The brain-body interface comprises many physiological interactions which can go awry in disease states. This article discusses the brain-heart interface and its interactions with the autonomic nervous system under conditions of normal homeostasis and in cerebrovascular disorders.
The Brain-Heart Interface and the Autonomic Nervous System
Direct and indirect projections of the autonomic nervous system control the cardiovascular system. These projections act via the parabrachial nucleus of the midbrain and pons (Figure 1). The parabrachial nucleus is a relay station that transmits signals between the cerebral cortex (especially limbic cortex), amygdala, hypothalamic paraventricular nucleus, vasomotor area of the lower brainstem (including the ventrolateral medulla, medullary raphe, nucleus of the solitary tract), and the thoracolumbar intermediolateral gray column of the spinal cord.
Autonomic visceral afferents from the thoracolumbar (sympathetic) and craniosacral (parasympathetic) levels ascend to the nucleus tractus solitarius. In addition, afferents from arterial baroreceptors in the aortic arch and carotid bodies also reach the nucleus tractus solitarius. This nucleus of the solitary tract also receives information about humoral (such as plasma electrolytes) and cerebrospinal chemical information from the area postrema (a circumventricular organ). Autonomic efferents include the anterior cingulate gyrus, amygdala, insula, hypothalamus, periaqueductal gray matter within the diencephalon, locus ceruleus, parabrachial nucleus of pons before final pathways within the medulla and interomediolateral spinal cord (Figure 1).
Arterial baroreceptors in the carotid sinus and aortic arch send information about arterial wall stretch to the nucleus tractus solitarius via the glossopharyngeal and vagal nerves. In so doing, the autonomic nervous system mediates heart rate (chronotropy), rate of nervous impulse transmission through the cardiac conduction tissue (dromotropy), and force of contraction (inotropy). Blood vessel diameter and tone are also mediated via the autonomic nervous system. Nucleus tractus solitarius inhibits the rostral ventrolateral medulla, excites the nucleus ambiguus and dorsal motor nucleus of vagus, producing a reduction in sympathetic tone and increase in vagal activity (including negative inotropic effects via the sinoatrial node as well as vasodilatory effects). Adrenergic neurons originating between T1 and L2 synapse with the entire arterial tree (Figure 2).
Counter-regulatory feedback with the sympathetic nervous system predominates. An example of such counter-regulatory feedback is the Cushing reflex. Increase in intracranial pressure from disease states, such as intracerebral hemorrhage, leads to decreased levels of oxygen and increased local levels of hydrogen ions and carbon dioxide around the vasomotor regions of the lower brainstem secondary to anaerobic metabolism. As a counter-regulatory measure, the systemic blood pressure is elevated in an attempt to increase blood flow to the brain. With this increase in blood pressure, heart rate is reflexively decreased via the arterial baroreceptors.
Other factors also affect the amount of autonomic nervous output from the vasomotor regions of the brainstem, including:
(1) Blood oxygen level,
(2) Blood carbon dioxide level,
(3) Pain stimulus,
(4) Chemoreceptors and baroreceptors in the carotid, pulmonary and aortic vessels sense corresponding changes,
(5) Nerve impulse feedback from the lungs secondary to lung inflation and deflation, and
(6) Regulatory signals between the cerebral cortex and brainstem
Heart Rate Variability & Baroreceptor Activity
Heart rate variability can reflect the balance of sympathetic and parasympathetic nervous activity. The QRS complex's RR interval time series reflect heart rate variability, sensing changes in atrioventricular conduction affecting cardiac output and stroke volume. Low frequency power (0.05-0.15 Hz) of heart rate variability is under the combined influence of sympathetic and parasympathetic tones, with sympathetic modulation by the sinus node. Increases in low frequency power represent decreased vagal activity. High frequency power (0.15-0.4 Hz) of heart rate variability reflects parasympathetic modulation of cardiac activity, a measure which is influenced by respirations. In respiratory sinus arrhythmias, heart rate oscillations are caused by ventilation with slight heart rate increases with each inspiratory cycle due to transient decreases in parasympathetic tone. Therefore, the high frequency to low frequency ratio can be regarded as a measure of sympathovagal balance.
As described, the autonomic nervous system adjusts blood pressures by adjusting heart rate, cardiac contractility and peripheral vascular resistance, where the baroreceptors measure blood pressure by sensing blood vessel stretch located in the aorta, carotid arteries and large veins. Baroreceptor activity sends afferent activity to regulate blood pressure through:
(1) Baroreflex - with systolic blood pressure as inputs and RR interval changes as outputs through the sinoatrial node, and
(2) Sympathetic vasomotor tone with diastolic blood pressure as inputs and outputs through muscle sympathetic nervous activity to control blood vessel constriction and peripheral vascular resistance.
Baroreceptor sensitivity reflects the capability of the baroreflex to adjust heart rates to changing conditions. The baroreceptor sensitivity can be regarded as the ratio of heart rate changes in response to fixed changes in blood pressure.
Interplay between Sympathetic and Parasympathetic Nervous System Innervation of Cerebral Vasculature
Parasympathetic innervation includes pterygopalatine ganglion (vasoactive intestinal peptide), otic ganglion (peptide histidine methionine) and carotid ganglion (nitric oxide). Cholinergic innervation is most densely distributed at cerebral vessel branching points, especially pial vessels. Sympathetic innervation includes the superior cervical ganglion (norepinephrine, neuropeptide Y) with neuronal synapses in the loop from hypothalamus, intermediolateral cell column of the spinal cord to superior cervical ganglion. Sympathetic nerve terminals are found in the outer media layer of cerebral vessels, most densely distributed in the anterior circulation with autoregulatory and chemical contributions from both the superior cervical ganglion and pontine locus ceruleus. Finally, sensory innervation is noted with transmitters from the trigeminovascular system (substance P, calcitonin gene related peptide, neurokinin A). Vasodilatory, anti-inflammatory and parasympathetic nitric oxide mediated effects of therapeutic agents may be used to partially overcome both primary and secondary injury cascades in stroke and brain hemorrhage patients.
Increase basal sympathetic discharges and disrupted autoregulation of sympathetic outflow, as observed in conditions including hypertension, ischemic and hemorrhagic strokes, renal insufficiency, heart failure, and liver dysfunction, result in vicious cycles of increased catecholamine release, increased activation of renin-angiotensin-aldosterone system, shunting of blood from venous to arterial system with resultant vascular congestion, predisposing to cerebral edema formation and hemorrhage. Targeting autonomic interactions in both vasculature and end organs such as the heart, liver, kidney and spleen, one can investigate for better ways of controlling autonomic nervous system responses in both states of health and disease.