Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs

1991 ◽  
Vol 70 (2) ◽  
pp. 504-510 ◽  
Author(s):  
D. W. Ray ◽  
A. Garland ◽  
C. Hernandez ◽  
S. Eappen ◽  
L. Alger ◽  
...  
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Time Course ◽  
Random Order ◽  
Quiet Breathing ◽  
Mechanically Ventilated ◽  
Abrupt Changes ◽  
Respiratory System Resistance ◽  
Humidified Air ◽  
Isocapnic Hyperpnea

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

Tachykinins mediate bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

1989 ◽  
Vol 66 (3) ◽  
pp. 1108-1112 ◽  
Author(s):  
D. W. Ray ◽  
C. Hernandez ◽  
A. R. Leff ◽  
J. M. Drazen ◽  
J. Solway
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Minute Ventilation ◽  
Response Curves ◽  
Mechanically Ventilated ◽  
Stimulus Response ◽  
Respiratory System Resistance ◽  
Water Saturated ◽  
And Control ◽  
Isocapnic Hyperpnea

We tested the hypothesis that tachykinins mediate hyperpnea-induced bronchoconstriction (HIB) in 28 guinea pigs. Stimulus-response curves to increasing minute ventilation with dry gas were generated in animals depleted of tachykinins by capsaicin pretreatment and in animals pretreated with phosphoramidon, a neutral metalloendopeptidase inhibitor. Sixteen anesthetized guinea pigs received capsaicin (50 mg/kg sc) after aminophylline (10 mg/kg ip) and terbutaline (0.1 mg/kg sc). An additional 12 animals received saline (1 ml sc) instead of capsaicin. One week later, all animals were anesthetized, given propranolol (1 mg/kg iv), and mechanically ventilated (6 ml/kg, 60 breaths/min, 50% O2 in air fully water saturated). Phosphoramidon (0.5 mg iv) was administered to five of the noncapsaicin-treated guinea pigs. Eucapnic dry gas (95% O2–5% CO2) hyperpnea “challenges” were performed by increasing the tidal volume (2–6 ml) and frequency (150 breaths/min) for 5 min. Capsaicin-pretreated animals showed marked attenuation in HIB, with a rightward shift of the stimulus-response curve compared with controls; the estimated tidal volume required to elicit a twofold increase in respiratory system resistance (ES200) was 5.0 ml for capsaicin-pretreated animals vs. 3.7 ml for controls (P less than 0.03). Phosphoramidon-treated animals were more reactive to dry gas hyperpnea compared with control (ES200 = 2.6 ml; P less than 0.0001). Methacholine dose-response curves (10(-11) to 10(-7) mol iv) obtained at the conclusion of the experiments were similar among capsaicin, phosphoramidon, and control groups. These findings implicate tachykinin release as an important mechanism of HIB in guinea pigs.

Role of eicosanoids in hyperpnea-induced airway responses in guinea pigs

1993 ◽  
Vol 75 (6) ◽  
pp. 2797-2804 ◽  
Author(s):  
A. Garland ◽  
J. E. Jordan ◽  
D. W. Ray ◽  
S. M. Spaethe ◽  
L. Alger ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Quiet Breathing ◽  
Leukotriene D4 ◽  
Mechanically Ventilated ◽  
Respiratory System Resistance ◽  
D4 Receptor ◽  
Airway Responses ◽  
Previous Demonstration

