Enhanced peripheral chemoreflex function in conscious rabbits with pacing-induced heart failure

Abstract

The present study aimed to determine whether peripheral and/or central chemoreflex function is altered in chronic heart failure (CHF) and whether altered chemoreflex function contributes to sympathetic activation in CHF. A rabbit model of pacing-induced CHF was employed. The development of CHF (3-4 wk of pacing) was characterized by an enlarged heart, an attenuated contractility, and an elevated central venous pressure. Renal sympathetic nerve activity (RSNA) and minute volume (MV) of ventilation in response to stimulation of peripheral chemoreceptors by isocapnic/hypoxic gases were measured in the conscious state. It was found that the baseline RSNA at normoxia was higher in CHF rabbits than in sham rabbits (35. 00 +/- 4.03 vs. 20.75 +/- 2.87% of maximum, P < 0.05). Moreover, the magnitudes of changes in RSNA and MV in response to stimulation of the peripheral chemoreceptors and the slopes of RSNA-arterial PO2 and MV-arterial PO2 curves were greater in CHF than in sham rabbits. Inhibition of the peripheral chemoreceptors by inhalation of 100% O2 decreased RSNA in CHF but not in sham rabbits. The central chemoreflex function, as evaluated by the responses of RSNA and MV to hyperoxic/hypercapnic gases, was not different between sham and CHF rabbits. These data suggest that an enhancement of the peripheral chemoreflex occurs in the rabbit model of pacing-induced CHF and that the enhanced peripheral chemoreflex function contributes to the sympathetic activation in the CHF state.

Carotid body function in heart failure

“…CB chemoreflex control of sympathetic nerve activity and ventilation is clearly enhanced in CHF rabbits ( Fig.1) (Sun et al 1999a. In fact, the augmented sympathetic drive occurs in the face of a potentiated ventilatory response that might be expected to attenuate the sympathetic response due to negative feedback from pulmonary afferents (Somers et al 1989).…”

“…Several lines of evidence also make it clear that augmented excitatory reflexes further boost activation of sympathetic outflow in CHF. These reflexes encompass sympathetic excitatory cardiac (Wang et al 1999), somatic (Sinoway and Li, 2004), peripheral ,Sun et al 1999a) and central chemoreceptor reflexes (Narkiewicz et al 1999). …”

“…For this reason, we have chosen a more controlled analysis of chemoreflex function in a rabbit model of pacing-induced CHF (Sun et al 1999a,1999b used extensively for the investigation of the regulation of sympathetic nerve activity in CHF (Zucker, 2006). Continuous rapid pacing of the rabbit heart (360-380 beats/ min) over the course of 3-4 weeks results in a dilated cardiomyopathy with progressive deterioration of left ventricular function (Sun et al 1999a).…”

“…For this reason, we have chosen a more controlled analysis of chemoreflex function in a rabbit model of pacing-induced CHF (Sun et al 1999a,1999b used extensively for the investigation of the regulation of sympathetic nerve activity in CHF (Zucker, 2006). Continuous rapid pacing of the rabbit heart (360-380 beats/ min) over the course of 3-4 weeks results in a dilated cardiomyopathy with progressive deterioration of left ventricular function (Sun et al 1999a). Characteristics of CHF in our paced rabbits used for study include a 40-50% reduction in ejection fraction and fractional shortening of the left ventricle without overt pulmonary edema, sympatho-humoral activation and altered autonomic reflexes as observed in patients with Class III CHF (Zucker, 2006,Sun et al 1999b.…”

“…In normal humans at rest, hyperoxia, which inhibits peripheral chemoreceptor activity, decreases sympathetic nerve activity (Seals et al 1991). In addition, animal models (Sun et al 1999a(Sun et al ,1999b and patients with chronic heart failure (CHF) exhibit increased chemoreflex drive under normoxic conditions. Thus, it is not unreasonable to suggest that chemoreflexes contribute to sympathetic tone, even in the absence of hypoxia.…”