Representations of the human circulatory system

There is no agreement about the robustness of intuitive representations of the circulatory system and their susceptibility to change by instruction. In this paper, we analyse to what extent students with varying degrees of biology instruction and different ages (High School Health Science and Social Science students and first and final year University Psychology students) have been able to change their intuitive beliefs into scientific representations of the workings of the human circulatory system. We analysed two aspects of the representation of the circulatory system: models of the circulatory system (the relationship between the heart and lungs in the blood pathway) and the circulatory system pattern (the blood pathway between organs). In relation to the models of the circulatory system, we found differences among the different groups of students according to the amount of biological instruction they had. The majority of participants (High School Social Science students and both University Psychology student groups) had an incomplete model, which did not include the lungs while the High School Health Science students group had a scientific representation. As for the circulatory system pattern, we did not find differences among groups. However, we cannot conclude that the representations of the two aspects of the circulatory system (model and pattern) are independent. The data in this study show that compulsory human physiology instruction did not enhance the acquisition of a scientific representation of the human circulatory system.     

An electron microscopic study of the circulatory system in Nereis japonica

Blood vessels in Nereis japonica were studied by electron microscopy. It was found that blood vessels regardless of location were similar in the basic organization of the basal lamina and the usual presence of collagen fibrils on the vessel wall. Differences arise, depending on whether the outside of the basal lamina is covered by peritoneal cells, by gut epithelium, or by epidermis. These relate to the location of the vessels in mesenteries, gut or epidermis, but do not reflect basic structural differences in the vessels themselves. Furthermore, it was concluded that true endothelial cells do not exist in the circulatory system of Nereis japonica and that, in this respect, the system is essentially different from that of vertebrates, in which endothelial cells line the vessels of a closed circulatory system. These considerations lead to the further conclusion that the vascular lumen in Nereis is essentially interstitial space and that the system, which has been known as a typical “closed” circulatory system in annelids, is actually an open circulatory system. Peritoneal cells covering the walls of internal vessels show various degrees of muscular differentiation and those possessing myofilaments may be called “myomesothelial cells.”     

Hemodynamic alterations in liver cirrhosis

In cirrhotic patients, portal hypertension is often associated with a hyperdynamic circulatory syndrome, with high cardiac output and reduced systemic vascular resistance and arterial pressure. The hyperdynamic circulatory syndrome is due to arterial vasodilation that mainly occurs in the splanchnic circulation, while vascular resistance in the other circulatory districts is normal or increased, accordingly with the degree of portal hypertension, liver impairment and activation of the renin-aldosterone and sympathetic nervous system. The mechanism(s) leading to splanchnic vasodilation is unclear. A favored hypothesis translocation of intestinal bacteria and/or some their products, such as endotoxin, into the interstitial space in the splanchnic organs results in the local release of vasodilating factors such as nitric oxide, carbon monoxide and others.     

Microfluidic models of the human circulatory system: versatile platforms for exploring mechanobiology and disease modeling

The human circulatory system is a marvelous fluidic system, which is very sensitive to biophysical and biochemical cues. The current animal and cell culture models do not recapitulate the functional properties of the human circulatory system, limiting our ability to fully understand the complex biological processes underlying the dysfunction of this multifaceted system. In this review, we discuss the unique ability of microfluidic systems to recapitulate the biophysical, biochemical, and functional properties of the human circulatory system. We also describe the remarkable capacity of microfluidic technologies for exploring the complex mechanobiology of the cardiovascular system, mechanistic studying of cardiovascular diseases, and screening cardiovascular drugs with the additional benefit of reducing the need for animal models. We also discuss opportunities for further advancement in this exciting field.     

