Brief History of the Cardiovascular System





Who really discovered the circulation of the blood? Although much has been written, the correct answer to this fundamental question remains largely unknown. The early history of the development of understanding of the cardiovascular system may be summarized chronologically as follows:


In 2625 BCE, the Chinese emperor Huang Ti (Nei Ching) realized that the heartbeat and the pulse go together. He may have had some understanding of the circulation of the blood, but evidence of this is lacking.


In 1550 BCE, the ancient Egyptians knew that the heart is the center of the vascular system. But they did not distinguish between arteries and veins. Regarding the pulse as the “voice” of the heart, they developed an extensive pulse lore.


In 330 BCE, Praxagoras of Cos first distinguished between arteries and veins. This distinction was further developed by his student, Herophilus of Alexandria, Egypt, about 300 BCE.


In approximately 330 BCE, Aristotle (Aristoteles) ( Fig. 1.1 ) discovered the cardiovascular system . Aristotle, the tutor and friend of Alexander the Great, was the first to realize that the heart sits at the center of a system of arteries and veins. Aristotle understood that both the arteries and the veins arise from the heart. Prior to that time, the veins were thought to originate from the liver. Aristotle said that the heart normally has three cavities (ventricles), apparently because he did not regard the right atrium as a cardiac chamber. Instead, he interpreted the right atrium as a dilatation of the great vein—our superior and inferior venae cavae.




Fig. 1.1


Aristotle (384–322 BCE) discovered the cardiovascular system about 330 BCE. Born in Stagira, Macedonia, he studied under Plato at the Academy (367–347 BCE), tutored Alexander the Great at the Macedonian court (342–339 BCE), and opened his own school, the Lyceum, in Athens (335 BCE). His was also called the Peripatetic school because of his practice of lecturing in the Lyceum’s covered portico or walking place (peripatos). Aristotle was a one-man university for the Athenians, the Arabs, the Jews, and later for the medieval Europeans.


In 300 BCE, Herophilus and Erasistratus of Alexandria saw chyliferous vessels in the mesentery of sheep. Erasistratus discovered that the heart is a pump. He was also the first to describe and name the tricuspid and bicuspid (mitral) valves. However, Erasistratus thought that the arteries contain air (which they do at autopsy, because the blood tends to drain into the more distensible veins). This erroneous concept impeded the discovery of the circulation of the blood.


In 25 CE, Rufus of Ephesus named what we call the base of the heart the “head” of the heart. He observed that on each side of the head of the heart there are soft, hollow, wing-like things that pulsate; he called them the “ears” of the heart because they were on both sides of the head of the heart. “Ears” in Latin is “auriculae,” which became auricles in medical English. So Rufus realized that the right atrium is indeed part of the heart because it beats, and he was the first to distinguish between auricles and ventricles.


In about 190 CE, Claudius Galen ( Fig. 1.2 ) of Pergamos in Asia Minor showed that arteries contain blood, not air, as had been previously thought. Galen believed that arterial blood is admixed with air, resulting in aerated (spirituous) blood, as opposed to venous blood. Galen contended that venous blood passes from the right ventricle into the left ventricle via invisible pores in the interventricular septum. He also thought that a small amount of blood passes from the right ventricle via the pulmonary artery and lungs into the left heart. So Galen had a partial understanding of the pulmonary (or lesser) circulation.




Fig. 1.2


Claudius Galen (c 130–201 CE) demonstrated that the arteries contain blood, not air as had previously been thought. Artery means air-containing in Greek (Greek arteria , from aer , air + terein , to keep or contain). Galen was a Greek from Pergamos in Asia Minor. After studying in Asia Minor, Greece, and Alexandria, he returned to Pergamos as physician to the gladiators—where no doubt he witnessed spurting arteries. From c 162 CE onward, he resided chiefly in Rome, where he became physician to Emperor Marcus Aurelius and wrote approximately 500 publications. Galen remained the pre-eminent medical authority until the publication by Andreas Vesalius (1514–1564) of De Humani Corporis Fabrica (The Construction of the Human Body) in 1543.


In about 1250 CE, Ibn al-Nafis deduced the existence of the pulmonary (lesser) circulation. , He thought that the pulmonary trunk is too large to be there only for the nutrition of the lungs, and hence he deduced that the blood of the right heart must flow to the left heart via the large pulmonary trunk and the lungs.


