Abstract
Carotid bodies (CBs) are peripheral chemoreceptors, which are primary sensors of systemic hypoxia and their activation produces respiratory, autonomic, and cardiovascular adjustments critical for body homeostasis. We have previously shown that carotid chemoreceptor stimulation increases directly recorded cardiac sympathetic nerve activity (cardiac SNA) which increases coronary blood flow (CoBF) in conscious normal sheep. Previous studies have shown that chemoreflex sensitivity is augmented in heart failure (HF). We hypothesized that carotid chemoreceptor stimulation would increase CoBF to a greater extent in HF than control sheep. Experiments were conducted in conscious HF sheep and control sheep (n = 6/group) implanted with electrodes to record diaphragmatic electromyography (dEMG), flow probes to record CoBF as well as arterial pressure. There was a significant increase in mean arterial pressure (MAP), CoBF and coronary vascular conductance (CVC) in response to potassium cyanide (KCN) in both groups of sheep. To eliminate the effects of metabolic vasodilation, the KCN was repeated while the heart was paced at a constant level. In this paradigm, the increase in CoBF and CVC was augmented in the HF group compared to the control group. Pre-treatment with propranolol did not alter the CoBF or the CVC increase in the HF group indicating this was not mediated by an increase in cardiac sympathetic drive. The pressor response to CB activation was abolished by pre-treatment with intravenous atropine in both groups, but there was no change in the CoBF and vascular conductance responses. Our data suggest that in an ovine model of HF, carotid body (CB) mediated increases in CoBF and CVC are augmented compared to control animals. This increase in CoBF is mediated by an increase in cardiac SNA in the control group but not the HF group.
Highlights
Heart failure (HF) is a severe, debilitating condition with poor survival rates and increasing prevalence (Swedberg et al, 2005)
The main findings from this study are: (1) Activation of the carotid bodies increases coronary blood flow (CoBF) and coronary vascular conductance (CVC) in both normal and HF sheep. The increase in both CoBF and CVC is significantly enhanced in the HF group compared to the control group
(2) Inhibition of muscarinic mechanisms using atropine abolished the mean arterial pressure (MAP) response to Carotid bodies (CBs) activation in heart failure similar to that reported in control animals previously
Summary
Heart failure (HF) is a severe, debilitating condition with poor survival rates and increasing prevalence (Swedberg et al, 2005). Carotid Body Reflex in HF provides inotropic support and maintains cardiac output (Watson et al, 2006) but over the long-term promotes disease progression and shortens life expectancy (Kaye et al, 1995) Both the disordered breathing and the autonomic dysfunction are strongly related to a higher mortality risk and poorer prognosis in patients (Cohn et al, 1984; Floras, 1993; Naughton et al, 1993; Leung et al, 2004). Studies have shown that the sensitivity of the chemoreflex is elevated in patients with HF (Chua et al, 1997; Schultz and Li, 2007) and animal models of HF (Sun et al, 1999; Del Rio et al, 2013) Interrupting the chemoreflex both acutely using intranasal oxygen (Xing et al, 2014) and chronically using denervation of the CB (Marcus et al, 2014) has been shown to reduce sympathetic nerve activity to the heart and the kidney
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