Guinea pigs mechanically hyperventilated with dry gas exhibit hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH). Tachykinins released from airway C-fiber neurons are the central mediators of guinea pig HIB but play only a contributory role in HIBVH. Recent studies suggest that eicosanoid mediators can provoke bronchoconstriction and bronchovascular hyperpermeability, are released by dry gas hyperpnea, and can themselves elicit or modulate tachykinin release. We therefore hypothesized that eicosanoids may participate in HIB and/or HIBVH. To test these hypotheses, we analyzed respiratory system resistance changes and Evans blue-labeled albumin extravasation into the airways of 60 tracheostomized and mechanically ventilated guinea pigs. Animals were subjected to 10 min of isocapnic dry gas hyperpnea or to quiet breathing of humidified gas and received as pretreatment either piroxicam, a cyclooxygenase (CO) inhibitor; A-63162, a 5-lipoxygenase (5-LO) inhibitor; BW-755c, a combined CO and 5-LO inhibitor; ICI-198,615, a leukotriene D4 receptor antagonist; or no drug. HIB was substantially (50–80%) reduced by each of the four eicosanoid-modulating drugs. In contrast, HIBVH was reduced only by BW-755c, and this effect occurred only within the extrapulmonary airways (42% reduction). These data indicate that both CO and 5-LO products, including leukotriene D4, participate in the pathogenesis of HIB but that, like tachykinins, they play only a small contributory role in HIBVH. Together with our previous demonstration that sensory neuropeptide release is critical for the occurrence of HIB, we conclude that the roles of eicosanoids and tachykinins in guinea pig HIB are interdependent.

Bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs

1988 ◽  
Vol 65 (2) ◽  
pp. 934-939 ◽  
Author(s):  
D. W. Ray ◽  
C. Hernandez ◽  
N. Munoz ◽  
A. R. Leff ◽  
J. Solway
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Room Temperature ◽  
Time Course ◽  
Minute Ventilation ◽  
Recovery Period ◽  
Dynamic Compliance ◽  
Base Line ◽  
Stimulus Response ◽  
Airway Response

We demonstrated spontaneous self-limited bronchoconstriction after eucapnic dry gas hyperpnea in 22 anesthetized, mechanically ventilated guinea pigs pretreated with propranolol (1 mg/kg iv). Eucapnic hyperpnea "challenges" of room temperature dry or humidified gas (5% CO2-95% O2) were performed by mechanically ventilating animals (150 breaths/min, 3-6 ml tidal volume) for 5 min. During a "recovery" period after hyperpnea, animals were returned to standard ventilation conditions (6 ml/kg, 60 breaths/min, 50% O2 in air, fully saturated at room temperature). After dry gas hyperpnea (5 ml, 150 breaths/min), respiratory system resistance (Rrs) increased in the recovery period by 7.7-fold and dynamic compliance (Cdyn) decreased by 79.7%; changes were maximal at approximately 3 min posthyperpnea and spontaneously returned to base line in 10-40 min. This response was markedly attenuated by humidification of inspired air. Four consecutive identical dry air challenges resulted in similar posthyperpnea responses in four animals. Increasing the minute ventilation during hyperpnea (by varying tidal volume from 3 to 6 ml) caused increased bronchoconstriction in a dose-dependent fashion in six animals. Neither vagotomy nor atropine altered the airway response to dry gas hyperpnea. We conclude that dry gas hyperpnea in anesthetized guinea pigs results in a bronchoconstrictor response that shares five similar features with hyperpnea-induced bronchoconstriction in human asthma: 1) time course of onset and spontaneous resolution, 2) diminution with humidification of inspired gas, 3) reproducibility on consecutive identical challenges, 4) stimulus-response relationship with minute ventilation during hyperpnea, and 5) independence of parasympathetic neurotransmission.

Airway function after cyclooxygenase inhibition during hyperpnea-induced bronchoconstriction in guinea pigs

2000 ◽  
Vol 89 (5) ◽  
pp. 1971-1978 ◽  
Author(s):  
O. E. Suman ◽  
J. D. Morrow ◽  
K. A. O'Malley ◽  
K. C. Beck
Keyword(s):  
Lung Function ◽  
Guinea Pig ◽  
Protective Effect ◽  
Respiratory System ◽  
Guinea Pigs ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Mechanically Ventilated ◽  
Airway Function ◽  
Respiratory System Resistance

