A simple cardiovascular system simulator: design and performance

A simple simulator has been constructed, evaluated and used for performance studies of prosthetic aortic valves, balloon assist devices and Koroktof sounds and ausculatory cuff blood pressure measurements. A direct drive piston pump is used. Elastic soft rubber tubes with distributed resistances allow modeling of normal and diseased pressure pulse waves. Pressure pulse amplitude amplification is modeled with tube segments of decreasing diameters. Satisfactory proximal pressure pulse shapes are obtained with a soft rubber tube of uniform diameter.     

Ultrastructure of the capsule of Bacillus megaterium ATCC 19213.

The ultrastructure of the firmly adherent capsule produced by Bacillus megaterium cultured on fructose mineral salts medium was examined using thin sectioning, freeze-etching, and critical point drying by transmission and scanning electron microscopy. The capsule material was shown to be fibrillar, with most fibrils containing bulbous protrusions. Two types of fibres were resolved. These were termed primary and cross-linking fibres. Primary fibres originated at the cell wall and had a diameter of 34-50 nm. They also contained bulbous protrusions and enlarged areas where branching occurred. Cross-linking fibres connected the primary fibres. The cross-linking fibres were much smaller, usually 15 micro m in diameter, and contained few enlarged areas. The primary fibres originated at sites on the cell wall approximately equidistant and 0.26 micro m apart.     

Simulation of a chain of collapsible contracting lymphangions with progressive valve closure

The aim of this investigation was to achieve the first step toward a comprehensive model of the lymphatic system. A numerical model has been constructed of a lymphatic vessel, consisting of a short series chain of contractile segments (lymphangions) and of intersegmental valves. The changing diameter of a segment governs the difference between the flows through inlet and outlet valves and is itself governed by a balance between transmural pressure and passive and active wall properties. The compliance of segments is maximal at intermediate diameters and decreases when the segments are subject to greatly positive or negative transmural pressure. Fluid flow is the result of time-varying active contraction causing diameter to reduce and is limited by segmental viscous and valvular resistance. The valves effect a smooth transition from low forward-flow resistance to high backflow resistance. Contraction occurs sequentially in successive lymphangions in the forward-flow direction. The behavior of chains of one to five lymphangions was investigated by means of pump function curves, with variation of valve opening parameters, maximum contractility, lymphangion size gradation, number of lymphangions, and phase delay between adjacent lymphangion contractions. The model was reasonably robust numerically, with mean flow-rate generally reducing as adverse pressure was increased. Sequential contraction was found to be much more efficient than synchronized contraction. At the highest adverse pressures, pumping failed by one of two mechanisms, depending on parameter settings: either mean leakback flow exceeded forward pumping or contraction failed to open the lymphangion outlet valve. Maximum pressure and maximum flow-rate were both sensitive to the contractile state; maximum pressure was also determined by the number of lymphangions in series. Maximum flow-rate was highly sensitive to the transmural pressure experienced by the most upstream lymphangions, suggesting that many feeding lymphatics would be needed to supply one downstream lymphangion chain pumping at optimal transmural pressure.     

As human pial arteries (internal diameter 200-1000 microm) get smaller, their wall thickness and capacity to develop tension relative to their diameter increase.

Pial arteries play a key role in the regulation of human cerebral blood flow. However, many of the features and mechanisms that regulate the tone and diameters of these vessels cannot be studied in situ. One approach is to study in vitro segments of arteries obtained during neurosurgical procedures. The ratios of arterial media thickness to lumen diameter and of the capacity to develop wall force to lumen diameter have important functional consequences and are known to change in disease. Experiments were carried out on pial arteries from normotensive humans to determine the way in which these parameters vary with vessel size. Vessel dimensions--media thickness and lumen diameter were derived from fixed sections using quantitative morphometry. Wall force was measured using a resistance artery myograph. The ratio of media thickness to lumen diameter and of maximum tension developed to lumen diameter both increased as vessel diameter decreased. These ratios do not change over the age range of 15-75 years. These findings show that although in vivo intralumenal pressure falls as human pial arteries become smaller, their media thickness and capacity to develop tone increase.     

