Entire Cardiovascular System Research Articles

Mathematical modelling of flow distribution in the human cardiovascular system.

The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

Endothelial cells as part of a vascular oxygen-sensing system: Hypoxia-induced release of autacoids

Higher developed organisms are equipped with many central and local control mechanisms, which enable an adequate blood and oxygen supply to tissues over a wide range of demands. Global adaptive responses include changes in the circulatory and ventilatory system as well as increases in the oxygen carrying capacity of the blood. At the level of the specialized organs there exist additional control systems for the regulation of local blood flow. Most systems make use of highly specialized cells which are able to sense the oxygen partial pressure of the transport medium, blood, and within the tissues. In the past years, it has been shown that the vascular endothelium lining the entire circulatory system can actively modulate the vascular tone and platelet functions by the release of autacoids, among them prostacyclin and endothelium-derived nitric oxide (EDRF). Recent experiments demonstrate that the release of EDRF is PO2-dependent, which suggests that endothelial cells may act as functional local oxygen sensors within the vascular system.

Automatic Adjustment of Pacing Parameters Based on Intracardiac Impedance Measurements

The selection of the parameters used for rate control is determined not only by technical feasibility, but also by patient considerations. Technical feasibility considerations include long-term stability and reliability of the sensor, as well as susceptibility to interference. The patient considerations relate to the patient's physical state, including the various physiological and pathologic conditions. The rate response must be in proportion to circulatory demand. The specificity of the rate response is of particular importance for the patient with low cardiac reserve. The development of future pacemakers aims at providing additional patient benefits, with a reduction of the effort associated with initial parameter selection and patient follow-up. This will be achieved by utilizing a better understanding of the integration of the control mechanisms for the entire cardiovascular system under physiological and pathological conditions. To support the development of the future pacemakers, we must utilize realistic multiparametric models of the cardiovascular system. These models will assist the evaluation of potential algorithms for integrating multisensor signals into a single pacing rate. The parameterization and validation of these models are important issues to be addressed. Intracardiac impedance measurements in conjunction with microprocessor controlled signal processing and improved lead technology provide a great variety of practical applications for physiological control of the pacing rate and the automatic adjustment of pacemaker parameters. The concepts of an "intelligent" pacemaker capable of automatic control in response to changes in the pacing requirements under a variety of physiological and clinical conditions are presented.

Endothelial modulation of coronary tone

T HE VASCULAR endothelium lining as a monolayer the entire circulatory system does not represent a passive diffusion barrier but displays the features of a distributed organ (1 to 1.5 kg) with a variety of biological functions. It serves as an antithrombogenic surface, and it is significantly involved in a well-regulated balance between coagulation and fibrinolysis. To this end its surface contains heparan sulfate and it is able to secrete antithrombin III, prostacyclin, and plasminogen activator. In combination with the negative surface charges of the endothelial glycocalyx, these compounds maintain the fluidity of the blood at the interface between the streaming blood and the vessel wall and prevent red cells from adhering. A number of compounds are synthesized by the endothelium, which may be involved in localized thrombus formation (Table 1). Other important functions comprise the metabolism of norepinephrine (NE), serotonin (5-HT), and adenine nucleotides and the conversion of angiotensin I and bradykinin (Bk) by angiotensin-converting enzyme and other peptidases (Table 2). (See Endothelial Metabolism and its Influence on Vascular Tone.) In spite of the fact that endothelial cells display such a variety of synthetic, secretory, and cleavage functions,’ it was not recognized until 1980 when Furchgott and Zawadzki* made pioneering observations as to how the endothelium exerts a significant role in the modulation of local vascular tone by the release of an endotheliumderived vascular relaxant factor (EDRF) (for recent reviews see references 3 through 7; see also Addendum). In this review we try to summarize recent findings regarding the regulatory function of this endothelium-derived relaxant factor under physiologic and pathophysiologic conditions. In addition, some biochemical properties of endothelial cells that may influence vascular homeostasis and vascular tone are briefly outlined. This role of the endothelium may be especially important in pathophysiologic conditions, when endothelial function is impaired (eg, under arteriosclerotic conditions and during hypercholesterolemia) and its local dilator potential is either reduced or absent. Under such conditions the net balance between dilatory signals from the endothelium, acting indirectly, and direct constrictor impulses affecting the vasculature is disturbed: failure of vasodilation may result in enhanced or excessive local vasoconstriction and spasm, and thus partial or complete ischemia. The decisive role of such an endotheliumdependent vasomotor balance becomes obvious when one considers that the majority of vasoactive agonists (such as [5-HT], histamine, adenosine diphosphate [ADP], adenosine triphosphate [ATP], acetylcholine (ACh), thrombin [Th], vasopressin) display an endothelium-dependent vasodilator activity in addition to a simultaneous direct constrictor effect on vascular smooth muscle. In this context it is surprising that various a-agonists or substances stimulating a-receptors (eg, NE and various ergot alkaloids like ergonovine, which are used to provoke spasm in Prinzmetal patients) exhibit a simultaneous endothelium-dependent dilator component. Consequently, the resultant action on the coronary arterial wall depends on the balance of these two opposing actions (Table 3). EDRF-mediated modulation of vascular tone has been primarily demonstrated in large conductance arteries like the coronaries’ (for review see reference 6), wherein vasomotion does not determine the rate of tissue perfusion unless critical stenoses are present. The role of EDRFmediated vasomotion in resistance vessels, which are responsible for control of tissue perfusion, has not yet been well established, because of difficulties in functionally inhibiting or destroying the endothelium in a defined manner without causing simultaneous damage to the adjacent tissue. The problems caused by increasing overlap with concurrent metabolically induced vasomotion in the microcirculation renders such a quantitative