Systems engineering analysis of aortic root blood pressure

This paper describes the aortic blood pressure as a function of aortic blood flow and the parameters of the blood and circulatory system. The method of performance involves the analogue of a multi-branched electrical to hydraulic transmission line applying graphical convolution to the blood flow-transform impedance relationship resulting in a theoretical pressure curve for the infinite aorta. The difference between the single pressure pulse and the computed adjusted infinite aorta pressure curve is described as the reflected wave. This reflected wave is then shown to be of reasonable configuration in time and velocity. The blood pressure is thus finally described completely by the physical parameters of the blood and the circulatory system and the blood flow.     

Effects of retinoid deficiency on the development of the heart and vascular system of the quail embryo

The regulatory role of retinoids in growth and differentiation has been examined in vitro and in vivo by light and scanning electron microscopy using retinoid-deficient and control quail embryos between the 5-15 somite stage, as well as 2- and 2.5-day-old embryos. Fertile, retinoid-deficient eggs were obtained from flocks of quail maintained on a retinoid- and carotenoid-deficient diet, supplemented only with small amounts of retinoic acid methyl ester as described by Thompson et al. 1969. As described previously, retinoid deprivation during embryonal development causes abnormalities in organs of epithelial and mesenchymal origin, most dramatically preventing the formation of the extraembryonal circulatory system in the avian embryo. Our in vivo studies show that the basis for the latter defect is the failure of the primitive heart tubes to open at their posterior end, thus preventing the formation of omphalomesenteric veins normally connecting the embryonal with the extraembryonal circulatory system. Early manifestation of the retinoid-deficient defect may result also in formation of a cardia bifida, late manifestation in development of a single dilated ventricle. In contrast, the extraembryonal vascular system of blood islands is well developed. Heart function as shown by the rate of heart beat is reduced in deficient embryos. Our in vitro studies demonstrate similar defects in the development of the circulatory system by culture of normal 24-h embryos on retinoid-deficient agar medium; conversely, normal development is observed upon culture of retinoid-deficient embryos on retinoid-containing agar medium.     

THE CIRCULATORY SYSTEM OF THE ALDER FLY SIALIS LUTARIA

This is a comprehensive account of the circulatory system of all stages of Sialis lutaria L. The circulatory organs and pathways are described. In the larva an organ for circulating blood within the terminal segment is described. In the adult, blood vessels are described in the appendages and over the surface of the brain. Associated with these vessels are two types of accessory circulatory organs, pulsatile and valvular. The rates of heart beat, of circulation and pulsation of the scutellar organs are recorded.     

A computerized respiratory system including test functions of lung and circulation

The design of a microcomputer-controlled ventilator for automatic performance of lung function and circulatory tests has been described. It incorporates the characteristics of normal mechanical ventilation and also allows one to perform a multitude of test procedures for lung function and circulatory studies in paralyzed animals. The major components of the setup are a pump assembly with solenoid valves to direct gas flow, an electromechanical servo system, and a MS-DOS microcomputer system. The pump assembly has been constructed as a relatively simple device. Great versatility is created by the use of a microcomputer for the control of the ventilator. The software can be easily adapted to several other types of experimental studies. Besides the keyboard input the ventilator can be controlled by a remote computer system. This allows one to run an experimental protocol automatically and to use it in closed-loop servo ventilation. The flexibility in the choice of the respiratory parameters makes the ventilator suitable for lung function and circulatory studies during artificial ventilation. The ventilator has been successfully used in different animal studies during the last 6 yr.     

An experimental study of vascular dynamics by an acceleration plethysmogram using artificial circulation devices

