bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen radicals in capsaicin-induced bronchoconstriction
Authors: Lai Y. L.
Published: December 2017

The role of oxygen radicals in capsaicin-induced bronchoconstriction was investigated using scavengers of the radicals. A total of 48 guinea pigs weighing 293 +/- 7 g were employed in this study, which consisted of two phases. In phase 1, 35 anesthetized paralyzed animals were divided into five groups: group 1A, control (n = 6); group 1B, chronic dimethylthiourea (DMTU, n = 12); group 1C, acute DMTU (n = 6); group 1D, superoxide dismutase (n = 4); and group 1E, catalase (n = 7). All animals were injected with capsaicin (16 micrograms/kg iv), and changes in respiratory compliance and maximal expiratory flow rate were used as indicators of bronchoconstriction. The capsaicin injection caused a marked airway spasm that was significantly ameliorated by chronic DMTU pretreatment, but no amelioration was noted with the other treatments. An additional study for group 1C was performed using a double dose of DMTU. Again no amelioration was found. In phase 2, 13 animals were divided into two groups: group 2A, substance P (SP, n = 7) and group 2B, chronic DMTU + SP (n = 6). There was no significant difference in SP-induced bronchoconstriction between animals in these two groups. These data suggest that capsaicin-induced airway constriction is modulated by oxygen radicals which may augment mainly on the biosynthesis and/or axonal transport of tachykinins.
Effects of acetazolamide on metabolic and respiratory responses to exercise at maximal O2 uptake
Authors: Rose R. J. , Hodgson D. R. , Kelso T. B. , McCutcheon L. J. , Bayly W. M. , Gollnick P. D.
Published: December 2017

Changes in blood gases, ions, lactate, pH, hemoglobin, blood temperature, total body metabolism, and muscle metabolites were measured before and during exercise (except muscle), at fatigue, and during recovery in normal and acetazolamide-treated horses to test the hypothesis that an acetazolamide-induced acidosis would compromise the metabolism of the horse exercising at maximal O2 uptake. Acetazolamide-treated horses had a 13-mmol/l base deficit at rest, higher arterial Po2 at rest and during exercise, higher arterial and mixed venous Pco2 during exercise, and a 48-s reduction in run time. Arterial pH was lower during exercise but not in recovery after acetazolamide. Blood temperature responses were unaffected by acetazolamide administration. O2 uptake was similar during exercise and recovery after acetazolamide treatment, whereas CO2 production was lower during exercise. Muscle [glycogen] and pH were lower at rest, whereas heart rate, muscle pH and [lactate], and plasma [lactate] and [K+] were lower and plasma [Cl-] higher following exercise after acetazolamide treatment. These data demonstrate that acetazolamide treatment aggravates the CO2 retention and acidosis occurring in the horse during heavy exercise. This could negatively affect muscle metabolism and exercise capacity.
Influence of single hindlimb support during simulated weightlessness in the rat
Authors: Stump C. S. , Overton J. M. , Tipton C. M.
Published: December 2017

Mature male rats (n = 16) were assigned to either 14 days of head-down suspension with one hindlimb supported (HDS) or to control cages (C) of similar dimensions. Hindlimb support during HDS preserved the muscle mass-to-body mass ratio (mg/100g) compared with C conditions for the soleus (48.3 +/- 1.0 to 41.7 +/- 1.0), plantaris (98.4 +/- 3.4 to 103.3 +/- 4.1), and gastrocnemius (484.7 +/- 18.5 to 507.2 +/- 13.9). However, the muscle mass-to-body mass ratio was significantly lower for the soleus (28.9 +/- 1.5), plantaris (83.9 +/- 3.6), and gastrocnemius (411.9 +/- 24.2) muscles from the freely hanging hindlimbs compared with the contralateral muscles from the supported hindlimbs or muscles from C animals. Citrate synthase activity (mumol.g-1.min-1) was significantly lower in soleus muscles from HDS rats in both the supported (19.4 +/- 2.3) and freely hanging (20.0 +/- 1.6) hindlimbs compared with C (28.5 +/- 3.1), whereas soleus muscle glycogen concentration (mg/g) was significantly higher in the freely hanging limbs from HDS rats (5.90 +/- 0.31) but not in the supported limbs (3.80 +/- 0.61) compared with C (4.34 +/- 0.50). Doppler flow probes were used to determine that iliac blood flow to freely hanging hindlimbs was significantly decreased after 48 (-19 +/- 5%) and 72 (-20 +/- 6%)h of HDS compared with presuspension values. In addition, iliac vascular resistance was significantly elevated at most time points during the 72 h of HDS in the freely hanging limbs but not the supported hindlimbs.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in insulation of body tissue and wet suits during underwater exercise at various atmospheric pressures
Authors: Iwamoto J. , Sagawa S. , Tajima F. , Miki K. , Tanaka H. , Shiraki K.
Published: December 2017

