Autonomic Control of Coronary Blood Flow in Control and Heart Failure Ovine Models

Abstract

Carotid bodies (CBs) are the main peripheral chemoreceptors that are strategically located at the bifurcation of the common carotid artery. They are the primary sensors of systemic hypoxia, and their stimulation elicits powerful reflex responses such as respiratory, autonomic, and cardiovascular adjustments critical for body homeostasis. Recent studies suggest that CB chemosensitivity is higher in patients with heart failure (HF) and animal models of HF. Activation of the CB is presumed to activate both the sympathetic and parasympathetic nerves to the heart but this has not been directly determined. In addition, the role of the CB in modulating coronary blood flow (CoBF) is unclear. I hypothesized that activation of the CB would increase directly recorded cardiac SNA, which would then lead to coronary vasodilation. I tested this in the conscious control animals. I also hypothesized that inactivation of the CB via hyperoxia would cause a reduction in CoBF in both control and HF groups. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA and diaphragmatic electromyography (dEMG), flow probes to record CoBF and cardiac output (CO) and a catheter to record mean arterial pressure (MAP). To eliminate the contribution of metabolic demand on coronary flow, the heart was paced at a constant rate during CB chemoreflex stimulation. Intra-carotid potassium cyanide (KCN) injection resulted in a significant increase in directly recorded cardiac SNA as well as a dose-dependent increase in MAP and CoBF. The increase in CoBF was augmented in the HF group when the influence of metabolic vasodilation was abolished. The increase in CoBF and coronary vascular conductance (CVC) to intracarotid KCN injection was abolished after propranolol infusion in the control group but not the HF group. The pressor response to activation of the CB was abolished by pre-treatment with intravenous atropine in both groups. My data suggests that CB-mediated increases in CoBF are mediated by an increase in cardiac SNA in the control group but not the HF group. Inactivation of the CBs using hyperoxia caused a significant decrease in MAP and CoBF in the HF group. To further examine the influence of pulmonary afferents, I used a novel airflow therapy, high nasal flow (HNF) and investigated the MAP, renal blood flow (RBF), and renal vascular conductance (RVC) responses to HNF in conscious normotensive and hypertensive sheep. HNF caused a significant decrease in blood pressure and increase in RVC in both groups. Taken together my studies suggest that CBs play an essential role in modulating blood flow to the heart and that HNF can be beneficial in conditions where the CB is hyperactive without causing impairment of blood flow to vital organs.