A constrained mixture model for developing mouse aorta

Mechanical stresses influence the structure and function of adult and developing blood vessels. When these stresses are perturbed, the vessel wall remodels to return the stresses to homeostatic levels. Constrained mixture models have been used to predict remodeling of adult vessels in response to step changes in blood pressure, axial length and blood flow, but have not yet been applied to developing vessels. Models of developing blood vessels are complicated by continuous and simultaneous changes in the mechanical forces. Understanding developmental growth and remodeling is important for treating human diseases and designing tissue-engineered blood vessels. This study presents a constrained mixture model for postnatal development of mouse aorta with multiple step increases in pressure, length and flow. The baseline model assumes that smooth muscle cells (SMCs) in the vessel wall immediately constrict or dilate the inner radius after a perturbation to maintain the shear stress and then remodel the wall thickness to maintain the circumferential stress. The elastin, collagen and SMCs have homeostatic stretch ratios and passive material constants that do not change with developmental age. The baseline model does not predict previously published experimental data. To approximate the experimental data, it must be assumed that the SMCs dilate a constant amount, regardless of the step change in mechanical forces. It must also be assumed that the homeostatic stretch ratios and passive material constants change with age. With these alterations, the model approximates experimental data on the mechanical properties and dimensions of aorta from 3- to 30-day-old mice.     

Influence of tensile strain on smooth muscle cell orientation in rat blood vessels.

Blood vessels are subject to tensile stress and associated strain which may influence the structure and organization of smooth muscle cells (SMCs) during physiological development and pathological remodeling. This study focused on the influence of the major tensile strain on the SMC orientation in the blood vessel wall. Several blood vessels, including the aorta, the mesenteric artery and vein, and the jugular vein of the rat were used to observe the normal distribution of tensile strains and SMC orientation; and a vein graft model was used to observe the influence of altered strain direction on the SMC orientation. The circumferential and longitudinal strains in these blood vessels were measured by using a biomechanical technique, and the SMC orientation was examined by fluorescent microscopy at times of 10, 20, and 30 days. Results showed that the SMCs were mainly oriented in the circumferential direction of straight blood vessels with an average angle of approximately 85 deg between the SMC axis and the vessel axis in all observed cases. The SMC orientation coincided with the principal direction of the circumferential strain, a major tensile strain, in the blood vessel wall. In vein grafts, the major tensile strain direction changed from the circumferential to the longitudinal direction at observation times of 10, 20, and 30 days after graft surgery. This change was associated with a decrease in the angle between the axis of newly proliferated SMCs and that of the vessel at all observation times (43 +/- 11 deg, 42 +/- 10 deg, and 41 +/- 10 deg for days 10, 20, and 30, respectively), indicating a shift of the SMC orientation from the circumferential toward the longitudinal direction. These results suggested that the major tensile strain might play a role in the regulation of SMC orientation during the development of normal blood vessels as well as during remodeling of vein grafts.     

Vascular wall extracellular matrix proteins and vascular diseases

Extracellular matrix proteins form the basic structure of blood vessels. Along with providing basic structural support to blood vessels, matrix proteins interact with different sets of vascular cells via cell surface integrin or non-integrin receptors. Such interactions induce vascular cell de novo synthesis of new matrix proteins during blood vessel development or remodeling. Under pathological conditions, vascular matrix proteins undergo proteolytic processing, yielding bioactive fragments to influence vascular wall matrix remodeling. Vascular cells also produce alternatively spliced variants that induce vascular cell production of different matrix proteins to interrupt matrix homeostasis, leading to increased blood vessel stiffness; vascular cell migration, proliferation, or death; or vascular wall leakage and rupture. Destruction of vascular matrix proteins leads to vascular cell or blood-borne leukocyte accumulation, proliferation, and neointima formation within the vascular wall; blood vessels prone to uncontrolled enlargement during blood flow diastole; tortuous vein development; and neovascularization from existing pathological tissue microvessels. Here we summarize discoveries related to blood vessel matrix proteins within the past decade from basic and clinical studies in humans and animals — from expression to cross-linking, assembly, and degradation under physiological and vascular pathological conditions, including atherosclerosis, aortic aneurysms, varicose veins, and hypertension.     