In 1505, Leonardo da Vinci ( Fig. 1.3 ) concluded that the human heart has “lower ventricles” (chambers) and “upper ventricles” (chambers) and that the upper chambers have “ears” (auricles). Hence the concept of Rufus of Ephesus concerning the auricles, which the influential Galen had opposed, was finally accepted after a lapse of some 1500 years.




Fig. 1.3


Leonardo da Vinci (1452–1519), Italian painter, sculptor, architect, musician, engineer, and scientist. In 1505, he confirmed the distinction between the upper cardiac chambers (“ventricles”) that have auricles (ears), and the lower cardiac chambers (“ventricles”) that do not have auricles. This distinction between auricles and ventricles had first been made by Rufus of Ephesus in about 25 CE but had been effectively opposed by Galen.

Reproduced from Hemmeter JC. The history of the circulation of the blood. In Hemmeter JC: Master Minds in Medicine. New York: Medical Life Press; 1927:226.


In 1543, Andreas Vesalius ( Fig. 1.4 ) of Brussels, Belgium, in his epochal De Humani Corporis Fabrica , described no openings in the interventricular septum but did not flatly contradict Galen’s dogma of invisible pores.




Fig. 1.4


Andreas Vesalius (1514–1564), Flemish anatomist from Brussels working in Padua, described no openings in the interventricular septum in his monumental work, De Humani Corporis Fabrica (1543). However, he did not flatly contradict Galen’s erroneous dogma of invisible pores in the interventricular septum. Although Vesalius is now widely regarded as the father of modern anatomy and modern medicine, he did not understand the circulation of the blood.

Reproduced with permission from Van Praagh R, Van Praagh S. Aristotle’s “triventricular” heart and the relevant early history of the cardiovascular system. Chest 1983;84:462.


In 1547, Giambattista Canano of Ferrara described a few of the valves in the azygos vein.


In 1553, Michael Servetus (Serveto) rediscovered the pulmonary (lesser) circulation, apparently unaware of the prior work of Ibn al-Nafis. Servetus also denied the permeability of the ventricular septum. At the insistence of Calvin, Servetus was burned at the stake in Geneva, Switzerland, on October 27, 1553, because of his unorthodox views on the Christian Holy Trinity. All but two copies of his 1553 book, Christianismi Restituto (The Restitution of Christianity), were also burned. Calvin is thought to have strongly disapproved of an earlier work of Servetus, De Trinitatis Erroribus libri septum ( On the Errors of the Trinity, in seven books), published in 1531.


In 1555, Andreas Vesalius, in the second edition of his Fabrica, stated that he could not understand how any blood could pass through the ventricular septum. But he deduced no further conclusions from this observation. We (R.V.P. and S.V.P.) a translated much of Book VI of the


a S.V.P. was my dear departed wife, Dr. Stella Van Praagh. She was born in Crete, Greece, and was an expert in ancient Greek. I am an old Latin scholar; we worked together on the translation.

Fabrica in order to see if Vesalius understood that the blood circulates, that is, flows in a circle. No evidence was found that he did.


In 1559, Matteo Realdo Columbo described the pulmonary circulation and the impermeability of the ventricular septum, claiming both as his discoveries.


In 1564, Bartholomaeus Eustacheus discovered the thoracic duct in the horse.


In 1571, Andreas Cesalpinus (Andrea Cesalpino in Italian), the physician and philosopher of Arezzo, first described the circulation of the blood in his Peripateticarum Quaestionum libri quinque ( Of Peripatetic Questions in five books). Regarding the title of his work, it should be recalled that the school of Aristotle (see Fig. 1.1 ) was known as the Peripatetic school. Hence peripatetic questions are scientific and philosophic matters considered in the Aristotelian way.


Cesalpino stated that the blood is in constant transition from arteries to veins in all parts of the body by means of tiny anastomoses that he defined as “vasa in capillamenta resoluta” (vessels resolved into hairlike vessels). This is where our term capillary comes from; capillus means hair (Latin).


Cesalpino coined the term circulatio, by which he meant that the blood flowed in a circle: from the veins to the right heart, then to the lungs, thence to the left heart, and then to the arteries.


Cesalpino also realized that the pulmonary artery is an artery (not a vein, as Galen had said) and that the pulmonary vein is a vein (not an artery, as Galen had stated).


In 1583, Andrea Cesalpino published De Plantis (Of Plants), in which he confirmed his theory that the blood circulates.


In 1593, Andrea Cesalpino published Questionum Medicarum libri II ( Medical Questions in two books) in which he gave experimental proof of the circulation of the blood. These were the same two experiments later used by Harvey :



  • 1.

