Lysle H. Peterson

Mechanical Properties of Arteries in Vivo

Methods have been assembled permitting the simultaneous recording of intra-arterial pressure and arterial diameter with sufficient accuracy so that the mechanical properties of arteries in vivo, under physiologic conditions, can be derived. The analysis necessitates finding the relationships between 5 simultaneous variables; hence the data were recorded on magnetic tape and processed by analog and digital computer technics. Analysis of the data established the fact that the mechanical properties of arteries can be described by a linear, first-order differential equation whose coefficients can be defined as the moduli of elasticity and viscosity. Furthermore, the magnitudes of the coefficients were evaluated. The strain which the arteries undergo as a result of arterial pulse pressure variations is normally between 0.01 and 0.04, i.e., between 1 and 4 per cent change in circumference. The total strain associated with marked constriction and dilation does not usually exceed 10 per cent. Therefore, it is established that the circumferential motion of arteries may be characterized as small strain. The fact that the strain is effectively small is confirmed by analytical consideration, i.e., stress-strain relationships can be linearized under physiologic conditions without introducing significant error. The mass of the artery wall does not play a significant role in determining the mechanical behavior of the arteries and can therefore be neglected in any such considerations. The harmonic content, i.e., the frequency spectrum, comprising the pressure and diameter pulsations associated with the cardiac cycle have been evaluated by Fourier analysis. The magnitudes of the coefficients relating pressure and strain are: elastic (Ep) varies from 1,000 to 6,000 Gm./cm.2 (with the exception of a value of 500 in the thoracic aorta of a 12-week-old puppy), viscous (Rp) from 10 to 150, and mass (Mp) from 0.0002 to 0.005. The magnitudes of the coefficients vary from individual to individual, from one site to another within the vascular tree and temporally in response to vasoactive factors. The effects of epinephrine, norepinephrine, acetylcholine and autonomic nerve stimulation on the mechanical properties and behavior of arteries are discussed. The differences between the pressure-strain relationships and the wall tension-strain relationships are discussed, since the mechanical properties of the wall material itself is not given directly by the pressure-strain relationships, i.e., radius and wall thickness must be considered. An analytical discussion is developed and mathematical equations are derived which relate pressure, wall tension, radius, strain, elasticity, viscosity and inertia in a tube which has been shown to be a reliable model of the living artery. It is concluded that the concept that the arteries function as a “peripheral heart,” i.e., rhythmically contract in synchrony with the heart, is not justified. Probable relationships of these properties to the structure and functions of the arterial system are discussed.

The Dynamics of Pulsatile Blood Flow

The theory of dynamic fluid motion involving the forces manifested by mass, acceleration, viscous friction and vessel wall tension have been considered and studied when arterial blood flow and pressure are pulsatile. These studies and considerations have resulted in the conclusion that arterial blood pressure is dependent upon all of these parameters and that the relationship of pressure and flow is more complex and nonlinear than heretofore generally believed.

A Technic of Vascular Catheterization with Small Plastic Catheters Its Utilization to Measure the Arterial Pulse Wave Velocity in Man

A method of vascular catheterization is presented in which small polyvinyl catheters are introduced into peripheral vessels through 18 to 21 gage needles and then advanced into the central vascular bed. This technic has been utilized in the study of hemodynamic events occurring in the central arterial vessels in man. The results obtained from 31 arterial catheterizations done in 21 subjects are reported. Utilizing this technic, it has been impossible to catheterize the pulmonary artery in man. However, the method has proved useful in the study of right atrial and central venous pressure changes.

Water and Electrolyte Content of Normal and Hypertensive Arteries in Dogs

This study was designed to establish values for the water and electrolyte content along the arterial tree in the dog under normal conditions and to determine how the normal electrolyte pattern was altered in renal hypertension. Determinations of vessel wall water, potassium, sodium, and chloride contents have shown that the water and electrolyte contents from the various sites along the arterial tree differ significantly from each other. Total water and potassium contents decrease progressively from the ascending aorta to the femoral and carotid sites, while the sodium and chloride contents showed the opposite trend. These differences were significant statistically. These trends may not persist along the entire vascular tree to very small arteries, as indicated by analysis of mesenteric arterial samples. Studies of vessel wall inulin space supported the view that these differences result from the relative distribution of cellular and noncellular material; thus the proximal aorta contains a relatively greater proportion of cellular (smooth muscle) material than more distal sites such as the femoral and carotid arteries. A review of the literature further supports these findings. In experimentally induced renal hypertension the same trends persist along the aorta, but the total water and sodium contents are significantly elevated at all sites.