Ventricular interaction with the loading system.

The purpose of this investigation was to develop a theoretical framework to predict stroke volume (and therefore cardiac output) when the ventricle is coupled with the arterial impedance. The ultimate objective is to arrive at an analytical description of cardiac output in the closed hydraulic loop of the entire circulatory system on the basis of the properties of the major system components. We developed the framework of analysis of ventriculo-arterial coupling by characterizing both the ventricle and arterial system in terms of the end-systolic pressure vs. stroke volume (Pes-SV) relationships. This approach, motivated by the load-insensitivity of ventricular end-systolic pressure-volume relationship (ESPVR), yielded stroke volume as the intersection between the ventricular Pes-SV relationship and arterial Pes-SV relationship. The theoretical outcome was validated by comparing the stroke volume predicted as a result of interaction between a given ventricular ESPVR and a set of arterial impedances against those SVs actually measured by imposing the same arterial impedance on the isolated canine ventricles. Furthermore, because of the mathematical simplicity of this approach, it enabled us to describe cardiac output in the closed circulatory loop with a small set of analytical equations. We conclude that the proposed framework is useful in analyzing the ventriculo-arterial coupling and various mechanisms which affect cardiac output in the closed circulatory loop.

Protective effects of buflomedil against exercise-induced reductions in regional erythrocyte deformability of patients with peripheral arterial disease.

Introduction Increases in blood viscosity may be present in several clinical conditions characterized by regional circulatory insufficiency which develop acutely or chronically (Chien 1972, Dintenfass 1971, Di Perri 1979, Dormandy 1970), such as myocardial infarction or peripheral occlusive arterial disorders (Di Perri et al 1977, Di Perri et al 1978, Forconi et al 1979). Patients with vascular disorders sometimes present a haemorrheological picture' entirely normal when at rest; however, alterations of the rheological parameters may appear in these cases under physical stress, for example during an exercise test in patients with angina pectoris, or while walking in patients with peripheral circulatory insufficiency (Di Perri et aI1977, Forconi et aI1977a, Forconi et al 1977b, Lake & Dintenfass 1975). In all of these situations, a cause-andeffect relationship appears to exist between the increase in blood viscosity and the onset of tissue ischaemia. Thus, definition of a syndrome with secondary blood hyperviscosity, quite different from similar clinical conditions, designated as primary hyperviscosity syndromes can be justified. Primary hyperviscosity syndromes may be induced by a primary increase in the total number of red blood cells (polycythaemic hyperviscosity), by a primary alteration in the internal RBC viscosity (sclerocythaemic hyperviscosity) or by an increase in plasma proteins (plasmatic hyperviscosity) (Wells 1970). Secondary hyperviscosity which develops under ischaemic conditions does not appear to be related to significant changes in the number of erythrocytes or to changes in the other nonerythrocyte rheological parameters, but rather seems attributable to changes in the internal viscosity of the RBC attendant with alterations in RBC deformability and aggregability. The haemodynamic effects of reduced erythrocyte deform ability affect the entire circulatory system, but the most important effects, from a physiopathological viewpoint, are exerted at the microcirculatory level, since the conditions of flow through the capillaries are closely related to the capacity of the RBC to change or deform their shape. A reduced number of perfused capillaries and a slowing of blood flow are consequences of diminished RBC deformability (Chien 1972, SchmidtSchonbein 1976). The ultimate effect of these phenomena is tissue ischaemia, followed by metabolic acidosis with an alteration in vascular regulation and a further deterioration of the rheological picture. Clinical situations of ischaemic vasculopathy exist in which blood hyperviscosity is not always present or, if present, is not pathological. Under these conditions, if the metabolic demands of a vascular region are

