Selective impairment of baroreflex-mediated vasoconstrictor responses in patients with ventricular dysfunction

Cardiac dysfunction in animals has been associated with impairment of arterial and cardiopulmonary baroreflex control of the circulation. Chronic heart failure in human beings is associated with neurohumoral excitation, which could result in part from impairment in the inhibitory influence of baroreflexes. We postulated that (1) patients with left ventricular dysfunction (LVD) have impaired baroreflex modulation of vascular resistance and (2) administration of a digitalis glycoside would immediately restore baroreflex sensitivity. Eleven patients with LVD (NYHA class, 2.8 +/- 0.2, mean +/- SEM; baseline left ventricular ejection fraction, 18 +/- 2%; cardiac index, 2.4 +/- 0.21/min/m2; and pulmonary capillary wedge pressure, 26.0 +/- 3.2 mm Hg) were compared with 17 normal control subjects. We measured forearm vasoconstrictor responses to simulated orthostatic stress with use of lower body negative pressure (LBNP) at -10 and -40 mm Hg to unload cardiopulmonary and arterial baroreceptors. Baseline forearm vascular resistance (FVR) was higher in patients with LVD than in normal subjects: FVRLVD, 68.8 +/- 15.3 U; FVRN, 23.2 +/- 2.1 U (p less than .001). During unloading of baroreceptors with LBNP -10 mm Hg, normal subjects developed vasoconstriction (delta VRN at LBNP -10 mm Hg, +5.7 +/- 1.6 U) but patients with LVD failed to have vasoconstriction and tended to develop vasodilation (delta FVRLVD at LBNP -10 mm Hg, -8.6 +/- 8.5 U) (p = .05, normals vs patients with LVD at LBNP -10 mm Hg). A more marked disparity in response was seen during unloading of baroreceptors of LBNP -40 mm Hg: delta FVRN at LBNP -40 mm Hg, +16.6 +/- 1.5 U; delta FVRLVD at LBNP -40 mm Hg, -10.3 +/- 9.6 U (p less than .001, normals vs patients with LVD). Despite high baseline values for FVR, patients with LVD developed vasoconstriction during intra-arterial infusions of norepinephrine, thereby excluding a nonspecific depression of vascular reactivity as the mechanism for abnormal responses to LBNP in patients with LVD. We also studied the short-term effects of administration of a digitalis glycoside, ouabain 0.0075 mg/kg (seven patients) or lanatoside C (Cedilanid-D) 0.02 mg/kg (three patients), on baroreflex-mediated vasoconstrictor responses to LBNP in the patients with LVD. Digitalis glycoside reduced baseline FVR from 71.8 +/- 16.6 to 48.6 +/- 12.0 U (p less than .02). Responses to LBNP tended to be normalized after administration of digitalis glycoside: delta FVR during LBNP -40 mm H