Accumulation of cholesterol precursors and plant sterols in human stenotic aortic valves

The pathogenesis of aortic valve stenosis (AS) is characterized by the accumulation of LDL-derived cholesterol in the diseased valves. Since LDL particles also contain plant sterols, we investigated whether plant sterols accumulate in aortic valve lesions. Serum samples were collected from 82 patients with severe AS and from 12 control subjects. Aortic valves were obtained from a subpopulation of 21 AS patients undergoing valve surgery and from 10 controls. Serum and valvular total cholesterol and noncholesterol sterols were measured by gas-liquid chromatography. Noncholesterol sterols, including both cholesterol precursors and sterols reflecting cholesterol absorption, were detected in serum samples and aortic valves. The higher the ratios to cholesterol of the cholesterol precursors and absorption markers in serum, the higher their ratios in the stenotic aortic valves (r=0.74, P<0.001 for lathosterol and r=0.88, P<0.001 for campesterol). The valvular ratio to cholesterol of lathosterol correlated negatively with the aortic valve area (r= -0.47, P=0.045), suggesting attenuation of cholesterol synthesis with increasing severity of AS. The higher the absorption of cholesterol, the higher the plant sterol contents in stenotic aortic valves. These findings suggest that local accumulation of plant sterols and cholesterol precursors may participate in the pathobiology of aortic valve disease.     

Valves of the small coronary veins in porcine hearts

The aim of the study was to investigate the existence of valves in small peripheral coronary veins of porcine hearts. The study was performed on 20 porcine hearts using standard histological methods. The veins in the subepicardial and intramyocardial regions of the anterior and posterior parts of the interventricular septum and in the wall of the right atrium were studied. Valves were present in intramyocardial veins (diameter of 75–180 μm), in the veins located just beneath the external surface of the myocardium (diameter 120–170 μm) and in the terminal segments of the ventricular veins (diameter 250 μm) opening into the stems of the anterior interventricular vein and middle cardiac vein. Valves were also recorded in most veins of the subepicardial space. The described rich presence of valves in the small coronary veins may contribute to a better comprehension of their hemodynamic properties. These findings may also help to improve the understanding of the efficacy of retrograde application of medications, a novel technique in cardiology and cardiac surgery.     

Scanning electron microscopy of the wall of the third ventricle in the brain of Rana temporaria. Part IV.

Summary The surface specializations of the wall of the third cerebral ventricle of Rana temporaria were investigated with the scanning electron microscope. These specializations can be divided into three types: cilia, large bulbous protrusions, and microvillus-like protrusions.Most parts of the ventricular surface are densely ciliated. In contrast, other regions are either scantily ciliated or devoid of cilia. Four areas of the ventricular surface are studded with numerous large bulbous protrusions. These large protrusions can be divided into two types: One type consists of intraventricular end bulbs of dendrites of secretory neurons. The other type is represented by large cytoplasmic extensions of ependymal cells.In the third ventricle of Rana, microvillus-like surface specializations of ependymal cells are ubiquitous structures. Generally, filiform protrusions of varying length are the predominant type. The microvillus-like specializations are transient structures, the number of which varies according to different physiological states of the ependymal cells.This investigation was supported by a grant from the Belgian Nationaal Fonds voor Geneeskundig Wetenschappelijk Onderzoek     

Biomechanical response of femoral vein to chronic elevation of blood pressure in rabbits

Venous diseases like iliofemoral deep vein thrombosis and valvular dysfunction induce venous hypertension. To know the effects of the hypertension on venous mechanics, blood pressure in the left femoral vein in the rabbit was chronically elevated by the constriction of the left external iliac vein. Wall dimensions and biomechanical properties of the femoral vein were studied in vitro at 1, 2, or 4 wk after surgery. Blood pressure measured immediately before the animal was killed was significantly higher in the left femoral vein than in the sham-operated, contralateral vein. Wall thickness was increased by blood pressure elevation even at 1 wk, which restored circumferential wall stress to a control level. The stress was kept at normal up to 4 wk. Vascular tone and vascular contractility were increased by the elevation of blood pressure; however, wall elasticity and compliance were kept at a normal level. These results are very similar to those observed in hypertensive arteries, indicating that not only arteries but veins optimally operate against blood pressure elevation.     