To clarify the independent changes of insulations of body tissues (Itissue) and wet suit (Isuit) in the wet-suited subject during underwater exercise, overall heat flow from the skin (Htissue) and wet suit (Hsuit) and esophageal (Tes), skin (Tsk), and wet suit temperatures were measured at 1, 2, and 2.5 atmospheres absolute (ATA) at critical water temperature (Tcw). The average Tcw in nine wet-suited men (23-38 yr) was 22.3 +/- 0.2, 26.3 +/- 0.2, and 28.0 +/- 0.4 degrees C (SE) at 1, 2, and 2.5 ATA, respectively. At Tcw of each pressure male volunteers wearing 5-mm neoprene wet suits completed three 2-h experiments while immersed up to the neck. During one experiment the subjects remained at rest, and in the other two they exercised on an underwater ergometer at two different intensities (2 and 3 met). Tes significantly declined (P less than 0.05) over 2 h from 37.1 to 36.5 degrees C during rest in each pressure. The 2-met exercise prevented Tes from falling in all pressures, and the 3-met exercise elevated Tes by 0.2-0.3 degrees C. There was no exercise-dependent difference in Isuit, but a pressure-dependent difference was remarkable. The Itissue at rest was identical for all pressures; however, it progressively decreased as a function of exercise intensity. It is concluded that overall Itissue is entirely determined by work intensity at Tcw, but not by atmospheric pressure. On the contrary, Isuit at Tcw is solely dependent on the pressure, but not on the work intensity.
Use of norepinephrine uptake to measure lung capillary recruitment with exercise
Authors: Dupuis J. , Goresky C. A. , Juneau C. , Calderone A. , Rouleau J. L. , Rose C. P. , Goresky S.
Published: December 2017

We used the multiple indicator-dilution technique with norepinephrine, a vascular endothelium surface marker, to study the pulmonary vascular changes in awake exercising dogs. The vascular space tracers, labeled erythrocytes and albumin, and a water space tracer, 1,8-octanediol, were injected with the norepinephrine, and right atrium-aortic root dilution curves were obtained in nine dogs, at rest and at two increasing levels of exercise. Extravascular lung water multiple tracer dilutional estimates increased with flow and rapidly approached a maximal asymptotic value representing 75% of the postmortem lung weight. The ratio of the extravascular lung water measured in this way to that measured gravimetrically also increased, to reach an asymptotic proportion of close to 100%. The transit time-defined central vascular space increased linearly with flow; the ratio of lung tissue space to lung vascular space, therefore, decreased with increasing flow. The mean tracer upslope norepinephrine extractions at rest and at the two levels of exercise were 17 +/- 1.2, 14 +/- 0.8, and 15 +/- 0.8% (SE). With the use of the Crone approximation, we computed permeability-surface area products for norepinephrine; these increased linearly with flow. If permeability does not change, the increase in the permeability-surface area product with flow can be attributed to capillary recruitment. We conclude that when all lung tissue has become accessible to 1,8-octanediol delivered via the perfused vascular space, there is nevertheless further recruitment, with increase in flow, of vascular surface that can extract norepinephrine.
Reflex changes in tracheal smooth muscle tone during high-frequency oscillation
Authors: Man G. C. , Teo K. K. , Kappagoda C. T. , Man S. F.
Published: December 2017

We examined the effect of high-frequency oscillatory ventilation (HFOV) on tracheal smooth muscle tension and upper airway resistance in anesthetized dogs. The animals were ventilated via a low tracheostomy by HFOV or conventional intermittent positive pressure ventilation (IPPV) with and without added positive end-expiratory pressure (PEEP). The transverse muscle tension of the trachea above the tracheostomy was measured and found to be lower during HFOV when compared with IPPV or IPPV with PEEP. When both vagi were cooled to 8 degrees C to interrupt afferent traffic from the lungs, there was no longer any difference between the modes of ventilation. In a second series of experiments, the airflow resistance of the upper airway above the tracheostomy was measured (Ruaw). During HFOV, Ruaw was significantly lower than during either IPPV or IPPV with PEEP. We conclude that HFOV induces a relaxation of tracheal smooth muscle and a reduction of upper airway resistance through a vagally mediated mechanism.
Mechanism of ethanol-induced vasodilation
Authors: Malpas S. C. , Robinson B. J. , Maling T. J.
Published: December 2017

The mechanism by which ethanol ingestion causes dermal vasodilation is unclear, but it may result from a direct action on central vascular control mechanisms. Forearm blood flow and peripheral skin temperatures were examined in five quadriplegics (lesions above T7) and five control subjects, before and after the ingestion of ethanol (0.75 ml/kg body wt). The lack of vasomotor efferent function was confirmed in the quadriplegics by the absence of vasodilation in response to radiant heating of the torso. There were no significant changes in peripheral temperatures or forearm blood flow after ethanol in the quadriplegics. The control subjects had a significant increase in forearm blood flow (1.12 +/- 0.2 ml.min-1.100 ml-1) and skin temperature (finger 2.4 +/- 0.4 degrees C, toe 3.4 +/- 0.3 degrees C) after ethanol. These data suggest that ethanol may induce peripheral vasodilation by modulation of central vasomotor control mechanisms.
Analysis of pulmonary arterial pressure profile after occlusion of pulsatile blood flow
Authors: Maarek J. M. , Hakim T. S. , Chang H. K.
Published: December 2017

