Major gaps in human evidence for structure and function of the vasa vasora limit our understanding of the link with atherosclerosis.

Atherosclerosis is the major pathology causing death in the developed world and, although risk factor modification has improved outcomes over the last decade, there is no cure. The role of the vasa vasora (VV) in the pathogenesis of atherosclerotic plaque is unclear but must relate to the predictability of diseased sites in the arterial tree. VV are small vessels found on major arteries and veins which supply nutrients and oxygen to the vessel wall itself while removing waste. Numerous studies have been carried out to investigate the anatomy and function of the VV as well as their significance in vascular disease. There is convincing evidence that VV are related to atherosclerotic plaque progression and vessel thrombosis, however, their link to the pathology of plaque initiation remains an interesting but neglected topic. We aim to present the evidence on the anatomy and functional behaviour of VV as well as their relationship to the initiation of atherosclerosis. At the same time, we wish to highlight inconsistencies in, and limitations of, the evidence available.

The vasa vasorum reach deep into the human thoracic aorta.

Only limited data are available on the extent of the vasa vasorum of the human thoracic aorta, although this could be important with regard to certain pathophysiological states, i.e. aortic aneurysm or atherosclerosis. A preliminary investigation shows that the vascularization of the human thoracic aorta reaches deeper layers than generally believed.

Morphology of the vasa vasorum in coronary arteries of the porcine heart: A new insight.

INTRODUCTION: The vasa vasorum interna were described during the last decade as a special kind of vessels originating directly from the lumen of the paternal artery and participating in the nourishment of its wall, especially of the aorta and coronary arteries. At the same time, their existence was repeatedly denied/negated by many other authors. AIM: The purpose of the actual study was the anatomical verification of the existence of the vasa vasorum interna in porcine coronary arteries. MATERIALS AND METHODS: The vascular supply was studied on the wall of the anterior interventricular branch of the left coronary artery on 36 hearts taken from healthy pigs. Light microscopy, vascular injections and scanning electron microscopy were used for the analysis of 141 samples. RESULTS: In only two cases small arteries resembling vasa vasorum interna and originating directly from the lumen of the coronary artery were found. But, in both cases these vessels ran without branching, passed over the whole thickness of adventitia and branched in the wider periarterial space. In contrast to this all feeding arteries of the vasa vasorum arose from the larger branches of the paternal artery, branched entirely in its adventitia and did not enter the media. CONCLUSION: Due to the very low incidence of these small arteries originating from the lumen of the paternal artery and the absence of their participation on the nourishment of the arterial wall we came to the conclusion that it is not suitable to use the term "vasa vasorum interna" for their designation.

Vasa vasorum: an old term with new problems.

PURPOSE: The aim of the study was to describe the origin of the Latin anatomical term vasa vasorum and its role in current medical research and to present examples of grammatical errors in its use. METHODS: Literary searches oriented on the term vasa vasorum were used to identify publications using it in the medical literature from the seventeenth century up to the present. RESULTS: The Latin term vasa vasorum was introduced by Ludwig in 1739. The vasa vasorum became an important topic in clinical research around the middle of the twentieth century, with implications in angiology, cardiology and cardiosurgery. We report 18 grammatical errors concerning the use of the term vasa vasorum, starting from the year 1959. A similar decline in the correct use of Latin terminology is also evident in other medical research disciplines. CONCLUSIONS: The numerous errors found in the use of Latin terminology in recent medical literature have occurred as a consequence of decreased use of Latin in the medical community. The only way to improve this situation is by improving awareness of international standard anatomical terminology, which is available worldwide in both Latin and English.

Ascending aorta of hooded seals with particular emphasis on its vasa vasorum.

The pressure-volume relationship in the ascending aorta ("windkessel") of the hooded seal was determined and the morphology of its vasa vasorum described in some detail. We found that the ascending aorta has a high compliance and can easily accommodate the entire stroke volume when the peripheral vascular resistance becomes much increased and maintain perfusion pressure during the much extended diastole and thereby reduce cardiac stroke work during diving. We also found that the 3- to 5-mm thick wall of the ascending aorta had a very elaborate vasa vasorum interna with a hitherto undescribed vascular structure that penetrates the entire vascular wall. If similar structures with similar importance for the nutrition of the wall of the vessel are found in humans, important implications for the understanding of pathological conditions, such as aneurisms, may be indicated.

