Microcirculatory Dysfunction in Chronic Venous Insufficiency (CVI)

The elevated ambulatory pressure in the peripheral venous system of chronic venous insufficiency (CVI) patients manifests itself not only in the form of disturbed macrocirculation but also and particularly in microangiopathic changes. For this reason, it is closely correlated with trophic disorders of the skin and can ultimately lead to ulceration. Using microcirculation research techniques, we are able to provide clear evidence of a typical microangiopathy in chronic venous insufficiency. Fifty CVI patients in Widmer stages I, II, and III were examined with fluorescence video microscopy, intravital video capillaroscopy, transcutaneous oxygen partial pressure measurement, TcpO₂ and laser Doppler flowmetry. The effects of compression therapy with individually fitted compression stockings on capillary morphology were studied over a period of 4 weeks in 20 CVI patients in Widmer stages I and II. The capillary pressure was measured during simulated muscle contraction using a servo‐null micropressure system. We periodically drew blood from the dorsalis pedis vein and a brachial vein of 11 healthy test persons and 8 patients with stage III CVI during experimental venous hypertension in order to evaluate the expression pattern of leukocyte adhesion molecules involved in inflammation: LFA‐1 (CD11a), Mac‐1 (CD11b), p150,95 (CD11c), CD18, VLA‐4 (CD49d), and L‐selectin (CD62L). In the same patients, we used immunohistochemical methods to examine clinically unaffected skin and the skin near an ulcer, focusing on the adhesion molecules ICAM‐1, VCAM‐1, and E‐selectin. The microangiopathic changes observed with worsening clinical symptoms include a decrease in the number of capillaries, glomerulus‐like changes in capillary morphology, a drop in the oxygen content (tcpO₂) of the skin, increased permeability of the capillaries to low‐molecular‐weight substances, increased laser Doppler flux reflecting elevated subcutaneous flow, and diminished vascular reserve. These microangiopathic changes worsen in linear proportion to the clinical severity of chronic venous insufficiency. In patients with venous ulcerations, the baseline expression of LFA‐1 and VLA‐4 on lymphocytes, Mac‐1 expression on the myeloid cell line, and L‐selectin expression on all three cell lines was not significantly different from that in healthy controls. During orthostatic stress, there was a significant reduction in the expression of L‐selectin in blood cells collected at foot level in the controls (p = 0.002), but not in the patients. Clinical improvement by compression therapy was accompanied by an increase in the number of nutritive capillaries, while the diameter of the capillaries and the dermal papillae was reduced. When ulcers healed in a short period (<6 weeks), we observed a concomitant increase in the number of capillaries (p < 0.05). Microangiopathy appears before trophic disorders of the skin develop. Even trophically normal skin areas may have dilated nutritive capillaries, an early sign of disturbed skin perfusion. These changes represent a plausible explanation for the development and to recurrency tendency of venous ulcers. The reduced expression of lymphocytic L‐selectin in healthy controls during the orthostatic stress test may be an indication that the cells are activated by venous stasis. Clinically effective therapeutic measures improve the impaired microcirculation of the skin in the ankle area.     

Changes in the microcirculation in slow and fast skeletal muscles with long term limitations of blood supply

STUDY OBJECTIVE--Long term limitation of blood flow leads to decreased muscle performance and to damage, particularly in predominantly oxidative muscles. This study was performed to assess to what extent such damage can be explained by changes in microcirculation in capillaries supplying glycolytic or oxidative muscle fibres. DESIGN--Velocity and intermittency of flow, capillary diameters and proportion of adhering leucocytes were measured in capillaries in the epi-illuminated superficial glycolytic layer of rat tibialis anterior and in oxidative soleus muscles five weeks after ligation of the common iliac artery. EXPERIMENTAL MATERIAL--Male Sprague Dawley rats (approximately 350 g) were used, under sodium pentobarbitone anaesthesia. MEASUREMENTS AND RESULTS--Pressure in the saphenous artery, distal to the ligation site, recovered to 61% of carotid mean pressure. In tibialis anterior with limited blood supply, capillary diameters were narrower, red blood cell velocity was greater and intermittency of flow was reduced, resulting in a calculated volume flow per capillary which was only marginally reduced compared with controls. In soleus with limited blood supply, the time spent stationary by red blood cells was increased and there was a greater adhesion of white blood cells to venular walls. In neither muscle did limitation of blood supply result in a change in capillarity. CONCLUSIONS--Long term limitation of blood supply does not diminish the capillary density or capillary to fibre ratio of anatomically present capillaries in oxidative or glycolytic muscles and does not affect blood flow in capillaries supplying glycolytic fibres appreciably; circulation in capillaries supplying oxidative fibres is impaired.     

Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium

Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte-rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte-rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross-sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte-rich areas (P <0.01). Since macrophages and macrophage-derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.     

Basement membrane thickening of postcapillary venules and capillaries in rheumatoid synovium. Immunoelectron microscopic and electron microscopic morphometric analysis

Pathologic changes in the basement membrane (BM) of postcapillary venules (PCV) and capillaries in rheumatoid arthritis (RA) synovium were studied by immunoelectron microscopy, using a monoclonal antibody against human type IV collagen, C(IV)22, and by electron microscopic morphometric analysis. The sublining region of RA synovium was classified into lymphocyte-rich areas, transitional areas, and interstitial areas, according to their pattern of cellular infiltration. In lymphocyte-rich areas, the BM of the PCV and capillaries were minimally thickened; disruption of the lamina densa was seldom seen. Transitional areas, which contained macrophages, lymphocytes, and plasma cells, had numerous PCV and capillaries. The BM was markedly thickened and partially multilamellated, and there were many disruptions in the lamina densa. The BM contained degenerated endothelial cells and cell debris. On immunostaining of this BM with monoclonal antibody C(IV)22, type IV collagen stained heavily, mainly in the disrupted lamina densa; this indicates that the thickening was, at least in part, the result of an increase in BM collagen. In uninfiltrated interstitial areas, BM were moderately thickened and multilamellated, and showed few disruptions of the lamina densa; there were similar increases in type IV collagen, but cell debris was seldom observed. Measurement of the BM width, the ratio of BM width to vessel diameter, and the fraction of vascular cross-sectional area occupied by BM demonstrated that the thickness of the BM of both PCV and capillaries was greatest in transitional areas and was smallest in lymphocyte-rich areas (P less than 0.01). Since macrophages and macrophage-derived factors have been found to promote synthesis of BM collagen type IV, and since transitional and interstitial areas are rich in macrophages and histiocytes, respectively, it is suggested that these mononuclear cells and the factors secreted by them play a significant role in the thickening of the BM of PCV and capillaries in RA synovitis.     

Ultrastructural and immunohistochemical studies of the intrahepatic peribiliary capillary plexus in normal livers and extrahepatic biliary obstruction in human beings.

Ultrastructural and immunohistochemical study was conducted on the intrahepatic peribiliary capillary plexus in normal livers and in those with extrahepatic biliary obstruction. In both conditions, capillaries positive for Ulex europaeus agglutinin I and type IV collagen were always present in the vicinity of the bile ducts. Immunoelectron microscopy showed the presence of type IV collagen on the basal lamina of these capillaries; Ulex europaeus agglutinin I was also positive on their cytoplasms. Under electron microscope, a considerable number of these capillaries were seen as being composed of fenestrated endothelium with a diaphragm and with extreme cytoplasmic attenuations that were dense at the sides facing the bile duct in comparison with the opposite sides in normal livers. In extrahepatic biliary obstruction, plasmalemmal pinocytic vesicles, multivesicular bodies and other cellular organellae such as rough endoplasmic reticulum and Weibel-Palade bodies increased in number in these capillaries, relative to normal livers, probably reflecting increased permeability and functional activities. These characteristic ultrastructural features of the peribiliary capillary plexus might be arranged to transport substances effectively by way of intrahepatic biliary epithelial cells in normal livers and also might be altered to meet the increased functional demands of extrahepatic biliary obstruction.     