Physical Factors Which Influence Vascular Caliber and Blood Flow

1. The radii of blood vessels constitute their major biological functions. 2. The radii of blood vessels are abnormally reduced in most forms of hypertension. 3. The radii of blood vessels are determined by distending pressure and by the geometry and stiffness of the wall material. The latter two factors determine the vessel tone. Thus, tone is defined by those factors which determine vessel radius with respect to distending pressure. 4. It is now possible to measure simultaneously the distending pressure and the factors which determine tone, as well as the radius of vessels. Thus, it is possible to quantitate the factors which determine vascular tone: elastic stiffness (E), viscous stiffness (R), radius (r), and wall thickness (8). 5. These factors have been studied in intact dogs, and the tone of the major vessels of the vascular tree has been mapped out. 6. As the vessel wall itself becomes stiffened, compensatory changes may occur in the geometry. As the vessel dilates and thins, the r/8 ratio enlarges, and the vessel becomes relatively more distensible. 7. Little is known about the changes within the vessel wall which are associated with the mechanical properties of the wall, such as smooth muscle, connective tissue, water and electrolyte concentrations and distributions, the nonhomogenous aspects of the tissue components, or the extent of isovolumetric considerations that are applicable. 8. One of the most challenging aspects of cardiovascular research is to define appropriately and measure the factors mentioned above. They certainly represent part of the key to understanding the etiology and development of hypertension.

Effect of Interaction of the Hypothalamus and the Carotid Sinus Mechanoreceptor System on Renal Hemodynamics in the Anesthetized Dog

The purpose of this investigation was to show how the operating characteristics of the reflex having carotid sinus pressure as an input and renal pressure and flow as an output are modified by graded stimulation of the posterior hypothalamus. Consequently, the effects of graded stimulation of the posterior hypothalamus on renal hemodynamics were investigated in the anesthetized dog. The carotid sinuses were isolated and subjected to controlled pulsatile pressures. In general, discrete stimulation of the hypothalamus caused a frequency-dependent increase in renal impedance, and stimulation of the carotid sinus caused a decrease. Concomitant stimulation of the hypothalamus and the carotid sinuses had a significant, nonalgebraic effect on the d-c impedance (renal resistance) but no effect on renal impedance at high frequencies. Hypothalamic stimulation modified the sensitivity of renal resistance to carotid sinus pressure. This reflex sensitivity to hypothalamic stimulation passed through a single maximum. The estimated characteristic renal impedance varied inversely with carotid sinus pressure due to active vasomotor changes in renal vascular mechanical properties, rather than to passive effects of concomitant blood pressure changes.

Systems Behavior, Feed-back Loops, and High Blood Pressure Research

A major challenge to those investigating the etiology and progress of hypertension, as well as of other diseases, results from the fact that the control and regulation of most bodily functions are comprised of multiple feedback loops involving many bodily “systems.” Thus, mechanisms which seem to offer clues as to the etiology of an abnormality, when investigated as an isolated function, fail to explain the etiology when sought in the intact experimental animal or patient. Examples of simple closed-loop systems are described to illustrate the effects of feed-back. A simplified diagram of several factors known to play a role in the control and regulation of the characteristies of the blood vessel wall is described to illustrate the multiplicity of the feed-back pattern which probably occurs. Furthermore, it is evident that almost none of the factors which constitute the loops have been evaluated sufficiently to permit characterization of the system. It is not surprising that apparently promising clues turn out to be disappointing and to become lost in the system. The medical investigator must learn to deal with methods of analyzing systems containing multiple factors and functions as well as to characterize the properties and behavior of the parts of the system.

Symposium on regulation of the cardiovascular system in health and disease: regulation of blood volume.

IS THERE any evidence that the blood volume is regulated? Or, put more specifically, is there any evidence that signalling systems, nervous or hormonal, respond to changes in the optimal level of blood volume and bring into play mechanisms that restore the blood volume to optimal levels? By examining what is known of the factors controlling blood volume we may see if any answer can at present be given to this question. Table 1 shows that the average healthy adult man has about 2 liters by volume of red cells (in number about 2 X 1013) and 3 liters of plasma. In a given healthy adult these values remain fairly constant, rarely varying by more than 5 to 10 per cent about a mean value over periods of weeks or months. Table 1 also shows approximate estimates for the volume of the red marrow. It has beenl calculated that the red marrow contains about 7 x 1011 red cell precursors, or approximately 3 per cent of the number of the circulating red cells.2 Many of the precursor cells, however, are a good bit larger than the mature red cell, so that, at a guess, we may take the volumes of the red cell precursors in the bone marrow to be about 5 per cent of that of the eirculating red cells. This volume is only a small fraction of the red cell volume.

Dispersion of Blood Pressure and Heart Rate in Essential Hypertension

The dispersion of the cardiovascular control system variables of heart period, systolic and diastolic blood pressure in a group of resting essential hypertensives has been compared with a group of normotensive subjects. Controlled variable dispersion in the absence of external perturbation was considered to be a measure of short term cardiovascular control system offset (error) from reference values (setpoint). The high blood pressure group demonstrated a greatly decreased controlled variable dispersion compared with the normal, implying the operation of a control system having a high closed loop gain, low system error and poor stability secondary to perturbation or stress. The extent of the changes in control system performance in essential hypertension was reduced by the adrenergic neuron blocking agent, guanethidine. These conclusions are consistent with and are discussed in relation to the known dynamic responses of heart rate and blood pressure to stress, together with the pathophysiology of the forward and feedback pathways of the cardiovascular control system, in essential hypertension.

Automation in Medicine

Health institutions appear to be ripe for automation. Acquisition, storage and utilization of medical information are almost entirely manual, and the cumulative experience of medicine is disseminated largely by preceptorship. The “systems approach” should and will be adapted to medicine. Computers will not replace physicians but they will effect major improvements in patient care, education, research and institution management.