Topologic distributions of vasa vasorum and lymphatic vasa vasorum in the aortic adventitia--Implications for the prevalence of aortic diseases.

BACKGROUND AND AIMS: Vasa vasorum (VV) and lymphatic vasa vasorum (LVV) form their own networks in the adventitia. VV supply the aorta with nutrition and oxygen; however, the distribution and role of LVV remains to be determined. The purpose of this study was to investigate differences in the distribution of VV and LVV along the aorta. METHODS: Aortic samples were obtained from 22 autopsy cases without medical history of aortic diseases. Aortic segments were classified as arch (Ar), descending thoracic (De), suprarenal abdominal (S-Ab), and infrarenal abdominal (I-Ab). Adventitial VV and LVV were identified immunohistochemically. RESULTS: VV were most dense in the arch aorta, becoming less dense along the aorta in more distal segments, with the lowest density occurring in the infrarenal abdominal aorta. There was a significant correlation between the numbers of VV and medial thickness in the total aortic segments (r = 0.518, p < 0.01). In contrast, there was no significant correlation between the number of LVV and medial thickness in any aortic segments. However, there was a significant correlation between the number of LVV and intimal thickness in I-Ab (r = 0.425, p < 0.05). CONCLUSIONS: The distributions of adventitial VV and LVV were characteristic along the aortic segments. Differences in the distributions may imply the prevalence of aortic diseases such as dissection, abdominal aortic aneurysm, and atherosclerotic occlusive disease in each aortic segment.

Atherosclerosis and atheroma plaque rupture: normal anatomy of vasa vasorum and their role associated with atherosclerosis.

Atherosclerosis is primarily a degenerative disorder related to aging with a chronic inflammatory component. There are differences in expression among different vascular beds, inflicting a range of vascular diseases. The majority of studies focus on the inner and medial vascular layers, which are affected at the development of atherosclerosis. Recent evidence shows that the outer layer of blood vessels, composed of the adventitial layer and the vasa vasorum, not only plays a significant role in maintaining vessel integrity, but also reacts to atheroma. What is not clear is the extent of contribution of the outer layer to the process of atherosclerosis. Is it involved in the initiation, progression, and clinical expression of atheroma? Is the inflammation associated with atheroma limited to being merely reactive or is there a proactive element? This paper provides an overview of the normal anatomy of vasa vasorum and potential mechanism of plaque formation due to vascular injury (vasa vasorum) and microhemorrhage.

Vasa vasora in the tunica media of goat aorta / Vasa vasora en la túnica media de la aorta de cabra

This study aimed at describing the distribution of vasa vasora in the tunica media of various parts of goat aorta, since this influences the physico-mechanical properties and disease occurrence. Specimens were obtained from ascending, arch, each vertebral level of descending thoracic and various segments of abdominal aorta of sixteen healthy adult male domestic goats (Capra hircus). They were fixed in 10 percent formaldehyde solution, and routinely processed for paraffin embedding. Seven micron thick sections were stained with Mason's Trichrome stain. Vasa vasora are present in the tunica media of all the aortic segments. In the proximal segments, they co-localize with muscle islands found in the adventitial half. Their density declines caudally, but they are still present in the tunica media even in the abdominal aorta where the thickness is less than 0.5mm and elastic lamellae less than 29. Vasa vasora in the goat aortic tunica media penetrate into the luminal half and are present even in relatively thin segments. This extent, which may enhance vascular health, suggests that the goat aortic wall is very active, a feature probably related to auxillary pump function of the muscle islands in the aortic wall.

El objetivo de este estudio fue describir la distribución de vasa vasora en la túnica media de diversas partes de la aorta de cabra, ya que esto influye en las propiedades físicas y la aparición de enfermedades. Las muestras se obtuvieron de 16 cabras machos adultos sanos (Capra hircus) desde la porción ascendente del arco aórtico, segmentos torácicos descendentes y de la parte abdominal de la aorta. Las muestras se fijaron en solución de formol al 10 por ciento, y fueron sometidas a procesamiento de rutina para inclusión en parafina. Secciones de siete micras de grosor se tiñeron con reacción tricrómica de Masson. Vasa vasora están presentes en la túnica media de todos los segmentos de la aorta. En los segmentos proximales, que localizan con islas de músculo que se encuentra en la mitad de la adventicia. Su densidad disminuye en sentido caudal, pero aún están presentes en la túnica media, incluso en la parte abdominal de la aorta, donde el espesor es inferior a 0,5 mm y láminas elásticas menos de 29. Vasa vasora en la túnica media de la aorta de la cabra penetran en el medio luminal y están presentes incluso en segmentos relativamente delgados. Esta medida, que puede mejorar la salud vascular, sugiere que la pared aórtica de la cabra es muy activa, una característica probablemente relacionada con la función de la bomba auxiliar de las islas del músculo en la pared aórtica.