In isolated canine lung lobes perfused with a pulsatile pump, arterial occlusions were performed and the postocclusion arterial pressure profiles were analyzed to estimate the pulmonary capillary pressure. A solenoid valve interposed between the pump and the lobar artery was used to perform arterial occlusions at several instants equally distributed within a pressure cycle. Double occlusions were also accomplished by simultaneously activating the solenoid valve and clamping the venous outflow of the lung lobe. To analyze an arterial occlusion pressure profile, we computed the best monoexponential fit of the pressure decay over a short period of time after the occlusion maneuvers. Two estimates of the capillary pressure were derived from this analysis: 1) the extrapolation of the exponential fit to the instant of occlusion, and 2) the point at which the recorded pressure decay curve merges with the exponential fit. The pressures thus determined were compared with the double occlusion pressure that provided an independent estimate of the pulmonary capillary pressure. Our results show that, under a wide range of conditions, the estimates of the capillary pressure obtained from the arterial occlusion data are nearly equal to the double occlusion pressures. Additionally, we estimated the capillary pressure variations within a pressure cycle by examining the occlusion pressures sampled at different instants of the cycle. The pulsatility of the pulmonary microvascular pressure varied with the pump frequency as well as the state of arterial and venous vasoaction. These variations are consistent with the representation of the lung vasculature as a low-pass filter.
PAF potentiates protamine-induced lung edema: role of pulmonary venoconstriction
Authors: Chen C. R. , Voelkel N. F. , Chang S. W.
Published: December 2017

We studied the synergistic interaction between platelet-activating factor (PAF) and protamine sulfate, a cationic protein that causes pulmonary endothelial injury, in isolated rat lungs perfused with a physiological salt solution. A low dose of protamine (50 micrograms/ml) increased pulmonary artery perfusion pressure (Ppa) but did not increase wet lung-to-body weight ratio after 20 min. Pretreatment of the lungs with a noninjurious dose of PAF (1.6 nM) 10 min before protamine markedly potentiated protamine-induced pulmonary vasoconstriction and resulted in severe lung edema and increased lung tissue content of 6-keto-prostaglandin F1 alpha, thromboxane B2, and leukotriene C4. Pulmonary microvascular pressure (Pmv), measured by double occlusion, was markedly increased in lungs given PAF and protamine. These potentiating effects of PAF were blocked by WEB 2086 (10(-5) M), a specific PAF receptor antagonist. Pretreatment of the lungs with a high dose of histamine (10(-4) M) failed to enhance the effect of protamine on Ppa, Pmv, or wet lung-to-body weight ratio. Furthermore, PAF pretreatment enhanced elastase-, but not H2O2-, induced lung edema. To assess the role of hydrostatic pressure in edema formation, we compared lung permeability-surface area products (PS) in papaverine-treated lungs given either protamine alone or PAF + protamine and tested the effect of mechanical elevation of Pmv on protamine-induced lung edema. In the absence of vasoconstriction, PAF did not potentiate protamine-induced increase in lung PS. On the other hand, mechanically raising Pmv in protamine-treated lungs to a level similar to that measured in lungs given PAF + protamine did not result in a comparable degree of lung edema. We conclude that PAF potentiates protamine-induced lung edema predominantly by enhanced pulmonary venoconstriction. However, a pressure-independent effect of PAF on lung vasculature cannot be entirely excluded.
Changes in upper airway resistance with lung inflation and positive airway pressure
Authors: Series F. , Cormier Y. , Couture J. , Desmeules M.
Published: December 2017

The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra-thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP.
Exercise training and incidence of cerebrovascular lesions in stroke-prone spontaneously hypertensive rats
Authors: Tipton C. M. , McMahon S. , Leininger J. R. , Pauli E. L. , Lauber C.
Published: December 2017

To assess the effects of moderate exercise [40-70% maximal oxygen uptake (VO2max)] on resting blood pressures, the presence of cerebrovascular lesions, and the life spans of stroke-prone hypertensive rats, nontrained and trained male and female rats were assigned to two experimental groups. The first (n = 48) were exercise trained after 38 days of age, whereas the second (n = 44) initiated exercise training when the animals were 134 days of age. To facilitate cerebrovascular lesions, the sodium concentrations in the rat chow and in the drinking solutions were increased. Symptoms utilized to denote the presence of cerebrovascular lesions were irritability, hyperresponsiveness, ataxia, lethargy, unwillingness to run, and combinations thereof. All brains were removed immediately after death, fixed, and evaluated grossly and microscopically for lesions. In the study with the younger animals, training was associated with a 7-9% increase in VO2max that was statistically significant only in animals with no histological evidence of cerebrovascular lesions. For the older animals, a significant 5-8% increase in VO2max was noted for animals with or without lesions. After 42 days of training for both groups, resting blood pressures for the trained groups with histological lesions were significantly lower. However, this trend did not continue, and the older trained rats appeared to have strokes earlier and to die sooner than their nontrained controls. Although 83% of the older animals had subjective evidence for a stroke before they died, the percentage of animals with lesions ranged from 42 to 58%, with the trained groups having higher percentages.(ABSTRACT TRUNCATED AT 250 WORDS)
Tracheal insufflation of tumor necrosis factor protects rats against oxygen toxicity
Authors: Tsan M. F. , White J. E. , Santana T. A. , Lee C. Y.
Published: December 2017

