Ventilation and metabolism among rat strains

Strohl, Kingman P.; Thomas, Alicia; Jean, Pamela St.; Schlenker, Evelyn H.; Koletsky, Richard J.; Schork, Nicholas J.

doi:10.1152/jappl.1997.82.1.317

Cited by 130 publications

(112 citation statements)

References 19 publications

(28 reference statements)

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“…Volumes ranging between 5 and 10 ml are frequently used for BAL in rats (26)(27)(28). However, these volumes are high compared to the tidal volume, which is close to 1 ml for a rat weighing 300 g (29). Therefore, in the present study the volume was limited to 1 ml in order to preserve the integrity of the pulmonary barrier as much as possible.…”

Section: Discussionmentioning

confidence: 99%

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Gontijo

Brillault

Grégoire

et al. 2014

Antimicrob Agents Chemother

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The aim of this study was to evaluate the biopharmaceutical characteristics of three fluoroquinolones (FQs), ciprofloxacin (CIP), moxifloxacin (MXF), and grepafloxacin (GRX), after delivery via a nebulized aerosol to rats. Bronchoalveolar lavages (BAL) were conducted 0.5, 2, 4, and 6 h after FQ intravenous administration and nebulized aerosol delivery to estimate epithelial lining fluid (ELF) drug concentrations. Plasma drug concentrations were also measured, and profiles of drug concentrations versus time after intravenous administration and nebulized aerosol delivery were virtually superimposable, attesting for rapid and complete systemic absorption of FQs. ELF drug concentrations were systematically higher than corresponding plasma drug concentrations, whatever the route of administration, and average ELF-to-unbound plasma drug concentration ratios post-distribution equilibrium did not change significantly between the ways of administration and were equal: 4.0 ؎ 5.3 for CIP, 12.6 ؎ 7.3 for MXF, and 19.1 ؎ 10.5 for GRX (means ؎ standard deviations). The impact of macrophage lysis on estimated ELF drug concentrations was significant for GRX but reduced for MXF and CIP; therefore, simultaneous pharmacokinetic modeling of plasma and ELF drug concentrations was only performed for the latter two drugs. The model was characterized by a fixed volume of ELF (V ELF ), passive diffusion clearance (Q ELF ), and active efflux clearance (CL out ) between plasma and ELF, indicating active efflux transport systems. In conclusion, this study demonstrates that ELF drug concentrations of these three FQs are several times higher than plasma drug concentrations, probably due to the presence of efflux transporters at the pulmonary barrier level, but no biopharmaceutical advantage of FQ nebulization was observed compared with intravenous administration.

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Section: Discussionmentioning

confidence: 99%

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Gontijo

Brillault

Grégoire

et al. 2014

Antimicrob Agents Chemother

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“…Other than the work by Strohl and collaborators (31), few studies allow direct comparisons of the hypercapnic ventilatory response between male and female rats. These authors reported no sex-related differences in ventilatory activity, but the fact that their experiments were performed under hyperoxic conditions (inspired O 2 fraction ϭ 0.93) makes it difficult to determine whether these results truly contrast with ours.…”

Section: Nms and Sex-specific Plasticity Of The Hypercapnic Ventilatomentioning

confidence: 99%

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Genest

Gulemetova²,

Laforest³

et al. 2007

Journal of Applied Physiology

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Genest S-E, Gulemetova R, Laforest S, Drolet G, Kinkead R. Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat. J Appl Physiol 102: 1416 -1421, 2007. First published December 21, 2006; doi:10.1152/japplphysiol.00454.2006.-Neonatal maternal separation (NMS) is a form of stress that exerts persistent, sex-specific effects on the hypoxic ventilatory response. Adult male rats previously subjected to NMS show a 25% increase in the response, whereas NMS females show a response 30% lower than controls (8). To assess the extent to which NMS affects ventilatory control development, we tested the hypothesis that NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats. Pups subjected to NMS were placed in a temperature-and humidity-controlled incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography chamber for measurement of ventilatory parameters under baseline and hypercapnic conditions (inspired CO2 fraction ϭ 0.05). After 20 min of hypercapnia, the minute ventilation response measured in NMS males was 47% less than controls, owing to a lower tidal volume response (22%). Conversely, females previously subjected to NMS showed minute ventilation and tidal volume responses 63 and 18% larger than controls respectively. Although a lower baseline minute ventilation contributes to this effect, the higher minute ventilation/ CO2 production response observed in NMS females suggests a greater responsiveness to CO2/H ϩ in this group. We conclude that NMS exerts sex-specific effects on the hypercapnic ventilatory response and that the neural mechanisms affected by NMS likely differ from those involved in the hypoxic chemoreflex.control of breathing; plasticity; hypercapnia; sexual dimorphism THE NEONATAL ENVIRONMENT is critical to proper development of neurophysiological function. The formation and fine tuning of neural circuits during early life require adequate sensory guidance, and conditions providing excessive or insufficient levels of stimulation can disrupt system development and compromise their subsequent performance throughout life. The olfactory, tactile, and auditory stimuli that the mother provides her offspring following birth are among the most potent environmental factors contributing to the "neonatal programming" of neural circuits (12,22). Although the life-long consequences of disrupting motherpup interactions have been mainly associated with behavioral and neuroendocrine dysfunction (1, 2, 20), less is known about the impact of mother-pup interaction on other homeostatic functions such as cardiorespiratory regulation. Accordingly, we showed that neonatal maternal separation (NMS) disrupts cardiorespiratory responses to moderate hypoxia in a persistent and sex-specific fashion (8,16). In addition to eliciting the well described enhancement of basal hypothalamo-pituitary-adrenal axis function in rats (34; for review see Ref. 5), we...