Angioarchitecture of the bovine spermatic cord.

We described the topography and morphometry of the testicular artery, pampiniform plexus veins, and indirect connections between them in the spermatic cord of the bull. Sixty microcorrosive casts of bovine spermatic cords were analyzed macroscopically, by stereomicroscopy, and by scanning electron microscopy. The average size of the testicles was 94.6 × 49.7 × 54.7 mm. The testicular artery formed a superiorly pointed cone-like structure with its base fixed to the proximal part of the gonad. The artery gave off one or two branches to the head of epididymis and to the deferens duct. The pampiniform plexus originated from intra-tunical veins. Veins of the pampiniform plexus were of smaller diameter but larger number than intra-tunical ones. The density of the veins of the pampiniform plexus was 9.37 ± 1.07 mm(-2) . The testicular vein began 90-121 mm above the superior pole of the testis. In 2.9% of specimens, the testicular vein was doubled. Numerous anastomoses among veins of pampiniform plexus were observed. Additionally, indirect anastomoses between the testicular artery and pampiniform plexus veins formed by the capillary network of the vasa vasorum of the testicular artery were visualized by scanning electron microscopy. In all cases, narrowings in the casts of the precapillary vessel were observed. We also documented the vasa vasorum of the testicular artery in bulls. The density of these vessels was 22.87 ± 11.48 mm(-2) . The indirect arteriovenous connections together with the presence of circular constrictions of the lumen in precapillary vessels may play a role in testicular blood flow regulation.

Quantification of vasa vasorum density in multi-slice computed tomographic coronary angiograms: role of computed tomographic image voxel size.

OBJECTIVE: This study is motivated by the possibility of using computed tomography (CT) to detect early coronary atherosclerosis by the increased CT values within the arterial wall resulting from vasa vasorum proliferation. METHODS: Coronary arteries (n = 5) with early atherosclerotic changes were injected with Microfil and scanned (micro-CT). Noise was added to the CT projection data sets (to represent the radiation exposure of current clinical CT scanners) and then reconstructed to generate 3-dimensional images at different voxel sizes. RESULTS: Higher CT values were detected because of contrast agent in vasa vasorum if voxel size was less than (150 microm)(3). Contrast in the main lumen increased the CT values dramatically at voxels greater than (100 microm)(3), whereas CT values of the same specimen without contrast in the main lumen remained constant. CONCLUSIONS: Voxel sizes less than (200 microm)(3) are needed to quantitate arterial wall opacification due to vasa vasorum proliferation.

Will the real plaque vasculature please stand up? Why we need to distinguish the vasa plaquorum from the vasa vasorum.

Many studies of experimental atherosclerosis and pathologic observations of human specimens have provided evidence supporting a correlation between vascularization of the atherosclerotic plaque and its natural growth and progression toward acute failure, associated with clinical events. The growing interest in the topic is illustrated by several excellent recent reviews discussing the molecular mechanisms that might play a role in the formation of plaque vasculature and that could explain some of the observed associations with pathologic features of experimental and human atherosclerotic lesions. At the same time, these reviews also emphasize that the field is still largely in uncharted territory. Hoping to spark some new investigations, we are taking this opportunity to question some of the common assumptions and to highlight less explored mechanisms. Finally, we are proposing to adopt the term vasa plaquorum to refer to the neovasculature located within the atherosclerotic plaque to distinguish it clearly from vasa vasorum, the native, supporting vasculature of the artery. We suggest that this new nomenclature offers a potential solution to eliminate ambiguity regarding implicit, but frequently neglected, differences between these structures. We think these points are relevant for future efforts to tailor diagnostic tools and therapeutic interventions targeting plaque neovascularization for the clinical management of atherosclerosis.