Tracheal insufflation of tumor necrosis factor (TNF; 5 micrograms or 1.2 x 10(5) U) markedly enhanced the survival of adult rats exposed to 100% O2: 12 of 17 rats (71%) survived for greater than 11 days, whereas 30 of 30 control (Hanks' balanced salt solution) insufflated rats (100%) died within 3 days of O2 exposure. Insufflation of gamma-interferon (5 micrograms) or intraperitoneal injection of up to 40 micrograms TNF did not afford any protection. At 55 h after O2 exposure, TNF-insufflated rats showed less pulmonary edema, as determined by the extravascular lung water content-to-bloodless lung dry weigh ratio and less alveolar capillary leak as determined by the protein content in the bronchoalveolar lavage fluid, than control insufflated rats similarly exposed. This protection against O2 toxicity by TNF insufflation was associated with increased lung superoxide dismutase, catalase, and glutathione peroxidase activities. The enhancement of lung antioxidant enzyme activities was noted at 55 h of O2 exposure, when control animals began to die of O2 toxicity. This temporal relationship suggests that TNF-induced increase in antioxidant enzyme activities contributes, at least in part, to the observed protection.
Respiratory changes in parasternal intercostal intramuscular pressure
Authors: Leenaerts P. , Decramer M.
Published: December 2017

In an attempt to obtain insight in the forces developed by the parasternal intercostal muscles during breathing, changes in parasternal intramuscular pressure (PIP) were measured in 14 supine anesthetized dogs using a microtransducer method. In six animals, during bilateral parasternal stimulation a linear relationship between contractile force exerted on the rib and PIP was demonstrated (r greater than 0.95). In eight animals, during quiet active inspiration, substantial (55 +/- 11.5 cmH2O) PIP was developed. During inspiratory resistive loading and airway occlusion the inspiratory rise in PIP increased in proportion to the inspiratory fall in pleural pressure (r = 0.82). Phrenicotomy and vagotomy resulted in an increase in the inspiratory rise in PIP of 21% and 99%, respectively. During passive deflation, when the parasternal intercostals were passively lengthened, large rises (320 +/- 221 cmH2O) in intramuscular pressure were observed. During passive inflation intramuscular pressure remained constant or even decreased slightly (-8 +/- 25 cmH2O) as expected on the basis of the passive shortening of the muscles. PIP thus invariably increased when tension increased either actively or passively. From PIP it is clear that the parasternals exert significant forces on the ribs during respiratory maneuvers.
Adrenergic responses to cognitive activity in a cold environment
Authors: Thomas J. R. , Ahlers S. T. , House J. F. , Schrot J. , Van Orden K. F. , Winsborough M. M. , Hesslink R. L. , Lewis S. B.
Published: December 2017

Adrenergic responses during physical stress such as cold exposure have been reported to differ from those responses observed during cognitive activity. Both the separate and the combined effects of cold and cognitive activity on catecholamine activity were examined in six male subjects. Alterations in plasma epinephrine and norepinephrine showed different patterns as a function of exposure to a 4 degrees C cold environment, a cognitive performance assessment battery (PAB), and the two conditions combined. Plasma epinephrine was not altered by exposure to cold and only slightly increased by PAB performance when given at 23 degrees C. However, epinephrine was substantially elevated by exposure to combined cold and PAB. Heart rate changes paralleled observed changes in epinephrine. Norepinephrine release was predominantly increased by cold exposure and was not altered by PAB performance.
Effect of exercise on redistribution and clearance of inhaled particles from hamster lungs
Authors: Sweeney T. D. , Tryka A. F. , Brain J. D.
Published: December 2017

Does exercise alter the redistribution and clearance of particles from the lungs? Sedentary hamsters and hamsters that were exercise trained by voluntary wheel running for the previous 5 wk were exposed to a 198Au-labeled aerosol for 25 min. Six trained and 6 sedentary animals were killed within 5 min after the exposure (day 0); the same number were killed 5 days later. The trained hamsters ran ad libitum during those 5 days. The lungs of all animals were excised, dried at total lung capacity, sliced into 1-mm-thick sections, and dissected into pieces that were counted for radioactivity and weighed. On day 0, trained hamsters had 80% more particles per milligram of lung than sedentary hamsters, although both were exposed under identical conditions of restraint. After five days, exercising hamsters cleared 38% of the particles present at day 0, whereas sedentary animals removed only 15%. Significant clearance was observed from the middle lung regions of sedentary hamsters and from all lung regions in exercising hamsters. We conclude that exercise can enhance the redistribution and clearance of particles from the lungs; the mechanisms responsible are as yet unclear.
Carbon monoxide-mediated brain lipid peroxidation in the rat
Authors: Thom S. R.
Published: December 2017