The histomorphologic changes at the saphenofemoral junction in varicosis of the greater saphenous vein

BACKGROUND: Insufficiency of the greater saphenous vein starts at its junction with the femoral vein, so that the histomorphologic changes at the saphenofemoral junction are of special interest. METHOD: In this study we examined which histologic changes occur in the vein walls 5 cm distal to the junction of the greater saphenous vein into the femoral vein and whether these changes correlate to the clinical severity of venous disease. For this the morphologic changes of 28 venous specimens were described qualitatively and the two layers of the media were measured at their thickest and thinnest points. RESULTS: The three-layered structure of the vessel wall with intima, media and adventitia was destroyed in 21% of the cases, the intima and media were fused into one another due to loss of the membrana elastica interna. In 93% the intima was thickened at circumscribed areas. Sprouting of capillaries into the intima was found only if varicosis lasted for longer than 15 years. Aneurysms were found in 29% of the specimen. In part of severe aneurysms the media was completely missing. The thickness of the circular muscle layer of the media varied more than that of the longitudinal muscle layer (difference between minimal and maximal thickness 400 +/- 130 microM compared to 190 +/- 90 microM). With increasing clinical severity of the chronic venous insufficiency the difference between minimal and maximal thickness of the circular muscle layer increased (330 +/- 90 microM at stage I according to Widmer, 490 +/- 130 at stage III). CONCLUSION: The coexistence of muscular hypertrophy and atrophy in varicose veins is regarded by us as a reaction to altered perfusion and pressure in the veins. Considering the frequently severe damage to the veins, indication for a vein sparing therapy has to be viewed with care.     

Immunohistochemical investigation of pericytes in chronic venous insufficiency.

Patients with chronic venous insufficiency show typical glomerulum like alterations of cutaneous capillaries. Objective of this study was to determine any changes of the alignment of pericytes around cutaneous capillaries in CVI patients. Skin biopsies from the area of the medial malleolus were taken from 42 patients with CVI, 5 healthy individuals and 11 cadavers without history of CVI. Sections were stained with HHF35, anti alpha and gamma muscle actin with the avidin-biotin-peroxidase method (ABC) and anti vimentin with the alkaline phosphatase anti-alkaline phosphatase technique (APAAP). The stage of stasis dermatosis was assessed and sections were examined for pericyte changes. Among the collective of 42 patients with CVI, 31 patients showed slight or severe pericyte changes, 11 patients were without changes. None of the sections from cadavers or healthy patients showed any pericyte changes. Pericytes are among other functions possibly involved in microvasculature regulation and wound healing. Thus destruction of the pericyte envelope might lead to microcirculatory dysfunction. This could be one of the causes that lead to leg ulcers in CVI.     

Pathophysiology of microcirculation in venous disease

Microcirculatory disturbances lead to chronic ulceration of the leg, and this symptom is a sign of a chronic venous insufficiency (CVI), caused by increased leg vein pressure and continous changes in vein pressure, which need medical treatment, and if a chronic capillary reaction present, treatment by applying a graduated compression bandage of the leg is mandatory. Subcutaneous tissue hypoxaemia and interstitial edema lead to worsening of the ulcer and need intensive and systematic wound care, because unhealed chronic wound with trophic changes of the skin is the major cause of further CVI changes of the leg. As chronic venous disease has complex etiologic basis, it needs diagnostics and treatment modality based on various approaches, and that microcirculatory pathophysiological approach should be considered in all kinds of the treatment of chronic venous insufficiency. Microcirculation pathology should be used as an approach in the treatment regiment of CVI, whilst the basic pathophysiology of the venous diseases, which is known as one of the causes of CVI. This approach will give better results of treatment and other pathologic disturbances which were caused by chronic vitious circle chain processes.     