    Cesalpino observed that when a vein is first divided, dark venous blood comes out, which then becomes lighter and lighter in color, which favored the theory that the blood is circulating.


  • 2.

    Cesalpino also observed that when veins are occluded, they always swell between the ligature and the capillaries, not between the ligature and the heart—as they should if Galen’s concept of centrifugal venous blood flow were correct.



Consequently, as the American physician, linguist, and historian John C. Hemmeter wrote in 1927, to Andrea Cesalpino of Arezzo “belongs the fame of being the first to have recognized and demonstrated the general circulation of the blood.” In 1583, in his outstanding work De Plantis, Cesalpino stated: the blood is led through the veins to the heart, and is distributed by the arteries to the entire body (… sanguiinem per venas duci ad cor, et per arterias in universum corpus distribui ). Cesalpino discovered the circulation of the blood without knowing about the valves in the veins.


In 1598, Carlo Ruini of Bologna published a book on the anatomy and diseases of the horse, in which it is clear that he understood the function of the valves of the heart.


In 1603, Hieronymus Fabricius ab Aquapendente (Fabrizio in Italian) described valves in the entire venous system in his work De Venarum Ostiolis , but he did not understand their function correctly. Fabricius was the tutor of William Harvey at Padua (1598–1602).


In Milan in 1622, Gaspare Aselli observed chyliferous vessels in the mesentery of the dog and called them lactiferous vessels.


In 1623, Paolo Sarpi , the famous theologian and canonist of the republic of Venice, as well as a student and friend of Fabricius, described the function of the venous valves correctly. From this understanding, he deduced the circulation of the blood. Unfortunately, however, the manuscripts of Sarpi in the library of the Servitians at Venice were destroyed in a monastery fire in September 1769. Hence, Paolo Sarpi may be regarded as the second “discoverer” (or first rediscoverer after Caesalpinus) of the circulation of the blood.


In 1628, William Harvey ( Fig. 1.5 ) of Folkestone, Kent, England, described the circulation of the blood in a 72-page book titled Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (Anatomic Experience Concerning the Motion of the Heart and Blood in Animals), and he demonstrated the circulation experimentally. After the publication of his little book at Frankfurt, Harvey was accused of plagiarism by many of his contemporaries (Micanzio, Vesling, Walaens, Riolan, Bartholin, and others). Harvey is now considered to have been the third “discoverer” (or the second rediscoverer, after Sarpi) of the circulation of the blood. Harvey deserves the credit not for discovering the circulation of the blood but for eventually persuading the scientific world, over considerable opposition, that the blood does indeed circulate.




Fig. 1.5


William Harvey of Folkestone, Kent, England, was the third “discoverer” of the circulation (in 1628), after Cesalpino (1571, 1583, 1593) and Sarpi (1623). Harvey deserves the credit for having persuaded the medical world, despite considerable opposition, that the blood does indeed circulate.


In 1648, while a student in Paris, Jean Pecquet discovered the thoracic duct in humans and realized that the lactiferous vessels do not return to the liver but to the thoracic duct and thence to the left subclavian vein.


In 1650, Olaf Rudbeck was a student at Uppsala University when he discovered the lymphatics of the liver and found that they too drained into the thoracic duct.


In 1661, at the University of Bologna, Marcello Malpighi, using a microscope, was the first to observe the motion of the blood in the capillaries of the lung in frogs. Malpighi had discovered the postulated capillaries of Caesalpinus.


In 1771, Lazzaro Spallanzani, again with the aid of a microscope, saw blood flowing in the umbilical vessels of the chick embryo. This was the first direct observation of the circulation of the blood in a warm-blooded animal.


Thus, the normal circulation of the blood and lymph was discovered and documented over approximately 4,400 years from 2625 BCE (Huang Ti; Nei Ching ) to 1771 CE (Lazzaro Spallanzani).


The story of the discovery and documentation of the abnormal circulation of the blood in infants and children is much more recent, being little more than 330 years old. Very largely, this is the history of congenital (as opposed to acquired) heart disease in infants and children.


For example:




  • The anomaly now known as the tetralogy of Fallot was first described by the Danish physician/priest Niels Stensen (1648–86) in 1671, the patient being a macerated stillborn fetus with cervical ectopia cordis.



  • The malformation now known as transposition of the great arteries was discovered and described by Matthew Baillie (1761–1823) of London, England, in 1797. However, by the dawn of the 19th century, congenital heart disease remained mostly unknown. Single left ventricle (LV) with absence of the right ventricular sinus and double-inlet LV was not discovered and reported until 1824 by Andrew F. Holmes (1797–1860) of Montreal, Canada.