Clinical and animal data suggest that the pathogenesis of CO poisoning extends beyond the inhibition of hemoglobin function, but no mechanism has been identified. Evidence of neurological compromise, particularly loss of consciousness, has been implicated as a marker for increased mortality and morbidity in clinical reports. Experiments were carried out with rats to assess whether CO exposure may cause brain lipid peroxidation. With the use of two methods, measurement of conjugated dienes and thiobarbituric acid reactivity, brain lipid peroxidation could be documented as a result of exposure to CO at a concentration sufficient to cause unconsciousness. Products of lipid peroxidation were increased by 75% over the base-line values 90 min after CO exposure. Unconsciousness was associated with a brief period of hypotension, so brief that in itself it caused no apparent insult. Lipid peroxidation occurred only after the animals were returned to CO-free air, and there was no direct correlation with the carboxyhemoglobin level. This work may provide an explanation for a number of currently poorly understood clinical observations regarding CO poisoning.
Increased leukotriene E4 excretion during antigen-induced bronchoconstriction in allergic sheep
Authors: Tagari P. , Abraham W. M. , McGolrick J. , Charleson S. , Soler M. , Ahmed A. , Cortez A. , Ford-Hutchinson A. W.
Published: December 2017

The metabolism of leukotrienes (LT) in the sheep was investigated to define markers of 5-lipoxygenase involvement in allergic responses, obtainable by noninvasive techniques. Intravenous administration of 14, 15-[3H]LTC4 (0.5 microCi/kg) revealed a rapid clearance from the circulation (half time = 90 s). Circulatory metabolism was apparent, with early formation (within 1 min) of LTD4 and LTE4 shown by reverse-phase high-pressure liquid chromatography (RP-HPLC). Urinary 3H excretion comprised 10% of the original dose. [3H]LTE4 (characterized by coelution with authentic standards during RP-HPLC analysis) was observed in early urine samples. By use of a sensitive and specific RP-HPLC radioimmunoassay analysis, immunoreactive material coeluting with LTE4 was detected in urine from allergic sheep. Excretion of this material was significantly increased during antigen-induced acute bronchoconstriction in eight conscious allergic sheep [preantigen, 65.70 +/- 24.27 (SE) pg; 0-1 h postantigen, 208.00 +/- 71.10 pg, P less than 0.05], but not during late responses. However, total postantigen LTE4 excretion (37.8 - 956.1 pg/8 h) was highly correlated (r = 0.976, P less than 0.001) with the severity of bronchoconstriction (445.3 - 2,409.1% specific pulmonary resistance per hour) assessed by measurement of the area under the curve of pulmonary function plotted against time. These findings represent an important demonstration of in vivo allergen-induced peptide LT generation in a physiologically characterized animal model of prolonged allergic bronchoconstriction and further substantiate an important role for LT in this model of allergic asthma.
Effect of dorsolateral pontine lesions on diaphragmatic activity during REMS
Authors: Hendricks J. C. , Kline L. R. , Davies R. O. , Pack A. I.
Published: December 2017

Muscle atonia is a feature of normal rapid-eye-movement sleep (REMS). The suppression of accessory respiratory muscle activity has been investigated and a role for sleep-disordered breathing hypothesized, but the suppression of diaphragmatic activity has rarely been considered. We hypothesized that the activity of the diaphragm was suppressed by an area of the dorsolateral pons during REMS. Lesions in this region have previously been shown to abolish the atonia of REMS. The diaphragmatic electromyogram (EMG) activity was analyzed in five naturally sleeping cats before and after pontine lesions leading to REMS without atonia. Although respiratory timing parameters were not altered by the lesion, the inspiratory rate of rise was significantly increased in all cats, and the brief pauses (40-100 ms) in the diaphragmatic EMG normally seen in REMS were virtually abolished. We conclude that the dorsolateral pons has a role in suppressing diaphragmatic activation during REMS. This suppression affects the average rate of rise of diaphragmatic activity and also leads to brief intermittent complete cessation of ongoing muscle activity. These decrements in diaphragm activity could jeopardize ventilation during REMS.
Head-down bed rest impairs vagal baroreflex responses and provokes orthostatic hypotension
Authors: Convertino V. A. , Doerr D. F. , Eckberg D. L. , Fritsch J. M. , Vernikos-Danellis J.
Published: December 2017

We studied vagally mediated carotid baroreceptor-cardiac reflexes in 11 healthy men before, during, and after 30 days of 6 degrees head-down bed rest to test the hypothesis that baroreflex malfunction contributes to orthostatic hypotension in this model of simulated microgravity. Sigmoidal baroreflex response relationships were provoked with ramped neck pressure-suction sequences comprising pressure elevations to 40 mmHg followed by serial R-wave-triggered 15-mmHg reductions to -65 mmHg. Each R-R interval was plotted as a function of systolic pressure minus the neck chamber pressure applied during the interval. Compared with control measurements, base-line R-R intervals and the minimum, maximum, range, and maximum slope of the R-R interval-carotid pressure relationships were reduced (P less than 0.05) from bed rest day 12 through recovery day 5. Baroreflex slopes were reduced more in four subjects who fainted during standing after bed rest than in six subjects who did not faint (-1.8 +/- 0.7 vs. -0.3 +/- 0.3 ms/mmHg, P less than 0.05). There was a significant linear correlation (r = 0.70, P less than 0.05) between changes of baroreflex slopes from before bed rest to bed rest day 25 and changes of systolic blood pressure during standing after bed rest. Although plasma volume declined by approximately 15% (P less than 0.05), there was no significant correlation between reductions of plasma volume and changes of baroreflex responses. There were no significant changes of before and after plasma norepinephrine or epinephrine levels before and after bed rest during supine rest or sitting.(ABSTRACT TRUNCATED AT 250 WORDS)
An antifibrotic agent reduces blood pressure in established pulmonary hypertension in the rat
Authors: Poiani G. J. , Tozzi C. A. , Choe J. K. , Yohn S. E. , Riley D. J.
Published: December 2017

