Key points• Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications.• Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea.• In a decerebrate, vagotomized, in situ rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO 2 ) and pharmacologically (with peripheral pituitary adenylate cyclase-activating peptide).• We also show that the central apnoeic threshold, i.e. the CO 2 level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation.• These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re-affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes.Abstract Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual-perfused in situ rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas-equilibrated medium. At varying levels of carotid body stimulation (CB P O 2 /P CO 2 : 40/60, 100/40, 200/15, 500/15 Torr), we decreased the brainstem perfusate P CO 2 in 5 Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40/60), the apnoeic threshold was 3.6 ± 1.4 Torr P CO 2 (mean ± SEM, n = 7). Stimulating carotid body afferent activity with either hypercapnia (60 Torr P CO 2 ) or the neuropeptide pituitary adenylate cyclase-activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO 2 reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO 2 .

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AimsTo design, construct and validate a pharmacokinetics simulator that offers students hands‐on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens.MethodsThe Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes.ResultsThe simulator effectively models one‐ and two‐compartment drug behaviour in a mathematically‐robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve‐fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported.ConclusionsThe ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands‐on pharmacokinetics learning opportunity for students that effectively complements didactic lectures.

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