Towards the sensory nature of the carotid body: hering, de castro and heymansdagger

Abstract

The carotid body or glomus caroticum is a chemosensory organ bilaterally located between the external and internal carotid arteries. Although known by anatomists since the report included by Von Haller and Taube in the mid XVIII century, its detailed study started the first quarter of the XX. The Austro-German physiologist Heinrich E. Hering studied the cardio-respiratory reflexes searched for the anatomical basis of this reflex in the carotid sinus, while the Ghent School leaded by the physio-pharmacologists Jean-François Heymans and his son Corneille focussed in the cardio-aortic reflexogenic region. In 1925, Fernando De Castro, one of the youngest and more brilliant disciples of Santiago Ramón y Cajal at the Laboratorio de Investigaciones Biológicas (Madrid, Spain), profited from some original novelties in histological procedures to study the fine structure and innervation of the carotid body. De Castro unravelled them in a series of scientific papers published between 1926 and 1929, which became the basis to consider the carotid body as a sensory receptor (or chemoreceptor) to detect the chemical changes in the composition of the blood. Indeed, this was the first description of arterial chemoreceptors. Impressed by the novelty and implications of the work of De Castro, Corneille Heymans invited the Spanish neurologist to visit Ghent on two occasions (1929 and 1932), where both performed experiences together. Shortly after, Heymans visited De Castro at the Instituto Cajal (Madrid). From 1932 to 1933, Corneille Heymans focused all his attention on the carotid body his physiological demonstration of De Castro's hypothesis regarding chemoreceptors was awarded with the Nobel Prize in Physiology or Medicine in 1938, just when Spain was immersed in its catastrophic Civil War.

Keywords: baroreceptor; blood circulation; carotid body; chemoreceptor; history of neuroscience; nobel prize; physiology; respiratory reflex.

Figure 1

De Castro describes fine structure of the carotid body in detail (1926). Original drawings from Fernando De Castro included in his first publication on the innervation of the carotid region (De Castro, 1926). (A) Arrival of the inter-carotid nerve (branch of the glossopharyngeal nerve; (c) to the carotid body (d) of a young human. Within the carotid body, different glomeruli with fine innervation can be identified, as well as sympathetic microganglia (e). (B) Illustration of the glomus caroticum of the young human. Glomic cells (coloured nuclei) are surrounded by sensitive innervation surrounds, but these fibres do not form a closed plexus is not formed around the carotid body.

Figure 2

De Castro describes fine structure of the carotid body in detail-II (1926). As in the previous figure, these are Fernando De Castro's original drawings from his first publication on the innervation of the carotid region (De Castro, 1926). (A) Illustration of the carotid body, where different glomeruli are close to the carotid artery (A). Incoming sympathetic nerve from the superior cervical ganglion (E) is a minor contribution to the innervation of the carotid body. The same can be said about the vagus nerve (LX) in the vicinity of the carotid body. By contrast, the most relevant contingent of afferents comes from the intercarotid nerve (C), branch of the glossopharyngeal nerve (IX). A sympathetic microganglion can be seen within the latter nerve (cg). (B) Detailed illustration of one of the sympathetic microganglia observed within the intercarotid nerve [see (A) and Figure 1A].

Figure 3

De Castro's detailed description of the baroreceptors in the carotid sinus (1928). Fernando De Castro's original drawings from his second publication on the innervation of the carotid region (De Castro, 1928). (A) Illustration of a type I (diffuse) baroreceptor close to the adventitia of the artery from a young human, stained with methylene blue. (B) Detailed illustration of a type II (circumscribed) baroreceptor of the human carotid sinus, stained by silver impregnation. The myelin trunk is marked by A. (C) Schematic distribution of the baro-receptors in the human carotid sinus. The symbols identify dense terminals in an increasing scale (o,+,>). The section of the artery (B) illustrates how the sensitive terminals are situated in the thinner part of the arterial wall. (D) Distribution of baroreceptor fine terminals (b,c) intermingled with the collagen fibres [in diffuse grey, (a)]; this allows to detect the changes in volume of the blood vessels. In some cases, these nerve terminals form a meniscus.

Figure 4

Corneille Heymans reflects on the work of Fernando De Castro on the innervation of the carotid sinus and carotid body. (A) Letter dated the 28th March 1929, in which Heymans invites Fernando De Castro to share experiences at his laboratory at Ghent University. The letter was sent to “Chez Lagoubie, La Roche-Chalais, Dordogne” (see envelop in upper-right corner), the family name of De Castro's French brother-in-law where the Spanish histologist was staying for a few days after the meeting of the Association d'Anatomistes held in Bourdeaux (France; see text, for details). (B) De Castro's sketch showing two dogs in parabiosis (the famous physiological technique in which the Heymans –father and son- were consumed masters). The hand-written notes (in Spanish) complete the information about this experiments. (C) Letter from Heymans, dated 12th May 1930, in which he asks Fernando De Castro whether he can visit him at his laboratory in the Cajal Institute (Madrid) during his stay in Barcelona along the entire month of June, where he had been invited to teach. (D) Photographic portrait of Fernando De Castro (circa 1926), reflecting the aspect of the Spanish neurohistologist at the time of his studies on the innervation of the carotid body and sinus.

Figure 5

The long friendship of Corneille Heymans and Fernando De Castro. (A) Letter from Heymans, dated 29th December 1939, in response to a previous letter from Fernando De Castro (dated 15th December 1939) where he congratulated the Belgian physio-pharmacologist for the award of the Nobel Prize in Physiology or Medicine. (B) Picture of the 1939 portrait of Corneille Heymans, dedicated to De Castro (see hand-writing in blue at the bottom-right corner of the image); Fernando De Castro kept this dedicated picture on his bureau until he died in 1967. (C) De Castro prepared to perform one of his famous and complicated nerve anastomosis in a cat; note the precarious conditions of his laboratory in Madrid (circa 1941). (D) Part of a big type II baro-receptor (stained with methylene blue), original drawing from De Castro published in his first paper once the Spanish Civil War finished (De Castro, 1940).