We have shown that administration of the antifibrotic agent cis-4-hydroxy-L-proline (cHyp) to rats at the onset of exposure to hypoxia prevents collagen accumulation in pulmonary arteries and the rise in pulmonary blood pressure. In this experiment, we tested whether cHyp is effective when administered after hypertension was already established. Rats were exposed to hypoxia (10% O2) for 21 days. Groups were hypoxic animals treated with cHyp (200 mg/kg sc twice daily) on days 10-21 (hypoxic cHyp) and saline-injected hypoxic animals (hypoxic). On day 21, we measured mean right ventricular pressure, hematocrit, collagen content of main and intrapulmonary arteries, and wall thickness of arterioles. Treatment reduced right ventricular pressure from 21 +/- 1 to 17 +/- 1 mmHg (P less than 0.05), hematocrit from 66 +/- 1 to 56 +/- 1% (P less than 0.05), hydroxyproline content of intrapulmonary arteries from 30 +/- 3 to 11 +/- 2 micrograms/vessel (P less than 0.05), and wall thickness from 27 +/- 3 to 16 +/- 2 microns (P less than 0.05). These results show that vascular collagen content is increased in established pulmonary hypertension and that cHyp treatment is effective in partially preventing the hemodynamic, structural, and biochemical changes if started after pulmonary hypertension is established. cHyp may also affect the rheological properties of blood.
Differential responses of the airways and pulmonary tissues to inhaled histamine in young dogs
Authors: Sly P. D. , Lanteri C. J.
Published: December 2017

Airway and pulmonary tissue responses to aerosolized histamine were studied in five mongrel puppies (8-10 wk old). Alveolar pressure was measured by use of alveolar capsules and respiratory mechanics calculated during tidal ventilation and flow interruptions. Aerosolized histamine caused an increase in the tissue viscoelastic properties, which was measured as an increase in pulmonary resistance during tidal ventilation. An increase in stress recovery of the pulmonary tissues was measured with the interrupter technique after aerosolized histamine. These data demonstrate that aerosolized histamine caused an increase in the tissue viscoelastic properties. The most reasonable explanation for the mechanism of this increase would seem to be via reflex pathways stimulated by centrally located receptors.
Evaluating pulmonary vascular permeability with radiolabeled proteins: an error analysis
Authors: Mintun M. A. , Warfel T. E. , Schuster D. P.
Published: December 2017

Using techniques of mathematical simulation, we compared two methods of evaluating pulmonary vascular permeability, i.e., transvascular protein flux. Both methods calculate a transport rate constant [pulmonary transcapillary escape rate (PTCER)] after making external radiation detection measurements of an intravenously administered radiolabeled protein. With one method, lung tissue time-activity data are acquired by positron emission tomography (PET) and are interpreted with a two-compartment model. With the other method, the time-activity data are acquired with simple detector probes and are interpreted by linear regression after normalizing for various physical factors (slope-intercept or SI method). The results show that significant errors in calculating PTCER can result from using the SI method, because it ignores the effects of back-flux on the tissue time-activity measurements. Both methods produce errors if the data analysis includes activity from vascular volumes not involved in tracer exchange with the extravascular compartment. Significant errors can also occur with the PET method, particularly when permeability is nearly normal, if pulmonary vascular volume changes significantly during the period of data collection. On balance, the PET method appears to be the method of choice for accurately evaluating pulmonary vascular permeability by protein flux measurements, although both methods may be useful in clinical applications.
Small-sample reproducibility estimates: an example using rebreathing measurements
Authors: Jensen R. L. , Crapo R. O. , Mason J. D. , Yanowitz F. G.
Published: December 2017

We developed a statistical technique to estimate the reproducibility of a parameter from a population in which only two repeated measurements can be made in a single individual. The following data were analyzed: acetylene cardiac output (Qc), lung tissue volume (Vti), and carbon monoxide diffusing capacity (DLCO) measured by rebreathing techniques in a population of 86 healthy subjects (51 men and 35 women). Each subject was measured twice with a computerized rebreathing system using a test gas of 10% He-0.3% C18O-0.7% C2H2-25% O2-balance N2 while sitting at rest. The estimated coefficients of variation for repeated measurements were 6.8, 10.3, and 5.7% for Qc, Vti, and DLCO, respectively. Chebyshev's inequality was used to estimate the imprecision for a single measurement of these parameters and for averages of two or more repeated values. A single measurement of Qc would be within 14.2% of a “true” mean 90% of the time, whereas an average of three consecutive measurements would be within 8.2% of the true mean 90% of the time. Single measurements of Vti and DLCO were found to be within 21.7 and 12.0%, respectively, of the true mean 90% of the time. When three consecutive measurements are averaged, Vti is within 12.6% and DLCO is within 6.9% of the true mean 90% of the time. We conclude that 1) rebreathing Qc is as reproducible as other measurements of cardiac output, 2) rebreathing measurements of DLCO are as reproducible as those made by the single-breath technique, and 3) an average of two to three measurements of Vti should be made to obtain values with a reasonable degree of precision.
Muscarinic receptors in airways: recent developments
Authors: Barnes P. J.
Published: December 2017

