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Response time and sensitivity of the ventilatory response to CO₂ in unanesthetized intact dogs: central vs. peripheral chemoreceptors

John Rankin Laboratory of Pulmonary Medicine, Department of Population Health Sciences, School of Medicine, University of Wisconsin, Madison, Wisconsin

Submitted 29 July 2005 ; accepted in final form 7 September 2005

We assessed the speed of the ventilatory response to square-wave changes in alveolar PCO₂ and the relative gains of the steady-state ventilatory response to CO₂ of the central chemoreceptors vs. the carotid body chemoreceptors in intact, unanesthetized dogs. We used extracorporeal perfusion of the reversibly isolated carotid sinus to maintain normal tonic activity of the carotid body chemoreceptor while preventing it from sensing systemic changes in CO₂, thereby allowing us to determine the response of the central chemoreceptors alone. We found the following. 1) The ventilatory response of the central chemoreceptors alone is 11.2 (SD = 3.6) s slower than when carotid bodies are allowed to sense CO₂ changes. 2) On average, the central chemoreceptors contribute 63% of the gain to steady-state increases in CO₂. There was wide dog-to-dog variability in the relative contributions of central vs. carotid body chemoreceptors; the central exceeded the carotid body gain in four of six dogs, but in two dogs carotid body gain exceeded central CO₂ gain. If humans respond similarly to dogs, we propose that the slower response of the central chemoreceptors vs. the carotid chemoreceptors prevents the central chemoreceptors from contributing significantly to ventilatory responses to rapid, transient changes in arterial PCO₂ such as those after periods of hypoventilation or hyperventilation ("ventilatory undershoots or overshoots") observed during sleep-disordered breathing. However, the greater average responsiveness of the central chemoreceptors to brain hypercapnia in the steady-state suggests that these receptors may contribute significantly to ventilatory overshoots once unstable/periodic breathing is fully established.

carotid body; chemosensitivity; control of breathing; sleep apnea

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