive stimulation at 40 pulses/s for 2 min. A computer-based image-processing system was used to histochemically determine muscle fiber-type proportions, CSA, and succinate dehydrogenase activities. The medial gastrocnemius muscle (MG) was used as a limb muscle control, with histochemical studies being performed on both the superficial (s) and deep/red (r) portions. Dexamethasone markedly attenuated the normal increment in body weight over the 3-wk period. DIA fatigue resistance was significantly reduced in the D compared with CTL and P animals. Dexamethasone had no effect on fiber-type proportions of the DIA or MGr (MGs contained only type II fibers). In the DIA, the CSA of type II fibers was reduced 33% in D and 18.5% in P animals compared with CTL. Although no significant atrophy was noted in the type I DIA fibers of either D or P animals, a trend toward significance was noted in D animals compared with CTL. In the MGs, the CSA of type II fibers was reduced 33% in D and 16.5% in P animals compared with CTL. Significant atrophy of type I and II fibers of the MGr was noted in D animals compared with CTL (33.8 and 35% reductions, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Gas dispersion in volume-cycled tube flow. II. Tracer bolus experiments
Authors: Gaver D. P. , Solway J. , Punjabi N. , Elad D. , Grotberg J. B. , Gavriely N.
Published: December 2017

We present a new method for rapid measurement of local gas dispersion in volume-cycled tube flow. After a small bolus of tracer gas (argon) was injected into the oscillating flow, the time-averaged effective diffusion coefficient (mean value of Deff/D) for axial transport of a tracer gas is evaluated from local argon concentration measurements taken by a mass spectrometer. Two methods are presented for the evaluation of mean value of Deff/D from the concentration measurements: one uses all the sampled data, and the other uses only the local peaks of the concentration. Experiments were conducted in two tubes (radius = 0.85 or 1.0 cm) over a range of frequencies (0.42 less than or equal to f less than or equal to 8.5 Hz) and tidal volumes (7 less than or equal to VT less than or equal to 48 ml). The experimental results show very good agreement with the theoretical predictions of Elad et al. (J. Appl. Physiol. 72: 312–320, 1992). In the absence of oscillations (static fluid), the resulting mean value of Deff/D converges to that of molecular diffusion. We also show that concentration data may be acquired at any radial or axial position, not necessarily at the tracer gas injection point, and the resulting mean value of Deff/D is independent of the spatial position of the sampling catheter. This method is of similar accuracy and is substantially faster than previous methods for measuring gas dispersion in oscillatory flows. The rapidity of these measurements may permit this method to be used for the in vivo assessment of gas transport properties within the pulmonary system.
Brain tissue pH and ventilatory acclimatization to high altitude
Authors: Goldberg S. V. , Schoene R. B. , Haynor D. , Trimble B. , Swenson E. R. , Morrison J. B. , Banister E. J.
Published: December 2017

31P nuclear magnetic resonance spectroscopy (31P-NMRS) was performed on brain cross sections of four human subjects before and after 7 days in a hypobaric chamber at 447 Torr to test the hypothesis that brain intracellular acidosis develops during acclimatization to high altitude and accounts for the progressively increasing ventilation that develops (ventilatory acclimatization). Arterial blood gas measurements confirmed increased ventilation. At the end of 1 wk of hypobaria, brain intracellular pH was 7.023 +/- 0.046 (SD), unchanged from preexposure pH of 6.998 +/- 0.029. After return to sea level, however, it decreased to 6.918 +/- 0.032 at 15 min (P less than 0.01) and 6.920 +/- 0.046 at 12 h (P less than 0.01). The ventilatory response to hypoxia increased [from 0.35 +/- 0.11 (l/min)/(-%O2 saturation) before exposure to 0.69 +/- 0.19 after, P = 0.06]. Brain intracellular acidosis is probably not a supplemental stimulus to ventilatory acclimatization to high altitude. However, brain intracellular acidosis develops on return to normoxia from chronic hypoxia, suggesting that brain pH may follow changes in blood and cerebrospinal fluid pH as they are altered by changes in ventilation.
Pulmonary C-fiber stimulation by capsaicin evokes reflex cholinergic bronchial vasodilation in sheep
Authors: Coleridge H. M. , Coleridge J. C. , Green J. F. , Parsons G. H.
Published: December 2017

We investigated changes in bronchial blood flow (Qbr) associated with capsaicin-induced stimulation of pulmonary C-fibers in seven anesthetized and two unanesthetized sheep. A Doppler flow probe chronically implanted around the common bronchial artery provided a signal (delta F, kHz) linearly related to bronchial arterial blood velocity (Vbr, cm/s), which was proportional to Qbr. An index of bronchial vascular conductance (Cbr, in arbitrary units) was calculated as the ratio of Vbr to systemic arterial pressure (Pa). Right atrial injection of capsaicin evoked a prompt pulmonary chemoreflex (apnea, bradycardia, and hypotension), with immediate increases in Vbr (average +34%) and Cbr (+63%) that reached a maximum approximately 7 s after the injection. A second increase in Vbr, but not in Cbr, occurred approximately 12 s later, coinciding with an increase in Pa. Vagal cooling (0 degrees C) prevented the pulmonary chemoreflex; it also abolished the immediate increases in Vbr and Cbr in four of six sheep and substantially reduced them in two sheep; it did not affect the late increases in Vbr and Pa. Results after atropine indicated that the immediate increases in Vbr and Cbr were mainly cholinergic. In two sheep a small residual vasodilation survived combined cholinergic and adrenergic blockade and may have been due to peripheral release of neurokinins.
Contractile properties of feline genioglossus, sternohyoid, and sternothyroid muscles
Authors: van Lunteren E. , Manubay P.
Published: December 2017

Despite a wealth of information about the respiratory behavior of pharyngeal dilator muscles such as the genioglossus, sternohyoid, and sternothyroid muscles, little is known about their contractile and endurance properties. Strips of these muscles (as well as of the diaphragm) were surgically removed from anesthetized cats and studied in vitro at 37 degrees C. The isometric contraction times of the muscles were 38 +/- 1, 31 +/- 1, 28 +/- 2, and 35 +/- 1 ms for genioglossus, sternothyroid, sternohyoid, and diaphragm, respectively. Contraction times were significantly longer for the genioglossus than for the sternohyoid and sternothyroid muscles and significantly longer for the diaphragm than for the sternohyoid muscle. Twitch-to-tetanic ratios were largest for the diaphragm and lowest for the sternohyoid muscle, and the force-frequency relationship of the sternohyoid was most rightward positioned and that of the diaphragm was most leftward positioned. During repetitive stimulation, the decrement in force was greatest for the diaphragm and least for the genioglossus muscle, with the force loss of the two hyoid muscles being intermediate in magnitude. The Burke fatigue index was significantly greater for the genioglossus than for the diaphragm, despite similar tension-time indexes during repetitive stimulation. These data indicate heterogeneity among pharyngeal dilator muscles in their contractile and endurance properties, that certain pharyngeal dilator muscle properties differ from diaphragmatic properties, and that pharyngeal muscles have relatively fast contractile kinetics yet reasonable endurance characteristics.