Recently there have been important advances in our understanding of muscarinic receptors in airways that have important implications for understanding airway control and for future therapy of airway diseases. The transduction mechanisms involved in muscarinic receptor activation are now better understood. Receptor-linked phosphoinositide hydrolysis leads to release of calcium ions from intracellular stores, resulting in contraction of airway smooth muscle. At least five subtypes of muscarinic receptor have now been cloned, although only three subtypes can be distinguished pharmacologically. M1 receptors are facilitatory to neurotransmission in airway parasympathetic ganglion cells and have also been identified in airway submucosal glands and on the alveolar walls of human lung. M2 receptors are located on postganglionic nerves and function as powerful feedback inhibitory receptors (autoreceptors) that are likely to be involved in modulation of reflex bronchoconstriction. These receptors may be dysfunctional in asthmatic airways. M3 receptors are present on airway smooth muscle and submucosal glands and mediate the classical muscarinic effects in airways. Molecular biology techniques should now allow further study of the factors that regulate transcription and expression of muscarinic receptors in airways.
Role of the glucose cycle in control of net glucose flux in exercising humans
Authors: Weber J. M. , Klein S. , Wolfe R. R.
Published: December 2017

The hepatic glucose cycle involves the production of plasma glucose from glucose 6-phosphate and the simultaneous conversion of glucose back to glucose 6-phosphate. We have evaluated the role of the glucose cycle in the regulation of plasma glucose concentration during exercise at 70% of maximal O2 uptake and during recovery in five normal volunteers. Total glucose flux was measured by use of [2-2H]glucose (Ra2), net glucose flux through the glucose cycle was determined with [6,6-2H2]glucose (Ra6), and the rate of glucose cycling was determined by Ra2 - Ra6. Gas chromatography-mass spectrometry was used for analysis of isotopic enrichment. At rest, 33% of total glucose flux was recycled. In exercise, total flux increased 300%, but so did glucose cycling, which means that there was no change in the percentage of flux recycled. In recovery, both total flux and the rate of recycling returned rapidly to the resting value. We therefore conclude that whereas total glucose production can respond extremely quickly to large changes in energy requirements caused by exercise, thereby enabling maintenance of a constant blood glucose concentration, glucose cycling does not have an important role in amplifying the control of net hepatic glucose flux through the glucose cycle.
Resorptive clearance and transepithelial potential difference in capsaicin-treated F344 rats
Authors: De Sanctis G. T. , App E. M. , Trask J. K. , De Sanctis B. I. , Remmers J. E. , Green F. H. , Man S. F. , King M.
Published: December 2017

The long-term effects of substance P (SP) depletion on epithelial integrity were assessed by measurements of airway transepithelial potential difference (PD) and resorptive clearance. Both techniques are highly sensitive to differences in epithelial permeability. PD (mV) was assayed with a KCl-saturated agar bridge technique in the lower trachea of Fischer 344 rats depleted of SP by neonatal capsaicin treatment. Capsaicin treatment is known to ablate a subpopulation of primary afferent fibers containing SP. Resorptive clearance (clearance in 1 h) was measured with 99mTc-labeled diethylenetriaminepentaacetic acid administered as a 100-microliters (100 microCi) bolus. Depletion of SP by neonatal treatment with capsaicin resulted in a highly significant increase in resorptive clearance (P less than 0.001). There was also a significant difference in PD in the lower trachea, the values being less negative for the capsaicin-treated rats (P less than 0.005). The increase in resorptive clearance may reflect the leakiness of the epithelial membrane, as also suggested by the decrease in PD. Aside from its known involvement as a neurotransmitter in neurogenic inflammation, SP may, under normal physiological conditions, have an additional role in the maintenance of epithelial barrier function.
Effects of cardiac oscillations and lung volume on acinar gas mixing during apnea
Authors: Mackenzie C. F. , Skacel M. , Barnas G. M. , Brampton W. J. , Alana C. A.
Published: December 2017

We evaluated the importance of cardiogenic gas mixing in the acini of 13 dogs during 2 min of apnea. 133Xe (1-2 mCi in 4 ml of saline) was injected into an alveolar region through an occluded pulmonary artery branch, and washout was measured by gamma scintillation scanning during continued occlusion or with blood flow reinstated. The monoexponential rate constant for Xe washout (XeW) was -0.4 +/- 0.08 (SE) min-1 at functional residual capacity (FRC) with no blood flow in the injected region. It decreased by more than half at lung volumes 500 ml above and 392 ml below FRC. With intact pulmonary blood flow, XeW was -1.0 +/- 0.08 (SE) min-1 at FRC, and it increased with decreasing lung volume. However, if calculated Xe uptake by the blood was subtracted from the XeW measured with blood flow intact, resulting values at FRC and at FRC + 500 ml were not different from XeW with no blood flow. Reasonable calculation of Xe blood uptake at 392 ml below FRC was not possible because airway closure, increased shunt, and other factors affect XeW. After death, no significant XeW could be measured, which suggests that XeW caused by molecular diffusion was small. We conclude that 1) the effect of heart motion on the lung parenchyma increases acinar gas mixing during apnea, 2) this effect diminishes above or below FRC, and 3) there is probably no direct effect of pulmonary vascular pulsatility on acinar gas mixing.
Chest wall motion of infants during spinal anesthesia
Authors: Pascucci R. C. , Hershenson M. B. , Sethna N. F. , Loring S. H. , Stark A. R.
Published: December 2017