Some contributions to the mathematical biology of blood circulation. Reflections of pressure waves in the arterial system

If, along the length of a blood vessel, there is a discontinuous change of diameter, the pressure waves will be reflected at the discontinuity. The transmission and reflection coefficients of the waves are calculated in terms of the ratio of the diameters and the ratio of the propagation velocities of the waves in the parts of the blood vessel. We obtain also the reflection coefficient in terms of the ratios of the diameters, of the elasticity moduli, and of the wall thicknesses. The possible clinical importance of the results is pointed out for cases of coarctation, arteriosclerosis, and other pathological conditions which might effect local changes in the structure of the blood vessel wall.     

Biomechanical and morphological properties in rat large intestine

Intestinal stress-strain distributions are important determinants of intestinal function and are determined by the mechanical properties of the intestinal wall, the physiological loading conditions and the zero-stress state of the intestine. In this study the distribution of morphometric measures, residual circumferential strains and stress-strain relationships along the rat large intestine were determined in vitro. Segments from four parts of the large intestine were excised, closed at both ends, and inflated with pressures up to 2kPa. The outer diameter and length were measured. The zero-stress state was obtained by cutting rings of large intestine radially. The geometric configuration at the zero-stress state is of fundamental importance because it is the basic state with respect to which the physical stresses and strains are defined. The outer and inner circumferences, wall thickness and opening angle were measured from digitised images. Subsequently, residual strain and stress-strain distributions were calculated. The wall thickness and wall thickness-to-circumference ratio increased in the distal direction. The opening angle varied between approximately 40 and approximately 125 degrees with the highest values in the beginning of proximal colon (F=1.739, P<0.05). The residual strain at the inner surface was negative indicating that the mucosa-submucosal layers of the large intestine in no-load state are in compression. The four segments showed stress-strain distributions that were exponential. All segments were stiffer in longitudinal direction than in the circumferential direction (P<0.05). The transverse colon seemed stiffest both in the circumferential and longitudinal directions. In conclusion, significant variations were found in morphometric and biomechanical properties along the large intestine. The circumferential residual strains and passive elastic properties must be taken into account in studies of physiological problems in which the stress and strain are important, e.g. large intestinal bolus transport function.     

Manual pressure distension of the human saphenous vein changes its biomechanical properties-implication for coronary artery bypass grafting

Patency rates of saphenous vein grafts following coronary artery bypass grafting (CABG) depend on multiple factors. Information regarding the impact of biomechanical properties of vein grafts on patency rates is not available. The objective of the present study was to evaluate whether uncontrolled manual pressure distension during routine preparation of the saphenous vein in CABG-induced changes in the biomechanical properties of the vein. The morphometric and stress-strain properties were studied in isolated segments of the saphenous vein from 12 patients undergoing elective CABG. Six segments were manually distended without pressure control and six were not distended. The mechanical test was performed as a ramp inflation using syringe pump. The vein dimensions were obtained from digitised images at different pressures as well as at the no-load and zero-stress states. The circumferences, the wall and lumen area, the wall thickness, and the outer diameter as function of the applied pressure were largest in the segments with uncontrolled manual distension compared to those without distension (P<0.05). The opening angle and the absolute value of the residual strains were lower (P<0.01) and the circumferential stress-strain curve shifted to the left, indicating the wall became stiffer with uncontrolled manual distension compared to those without distension (P<0.05). In conclusion, manual pressure distension changed the morphometric and biomechanical properties of the saphenous vein. The perspective is that studies on biomechanical properties on the saphenous vein may guide surgeons how to handle graft material without causing major changes of the biomechanical properties during harvesting and preparation.     

