Increased circadian variations in chemoreflex sensitivity in chronic heart failure

Abstract

Respiratory function follows a circadian pattern, and rhythmic changes in carotid body sensitivity to blood gases may contribute to these oscillations in ventilation. Recent studies have demonstrated that the isolated rat carotid body shows enhanced responses to hypoxic and hypercapnic stimulation in the presence of melatonin, a nocturnally released hormone. Carotid body dysfunction is known to occur in several pathological conditions, including chronic heart failure (CHF). CHF is characterized by tonic hyperactivity and exaggerated reactivity of the carotid bodies to hypoxia and hypercapnia. Thus, we've begun to examine circadian rhythms in chemoreflex breathing in CHF to determine if the already heightened hypoxic and hypercapnic responses in CHF are further augmented during the night. Male Sprague‐Dawley rats were divided into either control or CHF groups. Heart failure was induced via coronary ligation. Chemoreflex breathing was assessed during the day and then again 12 hours later during the night. Animals were exposed to room air (baseline), hypoxia (10 % O2) and hypercapnia (5 % CO2). Percent change in respiratory rate from day to night were similar between CHF (17.1 % increase) and control (16.9 % increase) rats when exposed to room air, but hypoxic and hypercapnic challenges induced large circadian differences in CHF (hypoxia: 20.9 % increase; hypercapnia: 23.9 % increase) but not in control (hypoxia: 8.2 % increase; hypercapnia: 13.9 % increase) rats. CHF rats also showed robust night time circadian differences in tidal volume when exposed to room air (31.6 % increase), hypoxia (27.9 % increase), and hypercapnia (43.8 %). In contrast, circadian variations in tidal volume were attenuated in control rats (room air: 11 % increase; hypoxia: 15.6 % increase; hypercapnia: 11.0 % increase). Minute ventilation showed similar differences between CHF and control rats with CHF significantly augmenting circadian variations. CHF rats showed a 53.1 % increase in minute ventilation during the night, and a 52.9 % increase and a 78.2 % increase in response to hypoxia and hypercapnia, respectively. Control rats, in contrast, showed only a 27.7 % increase in minute ventilation to room air, a 25.1 % increase in response to hypoxia, and a 26.9 % increase in response to hypercapnia. Therefore, the data suggest that circadian rhythms in ventilatory responses are amplified in CHF. Future research may directly assess the contribution of the carotid bodies to this phenomenon.