Abstract

When stimulated, carotid bodies (CBs) activate sympathetic activity causing hypertension. In hypertensive animals, CBs generate aberrant tone and their resection lowered blood pressure (McBryde et al. 2013. Nat.Communs 4, 2395). In this first prospective proof of concept study our primary outcome was safety and feasibility of unilateral (u) CB resection in drug resistant hypertensive patients; as a secondary outcome we measured blood pressure over a 12 month period. 15 participants with office blood pressure (OBP) 179±7/106±4 mmHg on 5.7±0.3 anti‐hypertensive drugs were studied at 1, 3, 6 and 12 months after removing either the right (n=11) or left (n=4) CB; the latter was confirmed histologically. Hypoxic ventilatory response, adverse events, office blood pressure (OBP), ambulatory BP, muscle sympathetic nerve activity (MSNA) and baroreflex sensitivity (BRS) were measured. The procedure was feasible as glomus cells were confirmed histologically in resected tissue from 14/15 patients. The intervention was safe as no serious adverse events or serious sleep apnoeas developed following the resection, and the hypoxic ventilatory drive was maintained. Overall, no change in either OBP or ambulatory BP was found. However, in 8/14 participants, day ambulatory BP was reduced at 3 and 6 months (−23±3, −26±4 mmHg, respectively; P<0.01) post resection and correlated temporally with reductions in MSNA (P<0.05), improved BRS (P<0.05); whole drug (anti‐hypertensive) equivalents were also reduced (P<0.01). Respiratory frequency and the ventilatory response to hypoxia were higher in responders (P<0.05) compared to the non‐responders indicative of heightened carotid body drive in these patients. In conclusion, uCB resection was feasible and safe. In a subset of patients (57%), resection lowered ambulatory BP (an effect that persisted for at least 6 months). Mechanistically, the fall in ABPM was associated with reduced MSNA and improvement in BRS. These data support the presence of aberrant carotid body drive in hypertensive patients, which can be interrupted to treat drug resistant hypertension. Cibiem funded the trial.Support or Funding InformationCibiem funded the trial.

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