The circulatory system appears organized and nowadays we cannot even think of any other way, or mean, or modification of the present system. This circulation not only provides necessary nutrition to the remotest cells but also is responsible for maintaining a temperature suitable for the organism. The whole system runs in a series, i.e., the arterial supply is in direct connection with the returning venous blood with resistors and a pump to maintain a constant flow. During ancient times the assumptions were different, and it was way before the sophisticated investigations were there. Observation, reasoning, and occasional cadaveric dissection were the only tools. Even the great Galen had little exposure to human dissection and surmised or extrapolated from the dissection of macaque monkeys. In or before the Hippocratic times, the Greeks were considered the most knowledgeable in medical matters. The Greeks including Hippocrates till Galen believed that circulation was made up of two systems – arterial and venous. The Greko-Romans also had an astounding idea that sputum and pleural effusions were formed by the brain and Galen forwarded a theory that venous blood was created in the liver and the venous blood crossed over across multiple invisible holes in the interventricular septum in the heart. Numerous peripheral unexplained anastomoses also were involved. Pneuma or air entered the blood via the lung veins and the invisible holes in the septum of the heart allowed admixture. That the arteries contained both air and blood was a belief of the times.
Intestinal digestion and production of nutrients that were carried to the cells by blood were accepted by all. Even before Galen, there was an ancient belief ---
1. The four elements of nature are the earth, wind, fire, and water.
2. These were embodiments of the four primary irreducible qualities, such as hot, cold, dry, and wet.
3. These represented the corresponding humour of the body like the blood, black bile, yellow bile, and phlegm.
4. The humors were food derived.
Diseases represented an imbalance of the humors and treatment was directed at restoration of this balance. There was an intimate relationship with blood that was being circulated. It was believed that the assimilated and absorbed intestinal food was converted into blood in the liver and the veins formed there. Yellow and black bile mixed with blood and were distributed throughout the body. Only a portion of blood entered the heart. The pneuma or air enters the blood in the lungs. In the left ventricle of the heart, which is reached via the invisible pores in the interventricular septum, the blood is mixed with vital spirits, and this arterial blood is distributed to the tissues. The humors, spirits, and heat flowed within the organs according to need and were the main reason behind living qualities. A small portion of arterial blood also went to the brain which underwent further refinement to psychic spirits.
Before Galen
The early historical accounts of heart dissection were recorded by the Greeks and the Egyptians they forwarded an idea intermingled with that of the religious beliefs, magic, and mystical facts. The Egyptians learned from mummification processes and animal dissection due to a religious and cultural ban on cadaveric dissections and understood that as the heart was more or less centrally positioned, it had some important functions. The heart was considered the seat of the soul and a recorder of the deeds of life. It was measured against feathers and lighter the heart, purer the soul of the departed individual. In the living, the Egyptians held the heart in high esteem and considered the heart to be the central organ of thought, emotion, soul, and production of bodily fluids. They also knew that vessels were distributed to the peripheral parts, but they confused them with similar tubular structures and considered these to transport many bodily fluids mixed with pneuma and vital spirits. Egyptians held the centre stage in medical practice from the 19th to 16th century B.C. The Egyptian medical papyri such as the Edwin Smith papyrus, the George Eber papyrus the German Heinrich Brugsh papyrus, etc., all are evidence of how a patient was cared for at that time and the prevailing thoughts and practice. For the next thousand years, no new document was found. By the 6th century, we find temples in Egypt were reconstructed and an adjacent attached “House of Healing” constructed. The priests were secretly taught healing technics and there are no records of how.
There was a lot of intermingling across the Mediterranean, especially between the Egyptians and the Greeks, and it was natural that the latter dominated the scene next.