Computerized fluoroscopy: New technique for the noninvasive evaluation of the aorta, coronary artery bypass grafts, and left ventricular function

A computerized fluoroscopy system has been developed on the basis of real-time digital processing of x-ray transmission data from traditional image-intensified fluoroscopy equipment. High-quality visualization of any part of the arterial system is obtained following intravenous injection of 0.5 to 0.75 ml/kg of iodinated contrast materials. This report describes the use of this technique to evaluate the aortic arch, left ventricular function, and coronary artery bypass graft patency. Fifty intravenous studies were performed in 25 patients. Among 20 patients with coronary artery bypass grafts, computerized fluoroscopy correctly identified 11 of 15 patent grafts and 11 of 11 occluded grafts as confirmed by standard coronary arteriography in 11 of these patients. Unlike computerized tomography, our technique gives a longitudinal view of the bypass graft much like direct coronary angiography. Aortic arch studies included demonstration of a right aortic arch with a small left subclavian artery, a coarctation, and a normal aortic arch in a trauma patient with a wide mediastinum. Segmental wall motion abnormalities were clearly identified by a modification of the technique which produces a negative outline on the ventriculogram in dyskinetic segments. Ejection fractions may be calculated by determining the amount of iodine in the ventricle in systole and diastole. This technique may also be used to evaluate carotid disease and peripheral vascular disease in patients undergoing coronary artery bypass procedures. Computerized fluoroscopy, therefore, allows evaluation of the entire cardiovascular system by the relatively noninvasive technique of intravenous angiography.

Structurally reduced distensibility of cardiovascular low-pressure' compartments in primary hypertension, as studied in spontaneously hypertensive rats (SHR).

Adult male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared to explore to what extent venous "unstressed" volume, compliance and wall distensibility are structurally altered in primary hypertension. The perfused, maximally vasodilated hindquarters and the entire, completely relaxed cardiovascular system during cardiac arrest were used for comparisons of "initial" volumes and pressure volume characteristics of the respective low-pressure compartments. In both preparations SHR and WKY showed identical "unstressed" venous volumes, computed by extrapolation to zero pressure from initial volumes and the nearly linear pressure-volume relationships, while venous compliance (delta V/delta P) was in each case about 20% reduced iun SHR. Consequently, the structurally determined wall distensibility of the low-pressure compartment, calculated as the square root of volume compliance/unstressed (or initial) volume, was significantly reduced in SHR; about 10%. Such venous "structural resetting" has important hemodynamic consequences, not least because it reinforces increase of venous return and cardiac filling pressure in SHR, caused by given sympathetic activations. Evidently, not only resistance, cardiac and barostat functions but also the venous capacitance function are structurally reset early in primary hypertension, implying a redesign of the entire cardiovascular system to operate at a higher pressure equilibrium.

Vasculogenesis of the bursa cloacalis (bursa of Fabricius) of the chick embryo.

