Effects of heart failure on baroreflex control of sympathetic neural activity

Abstract

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean ± SEM 21 ± 1 years) and in 11 patients with moderate to severe heart failure (age 48 ± 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 ± 2%, pulmonary capillary wedge pressure 27 ± 2 mm Hg, cardiac index 2.04 ± 0.22 liters/min/m 2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 μg/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 μg/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 ± 2 to 99 ± 3 mm Hg, p < 0.01) and in patients with heart failure (90 ± 2 to 99 ± 3 mm Hg, p < 0.01). The patients with heart failure exhibited significantly attenuated (p < 0.01 for normal vs heart failure) decreases in heart rate (93 ± 5 to 90 ± 6 beats/mm, p = not significant [NS]) compared with normal subjects (67 ± 3 to 58 ± 4 beats/min, p < 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 ± 2 to 80 ± 3 mm Hg, p < 0.001) and right atrial (4 ± 1 to 2 ± 1 mm Hg, p < 0.01) pressures with a resultant reflex increase in heart rate (68 ± 3 to 81 ± 4 beats/min, p < 0.001) and muscle sympathetic nerve activity (326 ± 74 to 746 ± 147 U/min, p < 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 ± 2 to 77 ± 2 mm Hg, p < 0.001) and right atrial (6 ± 1 to 1 ± 1 mm Hg, p < 0.001) pressures, but did not significantly alter heart rate (91 ± 6 to 97 ± 4 beats/ min, p = NS) or sympathetic nerve activity (936 ± 155 to 1179 ± 275 U/min, p = NS). When expressed as percent change in sympathetic nerve activity (U/min) per absolute change in moan arterial pressure (mm Hg) during nitroprusside infusion, the baroreflex sensitivity of the normal subjects (+ 14.7 ± 2.1% U/mm Hg) was significantly greater than that of patients with heart failure (+ 1.3 ± 1.7% U/mm Hg, p < 0.001). Similarly, when expressed as percent change in sympathetic neural activity (U/min) per absolute decrease in right atrial pressure during nitroprusside infusion, patients with heart failure exhibited a significantly diminished sensitivity (+ 9.7 ± 4.5%/mm Hg) than did the normal subjects (+ 59.8 ± 20.5%/mm Hg, p < 0.05). Thus, patients with moderate to severe heart failure demonstrate impaired baroreflex control of muscle sympathetic nerve activity and heart rate, which is most pronounced during conditions of baroreceptor deactivation.