Role of Cardiac Reflexes in the Control of Heart Rate

Abstract

Sometimes cardiovascular observations that we see in patients during anesthesia or in the intensive care unit have a well-established anatomical or physiological basis. This is the case for the Bainbridge reflex and its “reverse reflex.” However we do not always see the true magnitude of the reflex given that numerous perioperative factors that may alter the responsiveness of the cardiac sympathetic nerves (including aging, concurrent disease, cardiovascular drugs that alter normal heart rate control, surgical manipulations, and anesthetics). The beat-to-beat activity of the heart within the whole organism must be adaptable to the changing requirements of that organism. The automaticity of the heart is therefore subject to various neural stimuli that regulate the heart by either increasing or diminishing its automaticity. Regulation of heart rate is controlled by various afferent and efferent nerves. The afferent fibers run in the vagus nerves. Efferent fibers are in both the vagus and sympathetic nerves. The vagal components arise from the dorsal nucleus in the floor of the fourth ventricle, with the vagus interacting with the sinoatrial node and the atrioventricular node. The sympathetic input to the heart leaves the spinal cord via the ventral roots of the upper 5 (although mainly second and third) thoracic nerves, run in the white rami communicantes, and then by the Annulus of Vieussens to the middle cervical ganglion. From here, cardiac branches convey the sympathetic fibers to the heart from the stellate ganglion, the middle cervical ganglion, and the Annulus of Vieussens (Fig. 1).Figure 1: Diagram of the innervation of the heart. The preganglionic fibers are the myelinated white rami communicantes, while the postganglionic nonmyelinated fibers pass via the Annulus of Vieussens (also known as the ansa subclavia) to the middle cervical ganglion, and then to the heart as the cardiac accelerator nerves. The intracardiac ganglion is a network of fibers extending over the surface of both atria in the subepicardial tissue. The cardiac branches of the right vagus pass to the sinoatrial node, and from the left vagus to the atrioventricular node. M = medulla; SC = spinal cord; CI = cardio-inhibitory center; CA = cardio-accelerator center; LH = lateral horn cell; SG = stellate ganglion; 1, 2 = pre- and postganglionic fibers; RV = right ventricle; VA = vagal accelerator afferent; AN = aortic nerve; V = efferent vagal fibers; ICG = intracardiac ganglion. (Adapted from Starling and Lovatt Evans “Principles of Human Physiology, 13th edition,” Churchill Ltd, London 1962).Thus, the heart rate is controlled by these two groups of neurons, the cardio-inhibitory and cardio-accelerator centers located in the floor of the fourth ventricle. Heart rate is a balance of these 2 influences; at rest the heart rate is predominantly vagally controlled, with the sympathetic nervous system making only a minor contribution. Stimulation of the cardio-inhibitory center in the medulla exerts an effect primarily on the atria. Vagal stimulation may affect the heart in one of several ways: causing atrial standstill, slowing, flutter, or fibrillation. Pronounced vagal stimulation stops the activity of all parts of the atria, and in such cases the ventricles also cease beating. After a short pause, the ventricles recommence but at a slow “idio-ventricular” rhythm (despite continuing vagal stimulation). This “vagal escape” of the ventricles is due in part to an accelerator reflex arising from the carotid sinus in which the arterial pressure has fallen, and in part to the independent contraction of a ventricle temporarily “cutoff” from atrial control. Whether the vagus has any direct action on the mammalian ventricle is uncertain, but any such effect will be very slight compared with that on the atria. Vagal stimulation can also diminish conduction of the excitatory process from atria to ventricles, as manifest by an increase in the P–R interval of the electrocardiogram. In more pronounced circumstances, the ventricles may beat at a slower rhythm than the atria with a conduction block in the atrioventricular bundle. The tonic influence of the vagus is abolished in mammals if both vagi are sectioned; if a small dose of atropine is administered; or by lesioning of the cardio-inhibitory center. Stimulation of the accelerator center causes an increase in heart rate that is mediated via the sympathetic nerves. There are a number of extrinsic extraneural factors that will influence heart rate. These include peripheral stimulation, direct stimulation, impulses from higher cranial centers, and vascular reflexes. For example, while hypoxic and hypercapnic blood both directly stimulate the cardio-inhibitory center to cause a slowing of the heart rate, hypoxia and hypercapnia both stimulate the peripheral carotid body chemoreceptors leading to an increase the heart rate. An elevation of body temperature will increase the heart rate by increasing the rate of discharge of the sino-atrial node; whereas hypothermia depresses both higher centers and cardiac impulse conduction. Circulating catecholamines increase heart rate by direct stimulation of cardiac adrenoceptors. Both cranial centers are also subject to impulses arriving via various afferent nerves or from higher parts of the brain, giving rise to the changes in heart rate associated with the emotions. The 2 centers are often affected together, though in opposite directions, with excitation of the cardio-inhibitory center being accompanied by decreased activity of the cardio-accelerator center. Sudden fright in the conscious subject can result in intense vagal stimulation, vasodilatation, and hypotension with slowing of the heart, leading to the so-called “vasovagal attack.” The phenomenon of sinus arrhythmia may be due to the spread of respiratory neuron activity to adjacent cardiac center neurons. Elevation of intracranial pressure will slow the heart rate. Finally in humans there are important regions containing pressor receptors. These are in the media of the roots of the great vessels, namely the common carotid artery, subclavian arteries and arch of the aorta. The bifurcations of the common carotid arteries are dilated forming the carotid sinuses. Other pressor