Architectonic arrangement of the vasa vasorum of the human great saphenous vein.

OBJECTIVE: The detailed spatial arrangement of the vasa vasorum (VV) of the human great saphenous vein (HGSV) was demonstrated in qualitative and quantitative terms. MATERIALS AND METHODS: Segments of the HGSV taken from cadavers 12-24 h post mortem and from patients undergoing aortocoronary bypassing were studied by light microscopy of India-ink-injected specimens and by scanning electron microscopy of vascular corrosion casts. RESULTS: Arterial feeders were found to approach the HGSV from nearby arteries every 15 mm forming a rich capillary network within the adventitia and the outer two thirds of the media in normal HGSV, while in HGSV with intimal hyperplasia capillary meshes extended into the inner layers of the media. Within the media, capillary meshes ran circularly. Postcapillary venules drained centrifugally towards the adventitial venous vessels which finally formed venous drainers running adjacent to the arterial feeders. Three-dimensional morphometry of vascular corrosion casts of VV revealed that diameters of (i) arterial VV ranged from 11.6 to 36.6 microm, (ii) capillary VV from 4.7 to 11.6 microm and (iii) venous VV ranged from 11.6 to 200.3 microm. CONCLUSIONS: The 3D network of VV suggests these layers are metabolically highly active and therefore require a continuous blood supply. We conclude, therefore, that the VV network must be preserved during in situ bypassing.

The absence of lymphatics in normal and atherosclerotic coronary arteries in man: a morphologic study.

It has been suggested by various investigators that the impairment of lymphatic drainage from the coronary arteries may play a role in predisposition to coronary atherosclerosis, the pathogenesis of which is certainly multifactorial. In our study, no lymphatic vessels were found in the walls of the coronary arteries (adventitia, media and intima) in 51 human hearts from patients ranging in ages from 3 months to 83 years with normal coronary arteries, coronary atherosclerosis, and cardiomyopathy. Visualized lymphatics were located solely in the periadventitial area, and these lymphatics were more irregular in hearts from older persons. With injection, histology, and electronmicroscopy methods we could not detect penetration of lymphatics into the wall of coronary trunks in normal as well atherosclerotic arteries. In all coronary arteries studied, and particularly in the atherosclerotic lesions, blood vasa vasorum could be visualized. In the atherosclerotic areas, vasa vasorum (angiogenesis) could be seen penetrating into the media and intima. Many of the thin-walled vasa vasorum could easily be mistaken for lymphatics. The absence of lymphatics draining the epicardial coronary arteries may be a predisposing factor to coronary atherosclerosis.

Types of vascular wall as related to vasa vasorum in common tree shrew (Tupaia glis).

Blood vessels of the common tree shrew (Tupaia glis) were embedded in Araldite, sectioned at 0.5-1 microm thickness, and observed with light microscope (LM). It was found that the vascular wall could be classified into three categories: (1) those with proper vasa vasorum (PVV); (2) those with collaborative vasa vasorum in perimural tissues; (3) those without vasa vasorum. The PVV were located in the the tunica media, between the tunica media and the tunica adventitia, and in the tunica adventitia of the vascular wall. On studying the vascular casts with a scanning electron microscope (SEM), it was noted that what appeared to be vasa vasorum did not always conform to those found under the LM. Furthermore, the PVV seen in a particular blood vessel among different tree shrews were not always related to intraluminal partial pressure of oxygen, vascular size, and thickness of the wall. In contrast, the results of this study indicate that the activeness of the vascular wall in varying the amount of blood flow to certain organs is an important factor that is associated with the existence, density, and distribution of the vasa vasorum.

Three-dimensional arrangement of the vasa vasorum in explanted segments of the aged human great saphenous vein: scanning electron microscopy and three-dimensional morphometry of vascular corrosion casts.