Airway function deteriorates significantly on cessation of exercise or isocapnic hyperventilation challenges but is largely preserved during the challenge in humans and guinea pigs. PGE2, an endogenous bronchodilator, might be responsible for the preservation of lung function during hyperventilation (HV). We hypothesized that PGE2 might have a protective effect during HV, partially explaining the minimal changes in respiratory system resistance (Rrs) usually seen during HV in humans and guinea pigs. Therefore, changes in Rrs were measured during and after HV in anesthetized, mechanically ventilated guinea pigs treated with flurbiprofen (FBN) or placebo. With HV, there was an initial bronchodilation that was unaffected by FBN. Rrs then increased with time during HV, an effect that was blocked by FBN. After HV, Rrs increased further in all groups, but the increase in Rrs was less in the FBN-treated groups. FBN treatment reduced the PGE2 concentration slightly in lung lavage fluid compared with placebo. We found no enhancement or refractoriness of the Rrs response to repeat bouts of HV and no effect of FBN treatment on the response of Rrs to repeat HV. These results suggest that a constrictor PG is released during and possibly after HV and that the post-HV increase in Rrs is the sum of effects of the PG released during HV and a second constrictor mechanism operating after HV. We found no evidence for bronchodilator PG during or after HV in the guinea pig.

Oxygen radicals in bronchoconstriction of guinea pigs elicited by isocapnic hyperpnea

1993 ◽  
Vol 74 (2) ◽  
pp. 627-633 ◽  
Author(s):  
Z. X. Fang ◽  
Y. L. Lai
Keyword(s):  
Guinea Pigs ◽  
Oxygen Radicals ◽  
Recovery Period ◽  
Venous Catheter ◽  
Dynamic Compliance ◽  
Baseline Period ◽  
Intratracheal Administration ◽  
In Series ◽  
Humidified Air ◽  
Isocapnic Hyperpnea

The role of oxygen radicals in isocapnic hyperpnea-induced bronchoconstriction (HIB) of guinea pigs was investigated using scavengers of the radicals. In series 1, 50 young guinea pigs were randomly divided into seven groups: control 1, control 2, chlorisondamine, tetrodotoxin (TTX), acute dimethylthiourea (DMTU), tachykinin depletion, and 5% CO2 in air. Animals of the control 2 group received vehicle (saline) infusion while those of the control 1 group did not. Chlorisondamine was used to block ganglionic transmission, TTX to interrupt nerve conduction, DMTU to scavenge hydroxyl radicals, and chronic capsaicin pretreatment to deplete tachykinins. The animals in the last group were ventilated with dry 5% CO2 in air during hyperpnea. In series 2, 13 additional animals were used to test the effects of intratracheal administration of superoxide dismutase and catalase (SOD + CAT) on HIB. Each animal was anesthetized with pentobarbital sodium, cannulated with a tracheal cannula and venous catheter, paralyzed with gallamine triethiodide, and mechanically ventilated. During the baseline period, each animal was ventilated normally with humidified air. Then it was hyperventilated 15 min with a dry gas mixture of 95% O2–5% CO2, except animals in the last group of series 1. Subsequently, all animals returned to normal ventilation with humidified air for 45 min (recovery period). The maximal expiratory flow and dynamic compliance were obtained periodically during the recovery period. The isocapnic hyperpnea using 95% O2–5% CO2, but not 5% CO2 in air, caused bronchoconstriction that was significantly blocked by acute DMTU, acute SOD + CAT, and tachykinin depletion. In an additional group of six animals, acute DMTU did not significantly alter acetylcholine-induced airway constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatocyte Alterations in Guinea Pigs FED Polychlorinated Biphenyls (PCBs), Dibenzodioxins (PCDD), AND DIBENZOFURANS (PCDF)

1982 ◽  
Vol 40 ◽  
pp. 56-57
Author(s):  
J. N. Turner ◽  
D. N. Collins
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Dose Group ◽  
Methyl Cellulose ◽  
Uranyl Acetate ◽  
Target Organ ◽  
Office Building ◽  
Lead Citrate ◽  
Control Groups ◽  
Cooling Fluid