receptors reside in the atria and great veins.1 Afferents from all these pressor receptors pass to the medulla. Histological evidence exists for pressure receptor in the walls of the pulmonary vessels, of a type similar to those found in the carotid sinus and aortic arch. Changes in pressure in the pulmonary circulation can lead to reflex alterations in heart rate, systemic blood pressure, and the caliber of systemic arterioles.2,3 CARDIAC REFLEXES Following stimulation of baroreceptors in a horse model, the French physiologist Etienne-Jules Marey (1830–1904) observed that the pulse rate varies inversely as the arterial pressure through stimulation of the baroreceptors in the carotid sinus and aortic arch. Impulses were transmitted via the cardiac sinus and aortic nerves to cause excitation of the cardiac inhibitory center.4 However, the exact mechanism of this response was not recognized until the studies of Hering and Heymans in the early 1920s.5,6,7 An example of this reflex cardiac inhibition due to the rise in arterial pressure is seen when a small dose of norepinephrine is injected IV in humans. The slowing of the heart rate can be abolished or reversed by atropine, which blocks transmission at the vagal postganglionic nerve endings, and in animals by cutting the afferent side of the reflex arc, i.e., the carotid sinus and aortic nerves. Accelerator reflexes are seen following the lowering of arterial pressure, which causes a reduction in the number of impulses reaching the cardiac inhibitory center from the baroreceptors in the carotid sinus and aortic arch, thereby releasing vagal constraint.8,9 Thus it is clear from this experiment that baroreceptor impulse activity that occurs at normal levels of blood pressure is responsible, at least in part, for maintenance of normal cardiac vagal tone. Cardiac acceleration can result from a decrease in vagal tone when the arterial pressure falls. A fall in blood pressure causes a reduction in the number of impulses reaching the cardiac inhibitory center from baroreceptors in the carotid sinuses and aortic arch, and thereby reduces vagal inhibition. Francis Arthur Bainbridge was born in 1874; he was educated at Cambridge and St. Bartholomew's Hospital in London and then took posts in physiology. In 1911 he became a professor of physiology at Durham University. In 1915 he attained the chair of physiology at St. Bartholomew's Hospital, where he remained for the rest of his life (dying in 1921). Bainbridge is best remembered for demonstrating that an increase in pressure on the venous side of the heart increased heart rate due to denervation of cardiac vagal influences.10 The eponymous Bainbridge reflex is named after him, which is an increased heart rate due to an increase of the right atrial pressure. Bainbridge attributed this reflex response to be initiated by distension of the right atrium and great veins causing a rise in the pressure within them. Afferent impulses were believed to pass via the vagi and cause cardiac acceleration by a reduction in vagal tone (the main causative factor) and possibly also by an increase in sympathetic tone. For some time after this, researchers had difficulty repeating Bainbridge's experiments. However in 1955, Coleridge and Linden showed in a canine model that an increase of venous return caused cardiac acceleration to occur.11,12 They found that the response was not initiated by an increase in right atrial pressure (as proposed by Bainbridge). Studies using isolated perfusion techniques or mechanical distension with balloons to selectively increase atrial pressure produced inconsistent changes in heart rate.13 The possibility that the accelerator response in the whole animal was due, in part if not wholly, to a direct effect on the cardiac pacemaker cannot be excluded.14 Further analysis by Hainsworth suggests that the response was not that of a single reflex, but rather that the change in heart rate following the increase in venous inflow was a summation of a number of changes following activation of afferent nerve endings in the atria as well as those in the pulmonary veins and left ventricle.15 In this issue of the journal, Crystal and Salem present a detailed historical and physiologic review of the Bainbridge reflex.16 They conclude that there is limited evidence for or against the clinical importance of the reflex. To complicate matters, there is also evidence for the so-called “reverse Bainbridge reflex,” where a reduction in venous return may deactivate the receptors described by Bainbridge, and Coleridge and Linden, resulting in a reflex-induced reduction of heart rate. This reflex may have a role in the occurrence of the bradycardia not uncommonly seen during epidural or spinal anesthesia17–19 and during controlled hypotension (although evidence for a role during the latter appears inconclusive). There is also research showing that the occurrence of the Bainbridge reflex is species-dependent, the response being more pronounced in the dog when compared with the baboon and human; that there needs to be a low initial heart rate; and that there is an absence of general anesthesia (which may, of its own, influence cardiovascular reflexes).20 The magnitude of the human response may be less than in other species because of our low basal vagal tone compared with the dog.21 This would preclude an appreciable increase in heart rate following the withdrawal of the vagal component. Clarification of this suggestion should be possible using spectral analysis of the heart rate response. Today much anesthesia-related research is focused away from systems physiology to molecular biology, drug disposition and kinetic-dynamic modeling, and epidemiology and outcomes research. We should therefore be grateful to our predecessors for the painstaking ways in which fundamental physiology was “unraveled.” We are left needing to identify factors that may affect the “normal responses” of the body and, importantly, ways to prevent unexpected physiological scenarios that may affect our patients' ability to maintain physiologic homeostasis. DISCLOSURES Name: John William Sear, MA, BSc, PhD, MBBS, FFARCS, FANZCA. Contribution: This author wrote the manuscript. Attestation: John William Sear approved the final manuscript. This manuscript was handled by: Martin J. London, MD.