Colchicine Anti-Inflammatory Treatment Restores Normal Carotid Body Function and Improve Cardiac Function in HFpEF

Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a chronic low-grade inflammatory condition. Heightened carotid body (CB) chemoreflex sensitivity, a key feature of HF pathophysiology, exacerbates ventilatory instability, sympathetic drive, cardiac dysfunction and overall prognosis. Although inflammatory mediators are known to potentiate CB activity, it remains unclear whether anti-inflammatory therapy can mitigate the maladaptive chemosensory drive in HF. Since colchicine has emerged as a promising anti-inflammatory therapeutic strategy on HFpEF, we hypothesized that systemic colchicine administration would attenuate CB dysfunction and improve cardiorespiratory outcomes in a murine model of HFpEF. Male adult C57BL6 (P90) mice were randomly allocated into three groups: Control (n=6), HFpEF (n=10), and HFpEF+Colchicine (n=6; 200 µg/kg/day delivered i.p. via osmotic pump for 14 days). HFpEF was induced over 16-weeks following nitric oxide synthase inhibition with L-NAME in combination with a high-fat diet. PW Doppler echocardiography mode, photoplethysmography, whole body plethysmography and carotid sinus nerve (CSN) recordings were used to evaluate cardiac diastolic function (E/A ratio), arterial blood pressure, hypoxic ventilatory response (HVR), disordered breathing and CSN activity, respectively. Relative to Control, HFpEF mice exhibited significant (p< 0.05) increase in the E/A ratio (1.17 ± 0.05 vs. 1.45 ± 0.25, Control vs. HFpEF respectively), mean arterial blood pressure (83.19 ± 1.38 vs. 107.70 ± 1.42 mmHg, Control vs. HFpEF respectively), heightened CB-mediated chemoreflex gain (0.66 ± 0.45 vs. 1.83 ± 0.14 ΔVE/FIO 2 %, Control vs. HFpEF respectively) and a high incidence of apneas-hypopneas (6.07 ± 1.18 vs. 14.09 ± 2.67 events/hour, Control vs. HFpEF respectively). Accordingly, we also found that CB chemosensory activity was exacerbated in HFpEF compared to Control (94.98 ± 11.91 vs. 164.00 ± 14.16 Hz, Control vs. HFpEF respectively). Notably, we found that colchicine administration for 2 weeks to HFpEF mice was sufficient to completely restore normal CB chemosensory activity, chemoreflex drive and breathing disorders in HFpEF. Moreover, colchicine treatment in HFpEF significantly improves cardiac diastolic function as evidenced by a 1.2-fold reduction in the E/A ratio. Together, our findings strongly support the use of colchicine to restore normal CB function in HFpEF. Also, our results suggest that colchicine treatment may offer salutary benefit for the management of the HFpEF. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.