A Brief History of Arterial Blood Flow—From Harvey and Newton to Computational Analysis

View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector CLINICAL RESEARCH STUDIES From the Southern Association for Vascular Surgery Presidential address: A brief history of arterial blood flow—from Harvey and Newton to computational analysis Joseph P. Archie, Jr, PhD, MD, Raleigh, NC My education and interests have always pointed toward ships, and of fluids moving through vessels, like arterial fluid mechanics both as a researcher and as a clinical vascu- blood flow. The basis of solving these problems lies in lar surgeon trying to restore or maintain arterial blood accurately determining fluid flow patterns near solid walls. flow. In 1970 to 1971 I was a research fellow at the These problems are defined by physical laws represented Cardiovascular Research Institute of the University of by differential equations that have been known for cen- California Medical Center, San Francisco. The director of turies. Computational analysis, a numerical method of the Institute, Julius Comroe, wrote a small book entitled solving these equations, was developed years ago, awaiting Retrospectroscope: Insights Into Medical Discovery,1 in which the advent of high-speed computers to do the work. he makes a strong case for basic science research leading to When pulsatile flow in an arterial segment is smooth unexpected important findings, as opposed to targeted and undisturbed, the probability of myointimal hyperpla- research. The first correct description of human circulation sia, thrombosis, or atherosclerosis developing is low. The was given almost 400 years ago by William Harvey. During converse is true in segments that have disturbed flow. this same period the laws that govern physical science in These adverse hemodynamics are characterized by recircu- general and blood flow in particular were formulated lation zones, flow separation and reattachment, vortex mathematically by Isaac Newton. My retrospectroscope is propagation, and prolonged near-wall blood particle resi- a brief history of the basis of and advances in our knowl- dence times. Disturbed flows or nonuniform hemody- edge of arterial blood flow from the time of Harvey and namics produce both abnormally high and low arterial Newton to the present. Fundamental discoveries centuries wall shear stresses and high wall shear stress gradients. ago have come full circle to contribute to current vascular These stresses may trigger a cascade of adverse biological surgical knowledge and research. events in the arterial wall that may lead to the local devel- In the past few decades there have been major opment of myointimal hyperplasia, new or recurrent ath- advancements in unraveling the complexities of vascular erosclerosis, or thrombus formation. Although systemic biology. Understanding of the intricate characteristics of risk factors are involved in the development of arterial dis- arterial blood flow and the way in which they interact with eases, local flow-induced arterial wall forces also play a and contribute to vascular diseases is rapidly evolving. major role. With the advent of arterial repair, endarterec- During the 25-year history of this society there have been tomy, bypass grafts, and angioplasty and stenting we as major advances in vascular surgery. At the same time there vascular surgeons have some control over arterial geome- has been revolutionary progress in solving complex prob- try and therefore the way in which blood flows through lems involving the analysis, design, and optimization both them. Optimizing hemodynamics through design of arte- of solid bodies moving through fluids, such as aircraft and rial reconstructions is a realistic and valid application of the principles of fluid mechanics. Predicting native arteries at From the Carolina Cardiovascular Surgical Associates and The Department risk for developing atherosclerosis because of their geo- of Mechanical and Aerospace Engineering, North Carolina State metric-induced adverse hemodynamics is a potentially use- University. ful application of blood flow analysis. Competition of interest: nil. J Vasc Surg 2001;34:398-404. THE 17TH CENTURY: HARVEY AND Reprint requests: Joseph P. Archie, Jr, PhD, MD, Carolina Cardiovascular Surgical Associates, PA, 3000 New Bern Avenue, Suite 1100, Raleigh, NEWTON. NC 27610. William Harvey (1578-1657) was educated in astron- Copyright © 2001 by The Society for Vascular Surgery and The American Association for Vascular Surgery. omy, mathematics, biology, and medicine at Padua. While 0741-5214/2001/$35.00 + 0 24/6/116108 Harvey was a student there, Galileo was the professor of doi:10.1067/mva.2001.116108 astronomy. However, it is unclear what influence he had on 398 JOURNAL OF VASCULAR SURGERY Volume 34, Number 3 Archie 399 Harvey.2 Galileo was a proponent of the Copernican system way for Newton, his laws were mathematically verifiable of the universe, which held that the planets were in circular with their data. To do this