Plethysmogram has been widely known as a conventional non-invasive simple method to obtain information on peripheral circulatory kinetics. We made a quantitative assessment of the relationships between the various circulatory parameters, using the simple conventional measurement method of treating acceleration plethysmograms (the second derivatives of digital plethysmograms) as indicators of peripheral circulation kinetics. We designed a prototype model peripheral circulatory circuit, using an artificial heart, for the purpose of clarifying the relationship between physical factors and plethysmograms. In our models of the peripheral circulatory system, we made use of various types of matching silicon tubes, as well as canine carotid arteries, as substitutes for human arteries. We evaluated the mechanical characteristics, such as the pressure and volume characteristics of the silicon tubes and canine carotid arteries. Plethysmogram alterations were measured using a photoelectric digital plethysmogram. When we examined the acceleration plethysmogram b/a values, which indicate blood vessel extensibility and hardness, and the d/a values, which we were able to use as an index of peripheral circulatory kinetics, it was clear from out model testing that canine carotid arteries displayed b/a values that were closest to those found in the human fingertip; among artificial tubes, the closest was a tube with a diameter of 4 mm (0.18 mm in thickness). The b/a values of all types of tubes declined when the compliance of the arterial system was increased, and it was confirmed through model testing that b/a values are an indicator of blood vessel extensibility.     

Ghost Cells for Mechanical Circulatory Support In Vitro Testing: A Novel Large Volume Production

The aim of this work is to establish a large volume batch production system to produce sufficient volumes of ghost cells to facilitate hemolysis testing of mechanical circulatory support devices. A volume of more than 405 mL with a hematocrit of at least 28% is required to perform in vitro hemolysis testing of mechanical circulatory support devices according to international standards. The established ghost cell production method performed at the institute is limited to 3.1 mL of concentrated cells, that is, cells with 100% hematocrit, due to predominantly manual process steps. Through semi‐automation of the existing method by using the large volume batch production system, productivity is increased 60‐fold to 188 mL while almost doubling process efficiency to 23.5%. Time‐consuming manual work such as pipetting is now supported by sensor‐based process engineering. With the help of the large volume batch production system, the objective of producing large quantities of ghost cells is successfully achieved. Thus, this work lays the foundation for spatially resolved hemolysis evaluation of mechanical circulatory support devices in combination with the small‐scale fluorescent hemolysis detection method.     

Evolutionary origin of autonomic regulation of physiological activities in vertebrate phyla

Proper regulation of physiological activities is crucial for homeostasis in animals. Autonomic regulation of these activities is most developed in mammals, in which a part of peripheral nervous system, termed the autonomic nervous system plays the dominant role. Circulatory activity and digestive activity in vertebrates change in opposite phases to each other. The stage where circulatory activity is high and digestive activity is low is termed the "fight or flight stage" while the stage where circulatory activity is low and digestive activity is high is termed the "rest and digest stage". It has been thought that the autonomic nervous system originated in early vertebrate phyla and developed to its greatest extent in mammals. In this study, we compared the pattern of change of circulatory and digestive activities in several invertebrates and found that the two stages seen in mammals are also present in a wide variety of animals, including evolutionarily early-diverging invertebrate taxa. From this and other arguments we propose a novel possibility that the basic properties of the autonomic nervous system were established very early in metazoan evolution.     

Drosophila seminal fluid proteins enter the circulatory system of the mated female fly by crossing the posterior vaginal wall

Seminal fluid proteins from males of many insect species affect the behavior and physiology of their mates. In some cases, these effects result from entry of the proteins into the female's circulatory system. In the fruit fly Drosophila melanogaster, some seminal fluid proteins enter the female's circulatory system after transfer from the male while others remain confined within the reproductive tract. To address where and how seminal fluid proteins enter the hemolymph of the mated female, we compared the kinetics of transfer and localization in mated females of two seminal fluid proteins that enter the hemolymph (Acp26Aa and Acp62F) and one that does not (Acp36DE). We also generated transgenic flies that produce Acp26Aa tagged with Aequorea victoria green fluorescent protein (GFP) to monitor its transfer in vivo. We report that Acps enter the female circulatory system from the posterior vagina immediately after insemination. The ability of Acps to enter the female hemolymph correlates with their ability to cross the intima that lines the posterior vagina. The ventral posterior vagina is structurally unlike other parts of the female reproductive tract in that it lacks muscles. We hypothesize that it has higher permeability thus affording access to the female's circulatory system.     

