EFFECTS OF BETA-BLOCKADE ON NEUROHUMORAL RESPONSES AND NEUROCHEMICAL MARKERS IN PACING-INDUCED HEART-FAILURE

We investigated neurohumoral profiles and transmitter and neuroenzyme markers of cardiac autonomic innervation in control (unpaced) dogs and three groups of dogs with pacing-induced heart failure (paced, paced + beta-adrenergic blockade, and paced + cardiac denervation). Left ven tricular ejection fraction decreased significantly and to a comparable extent in all paced groups. Pacing increased plasma norepinephrine (N E); increases in NE were not attenuated but instead tended to be exagg erated by treatment with propranolol or cardiac denervation. Atrial hy pertrophy occurred in all paced groups compared with the control group . However, atrial and right ventricular hypertrophy were not as pronou nced in the paced plus cardiac denervation group as in the paced and p aced plus propranolol groups. Pacing also depleted neuropeptide Y and NE from all heart chambers; propranolol treatment did not modify these local tissue changes. Pacing caused selective depletion of neuroenzym es predominantly in the left ventricle; again, propranolol did little to modify these changes. In this study of paced animals with experimen tally maintained cardiac dysfunction, failure to modify noradrenergic responses with intrapericardial cardiac denervation suggests that nonc ardiac sources contribute predominantly to high plasma NE. Failure to modify neurohumoral, neuropeptide, and neuroenzyme responses with beta -antagonist suggests this treatment has little practical direct influe nce on sympathetic vasomotor activity or neuronal function in heart fa ilure