he had to invent a new complex orbits about the sun. This concept was at odds with church mathematics: calculus. When the Principia was published, doctrine that our planet was the center of the universe. Isaac Newton was the Lucasian Professor at Cambridge Being within Rome’s jurisdiction, Galileo was twice taken University, a much valued position he assumed at the age before the Inquisition and accused of heresy. He acquiesced of 28 after an astonishing ascension up the academic lad- both times, publicly renouncing Copernicanism. William der. Stephen Hawking, generally regarded as the most Harvey fared much better after returning home. England brilliant theoretical physicist since Einstein, has held this was free from church dogma, and with the resumption of post for the past two decades. While leading scientists of the acceptance of human dissection he turned his attention his day quickly recognized and understood Newton’s laws to physiologic deductions that were based on anatomic and mathematics, they were difficult for many to grasp. studies. In 1616 at the age of 38 he delivered a lecture to On seeing Newton on the Cambridge campus, a student the College of Physicians in London in which he described is reported to have said to his colleague “there goes a man the circulation to be driven by the heart with blood flowing who has written a book that even he doesn’t understand.” from the arteries to the veins in a “circular” manner.3 He Early in his career Newton was quite introverted and deduced this in part from his observation that venous valves worked alone with the help of an assistant. To my surprise, open toward the heart. This correct concept of the circula- he spent much time studying alchemy.5 He had an unusual tion was quite different from the Galen principle that had interest in blood, and his favorite color was red. Newton been accepted for more than 1400 years. Blood was was not a pleasant man. He was single-minded, was vin- thought to be produced in the liver and travel to the vari- dictive, was defensive, and carried on bitter disputes with ous organs and tissues through the veins where it was used other scientists. in some way, but not recirculated. Harvey postulated that Newton’s laws define velocity and acceleration, as well there were porosities in both the lungs and the systemic tis- as the concept of mass, force, and gravity. Set in mathe- sues that allowed passage of blood. Capillary beds were matical form they provide direct proof of their validity described and microscopically confirmed after his death. On through precisely and accurately predicting the orbits of the basis of anatomical studies of the human heart chamber planets and the paths and rates of projectiles. The two size and heart rate, he estimated resting cardiac output to major contributions of the Principia were the laws of be approximately 4 L/min, low but amazingly close. motion and the calculus, but it also contains a third impor- Harvey had no idea of the function of the lungs. It tant concept: fluid viscosity. Newton clearly saw that the would be another 50 years before Robert Boyle discov- forces necessary to move a fluid were directly proportional ered that lungs oxygenated blood and that oxygen was to the fluid’s velocity gradients. This force is called shear necessary to support life. The ancient Greeks recognized stress, the proportionality constant is the fluid viscosity, that air was vital to life but thought that arteries carried air the law is referred to as Newton’s law of shear, and a fluid and veins carried blood. This concept remained until that follows this law is appropriately called a Newtonian Harvey’s discoveries. A century before Harvey, Michael fluid. Fig 1 is a schematic that illustrates how fluid shear Servetus, a physician and Christian theologian, demon- stress at a point on a vessel wall, or wall shear stress, is strated the change in color of blood from dark to bright defined. The velocity gradient is the reciprocal of the slope red when it traversed the lungs. However, no one acted on of the velocity profile near the wall. In calculus terms this this information for more than a century, almost surely is the first derivative of the velocity near the wall with because it was in conflict with the Galen principle and respect to the radial distance from the wall. Newton’s con- church doctrine. At the age of 42, Servetus was convicted cept of a derivative is to let a finite gradient, such as by the Inquisition and burned at the stake.3 ∆V/∆R in Fig 1, become infinitely small. Thus, in theory, Isaac Newton (1642-1737) published his monumen- if the differential equations that represent Newton’s laws tal work The Principia Mathematica in 1684 at the age of can be solved for the velocities, then the velocities and 44.4 This culmination of more than 20 years of work set shear stresses are known for all locations and times in the down the physical laws of motion, gravity, and force that flowing fluid.

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