Vasculogenesis of the bursa cloacalis (bursa of Fabricius) was examined i 10- to 21-day chick embryos and in chicks during the first 5 days post-hatching. The entire circulatory system was injected with India ink, and the bursae were then removed and either cleared for examination in toto or sectioned serially. The bursa was supplied by three pairs of extrinsic blood vessels. At 10 and 11 days of incubation, most intrinsic vessels were arranged in a superficial, hexagonal network. In regions of developing plicae, the hexagonal plexus extended into the core of each plica, forming middle plical vessels. The latter were interconnected across interplical areas by cross-connecting vessels. The middle plical vessels gave rise to small capillary offshoots, which soon increased in complexity, forming delicate loops. Branches extended from these loops through the subepithelial lamina propria to incipient epithelial buds by 12 days of incubation. All epithelial buds were supplied by at least one such branch, and similar branches extended to the basal aspect of the epithelium in areas where epithelial buds had not yet formed. This observation is consistent with the hypothesis that blood vessels induce formation of epithelial buds. At about 15 days of incubation, the cortex and medulla of each developing lymphatic follicle were defined clearly, and an intricate, web-like, capillary network coursed throughout the follicular cortex. The medulla appeared to be devoid of capillaries. The diameters of all intrinsic and extrinsic bursal blood vessels gradually increased throughout development. During post-hatching stages, the diameters of the extrinsic vessels continued to increase, whereas those of the intrinsic vessels were markedly decreased from late pre-hatching stages.

Intravenous Angiography Using Computerized Fluoroscopy

During the past several years, we have developed dedicated digital algorithms for real time processing of X-ray transmission imaging data obtained from an image intensifier television fluoroscopy system. Three imaging modes called Mask Mode Fluoroscopy, Mask Mode Radiography, and Time Interval Difference (T. I. D.) Imaging have been tested in over 100 patients since installation of this. apparatus at the University of Wisconsin Clinical Science Center. Feasibility studies have been conducted to determine the capability of these techniques for imaging the entire cardiovascular system, including peripheral arteries, using intravenous injections of iodinated contrast material.

Critique of a large-scale organ system model: Guytonian cardiovascular model.

This paper reviews Guyton's model, which is large not only in the number of its components but also in the time scale that it spans. The evolution of this model is explained in three stages. To explain short-term regulations of cardiac output Guyton started with a drastically simplified model of the entire cardiovascular system, which emphasized the role of blood volume and the vascular capacity. Guyton's group then directed its efforts toward the analysis of long-term regulation of arterial pressure. Two slow-acting mechanisms were added to the model: (1) the marked increase or decrease of urinary output with only slight increase or decrease in arterial pressure (the renal function curve in the Guytonian model), and (2) long-term vascular autoregulation. This second-stage model explained the transient dynamics and steady equilibrium in renal hypertension. The current version of Guyton's model incorporates a variety of additional endocrine and neural mechanisms that parametrically control the renal function curve. The Guytonian model is a unique venture in modern cardiovascular physiology because of its size and the investigators' incessant efforts to test it against the real system behaviors.

Critique of a Large-Scale Organ System Model: Guytonian Cardiovascular Model

This paper reviews Guyton’s model which is large not only in the number of its components but also in the time scale that it spans. The evolution of this model is explained in three stages. Guyton started with a drastically simplified model of the entire cardiovascular system as a closed hydraulic loop. It accounted for short-term regulations of cardiac output with a special emphasis on the role of blood volume and the vascular capacity. Guyton’s research objective was then directed toward the analysis of longterm regulation of arterial pressure. Two slowly acting mechanisms were considered as particularly important: (1) the marked increase or decrease of urinary output with only slight increase or decrease in arterial pressure (the renal function curve in the Guytonian model) and (2) long-term vascular autoregulation which includes changes in the extent of vascularization as well as constriction or dilation of existing vessels to match the blood flow with the oxygen demand in tissues. This second-stage model explained the transient dynamics and steady equilibrium of renal hypertension. The current version of Guyton’s model incorporates a variety of additional endocrine and neural mechanisms which parametrically control the renal function curve. With the enormous growth, the identification (or estimation) capability of the model is bound to degrade while its use for multiple parameter sensitivity tests expands. The modeller’s group has attempted to minimize the hazards by frequent checks of model predictions with experimental studies. This interactive effort, plus their concern over these long-term regulatory mechanisms, make the Guytonian model a unique venture in modern cardiovascular physiology.

Effect of hypophysectomy and growth hormone replacement on the composition of canine aorta.

