Neurochemical indices of autonomic innervation of heart in different experimental models of heart failure.

Abstract

Parasympathetic neural regulation of the failing heart is impaired. In order to investigate parasympathetic mechanisms in experimental heart failure, measurements were made of choline acetyltransferase (CAT) activity and [3H]-quinuclidinyl benzilate (QNB) binding in hearts of 1) hamsters with skeletal and cardiac myopathy, 2) dogs with pulmonary artery constriction and tricuspid avulsion, and 3) guinea pigs with pulmonary artery constriction. Tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH) activities and norepinephrine levels served as indices of sympathetic innervation. In myopathic hearts, total CAT activity decreased (P less than 0.05) compared to age-matched controls. In canine and guinea pig right heart failure, total CAT activity was normal in contractile and specialized tissues. Alterations in [3H]-QNB binding paralleled CAT activity being decreased (P less than 0.05) only in myopathic hearts. In all three models, indices of sympathetic innervation were altered in ways qualitatively different from parasympathetic indices; TH and DBH activities were increased (P less than 0.05) in myopathic ventricles, decreased (P less than 0.05) in hypertrophied canine and guinea pig ventricles and non-hypertrophied canine ventricles, and normal in non-hypertrophied guinea pig ventricles. These results indicate that alterations in cardiac parasympathetic indices vary depending on the etiology of heart diseases and differ qualitatively from alterations in sympathetic indices. Selective determinants are necessary to explain the varied changes.