The vasa vasorum of skeletonized and nonskeletonized segments of five human great saphenous veins (GSVs), harvested during coronary bypass grafting, were cannulated, rinsed, and injected (casted) with the polymerizing resin Mercox-Cl-2B. After removal of the dry vascular tissue, the casts were examined using scanning electron microscopy. Stereopaired images (tilt angle, 6 degrees ) were taken, imported into a 3D morphometry system, and the 3D architecture of the vasa vasorum (arterial and venous vasa as well as capillaries) was studied qualitatively and quantitatively in terms of vasa diameters, intervascular and interbranching distances, and branching angles. Diameters of parent (d(0)) and large (d(1)) and small (d(2)) daughter vessels of arterial and venous bifurcations served to calculate asymmetry ratios (alpha) and area ratios (beta). Additionally, deviations of bifurcations and branching angles from optimal branches were calculated for selected arterial vasa. The arrangement of the vasa vasorum closely followed the longitudinally oriented connective tissue fibers in the adventitia and the circularly arranged smooth muscle cell layers within the outer layers of the media. Venous vasa by far outnumbered arterial vasa. Vasa vasorum changed their course several times in acute angles and revealed numerous circular constrictions, kinks, and outpouchings. Due to their spatial arrangement, the vasa vasorum are prone to tolerate vessel wall distension generated by acute increases in blood pressure or stretching of the vessel without severe impact on vessel functions. Preliminary comparisons of data from the bifurcations of cast arterial vasa vasorum, with calculated optimal bifurcations, do not yet give clear insights into the optimality principle(s) governing the design of arterial vasa vasorum bifurcations of the human GSVs.

Adventitial vasa vasorum heterogeneity among different vascular beds.

INTRODUCTION: Different vascular beds show substantial variation in their susceptibilities for development of vascular disease like atherosclerosis, and thereby exhibit a variety of different clinical presentations. Yet, the underlying mechanism of this heterogeneity is not well defined. Recent evidence suggests a role for the vasa vasorum (VV) in vascular disease. We hypothesized that there is a differential distribution structure of adventitial VV in different vascular beds. Hence, the current study was designed to characterize and compare the structure of the adventitial VV in the coronary and the peripheral circulation. METHODS: Samples of vessels from different vascular beds were obtained from 6 female crossbred domestic pigs. The samples were scanned using micro-computed tomography, and the images reconstructed and analyzed to characterize VV architecture, including vessel wall area, VV count, VV density, intravessel spatial distribution, mean diameter of first- and second-order VVs and the ratio of second- to first-order VVs. RESULTS: There were significant differences in VV density among different vascular beds. Density was highest in coronary arteries (2.91 +/- 0.26 vessels/mm2, P <.05, vs renal, carotid, and femoral arteries), intermediate in renal arteries (1.45+/- 0.22 vessels/mm2, P <.05, vs femoral artery) and carotid arteries (0.64 +/- 0.08 vessels/mm2, P <.05, vs femoral artery), and lowest in femoral arteries (0.23 +/- 0.05 vessels/mm2 ). A similar pattern for the ratio of second- to first-order VV was also observed. Random intravessel spatial distribution of VVs was seen in all vascular beds. CONCLUSION: The current study demonstrates a differential structure of the adventitial VV in different vascular beds. This intra- and intervessel heterogeneity in VV anatomy is a phenotypic variability that might determine a differential local response to systemic risk factors and, thereby, variable propensity for vascular disease among different vascular beds.

Vasa vasorum growth in the coronary arteries of newborn pigs.

Experimental studies have shown that a "plexus" of vasa vasorum already exists in fetal arteries. In this study we examine the further development of vasa vasorum in the newborn. Hearts from 1- and 6-month-old pigs were harvested and infused with Microfil via the aortic ostia of the coronary arteries at physiological pressure (100 mmHg). Coronary arteries (RCA, LAD, and LCX) were then isolated and scanned intact with micro-CT (20 microm cubic voxel size). Using Analyze 5.0 software we digitally isolated individual vasa vasorum trees (eight from 1-month-old and eight from 6-month-old pigs) and measured geometrical data such as interbranch segmental diameters, lengths, and branching angles as well as mother-daughter branch relationships for all segments of each vasa vasorum tree structure. Also, we determined the volume of vessel wall perfused by individual vasa vasorum trees. Our results show that the vasa vasorum architecture in newborn pigs is already tree-like, and this structure as well as the volume of vessel wall perfused by it expand in concert with the growth of the host coronary artery. We give quantitative details of this growth of vasa vasorum in terms of its branching architecture and hemodynamic capacity, based on direct measurements from 3D images of this microvasculature.

Impact of coronary vasa vasorum functional structure on coronary vessel wall perfusion distribution.

