Exercise Intolerance in Volume Overload Heart Failure Is Associated With Low Carotid Body Chemosensitivity

Mounting an appropriate ventilatory response to exercise is crucial to meeting metabolic demands during exercise and abnormal ventilatory responses may contribute to exercise-intolerance (EX-inT) in HF patients. We sought to determine if abnormal ventilatory chemoreflex control contributes to EX-inT in volume-overload HF rats. Cardiac function, hypercapnic (HCVR) and hypoxic (HVR) ventilatory responses and exercise tolerance were assessed at the end of a 6 weeks exercise training program. Exercise tolerant HF rats (HF+EX-T) completed all training sessions and benefit from exercise as evidenced by improvements in cardiac systolic function and reductions in HCVR, sympathetic tone and arrhythmias. Contrarily, HF rats that failed to complete training sessions (HF+EX-inT) showed no improvements in cardiac systolic function nor in HCVR, sympathetic tone, or arrhythmias but displayed a further compromise in cardiac diastolic function when compared to HF-sedentary rats. In addition, HF+EX-inT rats showed impaired HVR which was associated with increased arrhythmias susceptibility and mortality during hypoxic challenges (~60% survival). Finally, exercise tolerance was closely dependent on carotid body (CB) function since their selective ablation impaired exercise capacity in HF. Our results indicate that: i) exercise may have detrimental effects on cardiac function in HF-EX-inT, and ii) reduced CB chemoreflex contributes to EX-inT in HF.