Activation of brain catecholaminergic neurons by cardiac vagal afferents during acute myocardial ischemia in the rat.

The catecholamines, dopamine, norepinephrine, and epinephrine, have been found in brain regions associated with cardiovascular regulation.We wished to determine whether central catecholaminergic neurons participate in the reflex alterations of cardiac autonomic nerve traffic associated with acute myocardial ischemia.Five groups of rats treated with a-methyltyrosine, an inhibitor of catecholamine biosynthesis, were examined.The experimental interventions included left coronary artery ligation, ligation with the left ventricle painted with lidocaine, ligation and bilateral cervical vagotomy, sham operation, and sham operation plus vagotomy.An untreated group of resting rats was also examined.Dopamine, norepinephrine, and epinephrine were measured 90 minutes later in thoracic cord, cerebellum, pons medulla, midbrain, posterior and anterior hypothalamus, thalamus and frontal cortex.Norepinephrine turnover was increased in thoracic cord, pons medulla and posterior hypothalamus, and dopamine turnover was increased in posterior hypothalamus in the ligated rats relative to those subjected to sham operation.These increases were abolished by topical lidocaine or vagotomy.The turnover of all three catecholamines was increased in anterior hypothalamus in both ligated and Udocaine-treated rats, but not in vagotomized animals.Thus, there is a reflex activation of noradrenergic nerves in the posterior hypothalamus, pons medulla, and thoracic cord (bulbospinal fibers), and of dopaminergic nerves in the pons medulla after left coronary artery ligation in the rat.This reflex arises from receptors in the ischemic ventricle and the afferent limb is in the vagus nerve.Coronary artery ligation also activates catecholaminergic nerves in the anterior hypothalamus; the afferent signals travel in the vagus but do not appear to originate in the ischemic ventricle.CircRes 47: [166][167][168][169][170][171][172] 1980 THE predominant cause of sudden death in patients with coronary artery disease is ventricular fibrillation (Pantridge et al., 1975).Studies directed toward the amelioration of this problem have led to recognition of the importance of ischemia-induced cardio-cardiac autonomic reflexes in determining the propensity of the acutely ischemic heart to malignant arrhythmias (Lown and Verrier, 1976;Corr and Gillis, 1978).These reflex signals arise in receptors in the ischemic ventricle (Thoren, 1972;Uchida and Murao, 1974) and are conducted by unmyelinated and myelinated vagal (Constantin, 1963;Kolatat et al., 1967;Bishop and Peterson, 1978) and sympathetic afferents (Brown, 1967;Malliani et al., 1969) to be integrated in the central nervous system.The resultant inhibitory or excitatory efferent signals are carried by vagal and sympathetic nerve fibers, respectively (Constantin, 1963;Malliani et al., 1969;Bishop and Peterson, 1978).