In vitro contractility of normal and aneurysmal abdominal aorta muscle coat sections in human and animal material

The objective of the study was to demonstrate spontaneous contractile activity of the smooth muscle coat of the aorta in human and animal material. Spontaneous contractility of smooth muscle tissue, or tonus, is essential for the proper function of many internal organs as observed in the many types of muscle cells which make up the internal structures. The spontaneous contractile activity of the muscle tissue in blood vessels is particularly marked in resistance vessels, regulating circulation within organs or tissues. It can also be observed in large blood vessels such as arteries and veins. The contractile activity of muscular tissue isolated from arteries is the result of a number of factors, including endogenous paracrine substances, neurotransmitters released at postganglionic endings (mostly within the sympathetic system), cells capable of spontaneously generation of functional potentials (pacemaking cells) and the vascular endothelium. Pacemaking cells present in the aortic wall are an important factor in the development of the spontaneous contractility of the muscular coat of the aorta. They are capable of generating functional potentials, resulting in the constant tonus of the smooth muscular coat (comprising the aortic wall) due to tonic contraction. In vitro studies were carried out on abdominal aortic sections collected from 30 New Zealand rabbits with a body mass of 3-4 kilograms each and also on aneurysmal abdominal aortic sections collected during elective aneurysm repair procedures in humans (10 abdominal aortic sections). The 1.5 cm-long sections were mounted in chambers of an automated water bath. The sections were oriented in a transverse and longitudal fashion in order to compare contractility. The incubation medium consisted of Krebs-Henseleit buffer. Spontaneous contractile activity was observed during the study, characterized by rhythmic contractions of the muscular layer of the aorta. The contractile tension within the sections was 0.15 mN in the case of rabbit sections and 0.8 mN in the case of human sections. The average duration of a single contraction was 38.3 +/- 15.05 seconds. The average contraction frequency, i.e. the average number of contractions per minute, was 1.61 +/- 0.54 contractions per minute. The spontaneous contraction is modulated by many factors like endogenous paracrine substances, neurotransmitters or vascular endothelium.     

Distinct signalling pathways regulate sprouting angiogenesis from the dorsal aorta and the axial vein

Angiogenesis, the formation of new blood vessels from pre-existing vessels, is critical to most physiological processes and many pathological conditions. During zebrafish development, angiogenesis expands the axial vessels into a complex vascular network that is necessary for efficient oxygen delivery. Although the dorsal aorta and the axial vein are spatially juxtaposed, the initial angiogenic sprouts from these vessels extend in opposite directions, indicating that distinct cues may regulate angiogenesis of the axial vessels. We found that angiogenic sprouts from the dorsal aorta are dependent on vascular endothelial growth factor A (Vegf-A) signalling, and do not respond to bone morphogenetic protein (Bmp) signals. In contrast, sprouts from the axial vein are regulated by Bmp signalling independently of Vegf-A signals, indicating that Bmp is a vein-specific angiogenic cue during early vascular development. Our results support a paradigm whereby different signals regulate distinct programmes of sprouting angiogenesis from the axial vein and dorsal aorta, and indicate that signalling heterogeneity contributes to the complexity of vascular networks.     

Mechanisms of vascular adaptation to long-term orthostatic gravitational loading

Frequent symptoms and serious complaints related to orthostatic intolerance are among the important reasons for investigating the long-term control mechanisms of blood vessels especially those of veins. Previously we studied perfused and superfused saphenous vein segments from rats maintained in head-up tilt position for two weeks. It was found that passive lumen capacity and acute pressure induced myogenic response of these vessels increased substantially without measurable change in wall thickness. Sympathetic component of the smooth muscle cell membrane potential determined in vivo was also significantly enhanced in this vein, but no such change was seen in the saphenous artery and in the brachial vessels. In a separate study, rarefaction of microvessels was found in the hind limb oxydative muscles after two-week tilting, while muscular water content was unaltered. These results suggest that long-term gravitational loading may induce adaptive rearrangement of the blood vessel functions. The aim of the present study was to quantitate and compare the density of nerve fiber terminals as well as their synaptic vesicle population in the wall of saphenous vein and artery from tilted rats to those obtained from rats which were maintained in horizontal, control position. It was hypothetized that adaptation of blood vessels to long-term gravitational loading might include also a morphological restructuring of the vascular adrenergic innervation.     

