P.I. Korner,     Baker Medical Research Institute, Melbourne, Australia 3181

Publisher Summary

Circulation is a hydraulic regulator in which the heart adjusts cardiac output through intrinsic mechanisms determined by cardiac filling, afterload and inotropic state. In the peripheral circulation, the local autoregulatory properties of the regional beds adjust blood flow to each organ’s metabolic needs. This chapter illustrates a flow diagram that shows the major components of the circulatory control system. An optimum operation of CNS autonomic mechanisms involves a large number of integrations through neuron groups that are widely distributed from cortex to spinal cord. Noradrenergic and serotonergic neurons are a part of the network, but there are probably many other types of transmitters involved in the autonomic pathways. Anesthesia often distorts the integrative capacity of the CNS. During environmental disturbances, there are often changes in many peripheral receptors. Interactions that alter the properties of the arterial baroreflex have particular homeostatic importance as they can greatly alter the capacity of the body to correct for large circulatory perturbations.

Introduction

The circulation is a hydraulic regulator in which the heart adjusts cardiac output through intrinsic mechanisms determined by cardiac filling, afterload and inotropic state. In the peripheral circulation, the local ‘autoregulatory’ properties of the regional beds adjust blood flow to each organ’s metabolic needs. The flow diagram in Fig. 1 shows the components of this system important in overall circulatory control. A disturbance through its direct local effects on heart and vasculature will produce changes in arterial, cardiac and pulmonary pressures which are signalled to the CNS through the different groups of baroreceptors. This information together with changes in many other sensory modalities activates many regions in the CNS. The important difference of the closed-loop operation of this control system is the variety of sensory information it receives, contrasting with the classic open-loop analysis of cardiovascular reflexes where the activity of all inputs except that under study are maintained onstant or eliminated (1). The information reaching the CNS evokes a pattern of autonomic effector activity that is characteristic for the particular stimulus profile. These autonomic effects together with the direct local effects of the disturbance determine the final circulatory response.

Autonomic activity may also be initiated by the CNS instead of being evoked primarily from peripherally determined information. Highly characteristic autonomic patterns may be part of a voluntary motor act or can occur, in association with different types of behaviour (2). In the event, each type of autonomic response in the intact organism is determined by both reflex and behavioural factors. Thus disturbances starting primarily owing to changes in activity in peripheral receptors also alter behaviour which may modify the autonomic response (3). In turn changes in autonomic activity initiated by central ‘command’ will alter intravascular pressures and the activity of peripheral receptors which will again influence the autonomic response (2,3).

In this lecture I have limited discussion to integrations of autonomic responses evoked primarily from peripherally determined inputs, mainly because they are more readily subjected to quantitative study than behaviourally determined changes in autonomic function. The first part of the lecture considers the major design features of the CNS autonomic pathways. Even the simplest autonomic response is mediated through numerous integrative sites. Furthermore, the sympathetic nervous system is not just a system for uniform mass action, as was at one time envisaged by Cannon (4). Instead, its activity is often non-uniform, with an increase in some outflows and a decrease in others. Another aspect briefly considered is the number of different chemical transmitters linking the various components of the autonomic network (e.g. noradrenergic and serotonergic neurons). Parenthetically, anaesthesia can distort considerably the normal operation of this system.

The second part of the lecture considers the special problems of input-autonomic output relationships in the intact organism where the CNS is presented with a complex input profile. The autonomic responses frequently appear anomalous and are difficult to predict from classic reflex analysis as the sum of the individual reflex effects. Such non-linear behaviour is often due to interactions in the CNS and its main feature is that a given autonomic response to unit change in one input becomes markedly altered by the level of activity in one or more of the other inputs. Examples considered here are chemoreceptor-ventilatory interactions and CNS ‘resetting’ of arterial baroreceptor reflex properties. The latter can greatly modify the capacity of the circulatory control system to cope with environmental disturbances.

Organisation of CNS Autonomic Pathways

Up till 1960’s the classic cardiovascular centres of the pons and medulla were considered to have a very dominant role in the integration of reflex responses, including those arising from the arterial baroreceptors, chemoreceptors and visceral and somatic afferents (5). Brain regions such as the hypothalamus, limbic system and cortex were considered to play a role only in special regulatory tasks, e.g. exercise, temperature regulation and behaviour.

The current view considers that in the conscious intact animal, as far as we know, every type of autonomic response occurs through numerous integrations involving many parts of the brain (Fig. 2). Inputs from the heart and blood vessels reach the CNS through IX and X. cranial nerves and through spinal sympathetic afferents. They synapse to project to widely distributed integrative sites from which they project to the various autonomic motoneuron pools. There are thus elaborate connections longitudinally throughout the brain as well as links between different neuron groups at any particular level. Clearly in several of the suprapontine sites information from peripheral receptor groups must come into close contact with projections from mechanisms subserving central ‘command’.

There is thus a great deal of divergence and convergence of information, so that (i) a given input projects to numerous integrative sites in different parts of the brain (6); and (ii) a given group of autonomic motoneurons receives axons from any integrative sites (7).

With the wide distribution of neuron groups throughout the CNS it is important not to overemphasize the hierarchic nature of the different integrative sites by calling them ‘higher’ or ‘lower’ centres. The network is one allowing multiple access of information at numerous levels and has many outputs. Integrations performed by bulbo-spinal mechanisms such as the tractus solitarius and its nucleus, or by the autonomic interneurons of the spinal cord appear to be amongst the most complex of the autonomic network (3).

We do not yet know enough about the anatomical connections or the exact functions of the various integrative sites. Indeed, in many disturbances we are far from clear which the various neuron groups are that contribute to production of a particular autonomic response. It is for this reason that input-output analysis is still such an important tool of analysing the properties of the control system.

Examples of Integrative Activity

The various components that comprise the CNS autonomic pathway have both an ‘amplifier’ function where more volume is provided and fine ‘tuning’ function that helps to adjust the autonomic response to the particular stimulus. The suprapontine components of the network allow integration of information that overlaps but is not identical with that reaching bulbar or spinal mechanisms, but is no more important in the overall response.