TY - JOUR T1 - Parasympathetic Control of the Heart JF - Pharmacological Reviews JO - Pharmacol Rev SP - 119 LP - 155 VL - 25 IS - 1 AU - Charles B. Higgins AU - Stephen F. Vatner AU - Eugene Braunwald Y1 - 1973/03/01 UR - http://pharmrev.aspetjournals.org/content/25/1/119.abstract N2 - In the last decade, evidence has been obtained which indicates that the terminal innervation of the ventricles as well as the atria includes parasympathetic nerve fibers. The demonstration of ganglia within the ventricular myocardium suggested the presence of parasympathetic nerve fibers and the vagal nature of these ganglia was supported by their persistence after total surgical cardiac denervation and cardiac transplantation. Although it is now clear that parasympathetic fibers are present throughout the ventricles, their density is considerably sparser in these chambers than in the atria. Furthermore, the vagal trunkas receive abundant adrenergic fibers from the stellate ganglia via the ansa subclavia and actually are mixed parasympathetic-adrenergic trunks. The adrenergic and parasympathetic components of the trunks are unevenly distributed to the ventricles; it appears that greater numbers of adrenergic fibera terminate in the right ventricle and greater numbers of cholinergic fibers in the left ventricle. Cholinergic interventions produce their action upon the heart by a variety of mechanisms. The inhibitory actions appear to be closely related to their ability to decrease the duration of the action potential and subsequent cellular influx of ionic calcium. In addition ACH and choline esters decrease adenylate cyclase activity and cyclic adenosine 3' ,5'-monophosphate accumulation of broken cell preparationa from mammalian atria and ventricles. On the other hand, under special conditions, i.e., after atropine administration, cholinergic interventions may cause stimulatory effects through interactions with adrenergic and nonadrenergic mechanisms. There is now abundant evidence to indicate that ACH releases norepinephrine from depota in the heart; these depots are located predominantly in postganglionic adrenergic nerve fibers. In addition, particularly in the presence of conditions tending to lower intracellular ionic calcium, large doses of ACH produce positive inotropic effects on ventricular myocardium, in spite of prior depletion of cardiac catecholamine stores. Cholinergic and adrenergic influences interact synergistically and antagonistically in their actions upon the heart. It appears that under conditions involving a high level of sympathetic tone, the vagal center in the medulla is inhibited by higher centers in the hypothalamus. In addition, cholinergic and adrenergic mechanisms interact at the receptor level, the inhibitory actions of ACH on automaticity and contractility on atrial tissue predominating over the excitatory actions of catecholamines. Although an inhibitory effect of the vagi upon ventricular contractility has been questioned for many years, recent investigations have clearly indicated that stimulation of the vagosympathetic trunk produces a negative inotropic effect in the canine ventricle. In addition, there is now convincing evidence that stimulation of parasympathetic nerve fibers produces distinct vasodilatation in the coronary vascular bed, independent of its indirect effects on the determinants of myocardial oxygen requirements and myocardial extravascular compression. Parasympathetic nerve fibers serve as a component of the efferent limb of the baroreceptor, chemoreceptor, and of other cardiovascular and respiratory reflexes involved in the regulation of cardiac automaticity and contractility. Recent studies using a sensitive technique to evaluate the responsiveness of the baroreceptor reflex indicate that reflexly induced parasympathetic stimulation of the heart is attenuated by general anesthesia, during exercise, in hypertensive patients, and in normotensive, elderly patients. Observations in man and in experimental animals indicate that parasympathetic tone and parasympathetically medisted reflexes are profoundly depressed in heart failure and in various forms of heart disease. The Williams & Wilkins Co. ER -