3d Mechanical properties of the partially obstructed guinea pig small intestine

Background and aimsPartial obstruction of the small intestine results in severe hypertrophy of smooth muscle cells, dilatation and functional denervation. Hypertrophy of the small intestine is associated with alteration of the wall structure and the mechanical properties. The aims of this study were to determine three dimensional material properties of the obstructed small intestine in guinea pigs and to obtain the 3D stress–strain distributions in the small intestinal wall.MethodsPartial obstruction of mid-jejunum was created surgically in five guinea pigs that were euthanized 2 weeks after the surgery. Ten-cm-long segments proximal to the obstruction site were used for the stretch-inflation mechanical test using a tri-axial test machine. The outer diameter, longitudinal force and the luminal pressure during the test were recorded simultaneously. An anisotropic exponential pseudo-strain energy density function was used as the constitutive equation to fit the experimental loading curve and for computation of the stress–strain distribution.ResultsThe wall thickness and the wall area increased significantly in the obstructed jejunum (P<0.001). The pressure—outer radius curves in the obstructed segments were translated to the left of the normal segments, indicating wall stiffening after the obstruction. The circumferential stress and the longitudinal stress through the wall were higher in the obstructed segments (P<0.02). This was independent of whether the zero-stress state or the no-load states were used as the reference state.ConclusionThe mechanical behaviour of the obstructed small intestine can be described using a 3D constitutive model. The obstruction-induced biomechanical properties change was characterized by higher circumferential and longitudinal stresses in the wall and altered material constants in the 3D constitutive model.     

Allograft Tissue for Use in Valve Replacement

Homograft or allograft tissue has been available for use as replacement for diseased valves or reconstruction of major vessels for decades. However, with respect to replacement of diseased valvular tissue the search for the ideal valve still continues. In this review we will discuss the clinical indications, surgical techniques, and outcome of aortic homografts.     

Experimental studies of the effects of abnormal venous valves on fluid flow

The effects of variations in the venous valve anatomy are studied experimentally using an artificial system that mimics the bicuspid valves normally found in veins in the lower extremities. The artificial valves are constructed from thin-walled, latex tubing and polyurethane film. The experimental variables in the study are the gap width between the leaflet attachments at the vein wall and the ratio of the sinus depth to vein diameter. The results show that the antegrade mass flow rate is not affected to the same degree when compared to retrograde flow by the various valve configurations examined in this study. The results also indicate that increases in the gap width, which serve to increase the degree of imperfect wall attachment, have less effect on retrograde mass flow rate in valves with deeper sinuses.     

Histological studies of the dorsal nasal,Angularis Oculi,and facial veins of sheep (Ovis aries)

Selective brain cooling (SBC) requires vasoactivity in the superficial veins of the face of the animal. This vasoactivity is possible because of an adequate amount of smooth muscle in the tunica media of each of these superficial vessels, enabling it to act as a “muscle sphincter.” In this study, the angularis oculi, dorsal nasal, distal, and proximal parts of the facial veins in sheep were examined histologically to describe an anatomical basis for SBC. Measurements of the tunica media thickness, the lumen diameter, and the ratio of these measurements showed that the relative tunica media thicknesses in the angularis oculi vein and the dorsal nasal vein are statistically smaller (P < 0.001) than in the distal or the proximal parts of the facial vein. In the angularis oculi, dorsal nasal, and distal part of the facial vein, the tunicae mediae were composed of five to seven circularly arranged smooth muscle layers, suggesting their ability to vasoconstrict. The proximal part of the facial vein possesses both circularly and longitudinally arranged smooth muscle layers. The circular smooth muscle layers suggest a vasoconstrictory function, whereas the longitudinal smooth muscle layers imply a vasodilatory function in this part of the facial vein. Both the dorsal nasal and the proximal part of the facial vein, but not the angularis oculi or the distal part of the facial vein, possess endothelial valves near their confluences with other veins. It was concluded from this study that the angularis oculi and the distal part of the facial vein vasoconstrict, whereas the proximal part of the facial vein vasodilates, enabling the necessary changes in blood flow in SBC. J. Morphol. 237:275–281, 1998. © 1998 Wiley-Liss, Inc.     