Age and variability in the inguinal lymph nodes of adult humans]

Lymphatic nodes on the anterior surface of the femur, in the region of the femoral triangle were studied in 56 corpses of humans of either sex from 31 to 82 years of age, dead of accidental causes or of diseases not related to lymphatic nodes. The investigation was carried on by the method of interstitial and direct injection of the Gerota's mass to some regions of foot skin, external genitalia and the skin of the anterior wall of the abdomen. It has been established that the size of inguinal lymphatic nodes (both superficial and profound) in humans of either sex, are in direct dependence on the age of the person. The amount of inguinal lymphatic nodes in young people prevails over that in old people. The external diameter of the afferent and efferent vessels in elderly humans is greater than in young ones. The amount of afferent lymphatic vessels to inguinal lymphatic nodes in most cases prevails over the amount of efferent ones, independent of age and sex. The external diameter of the former is greater than that of the latter.     

Embryonic development of the proepicardium and coronary vessels

In the last few years, an increasing interest in progenitor cells has been noted. These cells are a source of undifferentiated elements from which cellular components of tissues and organs develop. Such progenitor tissue delivering stem cells for cardiac development is the proepicardium. The proepicardium is a transient organ which occurs near the venous pole of the embryonic heart and protrudes to the pericardial cavity. The proepicardium is a source of the epicardial epithelium delivering cellular components of vascular wall and interstitial tissue fibroblasts. It contributes partially to a fibrous tissue skeleton of the heart. Epicardial derived cells play also an inductive role in differentiation of cardiac myocytes into conductive tissue of the heart. Coronary vessel formation proceeds by vasculogenesis and angiogenesis. The first tubules are formed from blood islands which subsequently coalesce forming the primitive vascular plexus. Coronary arteries are formed by directional growth of vascular protrusions towards the aorta and establishing contact with the aortic wall. The coronary vascular wall matures by attaching smooth muscle cell precursors and fibroblast precursors to the endothelial cell wall. The cells of tunica media differentiate subsequently into vascular smooth muscle by acquiring specific contractile and cytoskeletal markers of smooth muscle cells in a proximal - distal direction. The coronary artery wall matures first before cardiac veins. Maturity of the vessel wall is demonstrated by the specific shape of the internal surface of the vascular wall.     

Blood collection from the tail of a rat

Techniques for blood collection from the rat include puncture of the heart, retro-orbital plexus, jugular vein, saphenous vein, tail blood vessels, carotid artery, abdominal aorta, and vena cava. Most techniques (except saphenous vein and tail blood vessel puncture) require anesthesia. The following discussion focuses on two methods of blood collection - ventral tail artery puncture and dorsal or lateral tail vein puncture.     

Circulatory system of rainbow trout Oncorhynchus mykiss (Walbaum): a corrosion cast study

The present study describes and visualizes the circulatory system of rainbow trout with emphasis on the heart and main blood vessels, employing corrosion cast methodology. Ten rainbow trout (Oncorhynchus mykiss (Walbaum) of 1000 g average weight were obtained from a commercial fish farm. Fish were anaesthetised using a benzocain solution in ethanol. After 40 min, the fish were killed using an overdose of the benzocain solution. The aorta caudalis and aorta coeliaco‐mesentric were cannulated and attempts were made to fill the blood vessels and heart with fluid artificial resin made on the basis of methylmetacrylate. The fish were further prepared by submersion for 12–24 h in a room temperature waterbath until polymerisation and hardening of the methylmetacrylate was complete. This was followed by 24–48 h submersion in a 25% solution of KOH to obtain full maceration of the organic tissues. Various parts of the heart and blood vessels were retained in their natural positions, thereby demonstrating the anatomical details of the main circulatory system. Main elements depicted included the sinus venosus, atrium, ventricle, bulbus arteriosus and related vessels such as the dorsal aorta, subclavian vein, hepatic vein, common cardinal vein, coeliaco‐mesenteric artery, gastero‐intestinal artery, and dorsal intestinal artery. Related smaller vessels were also determined.     

