Introduction. Chronic hypoxia (CH) is a key feature of chronic obstructive pulmonary disease (COPD), an illness associated with increased cardiac arrhythmia risk. CH induces hyperactivity of the carotid bodies which, via increased carotid sinus nerve input to the brainstem, leads to a chronic rise in breathing and heightened sympathetic nerve activity. Whilst it is known that carotid body hyperactivity in COPD patients contributes to vascular dysfunction, a potential role in mediating cardiac electrical remodelling remains uncertain.

Aims and Objectives. The current study assessed ECG parameters in normoxic (N) and chronically hypoxic (CH) animals, before and after acute bilateral carotid sinus nerve section (CSNX).

Method. Recordings of ECG, mean arterial blood pressure (mABP) and respiratory frequency (R_f) were made from adult male Wistar rats (150-350g) following exposure to either 10 days of ambient air (N, n=12 animals) or CH (F_iO₂=12%, n=13 animals), under alfaxalone anaesthesia (7–12 mg kg⁻¹h⁻¹, i.v.), before and after acute CSNX. For N, baseline measurements were made at F_iO₂=21%, for CH F_iO₂=12%. A subset of CH animals were treated with relative hyperoxia (F_iO₂=21%, n=6) after CSNX. Following experiments, animals were killed by overdose of alfaxalone anaesthesia, death confirmed by cervical dislocation. Data presented as mean±SD. Significance taken as p<0.05; paired t-test or one-sided Fisher’s exact test.

Results. At baseline, CH animals displayed an increase in R_f, a lower mABP, QTc prolongation and shorter QRS duration compared to N. Acute CSNX in N reduced mABP (N: 120±13 vs N+CSNX: 98±17 mmHg, p=0.004, n=12) and R_f (N: 98±12 vs N+CSNX: 82±17 bpm, p=0.0006, n=12), but ECG parameters were unaltered. In CH, CSNX decreased mABP (CH: 95±19 vs CH+CSNX: 78±21 mmHg, p=0.04, n=13) and R_f (CH: 113±12 vs CH+CSNX: 76±13 bpm, p<0.0001, n=13). CSNX also exacerbated QTc lengthening (CH: 68±6 vs CH+CSNX: 76±5 ms, p=0.004, n=13) and increased the occurrence of T-wave inversion (CH: 0/13 vs CH CSNX: 8/13, p=0.0008). 2/8 animals with T-wave inversion exhibited premature ventricular contractions. R-wave amplitude was also depressed by CSNX (CH: 0.36±0.17 vs CH+CSNX: 0.27±0.15 mV, p=0.008, n=13). In a subset of CH animals, treatment with hyperoxia reversed T-wave inversion caused by CSNX (CH+CSNX: 4/6 vs CH+CSNX+hyperoxia: 0/6, p=0.03) and restored the R-wave amplitude (CH+CSNX: 0.23±0.12 vs CH+CSNX+hyperoxia: 0.35±0.11 mV, p=0.01, n=6). However, hyperoxia did not attenuate the exaggerated QTc prolongation (CH+CSNX: 76±6 vs CH+CSNX+hyperoxia: 76±5 ms, p=0.8, n=6).

Conclusions. Complete removal of carotid body sensory input predisposes to pro-arrhythmia ventricular electrical modifications in CH animals. Some of these alterations, including T-wave inversion and R-wave amplitude depression, are likely driven by exaggerated hypoxia following dramatic decreases in R_f. Other modifications such as QTc prolongation which appear O₂ insensitive maybe due to changes cardiac autonomic nerve activity. Thus, the carotid body appears to have a heightened protective role in stabilising cardiac electrical activity in CH animals. Potential surgical removal of carotid bodies to improve vascular function in patients with COPD should be viewed with caution.