Biomechanics of the Chick Embryonic Heart Outflow Tract at HH18 Using 4D Optical Coherence Tomography Imaging and Computational Modeling

During developmental stages, biomechanical stimuli on cardiac cells modulate genetic programs, and deviations from normal stimuli can lead to cardiac defects. Therefore, it is important to characterize normal cardiac biomechanical stimuli during early developmental stages. Using the chicken embryo model of cardiac development, we focused on characterizing biomechanical stimuli on the Hamburger-Hamilton (HH) 18 chick cardiac outflow tract (OFT), the distal portion of the heart from which a large portion of defects observed in humans originate. To characterize biomechanical stimuli in the OFT, we used a combination of in vivo optical coherence tomography (OCT) imaging, physiological measurements and computational fluid dynamics (CFD) modeling. We found that, at HH18, the proximal portion of the OFT wall undergoes larger circumferential strains than its distal portion, while the distal portion of the OFT wall undergoes larger wall stresses. Maximal wall shear stresses were generally found on the surface of endocardial cushions, which are protrusions of extracellular matrix onto the OFT lumen that later during development give rise to cardiac septa and valves. The non-uniform spatial and temporal distributions of stresses and strains in the OFT walls provide biomechanical cues to cardiac cells that likely aid in the extensive differential growth and remodeling patterns observed during normal development.     

Biomechanical and morphometric properties of the arterial wall referenced to the zero-stress state in experimental diabetes

Morphometric and passive biomechanical properties were studied in isolated segments of the thoracic and abdominal aorta, left common carotid artery, left femoral artery and the left pulmonary artery in 20 non-diabetic and 28 streptozotocin (STZ)-induced diabetic rats. The diabetic and non-diabetic rats were divided into groups living 1, 4, 8, and 12 weeks after the induction of diabetes (n = 7 for each diabetic group) or sham injection (n = 5 for each group). The mechanical test was performed as a distension experiment where the proximal end of the arterial segment was connected via a tube to the container used for applying pressures to the segment and the distal end was left free. The vessel diameter and length were obtained from digitized images of the arterial segments at pre-selected pressures and at no-load and zero-stress states. Circumferential and longitudinal stresses (force per area) and strains (deformation) were computed from the length, diameter and pressure data and from the zero-stress state data. The zero-stress state was obtained by cutting vessel rings radially causing the rings to open up into a sector. Diabetes was associated with pronounced morphometric changes, e.g., wall thickness. With respect to the biomechanical data, the opening angle increased and reached a plateau in 4 weeks after which it decreased again (p < 0.05). The opening angle was smallest in the thoracic aorta and largest in the pulmonary artery. Furthermore, it was found that the circumferential stiffness of the arteries studied increased with the duration of diabetes. In the longitudinal direction significant differences were found 8 weeks after injection of STZ in all arteries except the pulmonary artery. In the 12 weeks group, the femoral artery was stiffest in the circumferential direction whereas the thoracic aorta was stiffest in the longitudinal direction. The accumulated serum glucose level correlated with the arterial wall thickness and elastic modulus (correlation coefficient between 0.56 and 0.81).     

