The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...

The Microbiota-Gut-Brain Axis

The vagus, the 10th cranial nerve, contains pathways that contribute to the regulation of the internal viscera, including the heart. Vagal efferent fibers do not originate in a common brainstem structure. The Polyvagal Theory is introduced to explain the different functions of the two primary medullary source nuclei of the vagus: the nucleus ambiguus (NA) and the dorsal motor nucleus (DMNX). Although vagal pathways from both nuclei terminate on the sinoatrial node, it is argued that the fibers originating in NA are uniquely responsible for respiratory sinus arrhythmia (RSA). Divergent shifts in RSA and heart rate are explained by independent actions of DMNX and NA. The theory emphasizes a phylogenetic perspective and speculates that mammalian, but not reptilian, brainstem organization is characterized by a ventral vagal complex (including NA) related to processes associated with attention, motion, emotion, and communication. Various clinical disorders, such as sudden infant death syndrome and asthma, may be related to the competition between DMNX and NA.

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Orienting in a defensive world: Mammalian modifications of our evolutionary heritage. A Polyvagal Theory

The control of arterial pressure during sleep was studied in 13 untreated, unsedated subjects aged 20 to 46, including 7 with hypertension. Arterial pressure was measured directly. A transient rise of arterial pressure up to 30 mm Hg was produced by the sudden intravenous injection of 0.25 to 2 µg of angiotensin. Linear plots were obtained in 10 of 13 subjects when the systolic pressures of successive pulses during the pressure rise were plotted against the pulse intervals which began the next beat. The relationship was disturbed by movement or arousal, and was better when pulse intervals falling in inspiration were discarded. The slope of the line (milliseconds of cardiac slowing per millimeter rise in systolic pressure) in the awake subject ranged from 2 to 15.5 msec/mm Hg, and from 4.5 to 28.9 during sleep. Reflex sensitivity was highest in dreaming sleep. In 7 of 10 subjects, baroreflex sensitivity increased significantly during sleep; in 6, the prevailing arterial pressure was inversely correlated wi...

Reflex Regulation of Arterial Pressure during Sleep in Man: A Quantitative Method of Assessing Baroreflex Sensitivity

https://www.gastrojournal.org/article/S0016-5085(02)00217-2/pdf

The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats.

The results of neural tracing studies suggest that vagal afferent fibers in cervical and thoracic branches innervate the esophagus, lower airways, heart, aorta, and possibly the thymus, and via abdominal branches the entire gastrointestinal tract, liver, portal vein, billiary system, pancreas, but not the spleen. In addition, vagal afferents innervate numerous thoracic and abdominal paraganglia associated with the vagus nerves. Specific terminal structures such as flower basket terminals, intraganglionic laminar endings and intramuscular arrays have been identified in the various organs and organ compartments, suggesting functional specializations. Electrophysiological recording studies have identified mechano- and chemo-receptors, as well as temperature- and osmo-sensors. In the rat and several other species, mostly polymodal units, while in the cat more specialized units have been reported. Few details of the peripheral transduction cascades and the transmitters for signal propagation in the CNS are known. Glutamate and its various receptors are likely to play an important role at the level of primary afferent signaling to the solitary nucleus. The vagal afferent system is thus in an excellent position to detect immune-related events in the periphery and generate appropriate autonomic, endocrine, and behavioral responses via central reflex pathways. There is also good evidence for a role of vagal afferents in nociception, as manifested by affective-emotional responses such as increased blood pressure and tachycardia, typically associated with the perception of pain, and mediated via central reflex pathways involving the amygdala and other parts of the limbic system. The massive central projections are likely to be responsible for the antiepileptic properties of afferent vagal stimulation in humans. Furthermore, these functions are in line with a general defensive character ascribed to the vagal afferent, paraventricular system in lower vertebrates.

Functional and chemical anatomy of the afferent vagal system.

Although a number of studies has been made on the distribution of nerve fibres in the vagus and its branches (Ranson, Foley & Alpert, 1933; Heinbecker & O'Leary, 1933; DuBois & Foley, 1936; Foley & DuBois, 1937; Daly & Evans, 1953; Evans & Murray, 1954a), few observations have been reported of differential sensory and motor counts in the nerve. DuBois & Foley (1936) determined the proportion of sensory and motor fibres in some of the cervical branches of the vagus. In a later paper (Foley & DuBois, 1937) they demonstrated that in the vagus nerve above the nodose ganglion in the cat the sensory group constituted 65-80% of the total fibre count. Daly & Evans (1953) studied the effects of electrical stimulation of the caudal cut end of the cervical vagus nerve in the cat after chronic division at various levels. Their results indicated that the motor functions of the vagus to the heart and bronchial musculature are conveyed by myelinated fibres, 2-4,u in size, and also by non-myelinated fibres. Large numbers of myelinated fibres of all sizes (1-14 ,u) and non-myelinated fibres in the thoracic vagus and its cardiac and bronchial branches survive chronic intracranial vagotomy and are therefore afferent in function. A similar study was made in the rabbit by Evans & Murray (1954 a). In this species, the motor functions of the vagus to the lungs are served almost entirely by non-myelinated fibres; afferent fibres are composed of myelinated fibres of all sizes (1-12,) and by a few non-myelinated fibres. These authors demonstrated further that the vagus nerves as they enter

Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat

It is well known that hypoxia causes tachycardia, but there is no general agreement as to the mechanism of this effect. Some workers have assumed it to be the result of a reflex arising from stimulation of the carotid body and aortic arch chemoreceptors (Asmussen & Chiodi, 1941; von Euler & Liljestrand, 1942; Whitehorn, Edelmann & Hitchcock, 1946; Dripps & Comroe, 1947; Alveryd & Brody, 1948), despite there being a number of conflicting reports of the effects of stimulation of the chemoreceptors on heart rate. Stimulation of the carotid bodies by various drugs injected into the common carotid artery of spontaneously breathing dogs caused bradycardia (Heymans, Bouckaert & Dautrebande, 1931 a, b; Heymans, Bouckaert, von Euler & Dautrebande, 1932; Heymans, Bouckaert, Farber & Hsu, 1936; Comroe & Schmidt, 1938; Heymans & Bouckaert, 1941), but perfusion of the carotid sinus region using Ringer's solution with either a high CO2 content or a low pH resulted in tachyeardia (Heymans, Bouckaert & Dautrebande, 1930; Heymans, Bouckaert & Samaan, 1935). More recently, Bernthal, Greene & Revzin (1951) excited the carotid bodies by hypoxic blood and found variable effects on heart rate. In every case chemoreceptor stimulation, whether by drugs, Ringer's solution or hypoxic blood, caused reflex hyperpnoea. On the other hand, in dogs in which the rate and depth of respiration were controlled by a pump, stimulation of the carotid bodies by either hypoxic or venous blood invariably caused bradycardia (Bernthal et al. 1951; Daly & Daly, 1957). In the cat Landgren & Neil (1952) found that stimulation of chemoreceptors by local application of various drugs to the carotid bodies invariably caused hyperpnoea, hypertension and tachycardia. In subsequent experiments, in which carotid body perfusion techniques were used, Neil (1956) showed that the tachycardia which occurs in systemic hypoxia was not the result of stimulation of the carotid body chemoreceptors.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1958.sp006092

The effects of stimulation of the carotid body chemoreceptors on heart rate in the dog.

It has been shown previously that stimulation of the carotid body chemoreceptors in dogs breathing spontaneously causes variable changes in heart rate (Bernthal, Greene & Revzin, 1951; Daly & Scott, 1958, 1959, 1962). A detailed study revealed that the change in heart rate was dependent upon at least two mechanisms. The first of these is a primary cardiac reflex arising from the chemoreceptors themselves, which causes slowing of the heart. The other mechanism was identified as occurring secondarily to the concomitant reflex increase in respiratory minute volume and causes an increase in heart rate. This secondary effect is due, at least in part, to a stretch reflex from the lungs and to a lowering of the arterial blood PCO2, and may be excluded by maintaining pulmonary ventilation constant by means of a pump (Daly & Scott, 1958, 1959). When pulmonary ventilation is maintained constant in this way during chemoreceptor stimulation, the primary cardiac reflex response becomes apparent (Daly & Scott, 1958). The purpose ofthe present investigation was to discover the mechanisms by which the primary cardiac response was brought about and to make observations on the changes in vascular resistance resulting from stimulation of the carotid bodies. Our results have been reported briefly elsewhere (Daly & Scott, 1961, 1962).

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1962.sp006950

An analysis of the primary cardiovascular reflex effects of stimulation of the carotid body chemoreceptors in the dog.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1954.sp005143

Observations on the volume of blood flow and oxygen utilization of the carotid body in the cat.

As far as we are aware there have been no previous reports in the literature concerning the effect of reflexes from the carotid body chemoreceptors on cardiac output. We have recently carried out such an investigation in the anaesthetized dog and in the first part of the paper the results obtained both in animals breathing spontaneously and ventilated artificially are described. Some of the mechanisms responsible for the observed cardiovascular responses in the two types of preparation were also studied, and these are described in subsequent sections of the paper. Some of our results have been reported briefly elsewhere (Daly & Scott, 1959, 1963).

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1963.sp007051

M. de Burgh Daly

Papers

Functional and histological studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera in the cat

The effects of stimulation of the carotid body chemoreceptors on heart rate in the dog.

An analysis of the primary cardiovascular reflex effects of stimulation of the carotid body chemoreceptors in the dog.

Observations on the volume of blood flow and oxygen utilization of the carotid body in the cat.

The cardiovascular responses to stimulation of the carotid body chemoreceptors in the dog