The circulatory system in Phreatoicidea: implications for the isopod ground pattern and peracarid phylogeny

The circulatory systems of four species of Phreatoicidea and two species of Oniscidea were studied on the basis of serial semi-thin sections and a corrosion cast method. A 3D computer reconstruction was used to visualize the circulatory organs in the head of the Phreatoicidea. In the Phreatoicidea, the circulatory system consists of a longitudinal dorsal heart extending from the third thoracic to the border between the fourth and fifth pleonal segments. It is equipped with two pairs of asymmetrically arranged ostia, while five pairs of lateral cardiac arteries and an unpaired anterior aorta extend from the heart. Entering the head, the aorta is accompanied by the two first lateral arteries, which supply the muscles of the mandibles. Four pairs of arteries branch off the aorta to supply both pairs of antennae, the eyes, and sinuses in the head. In addition, several minute capillaries extend from the aorta to supply the brain. The two oniscidean species were re-investigated with regard to some characters which have been controversially discussed. In these species, the heart extends from the border between the fifth and sixth thoracic segments to the fifth pleonal segment. Five pairs of lateral cardiac arteries and the unpaired anterior aorta lead off the heart. A ventral vessel was not observed. The ground pattern of the circulatory system in isopods is reconstructed with greater reliability through optimisation of its characters based on proposed phylogenetic relationships. The results do not support a phylogenetic position of the Isopoda as basal Peracarida or even basal Eumalacostraca.     

Vampiric Isolation of Extracellular Fluid from Caenorhabditis elegans

The genetically tractable model organism C. elegans has provided insights into a myriad of biological questions, enabled by its short generation time, ease of growth and small size. This small size, though, has disallowed a number of technical approaches found in other model systems. For example, blood transfusions in mammalian systems and grafting techniques in plants enable asking questions of circulatory system composition and signaling. The circulatory system of the worm, the pseudocoelom, has until recently been impossible to assay directly. To answer questions of intercellular signaling and circulatory system composition C. elegans researchers have traditionally turned to genetic analysis, cell/tissue specific rescue, and mosaic analysis. These techniques provide a means to infer what is happening between cells, but are not universally applicable in identification and characterization of extracellular molecules. Here we present a newly developed technique to directly assay the pseudocoelomic fluid of C. elegans. The technique begins with either genetic or physical manipulation to increase the volume of extracellular fluid. Afterward the animals are subjected to a vampiric reverse microinjection technique using a microinjection rig that allows fine balance pressure control. After isolation of extracellular fluid, the collected fluid can be assayed by transfer into other animals or by molecular means. To demonstrate the effectiveness of this technique we present a detailed approach to assay a specific example of extracellular signaling molecules, long dsRNA during a systemic RNAi response. Although characterization of systemic RNAi is a proof of principle example, we see this technique as being adaptable to answer a variety of questions of circulatory system composition and signaling.     

New Technologies to Prolong Life-time of Peptide and Protein Drugs In vivo

Most peptide and protein drugs are short-lived species in vivo with a circulatory half-life of several minutes. This is particularly valid for non-glycosylated proteins with a molecular mass of less than 50 kDa. Since peptide/protein drugs are not absorbed orally, prolonged maintenance of therapeutically active drugs in the circulatory system is of primary clinical importance. Another major obstacle of injected polypeptide drugs is the elevated concentration of 100–1000 times above the therapeutical level that may be present in the circulatory system shortly after administration. Such overdosing may lead to undesirable side effects such as over-stimulation or down-regulation of receptor sites. In this review we describe two new strategies that overcome these two problems of systemically injected peptide/protein drugs. The first strategy includes Fmoc and FMS derivatization of peptides, proteins and low molecular-weight drugs, converting them to inactive prodrugs that undergo reactivation with desirable pharmacokinetic patterns in body fluids. Based on this Fmoc/FMS-technology, we have developed a second strategy, reversible pegylation. Inactive pegylated peptide/protein drugs release the native active parental molecule at slow rates, and in homogeneous fashion under physiological conditions, thus facilitating prolonged therapeutic effects, following a single administration.     