Biologic characterization of human bone tumors I. Ewing's sarcoma

Summary Six cases of Ewing's sarcoma were investigated by electron and immunofluorescence microscopy. A layer of basement membrane-like deposits was found between typical principal and secondary tumor cells. To clarify the nature of these ultrastructural deposits, antibodies against collagen type IV were applied to frozen sections of corresponding tumor tissue. This reaction revealed type IV collagen as a regular component of basement membranes in nonneoplastic tumor capillaries, but it was equally able to localize collagen type IV between single tumor cells in capillary-free areas. With the same method, factor-VIII-associated protein, predominantly found in endothelial cells, could be demonstrated in some tumor cells. These results demonstrate that, in addition to anaplastic cells, some tumor cells are found in Ewing's sarcoma that share certain differentiating features with the endothelial cell.Supported by Bundesminister für Jugend, Familie und Gesundheit of the Federal Republic of GermanyDedicated to Prof. Dr. Gerhard Seifert on the occasion of his 60th birthday     

Transcutaneous oxygen tension and capillary morphologic characteristics and density in patients with chronic venous incompetence

The transparent oxygen electrode, recently developed by Huch and his co-workers, permits monitoring of transcutaneous oxygen tension (tcPO2) at defined sites on the capillaroscopic image obtained by videomicroscopy. This combined system has been applied to study the nutritional skin capillaries of patients with chronic venous incompetence (CVI). The results of 44 studies in 17 patients with CVI demonstrated a direct correlation between tcPO2 and density and morphologic characteristics of the superficial capillaries. The mean tcPO2 was 47.7 +/- 14.4 mm Hg at the site of incompetent perforating veins of the ankle without major trophic changes. There was no statistically significant difference between the mean values obtained in patients and control subjects (56.8 +/- 9.9 mm Hg). Videomicroscopic examination revealed dilated and tortuous capillaries surrounded by halo formations. In areas of hyperpigmentation, induration, and hyperkeratosis, significantly decreased mean tcPO2 (22.5 +/- 7.0 mm Hg; p less than .001) corresponded to reduced capillary density (less than 10 capillaries/mm2). In avascular skin areas (scar tissue, white atrophy) tcPO2 was measured at 0 mm Hg. No capillaries, or a greatly reduced number, were visible at such sites, resulting in a distance between capillary and cathode tip of the oxygen sensor of greater than 100 micron. The combined system of tcPO2 measurement and simultaneous videomicroscopy gives new pathophysiologic information on the development of skin ulcers and may be useful for the objective comparison of different therapeutic modalities at the microcirculatory level.     

Hypertension pulmonaire et insuffisance cardiaque : le rôle de la vascularisation pulmonaire

Left heart disease is the most common cause of pulmonary hypertension. Increased left-sided filling pressure leads to passive postcapillary venous hypertension. In some patients, pulmonary vasoconstriction and vascular remodeling may lead to a further increase in pulmonary pressure. When precapillary hypertension component is associated to left heart failure, the elevation of pulmonary pressure is out of proportion with left atrial pressure: transpulmonary gradient greater than 12 mmHg (mean pulmonary pressure - mean capillary pressure) and pulmonary vascular resistance greater than three Wood units. Precapillary pulmonary hypertension is common in severe systolic heart failure. Before cardiac transplantation, increased pulmonary vascular resistance greater than 3,5 Wood units are reported in 19 to 35% of patients. In those patients vasoreactivity tests are performed with inotropic and/or systemic and/or pulmonary agents to determine the risk of right heart failure after transplantation. There is no pulmonary vascular resistance level above which transplantation is contraindicated. Cardiac assistance may be used before and after transplantation when pulmonary hypertension is severe and not reversible with conventional treatment and/or pulmonary vasodilators. The contribution of precapillary PH in diastolic heart failure is not known but can be significant and lead to disproportionate PH particularly in elderly. The precapillary component of pulmonary hypertension could be a therapeutic target for specific pulmonary vasodilators. Until now pharmacological trials has been disappointing and those medications can be dangerous because of increasing blood flow to the pulmonary capillaries with a risk of pulmonary edema when left sided pressure are still elevated.     

