Regulation of Coronary Blood Flow by the Carotid Body Chemoreceptors in Ovine Heart Failure

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.

Cardiac Vagal Nerve Activity Increases During Exercise to Enhance Coronary Blood Flow

“…We have previously shown that atropine alone does not alter CoBF in sheep where HR has been fixed with cardiac pacing. 19 During administration of atropine during exercise, no statistically significant difference was observed in any hemodynamic parameters compared to controls measured during exercise (Figure 4D through 4I).…”

“…11,14,22 In exercise physiology, much of the study on vagal control of the heart has focused on the regulation of HR alone. 19,23,24 Historically, it has been thought that since HR increases, vagal tone must be withdrawn. 25,26 While this is a simplified assessment, the technical nature of studying cardiac vagal control in humans and conscious animal models, alongside the repeated conflation that cholinergic blockade equals vagal blockade, 4,6,26,27 means that, to date, most measures of vagal tone have been indirect.…”

“…A0257), was administered intravenously as a 5-mL bolus followed by a 30 mL/hour constant infusion throughout the exercise protocol and recovery. 19 VIP receptor antagonist [D-p-Cl-Phe, 5 Leu 16] -VIP (Tocris Bioscience, United Kingdom, catalog no. 3054) was administered intravenously as a bolus of 20 µg 10 minutes before exercise, and 5 µg bolus immediately before exercise (≈0.4 µg/kg for a 60 kg sheep; Please see the Major Resources Table in the Supplemental Material).…”

“…A0257), was administered intravenously as a 5-mL bolus followed by a 30 mL/hour constant infusion throughout the exercise protocol and recovery. 19…”

“…In the conscious condition, at rest, potassium cyanide (KCN; 30 µg/kg) was administrated intra-arterially, just below the carotid bifurcation, to selectively target the carotid body as previously described. 19 Exercise Test…”