Biomechanical remodelling of obstructed guinea pig jejunum

Data on morphological and biomechanical remodelling are needed to understand the mechanisms behind intestinal obstruction. The effect of partial obstruction on mechanical properties with reference to the zero-stress state and on the histomorphological properties of the guinea pig small intestine was determined in this study. Partial obstruction and sham operation were surgically created in mid-jejunum of guinea pigs. The animals survived 2, 4, 7, and 14 days. The age-matched guinea pigs that were not operated served as normal controls. The segment proximal to the obstruction site was used for histological analysis, no-load state and zero-stress state data, and distension test. The segment for distension was immersed in an organ bath and inflated to 10 cm H₂O. The outer diameter change during the inflation was monitored using a microscope with CCD camera. Circumferential stresses and strains were computed from the diameter, pressure and the zero-stress state data. The opening angle and absolute value of residual strain decreased (P<0.01 and P<0.001) whereas the wall thickness, wall cross-sectional area, and the wall stiffness increased after 7 days obstruction (P<0.05, P<0.01). Histologically, the muscle and submucosa layers, especially the circumferential muscle layer increased in thickness after obstruction. The opening angle and residual strain mainly depended on the thickness of the muscle layer whereas the wall stiffness mainly depended on the thickness of the submucosa layer. In conclusion, the histomorphological and biomechanical properties of small intestine (referenced for the first time to the zero-stress state) remodel proximal to the obstruction site in a time-dependent manner.     

Phagocytosis of cytoplasmic blebs derived from smooth muscle cells by fibroblast-like cells and macrophages in the post-partum rat uterus

Numerous blebs were observed in contact with smooth muscle cells (SMC) by light microscopy in the myometrium of the rat uterus after parturition. Electron-microscopically the cell surface of SMC showed bulbous protrusions, which often lacked a basement membrane and were less electron-dense than the surrounding cytoplasm or sometimes nearly electron-lucent. Many bulbous protrusions were separated from SMC and became the isolated structures which we called cytoplasmic blebs. These bulbous protrusions and cytoplasmic blebs were often found to be phagocytosed by fibroblast-like cells and macrophages. A series of these tissue changes in the uterine myometrium after delivery, possibly due to hypoxic conditions, contribute to a rapid involution of SMC which have enlarged during pregnancy.     

Intravascular ultrasound imaging of myocardial-infarction-related arteries after percutaneous transluminal coronary angioplasty reveals significant plaque burden and compensatory enlargement

We studied patients with acute myocardial infarction (MI) by intravascular ultrasound (IVUS) to elucidate the controversy as to the amount and severity of the atherosclerotic disease at the culprit lesion site in acute MI, as discrepancies exist between angiographic and pathological reports. Twenty-five consecutive patients (age 56 3 10.5 years), with acute MI, underwent IVUS study of the MI-related artery immediately following successful PTCA to the culprit lesion. The IVUS images were analyzed quantitatively and qualitatively and were compared with the angiography of the same arteries. At the PTCA site, 64% of the lesions had an area stenosis of 50-70% and the plaque cross-sectional area (CSA) averaged 0.5 3 0.18 of the arterial CSA. IVUS-defined atherosclerosis was found also in 72% of the segments proximal and distal to the culprit lesion with a plaque/artery CSA ratio of 0.25 3 0.2. The angiogram revealed only 30% of these segments to be abnormal (P 3 0.001). Sixty-nine per cent of all the plaques were defined as 'soft' (low echo-genecity) versus 31% 'hard' (high echo-genecity). The hard plaques were larger than the soft plaques (0.5 3 1.6 versus 0.37 3 0.19 CSA index, respectively, P 3 0.01). With the increase in plaque area there was a significant increase in arterial cross-sectional area. This was demonstrated for all the diseased segments with a correlation coefficient of 0.49 (P 3 0.0001) and for the diseased reference sites a similar correlation coefficient of 0.49 (P 3 0.003) was found. Contrary to coronary angiographic-based reports, this IVUS study revealed a significant atheromatous plaque burden at the culprit lesion of MI-related arteries as well as diffuse atherosclerosis in the reference segments proximal and distal to the lesion. The detection of compensatory enlargement may explain the discrepancies between the histopathological and the angiographic studies.