A fire involving an electric service transformer and its cooling fluid, a mixture of PCBs and chlorinated benzenes, contaminated an office building with a fine soot. Chemical analysis showed PCDDs and PCDFs including the highly toxic tetra isomers. Guinea pigs were chosen as an experimental animal to test the soot's toxicity because of their sensitivity to these compounds, and the liver was examined because it is a target organ. The soot was suspended in 0.75% methyl cellulose and administered in a single dose by gavage at levels of 1,10,100, and 500mgm soot/kgm body weight. Each dose group was composed of 6 males and 6 females. Control groups included 12 (6 male, 6 female) animals fed activated carbon in methyl cellulose, 6 males fed methyl cellulose, and 16 males and 10 females untreated. The guinea pigs were sacrificed at 42 days by suffocation in CO2. Liver samples were immediately immersed and minced in 2% gluteraldehyde in cacadylate buffer at pH 7.4 and 4°C. After overnight fixation, samples were postfixed in 1% OsO4 in cacodylate for 1 hr at room temperature, embedded in epon, sectioned and stained with uranyl acetate and lead citrate.

Evolution of crystal structure of dual layered molecular conductor (ET)4ZnBr4(C6H4Cl2) with temperature

CrystEngComm ◽  
2021 ◽  
Author(s):  
Gennady V. Shilov ◽  
Elena I. Zhilyaeva ◽  
Sergey M. Aldoshin ◽  
Alexandra M Flakina ◽  
Rustem B. Lyubovskii ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Electrical Resistivity ◽  
Single Crystal ◽  
Room Temperature ◽  
Organic Conductor ◽  
X Ray Diffraction ◽  
X Ray ◽  
Resistivity Measurements ◽  
Molecular Conductor ◽  
Abrupt Changes

Electrical resistivity measurements of a dual layered organic conductor (ET)4ZnBr4(1,2-C6H4Cl2) above room temperature show abrupt changes in resistivity at 320 K. Single-crystal X-ray diffraction studies in the 100-350 K range...

Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs

1992 ◽  
Vol 73 (5) ◽  
pp. 1847-1853 ◽  
Author(s):  
S. A. Shore ◽  
M. A. Martins ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Ace Inhibitor ◽  
Dynamic Compliance ◽  
Neutral Endopeptidase ◽  
Neurokinin A ◽  
Mechanically Ventilated ◽  
Arterial Blood ◽  
Airway Responses ◽  
Nep Inhibition

We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.

scholarly journals Room-temperature macromolecular crystallography using a micro-patterned silicon chip with minimal background scattering

2016 ◽  
Vol 49 (3) ◽  
pp. 968-975 ◽  
Author(s):  
Philip Roedig ◽  
Ramona Duman ◽  
Juan Sanchez-Weatherby ◽  
Ismo Vartiainen ◽  
Anja Burkhardt ◽  
...  
Keyword(s):  
Data Collection ◽  
Room Temperature ◽  
Structural Changes ◽  
Crystalline Silicon ◽  
Background Level ◽  
Sample Holder ◽  
Macromolecular Crystallography ◽  
Recent Success ◽  
Millisecond Range ◽  
Humidified Air

Recent success at X-ray free-electron lasers has led to serial crystallography experiments staging a comeback at synchrotron sources as well. With crystal lifetimes typically in the millisecond range and the latest-generation detector technologies with high framing rates up to 1 kHz, fast sample exchange has become the bottleneck for such experiments. A micro-patterned chip has been developed from single-crystalline silicon, which acts as a sample holder for up to several thousand microcrystals at a very low background level. The crystals can be easily loaded onto the chip and excess mother liquor can be efficiently removed. Dehydration of the crystals is prevented by keeping them in a stream of humidified air during data collection. Further sealing of the sample holder, for example with Kapton, is not required. Room-temperature data collection from insulin crystals loaded onto the chip proves the applicability of the chip for macromolecular crystallography. Subsequent structure refinements reveal no radiation-damage-induced structural changes for insulin crystals up to a dose of 565.6 kGy, even though the total diffraction power of the crystals has on average decreased to 19.1% of its initial value for the same dose. A decay of the diffracting power by half is observed for a dose ofD1/2= 147.5 ± 19.1 kGy, which is about 1/300 of the dose before crystals show a similar decay at cryogenic temperatures.

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