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“…Weight normalized values for basal ventilation on room air were similar to prior published values for the same rat strain (Strohl et al, 1997;Mouradian et al, 2012). Also as described before, the hypoxic ventilatory reflex of intact rats consisted of a selective increase in breathing frequency (Hodges et al, 2002).…”

Section: Recovery Of Normal Ventilation and Blood Gases A Week After supporting

confidence: 83%

Neural Control of Respiration by the Retrotrapezoid Nucleus.

Basting¹

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Rationale and objectives: Central respiratory chemoreceptors (CRCs) detect brain PaCO 2 and adjust lung ventilation to maintain PaCO 2 and pH constant regardless of the absolute level of lung ventilation. They perform this function in cooperation with the carotid bodies, sensory organs that respond to hypoxia in a pH-dependent manner. The existence of CRCs has been known for over a century but their cellular nature and location have remained highly controversial until recently. The retrotrapezoid nucleus (RTN), a collection of ~2000 glutamatergic neurons in rats that are activated by hypercapnia in vivo and by acidification in slices, had been identified as a CRC candidate just prior to my PhD work. My first objective was to seek additional and critical evidence that RTN neurons are CRCs by determining whether these neurons stimulate breathing in proportion to arterial PCO 2 in intact unanesthetized rats.Having verified that this was the case I tested a logical corollary of this theory namely that RTN is silenced under hypoxic conditions due to respiratory alkalosis. Then I proceeded to test whether RTN neurons sustain breathing automaticity during sleep. Finally, I tested whether RTN compensates for the lack peripheral chemoreceptor input.Methods: RTN neurons were bilaterally transduced to express the proton pump archaerhodopsin using a lentiviral vector. Using anesthetized rats, I confirmed that RTN neurons were silenced by activating archaerhodopsin with green light. I examined the effect of short periods of RTN inhibition (10s) on breathing (plethysmography), EEG and neck EMG in conscious rats in which arterial pH was changed by exposing the animals to various FiO 2 levels alone or with the addition of 3% FiCO 2 or acetazolamide (ACTZ). Rats were studied in different states of vigilance (quiet awake/non-REM/REM). Arterial blood gases (PaO 2 , PaCO 2 ), pHa and HCO 3 were measured under each condition.ii Results: RTN inhibition (bilateral) reduced breathing frequency and amplitude in direct proportion to arterial plasma pH (pHa) below a threshold of 7.53. Above this level, RTN inhibition had no effect suggesting that the nucleus was silent. In normoxia, RTN inhibition reduced breathing equally during non-REM sleep and quiet wake. By contrast RTN inhibition had very little effect on breathing during REM sleep.Conclusions: RTN drives breathing in direct proportion to arterial PCO 2 in intact unaesthetized rats, consistent with the theory that these neurons are CRCs. RTN neurons are silent above pHa 7.5 and increasingly active below this value. RTN regulates breathing automaticity about equally during non-REM sleep and quiet waking, conditions under which the respiratory pattern generator is autorhythmic. By contrast, RTN has a much reduced influence on breathing during Viar for surgery skills, science advice, life advice, wanted/unwanted music advice and so much more. Together, they made a dynamic group of personalities that provided a stimulating and encouraging atmosphere that will never be forgotten....

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Ventilation and metabolism among rat strains

Cited by 130 publications

References 19 publications

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Biopharmaceutical Characterization of Nebulized Antimicrobial Agents in Rats: 1. Ciprofloxacin, Moxifloxacin, and Grepafloxacin

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Neural Control of Respiration by the Retrotrapezoid Nucleus.

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