Individual and age-related differences in the anatomy of the main deferent lymphatic vessels of the human heart and their applied significance

One hundred human hearts of various age have been investigated. Structure, size of their main deferent lymphatic vessels are defined by the organ's form, sex and age of the persons. According to the position signs, extreme forms of their topography have been revealed. In the left--the course in the adventitia of the anterior wall of the pulmonary trunk and of the ascending aorta. In the left--the course in the adventitia of the right lateral wall of the ascending aorta and of the pulmonary trunk. The number of the extraorganic vessels, that bring lymph out of the heart, is from 1 up to 3. The anastomoses made between certain parts of the lymph nodes and the extraorganic lymphatic vessels in the transplanted and removed hearts are more economic.     

Relationship between hypertension, hypertrophy, and opening angle of zero-stress state of arteries following aortic constriction

Examination of changes occurring in the zero-stress state of an organ provides a way to study cellular growth in the organ due to change of physical stresses. The zero-stress state of the aorta is not a tube. It is a sector with an opening angle that varies with the location on the aorta and changes with cellular remodeling. Blood vessel remodeling can be induced by imposing a constriction on the abdominal aorta by a metal clip (aortic banding), which causes an increase of blood pressure, hypertrophy of the aortic wall, and large change of opening angle. The correlation of the opening angle with the blood vessel wall thickness and blood pressure changes in rat's aorta due to aortic banding is presented in this report. The opening angle changes daily following the aortic banding. Blood pressure rises in vessels of the upper body, but that in the lower body decreases at first and then rises to an asymptotic value. Blood vessel wall thickness increases in rough proportion to blood pressure. Vessel diameter changes also. But the most dramatic is the course of change of the zero-stress state. Typically, the time to reach 50 percent of asymptotic hypertrophy of blood vessel wall thickness is about 3-5 days. The corresponding time for blood pressure is about 7 days. The opening angle of the zero-stress state, however, increases rapidly at first, reaches a peak in about 2 to 4 days, then decreases gradually to a reduced asymptote. The exact values of the time constants depend on the location along the aortic tree. In general, the course of change of residual strain is very different from those of the blood pressure and the blood vessel wall thickness.     

Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent

To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.     

Blood-forming potential of vascular endothelium in the human embryo

Hematopoietic cells arise first in the third week of human ontogeny inside yolk sac developing blood vessels, then, one week later and independently, from the wall of the embryonic aorta and vitelline artery. To address the suggested derivation of emerging hematopoietic stem cells from the vessel endothelium, endothelial cells have been sorted by flow cytometry from the yolk sac and aorta and cultured in the presence of stromal cells that support human multilineage hematopoiesis. Embryonic endothelial cells were most accurately selected on CD34 or CD31 surface expression and absence of CD45, which guaranteed the absence of contaminating hematopoietic cells. Yet, rigorously selected endothelial cells yielded a progeny of myelo-lymphoid cells in culture. The frequency of hemogenic endothelial cells in the yolk sac and aorta reflected the actual blood-forming activity of these tissues, as a function of developmental age. Even less expected, a subset of endothelial cells sorted similarly from the embryonic liver and fetal bone marrow also exhibited blood-forming potential. These results suggest that a part at least of emerging hematopoietic cells in the human embryo and fetus originate in vascular walls.     

Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences

Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions—the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery—in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.     