The ancient Greeks were thinkers and forwarded the Egyptian beliefs further. Before the Hippocratic corpus, other stalwarts pondered circulation. In the Hippocratic corpus, there is a compilation called “On the Heart” that details the topographic anatomy and also mentions the presence of two ventricles as chambers of the heart. There was the mention of veins being distributed throughout the body in other treatises of the Hippocratic corpus, the collections 'On Nutriment” and ‘On Joints'. But these veins originated from the umbilicus and the purpose of their connection with the heart was not explained. Asclepios was considered the first person to possess significant knowledge about the cardiovascular system before Hippocrates organized, systematized, and showed the path to scientific thinking in medicine. After him comes the names of Alcmaen, Empedocles, Diogenes of Apollonia, etc. In the 4th century, the most notable Greek after Hippocrates was Synnesis, of Syria. There was a fierce debate among philosophers about the role of the heart and the brain and it was accepted that while the heart was the soul vascular supply to the brain regulated sleep and associated disorders.
The Greeks also have by this time advanced the name “cardia” for the heart, recognized the two ventricles, discarded Plato's theory that the heart is a knot of veins, and there were two auricles or ear-shaped venous dilatations as the veins approached the heart.
Aristotle’s appearance in the 3rd century B.C. showed a different scene and he was responsible for forwarding the cardio-centric theory. Though he documented extensive dissections in detail, there were some glaring mistakes. He maintained that there were three ventricles, and he was not sure of the position of the heart. He dissected the pulmonary system of vessels also.
The considered golden age for ancient Greek medicine was around the 4th century. The earliest references we have are those of Praxagorus, Aristotle, Herophilus, and Erasistratus. It was ironic that even during these early times Aristotle (340 B.C.) believed that the heart was the centre of all physiological mechanisms and the soul. Blood vessels originated here. Praxagorus around the same time was also able to differentiate between arteries and veins. Herophilus showed arteries had a thicker wall. The lung happened to be a notable exception. Though Erasistratus believed that both arteries and veins originated in the heart, he had also the flawed belief of the time that the arteries were full of pneuma or air. To explain blood coming out of arteries following an accidental prick, the ancient Greeks used to say that it was venous blood moving into arteries via invisible anastomoses. The 'heart' of the body was an innate property and linked intimately to soul and spirit and nature had a hand in it.
Galen was trained with these convoluted beliefs and mystical ideas of soul and spirits. He believed in them. Fitting in the right organ and attributing to it the proper physiological function was difficult at that time. He had good reasoning qualities and tried his best to conform to the vicaries of nature during his life demonstrations. He had his own beliefs and theorized that veins were the main carriers of blood, and they originated in the liver of the organism. He believed that the heart intrinsically pulsates and the lungs during respiration cool the innate heat and produce vital spirits. Pulsation of the arteries was an intrinsic property and the whole-body breaths. No part of the body was pure, and each part had something of a part of pneuma, soul, and vital spirit.
Galen was short on human dissection experience as there was a ban on such procedures. Though the school in Alexandria had permission and Galen was trained there, his experience was not adequate. He could get access only during a gladiatorial death and dissection of barbary monkeys. He mostly depended upon extrapolation from such dissections, reasoning, and imagination. Being the Emperor's physician, he was respected and believed by all.
Early treatment was based on an effort to restore balance. Bloodletting, and application with tightening, were mainstays in treatment procedures with the intent of diverting blood from the affected parts. Medicines were available substances that had observational relief of symptoms and agents hypothesized to have beneficial values.
Galen’s doctrines were followed for centuries. After the fall of the Roman Empire, the Church became powerful, and the religious beliefs of that period reconciled well with Galen’s views. This continued from 500 to 14000 A.D. covering the dark and Middle Ages. Though historically dissection was started in Salerno in the 12th century, human body dissection took off at the University of Bologna in Italy, for the next 3 centuries. Every attempt was directed at fitting the findings to Galen’s teachings.
The oriental practice was concerned with other things and was less interested in heart & circulation. The Arabs & Byzantines had better access to ancient Grecian medical practice and many writings were translated with their input. It was found that the Arab ibn Al-Nafis of Damascus gave the first description of lung circulation in the 13th century. The mere description of circulation to the lung is mired in controversy. Some say that it was Hippocrates who described a lung-based lesser circulation but its intimate relationship with the main circulatory system remains unexplained. They were so engrossed with soul, pneuma, vital spirits, and other mystical things, that a simplified explanation eluded them.