'Real' epidemiology of varicose veins and chronic venous diseases: the San Valentino Vascular Screening Project

The aim of this study was to evaluate the prevalence and incidence of venous diseases and the role of concomitant/risk factors for varicose veins (VV) or chronic venous insufficiency (CVI). The study was based in San Valentino in Central Italy and was a real whole-population study. The study included 30,000 subjects in eight villages/towns evaluated with clinical assessment and duplex scanning. The global prevalence of VV was 7%; for CVI, the prevalence was 0.86% with 0.48% of ulcers. Incidence (new cases per year) was 0.22% for VV and 0.18% for CVI; 34% of patients with venous disease had never been seen or evaluated. The distribution of VV and CVI in comparison with duplex-detected incompetence (DI) indicates that 12% of subjects had only VV (no DI), 2% had DI but no VV, 7.5% had DI associated with VV, 2% apparent CVI without DI, 3% DI only (without CVI), and 1.6% both CVI and DI. VV associated with DI are rapidly progressive and CVI associated with DI often progresses to ulceration (22% in 6 years). VV without significant DI (3%) and venous dilatation without DI tend to remain at the same stage without progression for a lengthy time. New cases per year appear to have a greater increase in the working population (particularly CVI) possibly as a consequence of trauma during the working period. In older age (>80 years), the incidence of CVI tends to decrease. Ulcers increase in number with age. Only 22% of ulcers can be defined as venous (due to venous hypertension, increased ambulatory venous pressure, shorter refilling time, obstruction and DI). Medical advice for VV or CVI is requested in 164 subjects of 1,000 in the population. In 39 of 1,000, there is a problem but no medical advice is requested and in only 61 of 1,000, the venous problem is real. In VV in 78% of limbs, there is only reflux, in 8% only obstruction, and in 14% both. In CVI, 58% of limbs have reflux, 23% obstruction, and 19% both. In conclusion, VV and CVI are more common with increasing age. The increase with age is linear. There was no important difference between males and females. These results are the basis for future real, whole population studies to evaluate VV and CVI.     

Comparison of Pycnogenol and Daflon in treating chronic venous insufficiency: a prospective, controlled study.

The aim of this study was to investigate the clinical efficacy of oral Pycnogenol (Horphag Research Ltd., UK) in patients with severe chronic venous insufficiency (CVI) in comparison to the combination of diosmin and hesperidin (Daflon, Servier, France). A group of 86 patients with severe chronic venous insufficiency (CVI), venous hypertension, ankle swelling) and previous history of venous ulcerations received either oral Pycnogenol (capsules) 150 mg or 300 mg daily for 8 weeks or Daflon, 1,000 mg/day. All patients completed the study without dropouts. At the end of the study, microcirculatory results indicated: a progressive decrease of skin flux at rest (RF); a significant decrease in capillary filtration (RAS); an improvement in the symptomatic venous score (ASLS); a reduction in edema; a significant improvement (increase) in pO(2) and a decrease in pCO(2) in the Pycnogenol group. A significant level of improvement was reached after 4 weeks of treatment in most patients (p < .05) of the Pycnogenol group while clinical improvement was significant only in 6 subjects in the Daflon group. The positive effects of treatment with Pycnogenol after 8 weeks were significantly larger in comparison with the Daflon group. In conclusion, this study confirms the fast clinical efficacy of Pycnogenol in patients with chronic venous insufficiency and venous microangiopathy and its superiority-considering the evaluated parameters-to the combination of diosmin and hesperidin.     