Noncoronary vasa vasorum have been described as networks of microvessels in the wall of arteries and veins. However, we have shown, using microcomputerized tomography (micro-CT) imaging methods, that porcine coronary vasa vasorum have a tree-like branching structure similar to the vasculature in general. In this study, we elucidate functional aspects of coronary vasa vasorum perfusion territories. Three pig hearts were injected with radiopaque Microfil via the coronary sinus to fill the left anterior descending coronary arteries (LADs) retrogradely at atmospheric pressure. In three other hearts, LADs were injected antegradely at 100-mmHg pressure via the left main carotid artery. Additionally, six LADs were injected in vivo with a suspension of 100- or 300-microm-diameter microspheres before harvesting of the hearts and injection of the LADs with Microfil. All harvested LADs were scanned intact with micro-CT (20 microm cubic voxels). The spatial density of vasa vasorum (no. of vasa/mm2) was measured in 20-microm-thick cross sections (at 0.4-mm intervals). Retrogradely injected LADs showed high and uniformly distributed vasa vasorum densities in the adventitia (means +/- SE; 5.38 +/- 0.09 vs. 3.58 +/- 0.1 vasa/mm2 in antegradely prepared LADs; P < 0.001). Antegradely prepared LADs showed patchy distributed, low-vasa-vasorum-density territories especially on the myocardial side of the coronary artery wall (epicardial density: 4.29 +/- 0.13 vasa/mm2 vs. myocardial density: 2.80 +/- 0.1 vasa/mm2, P < 0.001). Microembolization reduced vasa vasorum densities significantly (100-mum-diameter microspheres: 3.26 +/- 0.07 vasa/mm2, P < 0.05; 300-microm-diameter microspheres: 2.66 +/- 0.07 vasa/mm2, P < 0.001 vs. antegrade controls) and increased the size of low-vasa-vasorum-density territories. We conclude that coronary vasa vasorum are functional endarteries not connected via a plexus. This characteristic may have a significant impact on the spatial distribution of perfusion and drainage of the coronary vessel wall.

Functional anatomy and hemodynamic characteristics of vasa vasorum in the walls of porcine coronary arteries.

In this study vasa vasorum in the walls of porcine coronary arteries were examined, using three-dimensional (3D) micro-CT scanning techniques. These techniques leave the 3D structure of the vasa vasorum tree intact and thus provide a much more direct view of this structure than is possible from conventional histological sections. The study demonstrates-for the first time, we believe-both the different types and the fine architecture of these vasa vasorum. Furthermore, with the use of automated tree analysis software, it was possible to obtain quantitative geometrical data on the 3D structure of vasa vasorum trees that have not previously been available. The results indicate that despite the restrictive topology of the space in which they are present, the branching architecture of the vasa vasorum trees, which we surveyed, is surprisingly similar to that of vasculature in general. The volume of vessel wall tissue perfused or drained by a vasa vasorum tree was found to correlate well with the cross-sectional area of the root segment of the vasa vasorum tree, and the luminal surface area corresponding to this volume was found to be comparable with the surface area of an early atherosclerotic lesion. This is consistent with earlier findings that the ligation or removal of vasa vasorum leads to atherogenesis.

Vasa vasorum of the human great saphenous vein.

The distribution of the vasa vasorum of the human great saphenous vein (GSV) was studied on veins taken both post-mortem and peroperatively. It was found that the stems of feeding vessels approach the venous wall at intervals of 1.5-2.5 cm; their smaller branches first passed the fascial compartments of the GSV and then entered the adventitia at intervals of 0.5-1.5 cm on both the stem and the largest tributaries of the GSV. In the stem regions vasa vasorum arteries and veins ran together but, between neighboring stems, isolated venae vasorum were regularly found which opened individually into terminal segments of the largest tributaries of the GSV. Neither by dissection nor by injection methods were venae vasorum found to open directly into the lumen of the GSV stem. The total thickness of the media ranged between 500 and 1300 micro m, according to the state of constriction of the venous wall before fixation. Two structurally different layers of GSV tunica media were present: an inner loose layer and an outer dense layer, both of similar thickness. The innermost capillaries of the vasa vasorum network were found in all cases on the border between the two layers of media. No lymphatic was found in any of the layers of GSV wall. From the findings the authors recommend extremely careful dissection of the GSV wall during in situ grafting surgery, to ensure the best viability of the venous wall.