Physical constraints on body size in teleost embryos

All members of the subphylum "Vertebrata" display the characteristics of the vertebrate body plan. These characteristics become apparent during the phylotypic period, in which all vertebrate embryos have a similar body shape and internal organization. Phylogenetic constraints probably limit the morphological variation during the phylotypic period. Physical laws, however, also limit growth and morphogenesis in embryos. We investigated to what extent oxygen availability-as a physical constraint-might limit morphological variation during embryonic development. This paper gives an analysis of time-dependent diffusion into spherical embryos without a circulatory system. Equilibrium appeared to settle in about 1.5 min in running water and in about 10min in stagnant water. Hence, steady-state conditions were assumed and expressions for maximum body size were obtained for spherical, cylindrical and sheet-like embryos in running water and spherical embyros in stagnant water. Predictions of the model based on literature data suggest that in running water-both for spherical, cylindrical and sheet-like embryos-diffusion alone suffices to cover the oxygen needs of a teleost embryo in its phylotypic period. The size of carp (Cyprinus carpio) and African catfish (Clarias gariepinus) embryos is very close to the predicted maximum. This suggests that in these species the development of a functional circulatory system is correlated with the onset of oxygen shortage. Oxygen availability is therefore a potentially important physical constraint on embryonic morphology, though in most species the circulatory system becomes functional well in advance of the onset of oxygen shortage and other demands than oxygen delivery (e.g. nutrient distribution, waste disposal, osmoregulation) might require the development of a circulatory system.     

Low doses of ionizing radiation and circulatory diseases: a systematic review of the published epidemiological evidence

Recent analyses of mortality among atomic bomb survivors have suggested a linear dose-response relationship between ionizing radiation and diseases of the circulatory system for exposures in the range 0-4 Sv. If confirmed, this has substantial implications. We have therefore reviewed the published literature to see if other epidemiological data support this finding. Other studies allowing a comparison of the rates of circulatory disease in individuals drawn from the same population but exposed to ionizing radiation at different levels within the range 0-5 Gy or 0-5 Sv were identified through systematic literature searches. Twenty-six studies were identified. In some, disease rates among those exposed at different levels may have differed for reasons unrelated to radiation exposure, while many had low power to detect effects of the relevant magnitude. Among the remainder, one study found appreciable evidence that exposure to low-dose radiation was associated with circulatory diseases, but five others, all with appreciable power, did not. We conclude that the other epidemiological data do not at present provide clear evidence of a risk of circulatory diseases at doses of ionizing radiation in the range 0-4 Sv, as suggested by the atomic bomb survivors. Further evidence is needed to characterize the possible risk.     

The circulatory system of Amphioxus (Branchiostoma floridae). I. Morphology of the major vessels of the pharyngeal area

In order to clarify the morphology of the circulatory system of amphioxus the blood vessels were investigated using modern techniques of light and electron microscopy. The pattern of circulation in amphioxus is forward ventrally and backwards dorsally. In addition, circulating corpuscles, usually associated with the blood of higher chordates, are absent. The circulatory system of amphioxus consists of well defined contractile vessels and vascular spaces or sinuses within a connective tissue matrix. The contractile vessels have a discontinuous endothelial lining resting on a basal lamina and are enclosed by a simple layer of contractile myoepithelial cells. Discontinuous endothelial linings occur throughout the vascular tree, including major and minor afferent and efferent vessels and blood sinuses. This is in contrast to higher animals where the endothelium forms a more or less continuous lining along the inner surface of the boundary layer. It is suggested that the endothelial cells of amphioxus, like the endothelial cells in capillaries of higher chordates, most likely play a role in the physiology of the circulatory system by removing residues of filtration from the basal lamina, thereby facilitating an exchange of materials to and from the surrounding tissues.