Capillaries and flow redistribution play an important role in muscle blood flow reserve capacity

Perfusion of skeletal muscle varies considerably during rest, exercise, or when arteries are occluded. The extent that a muscle can adapt to changes in flow demand is often expressed as the ratio of the highest inducible flow and control flow, the microvascular blood flow reserve capacity (MBFRC). However, perfusion of the nutritive capillaries of skeletal muscle may not only be improved by the increase in blood flow proportional to the increase in arterial flow, but also by diverting originally shunted flow towards the muscle proper. Consequently, MBFRC is not a good measure of capillary flow reserve, unless the assessed flow in both conditions is purely nutritive in nature. Therefore, in critical conditions, flow measurements in large vessels are not appropriate to assess MBFRC. In muscle, capillaries are compliant, i.e., with varying transmural pressure capillary diameter varies. During high perfusion states, when capillary transmural pressure is increased, capillary compliance results in increased capillary diameter and, hence, in reduced resistance and increased exchange surface area. This results in improved perfusion and enlarged capillary exchange surface area. In low perfusion states, capillary diameter is reduced. This augments the detrimental effects of the low perfusion status. Operative restoration of perfusion pressure not only increases the driving force for perfusion, but also leads to (passive) dilatation of the capillary bed and an extra reduction in resistance to flow, and, hence, a disproportional increase in flow.     

Ultrastructure of capillaries in the red body (rete mirabile) of the eel swim bladder

The retea mirabilia are paired capillary organs located on the dorsal surface of the swimbladder of the common eel. They consist of bundles of closely apposed capillary segments which function in countercurrent exchange of gases and other solutes and concentrate oxygen in the swim bladder. Ultrastructural features of the afferent arterial capillaries and efferent venous capillaries were studied by scanning EM of corrosion casts and critical-point dried retes and transmission EM of thin sections and freeze-fractured retes. A loose association between endothelial cells in the venous capillaries is indicated by penetration of casting material into interendothelial clefts and the appearance of clefts bounded by cytoplasmic flaps in exposed critical-point dried specimens. In thin sections, open gaps between venous endothelial cells are bounded by cytoplasmic processes. Sections through arterial capillaries exhibit tight occluding junctions joining endothelial cells together and these can be seen in freeze-fracture replicas to extend without interruption along the length of the arterial capillaries. These studies indicate the absence of open or hydraulically conductive pathways across the arterial capillary walls and that they probably constitute a rate-limiting barrier in countercurrent exchange of solutes.     

Structural skin capillary rarefaction in essential hypertension

A reduction in the density of capillaries (rarefaction) is known to occur in many tissues in patients with essential hypertension. This rarefaction may play a role in increasing peripheral resistance. However, the mechanism underlying this capillary rarefaction is not understood. The aim of this study was to assess the extent of structural versus functional capillary rarefaction in the skin of dorsum of fingers in essential hypertension. The capillary microcirculation was examined with video microscopy before and after maximizing the number of perfused capillaries by venous congestion. The study group comprised 17 patients with essential hypertension (mean supine blood pressure, 155/96 mm Hg) and 17 closely matched normotensive controls (mean blood pressure, 127/77 mm Hg). We used intravital video microscopy with an epi-illuminated microscope to examine the skin of the dorsum of left middle phalanx before and after venous congestion at 60 mm Hg for 2 minutes. A significantly lower mean capillary density occurred at baseline in hypertensive subjects versus normotensive subjects. With venous occlusion, capillary density increased significantly in both groups; however, maximal capillary density remained significantly lower in the hypertensive subjects than in the normotensive subjects. The study strongly suggests that much of the reduction in capillary density in the hypertensive subjects is caused by structural (anatomic) absence of capillaries rather than functional nonperfusion.     

