Fractal structures in stenoses and aneurysms in blood vessels

Recent advances in the field of chaotic advection provide the impetus to revisit the dynamics of particles transported by blood flow in the presence of vessel wall irregularities. The irregularity, being either a narrowing or expansion of the vessel, mimicking stenoses or aneurysms, generates abnormal flow patterns that lead to a peculiar filamentary distribution of advected particles, which, in the blood, would include platelets. Using a simple model, we show how the filamentary distribution depends on the size of the vessel wall irregularity, and how it varies under resting or exercise conditions. The particles transported by blood flow that spend a long time around a disturbance either stick to the vessel wall or reside on fractal filaments. We show that the faster flow associated with exercise creates widespread filaments where particles can get trapped for a longer time, thus allowing for the possible activation of such particles. We argue, based on previous results in the field of active processes in flows, that the non-trivial long-time distribution of transported particles has the potential to have major effects on biochemical processes occurring in blood flow, including the activation and deposition of platelets. One aspect of the generality of our approach is that it also applies to other relevant biological processes, an example being the coexistence of plankton species investigated previously.

Disturbance and repair of solitary waves in blood vessels with aneurysm

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

About the arterial blood vessels pelvic opossum's (Didelphis albiventris) behaviour

The work consists of the study of 20 opossums (Didelphis albiventris); 7 females and 13 males, adults, natives of Jaboticabal county proceeding to a canulation and injection of the arterial system with neoprene latex-650 in the aorta artery (full-blooded). Right away the preparations were fixed by a 10% formaldehyde aqueous solution and afterwards dissected and formed a scheme. The analysis of the pieces showed that in the opossum, the end of the aorta always divides in the common iliac artery, right and left sides, both originating the external and internal iliac artery, on the right and left sides. The medium sacral artery results, medianly, from the aorta division's angle in 2 common iliac arteries in 8 cases (40% - 6 males and 2 females); this vessel comes from the left common iliac artery in 7 animals (35% - 5 males and 2 females) or comes from the right common iliac artery, in 5 preparations (25% - 3 females and 2 males). The deep iliac circumflex artery is born by the common iliac artery from the right side in 10 preparations (50% - 6 males and 4 females), can appear as well, concomitantly with the external and internal iliac artery, from the right side in 9 pieces (45% - 6 males and 3 females) and further from the right this vessels can emerge from the external iliac artery, in 1 case only (5% - 1 male).

Topography of the blood vessels in the hilum of the kidney of Myrmecophaga tridactyla

The study was undertaken in 10 formol-imbibed kidneys of great anteater (Myrmecophaga tridactyla). After the dissection the following characteristics were showed: kidney blood vessels are distributed in 2 different sites, namely hilar and extrahilar, amounting 3 to 6 in the right side 3 to 7 in the left side. Arterial branches in extrahilar region range from 1 to 2 in both sides and in hilar region they present from 1 to 4 in the right and 1 to 2 in the left. Venous roots occur in 1 to 2 vessels in the right and 1 to 3 vessels in the left, occupying only the hilar region, except one case where it was present in the right side.

Cell-free cryopreserved arterial allografts from multiorgan donors: a new strategy to fabricate artificial blood vessels suited for peripheral vascular surgery

Critical lower limb ischemia is a severe disease. A common approach is infrainguinal bypass. Synthetic vascular prosthesis, are good conduits in high-flow low-resistance conditions but have difficulty in their performance as small diameter vessel grafts. A new approach is the use of native decellularized vascular tissues. Cell-free vessels are expected to have improved biocompatibility when compared to synthetic and are optimal natural 3D matrix templates for driving stem cell growth and tissue assembly in vivo. Decellularization of tissues represent a promising field for regenerative medicine, with the aim to develop a methodology to obtain small-diameter allografts to be used as a natural scaffold suited for in vivo cell growth and pseudo-tissue assembly, eliminating failure caused from immune response activation. Material and methods. Umbilical cord-derived mesenchymal cells isolated from human umbilical cord tissue were expanded in advanced DMEM. Immunofluorescence and molecular characterization revealed a stem cell profile. A non-enzymatic protocol, that associate hypotonic shock and low-concentration ionic detergent, was used to decellularize vessel segments. Cells were seeded cell-free scaffolds using a compound of fibrin and thrombin and incubated in DMEM, after 4 days of static culture they were placed for 2 weeks in a flow-bioreactor, mimicking the cardiovascular pulsatile flow. After dynamic culture, samples were processed for histological, biochemical and ultrastructural analysis. Discussion. Histology showed that the dynamic culture cells initiate to penetrate the extracellular matrix scaffold and to produce components of the ECM, as collagen fibres. Sirius Red staining showed layers of immature collagen type III and ultrastructural analysis revealed 30 nm thick collagen fibres, presumably corresponding to the immature collagen. These data confirm the ability of cord-derived cells to adhere and penetrate a natural decellularized tissue and to start to assembly into new tissue. This achievement makes natural 3D matrix templates prospectively valuable candidates for clinical bypass procedures