The Muslims and the Arabs had better access to Greek compilations of that time. Even Avicenna, as he is known to the Westerners, integrated the early Greek teachings with that of Galen and mentioned mystical features in his book The Cannon of Medicine. It is recorded that Ibn Al-Nafis of Damascus in the 13th century described pulmonary circulation in detail. Another Syrian, Qusta Ibn Luca drew several figures and tried to show that his fellow countryman was right. The findings of the Spanish physician Michael Servatus, in the 14th century, and the Italian clinician Realdo Colombo at about the same time were incidental independent events. These were difficult times, and the general population was steeped in religious beliefs. Whoever was a non-believer of the ideas of the Church's ideas was burned at the stake. Michael Servatus along with his books suffered the same fate.
Vesalius was responsible for disproving the Galenian belief of invisible pores in the interventricular septum with his dissections on human cadavers. Renaissance occurred during the 14th century and ushered in new ideas and thoughts. It was not until the reign of Charles I and the early 15th century did William Harvey put forward his seminal work on circulation. He was the Lumleian lecturer at the King's College at that time and not only his work was path-breaking, but he also defended it and immortalized it in his book ‘De Motu Cordis et Sanguinis in Animalbus (1628)'. That circulation was continuous and a single system perfusing the whole body was monumentus. All his life he had to defend the idea that the heart acted as a pump and arterial blood is distributed evenly to the periphery and gets cooled before being returned by the one-way valved venous system. He summarised his findings in the 13th chapter of the book and was able to convince others that pulmonary circulation was, in fact, an integral part of the circulatory loop. He was at first not believed by his peers and then he had critics who he answered by performing and documenting experiments. The later book 'Exercitationes Duae Anatomical de Sanguinis, ad Joannem Riolanem, Filum, Parisiensem’ details the response.
It was astonishing to see men blindly following the doctrines of Galen for such a long time. Only some accurate drawings were seen by the great Leonardo da Vinci during the Renaissance period and the dynamics of blood flow were learned. He had his fingers in too many pies and the next notable discovery was of capillaries that connected the arterial and venous systems at the tissue level. Marcelo Malpighi was armed with a microscope and was able to visualize Harvey’s assumptions (1661).
Little happened thereafter and the anatomists recorded their findings as they observed. Leonardo da Vinci was one such keen observer and drew what he saw on dissection. However, Leonardo noticed that “all the veins and arteries arise from the heart. The reason for this is that the maximum thickness found in the veins and arteries occurs at the junction which they make with the heart. The more removed they are from the heart, the thinner they become and divide into smaller branches.”
Harvey’s work still is considered one of the greatest discoveries and he was the first to show a relationship between the heart and the blood that was flowing in the vessels connecting with it. Also, his work enabled physicians to discard mystical ideas about ‘pneuma’ and ‘spirit’. However rare it may be, he was instrumental in showing the possibility of air or gas embolism when introduced into the bloodstream. Harvey was a friend of King Charles I and was allowed dissection of carcasses and observation during the king’s deer hunts. Unifying and schematically linking circulation with the heart was not so easy, but his conviction ultimately made a mark. Further knowledge was acquired by observation and dissection thereafter and the events were experimentally proven and documented.