  • Corrected transposition of the great arteries was not discovered and reported until 1875 by Carl von Rokitansky (1804–78) of Vienna.



Thus, the seeds of the understanding of congenital heart disease were sown in the 19th century by Thomas B. Peacock, Carl von Rokitansky, E. Théremin, and others. It was in the 20th century that these seeds came to fruition. Many books appeared dealing with different aspects of heart in infants and children—cardiology, radiology, echocardiography, epidemiology, surgery, pathology, embryology, and etiology. Some of these books are listed alphabetically in Box 1.1 .



BOX 1.1

Some of the Books Concerning Heart Disease in Infants and Children That Have Appeared During the 20th Century


Authors and References





  • Abbott ME ,



  • Adams FH, Emmanouilides GC



  • Adams FH, Emmanouilides GC, Riemenschneider TA



  • Albou E, Lanfranchi J, Piton J-L, LeGoubey J



  • Allwork SP



  • Anderson RH, Shinebourne EA



  • Anderson WAD ,



  • Ando M ,



  • Anselmi G, Munoz H, Espino Vela J, Arguello C



  • Arey LB



  • Aziz KU



  • Bailey FR, Miller AM



  • Bankl ,



  • Barratt-Boyes BG, Neutze JM, Harris EA



  • Barth LG



  • Becker AE, Anderson RH



  • Behrman RE, Kliegman RM, Nelson WE, Vaughan VC III



  • Bergsma D, McKusick VA, Neill C, Rowe R, Lindstrom J, Jackson C, Rogers J



  • Berri GG



  • Beuren AJ



  • Bharati S, Lev M ,



  • Bharati S, Lev M, Kirklin JW



  • Bianchi T, Invernizzi G, Parenzan L



  • Bourne GH



  • Boyd W



  • Braunwald E



  • Bremer JL



  • Bucharin VA, Podzolkov VP



  • Burakovsky VI, Bukharin VA, Bockeria LA



  • Cassells DE



  • Castañeda AR, Jonas RA, Mayer JE, Hanley FL



  • Castellanos y Gonzalez



  • Christidès C, Cabrol C



  • Clark EB, Markwald RR, Takao A



  • Clark EB, Takao A



  • Cooley DA, Hallman GL



  • Corone P



  • Cotran RS, Kumar V, Robbins SL



  • Crupi G, Parenzan L, Anderson RH



  • Davies MJ, Anderson RH, Becker AE



  • Davis JA, Dobbing J



  • Davila JC



  • DeHaan RL, Ursprung H



  • De la Cruz y Toyos, Munoz Castellanos L, Espino Vela J, Attie Cury F



  • De Medeiros Sobrinho JH



  • De Vivie ER, Hellberg K, Ruschewski W



  • Donzelot E, D’Allaines F



  • Dordevic BS, Kanjuh VI, Saradnici I



  • Doyle EF, Engle MA, Gersony WM, Rashkind WJ, Talner NS



  • Dupuis C, Kachaner J, Freedom RM, Payot M, Davignon A



  • Edwards JE, Carey LLS, Neufeld HN, Lester RG



  • Edwards JE, Lev M, Abell MR



  • Eldredge WJ, Goldberg H, Lemole GM



  • Elliott LP, Schiebler GL



  • Emmanouilides GC, Riemenschneider TA, Allen HD, Gutgesell HP



  • Engle MA



  • Fawcett DW



  • Feigenbaum H



  • Feldt RH



  • Fenoglio JJ



  • Ferencz C, Rubin JD, Loffredo CA, Magee CA



  • Fitzgerald MJT



  • Fontana RS, Edwards JE



  • Fraser FC, Nora JJ



  • Freedom RM, Benson LN, Smallhorn JF



  • Freedom RM, Culham JAG, Moes CAF



  • Friedman WF, Lesch M, Sonnenblick EH



  • Fyler DC



  • Garson A, Bricker JT, McNamara DG



  • Gasser RF



  • Gasul BM, Arcilla RA, Lev M



  • Giuliani ER, Gersh BJ, McGoon MD, Hayes DL, Schaff HV



  • Godman MJ



  • Goodwin JF



  • Goor DA, Lillehei CW



  • Gould SE



  • Grant JCB ,



  • Gray H



  • Gross RE ,



  • Hallman GL, Cooley DA