Characterization of vascular cavity coatings and microscopic tube-shaped structures from Upper Cretaceous dinosaur bone: evidence of a bacterial origin for dinosaur blood vessels""

Recent claims of blood vessels extracted from dinosaur fossils challenge classical views of soft-tissue preservation. Alternatively, these structures may represent postdepositional,diagenetic biofilms that grew on vascular cavity surfaces within the fossil. Similar red, hollow, tube-shaped structures were recovered from well-preserved and poorly-preserved (abraded, desiccated, exposed) Upper Cretaceous dinosaur fossils in this study. Integration of light microscopy, scanning electron microscopy, and energy dispersive x-ray spectroscopy was used to compare these vessel structures to the fossils from which they are derived. Vessel structures are typically 100-400 μm long, 0.5-1.5 μm thick, 10-40 μm in diameter and take on a wide range of straight, curved, andbranching morphologies. Interior surfaces vary from smooth to globular and typically contain spheres, rods, and fibrous structures (< 2 μm in diameter) incorporated into the surface. Exterior surfaces exhibit 2-μm-tall converging ridges, spaced 1-3 μm apart, that are sub-parallel to the long axis of the vessel structure. Fossil vascular cavities are typically coated with a smooth or grainy orange layer that shows a wide range of textures including smooth, globular, rough, ropy, and combinations thereof. Coatings tend to overlay secondary mineral crystals and framboids, confirming they are not primary structures of the fossil. For some cavity coatings, the surface that had been in contact with the bone exhibits a ridged texture, similar to that of vessel structures, having formed as a mold of the intravascular bone surface. Thus, vessel structures are interpreted as intact cavity coatings isolated after the fossil is demineralized. The presence of framboids and structures consistent in size and shape with bacteria cells, the abundance of iron in cavity coatings, and the growth of biofilms directly from the fossil that resemble respective cavity coatings support the hypothesis that vessel structures result from ironconsuming bacteria that form biofilms on the intravascular bone surfaces of fossil dinosaur bone. This also accounts for microstructures resembling osteocytes as some fossil lacunae are filled with the same iron oxide that comprises vessel structures andcoatings. Results of this study show that systematic, high-resolution SEM analyses of vertebrate fossils can provide improved insight on microtaphonomic processes, including the role of bacteria in diagenesis. These results conflict with earlier claims of dinosaurblood vessels and osteocytes.

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Postmortem radiology of fatal hemorrhage: measurements of cross-sectional areas of major blood vessels and volumes of aorta and spleen on MDCT and volumes of heart chambers on MRI

OBJECTIVE: Autopsy determination of fatal hemorrhage as the cause of death is often a difficult diagnosis in forensic medicine. No quantitative system for accurately measuring the blood volume in a corpse has been developed. MATERIALS AND METHODS: This article describes the measurement and evaluation of the cross-sectional areas of major blood vessels, of the diameter of the right pulmonary artery, of the volumes of thoracic aorta and spleen on MDCT, and of the volumes of heart chambers on MRI in 65 autopsy-verified cases of fatal hemorrhage or no fatal hemorrhage. RESULTS: Most cases with a cause of death of "fatal hemorrhage" had collapsed vessels. The finding of a collapsed superior vena cava, main pulmonary artery, or right pulmonary artery was 100% specific for fatal hemorrhage. The mean volumes of the thoracic aorta and of each of the heart chambers and the mean cross-sectional areas of all vessels except the inferior vena cava and abdominal aorta were significantly smaller in fatal hemorrhage than in no fatal hemorrhage. CONCLUSION: For the quantitative differentiation of fatal hemorrhage from other causes of death, we propose a three-step algorithm with measurements of the diameter of the right pulmonary artery, the cross-sectional area of the main pulmonary artery, and the volume of the right atrium (specificity, 100%; sensitivity, 95%). However, this algorithm must be corroborated in a prospective study, which would eliminate the limitations of this study. Quantitative postmortem cross-sectional imaging might become a reliable objective method to assess the question of fatal hemorrhage in forensic medicine.