To test the extent to which diaphragmatic contraction moves the rib cage in awake supine infants during quiet breathing, we studied chest wall motion in seven prematurely born infants before and during spinal anesthesia for inguinal hernia repair. Infants were studied at or around term (postconceptional age 43 +/- 8 wk). Spinal anesthesia produced a sensory block at the T2-T4 level, with concomitant motor block at a slightly lower level. This resulted in the loss of most intercostal muscle activity, whereas diaphragmatic function was preserved. Rib cage and abdominal displacements were measured with respiratory inductance plethysmography before and during spinal anesthesia. During the anesthetic, outward inspiratory rib cage motion decreased in six infants (P less than 0.02, paired t test); four of these developed paradoxical inward movement of the rib cage during inspiration. One infant, the most immature in the group, had inward movement of the rib cage both before and during the anesthetic. Abdominal displacements increased during spinal anesthesia in six of seven infants (P less than 0.05), suggesting an increase in diaphragmatic motion. We conclude that, in the group of infants studied, outward rib cage movement during awake tidal breathing requires active, coordinated intercostal muscle activity that is suppressed by spinal anesthesia.
Sensation of dyspnea during hypercapnia, exercise, and voluntary hyperventilation
Authors: Chonan T. , Mulholland M. B. , Leitner J. , Altose M. D. , Cherniack N. S.
Published: December 2017

To determine whether the intensity of dyspnea at a given level of respiratory motor output depends on the nature of the stimulus to ventilation, we compared the sensation of difficulty in breathing during progressive hypercapnia (HC) induced by rebreathing, during incremental exercise (E) on a cycle ergometer, and during isocapnic voluntary hyperventilation (IVH) in 16 normal subjects. The sensation of difficulty in breathing was rated at 30-s intervals by use of a visual analog scale. There were no differences in the level of ventilation or the base-line intensity of dyspnea before any of the interventions. The intensity of dyspnea grew linearly with increases in ventilation during HC [r = 0.98 +/- 0.02 (SD)], E (0.95 +/- 0.03), and IVH (0.95 +/- 0.06). The change in intensity of dyspnea produced by a given change in ventilation was significantly greater during HC [0.27 +/- 0.04 (SE)] than during E (0.12 +/- 0.02, P less than 0.01) and during HC (0.30 +/- 0.04) than during IVH (0.16 +/- 0.03, P less than 0.01). The difference in intensity of dyspnea between HC and E or HC and IVH increased as the difference in end-tidal PCO2 widened, even though the time course of the increase in ventilation was similar. No significant differences were measured in the intensity of dyspnea that occurred with changes in ventilation between E and IVH. These results indicate that under nearisocapnic conditions the sensation of dyspnea produced by a given level of ventilation seems not to depend on the method used to produce that level of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs
Authors: Lee B. P. , Green J. , Chiang S. T.
Published: December 2017

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)
Diaphragmatic perfusion heterogeneity during exercise with inspiratory resistive breathing
Authors: Manohar M.
Published: December 2017

Regional distribution of diaphragmatic blood flow (Q; 15-microns-diam radionuclide-labeled microspheres) was studied in normal (n = 7) and laryngeal hemiplegic (LH; n = 7) ponies to determine whether the added stress of inspiratory resistive breathing during maximal exercise may cause 1) redistribution of diaphragmatic Q and 2) crural diaphragmatic Q to exceed that in maximally exercising normal ponies. LH-induced augmentation of already high exertional work of breathing resulted in diminished locomotor exercise capacity so that maximal exercise in LH ponies occurred at 25 km/h compared with 32 km/h for normal ponies. The costal and crural regions received similar Q in both groups at rest. However, exercise-induced increments in perfusion were significantly greater in the costal region of the diaphragm. At 25 km/h, costal diaphragmatic perfusion was 154 and 143% of the crural diaphragmatic Q in normal and LH ponies. At 32 km/h, Q in costal diaphragm of normal ponies was 136% of that in the crural region. Costal and crural diaphragmatic Q in LH ponies exercised at 25 km/h exceeded that for normal ponies but was similar to the latter during exercise at 32 km/h. Perfusion pressure for the three conditions was also similar. It is concluded that diaphragmatic perfusion heterogeneity in exercising ponies was preserved during the added stress of inspiratory resistive breathing. It was also demonstrated that vascular resistance in the crural and costal regions of the diaphragm in maximally exercised LH ponies remained similar to that in maximally exercising normal ponies.