  • Ham AW, Leeson TS



  • Hamilton HL



  • Hamilton WJ, Mossman HW



  • Harris P, Heath D



  • Hernández Rodríguez M



  • Hamburger V



  • Hudson REB



  • Hyman LH



  • Jones KL



  • Kahn DR, Strang RH, Wilson WS



  • Keck EW



  • Keibel F, Mall FP



  • Keith JD, Rowe RD, Vlad P



  • Kidd BSL, Keith JD



  • Kidd BSL, Rowe RD



  • Kirklin JW



  • Kirklin JW, Barratt-Boyes BG



  • Kirklin JW, Karp RB



  • Kissane JM



  • Kjellberg SR, Mannheimer G, Rudhe U, Jonsson B



  • Kreutzer EA ,



  • Krovetz LJ, Gessner IH, Schiebler GL



  • Langman J



  • Lansing AI



  • Lev M



  • Lewis T



  • Lieberman M, Sano T



  • Litwin SB



  • Lock JE, Keane JF, Fellows KE



  • Long WA



  • Lozsádi K



  • Lue H-C, Takao A



  • Macartney FJ



  • Marino B, Dallapiccola B, Mastroiacovo P



  • Marino B, Thiene G



  • Markowitz M, Gordis L



  • Mavroudis C, Backer CL



  • McKusick VA ,



  • Meszaros WT



  • Miller SW



  • Minot CS



  • Moller JH ,



  • Moss AJ, Adams FH



  • Moss AJ, Adams FH, Emmanouilides GC



  • Moulaert AJMG



  • Nadas AS



  • Nadas AS, Fyler DC



  • Nebesar RA, Kornblith PL, Pollard JJ, Michels NA



  • Neill CA, Clark EB, Clark C



  • Netter FH ,



  • Neufeld HN, Schneeweiss A



  • Nichols DG, Cameron DE, Greeley WJ, Lappe DG, Ungerleider RM, Wetzel RC



  • Nishimura H, Okamoto N



  • Nora JJ, Fraser FC



  • Nora JJ, Takao A



  • Norman JC



  • Okamoto N



  • Olsen EGJ



  • Ongley PA, Sprague HB, Rappaport MB, Nadas AS



  • Parenzan L, Carcassonne M



  • Patten BM



  • Pearson AA, Sauter RW



  • Perloff JK



  • Pexieder T ,



  • Pierson RN, Kriss JP, Jones RH, Macintyre WJ



  • Pomerance A, Davies MJ



  • Pongpanich B, Sueblinvong V, Vongprateep C



  • Potter EL



  • Potter EL, Craig JM



  • Pugh L



  • Quero Jiménez M, Arteaga Martínez M



  • Rashkind WJ



  • Ravitch MM



  • Robb GP



  • Robb JS



  • Robbins SL



  • Romanoff AL



  • Rosenquist GC, Bergsma D



  • Rowe RD, Freedom RM, Mehrizi A, Bloom KR



  • Rowe RD, Mehrizi A



  • Roberts WC



  • Rudolph AM



  • Rushmer RF



  • Sabiston DC, Spencer FC



  • Sade RM, Cosgrove DM, Castaneda AR



  • Shaher RM



  • Simeunovic SD



  • Smith CA



  • Spitzer A



  • Squarcia U



  • Stark J, de Leval M



  • Starling EH



  • Stewart JR, Kincaid OW, Edwards JE



  • Smith DW



  • Takahashi M, Wells WJ, Lindesmith GC



  • Taran LM



  • Taussig HB



  • Thiene G, Frescura C



  • Tucker BL, Lindesmith GC



  • Tucker BL, Lindesmith GC, Takahashi M



  • Van Mierop LHS, Oppenheimer-Dekker A, Bruins CLDC



  • Van Praagh R, Takao A,


    Van Praagh R, Van Praagh S



  • Venables AW



  • Vince DJ



  • Vlodaver Z, Neufeld HN, Edwards JE



  • Wagenvoort CA, Heath D, Edwards JE



  • Walmsley R, Watson H



  • Watson H



  • Wenink ACG, Oppenheimer-Dekker A, Moulaert AJ



  • White PD



  • Williams RG, Bierman FZ, Sanders SP



  • Williams RG, Tucker C



  • Wolstenholme GEW, O’Connor M



  • Wood P



  • Zimmerman HA


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Aug 8, 2022 | Posted by in CARDIOLOGY | Comments Off on Brief History of the Cardiovascular System

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