A technique to detect and to quantify fasciocutaneous blood vessels in small laboratory animals ex vivo

PURPOSE: A microangiographical technique is described, which allows visualization of small and capillary blood vessels and quantification of fasciocutaneous blood vessels by means of digital computer analysis in very small laboratory animals. MATERIALS AND METHODS: The left carotid artery of 20 nu/nu mice was cannulated (26 gauge) and a mixture of gelatin, bariumsulfate, and green ink was injected according to standardized protocol. Fasciocutaneous blood vessels were visualized by digital mammography and analyzed for vessel length and vessel surface area as standardized units [SU] by computer program. RESULTS: With the described microangiography method, fasciocutaneous blood vessels down to capillary size level can be clearly visualized. Regions of interest (ROIs) can be defined and the containing vascular network quantified. Comparable results may be obtained by calculating the microvascular area index (MAI) and the microvascular length index (MLI), related to the ROIs size. Identical ROIs showed a high reproducibility for measured [SU] < 0.01 +/- 0.0012%. CONCLUSION: Combining microsurgical techniques, pharmacological knowledge, and modern digital image technology, we were able to visualize small and capillary blood vessels even in small laboratory animals. By using our own computer analytical program, quantification of vessels was reliable, highly reproducible, and fast.

Overexpression of gastrin-releasing peptide receptors in tumor-associated blood vessels of human ovarian neoplasms

BACKGROUND: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin-releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. METHODS: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand (125)I-[D-Tyr(6), beta-Ala(11), Phe(13), Nle(14)]-bombesin(6-14) and the GRP-receptor subtype-preferring (125)I-[Tyr(4)]-bombesin. RESULTS: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. CONCLUSIONS: The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy.

Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels

In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels.

Effects of Carnoy's solution on blood vessels of the axillary fossa of rats

Carnoy's solution is applied to reduce the recurrence of odontogenic keratocysts and unicystic ameloblastomas. The deleterious action of this fixative on nerves has been studied but no attention has been paid to its effects on nearby vessels. The aim of this study was to investigate the effects of Carnoy's solution on blood vessels. The rat axillary artery and vein were surgically exposed, soaked with Carnoy's solution and kept in place for 2, 5 or 10 min, depending on the treatment group. The 5-min group was followed for 1, 2 and 3 weeks postoperatively. The vessels in the 2-min and 5-min exposure groups showed histological changes to the vessels, represented by focal loss of the endothelium and hyalinization of the wall. These alterations increased in the 10-min group. The vessels in the 3-week observation period revealed signs of recovery. It is concluded that Carnoy's solution can damage blood vessels but the process is reversible for exposure times less than 5 min.

Potential role of pre-existing blood vessels for vascularization and mineralization of osteochondral grafts: an intravital microscopic study in mice

BACKGROUND: The aim of this study was to develop an experimental model that allows to elude the potential role of the preexisting graft microvasculature for vascularization and mineralization of osteochondral grafts. ANIMALS AND METHODS: For that purpose, the II-IV metatarsals of fetal DDY-mice known to be nonvascularized at day 16 of gestation (M16) but vascularized at day 18 (M18) were freshly transplanted into dorsal skin fold chambers of adult DDY mice. Using intravital microscopy angiogenesis, leukocyte-endothelium interaction and mineralization were assessed for 12 days. RESULTS: Angiogenesis occurred at 32 hours in M18, but not before 57 hours in M16 (p = 0.002), with perfusion of these vessels at 42 hours (p = 0.005) and 65 hours (p = 0.1), respectively. Vessels reached a density three times as high as that of the recipient site at day 6, remaining constant until day 12 in M18, whereas in M16 vascular density increased from day 6 and reached that of M18 at day 12 (p = 0.04). Leukocyte-endothelium interaction showed sticker counts elevated by a factor of 4-5 in M18 as compared to M16. Mineralization of osteochondral grafts did not differ between M16 and M18, which significantly increased in both groups throughout the observation period. INTERPRETATION: We propose the faster kinetics in the angiogenic response to M18 and the elevated counts of sticking leukocytes to rest on the potential of establishing end-to-end anastomoses (inosculation) of the vascularized graft with recipient vessels.