So now we know that the heart has two ventricles and two atria, i.e., four (4) chambers. The atria are the receiving chambers, and the ventricles eject by muscular contraction to act as a pump and distribute blood throughout the circulatory system. The atrioventricular valves are at the entry of the ventricles and “sigmoid” or semilunar valves prevent backflow into the ventricles. The pulmonary system differs structurally due to the low pressures in the system, and this is a circulatory scheme where venous blood is in the arteries and oxygenated bright red blood is in the veins. Systole is the term for contraction of the heart, and diastole is the period of relaxation. There is an inherent conduction pathway with self-rhythmic signal generation allowing the heart to beat throughout life. Normally atrial contraction precedes ventricular contraction by milliseconds. Otherwise, contraction of the heart is a synchronous process enabling continuous circulation. The usual time taken for a period of a single relaxation and a single contraction is 0.8 seconds. Several events occur in a sequence during the cardiac cycle. In addition to clinical methods, several investigations and tests have evolved to diagnose heart ailments and to see the pathophysiology that may offer prognostic insights. Most of them can be represented graphically. Carl Wiggers, in 1906, was able to combine all the graphical parameters in one diagram in conjunction with the events in the cardiac cycle. This was an attempt basically at describing the normal physiological events and helping in teaching. Around the same period, Willem Einthoven developed doctors’ ability to depict the heart and its parts, functions, and illnesses depicting the magnified view of the inherent electrical activity of the heart. The venous pulse waveforms and simultaneous recording of carotid pulse with a photo-plethysmograph and recording of heart sound with time-event plotting on paper helped in finding out what was happening in a single cardiac cycle. The Wiggers diagram embodies all the available graphical modes and is an accurate testament to what happens during a cardiac cycle.
The Wiggers diagram has ruled for more than a hundred years. It has been a major physiological tool in understanding the function of the heart. Investigations to visualize the beating heart by echocardiography, CT scan, and MRI with further investigative combinations and modifications occurred in the latter part of this millennium. Interestingly enough, none of these find a place in modifications of the Wiggers diagram. The events in a single cardiac cycle may be summarized as follows:
1. Passive atrial filling with venous blood. 2. Atrial contraction in the late phase with the full opening of the atrioventricular valves for driving the blood into the passively filling ventricles. 3. Stretching of myocytes of the ventricles to the limits of Starling’s law. 4. Isovolumetric contraction and the first heart sound due to a closure of the atrioventricular valves. 5. Contraction of left and right ventricular muscle in unison, or systole, to pump blood into the respective systemic and pulmonary circulations. 6. Completion of the forced ejection, or systole, and the 2nd heart sound prevent backflow of ejected blood into the ventricles. 7. Closure of the semilunar or atrioventricular & ventriculoarterial valves is indicated by the 2nd heart sound. 8. Isovolumetric relaxation starts. 9. A small reverberative 3rd heart sound may be audible indicating turbulence of blood in mid diastole. 10. Total diastolic relaxation of the heart before spontaneous initiation of a new cycle.
In 2020 a new Wright diagram has been proposed separately indicating left and right ventricular and atrial cavitary pressure changes in conjunction with the events. This is the Wright’s table and is as follows:
Aristotle is considered the first person to recognize the heart as the central and most important organ of an individual. However, he could not alienate himself from the mystical ideas that surrounded the organ taught at that time. He was accurate as he was bold enough to state that the heart was “the source of all movement since the heart links the soul with the organs of life”. The rhythmical and constant beat of the heart from birth to death was well-known from the very beginning. That the upstroke of the pulse coincides with the contraction of the heart was also well known. Though early Egyptians are credited, this fact was universal, and some clinical practices even emphasized the importance of the pulse examination. The Ayurvedic practice had ‘vayu’, ‘pitta’, and ‘kaph’ as equivalents of the four humours in Western medicine. The pulse was also known as the ’nari’ with a deeper accent to the ‘r’ and the tip of the three fingers was used to examine the pulse. A thorough examination of the pulse and understanding of the physical and mental state of a person together with the ability to predict the course of the disease was considered supreme. The Greeks introduced the term ‘cardia' for the heart and also called the earlike projections, the ‘auricles’ after veins joined the heart. Leonardo da Vinci first recognized that the human heart was four-chambered. The thick-walled ventricles were the actual pumping chambers.
With Harvey’s revolutionary theory of the method of circulation, the horizon opened for the development of techniques for visualization of the beating organ.
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