title: Tonic arterial chemoreceptor activity contributes to cardiac sympathetic activation in mild ovine heart failure.
abstract: Heart failure (HF) is associated with a large increase in cardiac sympathetic nerve activity (CSNA), which has detrimental effects on the heart and promotes arrhythmias and sudden death. There is increasing evidence that arterial chemoreceptor activation plays an important role in stimulating renal sympathetic nerve activity (RSNA) and muscle sympathetic nerve activity in HF. Given that sympathetic nerve activity to individual organs is differentially controlled, we investigated whether tonic arterial chemoreceptor activation contributes to the increased CSNA in HF. We recorded CSNA and RSNA in conscious normal sheep and in sheep with mild HF induced by rapid ventricular pacing (ejection fraction <40%). Tonic arterial chemoreceptor function was evaluated by supplementing room air with 100% intranasal oxygen (2-3 l min(-1)) for 20 min, thereby deactivating chemoreceptors. The effects of hyperoxia on resting levels and baroreflex control of heart rate, CSNA and RSNA were determined. In HF, chemoreceptor deactivation induced by hyperoxia significantly reduced CSNA [90 ± 2 versus 75 ± 5 bursts (100 heart beats)(-1), P < 0.05, n = 10; room air versus hyperoxia] and heart rate (96 ± 4 versus 85 ± 4 beats min(-1), P < 0.001, n = 12). There was no change in RSNA burst incidence [93 ± 4 versus 92 ± 4 bursts (100 heart beats)(-1), n = 7], although due to the bradycardia the RSNA burst frequency was decreased (90 ± 8 versus 77 ± 7 bursts min(-1), P < 0.001). In normal sheep, chemoreceptor deactivation reduced heart rate without a significant effect on CSNA or RSNA. In summary, deactivation of peripheral chemoreceptors during HF reduced the elevated levels of CSNA, indicating that tonic arterial chemoreceptor activation plays a critical role in stimulating the elevated CSNA in HF.
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Xing
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Clive N
authors.initials: CN
authors.lastname: May
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Lindsea C
authors.initials: LC
authors.lastname: Booth
authors.affiliation: The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia r.ramchandra@auckland.ac.nz.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramchandra
mesh_terms: D000818:Animals; D001158:Arteries / Q000502:physiology; D017704:Baroreflex / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology*; D006321:Heart; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D018496:Hyperoxia / Q000503:physiopathology; D012756:Sheep; D013564:Sympathetic Nervous System / Q000502:physiology*