Characterization of vascular development in the mouse retina

The murine retina provides an ideal model for the study of vascular development. In this investigation we have examined the development of blood vessels in flat-mounted whole retinas from C57B6 mice ranging from birth to 4 months of age. Basement membrane components of blood vessels were visualized by indirect immunofluorescence with antibodies against type IV collagen and laminin. Endothelial cells (EC) were labeled with a plant lectin, Ricinus communis agglutinin I (RCA), and antibodies against angiotensin converting enzyme. Results show three stages of vascular differentiation. During the first stage (postnatal days P0-P10), vessels develop radially from optic disc to ora serrata within the presumptive nerve fiber layer. In the second stage beginning P4, vessels form within deeper retinal layers. In the third stage beginning P7, a capillary network develops as branches of radial vessels in the nerve fiber layer. The entire vascular system begins as a polygonal network of capillary-like vessels. Selective regression of various segments of these polygons leads to the ultimate arborous pattern of arteries, arterioles, veins, venules, and capillaries seen in the adult. Some individual EC appear to be left behind during this retraction process and pericytes may have a role in determining which vessel segments regress. This combination of flat-mounted whole retinas and probes specific for vascular elements provides an ideal system for the study of retinal vascularization and the characterization of vasculogenesis in general.     

Cardiovascular effects produced by a traditional fungal medicine, Fuscoporia obliqua extract, and microvessels in the left ventricular wall of stroke-prone spontaneously hypertensive rat (SHRSP)

Studies were carried out on stroke-prone spontaneously hypertensive rats (SHRSP) to determine the cardiovascular effects of a traditional medicine extracted from the fungus Fuscoporia obliqua. The rats received either a hot-water extract of Fuscoporia or tap water for 60 days. Heart rate and blood pressure were measured in the tail and venous blood was analyzed for glycated hemoglobin (HbA1c) and leukocyte number. Sections of the left ventricular wall were stained for alkaline phosphatase and dipeptidylpeptidase IV to distinguish the arteriolar from the venular portions of the capillaries. Capillary to myocyte ratio (C:M ratio) was also measured. Treated rats showed a significant decrease in arterial pressure, a mild increase in leukocyte and a trend towards a decrease in HbA1c. There was a trend towards an increase in total capillary density in the subendomyocardium accompanied by a decrease in the arteriolar capillary portions. C:M ratio showed no clear change. It is concluded that the hot-water extract of Fuscoporia has beneficial effects on cardiovascular function, hematological status and probably immunological function in SHRSP.     

Strength of the pulmonary blood-gas barrier.

The mammalian pulmonary blood-gas barrier is well known to be extremely thin. For example, in the human lung, half of the area of the barrier (the 'bulging' part) has a thickness of only 0.2-0.4 micron. We show here that the barrier is also immensely strong. This is an essential requirement because the capillary wall stresses during heavy exercise become very large (about 7 x 10(4) N/m2 = 70 kPa) when capillary pressure increases to 30 mmHg. Stress failure of the pulmonary capillary wall consistently occurs in experimental rabbit preparations at abnormally high pressures exceeding 40 mmHg and may be the cause of bleeding into the lung in galloping racehorses. The great strength of the thin side of the blood-gas barrier can be attributed to the extracellular matrix, especially the type IV collagen which is predominantly located in the very thin lamina densa. The alveolar wall is therefore particularly vulnerable to injurious agents which attack type IV collagen such as autoantibodies in Goodpasture's Syndrome and perhaps neutrophil elastase in emphysema. The combination of extreme thinness and great strength of the blood-gas barrier poses a unique design requirement.     

Distensibility of capillaries in the bat wing

Preliminary experiments in our laboratory have shown that the distensibility characteristics of the capillary compartment in the bat wing depended upon its location in the vascular tree. The capillaries were then divided into arteriolar, middle and venular segments (according to their proximity to precapillary sphincters or nonmuscular venules). The bat was enclosed in an airtight box, one wing protruding through a slit and extended over a glass plate for microscopic observations. Continuous recordings of the diameter of the capillary segments were obtained; after 5 min of control recordings, the box pressure was raised in steps of 25 mm Hg to a maximum of 100 mm Hg and then returned to control level. The duration of each step was 4 min. Each increase of the pressure led to the dilatation of the capillary, but its arteriolar segment appeared to be more distensible than the middle and venous ones. After shifting the box pressure, the diameter increase was gradual and capillary distensibility decreased with increasing pressure (the venular segment showed the most prominent reduction in distensibility). These findings suggest the existence of a longitudinal gradient of distensibility in the capillary compartment.