Publisher Summary This chapter discusses the effect of hypophysectomy and growth hormone (GH) treatment on the composition of canine aorta. Degenerative blood vessel diseases associated with diabetes mellitus are known to encompass the entire cardiovascular system. In an experiment described in the chapter, the abdominal segment in control dogs contained significantly more collagen and less elastin than did the thoracic segment. Neither hypophysectomy nor GH treatment affected the collagen content of either segment. Removal of the pituitary increased the elastin content of both thoracic and abdominal aortas. GH administration to hypophysectomized dogs returned the abdominal elastin content to normal, while causing only a slight decrease in elastin of the thoracic aorta. The results of the experiment indicated that hypophysectomy in the dog has a marked effect on the composition of the aortic wall and that GH therapy can reverse some of the alterations. The abdominal aorta appears to be a more sensitive target for GH, at least for effects on elastin and heparan sulfate. This is especially interesting as the abdominal aorta of man and many domestic animals is particularly prone to atherosclerosis.

AN ELECTRICAL ANALOGUE OF THE ENTIRE HUMAN CIRCULATORY SYSTEM.

To study the human cardiovascular system an electrical analogue has been designed. This analogue consists of two parts: An active part, the heart; and a passive part, the vessels. A fourfold pulse generator represents the action of the heart. The various parameters such as heart rate, A.V. delay, duration of systole and diastole, contraction speed and contraction force can be varied within physiological limits. The vessels have been considered as linear systems with differential equations like those of an electrical transmission line and are represented by about 600 lumped sections. Results obtained with the analogue have been compared with measurementsin vivo. It appears that the analogue is a good representation of the actual circulatory system.

BLOOD PRESSURE VARIATIONS IN THE TWO ARMS

Excerpt Heart disease and disease of the entire cardiovascular system are the causes of more disability and death than any other disease. Consequently, more and more attention is being directed to ...

Pulmonary Edema

EDEMA OF THE lungs produces shadows on roentgen examination which may be confused with those due to other conditions. Most frequently they simulate pneumonia. Other pulmonary diseases which cause diffuse shadows, such as coccidioidomycosis, Boeck's sarcoid, and miliary tuberculosis, may occasionally cause confusion, and pulmonary infarcts sometimes produce a picture resembling that of edema. It is the purpose of this paper to discuss the factors involved in the production of pulmonary edema, and to correlate these with the roentgen findings. Although the roentgen appearance of edema of the lungs varies considerably, certain constant features are seen in the majority of cases. (1) Edema tends to be diffuse and bilateral. Local or segmental involvement may occur, but it is the exception rather than the rule. (2) The apices and extreme bases tend to be clear. (3) There is often a diffuse increase in density of the lung fields, due to the increase in the caliber of the vascular shadows and small focal areas of alveolar edema. (4) A rather rapid shift in position or variation in extent is apparent on serial films. (5) The heart is usually enlarged. Causes of Pulmonary Edema Pulmonary edema is caused by or associated with a wide variety of pathological conditions. The present discussion will be limited to pulmonary edema o~curring in conjunction with (1) cardiac failure, (2) nephritis, and (3) excessive parenteral administration of fluids. Three basic physiological changes singly or in combination may cause pulmonary edema. They are increased intracapillary hydrostatic pressure, decreased osmotic pressure of the blood, and altered permeability of the capillary wall. The normal hydrostatic pressure in the alveolar capillaries is estimated at between 8 and 10 mm. Hg. This is approximately 15 mm. lower than in the capillaries of the systemic circulation. The osmotic pressure of the blood is constant throughout the entire cardiovascular system. It is normally 25 to 30 mm. Hg. This pressure is an attracting force opposing the hydrostatic pressure, which, if greater than the osmotic pressure, will cause fluid to diffuse out of the capillary into the interstitial tissues. The osmotic pressure of the blood is due largely to the serum protein, the normal level of which is about 7 gm. per cent. The constituents of the serum protein which create osmotic pressure are the serum albumin and globulin, which are normally present in a proportion of 4.4 gm. per cent albumin to 2.6 gm. per cent of globulin. The albumin molecule is considerably smaller than the globulin molecule. This, in conjunction with the greater relative quantity of albumin, causes it to. exert most of the osmotic pressure. Each gram per cent of serum albumin creates osmotic pressure estimated as 5.5 mm. Hg. Each gram per cent of serum globulin exerts a pressure of 1.4 mm. Hg.

Photomicrographic Moving Picture Using Living Animals: Changes in Blood Cells from Local Anesthetic, Blood Cells in Circulation, and Heart in Action, with Entire Circulatory System of Embryo Chick

Photomicrographic Moving Picture Using Living Animals: Changes in Blood Cells from Local Anesthetic, Blood Cells in Circulation, and Heart in Action, with Entire Circulatory System of Embryo Chick