The Fine Structure of Some Blood Vessels of the Earthworm, Eisenia foetida

The fine structure of the main dorsal and ventral circulatory trunks and of the subneural vessels and capillaries of the ventral nerve cord of the earthworm, Eisenia foetida, has been studied with the electron microscope. All of these vessels are lined internally by a continuous extracellular basement membrane varying in thickness (0.03 to 1 µ) with the vessel involved. The dorsal, ventral, and subneural vessels display inside this membrane scattered flattened macrophagic or leucocytic cells called amebocytes. These lie against the inner lining of the basement membrane, covering only a small fraction of its surface. They have long, attenuated branching cell processes. All of these vessels are lined with a continuous layer of unfenestrated endothelial cells displaying myofilaments and hence qualifying for the designation of "myoendothelial cells." The degree of muscular specialization varies over a spectrum, however, ranging from a delicate endowment of thin myofilaments in the capillary myoendothelial cells to highly specialized myoendothelial cells in the main pulsating dorsal blood trunk, which serves as the worm's "heart" or propulsive "aorta." The myoendothelial cells most specialized for contraction display well organized sarcoplasmic reticulum and myofibrils with thick and thin myofilaments resembling those of the earthworm body wall musculature. In the ventral circulatory trunk, circular and longitudinal myofilaments are found in each myoendothelial cell. In the dorsal trunk, the lining myoendothelial cells contain longitudinal myofilaments. Outside these cells are circular muscle cells. The lateral parts of the dorsal vessels have an additional outer longitudinal muscle layer. The blood plasma inside all of the vessels shows scattered particles representing the circulating earthworm blood pigment, erythrocruorin.     

Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation

Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [15O]CO or injections of diffusible 3-O-[11C]methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time (T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: T = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.     

Microanatomy of the heart and associated structures of two scorpions,Centruroides sculpturatus ewing and Uroctonus mordax thorell

Spiroid orientation of the circumferential heart wall muscles is described for Centruroides sculpturatus Ewing. This muscle arrangement accounts for differences in ostial position when the heart of this species is compared to that of Uroctonus mordax Thorell. Other differences, such as number of lateral arteries present, cannot be explained on the basis of circumferential muscle orientation. The histology of the heart and associated vessels, but not the supraneural vessel, was found to be similar in both species. The lateral, posterior, communicating and sternal arteries all possess a muscularis composed of irregularly spaced, apparently branched, striated muscle fibers. External to this is a covering of connective tissue. The lumina of these arteries, the aorta, and the supraneural vessel are lined with a homogeneous, PAS-positive membrane. This membrane is also seen in blood vessels which penetrate the nervous system. It was not observed in vessels accompanying major nerves. Findings are compared to those of other authors. Differences in the structure of the hearts of these two species are discussed in relation to the microanatomy of other arachnid hearts.     

Doppler evaluation of maternal and foetal vessels during normal gestation in queen

The aim of this work is to evaluate the haemodynamic characteristics of maternal and foetal vessels during normal pregnancy in queens, using colour Doppler and pulsed wave Doppler ultrasonography, in order to obtain information about maternal and foetal circulation. The blood waveforms of the uteroplacental arteries, aorta, caudal cava vein and umbilical cord of the fetuses were recorded weekly in seven healthy pregnant queens. Also, the measurements of peak systolic, end diastolic velocities, resistance and pulsatility indices were carried out. Uteroplacental blood flow was biphasic while the ones of the umbilical artery and aorta were first systolic and then diastolic. The caudal cava vein showed a typical waveform of venous vessels. During gestation the EDV and PSV of foetal vessels increased ( < 0.05) while the PI and RI of all vessels examined decreased ( < 0.05) except for the IP of the aorta. The Doppler ultrasonography, also in queens, can be used to evaluate the characteristics of maternal and foetal vessel flow and their progressive changes during pregnancy. This study can be considered the basis for further contribution in diagnosing and monitoring high-risk pregnancies in Veterinary Medicine.     

Effect of prostacyclin (PGI2) on platelet adhesion to rabbit arterial subendothelium.

The effect of prostacyclin on platelet aggregation and adhesion was investigated in everted pieces of rabbit abdominal aorta, from which the endothelium had previously been removed. Citrated human blood, to which different, concentrations of prostacyclin (0.1-100 ng/ml) were added, was perfused through the vessels, after which sections were examined and evaluated by light microscopy. Prostacyclin inhibited thrombus formation at concentrations greater than 0.1 ng/ml, whereas 20 ng/ml were required to reduce the amount of adhesion to the subendothelial surface. Thus prostacyclin prevents thrombus formation at much lower concentrations than are needed to inhibit platelet-vessel wall interaction.